SEMINARS IN LIVER DISEASE-VOL.

12, NO. 2, 1992

Hepatic Histopathology in the Acquired lmmunodeficiency Syndrome

Since the beginning of the acquired immune deficiency syndrome (AIDS) epidemic, careful analysis of hepatic biopsy and autopsy specimens has contributed to our knowledge of AIDS-associated hepatic histopathologic changes. In the past 10 years we have learned that the liver is frequently involved as part of systemic opportunistic infection and neoplasm. Up to three quarters of patients with AIDS have abnormalities in liver function and hepatomegaly." Often, however, the extent of liver enzyme elevation is out of proportion to the histologic abnormalities on biopsy; possible reasons for this disparity will be discussed. Early in the epidemic, liver biopsy was advocated not only to help in patient management, but also as a means for defining the range of hepatic abnormalities in AIDS. This cumulative experience is encompassed in a large number of original articles and In this article, we discuss the histopathologic changes of the liver in AIDS, emphasizing more recent literature and areas of active research. We also discuss the role of liver biopsy in patients with AIDS, an issue that remains unsettled.

HUMAN IMMUNODEFICIENCY VIRUS INFECTION OF THE LIVER Primary human immunodeficiency virus (HIV) infection of the liver has been documented (see Article by Lafon and Kirn in this issue of Seminars). Using imnu.~nohistochemicalstaining, p24 gag HIV- 1 protein has been identified in mononuclear inflammatory cells (Kupffer cells) and endothelial cells (sinusoidal lining cells) of the liver.I2.'"n vitro, multiplication of HIV has also been demonstrated in primary cultures of Kupffer

From the Satnuel Bronfmcrn Depurmwnt of Medicine (Division of Liver Diseases), rind the Lillian and Henry M . Strafton-Huns Popper Drportmer~tof Patholo,qy, Mount Sintri School of Medicine of'tkv City Urliversity o f N e w York, New York, New' York Reprint requests: Dr. Bach, Samuel Bronfman Department of Medicine. Mount Sinai School of Medicine of the City University of New York. New York. N Y 10029.

and endothelial cells.'4," CD4 receptors, which mediate cellular HIV binding and uptake, have been identified on Kupffer and endothelial cells, providing a potential mode of hepatic infection. '" Because Kupffer cells reside within the hepatic microcirculation, it is possible that early hepatic HIV infection of Kupffer cells occurs during viremia. Thus, Kupffer cells may represent an unsuspected storage reservoir for the AIDS v i r u ~ . ' ~ . ' ~

NONSPECIFIC HISTOLOGIC FEATURES Although liver lesions are frequent in AIDS, a specific etiology is often not evident. Unexplained histologic findings include granulomas, steatosis, focal hepatic necrosis, and sinusoidal cell abnormalities, including peliosis he pa ti^.^-"('-^.''-^^ Findings such as macrovesicular steatosis may be attributable to other concomitant conditions, including malnutrition, weight loss, disseminated infection, chronic debilitating illness, alcohol abuse, or total parented nutrition. Another finding, peliosis hepatis, has been a frequent unexplained finding.4,'h,'x One potential explanation has been that the lesion results from endothelial cell injury mediated by HIV. Others have proposed that the organism recently associated with bacillary angiomatosis may be responsible (see later).'." By electron microscopy, cytoplasmic collections of membranous rings have been noted within a large percentage of hepatocytes in patients with AIDS. Prominent Ito cells with lipid engorgement were also noted." These features may be secondary to other underlying conditions, including viral hepatitis, which, as discussed later, is common in these patients. More ultrastructural studies of liver are needed to determine the significance of these findings.

VIRAL HEPATITIS Hepatitis B,C,D Serologic markers of viral hepatitis, including hepatitis B and D viruses (HBV, HDV) are common in pa-

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NANCY BACH, M.D., NEIL D . THEISE, M.D., and FENTON SCHAFFNER, M.D.

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THEISE, SCHAFFNER

FIG. 2. A large microabscess, typical of cytomegalovirus hepatitis, consisting primarily of neutrophils expanding a sinusoid. (H&E; x 25)

tion. HSV may present as fulminant hepatitis in patients with AIDS. Necrotic hemorrhagic foci have been reported in the liver.3yPathologic examination may reveal Cowdry type A intranuclear inclusions, which cause an irregularly shaped eosinophilic intranuclear inclusion often surrounded by a halo.4' In the pediatric population, EBV has been reported to cause chronic active hepatitis; this has not been observed in adult^.^^-'^.^' NO particular pattern of disease has been reported in patients with AIDS. Disseminated adenovirus has also been reported in AIDS. Diagnosis is usually made at autopsy where hepatocytic necrosis with massive hemorrhagic foci have been identified. Light and electron microscopic examination may reveal "smokey" intranuclear inclusions adjacent to the n e c r o s i ~ . ' ~

acid-Schiff (PAS) reaction after diastase digestion combined with culture of tissue establish the diagnosis. Staining of MTB usually detects few to rare acid-fast bacilli (AFB), unlike MAI, in which large numbers of AFB are seen (Figs 3,4). Mycobacteria may stain within granulomas, sinusoidal lining cells, sinusoids, and foamy cells. Histologic examination is more sensitive than culture in detecting hepatic mycobacteria. Tissue culture, however, remains important to differentiate the species of Mvcohacterium. Culture may diagnose tuberculosis even in the absence of AFB or granulomas on biopsy.47 All biopsy specimens from patients with AIDS should therefore be stained for AFB and a specimen processed for AFB culture.

Bacillary Angiomatosis BACTERIAL INFECTIONS Mycobacteria Along with CMV, mycobacteria are the most common organism identified in liver biopsies in AIDS. Disseminated disease with Mycobacterium tuberculosis (MTB), Mycobacterium avium-intracellulare (MAI), Mycobacterium xenopi, and Mycobacterium kansasii may involve the l i v e r . 2 ~ y ~ " 0 ~ 1e 7incidence ~ 4 2 ~ 4 ~ofh MTB is increasing in both the general population as well as in those with AIDS. Given its potential as a public health hazard, this treatable disease requires prompt diagnosis .44.45 Liver biopsy typically reveals noncaseating granulomas, often poorly formed, along with large foamy macrophages and a paucity of lymphocyte^.^^"^^^^^^^^^ Special stains, including the Ziehl-Neelsen and periodic

Intensive examination of tissues from patients with AIDS has recently led to identification of a new pathogen. A gram-negative bacillus, associated with lesions of angiomatosis in their skin, was recently detected by polymerase chain reaction.4x Amplified sequences bore phylogenetic similarity to rickettsia, implicating a previously uncharacterized rickettsia-like organism as the likely etiology. This organism is closely related to Rochalimaea quintana.4x.4yBacilli may be identified by staining with either a Warthin-Starry, Brown-Hopps, Brown-Brenn, or Steiner's silver stain (Fig. 5 ) . In the immunocompromised host, the agent of bacillary angiomatosis can cause disseminated disease, which may include the liver. Several cases of bacillary angiomatosis associated with peliosis hepatis have been described, possibly explaining an abnormality previously considered 'nonspecific' in liver biopsies of AIDS patients?' It is not known whether all cases of peliosis

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FIG. 5. In bacillary angiomatosis many bacilli may be identified with the use of special stains such as the Warthin-Starry stain. Bacilli are often found in clumps (arrows) within the fibromyxoid stroma of the lesions. (Warthin-Starry; x 50)

FUNGAL INFECTIONS Disseminated disease due to Cryptococcus neoformans, Hi.stoplasma cup.sulatum, Cutzdidu ulbicans, and Coccidioid~simitis may all involve the liver in AIDS. Primary hepatic involvement with these fungi is uncomThe hepatic mycoses may mon but has been rep~rted.~." produce granulomas that are often poorly formed and the inflammatory response associated with these granulomas may be minimal. The yeast organisms can be identified with hematoxylin and eosin, D-PAS, or methenamine silver stain^.^ Organisms can be found in microabscesses, granulomas, or within the sinusoids of the liver.' 13.47

electron microscopic examination. These protozoa have been reported to be the cause of fatal hepatocellular necrosis in one individual infected with AIDS.s5

NEOPLASMS Opportunistic neoplasms commonly seen in AIDS, including Kaposi's sarcoma (KS), non-Hodgkin's lymphoma (NHL), and Hodgkin's disease, may all be found in the liver. Similar to involvement of the liver with opportunistic organisms, hepatic neoplasms are usually secondary rather than a primary disease. (See also Article by Herndier and Friedman in this issue of Seminars.)

PROTOZOAL INFECTIONS Kaposi's Sarcoma Protozoa commonly cause opportunistic infections in AIDS. Although protozoal infection of the biliary tract by cryptosporidium is frequently reported, infection of the liver is rare. (See Article by Cello in this issue of Seminars). Pneumocystis cariniipneurnonia (PCP) is one of the most common life-threatening opportunistic infections in AIDS. Only a handful of cases of Pneumocystis involving the liver, however, have been d o c ~ m e n t e d . "Mor~~ phologic changes in the liver in these cases included distension of the hepatic sinusoids with foamy eosinophilic material that stained positively with a methenamine silver stain. These extrapulmonic cases may be a consequence of inhaled pentamidine therapies for PCP which fail to protect extrapulmonic sites. Microsporidia (Encephalitozoon cuniculi) is another organism discovered in the liver after intensive

KS is the most common intrahepatic neoplasm found at autopsy in patients with AIDS. Formerly considered a rare indolent malignancy associated with skin lesions, this neoplasm can run a rather aggressive course in HIV-infected individuals. Cutaneous as well as visceral involvement may be seen in AIDS. Up to one third of patients with cutaneous KS also have hepatic involvement.'.4 Because of the asymptomatic nature of intrahepatic KS, diagnosis is usually made postmortem. Gross examination of the liver reveals purplish-brown nodules that frequently occur in the subcapsular and hilar regions of the 1iver.j Histologic examination reveals multifocal hemorrhagic nodules of varying size, mainly affecting the portal areas. Spindle-shaped cells with atypical angulated vascular channels are seen with extravasated red blood cells and vascular lake^."^^,^'

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SEMINARS IN LIVER DISEASE-VOLUME

Lymphoma NHL and Hodgkin's disease may complicate the course of AIDS. Both diseases behave atypically in this population. NHL is frequently of high-grade malignancy and of B-cell origin, unusual findings for an age to sex .~' matched HIV seronegative p o p u l a t i ~ n . ~ ~Extranodal involvement and diffuse disease are also frequently found in HIV-infected patients with NHL.jXRare cases of primary hepatic involvement have been reported in AIDS ,?.h.iY..MI Histopathologic subclassifications reveal that the majority of NHLs in this population are either small and noncleaved, large cell immunoblastic-plasmacytoid. or large and noncleaved cell. Hodgkin's disease involving the liver has also been reported to occur in HIV-infected individuals. As with NHL, the disease behaves more aggressively both histologically and clinically in HIV seropositive patients,SX.hi

.h2

DRUG-INDUCED LIVER DISEASE Medications cause biochemical histologic abnormalities of liver in up to 8% of patients with AIDS.' Table 1 lists some of the frequently used medications that have the potential for hepatotoxicity. Zidovudine (ZDV,AZT) and trimethoprim-sulfamethoxazole are two drugs frequently used in AIDS. Although acute cholestatic hepatitis has been reported with usage of ZDV, review of the large trials of this drug reveal that the potential for such hepatotoxicity is I O W . ~ " ~ ~ Trimethoprim-sulfamethoxazole has been implicated as causing granulomas, an otherwise unexplained finding in biopsies of some patients with AIDS."'."5 The incidence of this condition and the finding of abnormal liver biochemistries is increased in the population with AIDS." 2'3' deoxyinosine (didanosine, ddI), one of several drugs presently being tested for use in AIDS, was recently reported to precipitate fulminant hepatic failure. Examination of the liver at autopsy revealed micro- and macrovesicular steatosis, cholestasis, hepatocellular necrosis. and fibrosis."

ROLE OF LIVER BIOPSY Of all the issues regarding AIDS and the liver, the role of liver biopsy continues to generate the most controversy. At first, all agreed that liver biopsy was vital to learning more about the hepatic involvement in AIDS. With experience, however, the liver was found to be affected by the same infections and neoplasms that plagued other organ systems without being confined to the liver. Thus, many advocated less aggressive modalities of diagnosis, including bone marrow aspiration and biopsy, blood culture, and lymph node biopsy. Against this recommendation has been evidence that the yield of liver biopsy remains higher than these other procedures in the diagnosis of such potentially treatable diseases as CMV . ~ ~ marrow biopsy has infection and t u b e r c u l ~ s i s Bone

12, NUMBER 2, 1992

TABLE 1. Drugs Used in AlDS That Can Produce Hepatotoxicity

Trimethoprim\ull'arnethoxazole Ketoconazole Iwnia~id Rifampin Zidovudine Pentaniidine Diphenylhydantoin Prochlopera~ine

++ +t ++ t~

++ +

+ +

+

+

+ + ++

+

been reported to miss as many as 30% of cases of tuberculosis that have liver i n v ~ l v e m e n t . ~ ~ ~ ~ " Despite the high diagnostic yield of liver biopsy, which approaches 50%. lack of efficacious therapy for diseases diagnosed often dulls enthusiasm for this invasive procedure.?.X.17.3.J3371 Criteria for determining which patients will benefit from liver biopsy would therefore be useful. Indications for liver biopsy have traditionally included hepatomegaly, unexplained abnormalities in the results of hepatic tests, and fever of unknown origin. Several studies have suggested that the yield of liver biopsies is greater when the level of the biochemical abnormalities is higher. Hepatomegaly alone has not been found to be a good indication for liver b i o p ~ y . ' ~ . ~ ? Although, for the most part, results of liver biopsy do not influence morbidity and mortality, arguments in favor of its use can be made. Better criteria to define who will benefit from liver biopsy would be useful. At the present. liver biopsy remains appropriate in patients with persistent unexplained liver enzyme abnormalities who are symptomatic. Future protocols may define more precisely those patients in whom liver biopsy is likely to provide useful information.

SUMMARY Involvement of the liver with the same opportunistic organisms and neoplasms affecting other organs has been recognized since the beginning of the AIDS epidemic. In this overview of hepatic histopathologic features in AIDS, we review the range of opportunistic infections and neoplasms accompanying HIV infection. Hepatic disease may result from viral, bacterial, protozoal, or fungal infection, or secondary to drugs and neoplasms. Liver involvement in AIDS usually reflects disseminated rather than primary disease. CMV and mycobacteria are the most common organisms in liver identified in biopsy and autopsy studies. A variety of nonspecific features, including steatosis, granulomas, and sinusoidal abnormalities may also be seen. HIV-I itself was recently identified in the liver. Speculation regarding the significance of this finding has been discussed in this review. Hepatitis B, C, and D may also complicate the course of disease in patients with

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AIDS. Hepatitis B behaves differently in the population with AIDS than in immunocompetent patients. We concluded our review with a discussion of the present recommendations regarding the use of liver biopsies in these patients. This topic continues to be widely debated in the literature.

REFERENCES Godwin TA. Felix JC: Histopathology of the liver. (Abstr.) Lab Invest 56:27A, 1987. Schneiderman DJ, Arensen DM, Cello JP, et al: Hepatic disease in patients with the acquired immune deficiency (AIDS). Hepatology 7:925-930, 1987. Lebovics E, Thung SN, Schaffner F, Radensky P: The liver in the acquired immunodeficiency syndrome: A clinical and histological study. Hepatology 5:293-298, 1985. Glasgow BJ, Anders K, Layfield LJ. et al: Clinical and pathologic findings of the liver in the acquired immune deficiency syndrome (AIDS). Am J Clin Pathol 85:582-588, 1985. Leevy CB, Nurse-Bey H, Leevy CM. Yu J: Hepatic abnormalities in AIDS. (Abstr.). Gastroenterology 94:A561, 1988. Welch K, Finkbeiner W, Alpers CE, et al: Autopsy findings in the acquired immunodeficiency syndrome. JAMA 252: 1 1521159, 1984. Nakunuma Y, Liew CT, Peters RL. Govindarajan S: Pathologic features of the liver in acquired immunodeficiency syndrome (AIDS). Liver 6: 158-166, 1986. Gordon SC. Reddy KR, Gould EE. et al: The spectrum of liver disease in the acquired immunodeficiency syndrome. J Hepato1 2:475-84. 1986. Palmer M, Braly LF, Schaffner F: The liver in acquired immunodeficiency disease. Semin Liver Dis 7: 192-202, 1987. Schneiderman DJ: Hepatobiliary abnormalities in AIDS. Gastroenterol Clin North Am 17:615-629. 1988. Dworkin BM, Stahl RE. Giardina MA, et al: The liver in acquired immunodeficiency syndrome: Emphasis on patients with intravenous drug abuse. Am J Gastroenterol 82:23 1-236, 1987. Schmitt MP, Steffan AM, Jaeck D, et al: Human immunodeficiency virus multiplies in primary cultures of human Kupffer cells. Exp Cell Biol 59: 118-1 19, 1989. Housset C. Boucher 0 , Girard PM, et al: Immunohistochemical evidence for human immunodeficiency virus- 1 infection of Kupffer cells. Hum Pathol 2 1 :404-408, 1990. Schmitt MP, Steffan AM, Gendrault JL, et al: Multiplication of human immunodeficiency virus in primary cultures of human Kupffer cells-possible role of liver macrophage infection in the pathophysiology of AIDS. Res Virol 141:143-152, 1990. Steffan AM, Schmitt MP, Gendrault JL, et al: Productive infection of primary cultures of human immunodeficiency virus. Exp Cell Biol 57: 118-1 19, 1989. Scoazec YV, Feldmann G : Both macrophages and endothelial cells of the human hepatic sinusoid express the CD4 molecule. a receptor for the human immunodeficiency virus. Hepatology l2:505-5 10. 1990. Kahn SA, Saltzman BR. Klein RS, et al: Hepatic disorders in the acquired immune deficiency syndrome: A clinical and pathological study. Am J Gastroenterol 81: 1145-1 148, 1986. Czapar CA, Weldon-Linne M, Moore DM, Rhone DP: Peliosis hepatis in the acquired immunodeficiency syndrome. Arch Patho1 Lab Med 1 10:611-613, 1986. Sidhu GS, Stahl RE, El-Sadr W, et al: The acquired immunodeficiency syndrome: An ultrastructural study. Hum Pathol 16:377-386, 1985.

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Homann C, Krogsgaard K, Pedersen C , et al: High incidence of hepatitis B infection and evolution of chronic hepatitis B in patients with advanced HIV infection. J Acquir Immune Defic Syndr 4:416-420. 1991. Uribe M, Passarell L, Arista J , et al: The liver in AlDS patients. Usefulness of liver biopsy. Rev Invest Clin 3 9 : 3 5 4 0 , 1987. Krogsgaard K, Lindhardt BO, Nielsen JO, et al: The influence of HTLV-Ill infection on the natural history of hepatitis B virus infection in male homosexual HBsAg carriers. Hepatology 7:37-41, 1987. Kustgi VK. Hoofnagle JH, Gerin GL, et al: Hepatitis B virus infection in the acquired immunodeficiency syndrome. Ann Intern Med 101 :795-797, 1984. Perillo RP, Regenstein FG, Roodman ST: Chronic hepatitis B in asymptomatic homosexual men with antibody to the human immunodeficiency virus. Ann Intern Med 105:382-383, 1986. Goldin RD, Fish DE, Hay A, et al: Histological and immunohistochemical study of hepatitis B virus in human immunodeficiency virus infection. J Clin Pathol 43;203-205, 1990. Gerber MA. Thung SN: Molecular and cellular pathology of hepatitis B. Lab Invest S2:572-588, 1985. McDonald JA, Harris S , Waters JA. Thomas HC: Effect of human immunodeficiency virus (HIV) infection of chronic hepatitis B hepatic viral antigen display. J Hepatol 4:337-342. 1987. Dienes H. Popper H. Arnold W. Lobeck H: Histological detection in human hepatitis non-A non-B. Hepatology 2:562571, 1982. Grippon P. Ribiere 0, Cadranel JF. et al: Long-term delta antigenemia without appearance of delta antibody in two immunodeficient patients. (Letter.) Lancet 2: 103 1 , 1987. Martin P, Di Bisceglie AM, Kassianides C, et al: Non-A nonB hepatitis leads to rapidly progressive liver disease in patients with human immunodeficiency virus infection. (Abstr.) Gastroenterology 96: A200. 1989. Libanore M, Bicocchi R. Sighinolfi L. Ghinelli F: Fulminant NANB hepatitis in a patient with AIDS: A possible demonstration of direct hepatic injury by the viruses involved'? (Letter.) Infection 16:255, 1988. Macher AM, Reichert CM. Strauss SE, et al: Death in the AlDS patient: Role of cytomegalovirus. (Letter.) N Engl J Med 309: 1454, 1983. Snover DC, Horowitz CA: Liver disease in cytomegalovirus mononucleosis: A light microscopical and immunoperoxidase study of six cases. Hepatology 4:408-412. 1984. Bach N. Thung SN, Pervez F, Schaffner F: Comparison of immunohistochemistry vs in-situ hybridization for detection of CMV. (Abstr.) Gastroenterology 94:573A, 1989. Krilov LR. Rubin LG. Frogel M, et al: Disseminated adenovirus infection with hepatic necrosis in patients with human immunodeficiency virus infection and other immunodeficiency states. Rev lnfect Dis 12:303-307, 1990. Duffy LF, Daum F, Kahn E, et al: Hepatitis in children with acquired immune deficiency syndrome. Gastroenterology 90: 173-81, 1986. Thung SN. Gerber MA, Benkov KJ, et al: Chronic active hepatitis in a child with HIV infection. Arch Pathol Lab Med 112:914-16, 1988. Kamani N, Lightman H, Leiderman I. Krilov LR: Pediatric acquired immunodeficiency syndrome-related complex: Clinical and immunologic features. Pediatr Infect Dis J 7:383-388, 1988. Zimmerli W, Bianchi L, Gudat F, et al: Disseminated herpes simplex type-2 and systemic candida infection in a patient with previous asymptomatic human immunodeficiency virus infection. (Letter). J Infect Dis 157:597-598, 1988. MacSween RN, Anthony PP, Scheuer PJ (Eds): Pathology of

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the liver (2nd ed) London, Churchill-Livingstone. 1987. pp 225-228. Be~ssnerRS. Rappaport FS, Diaz JA: Fatal case of EpsteinBarr virus-induced lymphoproliferative disorder associated with a human immunodeficiency virus infection. Arch Pathol Lab Med 1 1:250-253. 1987. Horsburgh CR. Mason UG, Farhi DC, et al: Disseminated infection with mycobacterium avium- intracellulare. A report of 13 cases and a review of the literature. Medicine (Baltimore) 64:36-48, 1985. Orenstein MS. Tavitan A, Yonk B, et al: Granulomatous involvement of the liver in patients with AIDS. Gut 26:12201225, 1985. Glatt AE, Chirqwin K, Landcsman SH: Treatn~cntof infcctions associated with human immunodeficicncy vlrus. N Engl J Med 318:1439-1448. 1988. Selwyn PA. Hartel D. Lewis VA, et al: A prospcctivc study of the risk of tuberculosis among intravenous drug abuscrs with human immunodeficiency virus infection. N Engl J Med laochim HI.: Hiopsy diagnosis in human immunodeficiency virus infection and acquired immunodeficiency syndrome. Arch Pathol Lab Mcd 114:284-294, 1990. Prego V, Glatt AE, Roy V. ct al: Comparative analysis of blood culture for fungi and mycobactcria. liver biopsy and bonc marrow biopsy in thc diagnosis of fever of undetermined origin in human immunodeficicncy virus-infected patients. Arch lntern Mcd 150:333-336, 1990. Relman DA, Louht JS, Schmidt TM. et al: The agent of bacillary angiomatosis: An approach to the identification of uncultured pathogens. N Engl J Med 323:1573-1580, 1990. Slater LN, Welch DF. Hensel D. Coody DW: A newly recognized fastidious gram-negative pathogen as a cause of fever and bacterem~a.N Engl J Med 323: 1587-1593, 1990. Perkocha LA, Geaghan SM. Yen TSB. et al: Clinical and pathologic features of bacillary peliosis hepatis in association with human immunodeficiency virus infection. N Engl J Med 323:1581-1586. 1990. Schwartzrnan WA. Marchevsky A. Meyer RD: Epithelioid angiomatosis or cat-scratch disease with splenic and hepatic abnormalities in AIDS: Case report and review of the literature Scand J Infect Dis 22:121-133, 1990. Sachs JR, Greenfield SM. Sohn M. Turner JL: Disseminated pncumocystis carin~iinlcction in a patient with the acquired immune deficiency syndrome. Am J Gastroenterol 86:82-85. 1991. Grimes MM, LaPook JD, Bar MH, et al: Disseminated pneumocystls carini~~nfectionin a patient with immunodeficiency syndrome. Hum Pathol 18:307-308. 1987. Hagopian WA. Huseby JS: Pneumocystis hepatitis and choroiditis despite successful aerosolized pentamidine pulnlonary prophylaxis. Chest 96349-5 I , 1989. Terada S. Reddy KR, Jeffers LJ, et al: Microsporidian hepatitis in the acquired immunodeficiency syndrome. Ann lntern Med 107:61-62, 1987.

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Reichert CM, O'Leary TJ, Leven DL. et al: Autopsy pathology in the acquired immune deficiency syndrome. Am J Pathol 12:357-382, 1983. Friedman SL: Gastrointestinal and hepatobiliary neoplasms in AIDS. Gastroenterol Clin North Am 17:465-486, 1988. Knowles DM. Chamulak GA, Subar M, et al: Lymphoid neoplasia associated with the acquired immunodeficiency syndrome (AIDS). Ann lntern Med 108:744-753, 1988. Ziegler JL. Beckstead JA. Volderding PR, et al: Non-Hodgkin's lymphoma in 90 homosexual men: Relation to generalized lymphadenopathy and the acquired immunodeficiency syndrome. N Engl J Med 31 1:565-570, 1984. Caccamo D, Pervez NK, Marchevsky A: Primary lymphoma of the liver in the acquired immunodeficiency syndrome. Arch Pathol Lab Med 110:553-555, 1986. loachim HL. Cooper MC, Hellman GC: Hodgkin's disease and the acquired immunodeficiency syndrome. (Letter). Ann Intern Med 10 1 :876-877. 1984. Scheib RG, Siegel RS: Atypical Hodgkin's disease and the acq u ~ r e dimmunodeficiency syndrome. (Letter). Ann Intern Med 102:554. 1985. Richman DD, Fischl MA, Grieco MH. et al and the AZT Collaborative Working Group: The toxicity of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS-related complex. N Engl J Med 317:192-197. 1987. Dubin G , BraKman MN: Zidovudine-induced hepatotoxicity. Ann Intern Med 110:85-86, 1989. Gordin FM. Simon GL, Wofsky CB, et al: Adverse reactions to trimelhoprim-sulfamethoxazole in patients with the acquired immunodeficiency syndrome. Ann Intern Mcd 100:495-499. 1984. Schaffner F: The liver in HIV infection. Prog Liver Dis 9 5 0 5 522. 1990. Kew Lai K. Gang DL. Zawacki JK. Cooky TP: Fulminant hepatic failure associated with 2'3'-dideoxyinose (ddl). Ann lntern Med 115:283-284. 1991. Corner GM, Mukerjee S. Scholes JV. et al: Liver biopsies in the acquired immune deficiency syndrome: Influence of endemic disease and drug abuse. Am J Gastroenterol 84: 15251531. 1989. Shavin RE. Walsh TJ, Pollack AD: Late generalized tuberculosis: A clinical pathologic analysis and comparison of 100 cases in the periantibiotic and antibiotic eras. Medicine (Baltimore) 59:352-366, 1980. Alvarej. S. McCabe WR: Extrapulmonary tuberculosis revis~ t e d :A review of experience at Boston City and other hospitals. Med~cine(Baltimore) 63:25-55, 1984. Devars du Mayne JF, Marche C , Penalba C , et al: Hepatic lesions in acquired immunodeficiency: A study of 20 cases. Presse Med l 4 : l l 7 7 - I l 8 0 , 1985. Cappell MS, Schwartz MS. Biempica L: Clinical utility of liver biopsy in patients with serum antibodies to the human immunodeficiency virus. Am J Med 88:123-130, 1990.

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Hepatic histopathology in the acquired immunodeficiency syndrome.

Involvement of the liver with the same opportunistic organisms and neoplasms affecting other organs has been recognized since the beginning of the AID...
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