Hepatic Pigment Accumulation in HIV Patients on HAART Therapy.
Amanda R Doherty, Linda D Ferrell, Caryn G Morse, David E Kleiner. University of California, San Francisco; National Institute of Allergy and Infectious Diseases, Bethesda; National Cancer Institute, Bethesda
Background: Several highly active antiretroviral therapy (HAART) agents used in treating human immunodeficiency virus (HIV) inhibit multidrug-resistance protein 2 (MRP2), which functions in bile transport across the hepatocyte membrane. Hereditary defects in MRP2 result in Dubin-Johnson syndrome, which is characterized by accumulation of coarse granular pigment within hepatocytes. Similar pigment accumulation in hepatocytes has never been described in patients with HIV on HAART therapy.
Design: Liver biopsies in patients with HIV without hepatitis virus co-infection were reviewed. Clinical data were gathered including indication for biopsy, history of pre-existing liver disease, medications, and liver enzymes.
Results: We identified fifteen cases that showed coarse golden brown pigment within hepatocytes. The pigment granules tended to be larger and coarser than lipochrome, bile, or the pigment of Gilbert syndrome, and appeared similar to that of Dubin-Johnson syndrome. The pigment mimicked intracellular bile in one case, but was negative for bile on Hall's stain. Eleven cases (73%) showed diffuse distribution of pigment in all zones, three showed predominantly periportal pigment, and one showed predominantly centrizonal pigment. Seven cases also showed steatosis or steatohepatitis, one showed moderate hemosiderosis, and the others showed only mild chronic inflammatory changes. All patients were male with no history of pre-existing liver disease. The most common indication for biopsy was elevated liver enzymes, with average ALT of 128 IU/L (range 43-887 IU/L), AST 92 IU/L (range 29-664 IU/L), alkaline phosphatase 87 IU/L (range 54-136 IU/L), and GGT 143 U/L (range 24-574 U/L). Six patients (40%) had mildly elevated total bilirubin (average 1.3 mg/dL, range 0.3-3.9 mg/dL), which was unconjugated in two cases for whom data was available. One patient presented with jaundice and normal bilirubin. In 13 patients drug regimen data was available, and all were on HAART therapy. Mean duration of treatment was 13.5 years (range 6.3-17.2 years).
Conclusions: Patients with HIV on HAART therapy can develop pigment in the liver similar to that of Dubin-Johnson syndrome. The pigment is distinct from lipochrome or the pigment of Gilbert syndrome and rarely mimics intracellular bile. This finding may reflect altered function of MRP2 by HAART agents. In some cases it can be associated with hyperbilirubinemia or jaundice.
Category: Liver & Pancreas
Wednesday, March 2, 2011 9:30 AM
Poster Session V # 188, Wednesday Morning