Peginterferon alfa-2a results in a sustained response (SR) in a minority of patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB). This study investigated the role of early on-treatment serum hepatitis B surface antigen (HBsAg) levels in the prediction of SR in HBeAg-negative patients receiving peginterferon alfa-2a. HBsAg (Architect from Abbott) was quantified at the baseline and during treatment (weeks 4, 8, 12, 24, 36, and 48) and follow-up (weeks 60 and 72) in the sera from 107 patients who participated in an international multicenter trial (peginterferon alfa-2a, n 5 53, versus peginterferon alfa-2a and ribavirin, n 5 54). Overall, 24 patients (22%) achieved SR [serum hepatitis B virus (HBV) DNA level < 10,000 copies/mL and normal alanine aminotransferase levels at week 72]. Baseline characteristics were comparable between sustained responders and nonresponders. From week 8 onward, serum HBsAg levels markedly decreased in sustained responders, whereas only a modest decline was observed in nonresponders. However, HBsAg declines alone were of limited value in the prediction of SR [area under the receiver operating characteristic curve (AUC) at weeks 4, 8, and 12 5 0.59, 0.56, and 0.69, respectively]. Combining the declines in HBsAg and HBV DNA allowed the best prediction of SR (AUC at week 12 5 0.74). None of the 20 patients (20% of the study population) in whom a decrease in serum HBsAg levels was absent and whose HBV DNA levels declined less than 2 log copies/mL exhibited an SR (negative predictive value 5 100%). Conclusion: At week 12 of peginterferon alfa-2a treatment for HBeAg-negative CHB, a solid stopping rule was established with a combination of declines in serum HBV DNA and HBsAg levels from the baseline. Quantitative serum HBsAg in combination with HBV DNA enables on-treatment adjustments of peginterferon therapy for HBeAg-negative CHB. (HEPATOLOGY 2010;52:454-461)

During pregnancy several alterations in the immune status allow mothers to tolerate the genetically different foetal tissues. We investigated the evolution of liver disease during and after pregnancy in chronic hepatitis B patients. Between 1998 and 2006 there were 38 pregnancies in 31 chronic hepatitis B 's' antigen-positive women at our liver unit. Twenty-four subjects (63%) were hepatitis B 'e' antigen (HBeAg)-positive, 14 (37%) HBeAg-negative. In 13 pregnancies (34%), lamivudine therapy was started during the last trimester of pregnancy to lower hepatitis B virus (HBV) DNA levels to reduce the risk of vertical transmission. A significant increase in liver disease activity after pregnancy, defined as a three times increase in alanine aminotransferase (ALT) within 6 months after delivery, occurred in 17 of 38 patients (45%). In those treated with lamivudine during the last trimester of pregnancy, this occurred in even 8/13 patients (62%). Prediction during pregnancy of these exacerbations was not possible using HBV DNA, ALT level, HBeAg status or any other characteristic. The median maximal ALT of these exacerbations was 4.0 x ULN and none led to decompensated liver disease. In conclusion, a significant increase in liver inflammation occurs often after pregnancy. This may be due to a reactivation of the immune system after delivery. Based on our data we recommend monitoring closely and if necessary treating women with chronic HBV shortly after delivery.

Treatment with peginterferon alpha-2a resulted in a limited sustained response rate in HBeAg-negative chronic hepatitis B patients. Addition of ribavirin did not improve response to therapy.

alpha-GalCer (0.1-10 microg/kg) used as monotherapy for chronic hepatitis B infection resulted in a strong decrease of NKTs, but did not clearly affect HBV DNA and alanine aminotransferase levels. alpha-GalCer was poorly tolerated and is unlikely to be suitable as an alternative monotherapy to the current treatment regimen.

In chronic hepatitis B, it is difficult to predict an early therapeutic response. We investigated the viral decline during therapy with pegylated interferon alpha-2b (PEG-IFN) with or without lamivudine in 266 HBeAg-positive chronic hepatitis B patients. In patients treated with PEG-IFN and lamivudine, a uniform biphasic viral decline pattern was found during therapy and there were no marked differences in viral load between those who lost HBeAg at the end of follow-up (response) or not. In contrast, those treated with PEG-IFN monotherapy exhibited different viral decline patterns. A delayed decline of at least two log from baseline HBV DNA after week 4 but before week 32 was associated with the highest response rate (63%). In comparison, response was 52% for patients with an early decline (week 0-4), 38% for a late decline (week 32-52), 27% for a posttreatment decline (week 52-78) and 11% for patients with no substantial decline. The HBsAg loss was 22% in the delayed decline pattern compared to 4% for those with early decline and none for other decline patterns. In conclusion, different patterns of decline in viral load during treatment with PEG-IFN monotherapy were associated with different rates of HBeAg and HBsAg loss at the end of follow-up. Since there was a considerable response, even in patients with a late or posttreatment decline pattern, prediction of response based on viral decline during the first months of therapy was difficult. (HEPATOLOGY 2006;44:721-727.) Abbreviations: HBeAg, hepatitis B e antigen; HBV, hepatitis B virus; IFN, interferon alpha; ALT, alanine aminotransferase; HBsAg, hepatitis B surface antigen; antibody to hepatitis B surface antigen; antibody to hepatitis B e antigen; ROC, receiver operating characteristic. From the