Cholestatic disorders or unresolved veno-occlusive disease of the liver.Xx_NEWLINE_xXClinically important history of liver disease, including viral or other hepatitis or cirrhosisXx_NEWLINE_xXHistory of pituitary or adrenal dysfunction, active or symptomatic viral hepatitis or chronic liver diseaseXx_NEWLINE_xXClinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosisXx_NEWLINE_xXPatients must not have any other serious concurrent disease or have a history of serious organ dysfunction or disease involving the heart, kidney, liver, or other organ system that would put the patient at undue risk of undergoing therapyXx_NEWLINE_xXPatients must not have a history of chronic liver disease (or cirrhosis)Xx_NEWLINE_xXPatients has current active hepatic or biliary disease (with exception of patients with Gilbert’s syndrome, asymptomatic gallstones, or stable chronic liver disease per investigator assessment)Xx_NEWLINE_xXPatients with clinical or laboratory evidence of liver disease would be evaluated for the cause of liver disease, its clinical severity in terms of liver function, and the degree of portal hypertension; patients will be excluded if they are found to have fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction evinced by prolongation of the prothrombin time, ascites related to portal hypertension, bridging fibrosis, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin > 3 mg/dL, or symptomatic biliary diseaseXx_NEWLINE_xXClinically significant history of liver disease, including active viral or other hepatitis, current alcohol abuse, or cirrhosisXx_NEWLINE_xXPrior SOT of kidney, liver, heart, lung, pancreas, small bowel, or any combination of theseXx_NEWLINE_xXPatients with a history of venous occlusive disease of the liverXx_NEWLINE_xXParticipants who have undergone a liver transplant or those who are in the waiting list for liver transplantationXx_NEWLINE_xXPre-existing liver diseaseXx_NEWLINE_xXKnown history of chronic active hepatitis or liver cirrhosis (if suspected by laboratory studies, should be confirmed by liver biopsy).Xx_NEWLINE_xXMust not have active liver or biliary disease (with the exception of Gilbert’s syndrome or asymptomatic gallstones, liver metastases or otherwise stable chronic liver disease per investigator assessment);\r\n* Note: Stable chronic liver disease should generally be defined by the absence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosisXx_NEWLINE_xXLiver disease characterized by:\r\n* Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 3 x institutional ULN (>= 5 x ULN for subjects with concurrent liver metastasis) confirmed on two consecutive measurements OR\r\n* Absolute impaired excretory function (e.g., hyperbilirubinemia) or synthetic function or other conditions of decompensated liver disease such as coagulopathy, hepatic encephalopathy, hypoalbuminemia, ascites, and bleeding from esophageal varices OR\r\n* Impaired excretory function (e.g., hyperbilirubinemia) or synthetic function or other conditions of decompensated liver disease such as coagulopathy, hepatic encephalopathy, hypoalbuminemia, ascites, and bleeding from esophageal varices OR\r\n* Acute viral or active autoimmune, alcoholic, or other types of acute hepatitisXx_NEWLINE_xXAcceptable liver function:Xx_NEWLINE_xXAcceptable liver function:Xx_NEWLINE_xXEXCLUSION CRITERIA FOR SECOND-LINE THERAPY: Patients with chronic hepatitis C virus may be enrolled if there is no clinical/laboratory evidence of cirrhosis AND the patient’s liver function tests fall within the parametersXx_NEWLINE_xXEXCLUSION CRITERIA FOR THIRD-LINE THERAPY: Patients with chronic hepatitis C virus may be enrolled if there is no clinical/laboratory evidence of cirrhosis AND the patient’s liver function tests fall within the parametersXx_NEWLINE_xXAcceptable liver function:Xx_NEWLINE_xXLiver MRI (? 90 days prior to initiation of transplant conditioning) to document hepatic iron content is required for participants who are currently receiving ?8 packed red blood cell transfusions for ?1 year or have received ?20 packed red blood cell transfusions (cumulative). Participants who have hepatic iron content ?7 mg Fe/ g liver dry weight by liver MRI must have a liver biopsy and histological examination/documentation of the absence of cirrhosis, bridging fibrosis and active hepatitis (? 90 days prior to initiation of transplant conditioning).Xx_NEWLINE_xXHistory of chronic liver disease or evidence of hepatic cirrhosisXx_NEWLINE_xXHepatobiliary diseases including biliary tract diseases, autoimmune hepatitis, inflammation, fibrosis, cirrhosis of liver caused by viral, alcohol, or genetic reasons; Gilbert’s disease is allowed if total bilirubin (TBil) is =< 1.5 x ULNXx_NEWLINE_xXGood kidney and liver functionXx_NEWLINE_xXCurrent active liver or biliary disease.Xx_NEWLINE_xXTumor involvement > 50% of the liverXx_NEWLINE_xXCirrhotic liver disease from any causeXx_NEWLINE_xXSubjects who have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver involved with lymphoma or stable chronic liver disease per investigator’s assessment)Xx_NEWLINE_xXHave any other severe concurrent disease, or have a history of serious organ dysfunction or disease involving the heart, kidney, liver, or other organ system that may place the patient at undue risk to undergo treatmentXx_NEWLINE_xXPatients are stage IV (M1) with any combination of T and N with oligometastatic disease as defined by 5 or fewer total sites of metastatic disease involving 3 or fewer organ systems\r\n* Examples of patients eligible for trial\r\n** T3N2M1 non-small cell lung cancer (NSCLC) with 1 central nervous system (CNS) metastatic lesion, 2 liver lesions, and 1 adrenal lesion.\r\n** T4N1M1 colorectal cancer with 1 liver lesion, 4 bone lesions \r\n** T3N0M1 gastric cancer with 1 supraclavicular lymph node, 2 liver lesions, and 2 CNS lesionsXx_NEWLINE_xXPatients with clinical or laboratory evidence of liver disease will need to be evaluated for the cause of the liver disease, its clinical severity in terms of liver function and the degree of portal hypertension; patients will be excluded if they are found to have fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, bridging fibrosis, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction evidenced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin > 3 mg/dl, or symptomatic biliary diseaseXx_NEWLINE_xX? 3 lesions in the liverXx_NEWLINE_xXSubjects with chronic liver disease or dysfunctionXx_NEWLINE_xXAcceptable liver function, as specified below:Xx_NEWLINE_xXHepatic metastases on imaging meeting the following criteria:\r\n* Liver-only or liver-dominant metastases, defined as:\r\n** At least 10% liver parenchyma replacement by tumor, but less than 70% replacement of the hepatic parenchyma by tumor\r\n*** For the imaging sub-study: at least one liver lesion must measure greater than 2 cm in size\r\n*** For the imaging sub-study: treatment must only be performed using a single dose, and so arterial variant anatomy that would result in a split treatment will not be allowed\r\n** And, progression of the liver metastases demonstrated within the past twelve months defined as either:\r\n*** Appearance of any new liver lesion or\r\n*** 20% increase in size of at least one liver lesion\r\n** Presence of low-volume extrahepatic lesions (including primary tumor) is allowed if they are asymptomatic\r\n* SUVmax on 68Ga-DOTA-TOC PET of the liver metastases two times greater than the adjacent liver parenchymaXx_NEWLINE_xXParticipants with significant renal or liver diseaseXx_NEWLINE_xXHistory of liver allograft; prior hepatic resection is allowedXx_NEWLINE_xXInadequate liver function as evidenced by any of the following:Xx_NEWLINE_xXAcute or chronic liver or renal diseaseXx_NEWLINE_xXMK-1454+pembro (liver metastasis/lesions) Arm:Xx_NEWLINE_xXHas metastatic liver involvement that does not exceed 1/3 of the total liver volume in participants to be treated by liver IT injection. Hepatocellular carcinoma participants are excluded from eligibility of IT liver injection.Xx_NEWLINE_xXAdequate Liver Function defined as total bilirubin <=1.5 x upper limit of normal (ULN) for age, serum glutamic-pyruvic transaminase (SGPT) Alanine transaminase (ALT) <=2.5 x ULN (for the purpose of this study, the ULN for SGPT is 45 U/L), Serum albumin >=2 g/dL. Must not have active liver or biliary disease (with the exception of Gilbert's syndrome or asymptomatic gallstones, liver metastases or otherwise stable chronic liver disease per investigator assessment). NOTE: Stable chronic liver disease should generally be defined by the absence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, oesophageal or gastric varices, persistent jaundice, or cirrhosis. No known positivity of hepatitis B surface antigen (HBsAg), or of positive hepatitis C antibody.Xx_NEWLINE_xXEvidence of renal or liver dysfunction at screeningXx_NEWLINE_xXSerologically positive for HIV; serologically positive for Hepatitis B or Hepatitis C with evidence of liver dysfunction or documented liver cirrhosisXx_NEWLINE_xXAcute or currently active hepatic or biliary disease requiring antiviral therapy (with the exception of Gilbert’s syndrome, asymptomatic gallstones, liver metastases, or stable chronic liver disease per investigator assessment)Xx_NEWLINE_xXEXCLUSION CRITERIA FOR REGISTRATION: Acute or currently active hepatic or biliary disease requiring antiviral therapy (with the exception of patients with Gilbert’s syndrome, asymptomatic gallstones, liver metastases, or stable chronic liver disease per investigator assessment)Xx_NEWLINE_xXNo prior local, liver-directed therapy; prior surgical resection of oligometastatic liver disease is allowedXx_NEWLINE_xXHistory of cirrhotic liver diseaseXx_NEWLINE_xXKnown history of chronic liver diseaseXx_NEWLINE_xXAspartate amino transferase (AST) or Alanine amino transferase (ALT) >3 times ULN in patient without liver metastasis or liver cirrhosisXx_NEWLINE_xXParticipant has a history of liver diseaseXx_NEWLINE_xXSevere impairment of your kidney or liver functionXx_NEWLINE_xXKnown clinically significant liver disease, inherited liver disease and active viral diseaseXx_NEWLINE_xXAcute or chronic uncontrolled renal disease, pancreatitis or liver disease (with exception of patients with Gilbert's Syndrome, asymptomatic gall stones, liver metastases, or stable chronic liver disease per investigator assessment)Xx_NEWLINE_xXAcceptable liver function at Screening,Xx_NEWLINE_xXHave acceptable liver function defined as:Xx_NEWLINE_xXIntermediate stage HCC (Barcelona Clinic Liver Cancer [BCLC] class B), not eligible for curative treatment, but with Child-Pugh A or B; additionally, tumor cannot involve greater than 50% of the entire liverXx_NEWLINE_xXAcceptable liver function:Xx_NEWLINE_xXAcceptable liver function, serum creatinine and hematological statusXx_NEWLINE_xXPrior radioembolization to the liverXx_NEWLINE_xXAny past or present chronic inflammatory colon and/or liver disease, past intestinal obstruction, pseudo or subocclusion or paralysis.Xx_NEWLINE_xXChronic liver diseaseXx_NEWLINE_xXHave pre-existing alcoholic liver injury or significant liver disease.Xx_NEWLINE_xXLiver function abnormality; patients who have LFTs >= twice the upper limit of normal should be evaluated by a GI physician unless there is a clear precipitating factor (such as an azole, methotrexate, Bactrim or another drug); patients with fulminant liver failure, cirrhosis with evidence of portal hypertension or bridging fibrosis, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, or correctable hepatic synthetic dysfunction evidenced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin > 3 mg/dL, and symptomatic biliary disease will be excludedXx_NEWLINE_xXLiver dysfunction (or digestive involvement with protein loss)Xx_NEWLINE_xXIsolated liver sclerosis or pulmonary fibrosis, without active LCH.Xx_NEWLINE_xXAcceptable liver function:Xx_NEWLINE_xXCirrhosis of the liver, Child-Pugh Stage B or C, or history of liver transplant,Xx_NEWLINE_xXPatients who have severe liver disease including cirrhosis, grade III-IV elevations in liver function studies, or bilirubin in excess of 1.5 mg/deciliterXx_NEWLINE_xXPatients with documented liver cirrhosisXx_NEWLINE_xXImpaired liver function defined as a total bilirubin > 1.5 x normal range and AST or ALT > 2.5 x normal range unless secondary to Gilbert’s disease, hemolysis or leukemic involvement of the liverXx_NEWLINE_xXPatients with clinical or laboratory evidence of liver disease will be evaluated for the cause of liver disease, its clinical severity in terms of liver function, histology, and the degree of portal hypertension; patients with fulminant liver failure, cirrhosis with evidence of portal hypertension or bridging fibrosis, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, or correctable hepatic synthetic dysfunction evidenced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin > 3 mg/dL, and symptomatic biliary disease will be excludedXx_NEWLINE_xXPatient with clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis.Xx_NEWLINE_xXHas a history of liver disease (including but not limited to cirrhosis).Xx_NEWLINE_xXSubjects who have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver involvement or stable chronic liver disease per investigator assessment)Xx_NEWLINE_xXPresence of symptomatic liver failure including ascites and hepatic encephalopathyXx_NEWLINE_xXClinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosisXx_NEWLINE_xXAt least one symptomatic and/or progressive liver lesion over a period of up to 12 monthsXx_NEWLINE_xXLiver function:Xx_NEWLINE_xXLiver cirrhosis;Xx_NEWLINE_xXHigh screening liver function testsXx_NEWLINE_xXActive or symptomatic viral hepatitis or chronic liver diseaseXx_NEWLINE_xXClinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosisXx_NEWLINE_xXClinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosisXx_NEWLINE_xXGENERAL: Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; fatty liver; and inherited liver disease.Xx_NEWLINE_xXGood kidney and liver functionXx_NEWLINE_xXPresence of parenchymal liver metastases on imagingXx_NEWLINE_xXExisting major organ dysfunction > Grade 2, with the exception of hearing loss, hematological status, kidney and liver functionXx_NEWLINE_xXActive or symptomatic viral hepatitis or chronic liver diseaseXx_NEWLINE_xXPatients with recent (within 60 days preoperatively) history severe hepatic disease (defined as liver injury with encephalopathy plus impaired synthetic liver function (i.e. > 1.5).Xx_NEWLINE_xXAny evidence of metastasis to distant organs (liver, lung, peritoneum)Xx_NEWLINE_xXKnown clinically significant liver disease, including alcoholic hepatitis, cirrhosis, fatty liver disease, and inherited liver diseaseXx_NEWLINE_xXLiver lesion safely amenable to core needle biopsy.Xx_NEWLINE_xXKnown clinically significant liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; fatty liver; and inherited liver disease.Xx_NEWLINE_xXAnticipated liver transplantationXx_NEWLINE_xXPatients who have been previously treated with non-SBRT liver directed therapies (with the exception of intrahepatic Y90 infusion) may be enrolled on study; at least 3 months must have elapsed between the most recent liver-directed therapy and study entryXx_NEWLINE_xXAny condition that, in the opinion of the investigator, might be significantly exacerbated by the known side effects associated with the administration of pirfenidone e.g., presence of active GVHD of the liver as manifested by rising liver function tests (LFTs) prior to initiation of study treatmentXx_NEWLINE_xXUncontrolled adrenal insufficiency or active chronic liver diseaseXx_NEWLINE_xXIn patients who have received chronic transfusion therapy for >= 1 year and who have clinical evidence of iron overload by serum ferritin or magnetic resonance imaging (MRI), evaluation by liver biopsy is required; histological examination of the liver must document the absence of cirrhosis, bridging fibrosis and active hepatitis; the absence of bridging fibrosis will be determined using the histological grading and staging scale as described by Ishak and colleaguesXx_NEWLINE_xXClinically significant history of liver disease, including cirrhosis and current alcohol abuseXx_NEWLINE_xXActive or symptomatic viral hepatitis or chronic liver disease.Xx_NEWLINE_xXActive or symptomatic viral hepatitis or chronic liver disease.Xx_NEWLINE_xXSignificant liver metastasis or disease-related bone pain requiring scheduled narcoticsXx_NEWLINE_xXLiver function abnormalities: Patients with clinical or laboratory evidence of liver disease would be evaluated for the cause of liver disease, its clinical severity in terms of liver function, and the degree of portal hypertension; patients will be excluded if they are found to have fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction evinced by prolongation of the prothrombin time, ascites related to portal hypertension, bridging fibrosis, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin > 3 mg/dL, or symptomatic biliary diseaseXx_NEWLINE_xXKnown cirrhosis or chronic hepatic failureXx_NEWLINE_xXLiver metastases with no other metastatic sitesXx_NEWLINE_xXLiver cirrhosis or severe hepatic impairment with function test 3 times above ULN.Xx_NEWLINE_xXParticipants must have biopsy-proven diagnosis of a colorectal cancer with 1-4 liver metastases; there is no upper size limit and participants must have at least 800 mL of uninvolved liver; liver metastases may be diagnosed by imaging alone, no liver biopsy is required; extrahepatic disease is allowed if 1) it has been stable for 3 months prior to study entry, 2) the dominant disease burden is intrahepatic and 3) the patient is referred for definitive radiation therapy to the disease in the liverXx_NEWLINE_xXPatients with prior orthotropic liver transplantationXx_NEWLINE_xXAppropriate renal, liver, and hematologic lab valuesXx_NEWLINE_xXChild’s class C liver disease or worseXx_NEWLINE_xXEvidence of visceral metastasis to the liver.Xx_NEWLINE_xXPatients with diffuse/multifocal liver involvement are eligibleXx_NEWLINE_xXImpaired synthetic function or other conditions of decompensated liver disease, such as coagulopathy, hepatic encephalopathy, ascites, and bleeding from esophageal varicesXx_NEWLINE_xXKnown clinically significant liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; fatty liver; and inherited liver diseaseXx_NEWLINE_xXKnown pre-existing liver disease (e.g. cirrhosis, chronic hepatitis B or C, nonalcoholic steatohepatitis, sclerosing cholangitis)Xx_NEWLINE_xXKnown clinically significant liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; fatty liver; and inherited liver disease. Patients with acute leukemias, accelerated/blast phase chronic myelogenous leukemia, chronic lymphocytic leukemia, Burkitt lymphoma, plasma cell leukemia, or non-secretory myelomaXx_NEWLINE_xXCurrent active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, or stable chronic liver disease per investigator assessment)Xx_NEWLINE_xXActive liver disease, including viral or other hepatitis, or cirrhosisXx_NEWLINE_xXParticipants with prior Hepatitis B or C infection with inadequate liver functionXx_NEWLINE_xXSubjects with end-stage kidney disease and/or grade II liver dysfunctionXx_NEWLINE_xXLiver abnormalities: fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, alcoholic hepatitis, esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction as evidenced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis, or symptomatic biliary diseaseXx_NEWLINE_xXAny known active chronic liver diseaseXx_NEWLINE_xXNo history of severe prior or ongoing chronic liver diseaseXx_NEWLINE_xXLiver cirrhosisXx_NEWLINE_xXPatients who have undergone prior liver transplantation are ineligibleXx_NEWLINE_xXPatients with diagnoses of hepatocellular carcinoma (HCC) according to European Association for the Study of Liver disease (EASL) criteria for diagnosis; regional lymphadenopathy will be allowed\r\n* Any virus status accepted (e.g. hepatitis C, etc.)\r\n* Any prior liver treatmentXx_NEWLINE_xXHigh risk for post-embolization hepatic failure:\r\n* Child's C cirrhosis\r\n* > 80% liver involvement by tumorXx_NEWLINE_xXHistory of cirrhotic liver diseaseXx_NEWLINE_xXActive acute or chronic GVHD of the liverXx_NEWLINE_xXActive viral hepatitis A, B, or C or preexisting or acute liver disease;Xx_NEWLINE_xXAcceptable liver function within 7 days of day 1 of therapy defined as:Xx_NEWLINE_xXPatients must not have metastatic disease on staging work-up with blood cell count (CBC) and liver function studiesXx_NEWLINE_xXAny known active chronic liver diseaseXx_NEWLINE_xXLiver cirrhosis or chronic liver disease Child-Pugh B or CXx_NEWLINE_xXKnown clinically significant liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; fatty liver; and inherited liver diseaseXx_NEWLINE_xXKnown clinically significant liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; fatty liver; and inherited liver diseaseXx_NEWLINE_xXClinically significant liver disease, including active viral or other hepatitis, current alcohol abuse, or cirrhosisXx_NEWLINE_xXPatients with a history of pituitary or adrenal dysfunction or active or symptomatic viral hepatitis or chronic liver disease are not eligibleXx_NEWLINE_xXKnown clinically significant liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; fatty liver; and inherited liver diseaseXx_NEWLINE_xXPatients with evidence of liver metastasis are excludedXx_NEWLINE_xXAbnormal liver function tests (LFTs) in the context of active cGVHD involving other organ systems may also be permitted if the treating physician documents the LFTs as being consistent with hepatic cGVHD and a liver biopsy will not be mandated in this situationXx_NEWLINE_xXPatients must have liver-only metastases or predominant liver metastatic diseaseXx_NEWLINE_xXAcceptable liver and renal functions defined as:Xx_NEWLINE_xXClinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosisXx_NEWLINE_xXNo more than 10 lesions in the liverXx_NEWLINE_xXKnown history of significant liver diseaseXx_NEWLINE_xXNo evidence of disease-related symptoms and extramedullary disease, including the liver and spleenXx_NEWLINE_xXAcute or chronic liver disease or severe renal disease considered unrelated to the cancerXx_NEWLINE_xXActive or symptomatic viral hepatitis or chronic liver diseaseXx_NEWLINE_xXLiver cirrhosis with greater than grade 1 stage 1 inflammation/fibrosisXx_NEWLINE_xXPatients with Gilbert’s disease and absent hepatic pathology by history and clinical assessment maybe treated on study with bilirubin > the ULN for the institution if other liver function studies are within the normal rangeXx_NEWLINE_xXKnown liver diseaseXx_NEWLINE_xXCurrent active liver or biliary disease (with the exception of Gilbert's syndrome or asymptomatic gallstones or otherwise stable chronic liver disease per investigator's assessment)Xx_NEWLINE_xXSubjects with diagnosed active liver disease or with elevation of liver enzymes/bilirubin.Xx_NEWLINE_xXPatients must have liver metastasisXx_NEWLINE_xXIf elevated liver function tests develop at the time of initial presentation or develop during workup and are the result of mechanical obstruction of the biliary drainage by tumor compression or invasion, a biliary drain may be placed; if drainage allows the liver function tests to come within inclusion criteria, the patient may be enrolledXx_NEWLINE_xXFormal evaluation by the Liver Tumor Program at University of Taxes Southwestern (UTSW) and/or review at the Liver Tumor Board: all patients should be fairly and prudently informed of their treatment options; to this end, all patients must be evaluated before brachytherapy treatment for discussion and consideration of other options for treatment of liver cancer including surgical resectionXx_NEWLINE_xXPatients with a history of prior irradiation or other treatment to the liver or abdomen who after treatment on this protocol would have a cumulative dose to the liver or other normal tissues greater than the protocol defined constraintsXx_NEWLINE_xXPatients with parahepatic extension of disease with direct non-liver visceral involvementXx_NEWLINE_xX=< 3 liver lesionsXx_NEWLINE_xXSubjects who have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per treating physician assessment), sources for the determination of clinical significance by the treating physician will be included in the subject’s medical recordXx_NEWLINE_xXPatients with history of hepatic dysfunction or hepatic disease and abnormal liver function tests defined aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline (Alk) phosphatase (Phos), and or total bilirubin greater than 2.5 times the upper limit of normal; patients who have a history of hepatic dysfunction or hepatic disease and normal liver function tests will be eligible to participateXx_NEWLINE_xXKnown history of drug-induced liver injury, alcoholic liver disease, primary biliary cirrhosis, ongoing extra-hepatic obstruction caused by stones, cirrhosis of the liver or portal hypertensionXx_NEWLINE_xXKnown clinically significant liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; fatty liver; and inherited liver diseaseXx_NEWLINE_xXPatients who have undergone prior liver transplantation are ineligibleXx_NEWLINE_xXUncontrolled adrenal insufficiency or active chronic liver diseaseXx_NEWLINE_xXIdelalisib\r\n* Ongoing drug-induced liver injury, chronic active hepatitis C (hepatitis C virus [HCV]), chronic active hepatitis B (hepatitis B virus [HBV]), alcoholic liver disease, non-alcoholic steatohepatitis, primary biliary cirrhosis, extrahepatic obstruction caused by cholelithiasis, cirrhosis of the liver, portal hypertension, or history of autoimmune hepatitis\r\n* Ongoing symptomatic pneumonitis\r\n* Ongoing inflammatory bowel disease or autoimmune colitis\r\n* Ongoing cytomegalovirus (CMV) infection, treatment, or prophylaxis within the past 28 days prior to the screening test for active CMV\r\n* History of serious allergic reaction including anaphylaxis and epidermal necrolysisXx_NEWLINE_xXPHASE I AND II SCLC AND UROTHELIAL CARCINOMA EXPANSION COHORT: Any chronic or concurrent acute liver diseaseXx_NEWLINE_xXActive hepatitis B or C infection with abnormal liver functions (i.e., liver function tests [LFTs] > 2 X upper normal limits)Xx_NEWLINE_xXPatients must have histologically or cytologically confirmed colorectal cancer with liver metastases deemed resectable by a general or liver surgeon (resectability may involve the use of ablative techniques to some but not all liver metastases); those patients with known disease outside of the liver are not eligible (except for patients with primary lesions in place that are planned for resection or nonspecific lung metastases < 1cm)Xx_NEWLINE_xXNot have a reported history of liver disease (e.g. cirrhosis)Xx_NEWLINE_xXIndividuals with a reported history of liver disease (e.g. cirrhosis)Xx_NEWLINE_xXPatients with synchronous or metachronous diagnosis of resectable liver metastases by computed tomography (CT) or magnetic resonance imaging (MRI) of the abdomen: a) patients requiring percutaneous or intraoperative ablation of liver metastases < 2 cm in size are eligible; b) patients who underwent prior liver resection or ablation for colorectal liver metastases are eligibleXx_NEWLINE_xXKnown active or symptomatic viral hepatitis or chronic liver diseaseXx_NEWLINE_xXPre-existing liver diseases (i.e., cirrhosis, chronic hepatitis B or C, nonalcoholic steatohepatitis, and sclerosing cholangitis, etc.)Xx_NEWLINE_xXDiagnosis of hepatocellular carcinoma, cholangiocarcinoma, or liver metastasis from any histologyXx_NEWLINE_xXCompromised liver function as defined by any of the following:\r\n*  Cohort 1: Advanced cirrhosis group\r\n** Borderline Child-Pugh class A6\r\n** Child-Pugh class B\r\n*** The patients in this advanced cirrhosis group must have at least 400 ml of functional liver, as estimated on either diagnostic imaging (computed tomography [CT] or magnetic resonance imaging [MRI]) or single photon emission computed tomography (SPECT)/CT with Tc-99m sulfur colloid; there is no upper limit on the functional liver volume for these patients\r\n* Cohort 2: Low functional liver volume without underlying chronic liver disease\r\n** Previous irinotecan or oxaliplatin chemotherapy\r\n** Previous liver resection(s)\r\n*** These patients must have at least 400 ml of functional liver, as estimated by either diagnostic imaging computed tomography or magnetic resonance imaging (CT or MRI) or SPECT/CT with Tc-99m sulfur colloid\r\n* Cohort 3: History of prior liver-directed radiation therapy with either fractionated external beam radiation therapy (EBRT), stereotactic body radiation therapy (SBRT) or yttrium-90 radioembolization (Y90 RE); the interval between prior EBRT and re-irradiation on protocol should be equal to or greater than 12 months; the interval between prior Y90 RE and re-irradiation on protocol should be equal to or greater than 6 months; \r\n** Cirrhosis group:\r\n*** Child-Pugh class A5; \r\n*** Borderline Child-Pugh class A6; \r\n*** The patients in this group must have at least 400 ml of functional liver, as estimated on either diagnostic imaging (CT or MRI) or SPECT/CT with Tc-99m sulfur colloid; there is no upper limit on the functional liver volume for these patients\r\n*Low functional liver volume without underlying liver disease\r\n** Previous irinotecan or oxaliplatin chemotherapy\r\n** Previous liver resection(s)\r\n** These patients must have at least 400 ml of functional liver, as estimated by either diagnostic imaging (CT or MRI) or SPECT/CT with Tc-99m sulfur colloid; there is no upper limit on the functional liver volume for these patientsXx_NEWLINE_xXActive or symptomatic viral hepatitis or chronic liver diseaseXx_NEWLINE_xXActive or symptomatic viral hepatitis or chronic liver diseaseXx_NEWLINE_xXKnown clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosisXx_NEWLINE_xXAlanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 3 × ULN (>= 5 × ULN for patients with concurrent liver metastasis); OR impaired excretory function (e.g., hyperbilirubinemia) or synthetic function or other conditions of decompensated liver disease such as coagulopathy, hepatic encephalopathy, hypoalbuminemia, ascites, and bleeding from esophageal varices; OR acute viral or active autoimmune, alcoholic, or other types of hepatitisXx_NEWLINE_xXPrior treatment:\r\n* No prior liver radiation therapy or immunotherapy for cholangiocarcinoma\r\n* Only one previous single agent chemotherapy for ICC allowed\r\n* Patient may have prior liver resectionXx_NEWLINE_xXIn patients with liver metastases, there should be < 50% involvement of the liverXx_NEWLINE_xXNo distinction should be made between liver dysfunction due to metastases and liver dysfunction due to other causesXx_NEWLINE_xXSubjects must have measurable liver tumors that are suitable for injection.Xx_NEWLINE_xXLiver tumors must not be estimated to invade approximately more than one-third of the liver.Xx_NEWLINE_xXPre-existing liver diseaseXx_NEWLINE_xXMajor liver vascular invasionXx_NEWLINE_xXPatients with parenchymal liver metastases.Xx_NEWLINE_xXAt least one thoracic or liver lesion amenable to radiation, for group 5 we need one area that can safely receive SBRT or WFRT, not restricted to lung or liver sitesXx_NEWLINE_xXLiver cirrhosisXx_NEWLINE_xXKnown (and biopsy-confirmed) liver cirrhosis; or, a reported history of liver cirrhosis with a model for end-stage liver disease (MELD) score > 20Xx_NEWLINE_xXKnown significant liver disease including viral, alcoholic, active hepatitis B or C, and/or cirrhosisXx_NEWLINE_xXBilirubin < 1.5 x normal except in cases where abnormal liver function tests (LFTS) are due to involvement with T-NHLXx_NEWLINE_xXPatients with clinically important history of liver disease, including viral or other hepatitis or cirrhosis are ineligibleXx_NEWLINE_xXKnown or active hepatitis B or C with abnormal liver function testsXx_NEWLINE_xXPatients with liver cirrhosis or other serious active liver disease or with suspected alcohol abuseXx_NEWLINE_xXHistory of severe kidney disease (e.g chronic or acute kidney failure) with creatinine clearance below 30 and/or severe liver disease with liver tests over 4 times the upper normal levelXx_NEWLINE_xXPART 2: Patients with clinical or laboratory evidence of liver disease will be evaluated for the cause of liver disease, its clinical severity in terms of liver function, and the degree of portal hypertension; patients with fulminant liver failure, cirrhosis with evidence of portal hypertension or bridging fibrosis, alcoholic hepatitis, hepatic encephalopathy, or correctable hepatic synthetic dysfunction evidenced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin > 3 mg/dL, and symptomatic biliary disease will be excludedXx_NEWLINE_xXSubjects who have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment)Xx_NEWLINE_xXLiver dysfunction and/ or cirrhosisXx_NEWLINE_xXLiver function: total bilirubin =< 2.0 mg/dL\r\n* Note: in the event a participant has elevated levels of liver enzymes possibly related to underlying disease/disease progression, the participant will still be considered eligibleXx_NEWLINE_xXLiver function: ALT and AST =< 2.5 times the institutional upper limits of normal\r\n* Note: in the event a participant has elevated levels of liver enzymes possibly related to underlying disease/disease progression, the participant will still be considered eligibleXx_NEWLINE_xXLiver function criteria: total bilirubin =< 2.0 mg/dL\r\n* Note: in the event a participant has elevated levels of liver enzymes possibly related to underlying disease/disease progression, the participant will still be considered eligibleXx_NEWLINE_xXPatients must have a diagnosis of hepatocellular carcinoma confirmed by at least one of the following: \r\n* Histological confirmation; \r\n* Imaging results consistent with cirrhosis and at least one solid liver lesion of > 2 cm with early enhancement and delayed washout (American Association for the Study of Liver Diseases [AASLD] criteria for diagnosis of hepatocellular carcinoma [HCC]);\r\n* Alpha fetoprotein level > 400 ng/mL and evidence of at least one solid liver lesion > 2 cm, regardless of specific imaging characteristics on magnetic resonance imaging (MRI)Xx_NEWLINE_xXTumor involving > 50% of the liverXx_NEWLINE_xXHave any other severe concurrent disease, or have a history of serious organ dysfunction or disease involving the heart, kidney, liver, or other organ system that may place the patient at undue risk to undergo treatmentXx_NEWLINE_xXPatients with acute or chronic liver, renal disease or pancreatitisXx_NEWLINE_xXIs scheduled for liver transplantationXx_NEWLINE_xXHave any other severe concurrent disease, or have a history of serious organ dysfunction or disease involving the heart, kidney, liver, or other organ system that may place the patient at undue risk to undergo treatmentXx_NEWLINE_xXActive liver disease (i.e., cirrhosis, viral or autoimmune hepatitis, etc.)Xx_NEWLINE_xXOther serious medical conditions that may be expected to limit life expectancy to less than 2 years (e.g., liver cirrhosis).Xx_NEWLINE_xXThe patient has a history of liver disease (excluding Gilbert’s disease and non-active hepatitis C) and/or elevation of transaminases or bilirubin above the normal limitXx_NEWLINE_xXPatients have known chronic liver disease (i.e., cirrhosis)Xx_NEWLINE_xXAny evidence of metastasis to distant organs (liver, lung, peritoneum)Xx_NEWLINE_xXLiver cirrhosisXx_NEWLINE_xXHave acute or currently active/requiring anti-viral therapy hepatic or biliary disease (with the exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment)Xx_NEWLINE_xXConcomitant disease or malformation severely affecting the cardiovascular, pulmonary, liver or renal functionXx_NEWLINE_xXPatients with clinical or laboratory evidence of liver disease will be evaluated for the cause of liver disease, its clinical severity in terms of liver function and histology, and for the degree of portal hypertensionXx_NEWLINE_xXPatients with any of the following liver function abnormalities will be excluded:\r\n* Fulminant liver failure\r\n* Cirrhosis with evidence of portal hypertension (ascites or ultrasonographic evidence) or greater than 2+ bridging fibrosis if a liver biopsy is performed based on clinical suspicion (not required for trial)\r\n* Known esophageal varices with or without history or variceal bleed\r\n* Hepatic encephalopathy\r\n* Uncorrectable hepatic synthetic dysfunction evidenced by prolongation of the prothrombin time with international normalized ratio (INR) > 1.5 and not taking anti-coagulationXx_NEWLINE_xXPatients with a history of or active liver failureXx_NEWLINE_xXPatients who have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment)Xx_NEWLINE_xXPatient must have disease that is unresectable or borderline resectable with < 70% liver involvement by cancerXx_NEWLINE_xX5FU and oxaliplatin are known to be safe to be administered in patients with such abnormal liver function testsXx_NEWLINE_xXSubjects who have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, hepatic involvement by MCL, or stable chronic liver disease per investigator assessment)Xx_NEWLINE_xXSymptomatic liver or visceral organ metastasisXx_NEWLINE_xXHistory of chronic liver disease, veno-occlusive disease, or current alcohol abuseXx_NEWLINE_xXScans used to determine eligibility (CT scan of the chest/abdomen/pelvis and MRI of the liver) must be performed within 28 days prior to randomization. An MRI of the liver is required at screening to validate that CT accurately reflects the extent of disease in the liver. For patients with MRI intolerance, a 3-phase liver CT is to be done in place of liver MRI.Xx_NEWLINE_xXAcceptable liver functionXx_NEWLINE_xXExtensive liver tumor burden, defined as more than 75% of the liverXx_NEWLINE_xXDiagnosis of unresectable intrahepatic HCC. The histopathology confirmation criterion may be waived in patients with a radiographically identifiable liver mass, known laboratory or clinical risk factors for cancer or elevated tumor markers such as alphafetoprotein (AFP)^21 and clinical findings. Guidelines from the American Association for the Study of Liver Diseases (AASLD) and the European Association for the Study of the Liver (EASL) describe in detail the approach and algorithm for diagnosing HCC.Xx_NEWLINE_xXHistologically confirmed diagnosis of cancer with liver metastases, or histologically confirmed primary liver cancer (e.g. hepatocellular carcinoma, cholangiocarcinoma, or gallbladder carcinoma); subjects may have extrahepatic spread of malignancy, except they may not have brain metastases; subjects with a history of more than one invasive malignancy remain eligible for this study, but in these instances, a liver biopsy is required to document the histology of the liver tumor; an exception to this criterion is made for basal cell carcinomaXx_NEWLINE_xXNo liver surgery (including radiofrequency ablation), chemotherapy (including bevacizumab), immunotherapy, or liver radiotherapy within 4 weeks of enrollment in this clinical trialXx_NEWLINE_xXPrior liver resection of greater than 2 anatomic segments as defined by Couinaud; (subjects that have undergone prior liver wedge excisions or segmental resections are not excluded on this basis alone)Xx_NEWLINE_xXPatient with clinical or laboratory evidence of liver disease will be evaluated for the cause of liver disease, its clinical severity in terms of liver function, bridging fibrosis, and the degree of portal hypertension; the patient will be excluded if he/she is found to have fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction evinced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin > 3 mg/dL, and symptomatic biliary diseaseXx_NEWLINE_xXAdequate hepatic function; patients with clinical or laboratory evidence of liver disease will be evaluated for the cause of liver disease, its clinical severity in terms of liver function, histology, and the degree of portal hypertension; patients with fulminant liver failure, cirrhosis with evidence of portal hypertension or bridging fibrosis, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, or correctable hepatic synthetic dysfunction evidenced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin > 3 mg/dL, and symptomatic biliary disease will be excludedXx_NEWLINE_xXAdequate hepatic function; patients with clinical or laboratory evidence of liver disease will be evaluated for the cause of liver disease, its clinical severity in terms of liver function, histology, and the degree of portal hypertension; patients with fulminant liver failure, cirrhosis with evidence of portal hypertension or bridging fibrosis, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, or correctable hepatic synthetic dysfunction evidenced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin > 3 mg/dL, and symptomatic biliary disease will be excludedXx_NEWLINE_xXSevere liver dysfunction or pulmonary insufficiencyXx_NEWLINE_xXSevere liver dysfunction or pulmonary insufficiencyXx_NEWLINE_xXNo history of severe prior or ongoing chronic liver diseaseXx_NEWLINE_xXCurrent unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis.Xx_NEWLINE_xXSignificant liver, lung, heart, or kidney dysfunctionXx_NEWLINE_xXAcceptable liver functionXx_NEWLINE_xXNon-amyloidosis related chronic liver disease (with the exception of Gilbert's syndrome or clinically asymptomatic gallstones)Xx_NEWLINE_xXChronic liver disease or current active liver or biliary disease not attributable to amyloidosis (with the exception of Gilbert's syndrome or asymptomatic gallstones). Exclusion criteria for Group 3Xx_NEWLINE_xXChronic liver disease or current active liver or biliary disease not attributable to amyloidosis (with the exception of Gilbert's syndrome or asymptomatic gallstones).Xx_NEWLINE_xXHistory of chronic liver disease.Xx_NEWLINE_xXHistory of chronic liver disease.Xx_NEWLINE_xXHistologically or cytologically documented locally advanced recurrent or metastatic HCC or for patients with cirrhosis according to the American Association for the Study of Liver Diseases (AASLD) and Asian Pacific Association for the study of the liver (APASL) criteria. Current cirrhotic status of Child Pugh Class A (5-6 points), with no encephalopathy and/or clinically significant ascites (defined as requiring the use of diuretics or paracentesis treatment).Xx_NEWLINE_xXKnown history of drug-induced liver injury, chronic active hepatitis B virus (HBV), chronic active hepatitis C virus (HCV), alcoholic liver disease, non-alcoholic steatohepatitis, cirrhosis of the liver, portal hypertension, primary biliary cirrhosis, or ongoing extrahepatic obstruction caused by cholelithiasisXx_NEWLINE_xXPre-existing liver diseases (i.e. cirrhosis, chronic hepatitis B or C, nonalcoholic steatohepatitis, sclerosing cholangitis)Xx_NEWLINE_xXAcceptable liver functionXx_NEWLINE_xXLiver function tests documented within the screening period and on day -1 of treatment period:Xx_NEWLINE_xXChronic inflammatory liver condition.Xx_NEWLINE_xXPatients with acute or chronic liver, renal disease or pancreatitisXx_NEWLINE_xXPatients who have current active hepatic or biliary disease (with the exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver involvement by CLL, or stable chronic liver disease per investigator assessment) are NOT eligibleXx_NEWLINE_xXHistory of alcohol abuse or chronic liver disease (other than metastatic disease to the liver)Xx_NEWLINE_xXCurrent unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis. Stable chronic liver disease (including Gilbert's syndrome or asymptomatic gallstones) or hepatobiliary involvement of malignancy is acceptable if subject otherwise meets entry criteria.Xx_NEWLINE_xXSubjects in Arm A and Arm B should have measurable CT evidence of liver metastases or liver lesions that are not treatable by surgical resection or local ablation in consultation with hepatobiliary specialist.Xx_NEWLINE_xXSubjects must not be candidates for hepatic surgery or locoregional therapy of liver tumors with curative intent.Xx_NEWLINE_xXLiver tumors must not be estimated to invade approximately more than one-third of the liver.Xx_NEWLINE_xXChronic liver dysfunction prior to development of liver metastases (Child-Pugh C or greater).Xx_NEWLINE_xXKnown clinically significant liver disease defined as ongoing drug-induced liver injury, chronic active hepatitis C (HCV), chronic active hepatitis B (HBV), alcoholic liver disease, non-alcoholic steatohepatitis, primary biliary cirrhosis, extrahepatic obstruction caused by cholelithiasis, cirrhosis of the liver, portal hypertension, or history of autoimmune hepatitis.Xx_NEWLINE_xXCurrent active liver or biliary disease (with the exception of Gilbert's syndrome or asymptomatic gallstones, or otherwise stable chronic liver disease per investigator's assessment).Xx_NEWLINE_xXOngoing drug-induced liver injury, chronic active hepatitis C (HCV), chronic active hepatitis B (HBV), HIV, alcoholic liver disease, non-alcoholic steatohepatitis, cirrhosis of the liver, or portal hypertensionXx_NEWLINE_xXSevere liver diseaseXx_NEWLINE_xXSevere liver diseaseXx_NEWLINE_xXTotal bilirubin > 3 x ULN unless isolated hyperbilirubinemia is directly related to the acute infection or due to known Gilbert disease; manifestations of end-stage liver disease, such as ascites or hepatic encephalopathyXx_NEWLINE_xXHas evidence of significant liver diseaseXx_NEWLINE_xXENROLLMENT: Adequate liver function, as defined as serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 2.5 x upper limit of normal (ULN) for age (unless Gilbert’s disease or abnormal liver function due to primary disease).Xx_NEWLINE_xXUncontrolled adrenal insufficiency or active chronic liver diseaseXx_NEWLINE_xXAcute or chronic liver disease or severe renal disease considered unrelated to the cancerXx_NEWLINE_xXHCC patients only: prior regional treatments for liver metastasis are permitted including:\r\n* Selective internal radiation therapy such as brachytherapy, cyber knife, radiolabeled microsphere embolization, etc.\r\n* Hepatic artery chemoembolization\r\n* Hepatic artery embolization\r\n* Hepatic artery infusional chemotherapy\r\n* Radiofrequency ablation\r\n* NOTE: patients must be >= 4 weeks from treatment and show progressive measurable/evaluable disease in the liver after regional therapy or must have measurable disease outside the liverXx_NEWLINE_xXKnown clinically significant liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; fatty liver; and inherited liver diseaseXx_NEWLINE_xXCurrent active liver or biliary disease (with the exception of Gilbert's syndrome or asymptomatic gallstones, liver metastases or otherwise stable chronic liver disease per investigator assessment).Xx_NEWLINE_xXAcceptable liver functionXx_NEWLINE_xXAdequate performance status and hematological, liver and kidney functionsXx_NEWLINE_xXActive symptomatic viral hepatitis or chronic liver diseaseXx_NEWLINE_xXHistory of liver cirrhosis by radiologic, clinical or laboratory data, or biopsy despite normal liver function tests Phase II Expansion Arm A and Arm B:Xx_NEWLINE_xXHistory of liver cirrhosis by radiologic, clinical or laboratory data, or biopsy despite normal liver function testsXx_NEWLINE_xXARM A: Disease burden in liver not affecting more than 25% of liverXx_NEWLINE_xXARM B: Disease burden in liver not affecting more than 25% of liverXx_NEWLINE_xXDOSE ESCALATION COHORT: \r\n* Note: Subjects with bone metastasis and no liver metastasis on screening image may enroll if ALP is < 5 X ULN; subjects with liver metastasis may enroll if all of AST/ALT/ALP are < 5 X ULN; however, subjects with extensive liver metastasis occupying more than 50% of liver parenchyma will be excluded per epacadostat investigator’s brochureXx_NEWLINE_xXDOSE EXPANSION COHORT: \r\n* Note: subjects with bone metastasis and no liver metastasis on screening image may enroll if ALP is < 5 X ULN; subjects with liver metastasis may enroll if all of AST/ALT/ALP are < 5 X ULN; however, subjects with extensive liver metastasis occupying more than 50% of liver parenchyma will be excluded per epacadostat investigator’s brochureXx_NEWLINE_xXPatients with abnormal hepatic function will be eligible and will be grouped according to criteria; patients with active hemolysis should be excluded; no distinction should be made between liver dysfunction due to metastases and liver dysfunction due to other causes; this data will be captured in the case report form (CRF); registration laboratory investigations will be used to assign a patient to a hepatic function group; hepatic function tests should be repeated within 24 hours prior to starting initial therapy and may result in patients’ group assignment being altered if different to registration test resultsXx_NEWLINE_xXAlkaline phosphatase (ALP) =< 1.5 x ULN but =< 2.5 x ULN in case of liver metastases or =< 5 x ULN in the case of bone metastasis; in the presence of liver metastases the liver isoenzyme fraction must be measured and liver\r\nisoenzyme fraction (absolute value) must be =< 2 x UNLXx_NEWLINE_xXPatients with active hepatic or biliary disease (with exception of patients with Gilbert’s syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment)Xx_NEWLINE_xXHepatobiliary diseases including biliary tract diseases, autoimmune hepatitis, inflammation, fibrosis, cirrhosis of liver caused by viral, alcohol, or genetic reasons; Gilbert’s disease is allowed if TBil is =< 1.5 x ULNXx_NEWLINE_xXLiver: 1000 cGyXx_NEWLINE_xXEvidence of liver metastases or visceral diseaseXx_NEWLINE_xXPatients with acute or chronic liver, renal, lung disease or pancreatitisXx_NEWLINE_xXTotal bilirubin =< 1.5 x ULN; unless presence of Gilbert's syndrome, liver involvement by CLL or MM, or stable chronic liver disease per investigator's assessmentXx_NEWLINE_xXLiver disease, except Gilbert's syndrome, liver involvement by CLL or MM, or stable chronic liver disease per investigator's assessmentXx_NEWLINE_xXPrevious liver transplantationXx_NEWLINE_xXDecompensated liver disease in which pegylated interferon is contraindicatedXx_NEWLINE_xXAbsence of clinically relevant liver or kidney failure as deemed by the treating physicianXx_NEWLINE_xXKnown clinically significant liver disease, including active viral, alcoholic, or other hepatitis, cirrhosis, fatty liver, and inherited liver diseaseXx_NEWLINE_xXLiver function < 3 x normalXx_NEWLINE_xXSubjects who have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment)Xx_NEWLINE_xXPatients who have undergone liver transplantation are excludedXx_NEWLINE_xXPatients with acute or chronic liver, renal disease or pancreatitisXx_NEWLINE_xXHistory of liver disease, such as cirrhosis or chronic active hepatitis B and CXx_NEWLINE_xXPatients with current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment)Xx_NEWLINE_xXPatients with clinical or laboratory evidence of liver disease will need to be evaluated for the cause of the liver disease, its clinical severity in terms of liver function and the degree of portal hypertension; patients will be excluded if they are found to have: fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, bridging fibrosis, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction evidenced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin > 3mg/dl, or symptomatic biliary disease (Patients will be allowed on to the protocol with liver problems if gastroenterology approves the patient for HCT)Xx_NEWLINE_xXHistory or other evidence of decompensated liver diseaseXx_NEWLINE_xXHistory or other evidence of decompensated liver diseaseXx_NEWLINE_xXPoor liver function defined as bilirubin >= 2 mg/dl (not due to hemolysis, Gilbert’s or primary malignancy) orXx_NEWLINE_xXVisceral metastasis (excluding liver metastases) and/or lymphadenopathyXx_NEWLINE_xXPatient has known chronic liver disease, e.g. diagnosis of chronic active hepatitis or cirrhosisXx_NEWLINE_xXCholestatic disorders or unresolved veno-occlusive disease of the liver (defined as persistent bilirubin abnormalities not attributable to GVHD and ongoing organ dysfunction).Xx_NEWLINE_xXSignificant gastrointestinal disorder with diarrhea as a major symptom (example Crohn's disease, ulcerative colitis) or grade >= 2 diarrhea of any etiology at baseline; active hepatobiliary disease with the exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases, or stable chronic liver disease as determined by investigator's assessmentXx_NEWLINE_xXLiver disease.Xx_NEWLINE_xXLiver function defined as:Xx_NEWLINE_xXPre-existing liver diseases (i.e., cirrhosis, chronic hepatitis B or C, nonalcoholic steatohepatitis, and sclerosing cholangitis, etc.)Xx_NEWLINE_xXMust have colorectal cancer with unresectable metastatic disease to the liver (unresectable unilobar or bilobar disease) who have disease progression in the liver with oxaliplatin or irinotecan based first line chemotherapyXx_NEWLINE_xXClinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosisXx_NEWLINE_xXClinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosisXx_NEWLINE_xXOngoing liver injuryXx_NEWLINE_xXAbnormal liver function test resultsXx_NEWLINE_xXCoagulation function tests not suggestive of severe liver dysfunctionXx_NEWLINE_xXPatients with known history of liver disorders.Xx_NEWLINE_xXBilirubin < 2.0 x ULN unless subject has Gilbert’s disease, low-grade hemolysis, or liver involvement with lymphomaXx_NEWLINE_xXOrgan dysfunction as defined by the following:\r\n* Symptomatic coronary artery disease or cardiac ejection fraction < 35% (or, if unable to obtain ejection fraction, shortening fraction of < 26%); if shortening fraction is < 26% a cardiology consult is required with the principal investigator (PI) having final approval of eligibility; ejection fraction is required if age > 50 years or there is a history of anthracycline exposure or history of cardiac disease\r\n* Diffusing capacity of the lung for carbon monoxide (DLCO) < 35%, TLC < 35%, forced expiratory volume (FEV)1 < 35% and/or receiving supplementary continuous oxygen; the FHCRC PI of the study must approve of enrollment of all patients with pulmonary nodules\r\n* Liver function abnormalities: Patient with clinical or laboratory evidence of liver disease will be evaluated for the cause of liver disease, its clinical severity in terms of liver function, bridging fibrosis, and the degree of portal hypertension; the patient will be excluded if he/she is found to have fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction evinced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin > 3mg/dL, or symptomatic biliary diseaseXx_NEWLINE_xXPatients with known liver disease (alcoholic, drug/toxin induced, genetic, or autoimmune);Xx_NEWLINE_xXVisceral (ie, liver or lung) metastases as only sites of metastasesXx_NEWLINE_xXPatients with Gilbert's syndrome uncomplicated by other liver disease may be eligible if agreed upon by the investigator and medical monitor for the sponsor.Xx_NEWLINE_xXAcute or chronic liver, pancreatic or severe renal diseaseXx_NEWLINE_xXPatients who have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, or stable chronic liver disease per investigator assessment);Xx_NEWLINE_xXHave any other severe concurrent disease, or have a history of serious organ dysfunction or disease involving the heart, kidney, liver, or other organ system that may place the patient at undue risk to undergo treatmentXx_NEWLINE_xXPrior liver resection must have taken >2 months prior to randomizationXx_NEWLINE_xXPatients with clinical or laboratory evidence of liver disease will be evaluated for the cause of liver disease, its clinical severity in terms of liver function, and the degree of portal hypertension; patients will be excluded if they are found to have fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction evinced by prolongation of the prothrombin time, ascites related to portal hypertension, bridging fibrosis, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin > 3 mg/dL, or symptomatic biliary diseaseXx_NEWLINE_xXCancer that has spread to the liver or brainXx_NEWLINE_xXknown active or symptomatic viral hepatitis, chronic liver disease or liver cirrhosis;Xx_NEWLINE_xXParticipants with Hepatitis B or C are eligible on the condition that they have adequate liver function as defined by Inclusion Criterion 9.Xx_NEWLINE_xXClinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosisXx_NEWLINE_xXAny chronic or concurrent acute liver disease, including viral hepatitisXx_NEWLINE_xXChronic liver disease (e.g., cirrhosis)Xx_NEWLINE_xXCurrent active liver or biliary disease.Xx_NEWLINE_xXClinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosisXx_NEWLINE_xXAny other severe concurrent disease, or have a history of serious organ dysfunction or disease involving the heart, kidney, liver or other organ system that may place the patient at undue risk to undergo therapy with ibrutinib and rituximabXx_NEWLINE_xXAcceptable liver functionXx_NEWLINE_xXClinically confirmed diagnosis of HCC according to American Association for the Study of Liver Diseases (AASLD) criteria, including cirrhosis of any etiology or with chronic hepatitis B or C infection criteriaXx_NEWLINE_xXPatients with the following organ dysfunction:\r\n* Left ventricular ejection fraction < 35%\r\n* Corrected diffusion capacity of carbon monoxide (DLCO) < 35% or receiving supplemental continuous oxygen\r\n* Liver abnormalities: fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, alcoholic hepatitis, esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction as evidences by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis, or symptomatic biliary diseaseXx_NEWLINE_xXSubjects with known history, or clinical or laboratory evidence of liver diseaseXx_NEWLINE_xXAcute or chronic liver or severe renal diseaseXx_NEWLINE_xXKnown clinically significant liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; fatty liver; and inherited liver diseaseXx_NEWLINE_xXKnown chronic liver disease, autoimmune hepatitis, or sclerosing cholangitisXx_NEWLINE_xXKnown clinically significant liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; and inherited liver diseaseXx_NEWLINE_xXEligible study subjects must exhibit acceptable liver, renal, and coagulation function as assessed by laboratory tests.Xx_NEWLINE_xXHas a history or presence of inadequate liver, renal, hematopoietic and/or cardiac function parameters outside protocol-defined rangeXx_NEWLINE_xXLiver transaminases within 2.5 times ULNXx_NEWLINE_xXPatients with the diagnosis of hepatocellular carcinoma (HCC) currently being evaluated for liver transplantation and considered for downstagingXx_NEWLINE_xXPatients have known chronic liver disease (i.e., cirrhosis)Xx_NEWLINE_xXHepatobiliary diseases including biliary tract diseases, autoimmune hepatitis, inflammation, fibrosis, cirrhosis of liver caused by viral, alcohol, or genetic reasons; Gilbert’s disease is allowed if TBil is =< 1.5 x ULNXx_NEWLINE_xXPatients must have liver metastases.Xx_NEWLINE_xXHistory of current evidence of malabsorption or liver diseaseXx_NEWLINE_xXAcute or chronic liver disease or severe renal disease considered unrelated to the cancerXx_NEWLINE_xXAny of the following liver findings: ALT >2.5xULN, ALT > 5xULN with liver metastases/tumor infiltration, Bilirubin >1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%), Current active liver or biliary disease (with the exception of Gilbert's syndrome or asymptomatic gallstones, liver metastases or otherwise stable chronic liver disease per investigator assessment). NOTE: Stable chronic liver disease should generally be defined by the absence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, esophageal or gastric varices, persistent jaundice or cirrhosisXx_NEWLINE_xXPatients with any distant metastasis (liver, lung, bone, brain)Xx_NEWLINE_xXKnown clinically significant liver disease, including active viral, alcoholic, or other hepatitis, cirrhosis, fatty liver, and inherited liver diseaseXx_NEWLINE_xXPatients who have received liver transplantationXx_NEWLINE_xXHistory of clinically significant liver abnormalities other than liver metastasisXx_NEWLINE_xXHas clearly resectable colon cancer liver metastases (CCLM), for example oligometastatic disease involving only one lobe of the liver. Subjects with suspected resectable CCLM should undergo evaluation by a liver surgeon prior to enrollment to document the incurable nature of their disease.Xx_NEWLINE_xXFor patients with abnormal liver function tests (LFTs) as the sole manifestation of cGVHD, documented GVHD on liver biopsy will be required prior to enrollment; abnormal LFTs in the context of active cGVHD involving other organ systems may also be permitted if the treating physician documents the abnormal LFTs as being consistent with hepatic cGVHD, and a liver biopsy will not be mandated in this situationXx_NEWLINE_xXFor participants with abnormal liver function tests (LFTs) as the sole manifestation of cGVHD, documented GVHD on liver biopsy will be required prior to enrollment; abnormal LFTs in the context of active cGVHD involving other organ systems may also be permitted if the treating physician documents the abnormal LFTs as being consistent with hepatic cGVHD, and a liver biopsy will not be mandated in this situationXx_NEWLINE_xXActive or symptomatic viral hepatitis or chronic liver diseaseXx_NEWLINE_xXPatients must not have known liver disease such as cirrhosis, decompensated liver disease, active or chronic hepatitisXx_NEWLINE_xXPatients with acute or chronic liver, renal disease or pancreatitisXx_NEWLINE_xXCurrent active hepatic or biliary disease (with exception of subjects with Gilbert's syndrome, asymptomatic gallstones, liver metastases, or stable chronic liver disease per investigator assessment)Xx_NEWLINE_xXSubjects who have current active hepatic or biliary disease (with exception of participants with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment)Xx_NEWLINE_xXAcute or chronic liver or pancreatic disease.Xx_NEWLINE_xXKnown active liver disease (cirrhosis, chronic viral hepatitis, autoimmune liver disease or other known clinically significant active liver disease)Xx_NEWLINE_xXHistory of chronic liver disease.Xx_NEWLINE_xXOther serious medical conditions that may be expected to limit life expectancy to less than 1 year (e.g., liver cirrhosis).Xx_NEWLINE_xXAcceptable liver function defined as:Xx_NEWLINE_xXSubjects with liver cirrhosis (as determined by the investigator)Xx_NEWLINE_xXHistory of alcohol abuse or chronic liver disease (other than metastatic disease to the liver)Xx_NEWLINE_xXKnown liver disease, autoimmune hepatitis, or sclerosing cholangitis.Xx_NEWLINE_xXTotal bilirubin >1.5 x ULN if no liver metastases or >3 x ULN in the presence of liver metastases (except in the case of Gilbert's disease)Xx_NEWLINE_xXActive or symptomatic viral hepatitis or chronic liver diseaseXx_NEWLINE_xXActive severe kidney or liver diseaseXx_NEWLINE_xXKnown clinically significant liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; fatty liver; and inherited liver diseaseXx_NEWLINE_xXA history of cirrhosis or other chronic liver diseaseXx_NEWLINE_xXClinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosisXx_NEWLINE_xXSymptomatic liver or visceral organ metastasisXx_NEWLINE_xXActive or symptomatic viral hepatitis or chronic liver diseaseXx_NEWLINE_xXPregnant or nursing females 2. HIV or HTLV-1/2 seropositivity 3. Known history of myelodysplasia 4. Known history of chronic active hepatitis or liver cirrhosis (if suspected by laboratory studies, should be confirmed by liver biopsy).Xx_NEWLINE_xXPatients who have undergone prior liver transplantation are ineligibleXx_NEWLINE_xXBarcelona Clinical Liver Cancer Classification (BCLC) B or CXx_NEWLINE_xXSGOT and SGPT >= 5 x ULN; liver biopsy preferred for such patientsXx_NEWLINE_xXPrior liver transplantation and on immunosuppressionXx_NEWLINE_xXChemoembolization is allowed if >= 4 weeks from study entry; there are 3 possible scenarios:\r\n* If patient has hepatic disease only: they need to have progressed in the liver since chemoembolization and have measureable disease by RECIST 1.1 in order to be eligible\r\n* If patient has hepatic and extrahepatic disease: they will need to have progressed inside OR outside the liver and have measureable disease by RECIST 1.1 in order to be eligibleXx_NEWLINE_xXPatients with acute or chronic liver, renal disease or pancreatitisXx_NEWLINE_xXAcute or chronic liver disease or severe renal disease considered unrelated to the cancerXx_NEWLINE_xXObtained within 2 weeks from study entry: SGOT, SGPT =< 5 X ULN if liver metastasis presentXx_NEWLINE_xXActive or severe liver disease (acute or chronic hepatitis, cirrhosis)Xx_NEWLINE_xXREGISTRATION EXCLUSION CRITERIA: Clinically important history of active liver disease, including viral or other hepatitis or cirrhosisXx_NEWLINE_xXOther serious medical conditions that may be expected to limit life expectancy to less than 2 years (e.g., liver cirrhosis).Xx_NEWLINE_xXAny known active liver disease, e.g. due to HBV, HCV, autoimmune hepatic disorders, or sclerosing cholangitisXx_NEWLINE_xXSubjects who have current active hepatic or biliary disease (with the exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment)Xx_NEWLINE_xXLiver metastasesXx_NEWLINE_xXPatients with Gilbert’s disease and absent hepatic pathology by history and clinical assessment maybe treated on study with bilirubin > the ULN for the institution if other liver function studies are within the normal rangeXx_NEWLINE_xXHave a history of liver or renal dysfunctionXx_NEWLINE_xXCurrent active hepatic or biliary disease (with exception of liver disease secondary to chronic GVHD, or patients with Gilbert's syndrome, asymptomatic gallstones, or stable chronic liver disease per investigator assessment)\r\n* Patients with abnormal liver function tests (bilirubin, alkaline phosphatase, alanine aminotransferase [ALT], aspartate aminotransferase [AST]) due to chronic GVHD are specifically not excluded from the study; this is a common manifestation of chronic GVHD, and thus a major target for the study therapyXx_NEWLINE_xXActive chronic liver diseaseXx_NEWLINE_xXSubjects must have no evidence of cirrhosis of the liver; fibrosis of the liver can be tested by Fibroscan or by liver biopsy; these should be performed within approximately a one year period prior to entry onto the studyXx_NEWLINE_xXCurrent active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment)Xx_NEWLINE_xXPatients with a history of pituitary or adrenal dysfunction, active or symptomatic viral hepatitis, or chronic liver disease are not eligibleXx_NEWLINE_xXPrior liver directed therapies will be permitted (i.e. chemoembolization, radioembolization) as long as target lesions in the liver have demonstrated growth since the liver directed treatmentXx_NEWLINE_xXPrior peptide receptor radionuclide therapy (PRRT) will be permitted as long as target lesions in the liver have demonstrated growth since the liver directed treatmentXx_NEWLINE_xXCirrhosis of the liverXx_NEWLINE_xXSubjects who have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment) are ineligibleXx_NEWLINE_xXAbnormal liver function tests (bilirubin more than 1.5xULRR, and ALT, AST, or ALP more than 2.5xULRR or 5.0xULRR if related to liver metastases).Xx_NEWLINE_xXPresence of symptomatic liver failure including ascites and hepatic encephalopathyXx_NEWLINE_xXKnown hepatitis B virus carriers who have liver function tests within the accepted limits are eligibleXx_NEWLINE_xXHistory of serious organ dysfunction or disease involving the heart, kidney, liver or other organ system that may place the patient at undue risk to undergo treatmentXx_NEWLINE_xXSubjects who have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment)Xx_NEWLINE_xXAcute or chronic liver disease or severe renal disease considered unrelated to the cancerXx_NEWLINE_xXActive liver disease, including viral or other hepatitis, or cirrhosisXx_NEWLINE_xXSubjects who have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment)Xx_NEWLINE_xXAdequate liver function Total Serum Bilirubin <=1.5 x upper limit of normal (ULN) Transaminases (AST/ALT) <=2.5ULN (if liver metastases are present, then <=5ULN is allowed) ALP <=2.5ULN (if liver and/or bone metastases are present, then <=5ULN is allowed)Xx_NEWLINE_xXPresence of acute or chronic liver, renal disease, or pancreatitisXx_NEWLINE_xXLiver abnormalities: fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, alcoholic hepatitis, esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction as evidenced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis, or symptomatic biliary diseaseXx_NEWLINE_xXCurrent active hepatic or biliary disease (with the exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases, or stable chronic liver disease per investigator assessment)Xx_NEWLINE_xXPatients with liver cirrhosis or any other impaired hepatic function as determined by serum enzymesXx_NEWLINE_xXAny severe and/or uncontrolled medical conditions or other conditions that, in the treating physician’s opinion, could adversely impact their ability to participate in the study; NOTE: patients on chronic oxygen therapy, those with liver disease such as cirrhosis, chronic hepatitis or chronic persistent hepatitis, or uncontrolled infections will be excludedXx_NEWLINE_xXActive infection (febrile and requiring IV/oral [PO] antibiotics), including hepatitis C or human immunodeficiency virus (HIV), or significant medical illness including renal, cardiac, pulmonary disease, or current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment)Xx_NEWLINE_xXPatients with clinical or laboratory evidence of liver disease would be evaluated for the cause of liver disease, its clinical severity in terms of liver function, and the degree of portal hypertension; patients will be excluded if they are found to have fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction evinced by prolongation of the prothrombin time, ascites related to portal hypertension, bridging fibrosis, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin > 3 mg/dL, or symptomatic biliary diseaseXx_NEWLINE_xXLIVER (ONLY APPLIES TO PATIENTS WITH METASTATIC LIVER LESIONS NOT PREVIOUSLY TREATED WITH RT):Xx_NEWLINE_xXPatients cannot have more than 3 liver lesionsXx_NEWLINE_xXCombined diameter of all liver lesions must be =< 6 cmXx_NEWLINE_xXActive viral, alcoholic, or other hepatitis; cirrhosis; fatty liver; and inherited liver diseaseXx_NEWLINE_xXAdequate haematological, renal (creatinine < 2xULN), cardiac and liver functionsXx_NEWLINE_xXHistory of serious liver diseaseXx_NEWLINE_xXd. Liver disease such as cirrhosis of the liver, decompensated liver disease, chronic active hepatitis needing anti-viral therapyXx_NEWLINE_xXCurrent active liver or biliary disease (except Gibler's syndrome or asymptomatic gallstones, liver metastases, or otherwise stable chronic liver disease)Xx_NEWLINE_xXAbnormal/inadequate blood values, liver and kidney functionXx_NEWLINE_xXAdequate liver function Total Serum Bilirubin <=1.5 x upper limit of normal (ULN) Transaminases (AST/ALT) <=2.5ULN (if liver metastases are present, then <=5ULN is allowed) ALP <=2.5ULN (if liver and/or bone metastases are present, then <=5ULN is allowed)Xx_NEWLINE_xXDiagnosis of liver cirrhosisXx_NEWLINE_xXChronic or active hepatitis B or hepatitis C; if questions about liver health, discuss with principal investigator (PI) and strongly consider liver biopsyXx_NEWLINE_xXSignificant organ dysfunction that would prevent compliance with conditioning, GVHD prophylaxis, or would severely limit the probability of survival:\r\n * 1) Symptomatic coronary artery disease or ejection fraction < 35% or other cardiac failure requiring therapy (or, if unable to obtain ejection fraction, shortening fraction of < 26%); if shortening fraction is < 26% a cardiology consult is required with the principal investigator (PI) having final approval of eligibility\r\n * 2) Diffusion capacity of the lung for carbon monoxide (DLCO) < 40% total lung capacity (TLC) < 40%, forced expiratory volume in one second (FEV1) < 40% and/or receiving supplementary continuous oxygen; the Fred Hutchinson Cancer Research Center (FHCRC) study PI must approve enrollment of all patients with pulmonary nodules\r\n * 3) Liver function abnormalities: patient with clinical or laboratory evidence of liver disease will be evaluated for the cause of liver disease, its clinical severity in terms of liver function, bridging fibrosis, and the degree of portal hypertension; the patient will be excluded if he/she is found to have fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction evinced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin > 3 mg/dL, or symptomatic biliary diseaseXx_NEWLINE_xXAcute liver disease or previously diagnosed liver tumor (benign or malignant)Xx_NEWLINE_xXabnormal/inadequate blood values, liver, and kidney functionXx_NEWLINE_xXLiver abnormalities: fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, alcoholic hepatitis, esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction as evidenced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis, or symptomatic biliary diseaseXx_NEWLINE_xXSevere liver or renal insufficiencyXx_NEWLINE_xXPatient with known chronic liver disease (i.e., chronic active hepatitis, and cirrhosis)Xx_NEWLINE_xXPatients with clinical or laboratory evidence of liver disease would be evaluated for the cause of liver disease, its clinical severity in terms of liver function, and the degree of portal hypertension; patients will be excluded if they are found to have fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, hepatic damage with bridging fibrosis, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices or hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction evidenced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin > 3 mg/dl, or symptomatic biliary diseaseXx_NEWLINE_xXSerious concurrent medical conditions including: serious heart disease, heart conduction abnormalities, persistent infection, uncontrolled psychiatric illness, liver cirrhosis, chronic liver disease, active or symptomatic viral hepatitis, any other condition that may place the subject at an increased risk or confound the results of the study.Xx_NEWLINE_xXHas hepatic dysfunction defined as Model for End-Stage Liver Disease (MELD) Score >12.Xx_NEWLINE_xXOngoing drug-induced liver injury, chronic active hepatitis C (HCV), chronic active hepatitis B (HBV), alcoholic liver disease, non-alcoholic steatohepatitis, primary biliary cirrhosis, extrahepatic obstruction caused by cholelithiasis, cirrhosis of the liver, or portal hypertension.Xx_NEWLINE_xXSubjects with unresolved veno-occlusive disease of the liver.Xx_NEWLINE_xXOngoing drug-induced liver injury, chronic active hepatitis C (HCV), chronic active hepatitis B (HBV), alcoholic liver disease, non-alcoholic steatohepatitis, primary biliary cirrhosis, extrahepatic obstruction caused by cholelithiasis, cirrhosis of the liver, or portal hypertension would be exclusion for idelalisib therapy but ibrutinib would be an optionXx_NEWLINE_xXPreserved liver functionXx_NEWLINE_xXPresence of advanced liver disease.Xx_NEWLINE_xXPrior history of chronic liver disease (eg, chronic alcoholic liver disease, autoimmune hepatitis, sclerosing cholangitis, primary biliary cirrhosis, hemachromatosis, non-alcoholic steatohepatitis [NASH]).Xx_NEWLINE_xXOngoing liver injuryXx_NEWLINE_xXOngoing drug-induced liver injury, active hepatitis C, active hepatitis B , alcoholic liver disease, non-alcoholic steatohepatitis, primary biliary cirrhosis, extrahepatic obstruction caused by cholelithiasis, cirrhosis of the liver, or portal hypertension.Xx_NEWLINE_xXPatient's total bilirubin must be ? 1.5 x ULN. The hepatic requirements are waived for patients with known or suspected liver involvement who would otherwise be eligible. Cardiac Function:Xx_NEWLINE_xXKnown clinically significant liver disease, including active viral, alcoholic, or other hepatitis, cirrhosis, fatty liver, and inherited liver diseaseXx_NEWLINE_xXDONOR: No evidence of significant liver abnormalitiesXx_NEWLINE_xXIneligible for liver transplantation per institutional criteria:\r\n* Age > 65 \r\n* Biologic model for end-stage liver disease (MELD) score > 22\r\n* Evidence of extrahepatic disease \r\n* Vascular invasion on imagingXx_NEWLINE_xXHistory of chronic liver disease.Xx_NEWLINE_xXAnother concurrent illness which would preclude study conduct and assessment, uncontrolled: medical condition, active infection, risk of bleeding, diabetes mellitus, or pulmonary disease, or alcoholic liver disease, or primary biliary cirrhosis.Xx_NEWLINE_xXPatients regardless of eligibility to liver transplant, who have a comorbid disease that might preclude completion of study follow-up.Xx_NEWLINE_xXSubjects who have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver involvement with NHL or stable chronic liver disease per treating investigator assessment)Xx_NEWLINE_xXPatients with acute or chronic liver, renal disease or pancreatitisXx_NEWLINE_xXSubject has confirmed cholestatic hyperbilirubenemia due to bile duct obstruction. Subjects who have liver dysfunction due to metastasis alone are excluded.Xx_NEWLINE_xXAny other severe concurrent disease, or serious organ dysfunction or disease involving the heart, kidney, liver, or other organ system that may place the patient at undue risk to undergo the proposed therapyXx_NEWLINE_xXPrior surgery for the IHC; (liver resection is not allowed)Xx_NEWLINE_xXPatients must have liver-only or liver-predominant disease to be eligible for this study; liver predominant disease is defined dominant metastatic burden in the liver, with extra-hepatic disease that is judged by the investigator as unlikely to be life threatening within 3 monthsXx_NEWLINE_xXPatients with previous chemoembolization to liver metastasesXx_NEWLINE_xXSevere impairment of your kidney or liver functionXx_NEWLINE_xXEnd-stage liver disease unrelated to tumorXx_NEWLINE_xXOngoing liver injuryXx_NEWLINE_xXHave been treated with biologics (eg, antibodies targeting VEGFR or EGFR) after liver resection unless the administration of the biologic started prior to liver resection and continued after liver resection only to complete a pre-specified number of cycles.Xx_NEWLINE_xXPatients with liver metastases that replace greater than 30% of the liver parenchymaXx_NEWLINE_xXSigns or symptoms of progressive or uncontrolled liver diseaseXx_NEWLINE_xXPresence of main portal vein invasion by liver cancerXx_NEWLINE_xXHave other severe concurrent disease or serious organ dysfunction involving the heart, kidney, liver or other organ system that may place the patient at undue risk to undergo treatmentXx_NEWLINE_xXAcceptable liver functionXx_NEWLINE_xXAcceptable liver function:Xx_NEWLINE_xXSignificant liver disease or metastatic disease to the liverXx_NEWLINE_xXSubjects who have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment)Xx_NEWLINE_xXKnown clinically significant liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; fatty liver; and inherited liver diseaseXx_NEWLINE_xXClinically significant history of liver disease, including cirrhosis and current alcohol abuseXx_NEWLINE_xXConfirmed diagnosis of HCC by histological examination or by non-invasive criteria according to European Association for the Study of the Liver (EASL) or American Association for the Study of Liver Disease (AASLD) guidelines (Part 1, 2 and 3).Xx_NEWLINE_xXHepatobiliary diseases including biliary tract diseases, autoimmune hepatitis, inflammation, fibrosis, or cirrhosis of liver caused by viral, alcohol, or genetic reasons. Gilbert's disease is allowed if total bilirubin is ?1.5 × ULN.Xx_NEWLINE_xXPatients with abnormal liver function will be eligible and will be grouped according to the criteria described; patients with active hemolysis should be excluded; no distinction will be made between liver dysfunction due to metastases and liver dysfunction due to other causesXx_NEWLINE_xXKnown history of clinically significant liver disease, including active viral hepatitis and cirrhosisXx_NEWLINE_xXClinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosisXx_NEWLINE_xXHistory of cirrhotic liver diseaseXx_NEWLINE_xXClinically significant history of liver disease, including viral or other known hepatitis, current alcohol abuse, or cirrhosisXx_NEWLINE_xXPatients with history of hepatic dysfunction or hepatic disease and abnormal liver function tests; patients who have a history of hepatic dysfunction or hepatic disease and normal liver function tests will be eligible to participateXx_NEWLINE_xXKnown history of clinically significant liver disease, including active viral hepatitis and cirrhosisXx_NEWLINE_xXPatients with chronic hepatitis C virus may be enrolled if there is no clinical/laboratory evidence of cirrhosis AND the patient’s liver function tests fall within the parameters setXx_NEWLINE_xXKnown history of drug-induced liver injury, chronic active hepatitis B infection, chronic active hepatitis C infection, alcoholic liver disease, non-alcoholic steatohepatitis, primary biliary cirrhosis, ongoing extrahepatic obstruction caused by stones, cirrhosis of the liver, or portal hypertensionXx_NEWLINE_xXAcute or current active (requiring anti-viral therapy) hepatic or biliary disease (with the exception of subjects with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment)Xx_NEWLINE_xXPre-existing liver disease (e.g. cirrhosis, chronic hepatitis B or C, nonalcoholic steatohepatitis, sclerosing cholangitis)Xx_NEWLINE_xXOngoing drug-induced liver injury, chronic active Hepatitis C Virus (HCV), chronic active Hepatitis B Virus (HBV), HIV, alcoholic liver disease, non-alcoholic steatohepatitis, primary biliary cirrhosis, extrahepatic obstruction caused by cholelithiasis, cirrhosis of the liver, or portal hypertensionXx_NEWLINE_xXConfirmed to have HCC as described by the American Association for the Study of Liver Disease (AASLD).Xx_NEWLINE_xXPresence of ascites that preclude biopsy of liver lesions.Xx_NEWLINE_xXAcceptable liver functionXx_NEWLINE_xXActive liver disease with elevated transaminases > 2 x ULNXx_NEWLINE_xXOngoing drug-induced liver injury, alcoholic liver disease, non-alcoholic steatohepatitis, primary biliary cirrhosis, extrahepatic obstruction caused by cholelithiasis, cirrhosis of the liverXx_NEWLINE_xXPatients with > 3 liver metastases at time of enrollmentXx_NEWLINE_xXActive or symptomatic viral hepatitis or chronic liver diseaseXx_NEWLINE_xXClinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosisXx_NEWLINE_xXLiver function tests (LFTs) > 2 x nlXx_NEWLINE_xXPatients should have hepatic function (alkaline phosphatase, AST and ALT) < ULN and renal functions with serum creatinine - <1.5 x UNL. If a patient has liver metastasis and/or a history of liver disease - they will receive a lower dose of the drug per treatment protocol.Xx_NEWLINE_xXKnown history of clinically significant liver disease, including active viral hepatitis and cirrhosisXx_NEWLINE_xXActive or symptomatic viral hepatitis or chronic liver diseaseXx_NEWLINE_xXClinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosisXx_NEWLINE_xXPatients with known liver metastasesXx_NEWLINE_xXHistory of chronic liver disease.Xx_NEWLINE_xXCurrent active liver or biliary disease (with the exception of Gilbert's syndrome or asymptomatic gallstones, liver metastases or otherwise stable chronic liver disease per investigator's assessment).Xx_NEWLINE_xXActive or symptomatic viral hepatitis or chronic liver disease, including Child-Pugh class B and C liver diseaseXx_NEWLINE_xXAdvanced liver disease, including persistent aspartate transaminase (AST), alanine transaminase (ALT), or total bilirubin value >3 × the upper limit of normal, liver biopsy demonstrating cirrhosis, extensive bridging fibrosis, or active hepatitis.Xx_NEWLINE_xXLiver/renal dysfunctionXx_NEWLINE_xXLiver function:Xx_NEWLINE_xXActive or symptomatic viral hepatitis or chronic liver diseaseXx_NEWLINE_xXHistory of chronic liver diseaseXx_NEWLINE_xXTotal bilirubin =< 1.5 x ULN (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver involvement with NHL or stable chronic liver disease per investigator assessment)Xx_NEWLINE_xXSubjects who have currently active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver involvement with NHL or stable chronic liver disease per investigator assessment)Xx_NEWLINE_xXCurrent active liver or biliary disease (with the exception of Gilbert's syndrome or asymptomatic gallstones, or liver metastases).Xx_NEWLINE_xXPresence of less than 70% liver involvement by cancerXx_NEWLINE_xXPatients must not have current active hepatic or biliary disease (with exception of patients with Gilbert’s syndrome, asymptomatic gallstones, or stable chronic liver disease per investigator assessment)Xx_NEWLINE_xXKnown clinically significant history of liver disease consistent with Child-Pugh Class B or C, including active viral or other hepatitis, current drug or alcohol abuse, or cirrhosisXx_NEWLINE_xXKnown clinically significant liver disease, including active viral, alcoholic, or other hepatitis, cirrhosis, and inherited liver disease or current alcohol abuseXx_NEWLINE_xXAlkaline phosphatase =< 3 ULN; if total ALP is > 3 x ULN (in the absence of liver metastasis) or > 5 x ULN in subjects with liver metastasis AND the subject is known to have bone metastases, then liver ALP iso-enzyme should be used to assess liver function rather than total ALPXx_NEWLINE_xXClinically significant liver disease, including active viral, alcoholic or other hepatitis, cirrhosis, or current alcohol abuseXx_NEWLINE_xXActive or symptomatic viral hepatitis or chronic liver diseaseXx_NEWLINE_xXPulmonary or brain metastasis, liver metastasis is allowed if LFTs are not elevatedXx_NEWLINE_xXClinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosisXx_NEWLINE_xXPatients with acute or chronic liver, renal disease, or pancreatitisXx_NEWLINE_xXCurrent active liver or biliary disease. Exception: Subjects with Gilbert's syndrome or asymptomatic gallstones, liver metastases related to indolent NHL or otherwise stable chronic liver disease per investigator assessment, are eligible.Xx_NEWLINE_xXUveal Melanoma with liver metastasisXx_NEWLINE_xXHave received a liver transplant, or have liver cirrhosis with a Child-Pugh Stage of B or C.Xx_NEWLINE_xXHave hepatocellular cancer, liver cirrhosis with a Child-Pugh stage of B or higher, or have received a liver transplantXx_NEWLINE_xXClinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosisXx_NEWLINE_xXPatients with known liver diseaseXx_NEWLINE_xXHistory of liver disease, such as cirrhosis or chronic active hepatitis B and CXx_NEWLINE_xXUnderlying chronic liver disease with evidence of severe liver impairment.Xx_NEWLINE_xXClinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosisXx_NEWLINE_xXCurrent active liver or biliary disease (with the exception of Gilbert's syndrome or asymptomatic gallstones).Xx_NEWLINE_xXPatients with acute hepatitis or end stage liver diseaseXx_NEWLINE_xXHistory or current hepatitis or other liver diseaseXx_NEWLINE_xXHistory or current evidence of malabsorption or liver disease that would impair the absorption of Itraconazole as measured by liver function tests within the past one year prior to enrollmentXx_NEWLINE_xXliver, pancreatic or severe renal disease unrelated to disease under studyXx_NEWLINE_xXLiver cirrhosis with greater than grade 1 stage 1 inflammation/fibrosisXx_NEWLINE_xXAny other severe concurrent disease, or have a history of serious organ dysfunction or disease involving the heart, kidney, liver, or other organ system that may place the participant at undue risk to undergo treatmentXx_NEWLINE_xXhave acute or currently active/requiring anti-viral therapy hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease);Xx_NEWLINE_xXInadequate kidney, liver, blood clotting functionXx_NEWLINE_xXHave current active hepatic or biliary disease (with exception of subjects with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment).Xx_NEWLINE_xXPatients with advanced malignant hepatic tumors (liver metastases that replace more than 30% of the liver parenchyma)Xx_NEWLINE_xXActive liver disease including cirrhosis or hepatitisXx_NEWLINE_xXPatients must have acceptable neutrophil and platelet counts as well as adequate kidney and liver function.Xx_NEWLINE_xXInadequate liver function as evidenced by any of the following:Xx_NEWLINE_xXLiver function tests with values > 3 x ULNXx_NEWLINE_xXLiver metastasesXx_NEWLINE_xXHistory of veno-occlusive disease of the liverXx_NEWLINE_xXKnown history of chronic liver disease (other than Gilbert’s syndrome)Xx_NEWLINE_xXClinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosisXx_NEWLINE_xXActive uncontrolled stage 4 acute liver GVHD prior to administration of ibrutinibXx_NEWLINE_xXCurrent active liver or biliary disease (with the exception of Gilbert's syndrome or asymptomatic gallstones, liver metastases, or otherwise stable chronic liver disease per investigator assessment).Xx_NEWLINE_xXEvidence of severe uncontrolled systemic disease or other comorbidity that precludes liver surgeryXx_NEWLINE_xXPatients with history of severe liver disease, defined as and confirmed by albumin less than 3.Xx_NEWLINE_xXHistory of liver diseaseXx_NEWLINE_xXPatients with history of hepatic dysfunction or hepatic disease and abnormal liver function tests (previously documented alanine aminotransferase greater than 40 IU/dL and/or plasma aspartate aminotransferase greater than 45 IU/d); patients who have a history of hepatic dysfunction or hepatic disease but whose most recent liver function tests have been documented as normal will be eligible to participateXx_NEWLINE_xXPre-existing liver disease: elevated international normalized ratio (INR) > 1.4 or elevated transaminase levels, or patient medical history of cirrhosis, or liver diseaseXx_NEWLINE_xXPotential subjects will be excluded for a number of medical conditions that might represent a risk for riluzole (including history of allergic reaction to riluzole and evidence of liver disease) and potentially confound the relationship among CNS glutamate, inflammation and behavior/cognition, including: autoimmune or inflammatory disorders, chronic infectious diseases (e.g. human immunodeficiency virus [HIV], hepatitis B or C), pregnancy, neurologic disorders (including a history of serious head trauma or seizures), liver disease (as manifested as an elevation in liver transaminases), uncontrolled cardiovascular, metabolic, pulmonary or renal disease (as determined by medical history and laboratory testing)Xx_NEWLINE_xXNormal kidney and liver function (lab results must be within 45 days prior enrollment)Xx_NEWLINE_xXChronic liver diseaseXx_NEWLINE_xXPatients undergoing open elective liver resection for primary liver pathology (benign or malignant) or secondary metastatic liver disease, including patients undergoing concomitant surgical procedures (such as colorectal resection or debulking procedures), with no contraindication to the insertion of an epidural catheter (localized infection, septicemia, or pre-operative coagulopathy)Xx_NEWLINE_xXSignificant liver disease that would inhibit prescription of opioidsXx_NEWLINE_xXRecent cholecystectomy, liver resection, or biliary surgery within 12 months.Xx_NEWLINE_xXSignificant liver metastatic disease interfering with safe/effective percutaneous transhepatic biliary drainage (PTBD).Xx_NEWLINE_xXChronic hepatic diseaseXx_NEWLINE_xXPatients must have liver tumors requiring a major liver resection, defined as removing at least three anatomical segments in patients without liver disease and two segments in patients with cirrhosis/fibrosis of the liverXx_NEWLINE_xXClinical indication for a therapeutic liver resectionXx_NEWLINE_xXNo liver failureXx_NEWLINE_xXChronic liver disease or in participants without known liver disease, alanine aminotransferase (ALT) >= 3 x normalXx_NEWLINE_xXPatients with history of hepatic dysfunction or hepatic disease and abnormal liver function tests; patients who have a history of hepatic dysfunction or hepatic disease and normal liver function tests will be eligible to participateXx_NEWLINE_xXParticipants with end-stage liver disease (cirrhosis)Xx_NEWLINE_xXSevere liver disease (known cirrhosis Childs Pugh class B or C), or active hepatitisXx_NEWLINE_xXKnown clinically significant liver disease, including active viral, alcoholic, or other hepatitis, cirrhosis, fatty liver, and inherited liver disease (exception for participants in Arm A and Arm F)Xx_NEWLINE_xXDocumented liver disease with marked elevation of transaminases >3 x ULN or,Xx_NEWLINE_xXPatients with liver cirrhosisXx_NEWLINE_xXTotal bilirubin < 2.0 mg/dl; unless hepatic dysfunction is a manifestation of presumed cGVHD; for patients with abnormal liver function tests (LFTs) as the sole manifestation of active cGVHD, documented cGVHD on liver biopsy will be required prior to enrollment; abnormal LFTs in the context of active cGVHD involving other organ systems may also be permitted if the treating physician documents the abnormal LFTs as being consistent with active hepatic cGVHD, and a liver biopsy will not be mandated in this situationXx_NEWLINE_xXFor participants with abnormal liver function tests (LFTs) as the sole manifestation of cGVHD, documented GVHD on liver biopsy will be required prior to enrollment; abnormal LFTs in the context of active cGVHD involving other organ systems may also be permitted if the treating physician documents the abnormal LFTs as being consistent with hepatic cGVHD, and a liver biopsy will not be mandated in this situationXx_NEWLINE_xXPatients with normal hepatic function according to MD Anderson testing standards and no prior liver diseaseXx_NEWLINE_xXNo significant synthetic dysfunction of the liver; if there is a question of such, a liver biopsy should be performed for further assessmentXx_NEWLINE_xXHistory of hepatitis or liver diseaseXx_NEWLINE_xXPatients with liver cirrhosis (as determined by the investigator)Xx_NEWLINE_xXDiffuse intrahepatic metastases that involves > 10 % of the liverXx_NEWLINE_xXFor patients with abnormal liver function tests (LFTs) above the thresholds, documented cGVHD on liver biopsy will be required prior to enrollmentXx_NEWLINE_xXEvidence of severe uncontrolled systemic disease or other comorbidity that precludes liver or pancreatic surgeryXx_NEWLINE_xXActive or symptomatic viral hepatitis or chronic liver diseaseXx_NEWLINE_xXSevere liver disease (known cirrhosis Childs Pugh class B or C), or active hepatitisXx_NEWLINE_xXLiver: Subjects must have adequate liver functionXx_NEWLINE_xXAble to undergo:\r\n* Percutaneous or transjugular biopsy of cirrhotic liver at least 7 days prior to liver resection (surgical cohort), OR\r\n* A biopsy of the cirrhotic liver (non-surgical cohort)Xx_NEWLINE_xXWillingness to authorize collection of tissue from surgically-resected liver or clinical liver biopsy for analysesXx_NEWLINE_xXNon-surgical cohort only: pathology report from clinical liver biopsy (=< 3 months prior to pre-registration) demonstrates no histologic abnormalities associated with chronic hepatitis, steatohepatitis, fibrosis, or cirrhosisXx_NEWLINE_xXWomen with active liver disease, abnormal uterine bleeding, or prior diagnosis of endometrial hyperplasiaXx_NEWLINE_xXHistory of, or current, active or chronic liver disease even if transaminases have normalizedXx_NEWLINE_xXKnown non?alcoholic steatohepatitis (NASH) or non?alcoholic fatty liver disease (NAFLD)Xx_NEWLINE_xXModel for end-stage liver disease (MELD) > 20Xx_NEWLINE_xXHistory of severe kidney disease (e.g. chronic or acute kidney failure) with creatinine clearance below 30 and/or severe liver disease with liver tests over 4 times the upper normal levelXx_NEWLINE_xXPatients with clinical or laboratory evidence of liver disease should be evaluated in conjunction with the gastrointestinal (GI) consult service for the cause of the liver disease, its clinical severity, and the degree of portal hypertension; patients will be excluded if they are found to have fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, bridging fibrosis, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, refractory ascites related to portal hypertension, bacterial or fungal liver abscess, chronic viral hepatitis with total serum bilirubin > 3 mg/dl, or actively symptomatic biliary diseaseXx_NEWLINE_xXParticipants with a clinical diagnosis of cirrhosis based on the investigator's evaluation, confirmed by any one of following methods to define cirrhosis:\r\n* Established cirrhosis on liver biopsy (Meta-analysis of Histological Data in Viral Hepatitis [METAVIR] F4);\r\n* Computed tomography (CT) or magnetic resonance imaging (MRI) findings consistent with cirrhosis; nodular appearing liver with or without evidence of portal hypertension\r\n* Transient elastography (FibroScan) with a result > 12.5 kPa\r\n* FibroScan score > 0.75 and aspartate aminotransferase (AST) to platelet ratio index (APRI) > 2\r\n* Etiology of cirrhosis will not be considered in determining inclusion in the studyXx_NEWLINE_xXParticipant has ever experienced one or more hepatic decompensation events or a history of decompensated liver disease as listed below:\r\n* Clinical ascites\r\n* Variceal bleeding documented by endoscopy\r\n* Spontaneous bacterial peritonitis documented by positive culture\r\n* Hepatic encephalopathy\r\n* Hepatorenal syndrome (type 1 or 2)\r\n* Porto-pulmonary hypertension\r\n* Hepato-pulmonary hypertension\r\n* Any liver-related event which led to a hospitalization or a grade 4 eventXx_NEWLINE_xXAcute or chronic liver disease, evidence of hepatitis (infectious or autoimmune), cirrhosis or portal hypertensionXx_NEWLINE_xXHistory of hepatitis or liver dysfunctionXx_NEWLINE_xXKnown chronic liver disease (Child’s B cirrhosis)Xx_NEWLINE_xXAcute liver disease, unexplained transaminase elevations, or elevated serum calciumXx_NEWLINE_xXPatients with end stage liver disease or anticipated liver transplant within the next two years will be excluded; a history of liver transplant is not an exclusion per se, if patient does not meet stated hepatic criteriaXx_NEWLINE_xXPatients with history of pituitary or adrenal dysfunction, active or symptomatic viral hepatitis or chronic liver disease are not eligibleXx_NEWLINE_xXPatients with current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease)Xx_NEWLINE_xXCurrent active liver or biliary disease (with the exception of Gilbert's syndrome or asymptomatic gallstones, liver metastases or otherwise stable chronic liver disease per investigator's assessment).Xx_NEWLINE_xXSubject has known active liver disease, including viral hepatitis or cirrhosis.Xx_NEWLINE_xXactive (acute or chronic) or uncontrolled severe infection, liver disease such as cirrhosis, decompensated liver disease (except for Hep B and Hep C positive patients)Xx_NEWLINE_xXPatient must NOT be in liver failure as judged by the patient’s physicianXx_NEWLINE_xXHave known cirrhosis or other risk factors for HCC, based on American Association for the Study of Liver Diseases (AASLD) and European Association for the Study of the Liver (EASL) guidelines (applicable in each site jurisdictions)Xx_NEWLINE_xXIndividuals with history of liver disease in last 12 monthsXx_NEWLINE_xXPatients in liver failure as judged by the patient’s physicianXx_NEWLINE_xXLiver metastases on most recent prior M.D. Anderson CT examination.Xx_NEWLINE_xXPatients with liver failure are NOT eligible.Xx_NEWLINE_xXPatients with primary stage I, II, III liver cancer or metastatic tumor in the liver from any cancer siteXx_NEWLINE_xXDiagnosis of a non-HCC liver mass with one or more of the following:\r\n* Liver mass (>= 1 cm) that has suggestive imaging findings of a benign liver mass (adenoma, hemangioma, focal nodular hyperplasia)\r\n* Liver mass (>= 1 cm) that is biopsy proven metastatic disease (metastatic colorectal cancer, metastatic pancreatic cancer)\r\n* Liver mass (>= 1 cm) that is a non-HCC primary malignancy (cholangiocarcinoma)Xx_NEWLINE_xXHistory of liver disease within the last 12 monthsXx_NEWLINE_xXAcute renal dysfunction due to the hepato-renal syndrome or in the perioperative liver transplantation periodXx_NEWLINE_xXPatient has at least 1 focal lesion in liverXx_NEWLINE_xXPatient has:\r\n* Liver lesions that are untreated liver lesions or \r\n* Changing treatment regimen/type and/or receiving a new form of treatment and/or has been on a treatment break (‘holiday’) for liver lesionsXx_NEWLINE_xXPatients with confined liver disease or stable limited extrahepatic diseaseXx_NEWLINE_xXActive or symptomatic viral hepatitis or chronic liver diseaseXx_NEWLINE_xXPatients must have liver-dominant or liver-only metastatic disease from any primary histology; patients with primary hepatocellular or biliary cancer are also eligibleXx_NEWLINE_xXPatients not undergoing radioembolization to the liverXx_NEWLINE_xXPatients with primary or metastatic tumors in the lungs, liver, or pancreasXx_NEWLINE_xXHave acute or currently active/requiring anti-viral therapy hepatic or biliary disease (with the exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment)Xx_NEWLINE_xXGood kidney and liver functionXx_NEWLINE_xXPatients with confirmed or suspected liver lesionsXx_NEWLINE_xXBiopsy proven or clinically suspected advanced parenchymal liver diseaseXx_NEWLINE_xXClinically or radiographically suspected liver damage, hepatic steatosis, hepatitis, hepatic fibrosis or cirrhosisXx_NEWLINE_xXPersonal history of hepatitis or other liver diseasesXx_NEWLINE_xXEnd-stage liver disease unrelated to tumorXx_NEWLINE_xXVisceral (e.g. lung, liver) metastasesXx_NEWLINE_xXHistory of liver disease as defined with liver function tests (LFTs) above those in the inclusionXx_NEWLINE_xXHave a history of liver or renal dysfunctionXx_NEWLINE_xXHave a primary liver tumorXx_NEWLINE_xXThe presence of at least one lesion, measuring ? 2 cm, with characteristic arterial enhancement and venous washout in the setting of liver cirrhosis and/or hepatitis B or C infection.Xx_NEWLINE_xXCriteria 1, Participant is a candidate for hepatic surgery or local regional therapy of liver metastases with curative intentXx_NEWLINE_xXCriteria 2, More than one third of the liver is estimated to be involved with metastasesXx_NEWLINE_xXCurrent diagnosis of cancer, unstable cardiovascular disease, end-stage liver or kidney disease, or other major medical illnessXx_NEWLINE_xXSevere liver disease (e.g. cirrhosis, non-alcoholic steatohepatitis, sclerosing cholangitis)Xx_NEWLINE_xX