icon-    folder.gif   Conference Reports for NATAP  
  16th CROI
Conference on Retroviruses and Opportunistic Infections Montreal, Canada
February 8-11, 2009
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High Prevalence of Hepatic Fibrosis and Steatosis in HIV/AIDS Patients without Chronic Viral Hepatitis but with Chronically Elevated Transaminases on ART
  Reported by Jules Levin CROI Montreal Feb 8-12
C Morse1, A Jones1, M McLaughlin1, T Heller2, C Hadigan1, D Kleiner3, and Joseph Kovacs*4 1NIAID, NIH, Bethesda, MD, US; 2Natl Inst of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD, US; 3NCI, NIH, Bethesda, MD, US; and 4NIH, Bethesda, MD, US
Background: Mild, persistent transaminase elevations are common in HIV-infected patients on ART, even in those without hepatitis B or C co-infection, but their clinical significance is unknown.
Methods: HIV-infected adults with elevated (>upper limits of normal) aspartate aminotransferase (AST) or alanine aminotransferase (ALT) for longer than 1 year while receiving ART were enrolled. Subjects with chronic viral hepatitis or other known causes of chronic liver disease were excluded. Evaluations included a detailed metabolic assessment including oral glucose tolerance testing, CT imaging to examine the liver and measure visceral and subcutaneous fat, transient elastography, and liver biopsy. Non-parametric tests were used for statistical analysis.
Results: At enrollment, the median age of subjects (n = 24) was 50 years with a median CD4+ T cell count of 578 cells/mm3 and HIV viral load of <50 copies/mL. The median duration of HIV infection was 17.0 years and median duration of ART was 12.0 years. Median duration of elevated AST and ALT at biopsy was 5.5 years. CT imaging identified fatty infiltration of the liver in 6 of 24 subjects (25%). On liver biopsy, 9 subjects (37.5%) were found to have clinically significant liver disease: 8 had fibrosis including 6 with steatohepatitis and bridging fibrosis; 1 subject had nodular regenerative hyperplasia. All 6 subjects with steatohepatitis and fibrosis had evidence of steatosis on CT imaging. All 5 subjects with abnormal transient elastography (>8 kPa) had fibrosis on liver biopsy, and 3 additional subjects were found to have steatosis with associated inflammation but no fibrosis (mild steatohepatitis). Subjects with fibrosis did not differ significantly from those with normal liver biopsies in duration of HIV infection, history of opportunistic infection, current immune status, duration of ART, or current or previous ART. Serum transaminases were higher in the patients with fibrosis (AST 68 vs 39 U/L, p = 0.011; ALT 89 vs 61 U/L, p = 0.028). Steatohepatitis correlated with higher body mass index and homeostasis model assessment insulin resistance.
Conclusions: Significant liver disease was seen in 35% of HIV-infected adults with chronic transaminase elevations while receiving ART. CT imaging and transient elastography can help identify such patients, but normal studies do not exclude significant pathologic abnormalities. Longitudinal follow-up of this cohort will better characterize the natural history of chronic transaminase elevations in this population.