HBV DNA Loss within 24 Weeks Predicts Late Viral Breakthrough in Chronic Hepatitis B / 대한소화기학회지

BACKGROUND/AIMS: Sustained HBV DNA reduction is necessary for biochemical remission, histological improvement, and prevention of complications. We analyzed the time taken from HBV DNA loss to viral breakthrough after antiviral treatment in patients with chronic hepatitis B (CHB). The early fall of the HBV DNA level to undetectable levels assessed really whether it is related to late breakthrough. METHODS: A total of 91 patients whose HBV DNA levels dropped below undetectable levels were chosen from lamivudine-treated 306 patients and were analyzed retrospectively. The patients were divided into 4 groups (A48 wk) according to the time taken for the HBV DNA to decrease below undetectable levels. HBV DNA level was determined every 3 months. RESULTS: The mean time taken for loss of HBV DNA was 34+/-28 wk. The baseline ALT differed significantly among groups (A: 382+/-274, B: 340+/-30, C: 166+/-92, D: 54+/-100 IU/L) (p=0.007). Fifty nine of the 91 patients (64.8%) experienced viral breakthrough. The mean interval between HBV DNA loss and viral breakthrough was 65+/-40 wk and differed significantly between group A, B (82+/-43 wk) and group C, D (56+/-28 wk) (p=0.015). In multivariate analysis, only HBV DNA loss within 24 wk, was found to be independently associated with late viral breakthrough (p=0.035). Undetectable HBV DNA after 24 wk was associated with high odd ratio of 3.24 (95% CI, 1.09-9.67). CONCLUSIONS: HBV DNA loss within 24 wk after antiviral treatment could predict the late breakthrough.

Treatment Outcomes of Clevudine versus Lamivudine at Week 48 in Naive Patients with HBeAg Positive Chronic Hepatitis B

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.

Genotypic resistance to entecavir in chronic hepatitis B patients / 대한간학회지

BACKGROUND/AIMS: The prevalence and clinical characteristics of entecavir (ETV) resistance is not well known. The aim of this study was to determine the frequency of genotypic resistance in nonresponders and virologic breakthrough (VBT) patients. METHODS: The medical records of 76 chronic hepatitis B patients treated for a least 6 months from October 2006 to October 2008 were reviewed retrospectively. We divided patients into two groups: nucleoside analogue (NA)-naive patients (n=38) and LAM experienced patients (n=38). NA-naive and LAM experienced patients received ETV at 0.5 and 1.0 mg/day, respectively. The virologic response and VBT were investigated in both groups. We used the multiplex restriction fragment mass polymorphism (RFMP) method to test genotypic resistance at the rtI169, rtT184, rtS202, rtM204, and rtM250 sites. RESULTS: Age, gender, serum ALT, and HBV DNA level before treatment did not differ between the groups. Neither VBT nor nonresponse was observed in the NA-naive group, whereas VBT and nonresponse were observed in three patients each in the lamivudine (LAM)-experienced group; all six patients had YMDD mutation at study enrollment, all three patients with VBT had genotypic resistance to ETV, but the three nonresponse patients did not have genotypic resistance to ETV. CONCLUSIONS: We suspect that VBT is mostly associated with genotypic resistance to ETV. However, nonresponse might be associated with the continuance or reselection of the YMDD mutant in LAM-experienced patients.