Journal of Hepatology
Volume 48, Issue 5 , Pages 756-764 , May 2008

Hepatic steatosis in HIV/HCV co-infected patients: Correlates, efficacy and outcomes of anti-HCV therapy: A paired liver biopsy study

  • Maribel Rodríguez-Torres

      Affiliations

    • Fundacion de Investigacion de Diego, Ave. De Diego # 359, Suite 302, Santurce, PR 09909, USA
    • Corresponding Author InformationCorresponding author. Tel.: +1 787 722 1248; fax: +1 787 721 6098.
    • ,
  • Sugantha Govindarajan

      Affiliations

    • Rancho Los Amigos Medical Center, Downey, CA, USA
    • ,
  • Ricard Solá

      Affiliations

    • Universitat Autónoma de Barcelona, Barcelona, Spain
    • ,
  • Nathan Clumeck

      Affiliations

    • CHU Saint-Pierre, Brussels, Belgium
    • ,
  • Eduardo Lissen

      Affiliations

    • Virgen del Rocio, University Hospital, Seville, Spain
    • ,
  • Mário Pessôa

      Affiliations

    • Instituto de Infectologia Emilio Ribas, São Paulo, Brazil
    • ,
  • Peter Buggisch

      Affiliations

    • Universitätsklinik, Eppendorf, Hamburg, Germany
    • ,
  • Janice Main

      Affiliations

    • St. Mary’s Hospital, London, UK
    • ,
  • Jean DePamphilis

      Affiliations

    • Roche Nutley, NJ, USA
    • ,
  • Douglas T. Dieterich

      Affiliations

    • Mount Sinai School of Medicine, New York, NY, USA

Received 6 September 2007 ,Revised 20 December 2007 ,Accepted 14 January 2008.

References 

  1. Adinolfi L, Gambardella M, Andreana A, Tripodi MF, Utili R, Ruggiero G. Steatosis accelerates the progression of liver damage of chronic hepatitis C patients and correlates with specific HCV genotype and visceral obesity. Hepatology. 2001;33:1358–1364
  2. Weinman SA, Belalcazar LM. Hepatitis C: a metabolic liver disease. Gastroenterology. 2004;126:917–919
  3. Leandro G, Mangia A, Hui J, Fabris P, Rubbia-Brandt L, Colloredo G, et al. Relationship between steatosis, inflammation, and fibrosis in chronic hepatitis C: a meta-analysis of individual patient data. Gastroenterology. 2006;130:1636–1642
  4. Kumar D, Farrell GC, Fung C, George J. Hepatitis C virus genotype 3 is cytopathic to hepatocytes: Reversal of hepatic steatosis after sustained therapeutic response. Hepatology. 2002;36:1266–1272
  5. Castera L. Steatosis, insulin resistance and fibrosis progression in chronic hepatitis C. Minerva Gastroenterol Dietol. 2006;52:125–134
  6. Marchesini G, Bugianesi E, Forlani G, Cerrelli F, Lenzi M, Manini R, et al. Nonalcoholic fatty liver, steatohepatitis, and the metabolic syndrome. Hepatology. 2003;37:917–923
  7. Church T, Kuk J, Ross R, Priest EL, Biltoft E, Blair SN. Association of cardiorespiratory fitness, body mass index, and waist circumference to nonalcoholic fatty liver disease. Gastroenterology. 2006;130:2023–2030
  8. Hamaguchi M, Kojima T, Takeda N, Nakagawa T, Taniguchi H, Fujii K, et al. The metabolic syndrome as a predictor of nonalcoholic fatty liver disease. Ann Intern Med. 2005;143:722–728
  9. Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA, et al. Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation. 2005;112:2735–2752
  10. Mohsen A, Easterbrook P, Taylor C, Portmann B, Kulasegaram R, Murad S, et al. Impact of human immunodeficiency virus (HIV) infection on the progression of liver fibrosis in hepatitis C virus infected patients. Gut. 2003;52:1035–1040
  11. Agarwal K, Fiel M, Uriel AJ, Moorehead L, Kontorinis N, Thung S, et al. Correlation of insulin resistance with steatosis and fibrosis in hepatitis C and HIV co-infection: cross-sectional analysis of 101 patients. Hepatology. 2004;40:587A
  12. Neau D, Winnock M, Castera L, Bail BL, Loko MA, Geraut L, et al. Prevalence of and factors associated with hepatic steatosis in patients coinfected with hepatitis C virus and HIV: Agence Nationale pour la Recherche contre le SIDA et les hepatites virales CO3 Aquitaine Cohort. J Acquir Immune Defic Syndr. 2007;45:168–173
  13. Marks KM, Petrovic LM, Talal AH, Murray MP, Gulick RM, Glesby MJ. Histological findings and clinical characteristics associated with hepatic steatosis in patients coinfected with HIV and hepatitis C virus. J Infect Dis. 2005;192:1943–1949
  14. Monto A, Dove LM, Bostrom A, Kakar S, Tien PC, Wright TL. Hepatic steatosis in HIV/hepatitis C coinfection: prevalence and significance compared with hepatitis C monoinfection. Hepatology. 2005;42:310–316
  15. Gaslightwala I, Bini EJ. Impact of human immunodeficiency virus infection on the prevalence and severity of steatosis in patients with chronic hepatitis C virus infection. J Hepatol. 2006;44:1026–1032
  16. Jerico C, Knobel H, Montero M, Ordoñez-Llanos J, Guelar A, Gimeno JL, et al. Metabolic syndrome among HIV-infected patients: prevalence, characteristics, and related factors. Diabetes Care. 2005;28:132–137
  17. Fortgang IS, Belitsos PC, Chaisson RE, Moore RD. Hepatomegaly and steatosis in HIV-infected patients receiving nucleoside analog antiretroviral therapy. Am J Gastroenterol. 1995;90:1433–1436
  18. Miller KD, Cameron M, Wood LV, Dalakas MC, Kovacs JA. Lactic acidosis and hepatic steatosis associated with use of stavudine: report of four cases. Ann Intern Med. 2000;133:192–196
  19. Grunfeld C, Kotler DP, Shigenaga JK, Doerrler W, Tierney A, Wang J, et al. Circulating interferon-alpha levels and hypertriglyceridemia in the acquired immunodeficiency syndrome. Am J Med. 1991;90:154–162
  20. Shor-Posner G, Basit A, Lu Y, Cabrejos C, Chang J, Fletcher M, et al. Hypocholesterolemia is associated with immune dysfunction in early human immunodeficiency virus-1 infection. Am J Med. 1993;94:515–519
  21. Bergersen BM, Schumacher A, Sandvik L, Bruun JN, Birkeland K. Important differences in components of the metabolic syndrome between HIV-patients with and without highly active antiretroviral therapy and healthy controls. Scand J Infect Dis. 2006;38:682–689
  22. McGovern B, Ditelberg J, Taylor L, Gandhi RT, Christopoulos KA, Chapman S, et al. Hepatic steatosis is associated with fibrosis, nucleoside analogue use, and hepatitis C virus genotype 3 infection in HIV-seropositive patients. Clin Infect Dis. 2006;43:365–372
  23. Alberti A, Clumeck N, Collins S, Gerlich W, Lundgren J, Palù G, et al. Short statement of the first European Consensus Conference on the treatment of chronic hepatitis B and C in HIV co-infected patients. J Hepatol. 2005;42:615–624
  24. Tien PC. Management and treatment of hepatitis C virus infection in HIV-infected adults: recommendations from the Veterans Affairs Hepatitis C Resource Center Program and National Hepatitis C Program Office. Am J Gastroenterol. 2005;100:2338–2354
  25. Torriani FJ, Rodriguez-Torres M, Rockstroh JK, Lissen E, Gonzalez-García J, Lazzarin A, et al. Peginterferon Alfa-2a plus ribavirin for chronic hepatitis C virus infection in HIV-infected patients. N Engl J Med. 2004;351:438–450
  26. Lissen E, Clumeck N, Sola R, Mendes-Correa M, Montaner J, Nelson M, et al. Histological response to pegIFNα-2α (40KD) plus ribavirin in HIV–hepatitis C virus co-infection. AIDS. 2006;20:2175–2181
  27. Hung C, Kuo F, Wang J, Lu SN, Hu TH, Chen CH, et al. Impact of steatosis on long-term histological outcome in chronic hepatitis C after antiviral therapy. Antivir Ther. 2006;11:483–489
  28. Patton H, Patel K, Behling C, Bylund D, Blatt LM, Vallée M, et al. The impact of steatosis on disease progression and early and sustained treatment response in chronic hepatitis C patients. J Hepatol. 2004;40:484–490
  29. Poynard T, Ratziu V, McHutchison J, Manns M, Goodman Z, Zeuzem S, et al. Effect of treatment with peginterferon or interferon alfa-2b and ribavirin on steatosis in patients infected with hepatitis C. Hepatology. 2003;38:75–85
  30. Ishak K, Baptista A, Bianchi L, Callea F, De Groote J, Gudat F, et al. Histological grading and staging of chronic hepatitis. J Hepatol. 1995;22:696–699
  31. Kleiner DE, Brunt EM, Van Natta M, Behling C, Contos MJ, Cummings OW, et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology. 2005;41:1313–1321
  32. Satterthwaite FW. An approximate distribution of Estimates of Variance Components. Biometrics Bulletin. 1946;2:110–114
  33. Agresti Alan. Categorical data analysis. 2nd ed.. Wiley; 2002;
  34. Bani-Sadr F, Carrat F, Bedossa P, Piroth L, Cacoub P, Perronne C, et al. Hepatic steatosis in HIV–HCV coinfected patients: analysis of risk factors. AIDS. 2006;20:525–531
  35. Bugianesi E, Marchesini G, Gentilcore E, Cua IH, Vanni E, Rizzetto M, et al. Fibrosis in genotype 3 chronic hepatitis C and nonalcoholic fatty liver disease: role of insulin resistance and hepatic steatosis. Hepatology. 2006;44:1648–1655
  36. Lapadula G, Torti C, Paraninfo G, Castelnuovo F, Uccelli MC, Costarelli S, et al. Influence of hepatitis C genotypes on lipid levels in HIV-positive patients during highly active antiretroviral therapy. Antivir Ther. 2006;11:521–527
  37. Mokrzycki M, Harris C, May H, Laut J, Palmisano J. Lactic acidosis associated with stavudine administration: a report of five cases. Clin Infect Dis. 2000;30:198–200
  38. Jacobson DL, Tang AM, Spiegelman D, Thomas AM, Skinner SL, Gorbach SL, et al. Incidence of metabolic syndrome in a cohort of HIV-infected adults and prevalence relative to the US population (National Health and Nutrition Examination Survey). J Acquir Immune Defic Syndr. 2006;43:458–466
  39. Gazzaruso C, Sacchi P, Garzaniti A, Fratino P, Bruno R, Filice G. Prevalence of metabolic syndrome among HIV patients. Diabetes Care. 2002;25:1253–1254
  40. Tural C, Romero M, Solá R, Planas R, Viloria M, Gimenez M, et al. Insulin resistance in a prognostic factor of poor response to peg-interferon-alpha-2a + ribavirin in HCV+HIV patients. 13th Conferences on Retroviruses and Opportunistic Infections. Abstract 863.
  41. Romero-Gomez M, Del Mar Viloria M, Andrade RJ, Salmerón J, Diago M, Fernández-Rodríguez CM, et al. Insulin resistance impairs sustained response rate to peginterferon plus ribavirin in chronic hepatitis C patients. Gastroenterology. 2005;128:636–641
  42. Lonardo A, Lombardini S, Scaglioni F, Carulli L, Ricchi M, Ganazzi D, et al. Hepatic steatosis and insulin resistance: does etiology make a difference?. J Hepatol. 2006;44:190–196

☆ The authors who have taken part in the research of this paper declared that they have a relationship with the manufacturers of the drug involved and Dr. J. DePamphilis is employed by Roche Nutley, NJ, USA. They received funding from Roche for the conduct of the original APRICOT trial. This study was supported by a grant from Roche, Basel, Switzerland. Roche provided statistical analysis and initial editorial assistance for the preparation of this manuscript.

PII: S0168-8278(08)00066-4

doi: 10.1016/j.jhep.2008.01.015

Journal of Hepatology
Volume 48, Issue 5 , Pages 756-764 , May 2008

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