Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Sciences, Hiroshima, Japan.
Research Center for Hepatology and Gastroenterology, Hiroshima University, Hiroshima, Japan.
Liver Int. 2022 Aug;42(9):1935-1944. doi: 10.1111/liv.15150. Epub 2022 Jan 17.
Since its discovery in 1989, the road to a cure for hepatitis C virus (HCV) has been slow, but most patients can now expect to achieve a sustained virological response (SVR). With direct-acting antiviral (DAA) combination therapies such as glecaprevir/pibrentasvir and velpatasvir/sofosbuvir, 98% of patients successfully eradicate the virus, even if previous treatments failed or if resistance-associated substitutions (RASs) are present. Adverse events are rare or mild, and patients with compensated cirrhosis and other co-morbidities are often eligible for treatment. However, a small number of patients fail to eradicate the virus even after retreatment. The cause of failure is mainly due to emergence of NS5A P32 deletion mutants after initial DAA therapy in genotype 1b patients, although the reason is unknown for some patients. Alternative therapies that do not rely on NS5A inhibitors, such as sofosbuvir plus ribavirin, can be attempted in these patients. While scaled-up treatment efforts present a challenge, another problem is that many carriers are unaware of their infection. Long-term damage to the liver becomes irreversible, and patients who are not diagnosed in time can develop liver cancer or liver failure even after eliminating the virus. The long-term costs of treatment of advanced liver disease in undiagnosed patients relative to the immediate costs of DAA therapy should be considered. As no vaccine is yet available, eventual elimination of the virus requires identifying and treating undiagnosed cases and screening of high-risk populations such as injection drug users and men who have sex with men and female sex workers.
自 1989 年发现以来，治愈丙型肝炎病毒（HCV）的道路一直很漫长，但现在大多数患者都有望实现持续病毒学应答（SVR）。直接作用抗病毒（DAA）联合疗法，如 glecaprevir/pibrentasvir 和 velpatasvir/sofosbuvir，可使 98%的患者成功消除病毒，即使先前的治疗失败或存在耐药相关替代（RAS）。不良反应罕见或轻微，代偿性肝硬化和其他合并症患者通常有资格接受治疗。然而，仍有少数患者即使进行再治疗也无法消除病毒。失败的原因主要是由于基因型 1b 患者在初始 DAA 治疗后出现 NS5A P32 缺失突变体，尽管有些患者的原因尚不清楚。对于这些患者，可以尝试不依赖 NS5A 抑制剂的替代疗法，如索非布韦加利巴韦林。虽然扩大治疗力度带来了挑战，但另一个问题是许多携带者不知道自己感染了病毒。肝脏的长期损伤变得不可逆转，未及时诊断的患者即使在消除病毒后也可能发展为肝癌或肝功能衰竭。未诊断患者的晚期肝病治疗的长期成本相对于 DAA 治疗的直接成本应该被考虑。由于目前尚无疫苗，因此需要确定和治疗未诊断的病例，并对注射吸毒者、男男性行为者和性工作者等高危人群进行筛查，以最终消除病毒。
