Hepatic steatosis in human immunodeficiency virus: a prospective study in patients without viral hepatitis, diabetes, or alcohol abuse.
OBJECTIVE
Abnormal liver enzymes (LEs) are common in those infected with human immunodeficiency virus (HIV). Histologic data on those with abnormal LE without viral hepatitis are lacking.


METHODS
HIV-positive subjects without hepatitis C virus, hepatitis B virus, alcohol abuse, and diabetes mellitus with more than 1 abnormal LE, defined as 1.25 ULN in aspartate aminotransferase, alanine aminotransferase, or alkaline phosphatase, over 6 months were included. Subjects underwent a 2-hour oral glucose tolerance test, fasting lipids, insulin and glucose for insulin resistance (IR) by homeostasis model assessment for insulin resistance (HOMA-IR) and dual-energy X-ray absorptiometry for fat distribution. Biopsies were read blindly to clinical data, and scored by Ishak histologic activity index for inflammation and fibrosis and NAFLD activity score.


RESULTS
Fourteen patients underwent biopsy. All were on highly active antiretroviral therapy with undetectable HIV RNA and mean CD4 614. The histologic activity index scores for inflammation and fibrosis were 3.43(1.4) and 1.71(1.26), respectively, and 2 patients had advanced fibrosis (bridging fibrosis/cirrhosis). The majority (65%) of patients had steatosis: grade 1: 21%, grade 2: 28%, and grade 3: 14%. Hepatocyte ballooning was seen in 7 (40%) but nonalcoholic steatohepatitis (NASH) was diagnosed only in 4 (26%). NAFLD activity score of all biopsies of 3.07 (2.2; range, 0 to 5). HOMA-IR was higher in those with compared with those without steatosis (3.52 vs. 1.91; P = 0.11) and highest in those with NASH (4.89). Using multivariate logistic regression, only increased γ-glutamyl transpeptidase (P = 0.0009) predicted steatosis whereas HOMA-IR (P = 0.0046) predicted NASH.


CONCLUSIONS
Although steatosis is common in HIV patients with abnormal LE without diabetes mellitus, alcohol, or viral hepatitis coinfection, NASH was observed in only 26%. The only clinical or laboratory feature associated with biopsy proven steatosis and NASH were γ-glutamyl transpeptidase and a calculated measure of insulin resistance, respectively. Further studies are needed in this population to determine the long-term clinical significance.
Division of Gastroenterology, Hepatology, and Nutrition, Infectious Diseases, Virginia Commonwealth University Health System, Richmond, VA, USA. rksterli@vcu.edu
Richard K
RK
Sterling
Paula G
PG
Smith
Elizabeth M
EM
Brunt
D015502:Absorptiometry, Photon; D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D023241:Antiretroviral Therapy, Highly Active; D001219:Aspartate Aminotransferases / Q000097:blood; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D018791:CD4 Lymphocyte Count; D016009:Chi-Square Distribution; D004796:Clinical Enzyme Tests; D003430:Cross-Sectional Studies; D005234:Fatty Liver / Q000175:diagnosis / Q000209:etiology*; D005260:Female; D005951:Glucose Tolerance Test; D006678:HIV / Q000235:genetics / Q000276:immunology; D015658:HIV Infections / Q000150:complications* / Q000175:diagnosis / Q000188:drug therapy; D006801:Humans; D007333:Insulin Resistance; D008103:Liver Cirrhosis / Q000175:diagnosis / Q000209:etiology; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D065626:Non-alcoholic Fatty Liver Disease; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood; D012307:Risk Factors; D013997:Time Factors; D005723:gamma-Glutamyltransferase / Q000097:blood
D015415:Biomarkers; D012367:RNA, Viral; D005723:gamma-Glutamyltransferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase