Hepatic steatosis in HIV-HCV coinfected patients receiving antiretroviral therapy is associated with HCV-related factors but not antiretrovirals

BMC Research Notes

Eric Caumes⁷  Christine Katlama⁷  Jean-Michel Molina⁴  Philippe Bertheau⁵  Frderic Charlotte²  Marc-Antoine Valantin⁷  Patrick Miailhes⁶  Marguerite Guiguet⁷  Zahra Mokhtari³  Thi Dieu Ngan TA⁸  Valrie Martinez¹ 

[1] Service des Maladies Infectieuses et Tropicales, Hpital Piti-Salptrire, Universit Pierre et Marie Curie, APHP, 45/83 Boulevard de lHpital, 75013, Paris, France;Service dAnatomopathologie, Hpital Piti-Salptrire, Universit Pierre et Marie Curie, APHP, 45/83 Boulevard de lHpital, 75013, Paris, France;Departement of Internal Medicine, Hospital National Iranian oil company, Hafez Avenue, Tehran, Iran;Service des Maladies Infectieuses et Tropicales, Hpital Saint-Louis, Universit Denis Diderot, APHP, 1, avenue Claude Vellefaux, 75010, Paris, France;Service dAnatomopathologie, Hpital Saint-Louis, Universit Denis Diderot, APHP, 1, avenue Claude Vellefaux, 75010, Paris, France;Service de Maladies Infectieuses et Tropicales, 103 Grande-Rue de la Croix-Rousse, Hpital de la Croix-Rousse, Hospices Civils de Lyon, 69317 Lyon cedex 04, Paris, France;INSERM U943, UPMC Univ Paris 06, UMR S943, Paris, F-75013, France;Departement of Infectious Disease, Hanoi Medical University, 01, Ton That Tung Street, Hanoi, Vietnam

关键词: genotype 3;    antiretroviral drugs;    steatosis;    HCV;    HIV;   

Others  :  1166511
DOI  :  10.1186/1756-0500-5-180

 received in 2011-10-24, accepted in 2012-04-10,  发布年份 2012

【 摘 要 】

Background

In HIV and hepatitis C virus (HCV) coinfected patients, the role of antiretroviral therapy (ART) on hepatic steatosis (HS) remains controversial.

Methods

HIV/HCV coinfected patients receiving ART and previously untreated for HCV who underwent a liver biopsy were included. Cumulative duration of exposure to each antiretroviral was recorded up to liver biopsy date. Logistic regression analyses evaluated factors associated with steatosis and its severity.

Results

184 patients were included: median age 41years, 84% male, 89% Caucasian, 61% with a past history of intravenous drug use. HCV genotypes were 1 (55%), 2 (6%), 3 (26%), and 4 (13%). Median HCV-RNA was 6.18 log₁₀ IU/ml. HIV-RNA was undetectable (<400 copies/ml) in 67% of patients. Median CD4 count was 321/mm³. All patients had been exposed to nucleoside reverse transcriptase inhibitors (median cumulative exposure 56months); 126 received protease inhibitors (23months), and 79 non-nucleoside reverse transcriptase inhibitors (16months). HS was observed in 102 patients (55%): 41% grade 1; 5% grade 2, and 9% grade 3. In multivariate analysis, HCV genotype 3 and HCV viral load were moderately associated with mild steatosis but strongly with grade 2-3 steatosis. After adjustment for the period of biopsy, no association was detected between HS and exposure to any antiretroviral class or drug, or duration of ART globally or comparing genotype 3 to others.

Conclusions

Among our ART-treated HIV-HCV cohort predominantly infected with genotype 1, 55% of patients had HS which was associated with HCV-related factors, but not ART class or duration of exposure.

【 授权许可】

   
2012 Martinez et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

【 参考文献 】

• [1]Martin-Carbonero L, Benhamou Y, Puoti M, Berenguer J, Mallolas J, Quereda C, Arizcorreta A, Gonzalez A, Rockstroh J, Asensi V, et al.: Incidence and predictors of severe liver fibrosis in human immunodeficiency virus-infected patients with chronic hepatitis C: a European collaborative study. Clin Infect Dis 2004, 38(1):128-133. Epub 2003 Dec 2008
• [2]Mehta SH, Thomas DL, Torbenson M, Brinkley S, Mirel L, Chaisson RE, Moore RD, Sulkowski MS: The effect of antiretroviral therapy on liver disease among adults with HIV and hepatitis C coinfection. Hepatology 2005, 41(1):123-131.
• [3]Qurishi N, Kreuzberg C, Luchters G, Effenberger W, Kupfer B, Sauerbruch T, Rockstroh JK, Spengler U: Effect of antiretroviral therapy on liver-related mortality in patients with HIV and hepatitis C virus coinfection. Lancet 2003, 362(9397):1708-1713.
• [4]Lauer GM, Walker BD: Hepatitis C virus infection. N Engl J Med 2001, 345(1):41-52.
• [5]Graham CS, Baden LR, Yu E, Mrus JM, Carnie J, Heeren T, Koziel MJ: Influence of human immunodeficiency virus infection on the course of hepatitis C virus infection: a meta-analysis. Clin Infect Dis 2001, 33(4):562-569.
• [6]Macias J, Castellano V, Merchante N, Palacios RB, Mira JA, Saez C, Garcia-Garcia JA, Lozano F, Gomez-Mateos JM, Pineda JA: Effect of antiretroviral drugs on liver fibrosis in HIV-infected patients with chronic hepatitis C: harmful impact of nevirapine. AIDS 2004, 18(5):767-774.
• [7]Qurishi N, Kreuzberg C, Luchters G, Effenberger W, Kupfer B, Sauerbruch T, Rockstroh JK, Spengler U: Effect of antiretroviral therapy on liver-related mortality in patients with HIV and hepatitis C virus coinfection. Lancet 2003, 362(9397):1708-1713.
• [8]Mohsen AH, Easterbrook PJ, Taylor C, Portmann B, Kulasegaram R, Murad S, Wiselka M, Norris S: Impact of human immunodeficiency virus (HIV) infection on the progression of liver fibrosis in hepatitis C virus infected patients. Gut 2003, 52(7):1035-1040.
• [9]Soriano V, Martin-Carbonero L, Garcia-Samaniego J, Puoti M: Mortality due to chronic viral liver disease among patients infected with human immunodeficiency virus. Clin Infect Dis 2001, 33(10):1793-1795.
• [10]Thein HH, Yi Q, Dore GJ, Krahn MD: Natural history of hepatitis C virus infection in HIV-infected individuals and the impact of HIV in the era of highly active antiretroviral therapy: a meta-analysis. AIDS 2008, 22(15):1979-1991.
• [11]Bica I, McGovern B, Dhar R, Stone D, McGowan K, Scheib R, Snydman DR: Increasing mortality due to end-stage liver disease in patients with human immunodeficiency virus infection. Clin Infect Dis 2001, 32(3):492-497.
• [12]Sulkowski MS, Mehta SH, Torbenson M, Afdhal NH, Mirel L, Moore RD, Thomas DL: Hepatic steatosis and antiretroviral drug use among adults coinfected with HIV and hepatitis C virus. AIDS 2005, 19(6):585-592.
• [13]Pol S, Lebray P, Vallet-Pichard A: HIV infection and hepatic enzyme abnormalities: intricacies of the pathogenic mechanisms. Clin Infect Dis 2004, 38(Suppl 2):S65-S72.
• [14]Sterling RK, Contos MJ, Smith PG, Stravitz RT, Luketic VA, Fuchs M, Shiffman ML, Sanyal AJ: Steatohepatitis: Risk factors and impact on disease severity in human immunodeficiency virus/hepatitis C virus coinfection. Hepatology 2008, 47(4):1118-1127.
• [15]Bani-Sadr F, Carrat F, Bedossa P, Piroth L, Cacoub P, Perronne C, Degott C, Pol S: Hepatic steatosis in HIV-HCV coinfected patients: analysis of risk factors. AIDS 2006, 20(4):525-531.
• [16]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(6):1026-1032.
• [17]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(11):1943-1949. Epub 2005 Nov 1942
• [18]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(2):310-316.
• [19]McGovern BH, Ditelberg JS, Taylor LE, Gandhi RT, Christopoulos KA, Chapman S, Schwartzapfel B, Rindler E, Fiorino AM, Zaman MT, 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(3):365-372.
• [20]Neau D, Winnock M, Castera L, Bail BL, Loko MA, Geraut L, Dupon M, Ragnaud JM, Lacoste D, Lafon ME, 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(2):168-173.
• [21]Sanchez-Conde M, Berenguer J, Miralles P, Alvarez F, Carlos Lopez J, Cosin J, Pilar C, Ramirez M, Gutierrez I, Alvarez E: Liver biopsy findings for HIV-infected patients with chronic hepatitis C and persistently normal levels of alanine aminotransferase. Clin Infect Dis 2006, 43(5)):640-644.
• [22]Castera L, Loko MA, Le Bail B, Coffie P, De Ledinghen V, Trimoulet P, Winnock M, Dabis F, Neau D: Hepatic steatosis in HIV-HCV coinfected patients in France: comparison with HCV monoinfected patients matched for body mass index and HCV genotype. Aliment Pharmacol Ther 2007, 26(1112):1489-1498.
• [23]Borghi V, Puoti M, Mussini C, Bellelli S, Angeletti C, Sabbatini F, Prati F, Cossarizza A, Esposito R: HIV coinfection and antiretroviral therapy enhances liver steatosis in patients with hepatitis C, but only in those infected by HCV genotype other than 3. Antivir Ther 2008, 13(8):1057-1065.
• [24]Monto A, Alonzo J, Watson JJ, Grunfeld C, Wright TL: Steatosis in chronic hepatitis C: relative contributions of obesity, diabetes mellitus, and alcohol. Hepatology 2002, 36(3):729-736.
• [25]Sanyal AJ: Review article: non-alcoholic fatty liver disease and hepatitis Crisk factors and clinical implications. Aliment Pharmacol Ther 2005, 22(Suppl 2):48-51.
• [26]Hourigan LF, Macdonald GA, Purdie D, Whitehall VH, Shorthouse C, Clouston A, Powell EE: Fibrosis in chronic hepatitis C correlates significantly with body mass index and steatosis. Hepatology 1999, 29(4):1215-1219.
• [27]Hu KQ, Kyulo NL, Esrailian E, Thompson K, Chase R, Hillebrand DJ, Runyon BA: Overweight and obesity, hepatic steatosis, and progression of chronic hepatitis C: a retrospective study on a large cohort of patients in the United States. J Hepatol 2004, 40(1):147-154.
• [28]Sanyal AJ, Contos MJ, Sterling RK, Luketic VA, Shiffman ML, Stravitz RT, Mills AS: Nonalcoholic fatty liver disease in patients with hepatitis C is associated with features of the metabolic syndrome. Am J Gastroenterol 2003, 98(9):2064-2071.
• [29]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(11):1943-1949.
• [30]Brinkman K: Editorial response: hyperlactatemia and hepatic steatosis as features of mitochondrial toxicity of nucleoside analogue reverse transcriptase inhibitors. Clin Infect Dis 2000, 31(1):167-169.
• [31]Balasubramanyam A, Sekhar RV, Jahoor F, Jones PH, Pownall HJ: Pathophysiology of dyslipidemia and increased cardiovascular risk in HIV lipodystrophy: a model of 'systemic steatosis'. Curr Opin Lipidol 2004, 15(1):59-67.
• [32]Ogedegbe AE, Thomas DL, Diehl AM: Hyperlactataemia syndromes associated with HIV therapy. Lancet Infect Dis 2003, 3(6):329-337.
• [33]Brunt EM, Janney CG, Di Bisceglie AM, Neuschwander-Tetri BA, Bacon BR: Nonalcoholic steatohepatitis: a proposal for grading and staging the histological lesions. Am J Gastroenterol 1999, 94(9):2467-2474.
• [34]The French METAVIR Cooperative Study Group: Intraobserver and interobserver variations in liver biopsy interpretation in patients with chronic hepatitis C. Hepatology 1994, 20(1 Pt 1):15-20.
• [35]Tien PC, Grunfeld C: The fatty liver in AIDS. Semin Gastrointest Dis 2002, 13(1):47-54.
• [36]Bauerle J, Miquel R, Laguno M, Mallolas J, Murillas J, Gatell JM, Walker UA: Hepatic steatosis with stavudine in HIV/hepatitis C virus co-infection. AIDS 2005, 19(13):1441-1442.
• [37]Bauerle J, Miquel R, Laguno M, Mallolas J, Murillas J, Gatell JM, Walker UA: Hepatic steatosis with stavudine in HIV/hepatitis C virus co-infection. AIDS 2005, 19(13):1441-1442.
• [38]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(6):1026-1032.
• [39]Bani-Sadr F, Carrat F, Bedossa P, Piroth L, Cacoub P, Perronne C, Degott C, Pol S: Hepatic steatosis in HIV-HCV coinfected patients: analysis of risk factors. AIDS 2006, 20(4):525-531.
• [40]Castera L, Loko MA, Le Bail B, Coffie P, De Ledinghen V, Trimoulet P, Winnock M, Dabis F, Neau D: Hepatic steatosis in HIV-HCV coinfected patients in France: comparison with HCV monoinfected patients matched for body mass index and HCV genotype. Aliment Pharmacol Ther 2007, 26(1112):1489-1498.
• [41]Woreta TA, Sutcliffe CG, Mehta SH, Brown TT, Higgins Y, Thomas DL, Torbenson MS, Moore RD, Sulkowski MS: Incidence and risk factors for steatosis progression in adults coinfected with HIV and hepatitis C virus. Gastroenterology 2011, 140(3):809-817.
• [42]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(11):1943-1949. Epub 2005 Nov 1942
• [43]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(2):310-316.
• [44]Neau D, Winnock M, Castera L, Bail BL, Loko MA, Geraut L, Dupon M, Ragnaud JM, Lacoste D, Lafon ME, 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(2):168-173.
• [45]Sulkowski MS, Mehta SH, Torbenson M, Afdhal NH, Mirel L, Moore RD, Thomas DL: Hepatic steatosis and antiretroviral drug use among adults coinfected with HIV and hepatitis C virus. AIDS 2005, 19(6):585-592.
• [46]Browning JD, Szczepaniak LS, Dobbins R, Nuremberg P, Horton JD, Cohen JC, Grundy SM, Hobbs HH: Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology 2004, 40(6):1387-1395.
• [47]Martin-Carbonero L, Soriano V: Interplay between hepatitis C, liver steatosis and antiretroviral therapy in HIV-infected patients. AIDS 2005, 19(6):621-623.
• [48]Castera L, Hezode C, Roudot-Thoraval F, Lonjon I, Zafrani ES, Pawlotsky JM, Dhumeaux D: Effect of antiviral treatment on evolution of liver steatosis in patients with chronic hepatitis C: indirect evidence of a role of hepatitis C virus genotype 3 in steatosis. Gut 2004, 53(3):420-424.
• [49]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(5):1266-1272.
• [50]Loko MA, Salmon D, Carrieri P, Winnock M, Mora M, Merchadou L, Gillet S, Pambrun E, Delaune J, Valantin MA, et al.: The French national prospective cohort of patients co-infected with HIV and HCV (ANRS CO13 HEPAVIH): early findings, 20062010. BMC Infect Dis 2010, 10:303. BioMed Central Full Text
• [51]Adinolfi LE, 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(6):1358-1364.
• [52]Castera L, Chouteau P, Hezode C, Zafrani ES, Dhumeaux D, Pawlotsky JM: Hepatitis C virus-induced hepatocellular steatosis. Am J Gastroenterol 2005, 100(3):711-715.
• [53]Clement S, Negro F: Hepatitis C virus: the viral way to fatty liver. J Hepatol 2007, 46(6):985-987.
• [54]Hezode C, Roudot-Thoraval F, Zafrani ES, Dhumeaux D, Pawlotsky JM: Different mechanisms of steatosis in hepatitis C virus genotypes 1 and 3 infections. J Viral Hepat 2004, 11(5):455-458.
• [55]Patton HM, Patel K, Behling C, Bylund D, Blatt LM, Vallee M, Heaton S, Conrad A, Pockros PJ, McHutchison JG: The impact of steatosis on disease progression and early and sustained treatment response in chronic hepatitis C patients. J Hepatol 2004, 40(3):484-490.
• [56]Rubbia-Brandt L, Quadri R, Abid K, Giostra E, Male PJ, Mentha G, Spahr L, Zarski JP, Borisch B, Hadengue A, et al.: Hepatocyte steatosis is a cytopathic effect of hepatitis C virus genotype 3. J Hepatol 2000, 33(1):106-115.
• [57]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(9):1433-1436.
• [58]Sulkowski MS, Mehta SH, Chaisson RE, Thomas DL, Moore RD: Hepatotoxicity associated with protease inhibitor-based antiretroviral regimens with or without concurrent ritonavir. AIDS 2004, 18(17):2277-2284.
• [59]Y B: Systemic overview of HAART- associated liver enzyme elevations in patients infected with HIV and co-infected with HCV. In: 13 th Conference on Retroviruses and Opportunistic Infections 2006. Denver, CO, US; 2006.
• [60]Day CP, James OF: Steatohepatitis: a tale of two "hits"? Gastroenterology 1998, 114(4):842-845.
• [61]Bauerle J, Laguno M, Mauss S, Mallolas J, Murillas J, Miquel R, Schmutz G, Setzer B, Gatell JM, Walker UA: Mitochondrial DNA depletion in liver tissue of patients infected with hepatitis C virus: contributing effect of HIV infection? HIV Med 2005, 6(2):135-139.
• [62]Monto A, Alonzo J, Watson JJ, Grunfeld C, Wright TL: Steatosis in chronic hepatitis C: relative contributions of obesity, diabetes mellitus, and alcohol. Hepatology 2002, 36(3):729-736.