C型慢性肝炎・肝硬変に対する抗ウィルス療法の進歩

抄録

Hepatitis C virus (HCV) infection is one of the most prevalent infectious diseases in the world, with approximately 170 million people infected. Persistent HCV infection induces liver inflammation and fibrosis, increasing the risks of liver cirrhosis and hepatocellular carcinoma. The sustained virologic response rate of genotype 1 chronic hepatitis C patients on a previously used treatment regime (pegylated interferon and ribavirin therapy) was only 40%-60%. This combination therapy causes various adverse events and cannot be tolerated by or is contraindicated for some patients. The use of ribavirin in patients with an estimated glomerular filtration rate of <50 mL/min/1.73 m² is particularly problematic, because ribavirin and its metabolites are excreted by the kidneys. Recently, remarkable advances have been made in the treatment of patients with chronic hepatitis C, and interferon-free, direct-acting antivirals have become the primary treatment strategy instead of interferon-based treatments. Direct-acting antiviral treatments comprise combinations of NS3/4 protease inhibitors, NS5A inhibitors, and NS5B polymerase inhibitors. The combination of asunaprevir (NS3/4 protease inhibitor) and daclatasvir (NS5A inhibitor) was the first interferon-free treatment to be approved in Japan. Thereafter, several combination treatments have been approved, including ledipasvir (NS5A inhibitor)/sofosbuvir (NS5B polymerase inhibitor), ombitasvir (NS3/4 protease inhibitor)/paritaprevir (NS5A inhibitor)/ritonavir, ombitasvir/paritaprevir/ritonavir/dasabuvir (NS5B polymerase inhibitor), grazoprevir (NS3/4 protease inhibitor)/elbasvir (NS5A inhibitor) and glecaprevir (NS3/4 protease inhibitor)/pibrentasvir (NS5A inhibitor). All these treatments have demonstrated high efficacy and safety, with over 90% of the patients achieving a sustained virologic response. Thus, HCV has become easy to eliminate in most patients with hepatitis C. However, there may still be some patients who are currently infected with HCV, and identifying those who have not received treatment may be a problem. Lastly, considerable numbers of patients attending institutions without hepatologists or hemodialysis facilities are not receiving anti-HCV treatment, so cooperation is required between hepatologists and physicians working in other fields.