Page 216 - AIDSBK23C

Page 216

Kaposi's sarcoma is often distributed around large portal vein branches at the hilum, along the
biliary tracts, near the capsule, or even in the gallbladder. Sometimes the deposits of KS
resemble small hepatic hemangiomas that are usually solitary and occur in about 2% of all
persons. Microscopically, KS may have dilated vascular spaces similar to hemangioma, but
hemangiomas will not have atypical spindle cells. In rare cases the KS infiltration is extensive
enough to produce biliary tract obstruction or liver failure. Liver biopsy may miss the
predominantly central and focal lesions of KS.[872]

MALIGNANT LYMPHOMAS.-- Non-Hodgkin lymphoma (NHL) may appear in liver in
association with widespread dissemination and only rarely as a primary tumor. Persistent fever,
tender hepatomegaly, mildly abnormal liver function tests and an elevated lactate dehydrogenase
are typical clinical findings. By either ultrasound (US) or computed tomography (CT), NHL
may produce solitary or, more often, variably-sized multiple lesions. A mass that is hypoechoic
compared to surrounding hepatic parenchyma is a typical finding on US, while by CT there can
be various patterns of enhancement after intravenous contrast material administration, including
enhancement, a thin enhancing rim, or diffuse enhancement.[416] Lymphomatous infiltrates
most often appear in portal zones, but if extensive can be found throughout the hepatic lobules.
Large tumor masses are not common and may be identified by radiographic imaging procedures
to direct biopsy for diagnosis. Lymphoma can be distinguished from nonspecific lymphocytic
portal infiltrates by the larger monomorphous population of cells in the former, aided by
immunohistochemical staining.[883]

DRUG-INDUCED HEPATOTOXICITY.-- It is not surprising that hepatotoxicity can
appear in the course of AIDS because patients are treated with a variety of pharmacologic agents.
The patterns of hepatotoxicity may include hypersensitivity, idiosyncratic reaction,
mitochondrial injury, immune reconstitution inflammatory syndrome (IRIS), and steatosis.
Nucleoside and nonnucleoside reverse transcriptase inhibitors as well as protease inhibitors can
have hepatotoxicity with elevations in liver enzymes. Nevirapine and efavirenz are most often
implicated. In most cases these elevations are low and the patients remain asymptomatic.
Higher elevations may occur with concurrent hepatitis B or C infection. A hypersensitivity
reaction is seen most often with use nevirapine, abacavir, and efavirenz, with onset of fever and
eosinophilia within a week of starting therapy.[259,260] Mitochondrial toxicity leads to
impairment of fatty acid oxidation and microvesicular steatosis, and lactic acidosis in more
severe cases most often associated with use of didanosine or stavudine. The use of riboflavin
may help to ameliorate lactic acidosis. Immune reconstitution with liver injury is most likely to
occur when HBV or HCV infection is present. Drug hepatotoxicity is more likely to occur when
there is underlying hepatic fibrosis.[877,884]
Half of patients receiving prophylaxis for Pneumocystis jiroveci (carinii) with either
trimethoprim-sulfamethoxazole (TMP-SMX) or pentamidine have elevations in transaminases or
alkaline phosphatase that are two or more times normal, but severe hepatotoxicity is uncommon.
Sulfa drugs can also cause a granulomatous hepatitis. Both ketoconazole and fluconazole used
to treat fungal infections can be associated with transaminase elevations in 10 to 20% of cases.
Agents used to treat Mycobacterium tuberculosis, such as isoniazid and rifampin, can produce
enough abnormalities in liver function tests to alter the therapeutic regimen in 5% of cases. The
antiretroviral agent didanosine (ddI) is associated with transaminase elevations in one third of
treated patients.[873]