Comparison of Different Treatment Combinations for Chronic Hepatitis B Infection

Abstract

Chronic hepatitis B virus (HBV) infection is a leading cause of cirrhosis and hepatocellular carcinoma worldwide. Its prevalence approaches 10% in hyper endemic areas. The aim of treating chronic HBV infection is to halt progression of liver injury by suppressing viral replication or eliminating infection. This study was planned to evaluate the advantages of combination therapy with interferon-alpha plus second-generation nucleoside analogues (lamivudine or famciclovir), or vaccination with a pre-S2 and S proteins containing vaccine in chronic HBV infection. 29 patients were divided into three groups and were treated with the following combinations: (1) IFN-alpha2a 9 million units 3x week for 6 months with HBV vaccine 20 microg given on 0, 1 and 2 months; (2) IFN-alpha2a 6 million units 3x week plus famciclovir 250 mg 3x day for 6 months; (3) IFN-alpha2a 6 million units 3x week plus lamivudine 100 mg/day for 6 months. Complete response was suspected in 3 patients in group 1, in 4 patients in group 2, and in 7 patients in group 3. Partial response was suspected in 4, 1 and 2 patients in groups 1, 2 and 3, respectively. The results of the present study suggest that the combination of IFN-alpha with lamivudine is more effective than the combination of IFN-alpha with HBV vaccination or famciclovir.

Current therapeutic approaches in childhood chronic hepatitis B infection: A multicenter study

“…13 Lamivudine is able to cause normalization of aminotransferase activities at the end of treatment and the suppression of viral load in a high percentage (95.5%) of cases. 5 In groups 2 and 3 in the present study, high percentages of ALT normalization and HBV DNA clearance were seen in comparison with group 1.…”

“…Lamivudine resistance as a result of mutant/variant viruses is observed in 19% of children after 1 year, a figure that may increase by an average of 20% per year 13 . Lamivudine is able to cause normalization of aminotransferase activities at the end of treatment and the suppression of viral load in a high percentage (95.5%) of cases 5 . In groups 2 and 3 in the present study, high percentages of ALT normalization and HBV DNA clearance were seen in comparison with group 1.…”

“…The therapeutic endpoints for hepatitis B treatment are: sustained suppression of HBV replication, as indicated by hepatitis Bs antigen (HBsAg) and hepatitis Be antigen (HBeAg) loss, decrease serum HBV DNA to an undetectable level by a non‐polymerase chain reaction (PCR) method, and remission of disease, as shown by normalization of alanine aminotransferase (ALT) together with improvement in liver histology 4 . Eradication of HBV infection or long‐term suppression of viral replication will reduce both necroinflammatory processes in liver tissue and the risk of progression to cirrhosis 5,6 …”

“…4 Eradication of HBV infection or long-term suppression of viral replication will reduce both necroinflammatory processes in liver tissue and the risk of progression to cirrhosis. 5,6 Better understanding of HBV replication, natural history and the immunopathogenesis of chronic hepatitis B, together with the introduction of effective agents with different mechanisms of action, are the basis for better therapeutic strategies against chronic hepatitis B.…”

Therapeutic vaccination for treatment of chronic hepatitis B

“…In an attempt to improve immunogenicity, vaccines combining HBsAg with hepatitis B immunoglobulin were tested in untreated individuals, but ultimately this had similarly disappointing results (Supporting information, Table S2, (76)(77)(78)(79)(80)). Even in combination with nucleos(t)ide analogues or interferon treatment, vaccine therapy showed no additional benefit over nucleos(t)ide analogues alone (81)(82)(83)(84)(85)(86)(87). Another recombinant vaccine CVI-HBV-002 delivering the long, medium and small HBV surface proteins (surface/pre-S2/Pre-s1 regions) with adjuvant (L-pampo) is currently in Phase II clinical trials in chronic HBV patients, although results are yet to be reported (88).…”