Efficacy and Tolerability of Pegylated Interferon-α-2a in Chronic Hepatitis B

A Multicenter Clinical Experience

Dilip Ratnam; Anouk Dev; Tin Nguyen; Vijaya Sundararajan; Hugh Harley; Wendy Cheng; Alice Lee; Ferry Rusli; Robert Chen; Sally Bell; Stephen Pianko; William Sievert

Disclosures

J Gastroenterol Hepatol. 2012;27(9):1447-1453. 

In This Article

Abstract and Introduction

Abstract

Background and Aim: Pegylated interferon-α (PEG-IFN) provides potential advantages over nucleos(t)ide analogues in the treatment of chronic hepatitis B (CHB) given its finite course, durability and lack of drug resistance. Much of the evidence is derived from controlled studies and it is unclear whether these results can be replicated in an everyday, non-controlled setting. The aim of this study was to examine the efficacy and tolerability of PEG-IFN-α2A in CHB patients in a clinical setting.
Methods: Chronic hepatitis B patients treated with PEG-IFN-α2A (180 μg/week, 48 weeks) at five tertiary hospitals were retrospectively identified. Baseline demographic and clinical data, on-treatment virological and serological responses and adverse events (AE) were recorded. Treatment outcomes were defined as alanine aminotransferase (ALT) normalization, hepatitis B virus DNA < 351 IU/mL and hepatitis B e antigen (HBeAg) seroconversion.
Results: Sixty three HBeAg positive patients were identified (65% male, 80% born in Asia, 84% with viral loads > 6log IU/mL, 9.5% advanced fibrosis). Six months after therapy 46% achieved normalization of ALT, 16% had viral loads < 351 IU/mL and 32% achieved HBeAg seroconversion. 29 HBeAg negative patients were treated (75% male, 86% born in Asia, 48% had viral loads > 6log IU/mL, 24% advanced fibrosis). Six months post-treatment, 55% and 36% maintained a normalized ALT and HBV DNA < 351 IU/mL, respectively. Optimal viral suppression was maintained in 50–75% of patients over 2 years of follow up. 6.5% of all patients discontinued therapy due to AEs.
Conclusion: In everyday clinical practice PEG-IFN therapy in CHB is well tolerated and can achieve a similar efficacy to that seen in large controlled trials.

Introduction

Chronic infection with the hepatitis B virus (CHB) is a global health concern, affecting up to 400 million people worldwide. Between 20% to 40% of affected individuals will develop the most serious consequences of cirrhosis, hepatic decompensation and hepatocellular carcinoma (HCC), resulting in approximately 500 000 to 1.2 million deaths per year worldwide.[1] Treatment can reduce mortality from end stage liver disease.[2–6] Two classes of antiviral therapy are available—nucleoside or nucleotide analogues, and interferon-α (INF-α) (standard or pegylated forms). The choice of a particular therapy for a given individual can be complex, influenced by factors including age, serum alanine transasminase (ALT), histological findings, hepatitis B e-antigen (HBeAg) status, hepatitis B virus (HBV) viral load and genotype, previous therapy and tolerability of potential adverse effects. Globally, nucleos(t)ide analogues are the more commonly used option, often favored due to their combination of high antiviral potency, ease of use and high tolerability. However, this class has limitations such as the potential development of viral resistance, as well the need for long term therapy in many individuals.

Interferon-α acts against HBV by both immunomodulatory and direct antiviral mechanisms. Compared with the nucleoside analogues it is associated with higher rates of HBeAg to anti-HBe seroconversion, greater durability of response and lack of antiviral resistance.[7] However, it is not as potent at achieving viral suppression, is less convenient to use and is associated with a number of side effects. Pegylated interferon-α (PEG-IFN) was introduced approximately a decade ago with a view to improving efficacy, convenience and tolerability through its improved pharmacodynamic profile compared with standard interferon. While the evidence suggests that PEG-IFN is both effective and safe in the treatment of CHB, this data has been derived almost exclusively from a handful of controlled trials. Whether these results can be replicated in a day to day, non-controlled setting is unclear, particularly given concerns that tolerability of the drug may adversely affect adherence. In this study we performed a retrospective evaluation of the outcomes of PEG-IFN-α therapy for both HBeAg positive (HBeAg[+]) and HBeAg negative (HBeAg[−]) CHB patients treated in Australian tertiary hospitals, with the aim of determining effectiveness and tolerability in an everyday clinical setting.

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