Since the discovery of HBsAg in the early 1960s, presence of HBsAg in serum has only served to diagnose hepatitis B. Recent development in the quantitative measurement of serum HBsAg has enabled us to improve our understanding on the management of chronic hepatitis B. The surface antigen (sAg) level is at its highest in immune tolerance phase and decreases to the lowest level in immune control/inactive phase when HBeAg is cleared from the serum. Combination of serum sAg titer less than 1,000 IU/mL and serum HBV DNA less than 2,000 IU/mL can identify true inactive carrier from e antigen (eAg) negative hepatitis with diagnostic accuracy of 95%. During the natural course of chronic hepatitis B, changes or absolute level of sAg less than certain level can predict spontaneous sero-clearance of HBsAg. Although the decline of sAg is very slow in interferon (IFN)/pegylated interferon (PEG-IFN) or oral nucleos(-t)ide treated patients, interferon based therapy results in a greater decrease of sAg level and sAg loss. Lack of any decline in sAg titer during PEG-IFN therapy could identify the group of patients who do not response to IFN/PEG-IFN therapy. With the aid of serum HBV DNA, quantitative measurement of serum HBsAg level can be used to optimize the management of chronic hepatitis B in our daily practice.
Antiviral Agents/therapeutic use ; DNA, Viral/blood ; Hepatitis B Surface Antigens/*blood ; Hepatitis B e Antigens/blood ; Hepatitis B, Chronic/*diagnosis/drug therapy/genetics ; Humans ; Interferons/therapeutic use ; Liver Neoplasms/diagnosis ; Prognosis

Since the discovery of HBsAg in the early 1960s, presence of HBsAg in serum has only served to diagnose hepatitis B. Recent development in the quantitative measurement of serum HBsAg has enabled us to improve our understanding on the management of chronic hepatitis B. The surface antigen (sAg) level is at its highest in immune tolerance phase and decreases to the lowest level in immune control/inactive phase when HBeAg is cleared from the serum. Combination of serum sAg titer less than 1,000 IU/mL and serum HBV DNA less than 2,000 IU/mL can identify true inactive carrier from e antigen (eAg) negative hepatitis with diagnostic accuracy of 95%. During the natural course of chronic hepatitis B, changes or absolute level of sAg less than certain level can predict spontaneous sero-clearance of HBsAg. Although the decline of sAg is very slow in interferon (IFN)/pegylated interferon (PEG-IFN) or oral nucleos(-t)ide treated patients, interferon based therapy results in a greater decrease of sAg level and sAg loss. Lack of any decline in sAg titer during PEG-IFN therapy could identify the group of patients who do not response to IFN/PEG-IFN therapy. With the aid of serum HBV DNA, quantitative measurement of serum HBsAg level can be used to optimize the management of chronic hepatitis B in our daily practice.
Antiviral Agents/therapeutic use ; DNA, Viral/blood ; Hepatitis B Surface Antigens/*blood ; Hepatitis B e Antigens/blood ; Hepatitis B, Chronic/*diagnosis/drug therapy/genetics ; Humans ; Interferons/therapeutic use ; Liver Neoplasms/diagnosis ; Prognosis

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

<b>OBJECTIVEb>To investigate the alteration of HBV markers in liver allograft of HBV related recipients pre and post liver transplantation under Lamivudine or combination of Lamivudine with HBIG prophylaxis and explore the mechanism of HBV de nova infection in liver allograft after orthotopic liver transplantation, as well as seek to establish a optimal prophylactic protocol.

<b>METHODSb>The serial liver biopsy specimens of 90 liver allograft and sera of 78 liver transplant recipients during operation and after 1 week, 1 month, 3 months, 6 months, 12 months, 24 months post transplantation have been collected and detected for HBV markers with enzyme-linked radioimmunoassay, fluorescent quantitative assay for HBV-DNA in serology and with immunohistochemistry stain, HBV-DNA in situ hybridization in histology for detection of HBV markers in liver allograft samples.

<b>RESULTSb>Whether recipients with active replicative or inactive replicative HBV preoperatively, none of positive HBV-DNA, HBsAg and HBcAg in 100% liver biopsy specimens with HBV-DNA hybridization in situ and immunohistochemistry stains in histology within 2 hours after reperfusion.

<b>CONCLUSIONb>Whatever HBV replicative status the recipients have before surgery, no evidence of HBV particles direct invasion to the liver allograft from HBV related cirrhotics during operation under current prophylactic measures. However, the further supposed mechanism and its significance in HBV de nova infection of liver allograft remained to be disclosed further.

Adolescent ; Adult ; Aged ; Biomarkers ; blood ; Child ; DNA, Viral ; blood ; Female ; Hepatitis B Antigens ; blood ; Hepatitis B Surface Antigens ; blood ; Hepatitis B e Antigens ; blood ; Hepatitis B virus ; genetics ; growth & development ; Hepatitis B, Chronic ; diagnosis ; drug therapy ; surgery ; Humans ; Immunization, Passive ; Immunoglobulins ; administration & dosage ; Lamivudine ; therapeutic use ; Liver Transplantation ; Male ; Middle Aged ; Preoperative Care ; methods ; Secondary Prevention

BACKGROUND/AIMS: Lamivudine is a potent inhibitor of hepatitis B virus replication, but an increased incidence of YMDD mutation may be associated with its long term use. Thus, the decision to initiate therapy should be based on variables that are predictive of lamivudine-induced HBeAg loss. The objective of this analysis was to determine patient-dependent or laboratory variables that predict HBeAg loss. METHODS: We retrospectively analyzed 99 HBeAg-positive patients with chronic hepatitis B who were treated with lamivudine and followed up for more than 52 weeks. All patients had a liver biopsy before starting lamivudine therapy. HBeAg loss and HBeAg seroconversion after 52 weeks of treatment were defined as endpoints. RESULTS: The overall rates of HBeAg loss and HBeAg seroconversion were 41.4% (41/99) and 37.4% (37/99), respectively. The rates of HBeAg loss increased as pretreatment ALT levels increased (P=0.013) and were highest among patients with pretreatment ALT levels greater than 5 times the upper limit of normal, occurring in 56.8% of those patients. The rate of HBeAg loss was higher in patients with more active histologic disease on pretreatment liver biopsy (Grade 1 and 2 vs. Grade 3 and 4, 28.3% vs 56.5%, P=0.004). Similar results were seen with HBeAg seroconversion, though seroconversion occurred less frequently than HBeAg loss. Multivariate analysis showed that elevated baseline ALT levels (P<0.05) and histologic activity (P<0.05) were the best independent predictors of HBeAg loss and seroconversion in response to lamivudine. CONCLUSIONS: Pretreatment ALT levels and histologic activity were the most important predictors for response to lamivudine.
Adult ; Alanine Transaminase/*blood ; Antiviral Agents/*therapeutic use ; English Abstract ; Female ; Hepatitis B e Antigens/*blood ; Hepatitis B, Chronic/diagnosis/*drug therapy ; Humans ; Lamivudine/*therapeutic use ; Liver/*pathology ; Male ; Middle Aged

Antiviral Agents ; therapeutic use ; Congresses as Topic ; DNA, Viral ; blood ; Hepatitis B e Antigens ; blood ; Hepatitis B, Chronic ; diagnosis ; drug therapy ; Humans ; Nucleosides ; therapeutic use ; Patient Compliance ; Pyrimidinones ; therapeutic use ; Thymidine ; analogs & derivatives

Adolescent ; Adult ; Female ; Hepatitis B e Antigens ; blood ; Hepatitis B, Chronic ; blood ; diagnosis ; drug therapy ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Thymidine ; analogs & derivatives ; therapeutic use ; Treatment Outcome ; Young Adult

The authors assessed the efficacy and antiviral resistance of 48-week clevudine therapy versus lamivudine in treatment of naive patients with HBeAg positive chronic hepatitis B. In this retrospective study, a total of 116 HBeAg positive patients, who received 30 mg of clevudine once daily (n=53) or 100 mg of lamivudine once daily (n=63) for 48 weeks, were included. At week 48, clevudine therapy produced a significantly greater mean reductions in serum HBV DNA levels from baseline than lamivudine therapy (-5.2 vs. -4.2 log(10)IU/mL; P=0.005). Furthermore, a significantly higher proportion of patients on clevudine achieved negative serum HBV DNA by PCR (<13 IU/mL) at week 48 (60.4% vs. 38.1%; P=0.025). The incidence of virologic breakthrough in the clevudine group was significantly lower than in the lamivudine group (9.4% vs. 25.4%; P=0.031). However, rates of alanine aminotransferase normalization and HBeAg loss or seroconversion were similar in the two groups (83.0% vs. 81.0%, 11.3% vs. 11.1%; P=0.813, 1.000, respectively). In conclusion, clevudine is more potent for viral suppression and lower for antiviral resistance at week 48 than lamivudine in treatment of naive patients with HBeAg positive chronic hepatitis B.
Adult ; Antiviral Agents/administration & dosage ; Arabinofuranosyluracil/administration & dosage/*analogs & derivatives ; Drug Resistance, Viral ; Female ; Hepatitis B e Antigens/*blood ; Hepatitis B, Chronic/diagnosis/*drug therapy/*immunology ; Humans ; Lamivudine/*administration & dosage ; Male ; Treatment Outcome

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.
Aged ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Chlorambucil/*therapeutic use ; Female ; Hepatitis B/*diagnosis/virology ; Hepatitis B Antibodies/*blood/immunology ; Hepatitis B Surface Antigens/*blood/immunology ; Hepatitis B virus/isolation & purification/physiology ; Humans ; Leukemia, Lymphocytic, Chronic, B-Cell/complications/*drug therapy ; Prednisolone/*therapeutic use ; Virus Activation