Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019209 (hepatomegaly)
 5,798 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fifty patients with ulcerative colitis, 24 with Crohn's disease, and 50 controls were studied by liver function tests and abdominal ultrasound scan. Twenty-two percent of ulcerative colitis patients, 29% of Crohn's disease patients, and none of the controls showed abnormal liver function tests. All subjects with abnormal liver function tests also had changes in ultrasound liver scan, consisting of hepatomegaly and/or a dysechoic liver echo pattern. Furthermore, the same ultrasound changes were observed, in the absence of any liver function test abnormalities, in 58% of ulcerative colitis patients, 50% of Crohn's disease patients and 6% of controls (P less than 0.0005, inflammatory bowel disease versus controls). Overall, some evidence of liver involvement, as judged by abnormal liver tests and/or abnormal ultrasound liver scan, was detected in about 80% of inflammatory bowel disease patients. Six patients with minor abnormalities of liver function tests underwent liver biopsy and 5 of them had pericholangitis. Ultrasound liver scan may provide a useful tool to evaluate the occurrence of liver involvement in inflammatory bowel disease patients.
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PMID:Detection of liver involvement in inflammatory bowel disease by abdominal ultrasound scan. 159 85

From 1956 through 1989, 38 men and 26 women were seen at the Mayo Clinic with biopsy-proven AA. The underlying disorder was rheumatic disease in 42, infectious disease in 11, inflammatory bowel disease in 6, and other causes in 5. All patients were symptomatic at the time of diagnosis. Fifty-eight of the 64 patients had proteinuria or renal insufficiency. Fourteen also had significant symptoms of gastrointestinal amyloid, and 6 had amyloid goiter. None of the patients had symptomatic cardiac involvement, and only 3 had palpable hepatomegaly. Renal, gastric, rectal, fat, and marrow biopsies were positive for amyloid in 100%, 94%, 82%, 58%, and 46% of tested patients, respectively. The median survival of the entire group was 24.5 months. Thirty-five of the 47 deceased patients died as a direct result of their amyloidosis, primarily from complications of renal failure. Nine were successfully treated and had regression of the disease. Two with bronchiectasis responded to long-term cyclic antibiotic therapy, as did 1 patient with osteomyelitis. One patient with inflammatory bowel disease responded to surgical resection, and 1 with familial Mediterranean fever responded to colchicine. Four patients with rheumatic disease were treated with cyclophosphamide (in 2) and methotrexate (in 2), with complete resolution of their renal disease. All 9 successfully treated patients are alive, with a median follow-up of 58 months. Statistical analysis revealed that creatinine values greater than or equal to 2.0 mg/dl (P less than 0.003) and a serum albumin value less than 2.5 g/dl (P less than 0.02) were associated with a poorer survival. The single strongest variable associated with poor survival was a serum creatinine level greater than 2 mg/dl at presentation, with a median survival of 11.2 months compared to patients with a creatinine level less than 2.0 mg/dl, with a median survival of 56.9 months.
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PMID:Secondary systemic amyloidosis: response and survival in 64 patients. 206 9

Every physician managing patients with inflammatory bowel disease should be alert to the possibility of the development of hepatobiliary disorders, especially in patients with extensive colonic involvement. There is the question concerning type of follow-up study to be instituted in patients with IBD. Elevation of the level of serum alkaline phosphatase appears to be the most useful and consistent biochemical indicator of hepatic dysfunction (101). This should be estimated at six monthly intervals. A persistent elevation of the level of serum alkaline phosphatase or more overt clinical manifestations, such as pain in the right upper quadrant, hepatomegaly, obstructive jaundice or weight loss, would all indicate the need for further investigations. This would normally take the form of roentgenologic investigation of the biliary tree and biopsy of the liver. Once a patient with IBD has been diagnosed as having one or more hepatobiliary disorders, what is the appropriate management? Each instance should be treated individually according to the nature of the disorder. In general, most of these conditions are histologic abnormalities and are of little clinical importance. There is the question of whether or not there is a role for prophylactic colectomy. There has been conflicting evidence to both support and refute the rationale that colectomy will prevent the development of, or arrest, existing disease of the liver. In the view of the authors, based upon a large experience with the management of these patients, the indication for colectomy should be based upon the severity and extent of colonic disease and almost never upon the existence of associated hepatobiliary disorders.
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PMID:Hepatobiliary disorders in inflammatory bowel disease. 388 36

Two women, aged 19 and 28 yr, who had been on the contraceptive pill for at least 18 mo, developed abnormal levels of circulating liver enzymes, minimal hepatomegaly, and elevated erythrocyte sedimentation rate. Liver biopsy in both women showed a sinusoidal dilatation sparing the perihepatic venous regions. The liver function abnormality resolved on stopping the pill. Both patients also had clinically mild inflammatory bowel disease. The possibility of both liver and bowel abnormalities being effects of contraceptive steroids is discussed.
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PMID:Periportal sinusoidal dilatation, inflammatory bowel disease, and the contraceptive pill. 611 Jun 10

We report on 56 children with sclerosing cholangitis (SC) seen between 1972 and 1992. The first symptoms occurred at a mean age of 3.7 years; 15 infants had neonatal cholestatic jaundice. At diagnosis, cholestatic jaundice was present in 25 children, hepatomegaly in 54, splenomegaly in 41, and ascites in 12. Serum alkaline phosphatase activity was increased in 49 patients and gamma-glutamyltransferase activity in all patients tested. Most often the histopathologic findings were extensive portal fibrosis and neoductular proliferation. Cholangiography showed abnormal intrahepatic bile ducts in all children and abnormal extrahepatic bile ducts in 35 (63%). The children were separated into three groups: (1) those with SC of neonatal onset (27%); (2) those with SC of postneonatal onset associated with another disease (55%)--histiocytosis X in 14 children, immunodeficiency syndromes in 8, chronic inflammatory bowel disease or autoimmune hepatitis in 8, and congenital psoriasis in 1; and (3) those with SC of postneonatal onset without an associated disease (18%). Biliary cirrhosis was present in all but three children after 6 months to 19.3 years of follow-up. Eleven children died of portal hypertension or liver failure, and six died of a complication related to the associated disease. Fifteen children had liver transplantation; 11 of these are alive 6 months to 6 1/2 years later without recurrence of SC. The overall estimated median survival time of children with SC was 10 years from clinical onset. These results indicate that SC should be suspected in all children with a chronic cholestatic disease and increased serum gamma-glutamyl transferase activity, especially when diseases known to be associated with SC are present. The prognosis is poor, but liver transplantation should be considered except in those with severe immunodeficiency syndromes.
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PMID:Sclerosing cholangitis in children. 828 75

The kallikrein-kinin (K-K) (contact) system is activated during acute and chronic relapsing phases of enterocolitis induced in genetically susceptible Lewis rats by intramural injection of peptidoglycan-polysaccharide (PG-APS). Using the selective plasma kallikrein inhibitor P8720, we investigate whether activation of the K-K system plays a primary role in chronic granulomatous intestinal and systemic inflammation in this model. Group I (negative control) received human serum albumin intramurally. Group II (treatment) received PG-APS intramurally and P8720 orally. Group III (positive control) received PG-APS intramurally and albumin orally. P8720 attenuated the consumption of the contact proteins, high molecular weight kininogen (P<0.03), and factor XI (P<0.04) in group II vs. group III. P8720 decreased chronic intestinal inflammation measured by blinded gross (P<0.01) and histologic (P<0.0005) scores as well as systemic complications (arthritis, splenomegaly, hepatomegaly, leukocytosis, and acute-phase reaction) (P<0.01) in group II as compared with group III. We conclude that relapsing chronic enterocolitis and systemic complications are in part due to plasma K-K system activation, and that inhibition of this pathway is a potential therapeutic approach to human inflammatory bowel disease and associated extraintestinal manifestations.
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PMID:Specific inhibition of plasma kallikrein modulates chronic granulomatous intestinal and systemic inflammation in genetically susceptible rats. 950 76

A total of 51 cases (19 males and 32 females) of intrahepatic cholangiocellular carcinoma (CCC) from a low-endemicity area of primary liver cancer was analyzed during the periods from 1958 to 1979 and from 1984 to 1991. The mean annual age-adjusted incidence rate was 0.44 for males and 0.56 for females per 100,000 inhabitants. CCC was diagnosed before death in only 31%. There was a female predominance in patients over 70 years of age (p < 0.05). At presentation, malaise (85%), weight loss (73%) abdominal pain (50%) and hepatomegaly (80%) were common. The median survival time from diagnosis was 2 months. The mean age at the time of death was 72 years (range 41-92). At autopsy, cholelithiasis was found in 61% (81% in patients older than 70 years) and cirrhosis in 30% of patients. Cholelithiasis was more common in CCC (p < 0.01) than in hepatocellular carcinoma cases with the same mean age. Not one case of inflammatory bowel disease was found. The gross appearance of the tumor was predominantly massive (49%) or multinodular (35%). The most common histological features were tubular pattern of growth (82%) and abundant fibrous stroma. Metastases were particularly associated with the lymph nodes (41%), skeleton (26%) and lungs (16%).
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PMID:Incidence, etiologic aspects and clinicopathologic features in intrahepatic cholangiocellular carcinoma--a study of 51 cases from a low-endemicity area. 957 58

Azathioprine is a drug commonly used for the treatment of inflammatory bowel disease, organ transplantation and various autoimmune diseases. Hepatotoxicity is a rare, but important complication of this drug. The cases reported to date can be grouped into three syndromes: hypersensitivity; idiosyncratic cholestatic reaction; and presumed endothelial cell injury with resultant raised portal pressures, venoocclusive disease or peliosis hepatis. The components of azathioprine, 6-mercaptopurine and the imidazole group, may play different roles in the pathogenesis of hepatotoxicity. The strong association with male sex, and perhaps with human leukocyte antigen type, suggests a genetic predisposition of unknown type. Many of the symptoms of hepatotoxicity, such as nausea, abdominal pain and diarrhea, can be nonspecific and can be confused with a flare-up of inflammatory bowel disease. As well, the subtype resulting in portal hypertension can occur without biochemical abnormalities. A 63-year-old man with Crohn's disease who is presented developed the rare idiosyncratic form of azathioprine hepatotoxicity, but also had a severe disabling steroid myopathy, peripheral neuropathy, resultant deep venous thrombosis and pulmonary embolism related to immobility, and a nosocomial pneumonia. His jaundice and liver enzyme levels improved markedly on withdrawal of the drug, returning to almost normal in five weeks. Treating inflammatory bowel disease effectively while trying to limit iatrogenic disease is a continuous struggle. Understanding the risks of treatment is the first important step. There must be a low threshold for obtaining liver function tests, especially in men, and alertness to the need to discontinue the drug or perform a liver biopsy should patients on azathioprine develop liver biochemical abnormalities, unexplained hepatomegaly or signs of portal hypertension.
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PMID:Cholestatic hepatocellular injury with azathioprine: a case report and review of the mechanisms of hepatotoxicity. 981 67

Extracts from Boswellia serrata have been reported to have anti-inflammatory activity, primarily via boswellic acid-mediated inhibition of leukotriene synthesis. In three small clinical trials, boswellia was shown to improve symptoms of ulcerative colitis and Crohn's disease, and because of its alleged safety, boswellia was considered superior over mesalazine in terms of a benefit-risk evaluation. The goal of this study was to evaluate the effectiveness of boswellia extracts in controlled settings of dextran sulfate- or trinitrobenzene sulfonic acid-induced colitis in mice. Our results suggest that boswellia is ineffective in ameliorating colitis in these models. Moreover, individual boswellic acids were demonstrated to increase the basal and IL-1beta-stimulated NF-kappaB activity in intestinal epithelial cells in vitro as well as reverse proliferative effects of IL-1beta. We also observed hepatotoxic effect of boswellia with pronounced hepatomegaly and steatosis. Hepatotoxity and increased lipid accumulation in response to boswellia were further confirmed in vitro in HepG2 cells with fluorescent Nile red binding/resazurin reduction assay and by confocal microscopy. Microarray analyses of hepatic gene expression demonstrated dysregulation of a number of genes, including a large group of lipid metabolism-related genes, and detoxifying enzymes, a response consistent with that to hepatotoxic xenobiotics. In summary, boswellia does not ameliorate symptoms of colitis in chemically induced murine models and, in higher doses, may become hepatotoxic. Potential implications of prolonged and uncontrolled intake of boswellia as an herbal supplement in inflammatory bowel disease and other inflammatory conditions should be considered in future clinical trials with this botanical.
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PMID:Effects of Boswellia serrata in mouse models of chemically induced colitis. 1553 33

Glycogen storage disease type Ib (GSD Ib, OMIM 232220) is an inborn disorder of glucose metabolism, caused by mutations in the G6PT gene, encoding a glucose 6-phosphate transporter (G6PT). GSD Ib is mainly associated with fasting hypoglycaemia and hepatomegaly. Most GSD Ib patients also show neutropenia and neutrophil dysfunction and therefore are at risk of developing severe infections and inflammatory bowel disease (IBD). An increased risk for autoimmune disorders, such as thyroid autoimmunity and Crohn-like disease, has also been demonstrated, but no systematic study on the prevalence of autoimmune disorders in GSD Ib patients has ever been performed. We describe a 25-year-old patient affected by GSD Ib who developed 'seronegative' myasthenia gravis (MG), presenting with bilateral eyelid ptosis, diplopia, dysarthria, severe dysphagia, dyspnoea and fatigue. The repetitive stimulation of peripheral nerves test showed signs of exhaustion of neuromuscular transmission, particularly evident in the cranial area. Even in the absence of identifiable anti-acetylcholine receptor antibodies, seronegative MG is considered an autoimmune disorder and may be related to the disturbed immune function observed in GSD Ib patients.
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PMID:Myasthenia gravis in a patient affected by glycogen storage disease type Ib: a further manifestation of an increased risk for autoimmune disorders? 1843 26


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