I

REVIEWS

Hepatobiliary Complications in Patients With Human Immunodeficiency Virus Infection MAURIZIOBONACINI,M.D., Kansas City, Missouri

Human immunodeficiency virus (HIV) infection has been associated with a number of hepatic and biliary tract disorders. Case reports, series of liver biopsies, and postmortem studies that examined the hepatobiliary system were retrieved with a MEDLARS search and form the basis of this review. The liver and biliary tract are frequently involved with opportunistic infections (most commonly mycobacteria and cytomegalovirus) and neoplasms (mainly Kaposi’s sarcoma) in patients with HIV infection. The patients are often asymptomatic but may have elevated levels of serum liver enzymes. These abnormalities are nonspecific. Sulfa drugs, pentamidine, and ketoconazole are the medications used in HIV-related infections that are most likely to result in abnormalities on liver tests. Acalculous cholecystitis and sclerosing cholangitis also occur in HIV infection. Cytomegalovjrus and Cryptosporidizzm are the organisms most commonly associated with these conditions. Imaging studies of the liver may detect parenchymal abnormalities and guide liver biopsy. The role of this procedure in the diagnosis of opportunistic infections and neoplasms is controversial because these lesions are generally disseminated at the time liver abnormalities are evident. A liver biopsy is best used when other less invasive procedures have failed to provide a diagnosis. Endoscopic retrograde cholangiopancreatography is a useful diagnostic procedure with therapeutic potential in patients with abdominal pain, fever, or an elevated serum alkaline phosphatase level.

with the human immunodeficiency virus Iin nfection (HIV) is thought to affect over a million persons the United States [l]. Projections estimate the total number of cases of acquired immunodeficiency syndrome (AIDS) to reach 400,000 and result in about 300,000 deaths by 1993 [l]. During the past 10 years, gastrointestinal complications from HIV infection have been widely recognized, but hepatic and biliary involvement has been less emphasized. Hepatomegaly and/or elevated levels of serum liver enzymes are frequent findings during the evaluation of patients with HIV infection. Thus, it is important to be aware of the possible causes of liver and biliary involvement in this setting, since some are treatable. This review summarizes the data concerning hepatobiliary disease in HIV-seropositive patients and provides guidelines for its evaluation. The English literature was obtained using MEDLARS and the following headings: HIV infection and opportunistic infections, neoplssms, biliary tract disease, cholecystitis, and hepatotoxicity. Only the most relevant publications were selected.

PREVALENCESTUDIES Twenty-two autopsy [2-161 and liver biopsy [17-231 studies have described pathologic data from 635 patients with HIV infection (Table I). Despite some shortcomings, these studies provide an estimate of the prevalence of hepatobiliary disease in this population. Hepatomegaly was present in 60% of cases [7,17,20,21,23]; at autopsy, the liver weighed more than 1,800 g in 72% [2,5,6,13]. Jaundice was seen in only 11% of the patients [6,8,20,23]. At least one of the serum liver enzyme levels was elevated in 78% of the cases: transaminases (aspartate transaminase [AST] and/or alanine transaminase [ALT]) in 61% and alkaline phosphatase (AP) in 51% [5,6,8,17]. Neither type of enzyme elevation (transaminase or AP) can predict a particular infection or neoplasm [17,21]. Opportunistic infections of the liver were diagnosed in 34% of patients studied by biopsy [17-231 and 38% by autopsy [2-161. Hepatic neoplasms were more frequently found at autopsy (12%) than by biopsy (0.9%). Multiple lesions were found in 5% of cases [7]. Homosexual patients had hepatic cytomegalovirus (CMV) infection (15%) more often than acid-fast bacilli (AFB) (4%), while the opposite occurred in intravenous

From the Section of Gastroenterology. Department of Medicine, Truman Medical Center, Kansas City, Missouri. Requests for reprints should be addressed to Maurizio Bonacini, M.D.. Gold Unit, Room M5-217, University of Missouri-Kansas City School of Medicine, 2411 Holmes Street, Kansas City, Missouri 64108. Dr. Bonacini’s current address: Section of Gastroenterology. Anaheim Medical Center, 1236 North Magnolia Avenue, Anaheim, California 92801-2691. Manuscript submitted May 14. 1991, and accepted in revised form September 12, 1991.

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HEPATOBILIARY

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TABLE I

TABLE II

Opportunistic Infectionsand NeoplasmsInvolving the Liver in 635 PatientsWith HIV Infection 12-231

Yield of Different Testsfor the Diagnosisof Disseminated Mycobacferiumavium-intracellulare Infection [25-3 11

No. of Cases [%I Infections Cytomegalovirus Mycobacterium avium-intracellulare Unspecified acid-fast bacilli Crvotococcus neoformans H%oplasma capsulatum Mycobacterium tuberculosis Candida aibicans

4 (0.6)

Neoplasms Kaposi’s sarcoma Non-Hodgkin’s lymphoma

drug users (3% and 12% respectively). The overall prevalence of opportunistic infections did not differ in the two groups. Drug users were more likely to have cirrhosis and chronic active hepatitis (CAH) than homosexual patients [2-231.

HEPATIC DISORDERS Infections MYCOBACTERIA: Disseminated infection with Mycobacterium auium-intruceZZuZare (MAI) has been found in 20% to 55% of autopsies in patients with AIDS [24,25]. Also, autopsy and biopsy studies showed that 70 (11%) of 635 patients with HIV infection have MAI, and an additional 6% harbor unspecified AFB in the liver (Table I). The most common presentation is that of fever and weight loss. Biliary obstruction may result from large adenopathies in the hilar region [25]. The levels of liver enzymes (two- to three-fold elevation in ALT and AP) do not allow the clinician to separate MA1 from Mycobucterium tuberculosis [7,26]. Mycobacteria usually infiltrate the portal triads and liver parenchyma but may present as a mass lesion [27]. Granulomas are seen in 76% of liver specimens involved with MA1 [4-11,14,16-21,231. These lesions are poorly formed and usually do not show caseation [22]. The highest yield in the diagnosis of disseminated MA1 infection is obtained with blood cultures (80%) followed by histologic examination (69%) and culture (66%) of bone marrow; liver culture (47%) and histology (26%) have a lower yield (Table II) [25-321. Multi-drug regimens have shown some success in the treatment of disseminated MA1 infection [32]. The mean survival from diagnosis to death is 3 to 5 months [25,31]. Tuberculosis is an AIDS-defining illness in HIVseropositive patients [33]. Blacks, Latinos, and parenteral drug users are more likely to have HIV and tuberculosis than other groups [34]. The most com-

No. Positive/ No. Tested (%)

Test

I

/ BONAClNi

Blood culture*

821103 (80)

Bone marrow Histology* Culture

27139 (69) 50176 (66)

Lymph node (histology and/or culture)

10123 (43)

Liv$$sy 16134 (47) 9134 (26)

Histology *p ~0.05, versus liver biopsy culture.

mon manifestations are fever, cough, and constitutional symptoms [35,36]. Extrapulmonary disease occurs in 60% of patients with HIV infection and tuberculosis: 7.5% (three of 40) of these had hepatic M. tuberculosis [36]. Rarely, tuberculous abscesses of the liver have been reported [37]. Although patients with AIDS and tuberculosis experience more side effects from antituberculous drugs, the response to therapy is good [34]. The type and duration of therapy depend on drug susceptibility and tolerance [38]. In treated patients, the median survival after diagnosis is about 16 months [34]. Liver biopsy has been advocated as a rapid method of diagnosing disseminated mycobacterial infection [26]. However, more accessible sites such as blood or lymph nodes not only have a higher yield than liver biopsy [38], but only culture can reliably distinguish MA1 from M. tuberculosis since AFB are similar in appearance histologically. A novel, yet unidentified mycobacterium has been described in the liver, spleen, and ascitic fluid in a patient with AIDS [39]. CYTOMEGALOVIRUS: CMV is the most common infection detected at autopsy of patients with AIDS [24]. Evidence of hepatic involvement, based on the presence of intranuclear inclusion bodies and/or positive viral cultures, is also relatively common (Table I). However, unlike CMV infection of the lung, gut, and retina [40,41], its clinical expression in the liver is rarely symptomatic. Liver enzymes (mostly AP) are mildly elevated and the bilirubin level is usually normal [40]. Thus, CMV hepatitis in AIDS has been less frequently reported than biliary disease [40,42]. CMV inclusions in the hepatocytes, Kupffer cells, bile duct epithelium, and endothelial cells are characteristic but not always present [5,43,44]. Granulomas are occasionally seen. In situ hybridization [44] appears to be the most sensitive technique to diagnose liver involvement with CMV. April

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Hepatic CMV lesions can simulate liver metastases on computed tomographic (CT) scanning [45]. Treatments with both ganciclovir and foscarnet showed a high rate of virologic response in CMV esophagitis and colitis, but no data about hepatic disease have been published [41,46,47]. OTHER VIRUSES: Herpes simplex type 2 hepatitis has been reported only once in HIV infection: it caused submassive hepatic necrosis (AST greater than 5,000 III/L), hypoglycemia, and disseminated intravascular coagulation as the first manifestations of immunodeficiency [48]. Two fatal cases of adenovirus hepatitis complicated by coagulopathy have been recently published [49]. CRYPTOCOCCUS NEOFORMANS: Several patients with AIDS and cryptococcosis have extraneural disease [50-521. In 19% of these, the organism can be found in the liver by histology or culture [50-521. Positive cultures are less common in liver tissue (12%) than in blood (32%) or bone marrow (50%) [50-521. Moreover, in every instance of a positive liver culture, blood or bone marrow cultures grew the organism as well. The levels of liver enzymes and bilirubin may be elevated but the liver involvement is likely to remain asymptomatic [52]. Cryptococcal infection in AIDS is best treated with intravenous amphotericin B and oral flucytosine [53]. Long-term maintenance therapy is probably necessary [50]. HISTOPLASMA CAFWJLATUM: Histoplasmosis can also be a disseminated process in patients with AIDS and cause constitutional symptoms [54-571. Patients may or may not originate from endemic areas [56]. Liver involvement by histology or culture at biopsy or autopsy is found in 16% of disseminated cases and is usually asymptomatic [54-573. The levels of liver enzymes are not helpful in distinguishing patients with or without hepatic involvement [57]. On biopsy, silver stains show round organisms with occasional budding [54]; inflammation is usually mild [8] but granulomas may be seen [58]. Recently, detection of Histoplasma polysaccharide antigen in urine or blood proved to be a rapid and sensitive method for the detection of disseminated histoplasmosis [59]. Treatment and maintenance with intravenous amphotericin B have been successful [54,57,59]. PNEUMOCYSTISCARINII: P. carinii pneumonia is one of the most common infectious processes in AIDS. P. carinii can occasionally disseminate and result in widespread small foamy nodules that represent areas of eosinophilic necrosis [60]. The organisms are recognized histologically with silver stains; inflammatory changes are minimal [60,61]. Liver involvement is usually diagnosed at autopsy and is surprisingly frequent (39%) in patients with extrapubnonary pneumocystosis [61]. Transami406

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nase and AP elevations are usually moderate, but levels greater than 1,000 IU/L have been reported [61]. Since 50% of patients with disseminated disease had received aerosolized pentamidine, it has been suggested that this prophylactic regimen may facilitate P. carinii dissemination [61,62]. Intravenous pentamidine is the treatment of choice for disseminated disease [61,62]. OTHER INFECTIONS: Candida albicans has been cultured from the liver in postmortem studies [lo], and additional patients harbored candidal granulomas in the liver parenchyma [58]. Hepatic microabscesses have been reported in AIDS [63] but have been more often described in neutropenic patients. Disseminated coccidioidomycosis caused hepatic involvement with nodules and granulomas at postmortem [64]. Another invasive fungus, AspergiZlus fumigatus, has been recovered from multiple liver abscess cavities diagnosed by ultrasonography in a patient with terminal AIDS [65]. Bacillary angiomatosis [66] and cat scratch disease [67] have been shown to disseminate and to involve the liver in HIV-seropositive patients. Warthin-Starry silver stains reveal bacilli at histology, and electron microscopy is confirmatory. A rickettsia-like organism is the etiologic agent in both diseases [;66]. Mycoplasma incognitus may prove to be a pathogen resulting in serious liver injury in HIV-seropositive patients [68]. Liver parenchymal involvement with Leishmania [69], Encephalitozoon cuniculi [70], and schistosomiasis [23] has been observed in HIVseropositive patients. Viral Hepatitides Homosexual men and intravenous drug users are at high risk for acquiring both hepatitis and HIV, since these viruses are transmitted via the same route [71]. Fifty to 75% of chronic hepatitis B virus (HBV) carriers in these high-risk groups also harbor antibodies to HIV [72,73]. In addition, patients with HIV infection carry a high (nearly 20%) risk of becoming chronic carriers if they contract HBV [74]. They respond less frequently and with lower anti-hepatitis B surface antibody titers to a plasmaderived as well as a recombinant HBV vaccine than HIV-negative patients [75]; also, they lose this protection more frequently (43%) than HIV-negative controls (8%) after 4 years [76]. Vaccination seems advisable in HIV-positive individuals without markers of past HBV infection, but they should be tested for antibody response after the third dose of the vaccine [77]. Some studies have shown that serum transaminases [78,79] and histologic lesions [7,8,79] are less in HIV patients with chronic HBV infection, possibly because of immunosuppression. In contrast, others have found that HIV infection does not alter serum transaminases or HBV-DNA

HEPATOBILIARY

levels in chronic HBV infection [80,81]. Since most of the T lymphocytes present in the hepatic inflammatory infiltrate of chronic HBV infection are of the CD8 phenotype [82], it seems unlikely that a low level of circulating T4 cells would be an important factor in HBV replication [83]. In patients with HBV and HIV infection, the prevalence of anti-6 antibodies is about 25% [71,73,84]. In these patients, more intense liver inflammation activity may be present [84]. About 60% of HIV-positive drug addicts in Italy have antibodies against the hepatitis C virus (HCV) [85]. In contrast, Danish homosexuals have only a 4% HCV seropositivity rate [86]. HCV RNA by polymerase chain reaction was found in all sera of HIV-seropositive hemophiliacs (871. HCV infection may be frequent in HIV-seropositive patients and may contribute to the high prevalence of cirrhosis and CAH seen in this population [17,21,23,72,88]. Neoplasms LYMPHOMAS: Non-Hodgkin’s lymphomas (NHL) are a known complication of HIV infection. The majority are high- or intermediate-grade B-cell tumors, and extranodal presentation is common [89-911. Liver involvement has been reported in 14% of cases [89-941. This is most likely an underestimate, because few patients underwent a liver biopsy or an autopsy. Levels of hepatic enzymes are only mildly abnormal [94]. A CT scan may be helpful by localizing multiple low-density lesions and directing needle biopsy [93]. On occasion, ultrasonography can detect hepatic heterogeneity in the absence of CT lesions [95]. Lymphomas arising as primary neoplasms in the liver have been described [2,7,10]. Serum bilirubin, ALT, and AP levels were elevated and a sonogram revealed hypoechoic lesions [96]. Varied multi-drug regimens have been employed in patients with AIDS and lymphoma, but the median survival has been between 2 and 7.5 months despite chemotherapy [90-921. Hodgkin’s disease (HD) has also been reported in the context of AIDS. It is almost exclusively of the mixed cellularity (50%) or nodular sclerosis (40%) subtype [90,91,97-991. About 25% of patients have liver involvement at biopsy or autopsy, but no data on liver enzyme abnormalities are available [90,91,97-991. As in NHL, the stage is frequently more advanced and the prognosis poorer than for HD in immunocompetent patients [90,91]. Therapy has consisted of various chemotherapeutic regimens with or without radiotherapy [97,98]. Some patients with liver involvement have had a complete remission [98]. The median survival after therapy varies between 8 and 15 months [90,91,98]. KAPOSI'S SARCOMA: Hepatic Kaposi’s sarcoma (KS) is noted in 8.6% of patients with AIDS [2-231

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but leads to few if any symptoms and is rarely the cause of death [loo]. An elevated AP is a common finding [5]. CT scans of the abdomen may detect liver nodules representing KS [loll. Histologically, KS consists of spindle cell proliferation extending through the portal tracts [5,10]. While liver involvement is usually found in disseminated KS [5], one report has demonstrated that hepatic KS can be the first presentation of HIV disease 11021. In cases of symptomatic KS, the presence of liver involvement would not alter the multi-drug chemotherapeutic regimens [ 1031. Drug-Induced Hepatotoxicity Patients with HIV infection often need medications with known hepatotoxic potential. Trimethoprim-sulfamethoxazole and pentamidine are both used for the treatment of P. carinii pneumonia. A twofold or higher increase in serum transaminases or AP can occur in up to 50% of patients treated with either drug, but discontinuation is rarely necessary [104-1061. Sulfa drugs can also cause granulomatous hepatitis [8,17]. Ketoconazole may be responsible for transient transaminase elevation, which occurred in 21% of HIV-infected patients [107]. Oral fluconazole is used to treat various fungal infections; in 16% of 62 patients, an elevation of liver enzyme levels was noted, but a recurrence was observed in only one patient after rechallenge [ 1081. Zidovudine has demonstrated beneficial effects on the survival of patients with AIDS; a recent controlled study confirmed the absence of significant hepatotoxicity in the zidovudine-treated group [log]. Elevations of serum transaminases have been reported in up to a third of patients treated with 2’,3’-dideoxyinosine (dd1) [llO]. Ganciclovir (DHPG) hepatotoxicity, consisting of an irreversible fourfold increase in serum AST/ALT, has been documented in one AIDS patient [ 1111. Others have noted no change [112] or a mild increase (twofold) between pre- and post-therapy liver enzyme levels [41]. Antituberculous treatment resulted in liver enzyme abnormalities high enough to dictate therapeutic adjustments in 5% of treated patients [34]. Other potentially hepatotoxic drugs used in patients with HIV infection include antibiotics, anticonvulsants, and antiemetics [113]. In patients with HIV infection and elevated liver enzymes, a trial of medication withdrawal, when feasible, should be attempted in order to uncover possible drug hepatotoxicity [113]. Other Pathologic Findings Alcoholic liver disease may coexist with other lesions in patients with HIV infection, but its occurrence has not been emphasized. Approximately 29% of patients with AIDS were thought to be heavy April

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TABLE III Etiology of Hepatic GranulomasFound at Autopsy and Biopsy in Patients With HIV infection Biopsy (tl = 91)” MAI Idiopathic Unspecified AFB M. tuberculosis

19 :: 14

Hisfoplasma ~“tococcus

i

Medications Candida Microsporidiosis

2

Schisfosoma

1

-

s

i 1

s -

i

1

-

Al = Mycobacterium avium-intracehfare; AFB = acid-fast bacilli; CMV = cytomegalovirus. 6,14, 17-23,581.

2,4-8, 11,14,161.

alcohol users [6,8,21], 6% had alcoholic hepatitis [6,21], and 7% had micronodular cirrhosis attributed to alcohol [5,8,21]. In a predominantly heterosexual population of alcoholics, the seroprevalence of HIV infection was 4.5% [114]. Macrovesicular steatosis has been reported in about one third of livers in biopsy as well as postmortem studies. Its origin is probably multifactorial [6] but unlikely to be of major clinical significance in these patients. Liver granulomas are found in 25 (11%) of 230 autopsies and 91 (40%) of 227 biopsies (Table III). These are usually poorly formed and are constituted of histiocytes with little or no associated lymphocytic reaction [19,22,24]. The majority (41%) are attributed to MA1 infection and a third are idiopathic. Unspecified AFB (12%) and M. tuberculosis (4.7%) are occasionally found; in the latter, wellformed caseating granulomas can be seen [19]. Sinusoidal dilatation is frequently noted in liver samples of HIV-seropositive patients [2,19,115]. These changes can be seen in neoplastic, granulomatous, and drug-induced conditions [116]. Peliosis hepatis was found in eight (8%) of 99 biopsies in this population [19,22,115]. The lesions consist of bloodfilled cavities (1 mm to several cm in diameter) distributed throughout the liver parenchyma [115,116]. Recently, bacillary angiomatosis has been proposed as one of the causes of peliosis hepatis in patients with HIV infection, and treatment with erythromycin has resulted in dramatic improvement in some patients [117].

GALLBLADDERAND BILIARYTRACT DISEASE Acalculous cholecystitis has been well documented in HIV infection [118-1201. Right upper quadrant (RUQ) or epigastric pain is the most common presenting symptom. Fever occurs in 65%, but jaundice is uncommon (18%). There is a marked eleva408

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tion of the serum AP level with normal bilirubin and a modest elevation of the transaminases. Ultrasonography can show dilatation of the gallbladder, thickening of its wall, or both features, but may also demonstrate normal findings. Gallbladder specimens examined pathologically showed extensive edema, necrosis, and ulcerations but no calculi. The agents most commonly implicated have been CMV and Cryptosporidium, alone or in association [118-1201. Candida cholecystitis and obstruction of the cystic duct by KS, both responding well to cholecystectomy, have also been reported [121]. Bile duct abnormalities are present in over 50% of cases of acalculous cholecystitis [119-1221. Intrahepatic and extrahepatic sclerosing cholangitis, termed AIDS cholangiopathy, was first described in three patients complaining of RUQ pain and fever [122]. All three also had gallbladder involvement. Patients with cholangiopathy present with RUQ or epigastric pain (84%) and/or fever (65%) [123]. An elevated (twice normal) serum AP is present in 80%, but the bilirubin level was elevated in only 15% of cases. Twenty of 26 patients had an abnormal result on endoscopic retrograde cholangiopancreatography (ERCP) [123]. In 25% of cases, the ultrasonogram was normal in the presence of sclerosing cholangitis. Pathogens were identified in about 50% of evaluable patients; CMV and Cryptosporidium were the most common [123]. One patient had hepatic and bile duct infiltration with KS, and one had a primary Burkitt’s lymphoma of the bile ducts 11231. Endoscopic sphincterotomy was performed on the patients demonstrating papillary stenosis, with marked relief of pain in most patients. However, in general, the serum AP level continued to increase. This may be due to ongoing intrahepatic duct disease or parenchymal infiltration of the liver, since the bile ducts seem to remain patent after successful papillotomy [123].

DIAGNOSTICMETHODS Imaging Studies Ultrasonography is a good initial tool to evaluate gallbladder disease and bile duct dilatation [14]. In AIDS, the appearance of the gallbladder or its wall is not specific, and the echo pattern of the liver is not predictive of the histologic lesions [14]. In addition, in 25% of patients with an abnormal finding on ERCP, results of ultrasonography were normal [123]. CT scans are more sensitive for parenchymal lesions but also lack specificity [95]. Fine-needle aspiration should be used whenever a lesion is identified and the material obtained evaluated by cytologic and AFB stains [95]. The most sensitive method to diagnose biliary tract disease in patients with AIDS is an ERCP [123]. HIDA (dimethyl iminodia-

HEPATOBILIARY

cetic acid) scans can be helpful in showing cystic duct obstruction in acalculous cholecystitis [120]. Liver Biopsy The yield of liver biopsy in evaluating HIV-seropositive patients with fever, hepatomegaly, and/or abnormal levels of liver enzymes has been reviewed in several articles [17-231. Liver histology is rarely normal but most of the lesions found are trivial or nonspecific [7,17,19,21]. An opportunistic infection was diagnosed in 87 (33%) and neoplasms in seven (2.6%) of 265 biopsies, and most were potentially treatable [17-231. Although this procedure appears safe in HIV-infected patients, at least one death [54] has been reported. Most infections and neoplasms can be diagnosed by biopsy and culture of more accessible tissues like blood and bone marrow. If a less invasive evaluation has failed to uncover a diagnosis, then a liver biopsy is indicated; special stains (with immunohistochemistry and in situ hybridization) and cultures for mycobacteria, viruses, and fungi are then warranted [17,113].

CONCLUSIONS During the course of HIV infection, the liver and the biliary tract are frequently involved with opportunistic infections (sometimes multiple) and/or neoplasms. Chronic viral hepatitides and medications may affect patients independently of HIV infection. The emergence of new and sensitive techniques has increased our ability to diagnose “new” bacterial diseases [66] or neglected agents that may contribute to the immunodeficiency state [68]. In the future, some of these microbes may be found to significantly involve the liver or the biliary tract. Nonetheless, overt liver disease is likely to remain rare. The evaluation of the HIV-seropositive individual presenting with hepatomegaly or elevated liver enzyme levels should include (1) a careful search for potentially hepatotoxic drugs, (2) a careful review of past medical records for previously diagnosed disseminated opportunistic infections or neoplasms, (3) serology for HBV, HCV, and hepatitis 6 virus if the HBV surface antigen is positive, (4) blood cultures for bacteria, mycobacteria, fungi, and viruses, and (5) bone marrow examination in an effort to diagnose a disseminated infection or neoplasm. If the patient presents with abdominal pain, fever, jaundice, or an elevated serum AP level, ultrasonography and/or CT scanning of the RUQ is helpful in identifying liver masses and assessing the gallbladder and the bile ducts. If a mass is present, fine-needle aspiration should be done. In the case of bile duct dilatation, ERCP should be performed because it can be diagnostic as well as therapeutic in

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patients with papillary stenosis. Should the result of evaluation be negative, a liver biopsy (with special stains and cultures for mycobacteria, viruses, and fungi) is appropriate, but this decision needs to be individualized because only a third of the procedures will yield a potentially treatable disease.

ACKNOWLEDGMENT The secretarial

skills of Vicki Redinger are gratefully

acknowledged

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