Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Long-Evans Cinnamon (LEC) rats, an inbred strain of a mutant rat isolated from Long-Evans rats, develop hereditary hepatitis. To elucidate the role of copper metabolism in the development of the hepatitis in LEC rats, we examined the copper concentration in the tissues and serum levels of copper and ceruloplasmin. Copper concentration in the liver of LEC rats was over 40 times that of normal Long-Evans Agouti (LEA) rats, while the serum ceruloplasmin and copper concentrations in LEC rats decreased significantly. The hepatocytes of LEC rats show steatosis in cytoplasm and pleomorphism of mitochondria, resembling the histologic features of the liver in Wilson's disease. These findings suggest that the hereditary hepatitis in LEC rats is closely associated with copper toxicity, and may be dealing with a rat form of Wilson's disease. Thus the LEC rats will provide a unique and useful animal model for clarifying the mechanism and for developing treatment strategies for Wilson's disease and other abnormal copper metabolism in humans.
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PMID:Spontaneous hepatic copper accumulation in Long-Evans Cinnamon rats with hereditary hepatitis. A model of Wilson's disease. 202 51

In the last eighteen years, from 1972 to 1989, around 150 cases of Wilson's disease have been diagnosed in Costa Rica (6/100.000 inhabitants). In the San Juan de Dios Hospital, 120 cases have been studied during this period, seven of whom died with a picture of acute hepatic insufficiency, hemolytic anemia, encephalopathy, intestinal bleeding and renal insufficiency. In four of the cases, postmortem histopathologic studies were done with high resolution microscopy, which revealed extensive submassive necrosis of the liver, with severe cholestatic, lytic and acidophilic necrosis with nodular, irregular regeneration and specially microvacuolar steatosis, different from that observed in other forms of fulminant hepatitis. With the clinical, laboratory and histopathologic findings, we concluded that fulminant Wilson's disease is a well-defined pathological clinical entity of fatal evolution with no response to therapy, including early treatment with penicillamine and steroids.
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PMID:[Fulminant Wilson's disease in Costa Rica. Clinico-pathological study of 7 cases]. 215 63

The study of chronic liver disease has been hampered by insufficient information relative to the pathogenesis of the many forms of hepatitis. Consequently, well-designed treatment strategies are frequently lacking. Wilson's disease is characterised by excessive copper accumulation in the liver and other organs. While d-penicillamine is clearly effective, many patients may not tolerate its many adverse effects. Trientine, oral zinc and unithiol have all shown promise as therapeutic alternatives. Autoimmune chronic active hepatitis responds well to prednisone and azathioprine. Cyclosporin has also produced clinical improvement in several case reports but no comparison has yet been made with the current standard therapy. Recombinant interferon-alpha (IFN alpha) has demonstrated the ability to inhibit hepatitis B viral replication, and the combination of oral corticosteroids followed by IFN alpha is more effective than either agent alone in eliminating viral replication in patients with chronic active hepatitis B. Currently, primary sclerosing cholangitis (PSC) has no standard medical management, but corticosteroids and methotrexate may each have a future role in its treatment. Drug treatment for primary biliary cirrhosis (PBC) has been disappointing, and early reports of success with d-penicillamine were not confirmed in large well-controlled trials. While some reports of improvement with several agents have been described, larger studies are still needed. Alcoholic liver disease continues to be associated with significant morbidity and mortality and numerous investigators have researched several different medical avenues of treatment. Success reported with androgens and the antithyroid agent propylthiouracil in alcoholic liver disease will need confirmation by other research before these agents can be recommended for routine use. Finally, colchicine may prove to be effective in slowing the rate of fibrosis in cirrhosis, but this has yet to be conclusively proven.
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PMID:Current therapy of chronic liver disease. 219 64

Hepatolenticular degeneration (Wilson's disease) is a hereditary disease in which metabolic disorder of copper leads to its accumulation in the liver, brain, cornea and kidneys with consequent pathologic changes in those organs. Hereditary mechanism of the disease is autosomal recessive with prevalence of 30-100 per 1,000,000 inhabitants. Etiology of this disease is not yet explained. There are two hypotheses. The first one is that it is the disorder of ceruloplasmine metabolism caused by insufficient synthesis of normal ceruloplasmine, or synthesis of functionally abnormal ceruloplasmine. The second one is: the block of copper biliar excretion which is the consequence of the liver lysosomes functional defect. Pathogenetic mechanism of disease is firstly long-term accumulation of copper in the liver, and later, when the liver depo is full, its releasing in circulation and accumulation in the brain, cornea, kidneys and bones, which causes adequate pathologic changes. Toxic activity of copper is the consequence of its activity on enzymes, particularly on those with -SH group. There are two basic clinical forms of the disease: liver disease or neurologic disease. Before puberty the liver damage is more frequent, while in adolescents and young adults neurologic form of the disease is usual. The liver disease is nonspecific and characterized by symptoms of cirrhosis and chronic aggressive hepatitis. The only specificity is hemolytic anemia which, in combination with previous symptoms, is important for diagnosis of the disease. Neurologic symptoms are the most frequent consequence of pathologic changes in the basal ganglia. In our patients the most frequent symptoms were tremor (63%); dysarthria, choreoathetosis and rigor (38%); ataxia and mental disorders (31%); dysphagia and dystonia (12%), diplopia, hypersalivation, nystagmus and Babinski's sign (6%). Among pathologic changes in other tissues and organs the most important is the finding of Kayser-Fleischer ring in the cornea as a result of copper accumulation. Its importance for precise diagnosis is great. The diagnosis of the disease is based on anamnesis, clinical examination, specific and nonspecific laboratory tests. The therapy of choice is penicillamine. If we use it early, the result will be good remission in the majority of patients. Late diagnosis or delay in treatment cause death which is the result of bleeding from esophageal varices or basal ganglia disease. Immunologic damages caused by penicillamine demand interruption of therapy and substitution by three-ethyl-tetra-amine (TETA). We also use zinc salts and tetratiomolibdate in therapy of this disease. Pathogenesis, clinical picture and therapy of the disease are based on our own results.
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PMID:[Hepatolenticular degeneration]. 226 49

Eleven cases of Wilson's disease presenting as fulminant hepatic failure were analysed retrospectively to determine the specificity or otherwise of the histological findings. All cases were cirrhotic, eight with a micronodular pattern. There was marked parenchymal collapse with ductular proliferation and mild inflammation. Other features included cholestasis, hepatocyte necrosis, microvesicular fat and nuclear vacuolation. Orcein staining demonstrated copper-associated protein in the periphery of cirrhotic nodules in all cases and also variably within nodules in eight cases. Copper was demonstrable by the rhodanine method in similar locations but the staining reaction was qualitatively weaker in all cases. Characteristically, there was staining of both parenchymal and mononuclear phagocytic cells. This triad of cirrhosis, strong copper-associated protein deposition and copper positivity was not present in a control group of 20 cases of fulminant hepatic failure of other aetiology and with a similar clinical presentation. It is concluded that in the clinical context of fulminant hepatitis the presence of cirrhosis should raise the suspicion of Wilson's disease and that, with routinely processed and stained tissue, including autopsy tissue, the diagnosis can be made histologically.
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PMID:Hepatic morphology and histochemistry of Wilson's disease presenting as fulminant hepatic failure: a study of 11 cases. 280 95

End-stage liver disease affects nearly 300 children annually in the United States. Based upon the annual birth rate in the United States of 3.1 million, the incidence of the most prominent causes of liver disease in children (biliary atresia, alpha 1-antitrypsin deficiency, Wilson's disease, and neonatal hepatitis), and the frequency of end-stage liver disease in each disorder. Liver transplantation now offers these children at least a 65%, and in some series as high as 85%, chance of surviving at least 2 years postoperatively. Much of this improvement is attributable to advances in immunosuppression. However, one must not underestimate the importance of the tremendous knowledge that has been gained in the care of a large number of these patients over the last decade. The major barriers standing in the way of wider application of liver transplantation include the reluctance of primary care physicians to refer patients for early consideration, the growing crisis in the availability of donor organs, and the lack of adequate numbers of centers involved in performing adequate numbers of procedures. The major hurdles to overcome in order to affect further improvements in results include more specific immunosuppression, more accurate means of diagnosing rejection, better techniques of organ preservation, and further optimization of the care of both candidates preoperatively and recipients after transplantation.
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PMID:Liver transplantation therapy for children: Part 2. 305 17

Chronic hepatitis in children should be suspected if clinical features and abnormal liver function tests persist for over one month following an episode of acute hepatitis, in children who present with relapsing hepatitis, or those presenting coincidentally with features of chronic liver disease. Specific investigation must be undertaken to define aetiology. For example, hepatitis B, Wilson's disease and alpha 1-antitrypsin deficiency must be excluded. Early histological diagnosis by an experienced histopathologist is mandatory. Chronic persistent hepatitis requires no therapy, but careful follow-up is desirable, especially for hepatitis B-positive cases. If the histological appearances are those of chronic active hepatitis, distinction between HBV-associated and autoimmune varieties is necessary. Autoimmune CAH in children differs from that in adults in that the onset is often acute, response to immunosuppressants usually favourable, and withdrawal of therapy may be successful, especially if diagnosis is established early before serious liver damage occurs. Evidence is presented to suggest that autoimmune CAH is associated with a genetic predisposition to autoimmune disease, characterized by both antigen-specific and antigen-independent T suppressor cell defects. An antibody-dependent non-T cell cytotoxicity operates against liver cell surface antigens. HBV CAH, on the other hand, may respond poorly to immunosuppressants and appropriate therapeutic regimens are not defined. There is some evidence to suggest that early diagnosis and institution of therapy in autoimmune CAH may lessen the incidence of cirrhosis on follow-up. Further studies to understand the interaction between hepatocytes, inflammatory cells and non-parenchymal cells in the process of hepatic fibrosis may provide the means of active intervention in this area in the future.
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PMID:Chronic active hepatitis and related disorders. 308 42

We conducted a pilot study to assess the feasibility and efficacy of postdilution hemofiltration (PDHF) in the management of acute hepatic failure. From January 1984 through May 1986, we encountered seven patients with acute hepatic failure and entered these consecutive patients in the study; three had non-A, non-B hepatitis and one each had type B hepatitis, fulminant Wilson's disease (hepatolenticular degeneration), acute allograft (liver) failure, and acute fatty liver of pregnancy. Two of these seven patients were unable to undergo PDHF because of a precarious hemodynamic status. Of the five patients treated with PDHF, four had amelioration of hepatic encephalopathy; in two of these patients, a close temporal relationship was noted between the improvement and the procedure. Four patients had appreciable thrombocytopenia related to PDHF and bleeding complications. Our preliminary results support a possible role for PDHF as a temporary artificial liver support system for patients with acute hepatic failure.
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PMID:Postdilution hemofiltration in the management of acute hepatic failure: a pilot study. 327 72

During a multicentre study of chronic hepatitis in childhood diagnosed by biopsy, the spectrum of the disease has been evaluated in 196 consecutive patients, including 157 from Northern Italy and 39 from Southern Italy. Only 31% of patients in the former group and 27% in the latter were symptomatic when first seen: the majority of cases being seen after familial screenings for hepatitis B virus (HBV) markers or during intercurrent infections, thus suggesting that the frequency of chronic hepatitis in childhood might be largely underestimated in our area. In Southern and Northern Italy 83% of symptomatic and 95% of asymptomatic patients were hepatitis B surface antigen (HBsAg) positive in serum; only 15 (8.3%) of these children were born to mothers known to be HBsAg positive at delivery, but a high circulation of HBV was found in their families: in fact more than 65% of household contacts in Northern Italy and more than 90% in Southern Italy had serological evidence of past or ongoing HBV infection. These data indicate that, although familial screenings for HBV could have enhanced the percentage of HBsAg positive asymptomatic cases, chronic hepatitis in Italian children is mainly caused by HBV infection acquired in the familial setting through horizontal transmission. Such findings also emphasise the importance of mass vaccination of infants as the most effective means to prevent chronic type B hepatitis in childhood in our area. Among HBsAg positive children 55% had histological features of chronic active hepatitis and 85% were hepatitis Be antigen (HBeAg) positive in serum. Anti-HBe positive hepatitis was significantly more frequent in Southern than in Northern Italy in parallel with the significantly higher prevalence (17%) of hepatitis delta virus infection in that area. Of the 16 HBsAg negative cases included in the study three had autoimmune hepatitis, three Wilson's disease, one alpha1 antitrypsin deficiency, and nine had cryptogenic hepatitis, often associated to mild liver lesions resembling those seen in our adult patients with chronic non-A, non-B hepatitis unrelated to percutaneous exposure.
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PMID:Chronic hepatitis in childhood: the spectrum of the disease. 339 53

Fulminant or subfulminant liver failure, complicated by encephalopathy and in many cases by death is seen to be a syndrome that may result from numerous causes. Although viral hepatitis, drug-induced hepatitis, and hepatitis due to various types of poisonings, in decreasing frequency, account for 90% of all cases, a variety of miscellaneous conditions account for the remainder. Consideration of the possibility of these less common etiologies by the clinician is of considerable importance, since some, including massive malignant involvement (such as leukemia) or acute fulminant Wilson's disease, may respond to specific treatment measures. Thus, unless hepatic transplantation proves to be applicable in FHF of many etiologic diagnosis may continue to have important therapeutic indications in at least some cases with this syndrome.
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PMID:Fulminant and subfulminant liver failure: definitions and causes. 352 10


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