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...

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.

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The long-term histological and virological outcomes of spontaneous circulating hepatitis C virus (HCV) clearance were studied in chronic liver disease. Between 1979 and 1984, three patients underwent laparoscopy for chronic non-A, non-B liver disease, and two were found to have cirrhosis and one with chronic active hepatitis. After HCV assays became available in 1990, they were positive persistently for HCV antibody without serum HCV RNA. Reductions of antibody levels to HCV core and/or nonstructural proteins were observed, and liver biopsies were undertaken between 1995 and 2000. Liver biopsies at 11-19 years after laparoscopy disclosed marked alleviation of liver inflammation and fibrosis in each case although a low grade of inflammation remained. The two patients with cirrhosis no longer showed histological features of cirrhosis, and the poor liver function in one patient had been ameliorated. Liver specimens from two patients were subjected to polymerase chain reaction to detect positive and negative HCV RNA strands and hepatitis B virus DNA. Only the positive HCV RNA strand was detected for one patient who had previously cirrhosis. Liver specimens were examined from another six nonviremic HCV-seropositive individuals without chronic liver disease. Five patients displayed low-grade liver inflammation without evident fibrosis, but none had any viral genome in the liver. These findings suggest that spontaneous circulating HCV clearance in chronic liver disease confers favorable liver histological outcome, although occult HCV infection persists. J. Med. Virol. 69:41-49, 2003.

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