The long-term impact of acute self-limited hepatitis B on the liver is unknown. Fourteen patients were recalled at a median of 4.2 years (range, 1.8-9.5 years) after the onset of acute hepatitis B. All showed clinical and serologic recovery with circulating hepatitis B surface antigen (HBsAg) clearance. Antibody to HBsAg (anti-HBs) had developed in 12 patients. Nine underwent liver biopsies at a median of 7.2 years, and histologic findings were evaluated using Ishak scores. Serum samples and frozen liver tissue were subjected to real-time detection polymerase chain reaction (PCR) to quantify the surface and X regions of the hepatitis B virus (HBV) genome and qualitative PCR to detect the covalently closed circular (ccc) HBV DNA replicative intermediate. Three patients had low levels of circulating HBV DNA up to 8.9 years after the onset, whereas both HBV DNA surface and X regions were found in the liver of all 9 patients examined, including 7 negative for serum HBV DNA. Liver viral loads assessed by the 2 regions showed a significant correlation (r ‫؍‬ 0.946; P ‫؍‬ .008), and all patients tested positive for ccc HBV DNA. Liver fibrosis and mild inflammation persisted in 8 patients. The fibrosis stage had relation to peak serum HBV DNA in the acute phase (P ‫؍‬ .046) but not to liver viral loads in the late convalescent phase. T he clearance of circulating hepatitis B surface antigen (HBsAg) and appearance of antibody to HBsAg (anti-HBs) with normalization of liver function have been generally accepted as evidence of clinical and serologic recovery from acute hepatitis B. However, in chronic HBsAg carriers, there is growing evidence that hepatitis B virus (HBV) DNA sequences persist in the liver for years after seroclearance of HBsAg and seroconversion to anti-HBs. 1-3 Although the clinical and pathologic implications of occult HBV infection in the liver are unknown, viral eradication is unlikely to be achieved once chronic HBV infection has been established. The cytotoxic T-lymphocyte (CTL) response is weak or undetectable in chronic HBV infection. In contrast, a vigorous, polyclonal, and HBV-specific CTL response against multiple HBV epitopes is readily detectable during acute self-limited HBV infection. 4-7 HBV-specific CTLs further persist in the blood for several decades after recovery from acute hepatitis B. 7,8 In the face of an enhanced immune response leading to disease resolution, the virologic outcomes of acute self-limited hepatitis B may differ from those of HBsAg seroclearance and anti-HBs seroconversion in the course of chronic HBV infection.At present, the long-term histologic and virologic impact of acute self-limited hepatitis B on the liver is unexplored. Studies using polymerase chain reaction (PCR) to detect HBV DNA sequences have shown that low levels of circulating HBV DNA can persist after clinical and serologic recovery from acute hepatitis B but tend to disappear after long-term follow-up. 9,10 Peripheral blood mononuclear cells are known as the site of persistent HBV infection long afte...

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Dual infection with hepatitis B and C viruses is often encountered in endemic areas of both viruses. However, understanding of the clinical and virological implications is limited. The aim of this study was to investigate the role of each virus in liver injury and the interaction between the two viruses in dual infection with hepatitis B and C viruses. Three patients who had chronic infection with both hepatitis B and C viruses were examined, and a longitudinal study of both serum hepatitis B virus DNA and hepatitis C virus RNA levels over 4 years was undertaken. The results were correlated with serum alanine aminotransferase levels. Serum alanine aminotransferase values showed a relationship with hepatitis B virus replicative levels, but not with hepatitis C virus replicative levels in all 3 patients. Serial changes of replicative levels of both viruses were studied, and it was found that hepatitis C virus replicative levels were enhanced after the decline of hepatitis B virus replication in 1 of the 3 patients. In the remaining 2 patients, a transient rise of hepatitis C virus replicative levels in association with a decrease of hepatitis B virus replication was also observed during part of the follow-up period. These findings indicate that hepatitis B virus may play a dominant etiological role in liver injury, and that a suppressive action between hepatitis B and C viruses may occur in dual infection with both viruses.

Clinical relevance of occult hepatitis C virus (HCV) and/or hepatitis B virus (HBV) infection(s) remains uncertain years after interferon (IFN) therapy for chronic hepatitis C. By 1993, 38 sustained virological responders (SVRs) showing HCV RNA clearance at 6 months post-treatment and 37 biochemical responders (BRs) with end-of-treatment alanine aminotransferase (ALT) normalization and subsequent 6-month stabilization within 2 x the upper limit of normal (ULN) were enrolled. They were monitored for 4.4-12 years (median 6.8), then 15 SVRs and 15 BRs underwent paired liver biopsies. Biopsy samples were tested for positive and negative HCV RNA strands, and HBV DNA surface and X sequences. All SVRs showed sustained serum HCV RNA clearance during follow-up, but hepatocellular carcinoma (HCC) developed in 4 (11%) SVRs. On paired liver biopsies, histological improvement was significant, but mild inflammation persisted in 87% of SVRs. Nonetheless, no HCV RNA sequence was amplified from liver tissues, and HBV DNA sequences were found in only one SVR. As for BRs, biochemical flare-up of >2 x ULN occurred at a 5-year risk of 41% (95% CI 24.7-56.4). The event was unpredictable but controllable by retreatment in 70%. Liver tissues after follow-up contained positive and negative HCV RNA strands, but no HBV DNA sequence was amplified. These results suggest that SVRs, albeit free of occult HCV and/or HBV infection(s) over a decade, retain mild liver inflammation and the risk of HCC. Occult HBV was also shown uninvolved in flare-up during follow-up of BRs.

that antibodies to HCV envelope glycoproteins may have a We studied the heterogeneity in the E2/NS1 hypervarineutralizing effect, 4,5 and the genetic drift in HVR1 is thought able region 1 of the hepatitis C virus (HCV) genome in to provide HCV with a better chance for adaptation to imrelation to the natural course after infection. The submune pressure. 6,7 jects were composed of 38 chronic hepatitis C carriers Very recently, it has been shown that patients with a hetwho had been followed for 9 to 218 months after the erogenous HCV population are less likely to respond to interonset of non-A, non-B (type C) hepatitis, being tested feron therapy than those with a homogenous HCV populamonthly for serum alanine aminotransferase levels. The tion, [8][9][10] indicating that the HVR1 quasispecies nature may complexity of the sequence heterogeneity was assessed be useful for predicting responses to antiviral therapy, as is by single-strand conformation polymorphism analysis.the case with HCV replicative levels and genotypes. [11][12][13][14][15] Thus, The quasispecies complexity had no relation to the route the HVR1 quasispecies seem to play an important role in of infection, the time from infection and the duration of persistent HCV infection. aminotransferase elevation after the onset. However, itAt present, factors affecting the development of the HVR1 had a significant relationship with the degree of aminoquasispecies nature in the natural course of chronic HCV transferase elevation in the course of the disease. The infection remain to be worked out. In this study, the degree quasispecies complexity was directly correlated with of complexity of HVR1 quasispecies was assessed in chronic the first peak of serum aminotransferase at the onset (r HCV carriers using single-strand conformation polymor-Å .48, P õ .01) and the mean aminotransferase levels phism (SSCP) analysis. 10 The results were correlated with during the period of persistent aminotransferase elevathe clinical courses of the patients after infection to study tion (r Å .58, P õ .01). Twenty-three of the 38 patients factors affecting the HVR1 quasispecies nature. were further followed for 24 months with biweekly alanine transaminase (ALT) tests. Their aminotransferase PATIENTS AND METHODS levels remained within the normal range during followup, and no significant change was seen in the quasispePatients. Sixty-two patients had undergone detailed follow-up cies complexity after this asymptomatic period. How-after the onset of non-A, non-B (type C) hepatitis in a hemodialysis unit. Forty of the 62 patients received no blood transfusion after the ever among the 23 patients, the quasispecies complexity onset and were subjected to the study. The remaining 22 patients, increased in six cases (26%) and decreased in five (22%).who received blood products during the follow-up, were excluded A significant direct relation was seen between changes because possible superinfection with HCV in contaminated blood in the quasispecies complexity and the mean aminoproducts ca...