Efficacy and Safety of Ombitasvir plus Paritaprevir, Ritonavir and Ribavirin in Non-cirrhotic Treatment-naïve and Treatment-experienced Egyptians with Chronic HCV Genotype-4 Infection

Abstract

Hepatitis C virus genotype 4 (HCV-GT4) is a risk factor for cirrhosis, hepatocellular carcinoma and liver failure. A combination of three new direct-acting antivirals ombitasvir, paritaprevir, and ritonavir has been recommended for treatment of HCV-GT4 infection. The current study was aimed to assess the efficacy and safety of this combination plus ribavirin in non-cirrhotic, treatment-naïve and -experienced Egyptians with HCV-GT4 infection in a real-world setting. A total of 255 Egyptians with HCV-GT4 infection were enrolled, including 82 treatment-experienced and 173 treatment-naïve patients. All of them completed 12-week treatment protocol of ombitasvir, paritaprevir and ritonavir as an oral dose combination with ribavirin. Virological response (VR) was measured, as well as the biochemical parameters related to treatment efficacy and adverse events at baseline and after treatment, at 4 (VR4) and 12 (VR12) weeks post-treatment. The results showed that the VR4 rates were 98.8% in both groups, and VR12 rates were 97.7% and 96.3% in treatment-naïve and -experienced patients, respectively, with no significant differences found between the groups concerning VR4 (P=0.9) and VR12 (P=0.3). The most common adverse events were headache and fatigue, which were significantly more common (P=0.001 and 0.003, respectively) in treatment-experienced than in treatment-naïve group. The quadruple regimen was well-tolerated, and the reported adverse events were generally mild to moderate. This real-world setting study confirms that the combination of ombitasvir, paritaprevir, ritonavir, and ribavirin is highly effective in the treatment of HCV- GT4 infection with a good safety and tolerability profile.

Keywords

hepatitis C virus / genotype-4 / ombitasvir / paritaprevir / ribavirin

References

[1] KandeelA, GenedyM, El-RefaiS, et al.. The prevalence of hepatitis C virus infection in Egypt 2015: implications for future policy on prevention and treatment. Liver Int, 2017, 37(1): 45-53

[2] GowerE, EstesC, BlackS, et al.. Global epidemiology and genotype distribution of the hepatitis C virus infection. J Hepatol, 2014, 61: S45-S57 1 Suppl

[3] WahshEA, HusseinAK, GomaaAA, et al.. Real life Egyptian experience of daclatasvir plus sofosbuvir with Ribavirin in Naïve difficult to treat HCV patients. Infect Disord Drug Targets, 2020, 20(1): 43-48

[4] EASL. Recommendations on Treatment of Hepatitis C 2016. J Hepatol, 2017, 66(1): 153-194

[5] AhmedH, AhmedE, AbushoukAI, et al.. Safety and efficacy of sofosbuvir plus ledipasvir with and without ribavirin for chronic HCV genotype-1 infection: a systematic review and meta-analysis. Antivir Ther, 2017, 22(5): 369-379

[6] AhmedH, AbushoukAI, AttiaA, et al.. Safety and efficacy of sofosbuvir plus velpatasvir with or without ribavirin for chronic hepatitis C virus infection: a systematic review and meta-analysis. J Infect Public Heal, 2018, 11(2): 156-164

[7] AhmedH, AbushoukAI, MenshawyA, et al.. Meta-analysis of grazoprevir plus elbasvir for treatment of hepatitis C virus genotype 1 infection. Ann Hepatol, 2018, 17(1): 18-32

[8] AsselahT, BoyerN, SaadounD, et al.. Direct-acting antivirals for the treatment of hepatitis C virus infection: optimizing current IFN-free treatment and future perspectives. Liver Int, 2016, 36(Suppl 1): 47-57

[9] SievertW, AltraifI, RazaviHA, et al.. A systematic review of hepatitis C virus epidemiology in Asia, Australia and Egypt. Liver Int, 2011, 31(Suppl 2): 61-80

[10] RaySC, ArthurRR, CarellaA, et al.. Genetic Epidemiology of Hepatitis C Virus throughout Egypt. J Infect Dis, 2000, 182(3): 698-707

[11] KrishnanP, BeyerJ, MistryN, et al.. In vitro and in vivo antiviral activity and resistance profile of ombitasvir, an inhibitor of hepatitis C virus NS5A. Antimicrob Agents Chemother, 2015, 59(2): 979-987

[12] PoordadF, LandisCS, AsatryanA, et al.. High antiviral activity of NS 5A inhibitor ABT-530 with paritaprevir/ritonavir and ribavirin against hepatitis C virus genotype 3 infection. Liver Int, 2016, 36(8): 1125-1132

[13] PockrosP, ReddyR, MantryP, et al.. RUBY-I: ombitasvir/paritaprevir/ritonavir+ dasabuvir+/-ribavirin in non-cirrhotic HCV genotype 1-infected patients with severe renal impairment or end-stage renal disease. Hepatology, 2015, 62(Suppl 1): 716A

[14] PolepallyAR, BadriPS, EckertD, et al.. Effects of Mild and Moderate Renal Impairment on Ombitasvir, Paritaprevir, Ritonavir, Dasabuvir, and Ribavirin Pharmacokinetics in Patients with Chronic HCV Infection. Eur J Drug Metab Pharmacokinet, 2017, 42(2): 333-339

[15] PawlotskyJM. Hepatitis C Virus Resistance to Direct-Acting Antiviral Drugs in Interferon-Free Regimens. Gastroenterology, 2016, 151(1): 70-86

[16] PogorzelskaJ, FlisiakR. Real-world experience with ombitasvir/paritaprevir boosted with ritonavir and possibly combined with dasabuvir and ribavirin in HCV infection. Clin Exp Hepatol, 2016, 2(2): 34-37

[17] HézodeC, AsselahT, ReddyKR, et al.. Ombitasvir plus paritaprevir plus ritonavir with or without ribavirin in treatment-naive and treatment-experienced patients with genotype 4 chronic hepatitis C virus infection (PEARL-I): a randomised, open-label trial. Lancet, 2015, 385(9986): 2502-2509

[18] WakedI, ShihaG, QaqishRB, et al.. Ombitasvir, paritaprevir, and ritonavir plus ribavirin for chronic hepatitis C virus genotype 4 infection in Egyptian patients with or without compensated cirrhosis (AGATE-II): a multicentre, phase 3, partly randomised open-label trial. Lancet Gastroenterol Hepatol, 2016, 1(1): 36-44

[19] SterlingRK, LissenE, ClumeckN, et al.. Development of a simple noninvasive index to predict significant fibrosis in patients with HIV/HCV coinfection. Hepatology, 2006, 43(6): 1317-1325

[20] WernerCR, SchwarzJM, EgetemeyrDP, et al.. Second-generation direct-acting-antiviral hepatitis C virus treatment: Efficacy, safety, and predictors of SVR12. World J Gastroenterol, 2016, 22(35): 8050-8059

[21] IoannouGN, BesteLA, ChangMF, et al.. Effectiveness of Sofosbuvir, Ledipasvir/Sofosbuvir, or Paritaprevir/Ritonavir/Ombitasvir and Dasabuvir Regimens for Treatment of Patients With Hepatitis C in the Veterans Affairs National Health Care System. Gastroenterology, 2016, 151(3): 457-471

[22] AhmedH, AbushoukAI, MenshawyA, et al.. Safety and efficacy of ombitasvir/paritaprevir/ritonavir and dasabuvir with or without ribavirin for treatment of hepatitis C virus genotype 1: a systematic review and meta-analysis. Clin Drug Investig, 2017, 37(11): 1009-1023

[23] SmithDB, BukhJ, KuikenC, et al.. Expanded classification of hepatitis C virus into 7 genotypes and 67 subtypes: updated criteria and genotype assignment web resource. Hepatology, 2014, 59(1): 318-327

[24] DossW, ShihaG, HassanyM, et al.. Sofosbuvir plus ribavirin for treating Egyptian patients with hepatitis C genotype 4. J Hepatol, 2015, 63(3): 581-585

[25] MannsM, GaneEJ, WillemsBE, et al.. The safety and tolerability of SOF/VEL/VOX for 8 or 12 weeks in >1,000 patients treated in the POLARIS-1, POLARIS-2, POLARIS-3, and POLARIS-4 studies: an integrated analysis. J Hepatol, 2017, 66(Suppl 1): S722-S723

[26] AbergelA, MetivierS, SamuelD, et al.. Ledipasvir plus sofosbuvir for 12 weeks in patients with hepatitis C genotype 4 infection. Hepatology, 2016, 64(4): 1049-1056

[27] SaidEM, AbdulazizBA, El KassasM, et al.. High success rates for the use of sofosbuvir/ombitasvir/paritaprevir/ritonavir + ribavirin and sofosbuvir/simeprevir/daclatasvir+ribavirin in retreatment of chronic hepatitis C infection after unsuccessful sofosbuvir/daclatasvir therapy: a real-life experience. Arch Virol, 2020, 165: 1633-1639

[28] Abdel-MoneimA, AboudA, Abdel-GabbarM, et al.. Retreatment Efficacy of Sofosbuvir/Ombitasvir/Paritaprevir/Ritonavir + Ribavirin for Hepatitis C Virus Genotype 4 Patients. Dig Dis Sci, 2018, 63(5): 1341-1347

[29] AndreoneP, ColomboMG, EnejosaJV, et al.. ABT-450, ritonavir, ombitasvir, and dasabuvir achieves 97% and 100% sustained virologic response with or without ribavirin in treatment-experienced patients with HCV genotype 1b infection. Gastroenterology, 2014, 147(2): 359-365

[30] StauberRE, FaulerG, RainerF, et al.. Anti-HCV treatment with ombitasvir/paritaprevir/ritonavir ± dasabuvir is associated with increased bile acid levels and pruritus. Wiener klinische Wochenschrift, 2017, 129(21): 848-851

[31] McRaeMP, LoweCM, TianX, et al.. Ritonavir, saquinavir, and efavirenz, but not nevirapine, inhibit bile acid transport in human and rat hepatocytes. J Pharmacol Exp Ther, 2006, 318(3): 1068-1075