{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T08:56:30Z","timestamp":1789376190562,"version":"build-2803163510"},"reference-count":40,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":2403,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2009,2]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>\n                      Liver damage associated with chronic unexplained high serum transaminases in human immunodeficiency virus (HIV)-infected patients under combined antiretroviral therapy is unknown. Liver histology was prospectively investigated in patients presenting serum transaminase elevation for more than 6 months, after exclusion of alcohol abuse, hepatitis C virus (HCV) or hepatitis B virus (HBV) infection, autoimmune, and genetic liver diseases. In a subgroup of patients, liver mitochondrial activities were measured by spectrophotometry and mitochondrial DNA (mtDNA) by real-time polymerase chain reaction (PCR). Thirty patients were included with median values of alanine aminotransferase (ALT) levels: 80 U\/L, age: 46 years, body mass index: 23 kg\/m\n                      <jats:sup>2<\/jats:sup>\n                      , HIV RNA: 200 copies\/mL, CD4 count: 365\/mm\n                      <jats:sup>3<\/jats:sup>\n                      , duration of HIV infection: 13 years, and duration of treatment exposure: 118, 41, and 53 months for nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, and protease inhibitors, respectively. Histological anomalies were found in 22 of 30 patients. Steatosis was present in 18 patients, severe in nine patients, and associated with inflammation in 16 patients with a diagnosis of non-alcoholic steatohepatitis (NASH). Fibrosis was found in 18 patients, severe in six patients and associated with steatosis in 13 patients. Significant liver respiratory complex I defect, contrasting with high complex IV activity and normal mitochondrial DNA content, was observed in the group of patients compared with controls. The presence of NASH was correlated with high fasting glycemia and insulin levels, not with liver mitochondrial function or mitochondrial DNA content.\n                      <jats:italic toggle=\"yes\">Conclusions:<\/jats:italic>\n                      HIV-infected patients on combined antiretroviral therapy with chronic transaminase elevation of unknown origin have a high rate of liver lesions, mostly consistent with NASH related to insulin resistance. (Hepatology 2008.)\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/hep.22665","type":"journal-article","created":{"date-parts":[[2008,12,10]],"date-time":"2008-12-10T13:47:13Z","timestamp":1228916833000},"page":"436-442","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":132,"title":["Liver damage underlying unexplained transaminase elevation in human immunodeficiency virus-1 mono-infected patients on antiretroviral therapy #"],"prefix":"10.1097","volume":"49","author":[{"given":"Patrick","family":"Ingiliz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc-Antoine","family":"Valantin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudine","family":"Duvivier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fadia","family":"Medja","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Dominguez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fr\u00e9d\u00e9ric","family":"Charlotte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland","family":"Tubiana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thierry","family":"Poynard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Katlama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Lomb\u00e8s","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yves","family":"Benhamou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"R1-16-20260311","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.jhep.2005.11.027","article-title":"Hepatotoxicity of antiretrovirals: incidence, mechanisms and management.","volume":"44","author":"Nunez","year":"2006","journal-title":"J Hepatol"},{"key":"R2-16-20260311","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1093\/clinids\/14.3.773-a","article-title":"Interactions and toxicities of drugs used in patients with AIDS.","volume":"14","author":"Lee","year":"1992","journal-title":"Clin Infect Dis"},{"key":"R3-16-20260311","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1093\/clinids\/23.5.1117","article-title":"Reciprocal interactions between human immunodeficiency virus and hepatitis C virus infections.","volume":"23","author":"Zylberberg","year":"1996","journal-title":"Clin Infect Dis"},{"key":"R4-16-20260311","doi-asserted-by":"crossref","first-page":"1138","DOI":"10.1093\/infdis\/163.5.1138","article-title":"The influence of human immunodeficiency virus type 1 infection on the development of the hepatitis B virus carrier state.","volume":"163","author":"Bodsworth","year":"1991","journal-title":"J Infect Dis"},{"key":"R5-16-20260311","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1097\/00126334-200310010-00006","article-title":"Hospitalization rates differ by hepatitis C status in an urban HIV cohort.","volume":"34","author":"Gebo","year":"2003","journal-title":"J Acquir Immune Defic Syndr"},{"key":"R6-16-20260311","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1086\/318501","article-title":"Increasing mortality due to endstage liver disease in patients with human immunodeficiency virus infection.","volume":"32","author":"Bica","year":"2001","journal-title":"Clin Infect Dis"},{"key":"R7-16-20260311","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1097\/01.aids.0000163935.99401.25","article-title":"Hepatic steatosis and antiretroviral drug use among adults coinfected with HIV and hepatitis C virus.","volume":"19","author":"Sulkowski","year":"2005","journal-title":"AIDS"},{"key":"R8-16-20260311","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1086\/313912","article-title":"Hyperlactatemia and hepatic abnormalities in 10 HIVinfected patients receiving nucleoside analogue combination regimens.","volume":"31","author":"Lonergan","year":"2000","journal-title":"Clin Infect Dis"},{"key":"R9-16-20260311","doi-asserted-by":"crossref","first-page":"192","DOI":"10.7326\/0003-4819-133-3-200008010-00010","article-title":"Lactic acidosis and hepatic steatosis associated with the use of stavudine: report of four cases.","volume":"133","author":"Miller","year":"2000","journal-title":"Ann Intern Med"},{"key":"R10-16-20260311","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1097\/00002030-200002180-00001","article-title":"A syndrome of lipoatrophy, lactic acidemia and liver dysfunction associated with HIV nucleoside analog therapy: contribution to protease inhibitorrelated lipodystrophy syndrome.","volume":"14","author":"Carr","year":"2000","journal-title":"AIDS"},{"key":"R11-16-20260311","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1053\/j.gastro.2003.11.020","article-title":"Steatosis and hepatitis C virus: mechanisms and significance for hepatic and extrahepatic disease.","volume":"126","author":"Lonardo","year":"2004","journal-title":"Gastroenterology"},{"key":"R12-16-20260311","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1097\/00126334-200308150-00005","article-title":"The effect of HAART and HCV infection on the development of hyperglycemia among HIVinfected persons.","volume":"33","author":"Mehta","year":"2003","journal-title":"J Acquir Immune Defic Syndr"},{"key":"R13-16-20260311","first-page":"40","article-title":"Hepatitis C and steatosis.","volume":"13","author":"Monto","year":"2002","journal-title":"Semin Gastrointest Dis"},{"key":"R14-16-20260311","doi-asserted-by":"crossref","first-page":"1358","DOI":"10.1053\/jhep.2001.24432","article-title":"Steatosis accelerates the progression of liver damage of chronic hepatitis C patients and correlates with specific HCV genotype and visceral obesity.","volume":"33","author":"Adinolfi","year":"2001","journal-title":"HEPATOLOGY"},{"key":"R15-16-20260311","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1002\/hep.510290401","article-title":"Fibrosis in chronic hepatitis C correlates significantly with body mass index and steatosis.","volume":"29","author":"Hourigan","year":"1999","journal-title":"HEPATOLOGY"},{"key":"R16-16-20260311","doi-asserted-by":"crossref","first-page":"112","DOI":"10.7326\/0003-4819-132-2-200001180-00004","article-title":"Prevalence of and risk factors for hepatic steatosis in Northern Italy.","volume":"132","author":"Bellentani","year":"2000","journal-title":"Ann Intern Med"},{"key":"R17-16-20260311","doi-asserted-by":"crossref","first-page":"1844","DOI":"10.2337\/diabetes.50.8.1844","article-title":"Nonalcoholic fatty liver disease: a feature of the metabolic syndrome.","volume":"50","author":"Marchesini","year":"2001","journal-title":"Diabetes"},{"key":"R18-16-20260311","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1046\/j.1440-1746.17.s3.31.x","article-title":"Nonalcoholic steatohepatitis: definitions and pathogenesis.","volume":"17","author":"Day","year":"2002","journal-title":"J Gastroenterol Hepatol"},{"key":"R19-16-20260311","doi-asserted-by":"crossref","first-page":"1705","DOI":"10.1053\/gast.2002.36572","article-title":"AGA technical review on nonalcoholic fatty liver disease.","volume":"123","author":"Sanyal","year":"2002","journal-title":"Gastroenterology"},{"key":"R20-16-20260311","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1053\/jhep.2003.50161","article-title":"Nonalcoholic fatty liver, steatohepatitis, and the metabolic syndrome.","volume":"37","author":"Marchesini","year":"2003","journal-title":"HEPATOLOGY"},{"key":"R21-16-20260311","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1016\/S0025-6196(24)00530-5","article-title":"Nonalcoholic steatohepatitis: Mayo Clinic experiences with a hitherto unnamed disease.","volume":"55","author":"Ludwig","year":"1980","journal-title":"Mayo Clin Proc"},{"key":"R22-16-20260311","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1016\/S0016-5085(99)70506-8","article-title":"Nonalcoholic fatty liver disease: a spectrum of clinical and pathological severity.","volume":"116","author":"Matteoni","year":"1999","journal-title":"Gastroenterology"},{"key":"R23-16-20260311","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1097\/00004836-200203000-00013","article-title":"Update on nonalcoholic fatty liver disease.","volume":"34","author":"McCullough","year":"2002","journal-title":"J Clin Gastroenterol"},{"key":"R24-16-20260311","doi-asserted-by":"crossref","first-page":"1667","DOI":"10.1097\/01.ALC.0000091224.78880.47","article-title":"Recommendations on use of biomarkers in alcoholism treatment trials.","volume":"27","author":"Allen","year":"2003","journal-title":"Alcohol Clin Exp Res"},{"key":"R25-16-20260311","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1002\/hep.20701","article-title":"Nonalcoholic steatohepatitis clinical research network. design and validation of a histological scoring system for nonalcoholic fatty liver disease.","volume":"41","author":"Kleiner","year":"2005","journal-title":"HEPATOLOGY"},{"key":"R26-16-20260311","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/j.jhep.2005.03.023","article-title":"Clinical, biochemical and morphological features of hepatocerebral syndrome with mitochondrial DNA depletion due to deoxyguanosine kinase deficiency.","volume":"43","author":"Labarthe","year":"2005","journal-title":"J Hepatol"},{"key":"R27-16-20260311","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1023\/B:MCBI.0000049374.52989.9b","article-title":"Regional differences in oxidative capacity of rat white adipose tissue are linked to the mitochondrial content of mature adipocytes.","volume":"267","author":"Deveaud","year":"2004","journal-title":"Mol Cell Biochem"},{"key":"R28-16-20260311","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.1002\/hep.1840120505","article-title":"Fatty liver hepatitis (steatohepatitis) and obesity: an autopsy study with analysis of risk factors.","volume":"12","author":"Wanless","year":"1990","journal-title":"HEPATOLOGY"},{"key":"R29-16-20260311","doi-asserted-by":"crossref","first-page":"1695","DOI":"10.1053\/j.gastro.2003.08.032","article-title":"Insulin resistance is associated with chronic hepatitis C virus infection and fibrosis progression. corrected.","volume":"125","author":"Hui","year":"2003","journal-title":"Gastroenterology"},{"key":"R30-16-20260311","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1002\/hep.1840110114","article-title":"The natural history of nonalcoholic steatohepatitis: a followup study of fortytwo patients for up to 21 years.","volume":"11","author":"Powell","year":"1990","journal-title":"HEPATOLOGY"},{"key":"R31-16-20260311","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1002\/hep.20973","article-title":"Nonalcoholic fatty liver disease: from steatosis to cirrhosis.","volume":"43","author":"Farrell","year":"2006","journal-title":"HEPATOLOGY"},{"key":"R32-16-20260311","doi-asserted-by":"crossref","first-page":"2042","DOI":"10.1111\/j.1572-0241.2003.07659.x","article-title":"The natural history of nonalcoholic fatty liver disease: a clinical histopathological study.","volume":"98","author":"Harrison","year":"2003","journal-title":"Am J Gastroenterol"},{"key":"R33-16-20260311","first-page":"820","article-title":"Natural history of nonalcoholic steatohepatitis: a longitudinal study of repeated liver biopsies.","volume":"40","author":"Fassio","year":"2004","journal-title":"HEPATOLOGY"},{"key":"R34-16-20260311","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1111\/j.1464-5491.2005.01748.x","article-title":"Recent concepts in nonalcoholic fatty liver disease.","volume":"22","author":"Adams","year":"2005","journal-title":"Diabet Med"},{"key":"R35-16-20260311","doi-asserted-by":"crossref","first-page":"1735","DOI":"10.1097\/00002030-199814000-00004","article-title":"Adverse effects of reverse transcriptase inhibitors: mitochondrial toxicity as common pathway.","volume":"12","author":"Brinkman","year":"1998","journal-title":"AIDS"},{"key":"R36-16-20260311","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/S0168-8278(99)80020-8","article-title":"Zidovudineinduced mitochondrial disorder with massive liver steatosis, myopathy, lactic acidosis, and mitochondrial DNA depletion.","volume":"30","author":"Chariot","year":"1999","journal-title":"J Hepatol"},{"key":"R37-16-20260311","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1097\/00126334-200211010-00005","article-title":"Mitochondrial damage associated with longterm antiretroviral treatment: associated alteration or causal disorder?","volume":"31","author":"Vittecoq","year":"2002","journal-title":"J Acquir Immune Defic Syndr"},{"key":"R38-16-20260311","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1177\/135965350701200809","article-title":"A 6month interruption of antiretroviral therapy improves adipose tissue function in HIVinfected patients: the ANRS EP29 Lipostop Study.","volume":"12","author":"Kim","year":"2007","journal-title":"Antivir Ther"},{"key":"R39-16-20260311","doi-asserted-by":"crossref","first-page":"1752","DOI":"10.1172\/JCI21625","article-title":"Increased oxidative stress in obesity and its impact on metabolic syndrome.","volume":"114","author":"Furukawa","year":"2004","journal-title":"J Clin Invest"},{"key":"R40-16-20260311","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1097\/QAD.0b013e3282f3553b","article-title":"Intrahepatic mRNA expression in hepatitis C virus and HIVhepatitis C virus coinfection: infiltrating cells, cytokines, and influence of HAART.","volume":"22","author":"Kuntzen","year":"2008","journal-title":"AIDS"}],"container-title":["Hepatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fhep.22665","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.lww.com\/01515467-200902000-00016","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T18:02:22Z","timestamp":1773252142000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/01515467-200902000-00016"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,2]]},"references-count":40,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2009]]}},"URL":"https:\/\/doi.org\/10.1002\/hep.22665","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.1140857.597945","asserted-by":"object"}]},"ISSN":["0270-9139"],"issn-type":[{"value":"0270-9139","type":"print"}],"subject":[],"published":{"date-parts":[[2009,2]]}}}