Yun‐Fan Liaw

To examine the long-term effect of interferon (IFN) therapy in patients with chronic hepatitis B virus (HBV) infection, particularly on survival and hepatocellular carcinoma (HCC) prevention, 101 male patients with chronic hepatitis B in a randomized controlled trial were followed up for 1.1 to 11.5 years after the end of therapy. Of the 101 patients, 34 patients received a placebo (control), and 67 patients were treated with IFN (31 patients were treated with IFN alone and 36 patients were treated with IFN after prednisolone priming). Follow-up studies included clinical, biochemical, and virological aspects and HCC screening every 3 to 6 months. Twenty-eight (42%) of the 67 IFN-treated patients and 8 (24%) of the 34 untreated patients seroconverted by the end of the trial. During follow-up, 22 (56%) of the 39 patients who did not seroconvert in the treated group and 5 (19%) of the 26 patients who did not seroconvert in the control group showed a delayed sustained response (P <.005). The cumulative incidence of sustained response was highest in the steroid priming group (P =.049 vs. the IFN-alone group; P =.028 vs. the control group). HCC was detected in 1 (1.5%) of the 67 treated patients and 4 (12%) of the 34 untreated patients (P =.043). The interval between entry and HCC detection was 3.5 to 8.2 years. The cumulative incidence of HCC development was significantly higher in the control group than in the treated group (P =.013). In contrast, the cumulative survival rate was higher in the treated group than the control group (P =. 018). Multivariate analysis showed that IFN therapy, preexisting cirrhosis, and the patient's age at entry are significant independent factors for both survival and HCC development. The results suggest that IFN has long-term beneficial effects in terms of HBV clearance, reduction of HCC, and prolonging survival.

UNLABELLED: Spontaneous hepatitis B surface antigen (HBsAg) seroclearance in chronic HBV infection has long been suggested as a rare event in high endemic areas. The prevalence of HBsAg in the general population of Taiwan, however, decreased remarkably from 15%-20% before age 40 to 5%-10% after age 60 or 70. This study aimed to reexamine the rates of HBsAg seroclearance by a long-term follow-up of 1965 hepatitis B e antibody-positive asymptomatic adult carriers. Of these, 1076 (55%) were males, the mean (+/-SD) age was 35.6+/-9.2 years and the mean follow-up was 10.8+/-5.4 years. Hepatitis relapsed in 314 patients, 0.5 to 18 (mean+/-SD=5.8+/-4.4) years after the entry. The probability of hepatitis relapse correlated positively with male sex (P<0.0001) and age at entry (P<0.0001). Serum HBsAg cleared in 245 patients at the mean age of 47.8+/-9.6 years. The cumulative probabilities of HBsAg seroclearance were 8.1% after 10 years, but increased disproportionally to 24.9% and 44.7%, respectively, after 20 and 25 years. In multivariate analysis, the probability of HBsAg seroclearance correlated positively with age at entry (P<0.0001) and sustained remission of hepatitis (P<0.0001) and marginally significantly with male sex (P=0.053). CONCLUSION: Cumulative rate of HBsAg seroclearance in asymptomatic adult carriers from high endemic areas was approximately 40% after 25 years of follow-up. The low HBsAg seroclearance rates in previous studies might be due to the relative short period of follow-up.

In the reported Asian lamivudine trial, the rate of hepatitis B e antigen (HBeAg) seroconversion, defined as HBeAg/hepatitis B virus (HBV) DNA seroclearance and development of anti-HBe, during 52 weeks of treatment was only 13% to 16%. To evaluate whether any factors influenced HBeAg seroconversion, data from 345 patients in that trial were reanalyzed to correlate HBeAg seroconversion with variables including treatment, age, gender, body build, histology, baseline HBV-DNA levels, and alanine transaminase (ALT) levels. Exploratory analysis using stepwise modeling revealed that HBeAg seroconversion correlated highly with pretherapy ALT (P <.001) followed by lamivudine therapy (P =.013), but only marginally with baseline HBV-DNA (P =.071) and cirrhosis (P =.066) for lamivudine 100 mg and placebo comparison. Among these four variables, only pretherapy ALT still had a highly significant (P <.001) correlation and lamivudine therapy had a borderline association (P =.066) for lamivudine 25 mg and placebo comparison. Categorical analysis revealed that HBeAg seroconversion occurred earlier and the cumulative rate was significantly higher in patients with pretherapy ALT values over 2 times the upper limit of normal (ULN) as compared with treated patients with lower ALT levels or untreated control patients with the same ALT levels (P <.001, respectively). The highest HBeAg seroconversion rate was observed in 100 mg lamivudine-treated patients with ALT levels greater than 5 times the ULN (64%) compared with patients with ALT 2 to 5 times the ULN (26%, P =.03); and ALT less than 2 times the ULN, (5%, P <.001). These results suggest that pretherapy ALT is the strongest determinant for HBeAg seroconversion during lamivudine therapy, and should be considered in selecting patients for treatment.