No abstract available.
Hepatitis B virus/isolation & purification ; Hepatitis B, Chronic/diagnosis/*drug therapy/virology ; Humans ; Serologic Tests

Humans ; Hepatitis B Surface Antigens ; Hepatitis B/drug therapy* ; Hepatitis B virus/genetics* ; Antiviral Agents/therapeutic use* ; Hepatitis B, Chronic/diagnosis* ; DNA, Viral

PURPOSE: Although hepatitis B surface antigen (HBsAg)–negative, hepatitis B core antibody (anti-HBc)–negative patients are not considered to be at risk for hepatitis B virus (HBV)–related hepatitis, the actual risk remains to be elucidated. This study aimed to evaluate the risk of HBV-related hepatitis in HBsAg-negative, anti-HBc–negative patients receiving autologous stem cell transplantation (ASCT) for multiple myeloma (MM) or malignant lymphoma. MATERIALS AND METHODS: We retrospectively reviewed data from 271 HBsAg-negative patients (161 anti-HBc–negative and 110 anti-HBc–positive at the time of ASCT) who received ASCT for MM or lymphoma. The risk of HBV-related hepatitis was analyzed according to the presence of anti-HBc. HBV serology results at the time of ASCT were compared with those at the time of diagnosis of MM or lymphoma. RESULTS: Three patients (two anti-HBc–negative MMs and one anti-HBc–positive MM) developed HBV-related hepatitis after ASCT. The rate of HBV-related hepatitis did not differ among patients with or without anti-HBc status (p=0.843). HBV-related hepatitis more frequently occurred in MM patients than in lymphoma patients (p=0.041). Overall, 9.1% of patients (16.7% with MM and 5.4% with lymphoma) who were HBsAg–negative and anti-HBc–positive at the time of diagnosis had lost anti-HBc positivity during chemotherapy prior to ASCT. CONCLUSION: Our data suggest that HBsAg-negative, anti-HBc–negative patients at the time of ASCT for MM or lymphoma still might be at a risk for HBV-related hepatitis.
Diagnosis ; Drug Therapy ; Hepatitis B Surface Antigens ; Hepatitis B virus ; Hepatitis B* ; Hepatitis* ; Humans ; Lymphoma* ; Multiple Myeloma* ; Retrospective Studies ; Stem Cell Transplantation* ; Stem Cells*

Although safe and effective vaccines for hepatitis B virus (HBV) have been available for nearly three decades, this virus kills at least 600,000 people annually worldwide and remains the leading global cause of chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Because the HBV reverse transcriptase lacks a proofreading function, many HBV genotypes, subgenotypes, mutants, and recombinants exist. At least 10 HBV genotypes (HBV-A through J) with distinct geographic distributions have been identified; by definition, their complete genomic sequences diverge by more than 8%. HBV genotype is increasingly becoming recognized as an important factor in the progression and clinical outcome of HBV-induced disease. Infections by HBV-C or -D are significantly more likely to lead to cirrhosis and hepatocellular carcinoma than are infections by HBV-A or -B. Additionally, the hepatitis B e antigen seroconversion response to standard or pegylated interferon is more favorable in patients with HBV-A or -B than in those with HBV-C or -D. However, therapeutic responses to nucleos(t)ide analogues are generally comparable among HBV genotypes. In conclusion, genotyping of HBV is useful in identifying chronic hepatitis B patients who are at increased risk of disease progression, thereby enabling physicians to optimize antiviral therapy for these patients.
Antiviral Agents/therapeutic use ; Drug Resistance, Viral/genetics ; Genotype ; Hepatitis B/diagnosis/drug therapy/*epidemiology ; Hepatitis B virus/drug effects/*genetics/pathogenicity ; Humans ; Molecular Epidemiology ; Phenotype ; Prognosis

Hepatitis B virus (HBV) infection is the one of the most common causes of the liver diseases in Korea. Since the discovery of Australia antigen (hepatitis associated antigen, or HBsAg later), hepatitis associated antigen was tested widely. HBsAg was detected in 6.6~8.6% in 1980's. Later, it decreased to 5.7% in 1990's. Remarkably, seropositivity of the children deceased to 0.2% after the nationwide vaccination program. Although hepatitis B vaccines are highly effective, the failure rate of perinatal prophylaxis in babies born to HBsAg positive mother was reported to be 4.25%. Treatment of chronic hepatitis B was initiated after the introduction of interferon alpha. Lamivudine opened a new era of oral antiviral agent, and it has been widely used in Korea since 1999. Adefovir was proven to have a good efficacy for lamivudine-resistant chronic hepatitis B. Newer potent antiviral agents such as entecavir, clevudine, and telbivudine are available currently. Further studies are warranted for understanding factors influencing natural history, improving treatment outcomes, and overcoming vaccine non-response.
Acute Disease ; Antiviral Agents/therapeutic use ; Hepatitis B/diagnosis/drug therapy/*epidemiology/prevention & control ; Hepatitis B Surface Antigens/analysis ; Hepatitis B Vaccines/administration & dosage ; Hepatitis B, Chronic/epidemiology ; Humans ; Immunization Programs ; Korea/epidemiology ; Seroepidemiologic Studies

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.
Drug Resistance, Viral ; *Genetic Variation ; Genotype ; Hepatitis B/diagnosis/drug therapy/virology ; Hepatitis B virus/classification/*genetics ; Humans ; *Mutation ; Serotyping ; Virus Replication/genetics

Occult HBV infection is defined as the presence of HBV DNA in the liver (with or without detectable or undetectable HBV DNA in the serum) of individuals testing negative for HBsAg. Studies on occult HBV infection in hepatitis C patients have reported highly variable prevalence, because the prevalence of occult HBV infection varies depending on the hepatitis B risk factors and methodological approaches. The most reliable diagnostic approach for detecting occult HBV detection is through examination of liver DNA extracts. HCV has been suspected to strongly suppress HBV replication up to the point where it may be directly responsible for occult HBV infection development. However, more data are needed to arrive at a definitive conclusion regarding the role of HCV in inducing occult HBV infection. Occult HBV infection in chronic hepatitis C patients is a complex biological entity with possible relevant clinical implications. Influence of occult HBV infection on the clinical outcomes of chronic hepatitis C may be considered negative. However, recent studies have shown that occult HBV infection could be associated with the development of hepatocellular carcinoma and contribute to the worsening of the course of chronic liver disease over time in chronic hepatitis C patients. Nevertheless, the possible role of occult HBV infection in chronic hepatitis C is still unresolved and no firm conclusion has been made up until now. It still remains unclear how occult HBV infection affects the treatment of chronic hepatitis C. Therefore, in order to resolve current controversies and understand the pathogenic role and clinical impacts of occult HBV infection in chronic hepatitis C patients, well-designed clinical studies are needed.
Carcinoma, Hepatocellular/complications ; DNA, Viral/analysis ; Hepacivirus/genetics ; Hepatitis B/*complications/*diagnosis/drug therapy ; Hepatitis B virus/genetics ; Hepatitis C, Chronic/*complications/*diagnosis/drug therapy ; Humans ; Interferon-alpha/therapeutic use ; Liver/virology ; Liver Neoplasms/complications

BACKGROUND: Hepatitis B virus (HBV) detected in Korean patients almost belongs to genotype C, which is subdivided into subgenotype C1 (or Cs) and C2 (or Ce). It was recently reported that the risk of hepatocellular carcinoma is different between subgenotype C1 and C2. Thus, we studied the distribution of subgenotypes of HBV in Korean chronic hepatitis B (CHB) patients. METHODS: Specimens of 421 patients, who were diagnosed as CHB and underwent antiviral treatment, were used. After sequence analysis for HBV S gene, subgenotype was identified through phylogenetic analysis. Utilizing the same sequence data, the distribution of serotypes was also investigated. RESULTS: Among 421 patient specimens, genotype C was found in 419 (99.5%) and genotype B in 2 (0.5%). Among the genotype C strains, 417 strains were C2 subgenotype and 2 strains were mixed subgenotypes. However, C2 was evidently found even in the mixed sequences. Serotypes of 419 HBV with genotype C were classified as follows: adr, 385 (91.9%), adw, 22 (5.3%), ayr, 2 (0.4%) and mixed serotype, 10 (2.3%). Serotype of both HBV with genotype B was adw. CONCLUSIONS: It was found that HBV detected in Korean CHB patients under treatment almost all belong to the C2 (Ce) genotype.
Antiviral Agents/therapeutic use ; Blood Specimen Collection ; Genotype ; Hepatitis B virus/*classification/genetics ; Hepatitis B, Chronic/diagnosis/drug therapy/*virology ; Humans ; Korea ; Phylogeny ; Sequence Analysis, DNA ; Serotyping

BACKGROUND/AIMS: The post-treatment relapse patterns and efficacy of lamivudine re-treatment for relapsed patients have not been clarified. The aims of this study were to evaluate the relapse patterns after discontinuing therapy and the effects of lamivudine re-treatment for relapsed patients after HBeAg seroconversion. METHODS: Therapy was discontinued after HBeAg seroconversion in 121 patients. Sixty-six patients were relapsed and included in this study. The duration of lamivudine re-treatment therapy was from 6-35 (mean: 16) months. Post-retreatment monitoring continued for 1-40 (mean: 8.9) months. RESULTS: Among the relapsed 66 patients, 50 (75.8%) had HBeAg reappearance while 16 (24.2%) remained HBeAg negative and anti-HBe positive. The cumulative relapse rates at 3, 6, 12 and 24 months were 27%, 47%, 60% and 66%, respectively. Forty-two relapsers received lamivudine re-treatment. Among them, 33 were HBeAg positive and 9 were HBeAg negative and anti-HBe positive, Response was achieved in 31 of the 42 patients (73.8%). The cumulative response rates at 6, 9 and 12 months were 62%, 69% and 72%, respectively. Six patients (14.3%) developed viral breakthrough. All patients were HBeAg positive chronic hepatitis B. The duration of lamivudine re-treatment was the only predictable factor for response of lamivudine re-treatment. Therapy was discontinued after response in 21 patients. Eleven patients were relapsed, including 6 who were HBeAg positive and 5 who were HBeAg negative. Predictive factors for post-retreatment relapse were age and the duration of additional lamivudine therapy after response. CONCLUSIONS: The response rate of lamivudine re-treatment was significantly higher than in initial lamivudine treatments. The breakthrough and relapse rates, however, were similar in both initial and retreated lamivudine therapy.
Adult ; Antiviral Agents/*therapeutic use ; Female ; Hepatitis B e Antigens/blood ; Hepatitis B, Chronic/diagnosis/*drug therapy/virology ; Humans ; Lamivudine/*therapeutic use ; Male ; Recurrence ; Retreatment

Antineoplastic Agents ; pharmacology ; Hematopoietic Stem Cell Transplantation ; Hepatitis B ; diagnosis ; prevention & control ; Hepatitis B virus ; drug effects ; physiology ; Humans ; Neoplasms ; therapy ; Virus Activation