The outcome of acute hepatitis B virus (HBV) infection is variable, influenced by host and viral factors. From 1982 through 2004, 301 patients with acute HBV infection entered a multi-center cross-sectional study in Japan. Patients with fulminant hepatitis (n ‫؍‬ 40) were older (44.7 ؎ 16.3 vs. 36.0 ؎ 14.3 years, P < .0017), less predominantly male (43% vs. 71%, P ‫؍‬ .0005), less positive for hepatitis B e antigen (HBeAg) (23% vs. 60%, P < .0001), less infected with subgenotype Ae (0% vs. 13%, P < .05), and more frequently with Bj (30% vs. 4%, P < .0001) than those with acute self-limited hepatitis (n ‫؍‬ 261). Precore (G1896A) and core-promoter (A1762T/G1764A) mutations were more frequent in patients with fulminant than acute self-limited hepatitis (53% vs. 9% and 50% vs. 17%, P < .0001 for both). HBV infection persisted in only three (1%) patients, and they represented 2 of the 23 infected with Ae and 1 of the 187 with the other subgenotypes (9% vs. 0.5%, P ‫؍‬ .032); none of them received antiviral therapy. In multivariate analysis, age 34 years or older, Bj, HBeAg-negative, total bilirubin 10.0 mg/dL or greater, and G1896A mutation were independently associated with the fulminant outcome. In in vitro transfection experiments, the replication of Bj clone was markedly enhanced by introducing either G1896A or A1762T/G1764A mutation. In conclusion, persistence of HBV was rare (1%) and associated with Ae, whereas fulminant hepatitis was frequent (13%) and associated with Bj and lack of HBeAg as well as high replication due to precore mutation in patients with acute HBV infection.

Several hepatitis B virus (HBV) subtypes (subgenotypes), HBV/Aa (A1 : Asia/Africa), Ae (A2 : Europe), Bj (B1 : Japan) and Ba (B2 : Asia), have been reported with respect to clinical differences between patients infected with these subtypes (subgenotypes). HBV genotype distribution among patients with chronic liver diseases was investigated in the Philippines, where such studies have not been carried out previously. One hundred sera were obtained from such patients, consisting of 32 chronic hepatitis (CH), 37 cirrhosis and 31 hepatocellular carcinoma (HCC) patients. Nine complete genomes and 100 core promoter/precore genes of HBV were sequenced directly. Phylogenetic analyses revealed 51 HBV/A (Aa/A1), 22 HBV/B and 27 HBV/C strains. Interestingly, most HBV/C strains in the Philippines formed a specific cluster distinct from previous HBV/C strains (C1-4), indicating a novel subtype (subgenotype), HBV/C5. Moreover, most HBV/B strains fell within the specific cluster of the HBV/B subtype (subgenotype) B5, with viral characteristics of HBV/Ba (B2) carrying a recombination with HBV/C over the precore and core genes. Of the three genotypes, HBV/B and HBV/C were significantly more prevalent than HBV/A in cirrhosis and HCC patients (P<0?02). The prevalence of the core promoter mutations T1762/A1764 was higher in HCC patients with HBV/B and HBV/C. Multivariate analysis indicated that age [odds ratio (OR) 3?43; 95 % confidence interval (CI) 1?04-11?36; P=0?044] and the core promoter mutation (OR 14?08;; P<0?001) were significant factors for HCC development. In conclusion, novel HBV subtypes (subgenotypes) C5 and B5 are prevalent in the Philippines, as well as HBV/Aa (A1).

Although combination therapy with interferon and ribavirin has improved the treatment for chronic hepatitis C virus (HCV) infection, the detailed anti-HCV effect of ribavirin in clinical concentrations remains uncertain. To detect the anti-HCV effect of ribavirin in lower concentrations, a sensitive and accurate assay system was developed using the reporter replicon system with an HCV genotype 2a subgenomic replicon (clone JFH-1) that exhibits robust replication in various cell lines. This reporter replicon was generated by introducing the luciferase reporter gene (instead of the neomycin resistance gene) into the subgenomic JFH-1 replicon. To assess the replication of this reporter replicon, luciferase activity was measured serially up to day 3 after transient transfection of Huh7 cells. The luciferase activity increased exponentially over the time course of the experiment. After adjustment for transfection efficiency and transfected cell viability, the impacts of interferon and ribavirin were determined. The administration of interferon and ribavirin resulted in dosedependent suppression of replicon RNA replications. The 50% inhibitory concentration of interferon and ribavirin was 1.80 IU/ml and 3.70 g/ml, respectively. In clinical concentrations, replications were reduced to 0.09% and 53.74% by interferon (100 IU/ml) and ribavirin (3 g/ml), respectively. Combination use of ribavirin and interferon enhanced the anti-HCV effect of interferon by 1.46-to 1.62-fold. In conclusion, we developed an accurate and sensitive replicon system, and the antivirus effect of interferon and ribavirin was easily detected within their clinical concentrations by this replicon system. This system will provide a powerful tool for screening new antiviral compounds against HCV.Hepatitis C virus (HCV) is a major public health problem, infecting an estimated 170 million people worldwide. HCV causes chronic liver diseases, including cirrhosis and hepatocellular carcinoma, because most patients fail to clear the virus and the persistent infection that follows (1,11,20). Current therapy for HCV-related chronic hepatitis is based on the use of interferon (IFN). However, virus clearance rates are limited to approximately 10 to 20% of cases treated with IFN only (9,23,26). Combination therapy with IFN and ribavirin improves the HCV clearance rate, although the molecular mechanism responsible for this improvement is not yet fully understood (23,25,26). However, some direct antiviral mechanisms of ribavirin have been proposed (19). One possible mechanism is the direct inhibition of HCV RNA-dependent RNA polymerase, and another possibility is the RNA mutagen effect that drives a rapidly mutating RNA virus over the threshold to "error catastrophe." The detection of these direct anti-HCV effects has been hampered by the lack of an appropriate sensitive system for evaluating HCV replication.Although HCV belongs to the Flaviviridae family and has a genome structure similar to those of the other flaviviruses (3, 27), efficient cell culture systems a...

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