Injecting drug users with chronic hepatitis C: should they be offered antiviral therapy?

Chronic infection with the hepatitis C virus (HCV) is common in those who inject drugs [1]. The virus is transmitted readily by blood-contaminated needles, syringes or injecting paraphernalia, leading to high rates of infection in injectors—typically, approximately 50% of injectors are infected. Thus, injecting drug users (IDUs) constitute a large reservoir of chronic HCV infection. The natural history of chronic HCV infection is unclear, but up to 30% of patients will develop cirrhosis within 30 years [2] and increasing duration of infection may increase the proportion who develop cirrhosis [3]. Once cirrhosis has developed the outcome is poor, with up to 5% of patients per year developing a life-threatening complication, including decompensated cirrhosis or liver cancer [4]. Fortunately, current therapies for chronic HCV are effective, with more than 50% of patients achieving a sustained virological response that is believed to equate to a cure [5]. Current treatments for HCV involve a 6–12-month course of a long-acting (pegylated) interferon combined with the oral antiviral drug ribavirin. Therapy is effective but expensive, and as young patients respond better than older individuals [6] physicians are increasingly advocating early therapy. Unfortunately, antiviral therapy is associated with a wide range of side effects, such as mild depression, irritability and a flu-like syndrome. Mild anaemia and a decrease in white blood cells and platelets are also usual. Occasionally more severe side effects develop, including psychosis, and in a proportion of patients the anaemia and reductions in leucocytes and platelets necessitate dose reductions. Given that a large proportion of patients with chronic HCV are active injecting drug users (IDUs) the question arises as to whether they should be offered antiviral therapy. There are some ‘obvious’ objections to such an approach. IDUs are engaged in an illegal activity that has led to the acquisition of a virus which is expensive to eradicate. In a cash-limited health-care system some may question whether or not such patients ‘deserve’ to be treated. If patients with HCV and ongoing drug use are treated, then their life-style may put them at risk of re-infection, thereby nullifying any benefits. Furthermore, IDUs may have chaotic life-styles that make regular attendance at treatment centres unlikely and compliance with therapy is expected to be reduced. As injectors may be at increased risk of early death from the complications of drug abuse and because chronic HCV infection is a slow disease, eradicating HCV may be seen as a ‘low priority’ and it might be preferable to focus upon other health care priorities. Many authorities have therefore taken the view that ‘active injectors should not be treated’[7] and should be ‘forced’ to discontinue their illicit drug consumption before being considered for antiviral therapy. Whether such a position is motivated by medical concerns or by a moral compass that refuses to consider IDUs as ‘worthy’ of treatment is not always entirely clear. Given that injectors are engaged in an activity that is likely to transmit HCV it is possible that treating them and eradicating their virus might reduce onward transmission. Furthermore, refusing to treat active injectors may propagate a message that chronic HCV infection is not a ‘serious’ health-care concern and therefore attention to practices (safer injecting techniques) which reduce onward transmission is unnecessary. Hence, one might argue that treating injectors and persuading the injecting community that HCV is a very significant illness may have benefits that extend beyond those who are actually receiving therapy. A proportion of injectors with HCV will inevitably present end-stage liver disease and will present with the complications of cirrhosis, including variceal bleeding and liver cancer. Such complications require emergency treatment, which is invariably provided. Because the management of end-stage liver disease is expensive, and as treating HCV before complications develop is highly cost-effective [8], those who advocate not treating active injectors are supporting a policy whereby cheap therapies are discarded in favour of more expensive ones. The very long-term benefits of therapy for chronic HCV have not yet been demonstrated for any patient group and, with a disease process that takes decades to complete, it is inevitable that robust data confirming that therapy increases life expectancy will take years to accumulate. The argument that the benefits of therapy in injectors will be offset by an increase in premature death may be applied to any group infected with HCV. Indeed, it is not standard medical practice to quantify the risk: benefits of viral clearance in individual patients. For instance, diabetic patients or those with haemophilia do not have life expectancy calculations performed alongside a cost–benefit analysis of the advantages of therapy before being offered antiviral treatment, and it seems perverse that only active injectors are expected to provide ‘evidence’ of the benefits of therapy when other patients are not required to do so. In our experience of treating injectors in East London, the benefits of antiviral therapy extend well beyond viral eradication and include an enhanced sense of personal worth that is often associated with an improvement in life-style choices and an attempt to enhance the overall quality of health. Preventing injectors from receiving therapy because the life expectancy gains may be less than in non-injectors may deny patients opportunities to improve their overall health, with unquantifiable benefits to the individual and society as a whole. The arguments in favour of treating those who inject drugs would be invalidated by data showing that either injectors do not comply with therapy or rapidly re-infect themselves. Data showing that treating injectors was futile and doomed to fail would provide convincing evidence in favour of a policy of active attempts to reduce illicit consumption prior to starting antiviral therapy. To date, studies have failed to show any convincing evidence of compliance problems in those who inject drugs—studies with human immunodeficiency virus (HIV) medication and anti-tuberculosis medication indicate that injectors do comply with therapy (reviewed in [9]) and increasingly studies are emerging showing that therapy for chronic HCV in active injectors can be administered with good compliance and success rates [10]. Furthermore, the few studies to date that have examined re-infection rates show a very low rate of recurrent HCV in those who have eliminated the virus [11]. Whether the low infection rates seen are due to a protective immune response or to better use of safe injecting techniques is unclear. However, regardless of the mechanism it is clear that re-infection rates are low. The arguments in favour of treating IDUs are based upon a growing body of evidence which remains incomplete. Most of the studies have been performed by enthusiasts with an interest in treating injectors, and the total number of patients studied remains relatively small. Nevertheless, there is a clear body of emerging data indicating that IDUs can be treated successfully in specialist centres where appropriate facilities are available. The challenge for those looking to improve the care offered to IDUs with viral hepatitis is to ensure that all those who choose to inject drugs have access to services delivering antiviral therapy. Those who provide such services must ensure that the outcomes are subjected to regular audits and reviews to identify failings in service delivery that require further intervention. Without such service provision, many IDUs will develop avoidable complications of end-stage liver disease. Professor Foster has consultancy agreements and research contracts with a number of companies who market drugs for the treatment of hepatitis C. These include Roche, Gilead, Novartis and Chughai.