Relationship of Metabolic Abnormalities to Hepatic Steatosis in HIV
Condition: Steatohepatitis
MeSH terms: Fatty Liver
Study type: Observational

Summary: 
      Because NASH is now recognized as a significant cause of cirrhosis with associated morbidity
      and mortality, its recognition as a long term complication of HAART is important to the
      management of those living with HIV.
    

Detailed description: 
      Abnormal liver enzymes are frequently seen in those with HIV. Although many of these
      individuals are co-infected with HBV or HCV, histology in HIV patients with abnormal liver
      enzymes in the absence of viral hepatitis has not been explored. HAART has significantly
      improved the survival in those living with HIV. However, components of HAART, particularly
      protease inhibitors (PIs) and certain nucleoside reverse transcriptase inhibitors (NRTIs),
      are frequently associated with metabolic abnormalities including insulin resistance (IR),
      dyslipidemias, fat redistribution and lipodystrophy (LD). Both IR and dyslipidemia are
      pathogenic mechanisms associated with nonalcoholic fatty liver disease (NAFLD) and
      non-alcoholic steatohepatitis (NASH) which often present as asymptomatic liver enzyme
      elevations. Because NASH is now recognized as a significant cause of cirrhosis with
      associated morbidity and mortality, its recognition as a long term complication of HAART is
      important to the management of those living with HIV. In our HIV population without HCV or
      HBV, there is a higher prevalence of abnormal liver enzymes (AST 21%, ALT 16%, ALP 43%)
      compared to the general population (ALT 8%) and is independently associated with PI use. The
      relationship of liver enzyme abnormalities to IR, dyslipidemias, and the development hepatic
      steatosis/NASH in HIV patients is unknown. We hypothesize that Liver enzyme abnormalities in
      HIV positive patients without viral hepatitis co-infections on HAART are due to hepatic
      steatosis related to PI use and that a subset of these individuals has NASH. The Specific
      Aims focus on HIV positive patients with abnormal liver enzymes in the absence of viral
      hepatitis co-infections, diabetes, or alcohol abuse to answer the following three questions:
      (1) What is the spectrum of NAFLD?; (2) How does the spectrum compare in those that are on a
      PI compare to those that are not; and (3) What are the independent predictive factors
      associated with hepatic steatosis and NASH? These studies will (1) provide novel data on the
      histology of HIV infected patients with abnormal liver enzymes in the absence of viral
      coinfections and their relationship to IR, LD, dyslipidemias, and HAART use and (2) provide
      the necessary pilot data for a multicenter R0-1 grant to study the long-term impact of HAART
      on the development of steatohepatitis and subsequent hepatic fibrosis.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        HIV positive with abnormal liver enzymes in the absence of HCV/HBV coinfections.
      
Biospecimen description: 
      sera, liver tissue
    
Keywords: Steatosis; NASH