Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0008370 (cholestasis)
 9,378 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although the liver is particularly exposed to drugs and their metabolites, hepatic side-effects of antibiotics are far less frequent than other adverse effects such as gastrointestinal disorders or cutaneous reactions. However, the potential severity of hepatic side-effects for some drugs is stressed. Antibiotic related liver injuries cover most of the clinical and pathological expressions of hepatic dysfunction, including cytotoxic hepatitis (isoniazid), intrahepatic cholestasis (macrolides, penicillins, clavulanic acid), mixed hepatitis (sulphonamides), chronic active hepatitis (nitrofurantoin), or microvesicular steatosis (tetracycline). In most cases, toxicity is idiosyncratic, reactions occurring only in some susceptible individuals. The mechanisms underlying toxicity may be primarily metabolite-dependent (isoniazid), hypersensitivity-mediated (beta-lactams), or result from both processes (sulphonamides, erythromycin derivatives). In some cases, the liver is not the primary target organ for toxicity but appears to mediate the clinical expression of some adverse effects induced by antibiotics. The most significant example of this is hypoprothrombinaemia due to the inhibition of hepatic gamma-carboxylation of vitamin K-dependent clotting factors by sulphydryl group-containing cephalosporins. Inhibition of bilirubin conjugation or transport by rifampicin or fusidic acid may also be viewed as hepatic side-effects of antibiotics. Ascertaining the casual relationship of a given drug to an hepatic adverse effect may prove particularly difficult, because of the potential contribution of host status and concurrent medications. Diagnosis is based mainly on circumstantial evidence, i.e. the temporal relationship between drug administration (or withdrawal) and the time-course of liver dysfunction. Improving morbidity related to drug hepatotoxicity relies on a free flow of information between manufacturers and practitioners in order to optimize detection of potentially serious liver damage, and advances in pharmacogenetics toward a better identification of those at particular risk for developing drug-related liver toxicity.
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PMID:Hepatic side-effects of antibiotics. 804 Jan 6

Liver disease occurring in pregnancy can be categorized into three groups. The first group includes diseases unique to pregnancy and caused by it. Among these are hyperemesis gravidarum, cholestasis of pregnancy, and disorders associated with preeclampsia. Liver involvement may be expected in 50% of patients with hyperemesis gravidarum. Preeclampsia has been associated with both the HELLP syndrome (hemolysis, elevated liver tests, and low platelets), which includes hepatic infarction and rupture, and with acute fatty liver of pregnancy (AFLP). In patients with HELLP syndrome, liver test abnormalities do not correlate with liver injury. Therefore, this and other disorders associated with preeclampsia require aggressive treatment, primarily with delivery. The second group of liver diseases are those exacerbated by pregnancy. Viral infections involving the liver that are usually benign, such as hepatitis E and herpes simplex, are more likely to be exacerbated in pregnant women and are more likely to lead to fulminant hepatic failure. Cholelithiasis and Budd-Chiari syndrome are more prevalent in pregnant women. The third group is comprised of liver diseases that are preexisting in the pregnant patient and includes autoimmune chronic active hepatitis and Wilson's disease. The number of patients in the last group is small, as chronic liver disease is rare in women who are able to bear children.
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PMID:Hepatic disease in pregnancy. 810 83

This study was carried out to evaluated the role of the fibronectin (FN) in chronic liver diseases. For these reasons FN plasmatic concentration was assayed in patient with different degrees of chronic liver disease. For these reasons FN plasmatic concentration was assayed in patient with different degrees of chronic liver disease; the correlation between FN and the most common parameters of liver function was also evaluated. Moreover we also correlated FN plasma levels with laminin and the N-terminale peptide of type III procollagen, serum levels, that are through to be markers of fibrogenesis. 172 patients were studied: twenty-one patients suffering from chronic persistent hepatitis (CPH), 45 from chronic active hepatitis (CAH) and 106 from liver cirrhosis (LC). Last patients were also divided according the Child-Pugh's classification. Control group was composed of 74 healthy blood donors. Significant reduction of plasmatic levels of FN was found in the LC groups in comparison with control group (p < 0.0001) and also with CPH group (p < 0.01) and with CAH group (p < 0.0001). Lower values of FN were found in the LC group at advanced stage (Child-Pugh's B and C classes). In the group of CAH significant correlations with the parameters of cholestasis (GGT, APh, Tot. Bil. p < 0.005) were found, while in the group of LC significant correlations both with the parameters of synthesis (Alb. and Protr. time p < 0.01) and necrosis (AST/ALT p < 0.001). A negative correlation was also found between FN and spleen volume (p < 0.05). No correlation between FN and the parameters of fibrosis was found.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Plasma fibronectin in chronic liver diseases]. 821 Jun 24

The patterns of hepatic injury were studied in 100 patients with a diagnosis of sarcoidosis and clinical evidence of liver disease that led to diagnostic liver biopsy. Granulomas were present in all patients; they occupied from < 1% to > 90% of the total volume of tissue examined and were most often located in the portal/periportal region. In none of the 100 cases were infectious organisms identified by special stains, culture, or serology. In 99% of cases, these granulomas were noncaseating; in one of the 100 cases central caseation was noted. In addition to the granulomas present in all biopsies, three broad categories of histologic change were found: cholestatic (58%), necroinflammatory (41%), and vascular (20%). Among those with cholestasis, 19 patients had bile duct lesions similar to primary biliary cirrhosis, whereas another 13 had a pattern of periductal fibrosis reminiscent of primary sclerosing cholangitis. In 37 patients with chronic cholestasis, a decrease in the number of bile ducts (ductopenia) was noted. Twelve patients had an acute cholangitis suggestive of mechanical obstruction--although no clinical evidence of ductal obstruction was found. Necroinflammatory changes included spotty necrosis suggesting hepatitis of diverse etiologies (including viral infection and drug reaction) and chronic portal inflammation suggestive of chronic active hepatitis. Vascular changes consisted of sinusoidal dilatation (14 cases) and nodular regenerative hyperplasia (9 cases). In 6% of the patients, the only changes in the biopsy were those of granulomatous inflammation; each of these patients had a dominant mass ("sarcoidoma"), which had been biopsied to rule out tumor. Fibrosis was seen in 21% of the biopsies--periportal (13%), bridging (2%), or cirrhosis (6%). It is clear that sarcoidosis can cause progressive liver disease with a wide array of histologic features that can mimic those of other primary liver diseases.
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PMID:Hepatic sarcoidosis. Clinicopathologic features in 100 patients. 823 35

Liver transplantation of hepatitis B surface antigen (HBsAg)-positive patients has been associated with high morbidity and mortality secondary to hepatitis B (HB) recurrence in the graft. Eight patients of the Queensland Liver Transplant Service were HBsAg positive pretransplant. Six acquired HB infection of the graft, one developed serological recurrence of HB before early death from sepsis, and one HB e antigen-negative patient permanently cleared the virus. HB-infected grafts showed early expression of viral antigen, acute hepatitis, fibrosing cholestatic hepatitis, chronic active hepatitis, cirrhosis, or minimal changes associated with a carrier state. Only in the latter case was HB mild and nonprogressive. Cases of fibrosing cholestatic hepatitis progressed rapidly to liver failure; they showed fibrosis and plates of ductular epithelium extending from portal tracts into lobules, cholestasis, ballooning of hepatocytes, and prominent hepatocyte expression of viral antigens. Perioperative HB immunoglobulin proved ineffective in preventing HB recurrence. One other patient became HBsAg positive for the first time after retransplantation; he developed severe acute hepatitis, then chronic active hepatitis. Our biopsy findings support the view that, in liver allografts, the HB virus may be directly cytopathic.
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PMID:Hepatitis B virus infection in liver allografts. 831 8

Fasting serum levels of glycocholic acid were measured in 142 patients with benign diffuse liver diseases. A total of 63.4% of the whole group of patients, 86.6% of the cirrhotic patients and 31.7% of the noncirrhotic patients had increased serum levels of glycocholic acid. There were significant correlations with blood liver tests associated with liver disease severity such as prothrombin activity and albumin. There were highly significant differences in glycocholic acid levels according to the histological severity of the liver disease, especially when patients with cirrhosis or chronic active hepatitis were compared to the remaining patients and controls. However, discriminant analysis showed that prothrombin activity and albumin were better than glycocholic acid in predicting the histological severity of liver disease. Glycocholic acid serum levels were relatively independent of cholestasis and cytolysis and appeared to be more linked to liver dysfunction. In conclusion, fasting glycocholic acid measurement can be useful in the evaluation and follow-up of liver diseases as a marker of histological severity, and used in addition to other liver tests.
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PMID:Clinical value of the determination of fasting glycocholic acid serum levels in patients with liver diseases. A comparison with standard liver tests. 850 Jul 13

Proliferation of preexisting bile ducts, ductular metaplasia of hepatocytes and proliferation and differentiation of liver stem cells are discussed in the pathogenesis of neoductular structures in the liver. Under the condition of experimental bile duct obstruction and in extrahepatic bile duct stenosis neoductular structures are first the result of proliferation and sprouting of preexisting ducts and cholangioles. Especially in later stages of cholestasis but also in other chronic progredient liver diseases such as chronic alcoholic liver disease and chronic active hepatitis periportal hepatocytes may show a phenotypic shift towards ductular epithelia. In postnatal liver diseases hepatocytes first express keratin 7 and later keratin 19 during ductular transdifferentiation. This is in contrast to embryonal cholangiogenesis. In alpha-1-antitrypsin-deficiency, hemochromatosis, Wilson's disease, and chronic active hepatitis B cellular deposites typically located in hepatocytes such as alpha-1-AT, siderin, copper, HBs-Ag, and HBc-Ag can also be found in neoductular cells close to hepatocytes. These deposites seem to be retained during the ductular transdifferentiation of hepatocytes. Expression of bile duct-type integrin subtypes and TGF beta 1 in neoductular cells are involved in the changing parenchymal/mesenchymal interplay during neoductogenesis, resulting in periductular basal membrane and periductular fibrosis. In FNH the ductular transdifferentiation of hepatocytes is integrated in the histogenesis of micronodules and portal tract equivalents of these tumor-like lesions. Ductular structures in hepatoblastomas and especially in combined hepatocellular and cholangiocarcinomas (CHCC) may reflect the common embryologic derivation of hepatocytes and biliary epithelia. Non-neoplastic liver tissue in resection specimens of our CHCC showed a lower rate of cirrhosis, and a significantly higher Ki 67-LI of neoductular cells compared to liver tissue in resection specimens of HCC and liver metastases. 3 of 10 CHCC had developed in alpha-1-AT-deficiency, in which this protease-inhibitor was predominantly retained in periportal hepatocytes. These findings in non-neoplastic tumor-bearing liver tissue suggest that CHCC include a special histogenic type of primary liver carcinoma which in analogy to some experimental liver tumors might develop from periportal parenchymal cells.
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PMID:[Hepatic neoductules]. 860 Jun 93

Use of long-term total parenteral nutrition (TPN) is often presumed to be associated with serious hepatic dysfunction. In this retrospective study, we reviewed the complete charts of patients who had received TPN for more than 2.5 years, starting in infancy or childhood, for evidence of liver dysfunction. There were 16 male and 10 female patients with a total of 254.5 patient years on TPN. Seventeen patients have been on TPN since birth or early infancy. Thirteen of 26 patients derive > or = 90% of their calorie intake from TPN. Six patients had hepatomegaly; two of them also had splenomegaly. Twenty-one patients had normal transaminases, nine have had past episodes of raised enzymes ranging from 2.5 to 7.5 times normal. Seventeen patients always had normal bilirubin levels, five had past episodes of hyperbilirubinaemia, while four patients had persistently raised bilirubin levels (range 1.5-20.7 g/dl). Alkaline phosphatase was normal for age in all patients except two. Hepatic synthetic function, as measured by albumin, pre-albumin levels and prothrombin time, was within the normal range in all patients except one. Liver biopsies were performed in eight patients. Two biopsies showed cirrhosis, one showed chronic active hepatitis (CAH) with cholestasis, two patients had fibrosis, one showed cholestasis and two biopsies were normal. One patient with cirrhosis and one with CAH were positive for hepatitis C antibody. Another asymptomatic patient was positive for hepatitis B. Only the patient with CAH had hepatic decompensation. We conclude that clinical hepatic failure is uncommon in our group of patients on long-term TPN for 2.5 years or more. Cirrhosis and fibrosis, when found, could not be solely attributed to TPN.
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PMID:Chronic liver disease in children on long-term parenteral nutrition. 874 28

Asymptomatic chronic HBsAg carriers with normal liver function tests are, in general regarded as having no liver pathology. Most of the histologic findings in asymptomatic chronic carriers have been reported from areas with low incidence of Hepatitis B virus (HBV) infection, such as North America and Western Europe. It is well known that there are many differences in HBV infection between low and high endemic areas, but there have been few reports on the histologic findings of asymptomatic chronic HBsAg carriers from endemic areas. The present study was undertaken in Korea which is one of the endemic areas for HBV infection and was designed to assess the prevalence of chronic liver disease by peritoneoscopic liver biopsy among asymptomatic chronic HBsAg carriers and to make a basis for the follow-up of asymptomatic chronic HBsAg carriers according to the results obtained. One hundred and ten asymptomatic HBsAg-positive carriers with normal liver function tests and no hepatomegaly were included in the study. Final diagnosis by peritoneoscopic liver biopsy revealed that of the 110 asymptomatic carriers only 27 (24.5%) had a histologically normal liver, while 51 (46.4%) had chronic liver diseases, and the remaining 32 (29.1%) had nonspecific histologic abnormalities (nonspecific reactive changes in 18 cases, cholestasis in 6 cases, and fatty change in 8 cases). Of the 51 patients with chronic liver diseases, 3 had liver cirrhosis, 4 chronic active hepatitis with cirrhosis, 11 chronic active hepatitis and 33 chronic persistent hepatitis. The frequency of liver cirrhosis and chronic active hepatitis with cirrhosis was significantly high in the over 30 years of age group (12.1%) than in the under 30 years of age group (0%; p = 0.011 by Fisher's exact test). In conclusion, 46.4% of the Korean asymptomatic chronic HBsAg carriers with normal liver function tests and no hepatomegaly had chronic liver disease. This finding contrasted with reports from low incidence areas of HBV infection. Our results suggest that in endemic areas, a liver biopsy should be considered to assess the status of liver disease in asymptomatic chronic HBsAg carriers even if liver function tests are normal and hepatomegaly is absent, and the result can be used as a basis for the follow-up of each asymptomatic chronic HBsAg carriers.
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PMID:Peritoneoscopic liver biopsy findings in asymptomatic chronic HBsAg carriers with normal liver function tests and no hepatomegaly. 899 61

The aims of this study were to characterize the histological changes observed in 34 accessioned cases of canine chronic hepatitis and to correlate these changes with the clinical pathological data. Cases of chronic hepatitis were subdivided into 6 categories: chronic active hepatitis (10/34), chronic persistent hepatitis (7/32), chronic cholestatic hepatitis (6/34), fibrosing hepatitis with cirrhosis (3/34), chronic cholangiohepatitis (3/34), and miscellaneous secondary hepatitis (5/34). Iron accumulation was a consistent finding in all livers examined. Although all cases of chronic hepatitis had elevated liver enzymes, no correlation was detected between biochemical parameters and the severity of morphologic changes. Similarly, no correlation was detected between rhodanine staining for copper and morphologic or biochemical indicators of cholestasis. However, presence of copper correlated well with reticulo-fibrosis (r = 0.8) and bile duct hyperplasia, suggesting that changes in the hemodynamics of the hepatic acini due to fibrosis could influence storage of copper.
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PMID:Chronic hepatitis: a retrospective study in 34 dogs. 918 2


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