Durability of HBeAg seroconversion following antiviral therapy for chronic hepatitis B: relation to type of therapy and pretreatment serum hepatitis B virus DNA and alanine aminotransferase

Abstract

Background and aims: Interferon (IFN) induced hepatitis B e antigen (HBeAg) seroconversion is durable in 80-90% of chronic hepatitis B patients. Preliminary reports on the durability of HBeAg seroconversion following lamivudine are contradictory. We investigated the durability of response following IFN, lamivudine, or IFN-lamivudine combination therapy in a meta-analysis of individual patient data. Patients and methods: Twenty four centres included 130 patients in total with an HBeAg seroconversion (HBeAg negative, antibodies to hepatitis B e antigen positive) at the end of antiviral therapy: 59 with lamivudine, 49 with interferon, and 22 with combination therapy. Relapse was defined as confirmed reappearance of HBeAg. Results: The three year cumulative HBeAg relapse rate by the Kaplan-Meier method was 54% for lamivudine, 32% for IFN, and 23% for combination therapy (p=0.01). Cox regression analysis identified pretreatment hepatitis B virus (HBV) DNA, alanine aminotransferase (ALT), sex, and therapy as independent predictive factors of post-treatment relapse; Asian race, previous therapy, centre, and type of study were not predictive of relapse. The relative HBeAg relapse risk of lamivudine compared with IFN therapy was 4.6 and that of combination therapy to IFN therapy 0.7 (p overall =0.01). Conclusions: The durability of HBeAg seroconversion following lamivudine treatment was significantly lower than that following IFN or IFN-lamivudine combination therapy. The risk of relapse after HBeAg seroconversion was also related to pretreatment levels of serum ALT and HBV DNA, but independent of Asian race.

Liver stiffness in the hepatitis B virus carrier: A non-invasive marker of liver disease influenced by the pattern of transaminases

“…Since both these parameters are linked with the extent of liver disease activity in the immune competent HBV carrier, our results further support the hypothesis that the extent of necrosis and inflammation influence LS significantly [20,[22][23][24] . Accordingly, in the 83 untreated patients without cirrhosis, multivariate analysis showed that intra-hepatic necrosis and inflammation scores and ALT values were the only factors influencing FS (P = 0.035 and P < 0.001 respectively), in addition to the stage of liver disease.…”

Determinants for sustained HBeAg response to lamivudine therapy

“…6,7,31 Our data suggest that genotype C HBV infection may be responsible for the higher relapse rate in Asians, particularly Korean patients. 7,31 In the univariate analysis, our relapsers had a shorter duration of lamivudine therapy (9 vs. 13 months, respectively; P ϭ .041) and shorter additional therapy after HBeAg seroconversion (3 vs. 4.5, respectively; P ϭ .035). In addition, our patients with lamivudine therapy Ͻ12 months tend to have a higher relapse rate (57% vs. 37%, respectively), although the difference was only marginally significant.…”

“…A recent international study involving 59 patients treated with lamivudine (including 39 Korean patients) showed that high pretreatment HBV DNA and low pretherapy ALT were independent predictive factors of posttreatment HBeAg relapse. 31 In contrast, Dienstag et al 6 followed 40 patients (only 5 were Asians) for a median of 36.6 (4.8-45.6 months) months and found that low pretherapy ALT level was the only predictor for durable HBeAg response but at a marginally significant level (P ϭ .0724). The present study also showed that the median pretreatment levels of ALT were significantly lower in patients with durable HBeAg response (344 vs. 478 U/L, respectively; P ϭ .010).…”

Response predictors to treatment with pegylated interferon in chronic hepatitis B

“…If the sustained response for NA is assessed, a longer period of observation after drug withdrawal is necessary, as relapse can occur after the first year postreatment. 16 ers (loss of HBeAg 6 months postreatment) remained HBeAg-negative, whereas 58% of the initial responders presented levels of HBV-DNA < 2,000 UI/mL, three years after treatment. 30 Similarly, in a study conducted in Hong Kong, 46% of the initial responders remained HBeAg-negative and 29% presented levels of HBV-DNA < 5,000 UI/mL, three years after treatment.…”

“…[12][13][14] Most hepatitis flares, after HBeAg seroconversion occur within six months after interferon therapy withdrawal, but can occur later, and even a few years after lamivudine withdrawal. 15,16 As a consequence, seroconversion of HBeAg can be used as a response marker only when sustained for at least six months after the end of therapy, and may be the best marker for treatment with pegylated interferon compared to NA.…”