The influence of hepatic steatosis on the success of antiviral therapy for chronic hepatitis C

Tomislav Preveden; Maja Ružić; Maria K Pete

doi:10.2298/VSP150826190P

Tomislav Preveden Clinic for Infectious Disease, Clinical Center of Vojvodina, Novi Sad, Serbia; Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia
Maja Ružić Clinic for Infectious Disease, Clinical Center of Vojvodina, Novi Sad, Serbia; Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia
Maria K Pete Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia

DOI: https://doi.org/10.2298/VSP150826190P

Keywords: hepatitis c, fatty liver, genotype, age factors, interferon-alpha, ribavirin, treatment outcome,

Abstract

Background/Aim. Chronic hepatitis C and liver steatosis often appear simultaneously in the same person, and steatosis can lead to worsening of liver disease and reducing the success of the treatment of chronic hepatitis C. Treatment of one disease can influence and cause favorable impact on treatment of other diseases. The aim of this study was to determine the incidence of liver steatosis in patients with chronic hepatitis C and to examine the impact of steatosis of the liver and other predictors on the success of antiviral therapy for chronic hepatitis C. Methods. The study included 123 patients with chronic hepatitis C treated with pegylated interferon alfa 2a in combination with ribavirin. The patients were divided into two groups based on the presence of cirrhosis: the group I consisted of 43 (34.9%) patients with steatosis and the group II consisted of 80 (65.1%) patients without liver steatosis. The success of the treatment was evaluated on the basis of the stable virological response. Results. The presence of steatosis was determined in 34.96% of the patients. The overall success of antiviral therapy was found in 74.79% of the patients. The success of antiviral therapy was present in 62.79% of the patients with hepatic steatosis, and in 81.25% the patients without steatosis (p < 0.05). The success of antiviral treatments was seen in 80.95% of the patients with hepatic steatosis and the genotype of hepatitis C virus 3. The predictors of antiviral therapy success for chronic hepatitis C in our study were patient's age, duration of infection, genotype 3, steatosis and severe fibrosis or cirrhosis. Conclusion. Liver steatosis is often present in patients with chronic hepatitis C. It has negative impact on the efficacy of antiviral therapy in patients with infection with genotype non-3 hepatitis C virus. Therefore, hepatic steatosis in these patients must be eliminated or treated prior to application of antiviral therapy.

Author Biography

Maria K Pete, Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia

Lekar opšte prakse

References

Mohd HK, Groeger J, Flaxman AD, Wiersma ST. Global epidemi-ology of hepatitis C virus infection: New estimates of age-specific antibody to HCV seroprevalence. Hepatology 2013; 57(4): 1333−42.

Cornberg M, Razavi HA, Alberti A, Bernasconi E, Buti M, Cooper C, et al. Asystematic review of hepatitis C virus epidemiology in Europe, Canada and Israel. Liver Int 2011; 31(Suppl 2): 30−60.

Blachier M, Leleu H, Peck-Radosavljevic M, Valla DC, Roudot-Thoraval F. The burden of liver disease in Europe: a review of available epidemiological data. J Hepatol 2013; 58(3): 593−608.

Svirtlih N, Delic D, Simonovic J, Jevtovic D, Dokic L, Gvozdenovic E, et al. Hepatitis C virus genotypes in Serbia and Montenegro: The prevalence and clinical significance. World J Gastroenterol 2007; 13(3): 355−60.

Castera L, Chouteau P, Hezode C, Zafrani E, Dhumeaux D, Paw-lotsky J. Hepatitis C virus-induced hepatocellular steatosis. Am J Gastroenterol 2005; 100(3): 711−5.

European Association for the Study of the Liver. EASL Clinical Prac-tice Guidelines: management of hepatitis C virus infection. J Hepatol 2011; 55(2): 245−64.

Asselah T, Estrabaud E, Bieche I, Lapalus M, De Muynck S, Vidaud M, et al. Hepatitis C: Viral and host factors associated with non-response to pegylated interferon plus ribavirin. Liver Int 2010; 30(9): 1259−69.

Zhu Y, Chen S. Antiviral treatment of hepatitis C virus infection and factors affecting efficacy. World J Gastroenterol 2013; 19(47): 8963−73.

Persico M, Iolascon A. Steatosis as a co-factor in chronic liver diseases. World J Gastroenterol 2010; 16(10): 1171−6.

Arrese M, Riquelme A, Soza A, Barrera FM, Soza A. Insulin resis-tance, hepatic steatosis and hepatitis C: A complex relationship with relevant clinical implications. Ann Hepatol 2010; 9(Suppl 1): 112−8.

Rubbia-Brandt L, Quadri R, Abid K, Giostra E, Malé PJ, Mentha G, et al. Hepatocyte steatosis is a cytopathic effect of hepatitis C virus genotype 3. J Hepatol 2000; 33(1): 106−15.

Negro F. Hepatitis C virus-induced steatosis: An overview. Dig Dis 2010; 28(1): 294−9.

Kleiner DE, Brunt EM, Van NM, Behling C, Contos MJ, Cummings OW, et al. Design and validation of a histological scoring sys-tem for nonalcoholic fatty liver disease. Hepatology 2005; 41(6): 1313−21.

Younossi ZM, McCullough AJ. Metabolic syndrome, non-alcoholic fatty liver disease and hepatitis C virus: Impact on disease progression and treatment response. Liver Int 2009; 29(2): 3−12.

Negro F, Clément S. Impact of obesity, steatosis and insulin re-sistance on progression and response to therapy of hepatitis C. J Viral Hepat 2009;6(10): 681−8.

Koike K. Steatosis, liver injury, and hepatocarcinogenesis in he-patitis C viral infection. J Gastroenterol 2009; 44(19): 82−8.

Savvoula S, Dimitrios C, George P, Spilios M, Christos T, John G. The impact of host metabolic factors on treatment outcome in chronic hepatitis C. Gastroenterol Res Pract 2012; 2012: 420156.

Fierbinţeanu-Braticevici C, Mohora M, Tribus L, Petrişor A, Creţoiu SM, Creţoiu D, et al. Hepatocyte steatosis in patients infected with genotype 1 hepatitis C virus. Rom J Morphol Embryol 2010; 51(2): 235−42.

McHutchison JG, Lawitz EJ, Shiffman ML, Muir AJ, Galler GW, McCone J, et al. Peginterferon alfa-2b or alfa-2a with ribavirin for treatment of hepatitis C infection. N Engl J Med 2009; 361(6): 580−93.

Ferguson MC. Current therapies for chronic hepatitis C. Phar-macotherapy 2011; 31(1): 92−111.

Kuljić-Kapulica N, Jovanović D, Savić D, Ristanović E, Nozić D, Rajić R. Therapy of chronic hepatitis C: Virologic response moni-toring. Vojnosanit Pregl 2010; 67(11): 923−7. (Serbian)

Jovanović M, Konstantinović L, Kostić V, Vrbić M, Popović L. Effi-ciency of a combined peginterferon alpha-2a and ribavarin therapy in intravenous opiate substances abusers with chronic hepatitis C. Vojnosanit Pregl 2009; 66(10): 791−5.

Deborah Friedman N, Green JH, Weber HM, Stephen S, Lane SE, Ting AY, et al. Hepatitis C virus treatment in the 'real-world': How well do 'real' patients respond. J Clin Exp Hepatol 2014; 4(3): 214−20.

Ansaldi F, Orsi A, Sticchi L, Bruzzone B, Icardi G. Hepatitis C vi-rus in the new era: Perspectives in epidemiology, prevention, dignostics and predictors of response to therapy. World J Ga-stroenterol 2014; 20(29): 9633−52.

Szanto P, Grigorescu M, Dumitru I, Serban A. Steatosis in hepatitis C virus infection. Response to anti-viral therapy. J Gastrointestin Liver Dis 2006; 15(2): 117−24.

Soresi M, Tripi S, Franco V, Giannitrapani L, Alessandri A, Rappa F, et al. Impact of liver steatosis on the antiviral response in the hepatitis C virus-associated chronic hepatitis. Liver Int 2006; 26(9): 1119−25.

Thomopoulos KC, Theocharis GJ, Tsamantas AC, Siagris D, Dimitro-poulou D, Gogos CA, et al. Liver steatosis is an independent risk factor for treatment failure in patients with chronic hepatitis C. Eur J Gastroenterol Hepatol 2005; 17(2): 149−53.

Abdel-Aziz M, Abdel-Aziz A, El-Arman M. Non Alcoholic Fatty Liver Diseases in Chronic Hepatitis C: Impact on End Treatment Virologic Response. IJCRIMPH 2009; 1(9): 215−31.

Rodriguez-Torres M, Govindarajan S, Diago M, Morgan T, Anand B, Barange K, et al. Hepatic steatosis in patients with chronic hepa-titis C virus genotype 2 or 3 does not affect viral response in patients treated with peginterferon alpha-2a (40KD) (PE-GASYS) plus ribavirin (COPEGUS) for 16 or 24 weeks. Liver Int 2009; 29(2): 237−41.

Westin J, Lagging M, Dhillon AP, Norkrans G, Romero AI, Pawlotsky JM, et al. Impact of hepatic steatosis on viral kinetics and treatment outcome during antiviral treatment of chronic HCV infection. J Viral Hepatol 2007; 14(1): 29−35.

Sanyal AJ. Role of insulin resistance and hepatic steatosis in the progression of fibrosis and response to treatment in hepatitis C. Liver Int 2011; 31 Suppl 1: 23−8.

Cross TJ, Rashid MM, Berry PA, Harrison PM. The importance of steatosis in chronic hepatitis C infection and its management: A review. Hepatol Res 2010; 40(3): 237−47.

Werling K, Schaff Z, Dinya E, Tulassay Z. Effect of liver steatosis on therapeutic response in chronic hepatitis C virus genotype 1 infected patients in hungary. Pathol Oncol Res 2010; 16(2): 149−57.

Cross TS, Quaglia A, Nolan J, Hughes S, Harrison PM. Do steato-sis and steatohepatitis impact on sustained virological re-sponse (SVR) rates in patients receiving pegylated interferon and ribavirin for chronic hepatitis C infection. J Med Virol 2010; 82(6): 958−64.

Hwang SJ, Lee SD. Hepatic steatosis and hepatitis C: Still un-happy bedfellows. J Gastroenterol Hepatol 2011; 26(Suppl 1): 96−101.

Abenavoli L, Masarone M, Peta V, Milic N, Kobyliak N, Rouabhia S, et al. Insulin resistance and liver steatosis in chronic hepatitis C infection genotype 3. World J Gastroenterol 2014; 20(41): 15233−40.

Negro F. Facts and fictions of HCV and comorbidities: Steato-sis, diabetes mellitus, and cardiovascular diseases. J Hepatol 2014; 61(1 Suppl): S69−78.