Uticaj steatoze jetre na uspeh antivirusne terapije hroničnog hepatitisa C
Sažetak
Uvod/Cilj. Hronični hepatitis C i steatoza jetre se često javljaju udruženo kod iste osobe, a steatoza jetre može dovesti do pogoršanja bolesti jetre i može smanjiti uspeh lečenja hroničnog hepatitisa C. Lečenjem jedne bolesti povoljno se utiče na ishod lečenja druge bolesti. Cilj ovog rada bio je da se utvrdi učestalost steatoze jetre kod bolesnika sa hroničnim hepatitisom C i da se ispita uticaj steatoze jetre i drugih prediktora na uspeh antivirusne terapije hroničnog hepatitisa C. Metode. U studiju su bila uključena 123 bolesnika sa hroničnim hepatitisom C, koji su lečeni pegilovanim interferonom alfa 2a u kombinaciji sa ribavirinom. Bolesnici su na osnovu prisustva steatoze jetre podeljeni u dve grupe, grupu I sa 43 bolesnika i steatozom jetre i grupu II sa 80 bolesnika bez steatoze jetre. Uspeh lečenja ocenili smo na osnovu postignutog stabilnog virusološkog odgovora. Rezultati. Postojanje steatoze utvrđeno je kod 34,96% bolesnika. Ukupan uspeh antivirusne terapije postignut je kod 74,79% bolesnika. Uspeh antivirusne terapije zabeležen je kod 62,79% bolesnika sa steatozom jetre i kod 81,25% bolesnika bez steatoze (p < 0,05). Uspeh antivirusnog lečenja postignut je kod 80,95% bolesnika sa steatozom jetre i genotipom 3 virusa hepatitisa C. Prediktori uspešnosti antivirusne terapije hroničnog hepatitisa C u našem radu bili su starost bolesnika, dužina trajanja infekcije, genotip 3, steatoza i izražena fibroza jetre. Zaključak. Steatoza jetre često je prisutna kod bolesnika sa hroničnim hepatitisom C i ima negativan uticaj na efikasnost antivirusne terapije kod bolesnika sa infekcijom genotipom non-3 hepatitis C virusa. Zbog toga se steatoza jetre kod ovih bolesnika mora eliminisati ili lečiti pre primene antivirusne terapije.
Reference
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.