Adverse effects of antiviral therapy are more prevalent in elderly patients (age 
60 years) with chronic hepatitis C (CHC) than in their younger counterparts, and often interrupt or halt their treatment.1 Interferon and ribavirin treatment is, therefore, considered to have reduced efficacy in this group. Elderly patients with CHC, however, have an increased risk of developing hepatocellular carcinoma, and antiviral therapy is an effective way of reducing this risk and improving survival. However, the clinical utility of antiviral therapy in elderly patients is not clear and little information is available on their prognosis, with or without such therapy.
A 2009 retrospective study by Ikeda and colleagues investigated the clinical utility of antiviral therapy in a large cohort of elderly patients with CHC. This study analyzed data on 1,917 patients (aged 60 years) with HCV infection.2 A total of 454 individuals received interferon therapy. Survival and the risk of hepatocarcinogenesis were analyzed in three groups of patients, stratified according to their platelet count before therapy: high (>150 
109/l), intermediate (100–149 109/l) or low (<100 109/l). The study demonstrated that hepatocarcinogenesis was significantly and inversely correlated with platelet count. Interferon treatment for a subgroup of elderly patients with an intermediate or low platelet count conferred substantial advantages with regard to both hepatocarcinogenesis and survival. Among patients with a high platelet count and mild liver disease, interferon did not decrease the rate of hepatocarcinogenesis.
Several major clinical observations have contributed to the rationale for offering antiviral therapy to elderly patients with CHC. First, the prevalence of elderly patients with CHC in the US and Japan is increasing owing to a significant decrease in new, blood-borne HCV infections and improved life expectancy.3, 4 Second, a general consensus in the literature is that patients with CHC who respond to interferon therapy have a reduced risk of developing hepatocellular carcinoma.5 So, in terms of cost versus benefit, every patient with CHC should be considered a potential candidate for antiviral therapy. The guidelines of the Italian Association for The Study of Liver Disease recommend that interferon treatment should be given to elderly patients (defined as those aged 65 years) with CHC who have an increased risk of developing severe liver disease.6
The study by Ikeda and colleagues2 is important because it demonstrates that platelet count can be used as a simple indicator of the risk of hepatitis progression. Moreover, logistic regression analysis revealed that an intermediate or low platelet count, male sex and high serum alanine aminotransferase levels were independent factors associated with hepatocarcinogenesis. Conversely, rates of hepatocarcinogenesis in patients with a sustained virological response (SVR) were significantly lower than those in patients who did not respond to therapy or who did not receive interferon therapy.
The median age of elderly patients included in Ikeda et al.'s study was 64 years. Indeed, the majority of published studies on the treatment of hepatitis C in the elderly have examined populations aged 
65 years. No information is yet available on the effects of antiviral treatment in very elderly individuals (aged 75 years), who are still generally considered unsuitable for antiviral therapy.
In general, SVR rates to antiviral therapy are lower in elderly patients than in younger individuals (<60 years).7 Ikeda and colleagues' study reports an SVR rate of 35.6% in elderly patients with CHC, which confirms findings previously reported in the literature.7, 8 Such an SVR rate should be considered acceptable despite being lower than that generally achieved in young adults.
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Reductions in dosage of either interferon or ribavirin, and discontinuations of therapy owing to adverse effects, are more frequent in patients aged >60 years and should be taken into account when antiviral therapy is considered.8 In fact, dose adjustments may be an effective approach to treatment of some adverse events, particularly hematological ones, but the resultant suboptimal dosing and potential influence on virological response are a major concern. Older patients (>65 years) may be at risk of neurological adverse effects of interferon, such as confusion, lethargy, cognitive changes and depression, especially if they have a history of neurological and/or psychiatric disorders.9 Multiple adverse effects are common in this subgroup of patients, and are occasionally severe.
In view of Ikeda and colleagues' findings, a practical message can be agreed on: interferon treatment should be considered in elderly patients with CHC, but it should be initiated at age 
60 years to reduce the risk of adverse effects. Thus, an elderly patient with CHC but without decompensation and with an intermediate or low platelet count is a candidate for interferon therapy; however, close hematologic monitoring is mandatory for such patients. The clinical feasibility of managing elderly patients with low-dose, intermittent, long-term interferon therapy to achieve a sustained biochemical response without an increased risk of profound and irreversible adverse effects is not clear. Forthcoming studies that employ noninvasive methods to assess fibrosis, namely transient elastography, should improve the assessment of disease progression in elderly patients and enable the utility of such low-dose, long-term therapy to be elucidated.
Finally, are there any elderly patients with CHC who do not need interferon therapy? Future research should be dedicated to the follow-up of asymptomatic, elderly patients with CHC who have high platelet counts. Such patients should be monitored for hepatocarcinogenesis with liver ultrasonography performed every 6–12 months. Very old (age 75 years) patients with CHC should not be treated with interferon because of their short life expectancy and the high probability of severe adverse effects.
Practice point
- Interferon treatment should be considered in elderly (age 60–75 years) patients with CHC, but therapy should be initiated at age 60 years to reduce adverse effects
- Elderly patients with CHC but without decompensation and with an intermediate or low platelet count are candidates for interferon therapy; however, close hematologic monitoring of such individuals is mandatory
- Very old (age 75 years) patients with CHC should not be treated with interferon because of their short life expectancy and the high probability of severe adverse effects
