Health & Medical hepatitis

Hepatitis C Therapy in Elderly Patients

Hepatitis C Therapy in Elderly Patients

Abstract and Introduction

Abstract


Background & Aims: Age is frequently discussed as negative host factor to achieve a sustained virological response (SVR) to antiviral therapy of chronic hepatitis C. However, elderly patients often show advanced fibrosis/cirrhosis as known negative predictive factor. The aim of this study was to assess age as an independent predictive factor during antiviral therapy.

Methods: Overall, 516 hepatitis C patients were treated with pegylated interferon-α and ribavirin, thereof 66 patients ≥60 years. We analysed the impact of host factors (age, gender, fibrosis, haemoglobin, previous hepatitis C treatment) and viral factors (genotype, viral load) on SVR per therapy course by performing a generalized estimating equations (GEE) regression modelling, a matched pair analysis and a classification tree analysis.

Results: Overall, SVR per therapy course was 42.9 and 26.1%, respectively, in young and elderly patients with hepatitis C virus (HCV) genotypes 1/4/6. The corresponding figures for HCV genotypes 2/3 were 74.4 and 84%. In the GEE model, age had no significant influence on achieving SVR. In matched pair analysis, SVR was not different in young and elderly patients (54.2 and 55.9% respectively; P = 0.795 in binominal test). In classification tree analysis, age was not a relevant splitting variable.

Conclusions: Age is not a significant predictive factor for achieving SVR, when relevant confounders are taken into account. As life expectancy in Western Europe at age 60 is more than 20 years, it is reasonable to treat chronic hepatitis C in selected elderly patients with relevant fibrosis or cirrhosis but without major concomitant diseases, as SVR improves survival and reduces carcinogenesis.

Introduction


More than 170 million people worldwide are chronically infected with the hepatitis C virus (HCV), which is responsible for more than 100 000 cases of hepatocellular carcinoma (HCC) per year. It is estimated that about 1% of the Swiss population is infected with HCV. The likelihood of achieving a sustained virological response (SVR) to antiviral therapy depends on both viral and host characteristics. Overall, SVR rates of patients treated with the combination of pegylated interferon-α (PEG-IFN-α) and ribavirin for 48 weeks are around 55%. SVR is achieved in around 50% of patients infected with HCV genotype 1 treated for 48 weeks and around 80% of patients infected with HCV genotype 2 or 3 treated for 24 weeks. In patients with genotype 1 only, the new directly acting agents boceprevir and telaprevir can be combined with PEG-IFN-α and ribavirin, which has led to substantially improved SVR rates.

The increasing life expectancy in developed countries and the long-standing course of chronic hepatitis C make it likely that physicians will face a growing number of elderly patients with HCV-related liver disease in the next 10–20 years. As ageing is strongly associated with liver fibrosis progression, elderly patients are likely to have advanced liver disease and a high risk for liver-related complications. On the other hand, many clinicians are reluctant to treat HCV infection in the elderly, as these are considered to be more susceptible to develop treatment-related side effects. In turn, side effects may necessitate early termination of antiviral therapy, as it occurs in 10–14% of 'young' patients with chronic hepatitis C. Others argue that the role of antiviral therapy is doubtful in a patient group with only limited life expectancy. This argument, however, is challenged by studies showing that IFN-α-based therapy of chronic hepatitis C improves survival and reduces carcinogenesis in general and also in the elderly. In addition, a recent study (in non-elderly patients) has clearly shown the strong independent positive influence of antiviral therapy with PEG-IFN-α and ribavirin on the incidence of HCC.

The perception that the elderly tolerate antiviral therapy less well is not based on sound evidence. Indeed, limited data are currently available on antiviral therapy of chronic hepatitis C in elderly patients. Only few patients >60 years have been included in the largest trials of PEG-IFN-α and ribavirin, and no detailed analysis was performed in these trials to address the influence of age on achieving SVR. Furthermore, only few studies have focussed on therapy with PEG-IFN-α and ribavirin in elderly patients, of which three were performed in Japan, whereas three other reported data from Caucasian patients. The largest study was published recently and reported data on 378 patients with hepatitis C who had received an antiviral therapy after the age of 65 years. However, as many other studies, this study lacked a thorough statistical analysis of confounding factors.

This study examined how age might have an impact of SVR, considering all relevant negative confounders.

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