44 Liver abnormalities include (1) asymptomatic

elevation of serum ALT, alkaline phosphatase, and gamma glutamyl transferase as isolated laboratory abnormalities; (2) slowly progressive cholestatic jaundice; and (3) acute hepatocellular injury (hepatitic GVHD).37 Immunosuppressive therapy is not usually indicated when stable, minor elevation of serum enzymes is the only finding. In contrast, patients with jaundice may have histological findings of cholestatic GVHD—lymphocytic infiltration of bile ducts, extensive damage to, and Ruxolitinib cell line loss of, small bile duct epithelial cells, cholestasis, portal fibrosis and piecemeal necrosis.36, 44 Iron overload has been reported to mimic GVHD.15 Patients with steeply rising serum ALT with or without jaundice present a differential diagnosis

of viral infection, drug-injury, and hepatitic GVHD. Hepatitic GVHD is characterized by lobular hepatitis, portal inflammation, and damage to small bile ducts.37, 44 Cytochrome P450 1A2 appears to be a target antigen in GVHD. Acyclovir should be started pending results of viral tests, and if negative, treatment for GVHD started with a calcineurin inhibitor, prednisone 1-2 mg/kg/day, and ursodiol.37 Immunosuppressive drug treatment of cGVHD is successful in only half of patients: 50% are able to discontinue therapy after 5 years, 10% require treatment for longer, and 40% die without resolution of cGVHD.44 The Sorafenib molecular weight only liver-specific therapy is ursodeoxycholic acid (12-15 mg/kg/day), which results in normalization or improvement in liver enzymes.2, 45 Ductopenic GVHD is potentially reversible if ongoing immunologic destruction of epithelium ceases, but this process may take months

before resolution of jaundice.37 Liver transplantation, including living-donor 上海皓元医药股份有限公司 transplantation from the original hematopoietic cell donor,46 has been performed for patients with intractable hepatic GVHD. Hepatitis C virus infection in transplant survivors almost always results in chronic hepatitis.7, 47 In the first 10 years posttransplant, there is little liver-related morbidity.7 However, cirrhosis and end-stage liver disease are now prevalent among patients transplanted before the 1990s. Survivors of allogeneic transplant often have suboptimal platelet and granulocyte counts; the long half-life of pegylated interferon may be associated with rapid falls in these counts. Interferon-based therapy may also activate chronic GVHD. The serologic pattern of HBV infection may be atypical in HCT survivors, probably as a consequence of immunosuppression. Clearance of surface antigenemia is particularly likely if the donor was naturally anti-HBs-positive.1 Because HCT survivors are at increased risk of second malignancy or recurrent malignancy, HBV viral status should be reassessed prior to any chemotherapy (particularly rituximab and alemtuzumab) for these cancers.