Risk Factors for Treatment Failure with Oral Antivirals in HCV

Main Article Content

Parveen Malhotra
Vani Malhotra
Yogesh Sanwariya
Dixit
Sahil Girdhar
Shailesh Rathee
Shinepreet Kaur
Sanjeet

Abstract

Introduction: Chronic hepatitis C virus (HCV) infection is one of the major cause of cirrhosis of liver and leads to significant morbidity and mortality. In past, HCV therapy was limited to subcutaneous peg interferon plus oral ribavirin, a regimen that was generally poorly tolerated and provided low efficacy, with cure rates below 40% for HCV genotypes 1 and 4, and below 75% for HCV genotypes 2 or 3. The availability of oral direct-acting antiviral (DAA) as treatment for chronic hepatitis C has revolutionized the field. Although current HCV therapies rarely fail to achieve viral eradication, a subset of patients experience treatment failure.


Aim: To study the risk factors associated with treatment failure with oral antiviral drugs in patients of Chronic hepatitis C.


Materials & Methods: It was a retrorospective study done at Medical Gastroenterology Department, PGIMS, Rohtak in which six years data i.e.from 01.01.2015 to 31.12.2020, pertainining to Eighty Six (86) chronic hepatitis C patients who had treatment failure i.e. SVR failure on oral antiviral  drugs was analyzed.


Observations: Out of the total  86 patients, there was clear cut male predominance i.e. 54 (62.79 %) with rural background (villages) i.e.73 (84.88%). The age distribution in these 86 patients varied between 10-80 yrs of age and characterstically peak was seen in 31-40 yrs age group i.e.25 patients (29.06 %). The majority of patients had high baseline HCV viral load (> 4 lakhs I.U. /ml) i.e. 52 patients (60.46%). Out of  total  86 patients, , 50 patients (58.13%) were cirrhotic, 34 patients (39.53 %) were smokers, 33 patients (38.37%) were alcoholic, 26 patients (30.23 %) had past history of surgical intervention, 9 patients (10.46 %) were diabetic, 9 patients (10.46 %) had got tattoo, 8 patients (9.30%) had history of previous blood transfusion and 13 patients (15.11%) gave history of use of alternative medications.


Results: The direct risk factors associated with development of failed SVR in HCV patients are high baseline HCV RNA viral load, cirrhosis, rural background and indirect risk factors are smoking, alcohol and Diabetes Mellitus but large scale studies in future are required to confirm the same.

Article Details

How to Cite
Parveen Malhotra, Vani Malhotra, Yogesh Sanwariya, Dixit, Sahil Girdhar, Shailesh Rathee, Shinepreet Kaur, & Sanjeet. (2022). Risk Factors for Treatment Failure with Oral Antivirals in HCV . International Journal of Medical Science and Clinical Research Studies, 2(5), 308–314. https://doi.org/10.47191/ijmscrs/v2-i5-04
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References

I. Gower E, Estes C, Blach S, et al. Global epidemiology and genotype distribution of the hepatitis C virus infection. J Hepatol. 2014;61 (suppl):45–57.

II. Wedemeyer H, Dore G, Ward J. Estimates on HCV disease burden worldwide - filling the gaps. J Viral Hepat. 2015;22(suppl 1):1–5.

III. Riou J, Aït-Ahmed M, Blake A, et al. Hepatitis C virus seroprevalence in adults in Africa: a systematic review and meta-analysis. J Viral Hepat. Forthcoming.

IV. WHO. Global hepatitis report, 2017 [Internet]. World Health Organization. 2017. Available from: http://www.who.int/hepatitis

V. Maasoumy B, Wedemeyer H. Natural history of acute and chronic hepatitis C. Best Pract Res Clin Gastroenterol. 2012 Aug; 26(4): 401– 12.

VI. Wiese M, Fisher J, Lobermann M, et al. Evaluation of liver disease progression in the German Hepatitis C virus (1b)-contaminated anti-D cohort at 35 years after infection. Hepatology. 2014;59:49– 57.

VII. Lingala S, Ghany M. Natural history of hepatitis C. Gastroenterol Clin North Am. 2015;44:717–734.

VIII. EASL. Recommendations on treatment of hepatitis C 2015. J Hepatol. 2015;63:199–236.

IX. Pawlotsky JM, Negro F, Aghemo A, Berenguer M, Dalgard O, Dusheiko G, et al.; European Association for the Study of the Liver. Electronic address: easloffice@easloffice.eu; European Association for the Study of the Liver. EASL Recommendations on Treatment of Hepatitis C 2018. J Hepatol. 2018 Aug; 69(2): 461–511.

X. Van der Meer AJ, Wedemeyer H, Feld JJ, Dufour JF, Zeuzem S, Hansen BE, et al. Life expectancy in patients with chronic HCV infection and cirrhosis compared with a general population. JAMA . 2014 Nov; 312(18): 1927–8.

XI. Pascasio JM, Vinaixa C, Ferrer MT, Colmenero J, Rubin A, Castells L, et al. Clinical outcomes of patients undergoing antiviral therapy while awaiting liver transplantation. J Hepatol . 2017 Dec; 67(6): 1168–76.

XII. Carrat F, Fontaine H, Dorival C, Simony M, Diallo A, Hezode C, et al.; French ANRS CO22 Hepather cohort. Clinical outcomes in patients with chronic hepatitis C after direct-acting antiviral treatment: a prospective cohort study [Internet]. Lancet. 2019 Apr; 3 93(10179): 1 453–64. Treatment of Chronic HCV 169 Visc Med 2019;35:161–170 DOI: 10.1159/000500963

XIII. Younossi Z, Henry L. Systematic review: patient-reported outcomes in chronic hepatitis C—the impact of liver disease and new treatment regimens. Aliment Pharmacol Ther . 2015 Mar; 41(6): 497–520.

XIV. Cheung MC, Walker AJ, Hudson BE, Verma S, McLauchlan J, Mutimer DJ, et al.; HCV Research UK. Outcomes after successful direct acting antiviral therapy for patients with chronic hepatitis C and decompensated cirrhosis. J Hepatol . 2016 Oct; 65(4): 741–7.

XV. Sarrazin C. The importance of resistance to direct antiviral drugs in HCV infection in clinical practice. J Hepatol. 2016;64:486–504.

XVI. Terrault N. Difficult-to-cure populations with chronic hepatitis C: vanishing in the direct-acting antiviral era? Hepatology. 2015;62:4–7.

XVII. Barreiro P, Labarga P, Fernandez-Montero JV, et al. Rate and predictors of serum HCV-RNA >6 million IU/mL in patients with chronic hepatitis C. J Clin Virol. 2015;71:63–66.

XVIII. Soriano V, Labarga P, De Mendoza C, et al. New hepatitis C therapies for special patient populations. Exp Opin Pharmacother. 2016;17:217–229.

XIX. Soriano V, Vispo E, Poveda E, et al. Treatment failure with new hepatitis C drugs. Expert Opin Pharmacother. 2012;13:313–323.

XX. Buti M, Riveiro-Barciela M, Esteban R. Management of direct antiviral agent failures. J Hepatol. 2015;63:1511–1522.

XXI. Kau A, Vermehren J, Sarrazin C. Treatment predictors of a sustained virologic response in hepatitis B and C. J Hepatol. 2008;49:634–651.

XXII. Medrano J, Neukam K, Rallón N, et al. Modeling the probability of sustained virological response to therapy with pegylated interferon plus ribavirin in patients coinfected with HCV and HIV. Clin Infect Dis. 2010;51:1209–1216.

XXIII. Poordad F, McConeJ, Bacon B, etal. Boceprevir for untreated chronic HCV genotype 1 infection. N Engl J Med. 2011;364:1195–1206.

XXIV. Poordad F, Bronowicki J, Gordon S, et al. Factors that predict response of patients with hepatitis C virus infection to boceprevir. Gastroenterology. 2012; 143:608–618.

XXV. FDA Package insert for HARVONI. Available from: www.accessdata. fda.gov

XXVI. Kowdley K, Gordon S, Reddy K, et al. Ledipasvir and sofosbuvir for 8 or 12 weeks for chronic HCV without cirrhosis. N Engl J Med. 2014;370:1879–1888.

XXVII. Wyles D, Ruane P, Sulkowski M, etal. Daclatasvir plus sofosbuvir for HCV in patients coinfected with HIV-1. N Engl J Med. 2015;373:714–725.

XXVIII. Zeuzem S, Ghalib R, Reddy K, et al. Grazoprevir-elbasvir combination therapy for treatment-naive cirrhotic and non-cirrhotic patients with chronic hepatitis C virus genotype 1, 4 or 6 Infection: a randomized trial. Ann Intern Med. 2015;163:1–13.

XXIX. Kwo P, Gitlin N, Nahass R, et al. A phase 3 randomized open-label study to evaluate the efficacy and safety of 8 and 12 weeks of simeprevir plus sofosbuvir in treatment-naïve and –experienced patients with chronic HCV genotype 1 infection without cirrhosis: OPTIMIST-1. J Hepatol. 2015;62(suppl 2):270.

XXX. Prevention and management of treatment failure to new oral hepatitis C drugs Laura Benítez-Gutiérreza, Pablo Barreirob, Pablo Labargac, Carmen de Mendozaa, José V. Fernandez-Monterod, Ana Ariasa, José M. Peñab and Vicente Sorianob. EXPERT OPINION ON PHARMACOTHERAPY, 2016 http: // dx. doi. org / 10. 1080 / 14656566.2016.1182156

XXXI. Poynard T, Bedossa P, Opolon P. Natural history of liver fibrosis progression in patients with chronic hepatitis C:The OBSVIRC, METAVIR, CLINIVIR and DOSVIRC groups. Lancet 1997; 349:825-832.

XXXII. Poynard T, Raiziu V, Charlotte F, Goodman Z, Mc Hutchinson J, Albrecht J. Rates and risk factors of liver fibrosis progression in patients with chronic hepatitis C. J Hepatol 2001;34:764-767.

XXXIII. Seeff LB. Natural history of chronic hepatitis C. Hepatology 2002;36 (suppl):S35-S46.

XXXIV. Locasciulli A, Testa M, Pontisso P, Benvegnu L, Fraschini D, Corbetta A, et al. Prevalence and natural history of hepatitis C infection in patients cured of childhood leukemia. Blood 1977; 90:4628-4633.

XXXV. Kenny-Walsh E, for the Irish Hepatology Research Group .Clinical outcomes after hepatitis C infection from contaminated anti-D immune globulin. N Engl J Med 1999;340:1228-1233.

XXXVI. Ghany NG, Kleiner DE, Alter H, Doo E, Khokar F, Promrat K, et al. Progression of fibrosis in chronic hepatitis C. Gastroenterology 2003;124:97-104.

XXXVII. Shiffman ML, Stewart C, Hofmann CM, Contos MJ, Luketic VA, Sterling RK, Sanyal AJ. Chronic infection with hepatitis C virus in patients with elevated or persistently normal serum alanine aminotransferase levels: Comparison of hepatic histology and response to interferon therapy. J Infect Dis 2000;182:15951601.

XXXVIII. Persico M, Persico E, Suozzo R, Conte S, DeSeta M, Coppola L ,et al. Natural history of hepatitis C virus carriers with persistently normal aminotransferase levels. Gastroenterology 2000;118:760764.

XXXIX. Gholson CF, Morgan K, Catinis G, Favrot D, Taylor B, Gonzalez E, Balart L. Chronic hepatitis C with normal aminotransferase levels: A clinical histologic study. Am J Gastroenterol 1997; 92:1788-1792.

XL. Foster G, Irving W, Cheung M, et al. Cohort study of the impact of direct acting antiviral therapy in patients with chronic hepatitis C and decompensated cirrhosis. J Hepatol.

XLI. Saxena V, Nyberg L, Pauly M, et al. Safety and efficacy of simeprevir/sofosbuvir in hepatitis C infected patients with compensated and decompensated cirrhosis: a matched analysis. Hepatology. 2015;62:715–725.

XLII. Reddy K, Bourlière M, Sulkowski M, et al. Ledipasvir and sofosbuvir in patients with genotype 1 HCV and compensated cirrhosis: an integrated safety and efficacy analysis. Hepatology. 2015;62:79–86.

XLIII. Zeuzem S, Ghalib R, Reddy K, et al. Grazoprevir-elbasvir combination therapy for treatment-naive cirrhotic and non-cirrhotic patients with chronic hepatitis C virus genotype 1, 4 or 6 Infection: a randomized trial. Ann Intern Med. 2015;163:1–13.

XLIV. Manns M, Samuel D, Gane E, et al. Ledipasvir and sofosbuvir plus ribavirin in patients with genotype 1 or 4 hepatitis C virus infection and advanced liver disease: a multicenter, open-label, randomized, phase 2 study. Lancet Infect Dis.

XLV. Ferenci P, Kozbial K, Mandorfer M, et al. HCV targeting of patients with cirrhosis. J Hepatol. 2015;63:1015–1022.

XLVI. Fernandez-Montero JV, Soriano V. SOLAR-2: the sun also rises for cirrhotics. Lancet Infect Dis.

XLVII. Wiley TE, McCarthy M, Breidi L, Layton TJ. Impact of alcohol on the histological and clinical progression of hepatitis C infection. Hepatology 1998;28:805-809.

XLVIII. Harris DR, Gonin R, Alter HJ, Wright EC, Buskell ZJ, Hollinger FB, Seeff LB. The relationship of acute transfusion associated hepatitis to the development of cirrhosis in the presence of alcohol abuse. Ann Intern Med 2001;134:120-124.

XLIX. Peters MG, Terrault NA. Alcohol use and hepatitis C. Hepatology 2002;36(suppl):S220-S225.

L. Hassan MM, Spitz MR, Thomas MB, et al. Effect of different types of smoking and synergism with hepatitis C virus on risk of hepatocellular carcinoma in American men and women: case-control study. Int J Cancer. 2008;123:1883–91.

LI. Yu MW, You SL, Chang AS, et al. Association between hepatitis C virus antibodies and hepatocellular carcinoma in Taiwan. Cancer Res. 1991;51:5621–5.

LII. Fujita Y, Shibata A, Ogimoto I, et al. The effect of interaction between hepatitis C virus and cigarette smoking on the risk of hepatocellular carcinoma. Br J Cancer. 2006;94:737–9.

LIII. Sun CA, Wu DM, Lin CC, et al. Incidence and cofactors of hepatitis C virus-related hepatocellular carcinoma: a prospective study of 12,008 men in Taiwan. Am J Epidemiol. 2003;157:674–82.

LIV. Caronia S, Taylor K, Pagliaro L, Carr C, Palazzo U, Petrik J, O'Rahilly S, Shore S, Tom BD, Alexander GJ (1999) Further evidence for an association between non-insulin-dependent diabetes mellitus and chronic hepatitis C virus infection. Hepatology 30: 1059–1063

LV. Toyoda H, Kumada T, Nakano S, Takeda I, Sugiyama K, Kiriyama S, Tanikawa M, Sone Y, Hisanaga Y (2001) Impact of diabetes mellitus on the prognosis of patients with hepatocellular carcinoma. Cancer 91: 957–963