, Volume 41, Issue 2, pp 425–429 | Cite as

Absence of liver steatosis in HIV–HCV co-infected patients receiving regimens containing tenofovir or abacavir

  • V. Borghi
  • L. Bisi
  • L. Manzini
  • A. Cossarizza
  • C. Mussini
Clinical and Epidemiological Study



In human immunodeficiency virus–hepatitis C virus (HIV–HCV) co-infected patients, steatosis has been independently associated with a number of antiretroviral drugs, including stavudine, especially in patients with non-3 HCV genotypes. We retrospectively investigated the presence of steatosis among HIV–HCV co-infected and HCV mono-infected patients, and the role of tenofovir disoproxil fumarate (TDF) or abacavir (ABC) in determining hepatic steatosis.


Liver steatosis was retrospectively evaluated in all consecutive biopsies performed in the period 2000–2008 in HCV mono-infected and HIV–HCV co-infected patients. A steatosis rate of >5 % was considered to be significant, and a multivariate logistic analysis was performed to evaluate factors associated with steatosis.


In total, 393 HCV-infected patients underwent liver biopsy during the study period, of whom 205 (52.2 %) were co-infected with HIV. A steatosis rate of >5 % was diagnosed in 33.0 % of HCV mono-infected and in 47.8 % of HIV–HCV co-infected patients (P = 0.003). The rate of steatosis was higher in patients resuming antiretroviral therapy (54.7 %) than in naïve patients (33.3 %; P = 0.006). When the overall population was considered, steatosis was associated to HCV genotype 3 [odds ratio (OR) 4.53, 95 % confidence interval (CI) 2.71–7.58; P < 0.001]. In terms of the use of nucleos(t)ide drugs in HIV co-infected patients, multivariate analysis showed that only in patients with HCV genotypes other than genotype 3 was steatosis related to the use of stavudine (OR 5.38, 95 % CI 1.18-24.53; P = 0.03). The use of TDF (OR 1.07, 95 % CI 0.39–2.88; P = 0.898) or ABC (OR 0.592, 95 % CI 0.09–4.07; P = 0.594) was not associated with steatosis.


In HCV mono-infected and HIV–HCV co-infected patients, steatosis appears to be a virus-mediated effect of HCV genotype 3. In HIV patients infected with HCV genotypes other than genotype 3, the risk of developing steatosis was higher in those patients resuming antiretroviral regimens containing old drugs rather than the new antiretrovirals.


HIV–HCV coinfection Steatosis HAART 


Conflict of interest



  1. 1.
    Crum-Cianflone N, Dilay A, Collins G, Asher D, Campin R, Medina S, Goodman Z, Parker R, Lifson A, Capozza T, Bavaro M, Hale B, Hames C. Non-alcoholic fatty liver disease among HIV-infected persons. J Acquir Immune Defic Syndr. 2009;50(5):464–73.PubMedCrossRefGoogle Scholar
  2. 2.
    Guaraldi G, Squillace N, Stentarelli C, Orlando G, D’Amico R, Ligabue G, Fiocchi F, Zona S, Loria P, Esposito R, Palella F. Non-alcoholic fatty liver disease in HIV-infected patients referred to a metabolic clinic: prevalence, characteristics, and predictors. Clin Infect Dis. 2008;47(2):250–7.PubMedCrossRefGoogle Scholar
  3. 3.
    Ryan P, Blanco F, García-Gascó P, García-Merchán J, Vispo E, Barreiro P, Labarga P, González-Lahoz J, Soriano V. Predictors of severe hepatic steatosis using abdominal ultrasound in HIV-infected patients. HIV Med. 2009;10(1):53–9.PubMedCrossRefGoogle Scholar
  4. 4.
    Negro F. Insulin resistance and HCV: will new knowledge modify clinical management? J Hepatol. 2005;45:514–9.CrossRefGoogle Scholar
  5. 5.
    Cicconi P, Cozzi-Lepri A, Phillips A, Puoti M, Antonucci G, Manconi PE, Tositti G, Colangeli V, Lichtner M, Monforte A. ICoNA Study Group. Is the increased risk of liver enzyme elevation in patients co-infected with HIV and hepatitis virus greater in those taking antiretroviral therapy? AIDS. 2007;21(5):599–606.PubMedCrossRefGoogle Scholar
  6. 6.
    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):1057–65.PubMedGoogle Scholar
  7. 7.
    Leone S, Gregis G, Quinzan G, Velenti D, Cologni G, Soavi L, Ravasio V, Ripamonti D, Suter F, Maggiolo F. Causes of death and risk factors among HIV-infected persons in the HAART era: analysis of a large urban cohort. Infection. 2011;39(1):13–20.PubMedCrossRefGoogle Scholar
  8. 8.
    Zeremski M, Talal AH. Dideoxynucleoside analogues should be used cautiously in patients with hepatic steatosis. Clin Inf Dis. 2006;43:373–6.CrossRefGoogle Scholar
  9. 9.
    McGovern BH, Ditelberg JS, Taylor LE, Gandhi RT, Christopoulos KA, Chapman S, Schwartzapfel B, Rindler E, Fiorino AM, Zaman MT, Sax PE, Graeme-Cook F, Hibberd PL. Hepatic steatosis is associated with fibrosis, nucleoside analogue use, and hepatitis C virus genotype 3 infection in HIV-seropositive patients. Clin Infect Dis. 2006;43:365–72.PubMedCrossRefGoogle Scholar
  10. 10.
    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;19:585–92.PubMedCrossRefGoogle Scholar
  11. 11.
    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;42:310–6.PubMedCrossRefGoogle Scholar
  12. 12.
    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;192:1943–9.PubMedCrossRefGoogle Scholar
  13. 13.
    Bani-Sadr F, Carrat F, Bedossa P, Piroth L, Cacoub P, Perronne C, Degott C. ANRS HC02-Ribavic Study team. Hepatic steatosis in HIV–HCV coinfected patients: analysis of risk factors. AIDS. 2006;20:525–31.PubMedCrossRefGoogle Scholar
  14. 14.
    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;44:1026–32.PubMedCrossRefGoogle Scholar
  15. 15.
    Cossarizza A, Moyle G. Antiretroviral nucleoside and nucleotide analogues and mitochondria. AIDS. 2004;18:137–51.PubMedCrossRefGoogle Scholar
  16. 16.
    Fleischman A, Johnsen S, Systrom DM, Hrovat M, Farrar CT, Frontera W, Fitch K, Thomas BJ, Torriani M, Côté HC, Grinspoon SK. Effects of a nucleoside reverse transcriptase inhibitor, stavudine, on glucose disposal and mitochondrial function in muscle of healthy adults. Am J Physiol Endocrinol Metab. 2007;292:1666–73.CrossRefGoogle Scholar
  17. 17.
    Venhoff N, Setzer B, Melkaoui K, Walker UA. Mitochondrial toxicity of tenofovir, emtricitabine and abacavir alone and in combination with additional nucleoside reverse transcriptase inhibitors. Antivir Ther. 2007;12:1075–85.PubMedGoogle Scholar
  18. 18.
    Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services, National Institutes of Health, Bethesda. Available at: Accessed 20 Nov 2012.
  19. 19.
    Linee Guida Italiane sull’utilizzo dei farmaci antiretrovirali e sulla gestione diagnostico-clinica delle persone con infezione da HIV-1. Available at: Accessed 20 Nov 2012.
  20. 20.
    Ishak K, Baptista A, Bianchi L, Callea F, De Groote J, Gudat F, Denk H, Desmet V, Korb G, MacSween RN. Histological grading and staging of chronic hepatitis. J Hepatol. 1995;22:696–9.PubMedCrossRefGoogle Scholar
  21. 21.
    Negro F. Insulin resistance and HCV: will new knowledge modify clinical management? J Hepatol. 2005;45:514–9.CrossRefGoogle Scholar
  22. 22.
    Halfon P, Pénaranda G, Carrat F, Bedossa P, Bourlière M, Ouzan D, Renou C, Tran A, Rosenthal E, Wartelle C, Delasalle P, Cacoub P. Influence of insulin resistance on hepatic fibrosis and steatosis in hepatitis C virus (HCV) mono-infected compared with HIV–HCV co-infected patients. Aliment Pharmacol Ther. 2009;30:61–70.PubMedCrossRefGoogle Scholar
  23. 23.
    Maggiolo F, Roat E, Pinti M, Nasi M, Gibellini L, De Biasi S, Airoldi M, Ravasio V, Mussini C, Suter F, Cossarizza A. Mitochondrial changes during D-drug-containing once-daily therapy in HIV-positive treatment-naive patients. Antivir Ther. 2010;15:51–9.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • V. Borghi
    • 1
  • L. Bisi
    • 1
  • L. Manzini
    • 1
  • A. Cossarizza
    • 2
  • C. Mussini
    • 1
    • 2
  1. 1.Clinic of Infectious and Tropical Diseases, Azienda Ospedaliero–Universitaria Policlinico di ModenaUniversity of Modena and Reggio EmiliaModenaItaly
  2. 2.Department of Surgery, Medicine, Dentistry and Morphological SciencesUniversity of Modena and Reggio EmiliaModenaItaly

Personalised recommendations