{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T21:27:08Z","timestamp":1784755628575,"version":"3.55.0"},"reference-count":43,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":186,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2015,5]]},"abstract":"<jats:p>Liver disease complicates human immunodeficiency virus (HIV)\/acquired immune deficiency syndrome; however, liver pathology data are limited, particularly from high HIV prevalence countries. We investigated the spectrum and clinicopathological correlates of liver pathology in a high HIV burden setting. In a single\u2010center study, all HIV\/acquired immune deficiency syndrome patients with complete clinical and demographic data who underwent liver biopsy were analyzed and clinicopathologically assessed by hepatologists and one of two experienced liver pathologists. We evaluated 301 patients, with a median age of 34 (interquartile range 29\u201040) years. Women (n\u2009=\u2009143) were younger than men (n\u2009=\u2009158), with a median age of 33 (interquartile range 28\u201037) versus 35 (interquartile range 31\u201041) years, <jats:italic toggle=\"yes\">P =<\/jats:italic> 0.001. The majority, 76.1%, were black African. Median CD4 at time of biopsy was 127 (52\u2010260) cells\/mm<jats:sup>3<\/jats:sup>. Drug\u2010induced liver injury was the predominant finding (42.2%), followed by granulomatous inflammation (29%), steatosis\/steatohepatitis (19.3%), hepatitis B (19%), and hepatitis C coinfection (3.3%), with more than one pathology in 16.2%. With granulomatous inflammation, 52% met the criteria for tuberculosis immune reconstitution syndrome. By univariate analysis, cotrimoxazole and antiretroviral therapy conferred risk for drug injury (odds ratio [OR]\u2009=\u20092.78 [1.72\u20104.48], <jats:italic toggle=\"yes\">P<\/jats:italic>\u2009&lt;\u20090.001; OR\u2009=\u20091.69 [1.06\u20102.68], <jats:italic toggle=\"yes\">P<\/jats:italic>\u2009=\u20090.027). In multivariate analysis, cotrimoxazole was associated with a cholestatic or ductopenic injury (OR\u2009=\u20097.05 [2.50\u201019.89], <jats:italic toggle=\"yes\">P<\/jats:italic>\u2009&lt;\u20090.001; OR\u2009=\u200917.6 [3.26\u201095.3], <jats:italic toggle=\"yes\">P<\/jats:italic>\u2009&lt;\u20090.0001); efavirenz was associated with nonspecific hepatitis or submassive necrosis (OR\u2009=\u20094.3 [1.92\u20109.83], <jats:italic toggle=\"yes\">P<\/jats:italic>\u2009&lt;\u20090.001; OR\u2009=\u200910.46 [2.7\u201040.5], <jats:italic toggle=\"yes\">P<\/jats:italic>\u2009&lt;\u20090.001). Cholestatic injury was associated with female gender and a CD4 of &gt;200 cells\/mm<jats:sup>3<\/jats:sup>, and submassive necrosis was associated with younger age. Hepatitis B demonstrated no association. <jats:italic toggle=\"yes\">Conclusion<\/jats:italic>: In a high HIV burden area, drug\u2010induced liver injury due to antiretroviral therapy and cotrimoxazole was a frequent clinicopathological finding; <jats:italic toggle=\"yes\">Mycobacterium tuberculosis<\/jats:italic> was the leading opportunistic infection, with more than half of patients fulfilling criteria for tuberculosis immune reconstitution syndrome; liver biopsy remains a useful diagnostic procedure in this setting. (H<jats:sc>epatology<\/jats:sc> 2015;61:1721\u20131729)<\/jats:p>","DOI":"10.1002\/hep.27710","type":"journal-article","created":{"date-parts":[[2015,1,16]],"date-time":"2015-01-16T22:17:11Z","timestamp":1421446631000},"page":"1721-1729","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":40,"title":["A clinicopathological cohort study of liver pathology in 301 patients with human immunodeficiency virus\/acquired immune deficiency syndrome"],"prefix":"10.1097","volume":"61","author":[{"given":"Mark W.","family":"Sonderup","sequence":"first","affiliation":[{"name":"Division of Hepatology, Department of Medicine,University of Cape Town and Groote Schuur Hospital,Cape Town,South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Wainwright","sequence":"additional","affiliation":[{"name":"Department of Anatomical Pathology,University of Cape Town and Groote Schuur Hospital,Cape Town,South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pauline","family":"Hall","sequence":"additional","affiliation":[{"name":"Department of Anatomical Pathology,University of Cape Town and Groote Schuur Hospital,Cape Town,South Africa"},{"name":"Department of Anatomical Pathology,Royal Brisbane and Women's Hospital, University of Queensland,Brisbane,QLD,Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry","family":"Hairwadzi","sequence":"additional","affiliation":[{"name":"Division of Hepatology, Department of Medicine,University of Cape Town and Groote Schuur Hospital,Cape Town,South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. Wendy N.","family":"Spearman","sequence":"additional","affiliation":[{"name":"Division of Hepatology, Department of Medicine,University of Cape Town and Groote Schuur Hospital,Cape Town,South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2015,2,27]]},"reference":[{"key":"hep27710-bib-0005-20241017","first-page":"25","article-title":"The changing epidemiology of liver disease in HIV patients","volume":"15","year":"2013","journal-title":"AIDS Rev"},{"key":"hep27710-bib-0006-20241017","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1016\/S0140-6736(10)62001-6","article-title":"Increasing burden of liver disease in patients with HIV infection","volume":"377","year":"2011","journal-title":"Lancet"},{"key":"hep27710-bib-0007-20241017","doi-asserted-by":"crossref","first-page":"1632","DOI":"10.1001\/archinte.166.15.1632","article-title":"Liver\u2010related deaths in persons infected with the HIV: the D:A:D study","volume":"166","year":"2006","journal-title":"Arch Intern Med"},{"key":"hep27710-bib-0008-20241017","doi-asserted-by":"crossref","first-page":"1537","DOI":"10.1097\/QAD.0b013e32833a0918","article-title":"Factors associated with specific causes of death amongst HIV\u2010positive individuals in the D:A:D Study","volume":"24","year":"2010","journal-title":"AIDS"},{"key":"hep27710-bib-0009-20241017","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1002\/hep.1840070522","article-title":"Hepatic disease in patients with the AIDS","volume":"7","year":"1987","journal-title":"Hepatology"},{"key":"hep27710-bib-0010-20241017","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1002\/hep.1840050224","article-title":"The liver in the acquired immunodeficiency syndrome: a clinical and histologic study","volume":"5","year":"1985","journal-title":"Hepatology"},{"issue":"11","key":"hep27710-bib-0011-20241017","first-page":"170","article-title":"Liver biopsy findings in 501 patients infected with HIV","volume":"1996","journal-title":"J Acquir Immune Defic Syndr Hum Retrovirol"},{"key":"hep27710-bib-0012-20241017","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1046\/j.1440-1746.1999.01820.x","article-title":"Findings and benefit of liver biopsies in 46 patients infected with human immunodeficiency virus","volume":"14","year":"1999","journal-title":"J Gastroenterol Hepatol"},{"key":"hep27710-bib-0013-20241017","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/S1665-2681(19)32064-2","article-title":"Hepatobiliary diseases in patients with HIV treated with non\u2010HAART: frequency and clinical manifestations","volume":"4","year":"2005","journal-title":"Ann Hepatol"},{"key":"hep27710-bib-0014-20241017","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1258\/004947506778604832","article-title":"Hepatic histopathological findings in HIV patients at postmortem in Jos University hospital, Nigeria","volume":"36","year":"2006","journal-title":"Trop Doct"},{"key":"hep27710-bib-0015-20241017","doi-asserted-by":"crossref","first-page":"e47542.","DOI":"10.1371\/journal.pone.0047542","article-title":"Causes of death on ART: a post\u2010mortem study from South Africa","volume":"7","journal-title":"PLoS One"},{"key":"hep27710-bib-0016-20241017","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1086\/649922","article-title":"Incidence and risk factors for chronic elevation of ALT levels in HIV\u2010infected persons without hepatitis B or C co\u2010infection","volume":"50","year":"2010","journal-title":"Clin Infect Dis"},{"key":"hep27710-bib-0017-20241017","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1001\/jama.283.1.74","article-title":"Hepatotoxicity associated with antiretroviral therapy in adults infected with human immunodeficiency virus and the role of hepatitis C or B virus infection","volume":"283","year":"2000","journal-title":"JAMA"},{"key":"hep27710-bib-0018-20241017","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1097\/QAD.0b013e3282f0e2fd","article-title":"Antiretroviral drugs and liver injury","volume":"22","year":"2008","journal-title":"AIDS"},{"key":"hep27710-bib-0019-20241017","doi-asserted-by":"crossref","first-page":"730","DOI":"10.4065\/74.7.730","article-title":"Trimethoprim\u2010sulfamethoxazole","volume":"74","year":"1999","journal-title":"Mayo Clin Proc"},{"key":"hep27710-bib-0023-20241017","doi-asserted-by":"crossref","first-page":"e70126.","DOI":"10.1371\/journal.pone.0070126","article-title":"Population\u2010based CD4 counts in a rural area in South Africa with high HIV prevalence and high antiretroviral treatment coverage","volume":"8","year":"2013","journal-title":"PLoS One"},{"key":"hep27710-bib-0024-20241017","doi-asserted-by":"crossref","first-page":"2029","DOI":"10.1016\/S0140-6736(12)61814-5","article-title":"Health in South Africa: changes and challenges since 2009","volume":"380","year":"2012","journal-title":"Lancet"},{"key":"hep27710-bib-0025-20241017","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1016\/j.cld.2007.06.008","article-title":"Drug\u2010induced liver injury associated with HIV medications","volume":"11","year":"2007","journal-title":"Clin Liver Dis"},{"key":"hep27710-bib-0026-20241017","doi-asserted-by":"crossref","first-page":"506","DOI":"10.7196\/SAMJ.5650","article-title":"Burden of antituberculosis and antiretroviral DILI at a secondary hospital in South Africa","volume":"102","year":"2012","journal-title":"S Afr Med J"},{"key":"hep27710-bib-0027-20241017","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1097\/QAD.0b013e32814e6b08","article-title":"Hepatotoxicity in an African antiretroviral therapy cohort: the effect of tuberculosis and hepatitis B","volume":"21","year":"2007","journal-title":"AIDS"},{"key":"hep27710-bib-0028-20241017","doi-asserted-by":"crossref","first-page":"490","DOI":"10.2174\/157016207781662407","article-title":"Steatohepatitis in HIV\u2010infected subjects: pathogenesis, clinical impact and implications in clinical management","volume":"5","year":"2007","journal-title":"Curr HIV Res"},{"key":"hep27710-bib-0029-20241017","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/S1089-3261(03)00021-7","article-title":"Hepatotoxicity of antibiotics and antifungals","volume":"7","year":"2003","journal-title":"Clin Liver Dis"},{"issue":"Suppl. 2","key":"hep27710-bib-0030-20241017","first-page":"S80","article-title":"DILI associated with the use of non\u2010nucleoside reverse\u2010transcriptase inhibitors","volume":"38","year":"2004","journal-title":"Clin Infect Dis"},{"key":"hep27710-bib-0031-20241017","doi-asserted-by":"crossref","first-page":"1335","DOI":"10.1053\/j.gastro.2013.04.026","article-title":"Drug\u2010induced liver injury: Icelandic lessons","volume":"144","year":"2013","journal-title":"Gastroenterology"},{"key":"hep27710-bib-0032-20241017","doi-asserted-by":"crossref","first-page":"495","DOI":"10.7326\/0003-4819-100-4-495","article-title":"Adverse reactions to trimethoprim\u2010sulfamethoxazole in patients with the acquired immunodeficiency syndrome","volume":"100","year":"1984","journal-title":"Ann Intern Med"},{"key":"hep27710-bib-0033-20241017","doi-asserted-by":"crossref","first-page":"1670","DOI":"10.1056\/NEJM199306103282304","article-title":"Cutaneous disease and drug reactions in HIV infection","volume":"328","year":"1993","journal-title":"N Engl J Med"},{"key":"hep27710-bib-0034-20241017","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1086\/428093","article-title":"Severe hepatotoxicity associated with nevirapine use in HIV\u2010infected subjects","volume":"191","year":"2005","journal-title":"J Infect Dis"},{"key":"hep27710-bib-0035-20241017","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1053\/jhep.2002.30319","article-title":"Hepatotoxicity associated with nevirapine or efavirenz\u2010containing antiretroviral therapy: role of hepatitis C and B infections","volume":"35","year":"2002","journal-title":"Hepatology"},{"key":"hep27710-bib-0036-20241017","doi-asserted-by":"crossref","first-page":"e40180.","DOI":"10.1371\/journal.pone.0040180","article-title":"Liver enzyme abnormalities and associated risk factors in HIV patients on efavirenz\u2010based HAART with or without tuberculosis co\u2010infection in Tanzania","volume":"7","year":"2012","journal-title":"PLoS One"},{"key":"hep27710-bib-0037-20241017","doi-asserted-by":"crossref","first-page":"53","DOI":"10.2165\/00002018-200528010-00004","article-title":"Hepatotoxicity of antiretrovirals: incidence, mechanisms and management","volume":"28","year":"2005","journal-title":"Drug Saf"},{"issue":"Suppl. 2","key":"hep27710-bib-0038-20241017","first-page":"S57","article-title":"Hepatitis B in the HIV\u2010coinfected patient","volume":"45","year":"2007","journal-title":"J Acquir Immune Defic Syndr"},{"issue":"2","key":"hep27710-bib-0039-20241017","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1002\/(SICI)1096-9071(199610)50:2<117::AID-JMV3>3.0.CO;2-D","article-title":"Hepatitis E in South Africa: evidence for sporadic spread and increased seroprevalence in rural areas","volume":"50","year":"1996","journal-title":"J Med Virol"},{"key":"hep27710-bib-0040-20241017","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1111\/j.1468-1293.2004.00217.x","article-title":"Hepatic pathology in AIDS: a pathological study from Mumbai, India","volume":"5","year":"2004","journal-title":"HIV Med"},{"key":"hep27710-bib-0041-20241017","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1097\/01.qai.0000225729.79610.b7","article-title":"CD4 decline and incidence of opportunistic infections in Cape Town, South Africa: implications for prophylaxis and treatment","volume":"42","year":"2006","journal-title":"J Acquir Immune Defic Syndr"},{"key":"hep27710-bib-0042-20241017","doi-asserted-by":"crossref","first-page":"1164","DOI":"10.1164\/ajrccm\/144.5.1164","article-title":"Disseminated tuberculosis in the AIDS era","volume":"144","year":"1991","journal-title":"Am Rev Respir Dis"},{"key":"hep27710-bib-0043-20241017","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1111\/j.1469-0691.2004.00758.x","article-title":"Tuberculosis in HIV\u2010infected patients: a comprehensive review","volume":"10","year":"2004","journal-title":"Clin Microbiol Infect"},{"key":"hep27710-bib-0044-20241017","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1056\/NEJMoa0905848","article-title":"Timing of initiation of antiretroviral drugs during tuberculosis therapy","volume":"362","year":"2010","journal-title":"N Engl J Med"},{"key":"hep27710-bib-0045-20241017","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1016\/S1473-3099(08)70184-1","article-title":"Tuberculosis\u2010associated immune reconstitution inflammatory syndrome: case definitions for use in resource\u2010limited settings","volume":"8","year":"2008","journal-title":"Lancet Infect Dis"},{"key":"hep27710-bib-0046-20241017","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1002\/hep.1840150404","article-title":"Interactions between HIV\u20101, hepatitis delta virus and hepatitis B virus infections in 260 chronic carriers of hepatitis B virus","volume":"15","year":"1992","journal-title":"Hepatology"},{"key":"hep27710-bib-0047-20241017","first-page":"396","article-title":"Fibrosing cholestatic hepatitis: clinicopathologic spectrum, diagnosis and pathogenesis","volume":"1","year":"2008","journal-title":"Int J Clin Exp Pathol"},{"key":"hep27710-bib-0048-20241017","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1055\/s-0032-1316471","article-title":"Nonalcoholic fatty liver disease and HIV infection","volume":"32","year":"2012","journal-title":"Semin Liver Dis"},{"key":"hep27710-bib-0049-20241017","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1097\/MEG.0b013e328305b9e0","article-title":"Hepatic histopathology and clinical characteristics associated with antiretroviral therapy in HIV without viral hepatitis","volume":"20","year":"2008","journal-title":"Eur J Gastroenterol Hepatol"},{"key":"hep27710-bib-0050-20241017","first-page":"237","article-title":"Evaluation and interpretation of iron in the liver","volume":"15","year":"1998","journal-title":"Semin Diagn Pathol"}],"container-title":["Hepatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fhep.27710","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.lww.com\/01515467-201505000-00031","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,17]],"date-time":"2024-10-17T23:48:21Z","timestamp":1729208901000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/01515467-201505000-00031"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,2,27]]},"references-count":43,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2015]]}},"URL":"https:\/\/doi.org\/10.1002\/hep.27710","relation":{},"ISSN":["0270-9139","1527-3350"],"issn-type":[{"value":"0270-9139","type":"print"},{"value":"1527-3350","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,2,27]]},"assertion":[{"value":"2014-07-03","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-01-13","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}