Association between risk factors, basal viral load, virus genotype and the degree of liver fibrosis with the response to the therapy in patients with chronic hepatitis C virus infection

Vuk R. Vuković; Dejan Baskić; Željko Mijailović; Predrag Djurdjević; Danijela Jovanović; Slobodanka Mitrović; Suzana Popović

doi:10.2298/5755

Vuk R. Vuković Garrison Clinic, Kragujevac, Serbia
Dejan Baskić Center for Molecular Medicine and Stem Cell Research,Faculty of Medicinal Sciences, University of Kragujevac, Kragujevac, Serbia; Public Health Institute of Kragujevac, Kragujevac, Serbia
Željko Mijailović Department of Infectious Diseases, Clinical Center of Kragujevac, Kragujevac, Serbia
Predrag Djurdjević Department of Hematology, Clinical Center of Kragujevac, Kragujevac, Serbia
Danijela Jovanović Department of Hematology, Clinical Center of Kragujevac, Kragujevac, Serbia
Slobodanka Mitrović Center for Pathological Anatomy, Faculty of Medicinal Sciences, University of Kragujevac, Kragujevac, Serbia
Suzana Popović Center for Molecular Medicine and Stem Cell Research, Faculty of Medicinal Sciences, University of Kragujevac, Kragujevac, Serbia

DOI: https://doi.org/10.2298/5755

Keywords: hepatitis c, hepatitis, chronic, treatment outcome, risk factors, genotype, histological techniques, disease transmission, infections,

Abstract

Background/Aim. Hepatitis C is an important sociomedical problem worldwide due to frequent progression to chronic disease, occurrence of liver cirrhosis and hepatocellular carcinoma. Standard pegylated interferon alfa 2a plus ribavirin therapy results in resolution of infection only in 50% of patients. The aim of this study was to determine the association of various factors with response to the therapy in patients with chronic heptitis C virus (HCV) infection. Age and sex of patients, inoculation risk factors, histopathological changes in the liver, viral load and HCV genotype were analyzed. Methods. The study included a group of 121 patients with chronic HCV infection. The treatment was carried out 24 weeks for virus genotype 2 and 3, and 48 weeks for genotype 1 and 4. The degree of histopathological changes in the liver was determined by hematoxylin and eosin staining, whereas polimerase chain reaction was used for HCV genotyping. Results. In the group of non-responding patients genotype 1 was represented with 100%, while in the other groups, although predominantly present, its percentage was lower. Unresponsiveness to therapy and relapse of disease were associated with higher viral load and advanced fibrosis. Intravenous use of psychoactive substances, as a risk factor, was present in a high percentage in the group of patients with sustained response, while blood transfusion and dialysis were leading risk factors in the group of relapse responders and non-responders. Conclusion. The results of our study showed that the treatment outcome of chronic HCV infection was associated with baseline HCV ribonucleic acid, HCV genotype, route of infection and the degree of histopathological changes in the liver.

References

Lavanchy D. The global burden of hepatitis C. Liver Int 2009; 29( Suppl 1): 74−81.

Shepard CW, Finelli L, Alter MJ. Global epidemiology of hepatitis C virus infection. Lancet Infect Dis 2005; 5(9): 558−67.

Esteban JI, Sauleda S, Quer J. The changing epidemiology of hepatitis C virus infection in Europe. J Hepatol 2008; 48(1): 148−62.

Afdhal NH. The Natural History of Hepatitis C. Semin Liver Dis 2004; 24 Suppl 2: 3−8.

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(9055): 825−32.

Zein CO, Levy C, Basu A, Zein NN. Chronic hepatitis C and type II diabetes mellitus: a prospective cross-sectional study. Am J Gastroenterol 2005; 100(1): 48−55.

Fried MW, Shiffman ML, Reddy RK, Smith C, Marinos G, Gonçales FL, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med 2002; 347(13): 975−82.

Operskalski EA, Kovacs A. HIV/HCV co-infection: pathogenesis, clinical complications, treatment, and new therapeutic technologies. Curr HIV/AIDS Rep 2011; 8(1): 12−22.

Thompson C, Rogers G, Hewson P, Wright D, Anderson R, Cramp M, et al. Surveillance of cirrhosis for hepatocellular carcinoma: systematic review and economic analysis. Health Technol Assess 2007; 11(34): 1−206.

Knodell RG, Ishak KG, Black WC, Chen TS, Craig R, Kaplowitz N, et al. Formulation and application of a numerical scoring system for assessing histological activity in asymptomatic chronic active hepatitis. Hepatology 1981; 1(5): 431−5.

Berg T, Sarrazin C, Herrmann E, Hinrichsen H, Gerlach T, Zachoval R, et al. Prediction of treatment outcome in patients with chronic hepatitis C: significance of baseline parameters and viral dynamics during therapy. Hepatology 2003; 37(3): 600−9.

Pozzato G, Moretti M, Crocé LS, Sasso F, Kaneko S, Unoura M, et al. Interferon therapy in chronic hepatitis C virus: evidence of different outcome with respect to different viral strains. J Med Virol 1995; 45(4): 445−50.

Sarin SK, Kumar CK. Treatment of patients with genotype 3 chronic hepatitis C- current and future therapies. Liver Int 2012; 32(1 Suppl): 141−5.

Zein NN, Rakela J, Krawitt EL, Reddy KR, Tominaga T, Persing DH. Hepatitis C virus genotypes in the United States: epidemiology, pathogenicity, and response to interferon therapy. Collaborative Study Group. Ann Intern Med 1996; 125(8): 634−9.

Attaullah S, Khan S, Ali I. Hepatitis C virus genotypes in Pakistan: a systemic review. Virol J 2011; 8: 433.

Kamal SM, Nasser IA. Hepatitis C genotype 4: What we know and what we don't yet know. Hepatology 2008; 47(4): 1371−83.

Antonucci G, Angeletti C, Vairo F, Longo MA, Girardi E. Age and prediction of sustained virological response to hepatitis C virus (HCV) infection treatment based on 28-day decrease in HCV RNA levels. J Infect Dis 2009; 200(9): 1484−5.

Manns MP, McHutchison JG, Gordon SC, Rustgi VK, Shiffman M, Reindollar R, et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet 2001; 358(9286): 958−65.

Shiratori Y, Imazeki F, Moriyama M, Yano M, Arakawa Y, Yokosuka O, et al. Histologic improvement of fibrosis in patients with hepatitis C who have sustained response to interferon therapy. Ann Intern Med 2000; 132(7): 517−24.

Karino Y, Toyota J, Sugawara M, Miyazaki K, Kuwata Y, Yamazaki K, et al. Hepatitis C virus genotypes and hepatic fibrosis regulate 24-h decline of serum hepatitis C virus RNA during interferon therapy in patients with chronic hepatitis C. J Gastroenterol Hepatol 2003; 18(4): 404−10.