Real-world safety and efficacy of paritaprevir/ritonavir/ombitasvir plus dasabuvir ± ribavirin in patients with hepatitis C virus genotype 1 and advanced hepatic fibrosis or compensated cirrhosis: a multicenter pooled analysis.

Abstract

Paritaprevir/ritonavir, ombitasvir, and dasabuvir (PrOD) with or without ribavirin shows favorable results in hepatitis C virus genotype 1 (HCV-1) patients in terms of safety and efficacy, but real-world data remain limited for those with advanced hepatic fibrosis (fibrosis 3, F3) or compensated cirrhosis (F4). A total of 941 patients treated in four hospitals (the Keelung, the Linkuo, the Chiayi and the Kaohsiung Chang Gung Memorial Hospital) through a nationwide government-funded program in Taiwan were enrolled. Patients with HCV and advanced hepatic fibrosis or compensated cirrhosis received 12 weeks of PrOD in HCV-1b and 12 or 24 weeks of PrOD plus ribavirin therapy in HCV-1a without or with cirrhosis. Advanced hepatic fibrosis or compensated cirrhosis was confirmed by either ultrasonography, fibrosis index based on 4 factors (FIB-4) test, or transient elastography/acoustic radiation force impulse (ARFI). The safety and efficacy (sustained virologic response 12 weeks off therapy, SVR12) were evaluated. An SVR12 was achieved in 887 of 898 (98.8%) patients based on the per-protocol analysis (subjects receiving ≥1 dose of any study medication and HCV RNA data available at post-treatment week 12). Child-Pugh A6 (odds ratio: 0.168; 95% confidence interval (CI): 0.043-0.659, p = 0.011) was the only significant factor of poor SVR12. Fifty-four (5.7%) patients were withdrawn early from the treatment because of hepatic decompensation (n = 18, 1.9%) and other adverse reactions. Multivariate analyses identified old age (odds ratio: 1.062; 95% CI: 1.008-1.119, p = 0.024) and Child-Pugh A6 (odds ratio: 4.957; 95% CI: 1.691-14.528, p = 0.004) were significantly associated with hepatic decompensation. In conclusion, this large real-world cohort proved PrOD with or without ribavirin to be highly effective in chronic hepatitis C patients with advanced hepatic fibrosis or compensated cirrhosis. However, Child-Pugh A6 should be an exclusion criterion for first-line treatment in these patients.

• Authors: Chun-Hsien Chen, Chien-Hung Chen, Chih-Lang Lin, Chun-Yen Lin, Tsung-Hui Hu, Shui-Yi Tung, Sen-Yung Hsieh, Sheng-Nan Lu, Rong-Nan Chien, Chao-Hung Hung, I-Shyan Sheen
• Journal: Scientific reports (Sci Rep) Vol. 9 Issue 1 Pg. 7086 (05 08 2019) ISSN: 2045-2322 [Electronic] England
• PMID: 31068655 (Publication Type: Journal Article, Multicenter Study)

Chemical References

• Anilides
• Antiviral Agents
• Carbamates
• Cyclopropanes
• Lactams, Macrocyclic
• Macrocyclic Compounds
• Sulfonamides
• ombitasvir
• Ribavirin
• Uracil
• Proline
• 2-Naphthylamine
• dasabuvir
• Valine
• Ritonavir
• paritaprevir

Topics

• 2-Naphthylamine
• Aged
• Anilides (adverse effects, therapeutic use)
• Antiviral Agents (therapeutic use)
• Carbamates (adverse effects, therapeutic use)
• Cyclopropanes
• Drug Therapy, Combination
• Female
• Genotype
• Hepacivirus (genetics)
• Hepatitis C, Chronic (complications, drug therapy)
• Humans
• Lactams, Macrocyclic
• Liver Cirrhosis (complications, drug therapy)
• Macrocyclic Compounds (adverse effects, therapeutic use)
• Male
• Middle Aged
• Proline (analogs & derivatives)
• Retrospective Studies
• Ribavirin (adverse effects, therapeutic use)
• Ritonavir (adverse effects, therapeutic use)
• Sulfonamides (adverse effects, therapeutic use)
• Sustained Virologic Response
• Uracil (adverse effects, analogs & derivatives, therapeutic use)
• Valine