No abstract

C hronic hepatitis B (CHB) affects 400 million people worldwide and is a major cause of morbidity and mortality. Patients with CHB are at an increased risk of developing liver cirrhosis and its complications, such as hepatic decompensation and hepatocellular carcinoma (HCC), compared with matched controls from the normal population. 1-5 During their lifetime, 25% to 40% of CHB patients will develop serious complications. 5 Treatment of CHB aims at inactivation of liver disease as indicated by hepatitis B e antigen (HBeAg) seroconversion and disappearance of serum HBV DNA, measured by hybridization techniques. Spontaneous HBeAg seroconversion occurs in about 8 -12 % per year. 6 -8 Interferon alfa (IFN) has been reported to increase the HBeAg seroconversion rate to 33%. 8 Particularly for Caucasians, data on the long-term effects on disease progression and mortality are limited. To further evaluate factors that influence clinical outcome and survival, we performed a retrospective cohort study on all HBeAg positive CHB patients treated with IFN in our liver unit. Patients and MethodsPatients. Patients were identified through a search of our trial databases and our computerized hospital-wide patient information system. All HBeAg positive CHB patients treated with interferon between 1978 and 2002

Vertical transmission of hepatitis B virus (HBV) can occur occasionally despite vaccination of the child. This vaccination breakthrough has been associated with high maternal viraemia. We treated eight highly viraemic (HBV-DNA >/= 1.2 x 10(9) geq/mL) mothers with 150 mg of lamivudine daily during the last month of pregnancy. HBV-DNA, hepatitis B surface antigen (HBsAg), anti-HBs and anti-HBc of their offspring were measured at birth and at 3, 6 and 12 months, respectively. Twenty-four children, born to untreated HBsAg-positive mothers with HBV-DNA levels >/=1.2 x 10(9) geq/mL served as historical controls. All children received passive-active immunization at birth and were followed-up for 12 months. In the lamivudine group one of the eight children (12.5%) was still HBsAg and HBV-DNA positive at the age of 12 months. All other children seroconverted to anti-HBs and maintained seroprotection. In three children, HBV-DNA was temporarily detected by polymerase chain reaction. In the untreated historical control group, perinatal transmission occurred in seven of 25 children (28%). In highly viraemic HBsAg-positive mothers, reduction of viraemia by lamivudine therapy in the last month of pregnancy may be an effective and safe measure to reduce the risk of child vaccination breakthrough. This approach should be evaluated in a large controlled trial.

One year of Peg-interferon alpha-2b for HBeAg-positive patients led to HBsAg loss in 7%. Our study indicates that treatment with Peg-interferon alpha-2b is the best therapy to achieve HBsAg clearance in patients with genotype A.

Background and aims: Flares are a well known phenomenon during antiviral treatment for chronic hepatitis B. Little is known about the effect of flares on response. We investigated the timing and characteristics of flares, in relation to treatment response (hepatitis B e antigen loss). Patients: A total of 266 patients, participating in a global randomised controlled study, were assigned to 52 weeks of 100 mg pegylated (Peg)-interferon a-2b weekly, combined with either daily lamivudine 100 mg or placebo. Results: Sixty seven patients (25%) exhibited 75 flares, with 38 (51%) flares in the combination therapy and 37 (49%) in the monotherapy groups. Overall, 30% of patients with and 38% of patients without a flare responded to therapy (p = 0.25). In 24 patients (36%) the flare was followed by a decrease in hepatitis B virus (HBV) DNA (host induced flare). In 25 (38%) patients the flare was preceded by an increase in HBV DNA (virus induced flare). In 17 (26%) patients the flare did not meet one of these criteria (indeterminate flare). Of patients with host induced flare, 58% responded whereas only 20% of patients with virus induced flares responded (p = 0.008). Hepatitis B surface antigen loss (n = 8) was exclusively seen in patients experiencing a host induced flare. Multivariate logistic analysis showed that host induced flares was an independent predictor of response (p = 0.043). Conclusion: Flares are not more common in responders than in non-responders to Peg-interferon a-2b therapy. Virus induced flares, which occur after an increase in HBV DNA level, and most probably are indicative for increased expression of viral antigens, did not lead to treatment response. In contrast, host induced flares which were followed by a HBV DNA decrease were highly associated with treatment response.