The current standard of care for hepatitis C infection is peginterferon/ribavirin (PegIFN/RBV). We are entering the era where direct-acting antiviral agents (DAAs) will be added to PegIFN/RBV, leading to higher sustained response rates in genotype 1 infected individuals. Currently DAAs are directed toward specific proteins involved in hepatitis C replication with NS3/NS4A protease inhibitors furthest in development. Telaprevir and boceprevir are both NS3/NS4a inhibitors that significantly improve sustained response when added to PegIFN and RBV. The hepatitis C virus (HCV) polymerase inhibitors are another promising DAA class. These molecules are divided into nucleoside/nucleotide polymerase inhibitors and nonnucleotide/nucleoside polymerase inhibitors. Nucleoside/nucleotide polymerase inhibitors have a high barrier to resistance and appear to be effective across a broad range of genotypes. Nonnucleoside polymerase inhibitors have a lower barrier of resistance and appear to be genotype specific. Preliminary data with these compounds are also promising. A third class, NS5A inhibitors, has also shown potent HCV RNA suppression in preliminary studies as monotherapy and with PegIFN and RBV. Combinations of these agents are also entering clinical trials and indeed a preliminary report has demonstrated that the combination of an NS3/4A protease inhibitor and NS5B polymerase inhibitor can effectively suppress virus in genotype 1 individuals. Future studies will concentrate on combinations of direct-acting antiviral agents without and with PegIFN and RBV. Clinicians will need to be familiar with managing side effects as well as resistance as we enter this new era.
Antiviral Agents ; Genotype ; Hepacivirus ; Hepatitis ; Hepatitis C ; Oligopeptides ; Proline ; Protease Inhibitors ; Proteins ; RNA ; Standard of Care ; Viruses

Chronic hepatitis C infection is a major cause of liver disease and hepatocellular carcinoma worldwide. While hepatitis C has been treated for decades with some success, the introduction of direct acting antiviral agents has revolutionized the treatment of hepatitis C with finite, highly effective, well-tolerated therapy and there are few populations that cannot be successfully treated now or are complicated to manage. The World Health Organization has released elimination targets in an effort to eliminate viral hepatitis and reduce dramatically the morbidity and mortality caused by both viral hepatitis. While hepatitis C is straightforward to treat, it remains problematic to eliminate on a global scale. Diagnosis of hepatitis C remains the major gap in the cascade of care and numerous screening strategies will be required to reduce this gap. While historically, treatment of hepatitis C has been centralized, decentralized approaches will be required to diagnose, evaluate, and link to care the large population of individuals worldwide with hepatitis C across low-, middle-, and high-income countries. With the introduction of multiple pangenotypic treatment options and reduced cost for these therapies, assessment and treatment for those with hepatitis C has been simplified and made more accessible worldwide. There are multiple populations for whom care models are being developed and refined, including those when inject drugs, those who are incarcerated, those who present with sexually transmitted disease including the men who have sex with men population, amongst many others. While a vaccine for hepatitis C remains elusive these efforts continue. Multiple successful elimination efforts have been reported.

Chronic hepatitis C infection is a major cause of liver disease and hepatocellular carcinoma worldwide. While hepatitis C has been treated for decades with some success, the introduction of direct acting antiviral agents has revolutionized the treatment of hepatitis C with finite, highly effective, well-tolerated therapy and there are few populations that cannot be successfully treated now or are complicated to manage. The World Health Organization has released elimination targets in an effort to eliminate viral hepatitis and reduce dramatically the morbidity and mortality caused by both viral hepatitis. While hepatitis C is straightforward to treat, it remains problematic to eliminate on a global scale. Diagnosis of hepatitis C remains the major gap in the cascade of care and numerous screening strategies will be required to reduce this gap. While historically, treatment of hepatitis C has been centralized, decentralized approaches will be required to diagnose, evaluate, and link to care the large population of individuals worldwide with hepatitis C across low-, middle-, and high-income countries. With the introduction of multiple pangenotypic treatment options and reduced cost for these therapies, assessment and treatment for those with hepatitis C has been simplified and made more accessible worldwide. There are multiple populations for whom care models are being developed and refined, including those when inject drugs, those who are incarcerated, those who present with sexually transmitted disease including the men who have sex with men population, amongst many others. While a vaccine for hepatitis C remains elusive these efforts continue. Multiple successful elimination efforts have been reported.