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Background: We investigated hepatitis B virus (HBV) infection cases, who were HBsAg negative by radioimmunoassay (RIA) and HBV DNA positive for their clinical characteristics, the S gene mutation of hepatitis B virus (HBV), and usefulness of other HBsAg immunoassay., Methods: Among the patients requested for HBV DNA quantification, 16 patients positive in HBV DNA but negative in HBsAg RIA (BNIBT HBsAg Kit, China) were enrolled. The "a" determinant of HBV S gene was sequenced and clinical characteristics were reviewed. Additional HBsAg assay was performed using Architect HBsAg kit (Abbott laboratories, USA) employing chemiluminescent immunoassay method., Results: Eleven of the 16 patients showed multiple mutations in the "a" determinant. These patients received liver transplantation several years ago and have been treated with hepatitis B immune globulin (HBIG) and antiviral drugs. G145R mutation was found in 8 patients and G145K, D144G, and D144A were also frequently found. Among 9 of the 11 patients tested for HBsAg by Architect HBsAg kit, 8 showed positive results. Among 4 of the remaining 5 patients, only 2 showed weak positive results (< or = 1 IU/mL) in Architect HBsAg kit., Conclusions: HBV DNA-positive/HBsAg RIA-negative results were mostly observed in the patients treated with HBIG after liver transplantation, in whom HBIG escape mutations were found. Majority of these cases were positive in Architect HBsAg assay, and it is recommended to use other HBsAg immunoassay methods that are more sensitive than RIA in the detection limit as well as in the detection of escape mutant in hospitals performing liver transplantation.

Hepatitis B virus (HBV) is a partially double stranded DNA virus with genetic diversity represented by eight genotypes (A to H). Natural course and response to treatment could be affected by HBV genotypes. HBV shows high rates of turn over in the absence of proof-reading ability. As a result, large amounts of quasispecies are produced naturally or antiviral-associated. HBV consists of four open reading frames, namely preS/S gene, precore/core gene, polymerase gene, and X gene. Mutations on preS gene can result in undetectable HBsAg even in case that HBV is replicating. Surface gene mutation leads to decreased binding affinity to anti-HBs, which is associated with a vaccine escape mutant. Precore mutation abolishes HBeAg whereas mutations on basal core promoter gene down-regulate the HBeAg production. Mutations on basal core promoter are associated with increased HBV replication and high incidence of progressive liver diseases such as liver cirrhosis and hepatocellular carcinoma. Mutations on polymerase genes are often induced by antiviral therapy. Emergence of antiviral-resistant mutation is the major cause of treatment failure. Furthermore, existence of prior antiviral-resistant mutations limits the options of subsequent antiviral agents. Therefore, judicious use of antivirals and selection of the most potent drug with the lowest resistance rate are of the utmost importance for the prevention of antiviral-associated mutants. Detailed knowledge and understanding of HBV genetic diversity and mutant would be critical to establish strategies for the diagnosis and management of HBV infection.

It is generally accepted that seroconversion of hepatitis B virus (HBV) surface antigen (HBsAg) to an antibody to HBsAg (anti-HBs) indicates clearance of HBV. Here we report a case of severe hepatitis that manifested during chemotherapy in a female patient with chronic lymphocytic leukemia (CLL) who had been initially seronegative for HBsAg and seropositive for anti-HBs. The patient received chlorambucil and prednisolone for the treatment of CLL. After 6 months the serum levels of aminotransferases were increased, and HBsAg and HBV DNA were present in serum. Lamivudine was administered immediately after confirming the HBV reactivation, which considerably improved jaundice and aminotransferase levels after 3 weeks. The patient was able to resume the chemotherapy whilst continuing lamivudine treatment. This case report highlights the need for physicians to be aware of the potential risk of HBV reactivation even in an HBsAg-negative person but with detectable anti-HBc and/or anti-HBs, underscoring the need for future studies that explore the role of antiviral prophylaxis in this setting.

Background and Aims: The etiology of acute viral hepatitis in Korea has been dynamically changing during the recent years. The aim of this study was to investigate the recent etiology and the clinical features of acute viral hepatitis in a single center of Korea., Methods: We performed a retrospective analysis of a prospective cohort of 55 patients who were diagnosed with acute viral hepatitis A to E during the period from May 2005 to August 2006. In addition to the clinically acute manifestations, the confirmatory serological tests were performed for the diagnosis of acute hepatitis A, B, C and E., Results: The proportion of patients with acute viral hepatitis A, B, C, E and others were 56.4% (n=31), 12.7% (n=7), 18.2% (n=10), 9.1% (n=5) and 3.6% (n=2), respectively. The mean age of the patients with acute hepatitis A, B, C and E were 29.1+/-4.38, 38.7+/-11.72, 45.3+/-17.62 and 32.4+/-6.58 years, respectively. There was no fatal case. All cases of acute hepatitis B and six out of ten cases of acute hepatitis C recovered spontaneously. Four out of the five patients with acute hepatitis E had no history of travel to endemic area., Conclusions: The most common etiology of acute viral hepatitis in Korea is hepatitis A virus, and hepatitis C and B virus were the next most common causes. The sporadic cases of acute hepatitis E were not rare, and coinfection of HAV and HEV was observed. A multicenter, prospective study is warranted in the future.

Backgrounds/aims: Occult HBV infection is characterized by the presence of HBV infection with undetectable HBsAg. This study was carried out to find out the frequency of HBV infection in HBsAg- negative patients., Methods: Fifty-six HBsAg-negative patients including 17 anti-HCV positive patients were evaluated. Patients were grouped according to their serological status; group A (anti-HBc+, anti-HBs-, n=16), B (anti-HBc+, anti-HBs+, n=26), and C (anti-HBc-, anti-HBs+/-, n=14). DNA was extracted from frozen liver biopsy specimen, and HBV DNA level was measured with real-time PCR., Results: Overall frequency of detectable intrahepatic HBV DNA was 34% (19/56). The frequency was 56% (9/16) in group A, 31% (8/26) in group B and 14% (2/14) in group C (P=0.01). Intrahepatic HBV DNA levels were as follows; 2,010 +/- 6,660 copies/mg in group A, 6,180 +/- 29,530 copies/mg in group B and 350 +/- 1,220 copies/mg in group C. The frequency of occult HBV infection was not increased in anti-HCV positive patients., Conclusions: Intrahepatic HBV DNA is frequently detected in anti-HBc positive, HBsAg-negative patients, although the concentration is low.

Background/aims: Perinatal infection with hepatitis B virus (HBV) may occur despite immunoprophylaxis. One of the important mechanisms for perinatal prophylaxis failure, might include HBV surface gene variants. Therefore, we screened Korean children, in whom perinatal prophylaxis failed, for HBV surface gene variants., Methods: Thirty-one children with perinatal HBV prophylaxis failure were selected. To amplify the major hydrophilic region of the HBV surface gene, nested PCR with primers targeted to nucleotides 237 to 706 was performed, and then sequencing was done., Results: All cases were shown to be PCR positive for HBV-DNA and genotype C. Nine out of 31 (29%) with perinatal prophylaxis failure had a nucleotide substitution at the major hydrophilic region of the gene; but only two cases (6.5%) had an amino acid substitution. One case was infected by wild type and variants of I126S, and the other by wild type and S114A+I126S, respectively., Conclusions: In Korea, compared to the previous studies of other nations, gene surface variants such as G145R do not appear to play an important role in perinatal immunoprophylaxis failure.

Background/aims: Viral suppression of the hepatitis B virus (HBV) can be induced by lamivudine, but the relapse seen in many patients after cessation of lamivudine therapy is troublesome. We thought that the host immune response is important to prevent viral relapse. We compared the frequency of HBV-specific CD8+ T cells in the peripheral blood and their expansion capacity after exposure to viral antigen between the patients showing sustained HBeAg seroconversion after use of lamivudine and those patients without sustained response., Methods: We analyzed HBV-specific CD8+ T cells that were isolated from the blood of 14 patients with HLA-A2 who showed lamivudine induced HBeAg seroconversion (HBV DNA < 0.5 pg/mL, and the cells were negative for HBeAg) at the end of lamivudine therapy. The purified T cells were directly stained ex vivo, after they had been stimulate with synthetic peptide, using the HBV core 18-27-specific HLA tetramer (Tc 18-27) and monoclonal antibody to CD8. The HBV viral load was quantified by the Amplicor HBV Monitor assay., Results: In patients with a sustained HBeAg response (the sustained group) for a duration of 15.5 months of follow-up, the median number of Tc 18-27 cells out of the 5 X 10(4) CD8+ T cells was 49.5 (15-135). On the contrary, in patients who experienced relapse (the relapsed group) during a median of 7.5 months of follow-up, the median number of Tc 18-27 cells out of the 5 X 10(4) CD8+ T cells was 13.5 (0-95). Especially, among patients with a viral load of HBV DNA < 1 X 10(3) copies at the end of treatment, the median number of Tc 18-27 cells out of 5 X 10(4) CD8+ T cells was 87 (45-135) in sustained group compared to 12 (6-50) in the relapsed group. All patients in the sustained group demonstrated a vigorous expansion of the core 18-27-specific CD8+ T cells after stimulation with viral peptide, in contrast to only 3 out of 8 patients in the relapsed group., Conclusions: This study demonstrates that the frequency and functional responsiveness of the circulating HBV-specific CD8+ T cells may be important for obtaining a sustained HBeAg response to lamivudine.

Background/aims: Although several clinical trials have suggested that lamivudine treatment can be very effective in patients with decompensated HBV-associated cirrhosis, its role and clinical efficacy are still uncertain because of the study designs. The aim of this study is to evaluate the efficacy of lamivudine in consecutively enrolled patients with decompensated cirrhosis., Methods: Twenty-four patients with decompensated HBV-associated cirrhosis (Child-Pugh score > or =8) were enrolled consecutively and treated with lamivudine 100 mg or 150 mg daily for 2-51 months (median: 16 months). They were all positive for HBV DNA and 21 were positive for serum HBeAg. Eight were Child-Pugh class B and 16 were class C. Clinical improvement was defined as a decrease of Child-Pugh score of at least 2 points., Results: At 6(th) month after lamivudine, all the patients cleared serum HBV DNA. The cumulative rates for HBeAg loss were 28.6% at 6(th) and 46.6% at 12(th) month. The cumulative viral breakthrough rates at 12(th) and 24(th) month were 20.0% and 37.5%. Fourteen patients (60.8%) showed clinical improvement, while 8 (34.8%) showed no change and 1 got worse, at 6(th) month after lamivudine. Most clinical improvement developed within the initial 6 months. The cumulative mortality rates were 20.8% at 1 year and 37.5% at 2 year., Conclusions: These data suggest that lamivudine can result in clinical improvement in about 60% of patients with HBV-related decompensated cirrhosis. Because most improvement occurs within 6 months after starting lamivudine, liver transplantation should be actively considered in cases which do not show clinical improvement despite 6-month lamivudine treatment.