The Role of Tumor Necrosis Factor (TNF) in the Immune Response against Hepatitis B Virus (HBV) and the Use of TNF-Blocking Agents in Patients with HBV Infection and Rheumatic Diseases

Introduction

Hepatitis B virus (HBV) is a noncytopathic, enveloped, double-stranded DNA virus that causes acute and chronic liver disease. Approximately 2 billion people have been infected with HBV worldwide and 350 million remain chronically infected.

Abstract

Tumor necrosis factor-α (TNF-α) plays a critical role in the control of hepatitis B virus (HBV) infection through a variety of mechanisms. It amplifies host responses recruiting and activating macrophages and supporting the proliferation of HBV-specific cytotoxic T cells. It mediates death of infected hepatocytes through proapoptotic effects. It has direct antiviral effect, inhibiting virus replication.

Information on the use of TNF-blocking agents (TNFBA) in HBV-infected individuals is based only on reports of single cases or small series. Forty patients have been described, almost all HBsAg+ inactive carriers. Published data suggest a high risk of viral reactivation in these patients as increased serum HBV-DNA was demonstrated in almost 50% of them, but this risk seems to be reduced when TNFBA were administered together with an antiviral agent (p = 0.03). One case of reactivation has been described in an occult carrier (HBsAg-, anti-HBs+, anti-HBc+).

Based on these reports, we suggest that all patients candidate to TNFBA therapy should be tested for HBV markers, including HBsAg, anti-HBs, and anti-HBc. TNFBA should be avoided in patients with active HBV replication and should be used only with caution in HBsAg+ inactive carriers. In these patients, the risk of viral reactivation might be reduced by prophylactic antiviral drugs that should probably be prolonged for a long time after TNFBA discontinuation. In addition, potential occult carrier subjects that carry a low, but not negligible, risk of viral reactivation should be identified and monitored with particular care.

Keywords

tumor necrosis factor, hepatitis B virus, infliximab, etanercept, adalimumab