May 4, 2014

Maud Lemoine, MD, PhD1 Mark Thursz, MD, PhD1

1Hepatology & Gastroenterology Section, Imperial College, London, United Kingdom

Semin Liver Dis 2014;34:89–97.

Address for correspondence Mark Thursz, MD, PhD, Hepatology & Gastroenterology Section, Imperial College, Norfolk Place, London W2 1NY, United Kingdom (e-mail: m.thursz@imperial.ac.uk).

Abstract

With the advent of all oral direct-acting antiviral drugs with a broad range of genotypic activity and a low incidence of side effects, we are entering an exciting new era in the therapeutics of hepatitis C virus (HCV). However, it is not yet clear who will benefit from these innovations: Will the advantages be limited to HCV patients in industrialized nations or could the whole community of HCV-infected individuals be given access to treatment? As the majority of people infected with HCV live in resource-limited settings it is important to overcome the barriers that restrict access to treatment in these areas. Drug costs, public and professional education, simplified diagnostics, and political imperative all need to be addressed before the majority of HCV-infected individuals can benefit from the new generation of HCV antivirals.

Hepatitis C virus (HCV) infection is prevalent in every country where it has been sought making it a global health problem with an estimated prevalence of over 184 million people worldwide.1 However, the prevalence rates of infection are highly heterogeneous with a disproportionate burden of infection in countries with limited health care resources. In addition to heterogeneity in the prevalence of infection there is also heterogeneity in the distribution of viral genotypes; in most developed countries genotypes 1 and 3 dominate whereas genotypes 4, 5, and 6 aremore common in countries with limited healthcare resources.2

Over the past 15 years HCV genotype 1 has been regarded as themost difficult to treat, requiring 48 weeks of pegylated interferon and ribavirin (PegIFN/RBV) and achieving sustained virological response (SVR) rates of only 45%. However, the development of new direct-acting antivirals (DAAs) which are frequently targeted at genotype 1 have made this genotype easier to treat. New IFN-free DAA combinations have also significantly improved SVR rates in HCV genotype 2 and 4 infected patients. However, results are still unsatisfactory in genotype 3 and data in genotypes 5 and 6 are limited.

There are important differences in the dominant routes of transmission between geographical regionswith intravenous drug use being the most common route of transmission in Europe, North America, and Australasia and iatrogenic transmission being more important in most resource-limited settings.3 Preventive strategies are essential to the control of the HCV epidemic, but the variation in routes of transmission will require a tailored approach to infection control according to the local population needs. The priority in resource-limited countries will be control of transmission in health care facilities whereas the priority in affluent countries will be the interruption of transmission among people who inject drugs (PWID).

Although there is significant variation between countries in the routes of transmission, prevalence and burden of disease there is consistency in resource-limited settings for the poor access to treatment.

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