Acute hepatic failure (AHF) in India almost always presents with encephalopathy within 4 weeks of the onset of acute hepatitis. Further subclassification of AHF into hyperacute, acute and subacute forms may not be necessary in this geographical area, where the rapidity of onset of encephalopathy does not seem to influence survival. Viral hepatitis is the cause in approximately 95–100% of patients, who therefore constitute a more homogeneous population than AHF patients in the West. In India, hepatitis E (HEV) and hepatitis B (HBV) viruses are the most important causes of AHF; approximately 60% of cases are caused by to these viruses. Hepatitis B virus core mutants are very important agents in cases where hepatitis B results in AHF in this country. Half of the patients with AHF admitted to our centre are female, one‐quarter of whom are pregnant. Therefore, pregnant females who contract viral hepatitis constitute a high‐risk group for the development of AHF. However, the outcome of AHF in this group is similar to that in non‐pregnant women and men. No association with any particular virus has been identified among sporadic cases of AHF.
In our centre, approximately one‐third of AHF patients survive with aggressive conservative therapy, whereas two‐thirds of deaths occur within 72 h of hospitalization. Cerebral oedema and sepsis are the major fatal complications. Both fungal and Gram‐negative bacteria are major causes of sepsis. Among patients with AHF, despite the presence of sepsis, its overt clinical features (i.e. fever, leucocytosis) may be absent and objective documentation of the presence of sepsis in such patients is achieved by repeated culture of various body fluids. It should be possible to develop simple, clinical prognostic markers for AHF in this geographical region, in order to identify patients suitable for liver transplantation.

Chronic infection with hepatitis B virus (HBV) in humans is strongly linked to the development of hepatocellular carcinoma (HCC). Activation of growth-regulatory genes may play a crucial role in carcinogenesis. Proto-oncogene expression has been shown to be higher in HCC tissue with integrated HBV DNA than in the normal liver. Earlier, we showed that the 3' end of the HBV major surface gene (S) (426-855 nucleotides of the S region) is a transactivator of the X promoter-enhancer regulatory element in co-transfection experiments. This region expresses a truncated carboxy terminal S protein extending from amino acid residues 102 to 226. In this study, the truncated S protein (trc-S) was examined for its enhancing activity on several viral and cellular regulatory elements. The results indicate that trc-S activates rous sarcoma virus long terminal repeat (LTR), human T-lymphotropic virus 2 LTR, human immunodeficiency virus 1 LTR, and the c-jun and c-fos promoters. Electrophoretic mobility shift assays carried out to investigate its DNA-binding properties established that trc-S binds to HBV X promoter and oligonucleotides representing binding sites for the AP1 and TFIID transcription factors. The specificity of this interaction was confirmed by using competition experiments and supershift assays. These experiments suggest that trc-S is a transactivator of several cellular and viral promoters and that this activity is mediated by direct interaction with DNA.

Hepatitis G virus (HGV)/GB virus-C (GBV-C) has been identified as a blood-borne agent with disputed pathogenicity. This virus belongs to the flaviviridae with a distant relationship to hepatitis C virus (HCV). Genetically divergent HGV isolates have been reported from different parts of the world. This study describes the prevalence of HGV in multitransfused thalassaemic children in India and genomic sequence variations in 11 HGV isolates from the same geographical location. Hepatitis G virus RNA was detected in 39.7% multitransfused thalassaemic children. The seroprevalence of hepatitis B virus (HBV) and HCV was 23.8% and 17.1%, respectively, and 11.4% had dual infection. The nucleotide sequence of a 166 bp HGV genomic segment from the putative capsid-envelope region (nucleotide; nt 578-743) from 11 Indian isolates was compared to the sequences available in the nucleotide databases. The isolates from India were 81.3-94.5% homologous to the isolates from other parts of the world. On phylogenetic analysis, it was observed that HGV isolates from India may belong to two genetically divergent types.

Liver Biopsy in Modern Medicine 336 associated antigen, Glial Fibrillary Acidic Protein (GFAP), is induced on pro-fibrotic cells such as HSCs, and is a definitive marker of fibrogenic pathway activation in this latter cell type (29). Studies of fibrosis mechanisms in human liver are limited. One longitudinal study, after liver transplantation, reported that increased density of GFAP in liver biopsy specimens predicted subsequent advanced fibrosis or cirrhosis (9). Although cells harboring GFAP were only presumed to be activated HSCs, the study concluded that 30% of cells in cirrhotic livers may be activated HSCs. However, the possibility of a direct effect of HCV on GFAP expression in hepatocytes was not investigated. The present study therefore examined the effect of HCV on hepatic fibrosis marker expression, using two human hepatoma cell line model systems, capable of supporting either non-productive HCV replication (HCV replicon, (22)), or productive HCV infection (genotype 2a infectious clone JFH1; (44)). The study also examined liver biopsy samples from HCV infected patients for the simultaneous presence of GFAP and HCV replicative intermediate RNA. Finally, microarrays were used to analyze expression of multiple cellular genes linked with liver fibrosis, in human hepatoma cell lines plus or minus HCV. The effect of HCV on differential expression of 153 genes (1, 3, 17, 28, 37) either involved in, or associated with, with the process of liver fibrosis, is reported. 2. Methods 2.1 Human liver biopsy specimens Thirty-two liver biopsy specimens, obtained under informed consent and per IRB-approved protocol, were available for study. All 32 subjects had chronic, active (viremic) HCV genotype 1 infections. During procurement, the specimens were immediately preserved in OCT buffer and snap frozen at the bedside. Parallel sections of the liver biopsies were reviewed by a single pathologist who was blinded to HCV status and all other data. Liver fibrosis severity, staged as 0 (no fibrosis) through 4 (cirrhosis), was assigned according to the system described by Batts and Ludwig (5). For the present study, the liver specimens were de-identified for all information except HCV replication status and fibrosis severity. Fresh thin sections were obtained for the GFAP immunostaining experiments described below. Parallel sections of all 32 liver biopsy specimens were assayed for GFAP expression by immunocytochemistry. 29 of the specimens had been previously analyzed for both HCV genomic (G) and replicative intermediate (RI) RNAs by strand-specific in situ hybridization (ISH). Details of the ISH assay, and assay results for a larger sample of hepatitis C cases, were previously reported (31). Of 29 specimens with both GFAP and HCV replication data, HCV RNA was determined as either positive (G+RI+; 20 specimens), or negative (G-RI-; 9 specimens), and GFAP staining level (% of cells per biopsy staining positive for GFAP, or %GFAP) was then analyzed as a function of HCV infection/replication status, and fibrosis stage. 2.2 Hepat...