Combination Therapy with Antiviral Drugs and Hepatitis B Vaccine in Incidentally-Detected and Asymptomatic Chronic Hepatitis Virus B Carriers at Bangladesh

Abstract

Asymptomatic chronic hepatitis B virus (HBV) carriers are at risk of developing complications of liver disease, but these patients are not recommended for treatment with antiviral drugs. In fact, antiviral drugs are ineffective in these patients in the immune tolerance phase, when they have inadequate levels of host immunity. We postulated that combination therapy of an immune modulator and antiviral drugs may have potential to help these patients. Twenty-five patients with incidentally-detected asymptomatic chronic HBV were immunized with hepatitis B vaccine (10 microg of hepatitis B surface antigen) intramuscularly five times (at 0, 1, 2, 6, and 12 mo) to induce HBV-specific immunity. The patients were also treated with lamivudine (100 mg) daily for 12 mo. The combination therapy was safe for all patients with asymptomatic chronic HBV, and no increases in alanine aminotransferase or liver damage were detected in any patient. Although all of the patients were expressing HBV DNA in their serum before treatment, HBV DNA became undetectable in 16 of 25 patients, and was reduced in 9 of 25 patients at the end of the combination therapy. Combination therapy with the antiviral agent lamivudine and an immune modulator (hepatitis B vaccine) represents a potential therapeutic option for the control of HBV without liver damage in asymptomatic chronic HBV carriers.

Hepatitis B: From Blumberg to Bangladesh

“…Our trial with antiviral agent lamivudine combined with immune modulator (hepatitis B vaccine) in incidentally diagnosed chronic hepatitis B patients had an encouraging result. 6 In Bangladesh, ongoing trial of chronic hepatitis B treatment by combined vaccine of surface and core antigen (HBsAg and HBcAg) by nasal route is found to be encouraging. [7][8][9] In a 20 weeks treatment, HBV-DNA was undetectable in 33.3% at the end of treatment and was 50% on 12 months of treatment follow-up.…”

Hepatitis B (HB) immunoglobulin plus HB vaccine for intrauterine HB virus infection

“…reported a vaccination protocol that involved the HBV vaccine with multiple doses of a new adjuvant that led to a sustained antibody response to HBsAg in 16 out of 20 patients . Also, HB vaccine was used as an immune modulator for reducing HBV‐DNA in chronic HBV carriers . In addition, according to a previous report, protection through HBV vaccination may be more effective in newborns in whom the HB vaccine induced higher antibody and T‐helper (Th)2 responses than in adults .…”

Epidemiology of Viral Hepatitis and Liver Diseases in Bangladesh

“…Several clinical trials have been conducted in Bangladesh, like combination therapy with lamivudine and vaccine in CHB 9 and interferon and lamivudine in pediatric patients with CHB, 10 which showed limited success and the more recent study of combination therapy with half dose and shorter duration pegylated interferon in combination with entecavir in CHB, which was very promising. 11 However, the study currently ongoing in Bangladesh, that deserves special mention, is the phase III clinical trial involving a therapeutic vaccine (NASVAC) head to head with pegylated interferon in 160 CHB patients.…”