Halil Degertekin

Quantitative HBsAg and HDV-RNA levels in chronic delta hepatitis.

Background: Hepatitis delta virus (HDV) causes severe liver disease.

A severe hepatitis flare in an HBV-HCV coinfected patient during combination therapy with Α-interferon and ribavirin

We report a reactivation of hepatitis B virus infection and a severe hepatitis flare in a patient with chronic hepatitis due to dual infection with hepatitis B and C viruses during combination therapy with alpha-interferon and ribavirin. Pretreatment, HCV was the dominant virus, with detectable serum HCV-RNA but undetectable HBV-DNA. The patient responded to therapy, with the disappearance of HCV-RNA and normalization of serum alanine aminotransferase (ALT) at months 1 and 6. In the seventh month of therapy, an ALT flare was observed, and serum HBV-DNA became detectable. The patient had a severe hepatitis flare leading to impending hepatic failure. Treatment was discontinued and the patient had marked clinical and biochemical improvement and recovered with normalization of liver function test results within 1 month. Two months later, serum HBV-DNA was again undetectable, both by hybridization and polymerase chain reaction (PCR) assays. The patient had a rapid progression to cirrhosis in a year. At month 24, 17 months after the end of therapy, serum HCV-RNA reappeared, with a level of 2.4 × 105 copies/ml. In conclusion, severe HBV reactivation may occur during interferon plus ribavirin therapy in patients with chronic hepatitis C who are also hepatitis B surface antigen (HBsAg)-positive, and thus more careful monitoring than usual should be considered. Longterm follow-up is recommended, because very late HCV relapses may occur in coinfected patients. These data exemplify the complexity of viral dominance in patients infected with multiple hepatitis viruses, and this has significant importance for treatment decisions. Lamivudine may be administered early in HCV-RNA/HBsAg-positive patients who are at high risk of liver failure once reactivation of HBV occurs during interferon therapy.

The lack of effect of therapeutic vaccination with a pre-S2/S HBV vaccine in the immune tolerant phase of chronic HBV infection.

Background/Aims Even if the results are controversial and preliminary, several reports suggest that the HBV vaccine might be effective in treating HBV infection. In this study, we aimed to evaluate the efficacy and safety of specific anti-HBV vaccination for the immune tolerance phase of chronic HBV infection in a randomized, controlled study. Patients and Methods The 47 subjects included patients that were treatment-naive with hepatitis B e antigen positivity, active hepatitis B virus replication as measured by hepatitis B virus DNA levels, persistently normal alanine transaminase levels, and with minimal or absent disease activity by liver biopsy. Thirty patients were given three intramuscular injections of 20 &mgr;g of a pre-S2/S vaccine (GenHevac-B) on days 0, 30, and 60, and the remaining 17 patients were included in the control group. The efficacy of vaccination was evaluated by testing for loss of serum HBV DNA or decrease in its level and for HBeAg seroconversion. A significant decrease in HBV DNA levels was accepted as a decrease of >50% of initial values. The complete response was defined as loss of HBV DNA in serum with HBeAg seroconversion. Postvaccination follow-up lasted 12 months after the first dose. Results No significant effects were observed in the vaccination population in the reduction of HBV DNA to undetectable levels, or to <50% of prevaccination levels, in HBeAg/anti-HBe seroconversion, or in transaminase levels. There was an early clearance/decrease in HBV DNA levels in five vaccinated patients by 3 months, and none in controls (P = 0.143), and two of them had sustained responses later. At the end of follow-up, complete response is almost similar in study as well as control group (13% vs. 12%, P > 0.05). Disappearance of serum HBV DNA was more frequently observed in those patients who had pretreatment viremia of <100 pg/mL in both groups. The median levels of HBV DNA and alanine transaminase activity between baseline and 12 months did not differ significantly in both groups. All patients remained HBsAg positive and none developed anti-HBs. No serious adverse event was encountered in vaccinated patients, and the therapy was well tolerated. Follow-up lasted a median of 16 months (range 12–30 months) for the study group and 18 months (range 12–31months) for the control group. Conclusions Immunotherapy with specific anti-HBV vaccine in the immune tolerance phase of chronic HBV infection did not offer additional benefit. New immunotherapeutic strategies to control HBV infection by specific HBV vaccines in chronically infected subjects are needed.

A 12-month course of combination therapy with interferon-alfa and lamivudine in patients with chronic hepatitis delta virus: A single-center, prospective, open-label, uncontrolled study

Abstract Background: Chronic hepatitis delta virus (HDV) is a severe and rapidly progressive liver disease for which no therapy has been proved to be effective. Objective: The aim of this study was to investigate the efficacy and tolerability of long-term therapy with a combination of recombinant interferon (IFN)-alfa and lamivudine. Methods: In this single-center, prospective, open-label, uncontrolled study, patients aged 18 to 60 years with chronic HDV were eligible. Patients were treated with a combination of 10 million units of IFN-alfa-2b subcutaneously 3 times weekly and lamivudine 100 mg once daily for 12 months. The primary outcome measures were biochemical and histologic response at the end of treatment and at least 12 months thereafter. Results: Twelve patients (10 men, 2 women; mean age, 33.9 years [range, 19–49 years]) were enrolled (6 treatment-naive patients, 6 previously treated patients). Normalization or decrease of >50% from baseline in serum alanine aminotransferase (ALT) level occurred in 8 (66.7%) of 12 patients at month 12 of treatment. Of the 12 patients, 10 (83.3%) completed the trial; 1 (8.3%) was withdrawn because of severe leukopenia and 1 (8.3%) was lost to follow-up. Relapses occurred in 5 of 8 (63.3%) initial responders shortly after the cessation of therapy. In 3 (25%) patients whose ALT levels became normal at the end of the therapy, the complete biochemical responses persisted for up to 3 years (mean, 31 months). The treatment was associated with a marked improvement in histologic activity. Conclusions: In this study, combination therapy with IFN-alfa and lamivudine was well tolerated and reduced hepatic inflammation was found. Further controlled trials are needed to show possible beneficial effects of this model of therapy and to determine the optimal dose and duration of therapy for chronic HDV.