Register      Login
Sexual Health Sexual Health Society
Publishing on sexual health from the widest perspective
RESEARCH ARTICLE

Liver disease, HIV and aging

Oluwaseun Falade-Nwulia A B C and Chloe L. Thio A
+ Author Affiliations
- Author Affiliations

A Division of Infectious Diseases, Johns Hopkins University, School of Medicine, 855 N Wolfe Street, Suite 520, Baltimore, MD 21231, USA.

B Critical Care Medicine Department, National Institutes of Health, 10 Center Drive, Rm 2C145, Bethesda, MD 20892, USA.

C Corresponding author. Email: faladeoo@cc.nih.gov

Sexual Health 8(4) 512-520 https://doi.org/10.1071/SH10163
Submitted: 20 December 2010  Accepted: 14 April 2011   Published: 29 July 2011

Abstract

The life expectancy of HIV-infected patients has increased due to the efficacy of highly active antiretroviral therapy (HAART) in controlling HIV replication; thus, the population living with HIV infection is steadily aging. Liver-related morbidity and mortality has emerged as a leading problem in HIV-infected patients. Since aging, HIV infection and HAART all affect the liver, understanding the impact of the combination of these factors on liver disease is crucial for optimisation of care in the aging HIV-infected population. This review will focus on the current understanding of liver disease in older (>50 years old) HIV-negative individuals and in HIV-infected individuals. Areas for future research in the area of HIV, liver disease and aging will also be discussed.

Additional keywords: cirrhosis, hepatitis, highly active antiretroviral therapy.


References

[1]  Gebo KA. HIV and aging: implications for patient management. Drugs Aging 2006; 23 897–913.
HIV and aging: implications for patient management.Crossref | GoogleScholarGoogle Scholar |

[2]  Effros RB, Fletcher CV, Gebo K, Halter JB, Hazzard WR, Horne FM, et al Aging and infectious diseases: workshop on HIV infection and aging: what is known and future research directions. Clin Infect Dis 2008; 47 542–53.
Aging and infectious diseases: workshop on HIV infection and aging: what is known and future research directions.Crossref | GoogleScholarGoogle Scholar |

[3]  Weber R, Sabin CA, Friis-Moller N, Reiss P, El-Sadr WM, Kirk O, et al Liver-related deaths in persons infected with the human immunodeficiency virus: the D:A:D study. Arch Intern Med 2006; 166 1632–41.
Liver-related deaths in persons infected with the human immunodeficiency virus: the D:A:D study.Crossref | GoogleScholarGoogle Scholar |

[4]  Salmon-Ceron D, Rosenthal E, Lewden C, Bouteloup V, May T, Burty C, et al Emerging role of hepatocellular carcinoma among liver-related causes of deaths in HIV-infected patients: the French national Mortalite 2005 study. J Hepatol 2009; 50 736–45.
Emerging role of hepatocellular carcinoma among liver-related causes of deaths in HIV-infected patients: the French national Mortalite 2005 study.Crossref | GoogleScholarGoogle Scholar |

[5]  Soriano V, Vispo E, Labarga P, Medrano J, Barreiro P. Viral hepatitis and HIV co-infection. Antiviral Res 2010; 85 303–15.
Viral hepatitis and HIV co-infection.Crossref | GoogleScholarGoogle Scholar |

[6]  Sherman KE, Freeman S, Harrison S, Andron L. Prevalence of antibody to hepatitis C virus in patients infected with the human immunodeficiency virus. J Infect Dis 1991; 163 414–5.
Prevalence of antibody to hepatitis C virus in patients infected with the human immunodeficiency virus.Crossref | GoogleScholarGoogle Scholar |

[7]  Rumi MG, Colombo M, Gringeri A, Mannucci PM. High prevalence of antibody to hepatitis C virus in multitransfused hemophiliacs with normal transaminase levels. Ann Intern Med 1990; 112 379–80.

[8]  Hayashi PH, Flynn N, McCurdy SA, Kuramoto IK, Holland PV, Zeldis JB. Prevalence of hepatitis C virus antibodies among patients infected with human immunodeficiency virus. J Med Virol 1991; 33 177–80.
Prevalence of hepatitis C virus antibodies among patients infected with human immunodeficiency virus.Crossref | GoogleScholarGoogle Scholar |

[9]  van de Laar TJ, Matthews GV, Prins M, Danta M. Acute hepatitis C in HIV-infected men who have sex with men: an emerging sexually transmitted infection. AIDS 2010; 24 1799–812.
Acute hepatitis C in HIV-infected men who have sex with men: an emerging sexually transmitted infection.Crossref | GoogleScholarGoogle Scholar |

[10]  Matthews GV, Hellard M, Kaldor J, Lloyd A, Dore GJ. Further evidence of HCV sexual transmission among HIV-positive men who have sex with men: response to Danta et al. AIDS 2007; 21 2112–3.
Further evidence of HCV sexual transmission among HIV-positive men who have sex with men: response to Danta et al.Crossref | GoogleScholarGoogle Scholar |

[11]  Urbanus AT, van de Laar TJ, Stolte IG, Schinkel J, Heijman T, Coutinho RA, et al Hepatitis C virus infections among HIV-infected men who have sex with men: an expanding epidemic. AIDS 2009; 23 F1–7.
Hepatitis C virus infections among HIV-infected men who have sex with men: an expanding epidemic.Crossref | GoogleScholarGoogle Scholar |

[12]  Danta M, Brown D, Bhagani S, Pybus OG, Sabin CA, Nelson M, et al Recent epidemic of acute hepatitis C virus in HIV-positive men who have sex with men linked to high-risk sexual behaviours. AIDS 2007; 21 983–91.
Recent epidemic of acute hepatitis C virus in HIV-positive men who have sex with men linked to high-risk sexual behaviours.Crossref | GoogleScholarGoogle Scholar |

[13]  Thomas DL. Hepatitis C and human immunodeficiency virus infection. Hepatology 2002; 36 S201–9.
Hepatitis C and human immunodeficiency virus infection.Crossref | GoogleScholarGoogle Scholar |

[14]  Mehta SH, Cox A, Hoover DR, Wang XH, Mao Q, Ray S, et al Protection against persistence of hepatitis C. Lancet 2002; 359 1478–83.
Protection against persistence of hepatitis C.Crossref | GoogleScholarGoogle Scholar |

[15]  Villano SA, Vlahov D, Nelson KE, Cohn S, Thomas DL. Persistence of viremia and the importance of long-term follow-up after acute hepatitis C infection. Hepatology 1999; 29 908–14.
Persistence of viremia and the importance of long-term follow-up after acute hepatitis C infection.Crossref | GoogleScholarGoogle Scholar |

[16]  Alter MJ, Margolis HS, Krawczynski K, Judson FN, Mares A, Alexander WJ, et al The natural history of community-acquired hepatitis C in the United States. The Sentinel Counties Chronic non-A, non-B Hepatitis Study Team. N Engl J Med 1992; 327 1899–905.
The natural history of community-acquired hepatitis C in the United States. The Sentinel Counties Chronic non-A, non-B Hepatitis Study Team.Crossref | GoogleScholarGoogle Scholar |

[17]  Thomas DL, Astemborski J, Rai RM, Anania FA, Schaeffer M, Galai N, et al The natural history of hepatitis C virus infection: host, viral, and environmental factors. JAMA 2000; 284 450–6.
The natural history of hepatitis C virus infection: host, viral, and environmental factors.Crossref | GoogleScholarGoogle Scholar |

[18]  Poynard T, Bedossa P, Opolon P. Natural history of liver fibrosis progression in patients with chronic hepatitis C. Lancet 1997; 349 825–32.
Natural history of liver fibrosis progression in patients with chronic hepatitis C.Crossref | GoogleScholarGoogle Scholar |

[19]  Asahina Y, Tsuchiya K, Tamaki N, Hirayama I, Tanaka T, Sato M, et al Effect of aging on risk for hepatocellular carcinoma in chronic hepatitis C virus infection. Hepatology 2010; 52 518–27.
Effect of aging on risk for hepatocellular carcinoma in chronic hepatitis C virus infection.Crossref | GoogleScholarGoogle Scholar |

[20]  Freeman AJ, Dore GJ, Law MG, Thorpe M, Von Overbeck J, Lloyd AR, et al Estimating progression to cirrhosis in chronic hepatitis C virus infection. Hepatology 2001; 34 809–16.
Estimating progression to cirrhosis in chronic hepatitis C virus infection.Crossref | GoogleScholarGoogle Scholar |

[21]  Tong MJ, el-Farra NS, Reikes AR, Co RL. Clinical outcomes after transfusion-associated hepatitis C. N Engl J Med 1995; 332 1463–6.
Clinical outcomes after transfusion-associated hepatitis C.Crossref | GoogleScholarGoogle Scholar |

[22]  Poynard T, Ratziu V, Charlotte F, Goodman Z, McHutchison J, Albrecht J. Rates and risk factors of liver fibrosis progression in patients with chronic hepatitis C. J Hepatol 2001; 34 730–9.
Rates and risk factors of liver fibrosis progression in patients with chronic hepatitis C.Crossref | GoogleScholarGoogle Scholar |

[23]  Marcus EL, Tur-Kaspa R. Chronic hepatitis C virus infection in older adults. Clin Infect Dis 2005; 41 1606–12.
Chronic hepatitis C virus infection in older adults.Crossref | GoogleScholarGoogle Scholar |

[24]  Graham CS, Baden LR, Yu E, Mrus JM, Carnie J, Heeren T, et al Influence of human immunodeficiency virus infection on the course of hepatitis C virus infection: a meta-analysis. Clin Infect Dis 2001; 33 562–9.
Influence of human immunodeficiency virus infection on the course of hepatitis C virus infection: a meta-analysis.Crossref | GoogleScholarGoogle Scholar |

[25]  Fried MW, Shiffman ML, Reddy KR, Smith C, Marinos G, Goncales FL, et al Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med 2002; 347 975–82.
Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection.Crossref | GoogleScholarGoogle Scholar |

[26]  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; 358 958–65.
Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial.Crossref | GoogleScholarGoogle Scholar |

[27]  Hadziyannis SJ, Sette H, Morgan TR, Balan V, Diago M, Marcellin P, et al Peginterferon-alpha2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose. Ann Intern Med 2004; 140 346–55.

[28]  Carrat F, Bani-Sadr F, Pol S, Rosenthal E, Lunel-Fabiani F, Benzekri A, et al Pegylated interferon alfa-2b vs standard interferon alfa-2b, plus ribavirin, for chronic hepatitis C in HIV-infected patients: a randomized controlled trial. JAMA 2004; 292 2839–48.
Pegylated interferon alfa-2b vs standard interferon alfa-2b, plus ribavirin, for chronic hepatitis C in HIV-infected patients: a randomized controlled trial.Crossref | GoogleScholarGoogle Scholar |

[29]  Chung RT, Andersen J, Volberding P, Robbins GK, Liu T, Sherman KE, et al Peginterferon alfa-2a plus ribavirin versus interferon alfa-2a plus ribavirin for chronic hepatitis C in HIV-coinfected persons. N Engl J Med 2004; 351 451–9.
Peginterferon alfa-2a plus ribavirin versus interferon alfa-2a plus ribavirin for chronic hepatitis C in HIV-coinfected persons.Crossref | GoogleScholarGoogle Scholar |

[30]  Torriani FJ, Rodriguez-Torres M, Rockstroh JK, Lissen E, Gonzalez-Garcia 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; 351 438–50.
Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection in HIV-infected patients.Crossref | GoogleScholarGoogle Scholar |

[31]  Gianmario Borroni MA, Aurora Bortoli A, Asiraghi AC, Cazzaniga M, Ceriani R, Guerzoni P, et al Older age increases the risk of relapse in genotype-1 chronic hepatitis patients showing complete early virologic response during peginterferon and ribavarin therapy. Hepatology 2010; 52 809A [Abstract]

[32]  Thabut D, Le Calvez S, Thibault V, Massard J, Munteanu M, Di Martino V, et al Hepatitis C in 6,865 patients 65 yr or older: a severe and neglected curable disease? Am J Gastroenterol 2006; 101 1260–7.
Hepatitis C in 6,865 patients 65 yr or older: a severe and neglected curable disease?Crossref | GoogleScholarGoogle Scholar |

[33]  Nudo CG, Wong P, Hilzenrat N, Deschenes M. Elderly patients are at greater risk of cytopenia during antiviral therapy for hepatitis C. Can J Gastroenterol 2006; 20 589–92.

[34]  Bhattacharya D, Umbleja T, Carrat F, Chung RT, Peters MG, Torriani F, et al Women experience higher rates of adverse events during hepatitis C virus therapy in HIV infection: a meta-analysis. J Acquir Immune Defic Syndr 2010; 55 170–5.
Women experience higher rates of adverse events during hepatitis C virus therapy in HIV infection: a meta-analysis.Crossref | GoogleScholarGoogle Scholar |

[35]  Mason AL, Lau JY, Hoang N, Qian K, Alexander GJ, Xu L, et al Association of diabetes mellitus and chronic hepatitis C virus infection. Hepatology 1999; 29 328–33.
Association of diabetes mellitus and chronic hepatitis C virus infection.Crossref | GoogleScholarGoogle Scholar |

[36]  Howard AA, Klein RS, Schoenbaum EE. Association of hepatitis C infection and antiretroviral use with diabetes mellitus in drug users. Clin Infect Dis 2003; 36 1318–23.
Association of hepatitis C infection and antiretroviral use with diabetes mellitus in drug users.Crossref | GoogleScholarGoogle Scholar |

[37]  Butt AA, Fultz SL, Kwoh CK, Kelley D, Skanderson M, Justice AC. Risk of diabetes in HIV infected veterans pre- and post-HAART and the role of HCV coinfection. Hepatology 2004; 40 115–9.
Risk of diabetes in HIV infected veterans pre- and post-HAART and the role of HCV coinfection.Crossref | GoogleScholarGoogle Scholar |

[38]  Bedimo R, Westfall AO, Mugavero M, Drechsler H, Khanna N, Saag M. Hepatitis C virus coinfection and the risk of cardiovascular disease among HIV-infected patients. HIV Med 2010; 11 462–8.

[39]  Thio CL, Seaberg EC, Skolasky R, Phair J, Visscher B, Munoz A, et al HIV-1, hepatitis B virus, and risk of liver-related mortality in the Multicenter Cohort Study (MACS). Lancet 2002; 360 1921–6.
HIV-1, hepatitis B virus, and risk of liver-related mortality in the Multicenter Cohort Study (MACS).Crossref | GoogleScholarGoogle Scholar |

[40]  Konopnicki D, Mocroft A, de Wit S, Antunes F, Ledergerber B, Katlama C, et al Hepatitis B and HIV: prevalence, AIDS progression, response to highly active antiretroviral therapy and increased mortality in the EuroSIDA cohort. AIDS 2005; 19 593–601.
Hepatitis B and HIV: prevalence, AIDS progression, response to highly active antiretroviral therapy and increased mortality in the EuroSIDA cohort.Crossref | GoogleScholarGoogle Scholar |

[41]  Spradling PR, Richardson JT, Buchacz K, Moorman AC, Brooks JT. Prevalence of chronic hepatitis B virus infection among patients in the HIV Outpatient Study, 1996–2007. J Viral Hepat 2010; 17 879–86.
Prevalence of chronic hepatitis B virus infection among patients in the HIV Outpatient Study, 1996–2007.Crossref | GoogleScholarGoogle Scholar |

[42]  Floreani A, Chiaramonte M, Naccarato R. Acute hepatitis in elderly patients. Arch Intern Med 1983; 143 1829
Acute hepatitis in elderly patients.Crossref | GoogleScholarGoogle Scholar |

[43]  Chiaramonte M, Floreani A, Naccarato R. Hepatitis B virus (HBV) in the elderly: an underestimated problem? Biomed Pharmacother 1987; 41 121–3.

[44]  Cleveland JL, Siew C, Lockwood SA, Gruninger SE, Chang SB, Neidle EA, et al Factors associated with hepatitis B vaccine response among dentists. J Dent Res 1994; 73 1029–35.

[45]  Bodsworth NJ, Cooper DA, Donovan B. The influence of human immunodeficiency virus type 1 infection on the development of the hepatitis B virus carrier state. J Infect Dis 1991; 163 1138–40.
The influence of human immunodeficiency virus type 1 infection on the development of the hepatitis B virus carrier state.Crossref | GoogleScholarGoogle Scholar |

[46]  Landrum ML, Fieberg AM, Chun HM, Crum-Cianflone NF, Marconi VC, Weintrob AC, et al The effect of human immunodeficiency virus on hepatitis B virus serologic status in co-infected adults. PLoS ONE 2010; 5 e8687
The effect of human immunodeficiency virus on hepatitis B virus serologic status in co-infected adults.Crossref | GoogleScholarGoogle Scholar |

[47]  Mai AL, Yim C, O’Rourke K, Heathcote EJ. The interaction of human immunodeficiency virus infection and hepatitis B virus infection in infected homosexual men. J Clin Gastroenterol 1996; 22 299–304.
The interaction of human immunodeficiency virus infection and hepatitis B virus infection in infected homosexual men.Crossref | GoogleScholarGoogle Scholar |

[48]  Fung J, Seto WK, Lai CL, Yuen J, Wong DK, Yuen MF. Profiles of HBV DNA in a large population of Chinese patients with chronic hepatitis B: implications for antiviral therapy. J Hepatol 2011; 54 159–200.

[49]  Kawaoka T, Suzuki F, Akuta N, Suzuki Y, Arase Y, Sezaki H, et al Efficacy of lamivudine therapy in elderly patients with chronic hepatitis B infection. J Gastroenterol 2007; 42 395–401.
Efficacy of lamivudine therapy in elderly patients with chronic hepatitis B infection.Crossref | GoogleScholarGoogle Scholar |

[50]  Dore GJ, Cooper DA, Barrett C, Goh LE, Thakrar B, Atkins M. Dual efficacy of lamivudine treatment in human immunodeficiency virus/hepatitis B virus-coinfected persons in a randomized, controlled study (CAESAR). The CAESAR Coordinating Committee. J Infect Dis 1999; 180 607–13.
Dual efficacy of lamivudine treatment in human immunodeficiency virus/hepatitis B virus-coinfected persons in a randomized, controlled study (CAESAR). The CAESAR Coordinating Committee.Crossref | GoogleScholarGoogle Scholar |

[51]  Thio CL, Locarnini S. Treatment of HIV/HBV coinfection: clinical and virologic issues. AIDS Rev 2007; 9 40–53.

[52]  Benhamou Y, Bochet M, Thibault V, Di Martino V, Caumes E, Bricaire F, et al Long-term incidence of hepatitis B virus resistance to lamivudine in human immunodeficiency virus-infected patients. Hepatology 1999; 30 1302–6.
Long-term incidence of hepatitis B virus resistance to lamivudine in human immunodeficiency virus-infected patients.Crossref | GoogleScholarGoogle Scholar |

[53]  Matthews GV, Bartholomeusz A, Locarnini S, Ayres A, Sasaduesz J, Seaberg E, et al Characteristics of drug resistant HBV in an international collaborative study of HIV–HBV-infected individuals on extended lamivudine therapy. AIDS 2006; 20 863–70.
Characteristics of drug resistant HBV in an international collaborative study of HIV–HBV-infected individuals on extended lamivudine therapy.Crossref | GoogleScholarGoogle Scholar |

[54]  Floreani A. Liver disorders in the elderly. Best Pract Res Clin Gastroenterol 2009; 23 909–17.
Liver disorders in the elderly.Crossref | GoogleScholarGoogle Scholar |

[55]  Price JC, Thio CL. Liver disease in the HIV-infected individual. Clin Gastroenterol Hepatol 2010; 8 1002–12.
Liver disease in the HIV-infected individual.Crossref | GoogleScholarGoogle Scholar |

[56]  Sotaniemi EA, Arranto AJ, Pelkonen O, Pasanen M. Age and cytochrome P450-linked drug metabolism in humans: an analysis of 226 subjects with equal histopathologic conditions. Clin Pharmacol Ther 1997; 61 331–9.
Age and cytochrome P450-linked drug metabolism in humans: an analysis of 226 subjects with equal histopathologic conditions.Crossref | GoogleScholarGoogle Scholar |

[57]  Nunez M, Lana R, Mendoza JL, Martin-Carbonero L, Soriano V. Risk factors for severe hepatic injury after introduction of highly active antiretroviral therapy. J Acquir Immune Defic Syndr 2001; 27 426–31.

[58]  Moyle G. Clinical manifestations and management of antiretroviral nucleoside analog-related mitochondrial toxicity. Clin Ther 2000; 22 911–36, discussion 898.
Clinical manifestations and management of antiretroviral nucleoside analog-related mitochondrial toxicity.Crossref | GoogleScholarGoogle Scholar |

[59]  Risk factors for lactic acidosis and severe hyperlactataemia in HIV-1-infected adults exposed to antiretroviral therapy. AIDS 2007; 21 2455–64.
Risk factors for lactic acidosis and severe hyperlactataemia in HIV-1-infected adults exposed to antiretroviral therapy.Crossref | GoogleScholarGoogle Scholar |

[60]  Junaidi O, Di Bisceglie AM. Aging liver and hepatitis. Clin Geriatr Med 2007; 23 889–903.
Aging liver and hepatitis.Crossref | GoogleScholarGoogle Scholar |

[61]  Tseng ARJ, Walmsley S, Sterling S, Salit I. Polypharmacy in older patients: a study of medication use and potential drug interactions in an aging ambulatory HIV clinic population. Reviews in antiviral therapy & infectious diseases. Abstract presented at the 1st International Workshop on HIV & Aging; 2010 Oct 4–5; Baltimore, MD, USA.

[62]  Marzolini C, Elzi L, Gibbons S, Weber R, Fux C, Furrer H, et al Prevalence of comedications and effect of potential drug–drug interactions in the Swiss HIV Cohort Study. Antivir Ther 2010; 15 413–23.
Prevalence of comedications and effect of potential drug–drug interactions in the Swiss HIV Cohort Study.Crossref | GoogleScholarGoogle Scholar |

[63]  Fountain FF, Tolley E, Chrisman CR, Self TH. Isoniazid hepatotoxicity associated with treatment of latent tuberculosis infection: a 7-year evaluation from a public health tuberculosis clinic. Chest 2005; 128 116–23.
Isoniazid hepatotoxicity associated with treatment of latent tuberculosis infection: a 7-year evaluation from a public health tuberculosis clinic.Crossref | GoogleScholarGoogle Scholar |

[64]  Culberson JW. Alcohol use in the elderly: beyond the CAGE. Part 1 of 2: prevalence and patterns of problem drinking. Geriatrics 2006; 61 23–7.

[65]  Galvan FH, Bing EG, Fleishman JA, London AS, Caetano R, Burnam MA, et al The prevalence of alcohol consumption and heavy drinking among people with HIV in the United States: results from the HIV Cost and Services Utilization Study. J Stud Alcohol 2002; 63 179–86.

[66]  Nkhoma EVV, Mynepalli L, Logie J. Comorbidities and co-infections among HIV patients 50 years and older. Reviews in antiviral therapy & infectious diseases. Abstract presented at the 1st International Workshop on HIV & Aging; 2010 Oct 4–5; Baltimore, MD, USA.

[67]  Meier P, Seitz HK. Age, alcohol metabolism and liver disease. Curr Opin Clin Nutr Metab Care 2008; 11 21–6.
Age, alcohol metabolism and liver disease.Crossref | GoogleScholarGoogle Scholar |

[68]  Seitz HK, Stickel F. Alcoholic liver disease in the elderly. Clin Geriatr Med 2007; 23 905–21.
Alcoholic liver disease in the elderly.Crossref | GoogleScholarGoogle Scholar |

[69]  Forrest EH, Evans CD, Stewart S, Phillips M, Oo YH, McAvoy NC, et al Analysis of factors predictive of mortality in alcoholic hepatitis and derivation and validation of the Glasgow alcoholic hepatitis score. Gut 2005; 54 1174–9.
Analysis of factors predictive of mortality in alcoholic hepatitis and derivation and validation of the Glasgow alcoholic hepatitis score.Crossref | GoogleScholarGoogle Scholar |

[70]  Potter JF, James OF. Clinical features and prognosis of alcoholic liver disease in respect of advancing age. Gerontology 1987; 33 380–7.
Clinical features and prognosis of alcoholic liver disease in respect of advancing age.Crossref | GoogleScholarGoogle Scholar |

[71]  Begriche K, Igoudjil A, Pessayre D, Fromenty B. Mitochondrial dysfunction in NASH: causes, consequences and possible means to prevent it. Mitochondrion 2006; 6 1–28.
Mitochondrial dysfunction in NASH: causes, consequences and possible means to prevent it.Crossref | GoogleScholarGoogle Scholar |

[72]  Guaraldi G, Squillace N, Stentarelli C, Orlando G, D’Amico R, Ligabue G, et al Nonalcoholic fatty liver disease in HIV-infected patients referred to a metabolic clinic: prevalence, characteristics, and predictors. Clin Infect Dis 2008; 47 250–7.
Nonalcoholic fatty liver disease in HIV-infected patients referred to a metabolic clinic: prevalence, characteristics, and predictors.Crossref | GoogleScholarGoogle Scholar |

[73]  Crum-Cianflone N, Dilay A, Collins G, Asher D, Campin R, Medina S, et al Nonalcoholic fatty liver disease among HIV-infected persons. J Acquir Immune Defic Syndr 2009; 50 464–73.
Nonalcoholic fatty liver disease among HIV-infected persons.Crossref | GoogleScholarGoogle Scholar |

[74]  Guaraldi G, Stentarelli C, Orlando G, Zona S, Carli F, Ballestri S, et al Nonalcoholic fatty liver disease in HIV-infected persons: epidemiology and the role of nucleoside reverse transcriptase inhibitors. J Acquir Immune Defic Syndr 2010; 53 278
Nonalcoholic fatty liver disease in HIV-infected persons: epidemiology and the role of nucleoside reverse transcriptase inhibitors.Crossref | GoogleScholarGoogle Scholar |

[75]  Jimba S, Nakagami T, Takahashi M, Wakamatsu T, Hirota Y, Iwamoto Y, et al Prevalence of non-alcoholic fatty liver disease and its association with impaired glucose metabolism in Japanese adults. Diabet Med 2005; 22 1141–5.
Prevalence of non-alcoholic fatty liver disease and its association with impaired glucose metabolism in Japanese adults.Crossref | GoogleScholarGoogle Scholar |

[76]  Browning JD, Szczepaniak LS, Dobbins R, Nuremberg P, Horton JD, Cohen JC, et al Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology 2004; 40 1387–95.
Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity.Crossref | GoogleScholarGoogle Scholar |

[77]  Williams CH, Stengel J, Asike MI, Torres DM, Shaw J, Contreras M, et al Prevalence of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis among a largely middle-aged population utilizing ultrasound and liver biopsy: a prospective study. Gastroenterology 2011; 140 124–31.

[78]  Frith J, Day CP, Henderson E, Burt AD, Newton JL. Non-alcoholic fatty liver disease in older people. Gerontology 2009; 55 607–13.
Non-alcoholic fatty liver disease in older people.Crossref | GoogleScholarGoogle Scholar |

[79]  Angulo P, Keach JC, Batts KP, Lindor KD. Independent predictors of liver fibrosis in patients with nonalcoholic steatohepatitis. Hepatology 1999; 30 1356–62.
Independent predictors of liver fibrosis in patients with nonalcoholic steatohepatitis.Crossref | GoogleScholarGoogle Scholar |

[80]  Grinspoon S, Carr A. Cardiovascular risk and body-fat abnormalities in HIV-infected adults. N Engl J Med 2005; 352 48–62.
Cardiovascular risk and body-fat abnormalities in HIV-infected adults.Crossref | GoogleScholarGoogle Scholar |

[81]  McGovern BH, Ditelberg JS, Taylor LE, 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; 43 365–72.
Hepatic steatosis is associated with fibrosis, nucleoside analogue use, and hepatitis C virus genotype 3 infection in HIV-seropositive patients.Crossref | GoogleScholarGoogle Scholar |

[82]  Clifford GM, Rickenbach M, Polesel J, Dal Maso L, Steffen I, Ledergerber B, et al Influence of HIV-related immunodeficiency on the risk of hepatocellular carcinoma. AIDS 2008; 22 2135–41.
Influence of HIV-related immunodeficiency on the risk of hepatocellular carcinoma.Crossref | GoogleScholarGoogle Scholar |

[83]  Puoti M, Bruno R, Soriano V, Donato F, Gaeta GB, Quinzan GP, et al Hepatocellular carcinoma in HIV-infected patients: epidemiological features, clinical presentation and outcome. AIDS 2004; 18 2285–93.
Hepatocellular carcinoma in HIV-infected patients: epidemiological features, clinical presentation and outcome.Crossref | GoogleScholarGoogle Scholar |

[84]  Brau N, Fox RK, Xiao P, Marks K, Naqvi Z, Taylor LE, et al Presentation and outcome of hepatocellular carcinoma in HIV-infected patients: a U.S.–Canadian multicenter study. J Hepatol 2007; 47 527–37.
Presentation and outcome of hepatocellular carcinoma in HIV-infected patients: a U.S.–Canadian multicenter study.Crossref | GoogleScholarGoogle Scholar |

[85]  O’Connor S, Ward JW, Watson M, Momin B, Richardson LC. Hepatocellular carcinoma – United States, 2001–2006 (reprinted from vol 59, pg 517–520, 2010). JAMA 2010; 303 2349–50.

[86]  Patel P, Hanson DL, Sullivan PS, Novak RM, Moorman AC, Tong TC, et al Incidence of types of cancer among HIV-infected persons compared with the general population in the United States, 1992–2003. Ann Intern Med 2008; 148 728–36.

[87]  Kramer JR, Giordano TP, Souchek J, Richardson P, Hwang LY, El-Serag HB. The effect of HIV coinfection on the risk of cirrhosis and hepatocellular carcinoma in U.S. veterans with hepatitis C. Am J Gastroenterol 2005; 100 56–63.
The effect of HIV coinfection on the risk of cirrhosis and hepatocellular carcinoma in U.S. veterans with hepatitis C.Crossref | GoogleScholarGoogle Scholar |

[88]  Bruix J, Sherman M. Management of hepatocellular carcinoma: an update. Hepatology 2011; 53 1020–2.
Management of hepatocellular carcinoma: an update.Crossref | GoogleScholarGoogle Scholar |

[89]  Bruix J, Sherman M. Management of hepatocellular carcinoma. Hepatology 2005; 42 1208–36.
Management of hepatocellular carcinoma.Crossref | GoogleScholarGoogle Scholar |