Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Porphyrias are divided into erythropoietic and hepatic manifestations. Erythropoietic porphyrias are characterized by cutaneous symptoms and appear in early childhood. Erythropoietic protoporphyria is complicated by cholestatic liver cirrhosis and progressive hepatic failure in 10%, of patients. Acute hepatic porphyrias (delta-aminolaevulinic acid dehydratase deficiency porphyria, acute intermittent porphyria, hereditary coproporphyria and variegate porphyria) are characterized by variable extrahepatic gastrointestinal, neurological-psychiatric and cardiovascular manifestations requiring early diagnosis to avoid life-threatening complications. Acute hepatic porphyrias are pharmacogenetic and molecular regulatory diseases (without porphyrin accumulation) mainly induced by drugs, sex hormones, fasting or alcohol. The disease process depends on the derepression of hepatic delta-aminolaevulinic acid synthase following haem depletion. In contrast to the acute porphyrias, nonacute, chronic hepatic porphyrias such as porphyria cutanea tarda are porphyrin accumulation disorders leading to cutaneous symptoms associated with liver disease, especially caused by alcohol or viral hepatitis. Alcohol, oestrogens, haemodialysis, hepatitis C and AIDS are triggering factors. Porphyria cutanea tarda is the most common porphyria, followed by acute intermittent porphyria and erythropoietic protoporphyria. The molecular genetics of the porphyrias is very heterogenous. Nearly every family has its own mutation. The mutations identified account for the corresponding enzymatic deficiencies, which may remain clinically silent throughout life. Thus, the recognition of the overt disorder with extrahepatic manifestations depends on the demonstration of biochemical abnormalities due to these primary defects and compensatory hepatic overexpression of hepatic delta-aminolaevulinic acid synthase in the acute porphyrias. Consequently, haem precursors are synthesized in excess. The increased metabolites upstream of the enzymatic defect are excreted into urine and faeces. The diagnosis is based on their evaluation. Primary enzymatic or molecular analyses are noncontributary and may be misleading. Acute polysymptomatic exacerbations accompany a high excretory constellation of porphyrin precursors delta-aminolaevulinic acid and porphobilinogen. Homozygous or compound heterozygous variants of acute hepatic porphyrias may already manifest in childhood.
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PMID:Erythropoietic and hepatic porphyrias. 1111 26

The relationship between grade of pulmonary hypertension and factors associated with human immunodeficiency virus among patients with HIV infection is poorly documented. This report documents the most extensive attempt made thus far to determine whether a relationship exists between degree of pulmonary hypertension and the following conditions: HIV risk factor, degree of immunosuppression, presence or absence of AIDS, and presence or absence of liver cirrhosis. A retrospective study involving a search of the published literature on primary pulmonary hypertension among HIV cases from 1987 to 1998, using the Medline and Aidsline databases was conducted. Patients for whom secondary causes of pulmonary hypertension could be excluded were selected, and the following information for each was recorded: age, gender, risk factors for HIV infection, HIV disease stage according to the Centers for Disease Control, previous opportunistic and neoplastic diseases, CD4+ cell count (cells/L), presence or absence of liver cirrhosis, pulmonary systolic artery pressure level, and lung pathology specimens. Information about the patient's survival time was also recorded. Seventy-six patients were judged to have primary pulmonary hypertension and were included in the study. While no correlation was found between pulmonary systolic artery pressure level and CD4+ cell counts, a statistically significant difference was found between HIV-positive patients with and without AIDS as determined by the Centers for Disease Control criteria with regard to the degree of pulmonary hypertension, expressed as pulmonary systolic artery pressure level (85.4 +/- 17 mm Hg vs 71.8 +/- 15 mm Hg, p < 0.013). Although a higher PAPS was present in HIV cirrhotic patients, a statistically significant difference was not found between degree of pulmonary hypertension and evidence of hepatic cirrhosis (85 +/- 21 mm Hg vs 73.1 +/- 15 mm Hg, p < 0.062). Patients with AIDS and primary pulmonary hypertension present a higher degree of pulmonary hypertension than non-AIDS patients. Pulmonary hypertension associated with HIV seems to be related to a cytokine-related stimulation and proliferation of endothelium. High levels of cytokines present in AIDS patients can favor pulmonary hypertension, but the role of a host response to HIV--determined by one or more HLA subtypes--is suspected to enhance high cytokine production levels.
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PMID:Primary pulmonary hypertension in HIV patients: a systematic review. 1120 29

Redox processes have been implicated in various biologic processes, including signal transduction, gene expression, and cell proliferation, and several molecules have been identified as redox regulators in cell activation. Glutathione is the oldest and most investigated molecule among them. Although details of the mechanisms by which glutathione regulates various aspects of cell biology remains to be characterized, the relationship between immunodeficiency and cellular glutathione status is well established. Redox dysregulation contributes to the pathogenesis of acquired immunodeficiency syndrome (AIDS). Human immunodeficiency virus (HIV)-infected patients and simian immunodeficiency virus (SIV)-infected rhesus macaques have, on the average, significantly decreased plasma cysteine and intracellular glutathione levels. Liver contains abundant levels of reducing factors. However, glutathione levels in serum and peripheral blood mononuclear cells of cirrhosis patients are lower compared to values detected in healthy individuals. In the present article, the significance of glutathione in regulating the functions of lymphocytes, especially those of liver-associated lymphocytes, has been described. A novel strategy for immune therapy of liver neoplasms with the use of redox-modulating agents has been proposed.
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PMID:Liver immunity and glutathione. 1122 52

Several studies have suggested that the progression of hepatitis C virus (HCV) infection is more severe in patients infected by the human immunodeficiency virus (HIV). Two national retrospective multicenter cohort surveys were performed in France that included 17,487 HIV-infected patients during 1995 and 26,497 during 1997. The following data was evaluated: total number of deaths; number of deaths linked to AIDS, cirrhosis, or hepatocellular carcinoma (HCC); and number of deaths related to other (non-HCV--linked) causes. In 1995, the causes of death were as follows: AIDS, 1307 (7.47%); cirrhosis or HCC, 21 (0.12%); and other (non-HCV--linked) causes, 99 (0.56%). In 1997, the causes of deaths were as follows: AIDS, 459 (1.73%); cirrhosis or HCC 36 (0.13%); and other (non-HCV--linked) causes, 48 (0.18%). Comparative results between the 1995 and 1997 surveys showed a dramatic decrease in AIDS-related mortality rates (7.47% vs. 1.73%; P<.001) but not in HCV-related mortality rates (0.06% vs. 0.07%; P=.79). In France, despite the high prevalence of HCV infection in HIV-positive patients, the mortality rate in 1995 and 1997 caused by HCV-related cirrhosis or HCC was low.
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PMID:Mortality among human immunodeficiency virus-infected patients with cirrhosis or hepatocellular carcinoma due to hepatitis C virus in French Departments of Internal Medicine/Infectious Diseases, in 1995 and 1997. 1164 33

We performed limited autopsy with histological examination of tissue cores obtained percutaneously using the Tru-Cut needle and the Jamshidi trocar in 150 adult HIV-positive patients. Data were compared retrospectively with the antemortem clinical diagnosis. Eighty-one percent of the patients were male, and 78% were intravenous drug users. Specimens were obtained from the brain, liver, lung, bone marrow, and kidney of most patients. The main findings included liver cirrhosis in 22 cases (associated with HCV infection in 81%), Pneumocystis carinii pneumonia in 21, Cytomegalovirus (CMV) infection in 19, Mycobacterium avium-intracellulaire (MAI) infection in 17, bacterial pneumonia in 14, tuberculosis in 12, and lymphoma in 13 cases. Forty-six (30.6%) patients had at least one clinical diagnosis that was confirmed by autopsy, i.e., there was 40.6% agreement between pre- and postmortem findings. Forty-six (30.6%) patients had at least one clinical diagnosis that was not confirmed at autopsy, whereas 41 (27.3%) had at least one AIDS-related or unrelated disease that was not suspected clinically. The results obtained by limited autopsy are principally comparable to those achieved by full necropsy, with the advantages of decreasing the contagious risk, saving cost and time, including a rapid final diagnosis, and easily obtaining the consent for postmortem examination so that necropsy studies may be performed on a larger number of patients, thus contributing to a better understanding of the spectrum of HIV infection in our environment.
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PMID:Value of limited necropsy in HIV-positive patients. 1179 36

The involvement of the gastrointestinal tract in the co-infection of HIV and Leishmania is rarely reported. We report the case of an HIV-infected adult man co-infected with a disseminated form of leishmaniasis involving the liver, lymph nodes, spleen and, as a feature reported for the first time in the English literature, the pancreas. Light microscopy showed amastigote forms of Leishmania in pancreatic macrophages and immunohistochemical staining revealed antigens for Leishmania and also for HIV p24. Microscopic and ultrastructural analysis revealed severe acinar atrophy, decreased zymogen granules in the acinar cytoplasm and also nuclear abnormalities such as pyknosis, hyperchromatism and thickened chromatin. These findings might correspond to the histologic pattern of protein-energy malnutrition in the pancreas as shown in our previous study in pancreas with AIDS and no Leishmania. In this particular case, the protein-energy malnutrition may be due to cirrhosis, or, Leishmania or HIV infection or all mixed. We believe that this case represents the morphologic substratum of the protein energy malnutrition in pancreas induced by the HIV infection. Further studies are needed to elucidate these issues.
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PMID:Pancreatic involvement in co-infection visceral leishmaniasis and HIV: histological and ultrastructural aspects. 1134 Apr 79

High concentrations of nitric oxide (NO) are generated by the inducible form of the enzyme nitric oxide synthase (iNOS), which is expressed in activated macrophages and in hepatocytes. Increased expression of iNOS in hepatocytes or macrophages might be expected in chronic HCV liver disease and HIV infections. This might in turn be reflected in increased serum NO levels in these two conditions. In view of the discrepant findings in published reports, we measured serum NO levels in a large number of chronic HCV-infected patients and patients with chronic HIV infections with or without AIDS-related opportunistic infection. We also localized HCV and iNOS antigens by immunohistochemistry, in liver biopsy tissue from patients with chronic HCV-related hepatitis, HCV-related cirrhosis, and HCV-related hepatocellular carcinoma. A group of 121 subjects with serological evidence of HCV with or without HIV infection were studied. These were compared with 14 controls without HIV or HCV disease (group A). Among the subjects with HCV, 35 were negative for HIV (group B), 66 were HIV positive (group C), and 20 had AIDS-related opportunistic infection (group D). The serum NO concentration was determined by the Brucine method. A well-characterized commercially available antibody (HCV88) directed against a synthetic NS3 peptide fragment of HCV, which localizes to the hepatocyte nuclei, and an antibody to human macrophage iNOS, were both used to detect these proteins in liver biopsy tissue by immunohistochemistry. Mean serum NO values in HIV negative/HCV negative control patients (group A) (54.6+/-12 microM) were similar to those in HIV negative/HCV positive patients (group B) (55.0+/-13 microM) and HIV positive without AIDS-related disease/HCV positive patients (group C) (47.2+/-25 microM). By contrast, the mean serum NO (70.1+/-24 microM) was significantly increased in HCV-positive patients with AIDS-related infection (group D) compared to controls (P = 0.02). HCV NS3 and iNOS antibody staining hepatocytes were not detected in any of the control non-HCV-infected biopsy samples. In early chronic HCV hepatitis (fibrosis scores F0-F2), HCV NS3 antigen localized focally to only a small number of hepatocytes. In cirrhosis (fibrosis score F4) with or without hepatocellular carcinoma, the majority of hepatocyte nuclei stained positively with HCV NS3 antibody. The majority of hepatocytes in chronic HCV hepatitis expressed iNOS, irrespective of histological disease severity. The staining was present uniformly in the cytoplasm. In chronic HCV and HIV coinfection, the pattern and number of iNOS staining cells were similar to that in patients with chronic HCV infection alone. In conclusion, there is widespread expression of iNOS in hepatocytes in chronic HCV liver disease, irrespective of liver disease stage. However, elevated NO levels in serum were related only to active AIDS-related bacterial, protozoan, and fungal infections, rather than to chronic viral infection with HCV or HIV alone. NO may play a role in the local control of chronic viral infections at tissue level, but this is not reflected in serum levels.
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PMID:Nitric oxide and chronic HCV and HIV infections. 1134 51

Thrombopoietin (TPO) is primarily produced by hepatocytes and regulates the production and differentiation of megakaryocytes and platelets in the bone marrow. The endogenous TPO level is increased when the megakaryocyte count is low, and high in aplastic anaemia and after myeloablative chemotherapy. TPO is cloned and manufactured by a recombinant technique for clinical use. Treatment with recombinant human TPO (rhTPO) after intensive chemotherapy may reduce the need for platelet transfusions. Administration of granulocyte colony-stimulating factor in combination with rhTPO has enhanced the mobilisation and harvest product of haematopoietic stem cells. Whether rhTPO is effective in the treatment of the myelodysplastic syndrome, aplastic anaemia, and other conditions with bone marrow insufficiency (including AIDS) is not yet known. In liver cirrhosis, the endogenous TPO level rapidly increases after liver transplantation. Accordingly, substitution of rhTPO may be indicated in advanced liver failure complicated by thrombocytopenia and bleeding.
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PMID:[Clinical use of recombinant human thrombopoietin. Status and perspectives]. 1136 Mar 68

The First International Conference on Therapies for Viral Hepatitis, held in December 1995, brought together researchers, clinicians, and pharmaceutical manufacturers devoted to finding more effective ways to treat several varieties of hepatitis. Hepatitis B (HBV) affects an estimated 300 to 350 million people; up to 25 percent of that number will die of liver cirrhosis or hepatocellular carcinoma. The only currently available treatment is interferon, which is effective in only forty percent of the cases and has dose-limiting side effects. Nucleoside analog drugs have gained increasing attention because of their use in treating opportunistic infections in HIV-positive patients. Hepatitis C (HCV) affects only 75 to 100 million but is potentially more dangerous, since 85 percent of those with the disease will develop persistent and chronic liver infections and 70 percent will develop chronic liver disease. Hepatitis D (HDV) requires HBV for its replication cycle, and appears to respond to treatment for HBV. However, interferon is not effective in cases where the patient has both HBV and HDV. Hepatitis G (HGV) causes transfusion-associated non-ABC hepatitis with mild symptoms, and it is unclear if HGV causes chronic liver disease. Regimens for chronic viral hepatitis are desperately needed.
J Int Assoc Physicians AIDS Care 1996 Feb
PMID:First International Conference on Therapies for Viral Hepatitis. 1136 35

Dr. Douglas Dieterich, a gastroenterologist and Associate Professor of Medicine at New York University School of Medicine, is a director of a American Foundation for AIDS Research-sponsored clinical trial for people with hepatitis C and HIV. Dr. Dieterich suggests that individuals who use intravenous drugs, those with a family history of hepatitis C, or those who received a blood transfusion prior to 1990 get a hepatitis antibody test followed by a hepatitis C PCR test to detect the infection. Up to 40 percent of HIV-positive individuals also have hepatitis C, however many patients go undiagnosed. Dr. Dieterich recommends a more aggressive treatment approach for HIV-positive individuals, including a liver biopsy to determine the degree of cirrhosis. The Food and Drug Administration (FDA) advises that patients who were previously treated for hepatitis C with alpha interferon alone should be re-treated with interferon plus ribavirin. However, caution must be used in treating people with advanced hepatitis, who will initially worsen with interferon treatment. Patients with coronary artery disease need to have a stress test prior to taking ribavirin. Side effects experienced with alpha interferon are numerous but not serious and are manageable with non-prescription medicines. According to Dr. Dieterich, choosing a physician to treat hepatitis C should not be limited to gastroenterologists, but should also include specialists in infectious diseases, internists, and primary care physicians specializing in HIV.
AIDS Treat News 1998 May 15
PMID:Hepatitis C important treatment advance: interview with Douglas Dieterich, M.D. Interview by John S. James. 1136 6


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