Brief Report Combination Therapy with Antiviral Drugs and Hepatitis B Vaccine in Incidentally-Detected and Asymptomatic Chronic Hepatitis Virus B Carriers at Bangladesh Mamun Al-Mahtab, 1,4 Salimur Rahman, 1,4 Sheikh Mohammad Fazle Akbar, 2 Sakirul Islam Khan, 3,4 Helal Uddin, 4 Fazal Karim, 5 and Faroque Ahmed 5 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 mg 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. Introduction C hronic hepatitis B virus (HBV) infection represents a major global public health problem, affecting about 350 million patients. Of these about 300 million may be asymp- tomatic. All chronically HBV-infected subjects, both symp- tomatic and asymptomatic, are the permanent reservoir of the virus responsible for transmission of the virus to healthy subjects. In addition, chronically HBV-infected persons may develop complications, such as cirrhosis, hepatic decompen- sation, and hepatocellular carcinoma (3). Most professional organizations recommend antiviral treatment for patients with chronic hepatitis B (CHB) with evidence of liver damage (9). Clinical trials have shown that these drugs are moderately effective in CHB patients during their immune clearance phase, but they are not effective during the immune tolerance phase of chronic HBV infection (i.e., asymptomatic chronic HBV carriers) (6). However, liver biopsy specimens from asymptomatic HBV carriers have exhibited features of mod- erate to severe liver damage, and many of them are prone to develop severe liver disease with complications (1,7,8). In this complex situation, we postulated that if HBV-specific im- munity could be induced in asymptomatic chronic HBV car- riers with an immune modulator such as hepatitis B vaccine, then antiviral drugs might be effective in these patients. Materials and Methods To test our hypothesis, a group of HBV-infected patients without any subjective symptoms of liver diseases were en- rolled in this study. HBV infection was detected incidentally in several hundred apparently healthy subjects when they 1 Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh. 2 Department of Medical Sciences, Toshiba General Hospital, Tokyo, Japan. 3 Department of Animal Science, Bangladesh Agricultural University, Mymensingh, Bangladesh. 4 Viral Hepatitis Foundation Bangladesh, Dhaka, Bangladesh. 5 Department of Hepatology, Dhaka Medical College, Dhaka, Bangladesh. VIRAL IMMUNOLOGY Volume 23, Number 3, 2010 ª Mary Ann Liebert, Inc. Pp. 335–338 DOI: 10.1089=vim.2009.0104 335