Lamivudine vs lamivudine and interferon combination treatment of HBeAg(−) chronic hepatitis B

Abstract

To determine whether combination treatment of HBeAg(-) chronic hepatitis B is beneficial we studied 78 patients with HBeAg(-), HBV DNA-positive chronic hepatitis B who were randomized to lamivudine, 100 mg, qd, for 12 months or lamivudine-interferon (9 MU, t.i.w.) in combination. In the combination arm, 2 months of lamivudine treatment preceded 10 months of combination treatment. Biochemical, virologic and histologic responses were assessed at the end of treatment, after six and a median 27 months of drug-free follow-up (short- and long-term follow-up, respectively). Virologic response was defined as undetectable HBV DNA with a hybridization assay and biochemical response as normal alanine aminotransferase (ALT). Change in HBV DNA was also assessed by real-time polymerase chain reaction (PCR). Presence of YMDD mutants at the end of treatment was investigated with a line probe assay. Both treatment regimes led to a median 2 log decline in HBV DNA levels. Virologic end of treatment responses were 90 and 92% with mono- and combination treatment, respectively. Corresponding virologic responses at short- and long-term follow-up were 59 and 54%, and 27 and 25%, respectively. Patients having a baseline HBV DNA value > or =200 pg/mL were more likely to relapse within 6 months off therapy than those patients with a baseline HBV DNA level <200 pg/mL (P = 0.041). YMDD mutants were observed in 53% of patients receiving lamivudine compared with 24% of patients receiving the combination regime (P = 0.017). In conclusion, efficacy of combination treatment is similar to lamivudine monotherapy. However, combination treatment decreases the development of YMDD mutant strains compared with lamivudine monotherapy.

Pegylated Interferon Alfa-2b Monotherapy and Pegylated Interferon Alfa-2b plus Lamivudine Combination Therapy for Patients with Hepatitis B Virus E Antigen-Negative Chronic Hepatitis B

“…Another controversial issue is whether to use nucleoside/nucleotide analogues alone, IFN alfa alone, or both in combinations. Previous studies showed that the combination of IFN alfa and lamivudine does not increase the rate of treatment success in patients with HBeAg-negative CHB (10)(11)(12). In two largescale, randomized, controlled studies of patients with HBeAgpositive CHB, similar virological response rates occurred whether PEG-IFN alfa-2a or PEG-IFN alfa-2b was administered as monotherapy or in combination with lamivudine (5, 7).…”

Serum connective tissue markers as predictors of advanced fibrosis in patients with chronic hepatitis B and D

“…Of these, 43 had HBeAg (+) chronic hepatitis B, 40 had HBeAg (-), anti-HBe (+) and HBV DNA (+) chronic hepatitis B, and 33 suffered from chronic delta hepatitis. Sera were either obtained at baseline from patients who had participated in various clinical trials (22)(23)(24), or were obtained during evaluation of candidates for eventual treatment. In this context, patients represented a homogeneous cohort, since all of them had clinically compensated liver disease with a serum albumin >3.5 g, a normal bilirubin, and a prothrombin time not beyond 3 seconds of the normal range.…”

Establishment of a Novel Quantitative Hepatitis D Virus (HDV) RNA Assay Using the Cobas TaqMan Platform To Study HDV RNA Kinetics

“…Pegylated alfa interferon has also been used in small trials to treat delta hepatitis, and the sustained virological response rates were about 20% (2, 7, 21). The nucleoside and nucleotide analogues used for the treatment of HBV infection are ineffective against HDV (22,23,39,40,42). No study has systematically investigated the effect of tenofovir or entecavir, two potent HBV polymerase inhibitors that have recently been approved for use for the treatment of hepatitis B, on HDV replication (5,8).…”