In genome and transcriptome analyses of HCC samples, we found mutations in genes in the TGF-β signaling pathway in almost 40% of samples. These correlated with changes in expression of genes in the pathways; up-regulation of genes in this pathway would contribute to inflammation and fibrosis, whereas down-regulation would indicate loss of TGF-β tumor suppressor activity. Our findings indicate that therapeutic agents for HCCs can be effective, based on genetic features of the TGF-β pathway; agents that block TGF-β should be used only in patients with specific types of HCCs.

Hepatitis B virus (HBV)-associated acute liver failure (ALF) is a dramatic clinical syndrome due to a sudden loss of hepatic cells leading to multiorgan failure. The mechanisms whereby HBV induces ALF are unknown. Here, we show that liver tissue collected at the time of liver transplantation in two patients with HBVassociated ALF is characterized by an overwhelming B cell response apparently centered in the liver with massive accumulation of plasma cells secreting IgG and IgM, accompanied by complement deposition. We demonstrate that the molecular target of these antibodies is the hepatitis B core antigen (HBcAg); that these antibodies display a restricted variable heavy chain (V H ) repertoire and lack somatic mutations; and that these two unrelated individuals with ALF use an identical predominant V H gene with unmutated variable domain (IGHV1-3) for both IgG and IgM anti-HBc antibodies, indicating that HBcAg is the target of a germline human V H gene. These data suggest that humoral immunity may exert a primary role in the pathogenesis of HBV-associated ALF.

The influence of steatosis and of other donor and recipient characteristics in affecting liver performance post-orthotopic liver transplantation (OLT) was evaluated in 311 consecutive liver transplantations made in 278 patients. Donor variables considered were age, sex, blood group, cause of death, intensive care unit (ICU) days, need for vasopressors, hepatic enzymes and bilirubin, total and warm ischemia time, and macro- and microvescicular steatosis. Recipient variables considered were age, sex, blood group, biliary output, and post-OLT peak levels of hepatic enzymes. Patient and graft survival were the main outcome indicators. In the multivariate analysis, macrovescicular steatosis involving 25% or more of the hepatocytes was the only variable independently associated with shorter patient survival (p < 0.05). Five (62.5%) of the eight livers with macrovescicular steatosis involving 25% or more of the hepatocytes incurred in a delayed non-function (DNF) and one (12.5%) in a primary non-function (PRNF). The incidence of DNF and PRNF in the group with macrovescicular steatosis involving less than 25% of the liver cells was 1.6% (p < 0.001) and 2.3%, respectively. Microvescicular steatosis of any degree was not associated with a worse prognosis. Macrovescicular steatosis involving 25% or more of the hepatocytes identifies marginal livers, the use of which significantly increases the risk of graft non-function post-OLT.

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Occult Hepatitis B virus (o-HBVIn liver from patients with acute HBV infection, previous studies have reported that low levels of HBV replicative intermediates [HBV RNA and supercoiled (ccc) DNA] can be detected several years after clinical recovery from acute hepatitis. 4 -6 Moreover, o-HBV has been demonstrated in woodchucks infected with the Woodchuck Hepatitis virus (WHV) 7-10 ; after recovery from acute WHV infection a lifelong occult WHV infection develops with a low level of WHV replication both in liver and in lymphatic tissue.Although low serum levels of HBV DNA are distinctive features of o-HBV, 1,2 all patients remain persistently HBsAg negative without any biochemical or histological evidence of chronic hepatitis.The persistence of the HBV infection in HBsAgnegative carriers without clinical signs of chronic hepatitis appears to be the expression of a particular virushost interaction; it could be due to a strong active longlived CTL response capable of containing HBV expression and replication at very low level. [11][12][13] Latent HBV infection can be frequently detected by surrogate markers of previous HBV exposure (antibodies against surface and/or core antigens). It carries no risk of progression to cirrhosis or hepatocellular carci-