Page 217 - AIDSBK23C

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The protease inhibitors, and ritonavir in particular may be associated with elevation in
transaminases, while saquinavir and indinavir more often are causes for hyperbilirubinemia. The
risk for hepatotoxicity occurs five times more often for ritonavir than for other protease
inhibitors. The overall rate of hepatoxicity with antiretroviral therapy is about 10%. The risk for
hepatotoxicity appears to be increased in persons with hepatitis B or C infection, but 88% of
persons with viral hepatitis B or C do not develop hepatotoxicity.[260,264]

HEPATIC STEATOSIS.-- A common clinical and pathologic finding in liver with AIDS
is hepatomegaly, seen in about two thirds of cases. Steatosis (fatty metamorphosis) is a common
histopathologic finding, seen in about one third of AIDS patients on biopsy or at autopsy, but it
is often of a mild to moderate degree and periportal in distribution, and may result from chronic
alcoholism. Non-alcoholic fatty liver (NAFL) is increasingly common because of etiologies
including diabetes mellitus, hepatitis B or C infection, and HIV associated lipodystrophy, or
antiretroviral therapy with nucleoside analogues.[885] NAFL may progress to non-alcoholic
steatosis (NASH) and to cirrhosis. Risk factors include male sex, elevated serum alanine
aminotransferase, and increased waist circumference. Continued hepatic mitochondrial injury
plays a role in this progression, particularly with use of nucleoside reverse transcriptase
inhibitors. Progression to nonalcoholic steatohepatitis (NASH) and to cirrhosis occurs in a
minority of cases.[885,886,887]

MISCELLANEOUS FINDINGS.-- Liver biopsy in adult AIDS patients will often show
granulomas, and most of these are due to mycobacterial infection (Table 5). In some series, up
to one-third of cases had granulomas. Persons with a history of injection drug use are often
likely to have a concomitant history of chronic alcoholism, with findings ranging from steatosis
to portal fibrosis to micronodular cirrhosis, and polarizable talc crystals may be found in portal
regions. Hepatomegaly may also result from acute or chronic passive congestion with cardiac
failure, usually late in the course of AIDS. Hemosiderin deposition, particularly in Kupffer cells,
is common in AIDS, though usually not as extensive as in spleen. It is potentiated by chronic
disease and transfusion therapy and can be quite marked.[871,873]
Idiopathic noncirrhotic portal hypertension is a cryptogenic disease associated with HIV
infection that may be related to antiretroviral therapy, direct effects of HIV, gut microbe
translocation, and thrombophilia. Nodular regenerative hyperplasia may be present. Abnormal
liver function tests may include decreased serum albumin and increased gamma-
glutamyltranspeptidase. Complications may include ascites, portal thrombosis, and variceal
bleeding.[888]
Peliosis hepatis, the presence of multiple small blood-filled lakes in hepatic parenchyma
without surrounding epithelium or endothelium, has been rarely reported in AIDS. It must be
distinguished from Kaposi's sarcoma, which has atypical spindle cells, whereas peliosis does not.
Bacillary angiomatosis with small bacilli of the species Bartonella henselae identified singly or
in clusters by Warthin-Starry staining or by immunocytochemical methods can be identified
within peliotic spaces. Clinical findings include fever, lymphadenopathy, cutaneous or
subcutaneous vascular lesions, osteolytic lesions, and abdominal symptoms. The CD4 count is
typically <200/µL. The hepatic alkaline phosphatase is increased. Hepatic Bartonella infection
may also manifest with multiple granulomas, often in the form of stellate abscesses surrounded
by three distinct zones: an inner layer of palisading macrophages, an intermediate rim of