title: A clinicopathological cohort study of liver pathology in 301 patients with human immunodeficiency virus/acquired immune deficiency syndrome.
abstract: 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-center 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 29-40) years. Women (n = 143) were younger than men (n = 158), with a median age of 33 (interquartile range 28-37) versus 35 (interquartile range 31-41) years, P = 0.001. The majority, 76.1%, were black African. Median CD4 at time of biopsy was 127 (52-260) cells/mm(3) . Drug-induced 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] = 2.78 [1.72-4.48], P < 0.001; OR = 1.69 [1.06-2.68], P = 0.027). In multivariate analysis, cotrimoxazole was associated with a cholestatic or ductopenic injury (OR = 7.05 [2.50-19.89], P < 0.001; OR = 17.6 [3.26-95.3], P < 0.0001); efavirenz was associated with nonspecific hepatitis or submassive necrosis (OR = 4.3 [1.92-9.83], P < 0.001; OR = 10.46 [2.7-40.5], P < 0.001). Cholestatic injury was associated with female gender and a CD4 of >200 cells/mm(3) , and submassive necrosis was associated with younger age. Hepatitis B demonstrated no association.
  
  
  CONCLUSIONS
  In a high HIV burden area, drug-induced liver injury due to antiretroviral therapy and cotrimoxazole was a frequent clinicopathological finding; Mycobacterium tuberculosis 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.
authors: Division of Hepatology, Department of Medicine, University of Cape Town and Groote Schuur Hospital, Cape Town, South Africa.
authors: Mark W
authors: MW
authors: Sonderup
authors: Helen
authors: H
authors: Wainwright
authors: Pauline
authors: P
authors: Hall
authors: Henry
authors: H
authors: Hairwadzi
authors: C Wendy N
authors: CW
authors: Spearman
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000150:complications / Q000188:drug therapy; D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects*; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology* / Q000473:pathology*; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy*; D006801:Humans; D008107:Liver Diseases / Q000209:etiology* / Q000473:pathology*; D008297:Male
chemical_list: D019380:Anti-HIV Agents