Background: Serum alanine aminotransferase (ALT) activity, the variable most commonly measured to assess hepatic disease, fails to identify many patients with hepatic injury. Current standards for "normal" ALT level were defined by using populations that included persons with subclinical liver disease. There is no study regarding normal level of ALT and its modulating factors in healthy Thai people. Objective: To definitions of Normal ranges for serum ALT level in Thai people. Design: Prospective observational study Setting: Phramongkutklao hospital and Army Institute of Pathology Pramongkutklao Medical center(A.I.P.), Bangkok, Thailand Participants: 200 persons who were first-time blood donors from August through December 2007 were negative for anti-hepatitis C virus(HCV), negative HBsAg(HBV), and had no contraindications to donation. Measurements: Univariate and multivariate analyses examined associations between clinical and laboratory factors and ALT levels. Normal ranges for ALT were computed from the population at lowest risk for liver disease. Results: Serum ALT activity was independently related to body mass index, age, alcoholic consumption and to laboratory indicators of abnormal lipid or carbohydrate metabolism. Normal ranges for serum ALT level in Thai people upper limits for men 26 U/L and for women 21.67 U/L. Conclusion: In men serum ALT is strongly associated with body mass index, age, alcoholic consumption and to laboratory indicators of abnormal lipid or carbohydrate metabolism. The normal range of ALT should be defined for male and female separately. Background: The open-label rollover study ETV-060 was conducted after ETV phase II clinical study ETV-047 for nucleoside-na ve adult CHB patients in Japan. In this analysis, we report ETV long-term efficacy and safety in patients who were switched from 24-week LVD treatment to ETV therapy. Methods: Ninety-seven percent (33/34) of LVD-treated patients from ETV-047 were rolled over into ETV-060 treated with 0.5mg of ETV. Thirty patients completed 96 weeks of ETV therapy and were evaluated for HBV DNA level, ALT normalization, HBeAg seroconversion, resistance and safety. Results: Comparing to baseline before switching to ETV, after 96 week of ETV treatment, the proportion of patients achieving undetectable HBV DNA (<400 copies/ml) increased from 21% to 90%. Increases were also observed for ALT normalization (81% to 90%) and HBeAg seroconversion (10% to 19%). Three patients had detectable HBV DNA at Week 96 after ETV treatment and samples from two were tested for resistance. Neither demonstrated substitutions associated with ETV or LVD resistance. Five patients had Grade 3-4 laboratory abnormalities, including increased AST/ALT and increased lipase levels. Conclusions: Switching patients from LVD therapy to ETV resulted in increased proportions of patients achieving HBV DNA suppression, ALT normalization and HBeAg seroconversion, with no evidence of ETV resistance. ETV was well tolerated during treatment. Backgrounds/aims: Hepatitis B virus (HBV) reactivation in patients undergoing chemotherapy hampers an adequate administration of cytotoxic agents and even causes an treatment failure. Prophylaxis failure occasionally results from viral breakthrough or withdrawal flare. The aims of this study were to identify predictors of anti-viral prophylaxis failure and to determine the optimal strategy for anti-viral prophylaxis. Methods: Cancer patients with positive HBsAg who underwent cytotoxic chemotherapy in a tertiary medical center from January 2005 to June 2008 were included. Prophylactic lamivudine was started with initiation of chemotherapy, continued during the chemotherapy, and discontinued within 6 months after the completion of chemotherapy. All patients were followed up even after withdrawal of lamivudine. Results: 115 patients were enrolled. Twenty-nine patients (23.7%) had hematologic malignancies and eighty-six (76.3%) had solid tumors. Median follow-up duration was 15.9 months and twenty-six patients (22.6%) experienced the prophylaxis failure: viral breakthrough (11 patients, 9.6%), withdrawal flare (15 patients, 13.0%). YMDD mutation developed in four patients. Withdrawal flare occurred at a median 2.5 months after discontinuation of lamivudine. Using log-rank test and Cox multi-variate analysis, our results showed that the type of underlying malignancies (HR 2.46, 95% CI, 1.11-5.43; P=0.026) and baseline HBV DNA titer (HR 3.91, 95% CI, 1.63-9.39; P=0.002) were significant independent risk factors for antiviral prophylaxis failure. Conclusion: Cancer patients with high viral load of HBV and hematologic malignancies may need more prolonged and potent anti-viral prophylaxis to avoid interruption or delay of chemotherapy. Back Ground: The usefulness of hepatitis B virus (HBV) DNA and HBV core-related antigen (HBcrAg) was evaluated for timing hepatitis flare after viral breakthrough or withdrawal of antiviral treatment in chronic hepatitis B. Method: A total of 32 events of HBV reactivation due to withdrawal of lamivudine (LAM) or emergence of mutants resistant to LAM or adefovir dipivoxil (ADV) virus were analyzed in 25 patients with chronic hepatitis B (20 men, median age 56 years [range: 30-66]). They were followed monthly for serum ALT, HBV DNA and HBcrAg before, during and after the treatment. Result: High ALT flare (ALT > 100 IU/ml) after viral breakthrough or withdrawal was related with baseline HBeAg positivity (p=0.016), HBcrAg level at HBV DNA elevation (p=0.038) and duration from HBcrAg elevation to salvage therapy (p=0.044). In multivariate analysis, HBcrAg > 4.0 log U/ml (OR 22.9, 95%C.I. 1.7-304.1, p=0.018) and Salvage therapy after 8 weeks from HBcrAg elevation (OR 10.6, 95%C.I. 1.6-71.4, p=0 .015) were selected as related factor with high ALT flare. After appearance of resistant-virus or withdrawal of LAM or ADV therapy, HBV DNA re-elevated without increase of HBcrAg, then HBcrAg elevated with HBV DNA. Re-elevations of ALT occurred in 27 of the 32 (84%) events. In 23 of the 27 (85%) events, ALT re-elevated within 8 weeks from the start of HBcrAg increase. Conclusion: HBcrAg was useful for timing the re-elevation of ALT after HBV DNA re-elevation induced by drug-resistant virus or withdrawal of LAM or ADV therapy. Background and Objectives: The aim of the study was to observe the efficacy of a patient's therapy for switching lamivudine + placebo to adefovir dipivoxil (ADV), and modeling the viral dynamics. Methods: The studied object was a Chinese CHB patient with lamivudine mutation. Used the LVD + placebo for 12 weeks' therapy. Then switched ADV for another 95 weeks. After that stopping the treatment and following up for 24 weeks. Based on our modified basic virus infection model, we introduce a personalized model consisting of four variables: x, y, v, e , representing uninfected cells, infected cells, free virus, and CTL cells, respectively. Results: Selected the model parameters, the simulation data of HBV DNAs of our model are good in agreement with the clinical ones. Observe that after 24 weeks' treatment cessation, the benefit (HBV DNA < 250 copies/mL) for suppressing HBV replication can still be kept. Numerical simulation show that if the patient's immune functions can be kept after therapy stops, it needs 9 years to replace all infected cells by normal ones. Conclusion: For LVD mutation patients, LVD+ placebo to AVD therapy scheme may help patients to suppressing HBV replication. Further researches are promising. Acknowledgments: This work is jointly supported by the NNSF of China Background: G-A-1896 pre-Core mutants (P-C-mt) cause HBeAg-negative chronic hepatitis (CHB) in genotype D infected Mediterranean adults. We studied their emergence during chronic HBV infection in children. Methods: Eighty consecutive HBsAg carriers (50/30 males/females, age 11y, range 0.2-17y) with vertical (66%) or intra-familial (16%) transmissions were followed-up for 12.5y (range 1-25 y). HBV genotype and HBeAg status were determined at the admission, HBeAg/anti-HBe every 2 years thereafter. During the follow-up, HBV-DNA was measured in 185 sera (1-7 sera/patient) (Cobas-Amplicor, Roche); P-C populations were characterized by direct sequencing (DS), by oligo-hybridization (OHA) and allele-specific-PCR (AS-PCR) with 30%, 10% and 0.1% sensitivities, respectively. Results: Seven children were genotype A and 73 D; 70 (87.5%) were HBeAg-positive. Fifty-five (78.6%) underwent HBeAg/anti-HBe seroconversion (median age 13y, range 1.3-27y). Baseline HBV-DNA (cp/ml) was lower in seroconverters (7.9+1.9 vs 9,4+0,6, ANOVA p=0.012). DS/OHA P-C-mt were 4.2% at the admission and 45.8% after follow-up; AS-PCR P-C-mt 33.3% and 50% respectively. After seroconversion 47 (85.5%) became inactive carriers, 6 (14.5%) lost HBsAg (5 genotype D/P-C-wt); 8 P-C-mt had CHB. HBV-DNA (cp/ml) was lower in 31 P-C-wt than in 14 P-C-mt inactive carriers (3.42+1.05 vs 4.58+0.91; ANOVA p=0.007). Conclusions: In genotype-D infected children P-C-mt is selected progressively after HBeAg/anti-HBe seroconversion to become predominant in HBeAg-negative CHB. Early and efficacious immune control of HBV replication avoids P-C-mt selection and leads to HBsAg loss. , a, , d, k, u, m, n , k1 ,k2 and k3. Here k1, k2, and k3 are the rate of CTL production and dead, killing virus, respectively. Results: The patients with HBV DNA levels less than 1000 copies/ml were reported in 17.5% (7/40). A patient whose HBV DNA levels were higher than 40000 copies/ml can keep treatment benefits even stopping the therapy for over ten weeks. The simulation data of our model are in agreement with the patient's HBV DNA data. Our simulation also shows that it needs to spend about 18 years for clearing all infected cells. Conclusion: The simulation result implies that some Chinese patients may need long term's therapy to clear all infected cells. Patients' CTLs assays are needed to confirm the effectiveness of the personalized modeling, and help doctors to decide whether stop the drug treatment even patients' HBV DNAs are higher than undetectable levels. Background/Aim: Recent reports have shown that programmed death 1(PD-1) expression is associated with T cell exhaustion and persistent viral infection. We studied longitudinally 28 chronic hepatitis B(CHB) patients undergoing treatment with nucleos(t)ide analogues or pegylated interferon-(PEG-IFN-) in 12-16 weeks to determine the relationship between PD-1 expression levels on T cells and early reduction of viral load induced by treatment. Methods: Our investigations were focused on three points: baseline (time point 1, T1), treatment weeks 4-6(time point 2, T2) and treatment weeks 12-16(time point 3, T3). PD-1 expression on total CD4 and CD8 T cells in CHB patients during antiviral therapy was detected by flow cytometry. Serum Hepatitis B virus (HBV)-DNA load was measured by real time polymerase chain reaction. Results: Between T1 and T2, PD-1 expression on total CD8 (P<0.01) and CD4 T cells (P<0.01) dropped concurrently with treatment-induced HBV-DNA decline(P<0.01). Between T2 and T3, however, only the HBV-DNA levels reduced significantly (P<0.01). Conclusion: Early suppression of HBV replication induced by antiviral treatment results in a significant decrease in PD-1 expression on total CD8 and CD4 T cells in CHB patients.