Efficacy and safety of сepeginterferon alfa-2b in double treatment regimen (cepeginterferon alfa-2b and ribavirin) of antiviral therapy in patients with chronic hepatitis C genotypes 2 and 3. Experience of real clinical practice

The objective: to analyze the experience of use of cepeginterferon
alfa-2b and ribavirin in patients with chronic hepatitis C genotypes 2 and 3 in clinical practice, to evaluate the efficacy, safety and tolerability of this treatment regimen.

Materials and methods. From 2013 to 2016 a total of 73 patients with chronic hepatitis C (CHC) received antiviral therapy with cepeginterferon alfa 2b (cePEG-IFN alfa-2b) and ribavirin in the Center for Gastroenterology and Hepatology of FSBE «Vishnevsky Third Military Clinical Hospital» of Russian Ministry of Defence. Treatment efficacy was assessed by the rate of sustained virologic response (SVR) on 24 week after completion of antiviral therapy. All cases of deterioration of the patient’s condition and laboratory abnormalities were registered throughout the treatment period and follow up. Severity of adverse events was assessed in accordance with the classification of CTCAE (Common Terminology 
Criteria for Adverse Events).

Results. 73 CHC patients genotype 2/3 received cePEGIFN alfa-2b 1.5 μg/kg/week and ribavirin 800-1400 mg/day based on body weight for 24 weeks. SVR 24 was registered in 94,7% (n=54) of patients with HCV genotype 3 and in 93,7% (n =15) patients with genotype 2. During the first 12 weeks of therapy the normalization of serum transaminase activities was registered. All adverse events were typical for interferon/ribavirin treatment regimen.

Conclusion. According to our data the use of double treatment regimen (CePEG-IFN alfa-2b and ribavirin) is reasonable in patients who don’t have negative predictive factors of response to IFN-based therapy. The SVR rate in this group of patients was 94.5%.

1. Global, regional, and national age-specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet 2015; 385: 117-171

2. Federal Service for Surveilance on Consumer Rights Protection and Human Wellbeing. On the state sanitary and epidemiological wellbeing of the population in the Russian Federation in 2014: State report. Moscow : Rospotrebnadzor, 2015. (in Russian). http://rospotrebnadzor.ru/activities/statisticalmaterials/statictic_details.php?ELEMENT_ID=5525

3. Pimenov N. N., Chulanov V. P., Komarova S. V. et al. Hepatitis C in Russia: current epidemiology and approaches to improving diagnosis and surveillance// Jepidemiologija i infekcionnye bolezni– 2012. – 3. С. 4-10.

4. Yushchuk N.D., Znoiko O.O., Dudina K.R. i soavt. Sotsial›no-ekonomicheskoe bremya gepatita S: metodologiya otsenki i trudnosti rascheta v Rossiiskoi Federatsii. Доступно по: http://www.healtheconomics.ru/item/14159-sotsialnoekonomicheskoe-bremya-gepatita-s-metodologiya-otsenki-itrudnosti-rascheta-v-rossijskoj-federatsii

5. EASL Recommendations on Treatment of Hepatitis C 2015. J. Hepatol. 2015; 63: 199–236.

6. Jhaveri R, McHutchison J, Patel K, Qiang G, Diehl AM. Specific polymorphisms in hepatitis C virus genotype 3 core protein associated with intracellular lipid accumulation. J Infect Dis. 2008; 197: 283–291.

7. Nkontchou G, Ziol M, Aout M, et al. HCV genotype 3 is associated with a higher hepatocellular carcinoma incidence in patients with ongoing viral C cirrhosis. J Viral Hepat. 2011; 18: 516–522.

8. Mayevskaya M.V, Znoyko O.O., Klimova Ye.A. et al. Treatment of chronic hepatitis C by cepeginterferon alpha-2b in combination to ribavirin (Final results of randomized comparative clinical study). Russian Journal of Gastroenterology, Hepatology and Coloproctology. 2014; 2(24): 53-64 (in Russian)

9. https://clinicaltrials.gov/ct2/results?term=NCT01889433

10. Nagimova F, Rassokhin V, Linkova Y et al. Cepeginterferon alfa-2b in combination with ribavirin for treatment of chronic hepatitis C in patients co-infected with HIV-1 (final results of a multicenter randomized study). Infekcionnye bolezni. 2016;14(1):5-13.

11. Miyake Y., Iwasaki Y., Yamamoto K. Meta-analysis: reduced incidence of hepatocellular carcinoma in patients not responding to interferon therapy of chronic hepatitis C. Int J Cancer. 2010; 127:989-996

12. Nazir S., Amanullah, Mufariq S., Usman K. Preventive role of interferon in hepatocellular carcinoma in non-responder hepatitis B and C patients. JPMI . 29 (4): 284-287

13. Asselah T, Thompson AJ, Flisiak R, et al. A Predictive Model for Selecting Patients with HCV Genotype 3 Chronic Infection with a High Probability of Sustained Virological Response to Peginterferon Alfa-2a/Ribavirin. Liu C-H, ed. PLoS ONE. 2016;11(3): 0150569.

14. Kogure T, Ueno K, Fukushima K, Nagasaki F, Inoue J, Kakazu E, et al. Fulminant hepatic failure in a case of autoimmune hepatitis in hepatitis C during peg- interferon-alpha 2b plus ribavirin treatment. World J Gastroenterology. 2007; 13:4394-4397

15. Lorke J, Erhardt A, Haussinger D. Induction of autoimmune hepatitis by pegylated interferon alpha-2b in chronic hepatitis C. Clin Gastroenterol Hepatol. 2004;2(12): xx

16. Shindo M, Di Bisceglie AM, Hoofnagle JH. Acute exacerbation of liver disease during interferon alpha therapy for chronic hepatitis C. Gastroenterology. 1992; 102: 1406-1408

17. Papo T, Marcellin P, Bernuau J, Durand F, Poynard T, Benhemou JP. Autoimmune chronic hepatitis exacerbated by alpha-interferon. Ann Intern Med. 1992; 116:51-53

18. Eisenburg J. Interferon or C virus-induced autoimmune chronic hepatitis? Report of personal observations and review of the literature. Fortschr Med. 1994; 112:317- 321