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Query: EC:3.1.3.1 (alkaline phosphatase)
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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. Cytomegalovirus and Cryptosporidium 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.
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PMID:Hepatobiliary complications in patients with human immunodeficiency virus infection. 155 86

Patients with the acquired immune deficiency syndrome (AIDS) frequently develop hepatic dysfunction. Although hepatic injury may indirectly result from malnutrition, hypotension, administered medications, sepsis, or other conditions, the hepatic injury is frequently due to opportunistic hepatic infection, directly related to AIDS. Infection with Mycobacterium avium intracellulare typically occurs in patients with advanced immunocompromise and with systemic symptoms due to widely disseminated infection. In contrast, hepatic tuberculosis often occurs with less advanced immunocompromise. Cytomegaloviral infection may produce a hepatitis. Cytomegaloviral and cryptosporidial infections have been implicated as causes of acalculous cholecystitis and of a secondary sclerosing cholangitis. About 10-20% of patients with AIDS have chronic hepatitis B infection. These patients tend to develop minimal hepatic inflammation and necrosis. The clinical findings in patients with hepatic cryptococcal infection are usually due to concomitant extrahepatic infection. Hepatic histoplasmosis usually develops as part of a widely disseminated infection with systemic symptoms. Hepatic involvement by Kaposi's sarcoma is rarely documented ante mortem because an unguided liver biopsy is an insensitive diagnostic procedure. Patients with non-Hodgkin's lymphoma of the liver typically have lymphadenopathy, hepatomegaly, and systemic symptoms. As a pragmatic approach, patients with liver dysfunction and HIV-related disease should have a sonographic or computerized tomographic examination of the liver. Patients with dilated bile ducts should undergo endoscopic retrograde cholangiopancreatography because opportunistic infection may produce biliary obstruction. Patients with a focal hepatic lesion should be considered for a guided liver biopsy. Patients with a significantly elevated serum alkaline phosphatase level should be considered for a percutaneous liver biopsy. When performed for these indications, liver biopsy will demonstrate a significant disease involving the liver in about 50% of patients with AIDS and in about 25% of patients who are HIV seropositive but who are not known to have AIDS. The clinical impact of a diagnostic biopsy is blunted by a lack of efficacious therapy for many opportunistic infections.
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PMID:Hepatobiliary manifestations of the acquired immune deficiency syndrome. 198 33

We have observed many patients with AIDS who have unexplained marked elevations in serum alkaline phosphatase. To determine the frequency of alkaline phosphatase elevations in patients with AIDS, and to identify diagnoses, medications, and demographic factors associated with such elevations, we conducted a retrospective study of the first 90 consecutive AIDS cases in hospitals affiliated with the University of Colorado Health Sciences Center in Denver, Colorado. We found elevations of alkaline phosphatase in excess of 1,000 IU/L in 17% of consecutive patients with AIDS. This level of elevation was less frequent in patients with Kaposi's sarcoma but there was otherwise no significant association with diagnoses or medications, or transmission categories for AIDS. The majority of the patients with elevations to this level did not have documented opportunistic infections or biliary tract dilatation previously described in the "cholangitis" syndrome in AIDS patients. Other explanations for these elevations for this common laboratory finding may exist.
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PMID:Marked elevations of serum alkaline phosphatase in patients with AIDS. 199 1

Blood serum alkaline phosphatase (AP) level was found elevated in the patients suffering from eczema, neurodermatitis, eczema with large skin sites involved, and in those with trophic ulcers of various origins, as against normal subjects and reference patients with sarcoidosis and Kaposi's sarcoma. Elevated level of the enzyme activity is directly related to exacerbation stage and size of the skin site involved; this level reduced after therapy and this reduction was associated with clinical improvement. No concomitant visceral abnormalities (calculous cholecystitis, liver cirrhosis, or malignant tumors) were detected in the examinees, that might influence the blood serum AP activity.
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PMID:[The alkaline phosphatase activity of the blood serum as a factor reflecting the chronic inflammatory process in the skin in generalized forms of psoriasis, neurodermatitis, eczema and trophic ulcers]. 209 93

Thirty four patients positive for human immunodeficiency virus (HIV) who had lymphadenopathy were investigated using fine needle aspiration. Cytological analysis included immunocytochemical investigation with the alkaline phosphatase-antialkaline phosphatase (APAAP) method. All patients had confirmation of cytological diagnosis by lymph node biopsy. Fifteen aspirates with follicular hyperplasia were evaluated. Eleven patients showed B cell predominance. The B cell population did not show light chain restriction. Ten patients with B cell non-Hodgkin's lymphoma (five with Burkitt's lymphoma and five with B cell immunoblastic lymphoma) were investigated. Nine out of 10 cases were monoclonal with respect to their light chain determinants; only one case with Burkitt's lymphoma with partial lymph node metastasis did not show light chain restriction. The cytological diagnosis included two mycobacterial infections and four cystic lesions. Histological investigation was necessary to diagnose the extent of lymph node disease caused by Kaposi's sarcoma. These findings indicate that the immunocytological investigation of lymph node aspirates is useful for evaluating lymphadenopathy in HIV positive patients.
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PMID:Immunocytochemical analysis of lymph node aspirates in patients with human immunodeficiency virus infection. 222 33

This study reviews data on the histogenesis of Kaposi's sarcoma and angiosarcoma derived from clinical features, histology, electron microscopy, enzyme histochemistry, and immunochemistry of both diseases. Their hemorrhagic clinical appearance contrasts the predominantly lymphatic histologic features of vessels in early lesions. Investigations performed to resolve the debate whether these tumors arise from blood vessel or lymphatic endothelium show remarkably similar results for both conditions. Electron microscopy reveals Weibel - Palade bodies in a minority of cases, but features consistent with less well-differentiated blood vessel endothelium may be seen in a greater proportion of tumors. Enzyme histochemistry generally shows absence of adenosine triphosphatase and alkaline phosphatase in tumor cells; a pattern of enzymes similar to that found in normal lymphatic endothelium. Conflicting data arises from the large number of immunohistochemical studies performed on both conditions. Factor VIII-related antigen and Ulex europaeus agglutinin-I have been most frequently employed, but the specificity of these agents for blood vessel endothelium is debatable. Panendothelial markers show consistent labeling of both tumors, but marker studies employing a wide range of monoclonal antibodies specific for blood vessel endothelium have shown occasional positive labeling of tumor cells. A number of studies have claimed absence of labeling with specific blood vessel monoclonal antibodies, but at present no study employing a specific marker for lymphatic endothelium has been reported. Although the demonstration of specific markers for blood vessel endothelium in these tumors has been variable, the data would be compatible with lesions arising from undifferentiated stem cells that proliferate with varying degrees of differentiation toward blood vessel endothelium. An alternative hypothesis for the histogenesis of Kaposi's sarcoma would be one of multicentric hyperplasia containing lymphatic venular anastamoses with elements of both lymphatic and blood vessel endothelium.
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PMID:Histogenesis of Kaposi's sarcoma and angiosarcoma of the face and the scalp. 266 17

A 44-yr-old homosexual male with symptomatic human immune deficiency virus (HIV) infection presented with abdominal pain, hepatosplenomegaly, and rising serum alkaline phosphatase. Laparoscopy revealed multiple purplish nodules on the surface of the liver. Histopathology of the lesions was consistent with Kaposi's sarcoma. Six weeks later, cutaneous Kaposi's sarcoma became apparent on the head and neck. This case is unusual because, in all previously published cases, with the exception of one, intrahepatic Kaposi's sarcoma was found on autopsy. Moreover, all patients had evidence of extrahepatic Kaposi's sarcoma prior to the documentation of liver involvement.
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PMID:Hepatic involvement as the primary manifestation of Kaposi's sarcoma in the acquired immune deficiency syndrome. 281 78

Clinical data and histologic sections of the liver, including immunohistochemical studies for hepatitis B surface and core antigens, were reviewed in 42 autopsy cases of the acquired immune deficiency syndrome (AIDS). Hepatomegaly, elevation of serum transaminases, and mild elevation of alkaline phosphatase were commonly observed clinical and biochemical abnormalities. Mildly elevated alkaline phosphatase and normal bilirubin levels were present in patients with Mycobacterium avium-intracellulare (MAI) infection, cytomegalovirus (CMV) infection, and Kaposi's sarcoma (KS). Histologic sections demonstrated liver involvement by MAI in eight cases; KS in six cases; cryptococcus in three cases; and CMV in two cases. One case of MAI infection was associated with marked central vein sclerosis, a finding previously unreported. Thirty-two (76%) of 42 cases had serologic or pathologic evidence of hepatitis exposure. Two patients had histologic evidence of chronic active hepatitis. The pathologic processes involving the liver appeared to be secondary to the infections and neoplasms for which this population is susceptible and did not significantly contribute to morbidity or mortality. No findings specific or pathognomic for AIDS were identified in the liver.
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PMID:Clinical and pathologic findings of the liver in the acquired immune deficiency syndrome (AIDS). 298 50

Previous studies utilizing enzyme histochemistry, electron microscopy, and immunohistochemistry have failed to establish the cell of origin in Kaposi's sarcoma. The authors have rigorously tested the prevailing hypothesis that the lesion defined as Kaposi's sarcoma is derived from vascular endothelial cells. They use seven markers to characterize endothelial cells: three antigens (Factor VIII-related antigen, HLA-DR/Ia, macrophage/endothelial antigens), three enzymes (5'-nucleotidase, ATPase, alkaline phosphatase), and lectin binding (Ulex europaeus I). They applied the markers first to normal skin and lymph node, and then to biopsy specimens from 40 patients with Kaposi's sarcoma. Normal blood vessel endothelium was positive for all seven markers, but normal lymphatic endothelium was negative for all of the markers except 5'-nucleotidase and Ulex europaeus lectin. The neoplastic cells in 40 cases of Kaposi's sarcoma closely resembled those of normal lymphatic endothelium but not those of blood vessel endothelium. This suggests that Kaposi's sarcoma may originate in lymphatic endothelium.
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PMID:Evidence for the origin of Kaposi's sarcoma from lymphatic endothelium. 298 60

Up to 30% of patients with acquired immunodeficiency syndrome (AIDS) suffer from Kaposi's sarcoma (AIDS-KS). The histogenesis and neoplastic nature of this tumor is still controversial. We have established cell cultures of KS biopsies from 7 patients with AIDS. All donors were seropositive for the human immunodeficiency virus I (HIV-I), cytomegalovirus (CMV) and hepatitis B virus (HBV). The tumors were histologically shown to be KS. Cell cultures derived from these tumors all expressed the endothelial cell marker BMA 120 antigen. Most of these cultures were positive for acetylated low-density lipoprotein (acLDL) uptake and alkaline phosphatase (AP) expression, and negative for factor-VIII-related antigen (FVIII-RAg). The staining pattern was heterogeneous with respect to number of endothelial cell markers expressed in each culture. We conclude from subcloning experiments that the cultured cells cease to express acLDL receptor and AP, but not the antigen detected by the monoclonal antibody (MAb) BMA 120. The cells grew well in culture up to 50 passages and showed a fibroblast-like morphology. Assays performed to investigate their degree of malignancy revealed a significantly increased passage number under reduced serum conditions as compared to normal fibroblasts but no tumor formation in nude mice. Neither HIV, HBV nor CMV sequences were found in any of the cell lines tested. We conclude that AIDS-KS is an endothelial-cell-derived neoplasm of low malignancy and that HIV, HBV and CMV are not directly involved in its genesis.
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PMID:Cultured, AIDS-related Kaposi's sarcoma cells express endothelial cell markers and are weakly malignant in vitro. 314 Dec 99


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