Addition of ribavirin to daclatasvir plus asunaprevir for chronic hepatitis C 1b patients with baseline NS5A resistance-associated variants improved response

作者：Hong Chun Ming; Liu Chun Jen; Yeh Shiou Hwei; Chen Pei Jer^*

来源：Journal of the Formosan Medical Association, 2017, 116(4): 295-299.

DOI：10.1016/j.jfma.2016.11.014

• direct-acting antivirals
• hepatitis C
• resistance-associated variant

Background/purpose: Daclatasvir is a nonstructural protein 5A inhibitor with potent activity against hepatitis C virus genotypes 1-6 in vitro, and asunaprevir is a nonstructural protein 3 protease inhibitor with activity against genotypes 1, 4, 5, and 6. Despite a 90% sustained virologic response (SVR) rate, the SVR rate in patients with baseline NS5A-L31/Y93H polymorphisms decreased to around 40%. Therefore, an alternative regimen under the consideration of cost-effectiveness would be important. Whether the addition of ribavirin could improve the SVR rate among this group of patients remains unknown and hence our case series was reported.
Methods: For six adult chronic hepatitis C 1b patients with a pre-existing NS5A-Y93H (> 20%) polymorphism, we added ribavirin (800 mg/d) to daclatasvir/asunaprevir for 24 weeks and followed through 12-weeks post-treatment. Four of these patients received interferon/ribavirin treatment before but relapsed, while the other two were naive cases. Two of them had liver cirrhosis and one had hepatocellular carcinoma postcurative therapy. The primary efficacy end-point was undetectable hepatitis C virus RNA (hepatitis C virus RNA level of < 25 IU/mL) at 12 weeks after the end of the treatment (SVR12).
Results: In total, five cases reached SVR12 eventually (SVR rate: 83%; 95% confidence interval: 18.6-99.1%). However, the viral load of one remaining patient rebounded from the 24(th) week of treatment. No patients developed significant adverse effects during and after the treatment.
Conclusion: In genotype 1b chronic hepatitis C patients with NS5A-Y93H polymorphism, the addition of ribavirin to daclatasvir/asunaprevir may increase the SVR12 rate with minimal side effects, and thus deserves more comprehensive trials in resource-limited areas.

• 出版日期2017-4