HIV Accelerated Liver Disease in Uganda

With improved survival following the introduction of highly active antiretroviral therapy
(HAART), liver disease has become a leading cause of death among HIV-infected persons in
Western cohorts, primarily affecting those co-infected with hepatitis B or C viruses (HBV,
HCV). However, data are sparse on liver disease in HIV-infected populations from Uganda and
other African nations, where the etiologies of liver disease are broader and include
aflatoxin, schistosomiasis and other infectious and environmental agents. Our previous
noninvasive study in rural, Rakai, Uganda indicates that the prevalence of significant liver
fibrosis is high among HIV-infected individuals (17%) and is 50% higher than in
HIV-uninfected persons, although the prevalence of viral hepatitis B co-infection is low
(5%). The study presented here is a biopsy-based study that follows up on these results with
the objectives of defining the etiology of liver disease and describing the mechanisms of
HIV-accelerated liver fibrosis in this setting.

- INCLUSION CRITERIA:

1. Adults aged 18 and older

2. Persons who are able and willing to provide informed consent

3. Persons who have a transient elastography score >=9.0 kPa or have other evidence
of liver disease, and who are willing to undergo an ultrasound and liver biopsy

i) Other evidence of liver disease: Persons with an LSM <9.0 kPa who demonstrate
liver transaminases at least 2-times greater than the upper limit of normal;
those with persistently abnormal liver

transaminases over a period of three months during the year preceding enrollment;
those who show abnormalities on their ultrasound; those with other laboratory
tests indicating the possibility of liver disease; and/or those who have a
clinical or medical indication for a liver biopsy.

4. Persons who are willing to have tissue samples undergo genetic testing

5. Persons who agree to have samples stored for the purpose of future research

EXCLUSION CRITERIA:

1. Women who are pregnant

2. Persons with a cardiac device (i.e., pacemaker)

3. Participants who are not able to follow study instructions

4. Safety laboratory data indicating possible excess risk of bleeding including platelets
<75,000 and an INR>=1.5. These safety laboratory values will be ascertained by
obtaining a Complete Blood Count (CBC) and a Prothrombin Time (PT).

5. Evidence of decompensated liver disease including ascites, or hepatic encephalopathy

6. Persons who have any condition deemed, by the investigators, to be a contraindication
to study participation