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)

Non-A, non-B or seronegative hepatitis is the leading indication for liver transplantation in patients with fulminant hepatic failure (FHF). We examined protocol annual review liver allograft biopsy specimens in consecutive adult patients transplanted for FHF in an attempt to determine the extent of the histological changes. One hundred eleven biopsy specimens from 41 patients transplanted for fulminant seronegative hepatitis and 34 from a comparison group of 16 patients transplanted for other causes of FHF (11 paracetamol overdose, 2 idiosyncratic drug reaction, 3 Wilson's disease) were available. Specimens were analyzed using standard proforma without knowledge of the original diagnosis. Chronic hepatitis was present in 29 patients (71%) transplanted for fulminant seronegative hepatitis (23 mild, 3 moderate, and 3 severe) compared with 5 patients (31%, all mild) transplanted for other causes of FHF. Twenty-five patients (61%) grafted for seronegative FHF had fibrosis (13 mild, 9 moderate, and 3 severe) in contrast to 4 fibrosis (25%) (all mild) in the comparison group. Excluding early allograft failure because of primary graft nonfunction or vascular complications, six patients with seronegative FHF required retransplantation (2 = chronic rejection; 1 = severe hepatitis with panacinar necrosis, resembling original liver; and 3 = chronic hepatitis with precirrhotic fibrosis and prominent cholestasis of unknown cause). One patient in the comparison group had a second graft (chronic rejection). Posttransplantation chronic hepatitis is more frequent and severe in patients transplanted for seronegative hepatitis. Graft survival may be adversely influenced by the development of chronic hepatitis, which may represent persistent or recurrent disease.
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PMID:Posttransplantation chronic hepatitis in fulminant hepatic failure. 909 11

Etheno adducts in DNA are formed from the carcinogens vinyl chloride and urethane, and also from products of lipid peroxidation (LPO), such as trans-4-hydroxy-2-nonenal. Using an ultrasensitive detection method, the formation of etheno-DNA adducts in the liver was demonstrated in LEC rats (a strain with hereditary abnormal copper metabolism) that develop hepatitis and hepatocellular carcinoma. Wilson's disease and primary haemochromatosis are human genetic disorders that cause copper or iron accumulation resulting in a high risk for primary liver cancers. Levels of etheno adducts were also significantly elevated in the liver of these patients. In a group of male and female volunteers kept on a controlled diet, the effect of dietary fatty acid composition on the endogenous formation of lipid peroxidation-derived DNA adducts was determined in DNA from white blood cells. Dietary omega-6-polyunsaturated fatty acids greatly increased LPO-derived etheno-DNA adducts in vivo, in females. Thus, exocyclic DNA adducts are promising biomarkers for elucidating the effect of dietary fat intake, oxidative stress and protective dietary antioxidants on endogenous DNA damage and thus may provide a possible mechanistic link with elevated risk for diet-related cancers.
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PMID:Etheno-DNA base adducts as tools in human cancer aetiology and chemoprevention. 949 54

We have studied the DNA binding activities of transcription factors in the liver of Long-Evans Cinnamon (LEC) rats, an animal model of Wilson's disease. Owing to a genetic defect, this strain of rats accumulates excessive copper in the liver and develops severe hepatitis and hepatocellular carcinoma. We found that the DNA binding activity of the serum response factor (SRF) was higher in the liver of LEC rats (approximately 2-fold) than in that of Wistar rats. There was a close correlation between the intensity of the activity and the concentrations of copper in the nuclear protein. The DNA binding activity of Sp1, on the other hand, showed similar levels in both LEC and Wistar rats. SRF may play an important role in the development of hepatocellular carcinoma in LEC rats by mediating the proto-oncogene c-fos induction. We suggest that the copper in nuclear protein may be involved in the activation of SRF.
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PMID:Activation of serum response factor in the liver of Long-Evans Cinnamon (LEC) rat. 957 Mar 63

HCV infection and interferon-alpha (IFN-alpha) therapy have been associated with autoimmunity. To assess whether chronic liver disease (CLD) due to HCV infection or its treatment with IFN-alpha cause autoimmune manifestations, the prevalence of tissue autoantibodies in 51 children with chronic HCV infection and 84 with other CLD was analysed by standard techniques. Sixty-five percent of patients with chronic HCV infection, 66% with chronic hepatitis B infection and 60% with Wilson's disease were positive for at least one autoantibody. In the 51 subjects with chronic HCV infection (29 treated with IFN-alpha, 22 untreated), tested on 165 occasions over a median of 9 months (range 5-42 months), autoantibodies to nuclei (ANA), smooth muscle (SMA), gastric parietal cell (GPC) and/or liver kidney microsomal type 1 (LKM-1) were similarly prevalent in treated and untreated patients (90% versus 68%, P = 0.12). Positivity for SMA was present in 67%, GPC in 32%, ANA in 10%, LKM-1 in 8% of cases. Treatment with IFN-alpha had to be suspended due to transaminase elevation in one SMA-positive, one ANA-positive but in three of four LKM-1-positive patients. Our results show that: (i) autoantibodies are common in viral-induced hepatitis and Wilson's disease; (ii) positivity for SMA, GPC, ANA is part of the natural course of chronic HCV infection, their prevalence being unaffected by IFN-alpha; and (iii) IFN-alpha should be used cautiously in the treatment of LKM-1/HCV-positive patients.
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PMID:Autoantibody prevalence in children with liver disease due to chronic hepatitis C virus (HCV) infection. 964 17

Hepatocellular carcinoma (HCC) is the most frequent primary cancer of the liver and the most frequent tumour in males, worldwide. The annual incidence of HCC is maximum in Asian and African countries, lower in western countries where it is close to 4/100,000 inhabitants. In 90% of the cases, HCC complicates course of liver cirrhosis, with an annual incidence in cirrhoties of 2 to 6%. Risk factors for HCC in cirrhotics are male gender (sex-ratio: 4/1), age (above 50 years old), macronodular cirrhosis and large cell dysplasia. HCC can complicate the course of cirrhosis of any cause, but might be less frequent in primary biliary cirrhosis, Wilson's disease and auto-immune hepatitis. Currently, the diagnosis of HCC is usually considered in the presence of a focal nodular lesion, during systematic ultrasonographic examination of the liver. In high incidence areas, HCC can still be diagnosed because of HCC-related symptoms. In the case of a focal lesion discovered on a cirrhotic liver, the diagnosis of HCC can be confirmed by studying the behaviour of the lesion of helical CT scan of the liver (enhancement of the tumour during the arterial phase) or MRI (hyperintensity of the tumour on T2 relaxation time); study of peritumour vessels can also be helpful. Serum alpha-foeto-protein level, when higher than 300 to 500 micrograms/L is very specific of HCC. When aggressive treatment of HCC is considered and when the diagnosis of HCC remains uncertain, HCC can be assessed by means of cytological or histological study of the tumour on samples taken by fineneedle aspiration (80% sensitivity) or liver biopsy during laparoscopic laparotomy. Forthcoming improvements in imaging technology might eliminate the need for such invasive diagnostic techniques in the future.
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PMID:[Epidemiology and diagnosis of hepatocellular carcinomas in cirrhosis]. 975

We present the case of a 53 year-old patient with idiopathic thrombocytopenia associated with Wilson's disease. Idiopathic thrombocytopenia was diagnosed in August of 1994, and as the response to corticosteroid therapy was poor, the patient underwent a splenectomy in October of the same year. A liver biopsy, which was performed during the operation, showed Wilson's disease in the form of mild, chronic, active hepatitis. The serum ceruloplasmin was low, and the Kayser Fleischer's ring was positive. MRI of the brain showed cortical reductive changes with areas of copper accumulation in the white brain matter. An unusual presentation of Wilson's disease associated with idiopathic thrombocytopenia has not been published as of yet. The diagnosis of Wilson's disease was made at an advanced, adult age, which may implicate a heterozygous genetic configuration.
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PMID:Idiopathic thrombocytopenia associated with Wilson's disease. 984 Jan 46

Anti-liver cytosol 1 autoantibody (LC1) characterizes a severe form of autoimmune hepatitis (AIH), staining the cytoplasm of periportal hepatocytes and targeting an unidentified 60-kD liver cytosolic antigen. To identify its target, we used high-titre anti-LCI+ sera from two patients with AIH to screen 18 cytoplasm enzymes with periportal location by double immunodiffusion (DDI). Both sera gave a broad precipitin line against human liver cytosol, suggesting that they may recognize two distinct antigens, a possibility confirmed by the appearance of two precipitin lines when DDI conditions were optimized (0.8% agarose and 3% polyethylene glycol (PEG)). Experiments by DDI and Western blot (WB) identified a liver cytosolic autoantigen of 50 kD, different from LC1, giving a line of identity with argininosuccinate lyase (ASL). Reactivity to ASL was then investigated by DDI and WB in 57 patients with AIH, 17 with primary biliary cirrhosis (PBC), 15 with chronic hepatitis B virus (HBV) infection, 13 with alphal-antitrypsin deficiency, 17 with Wilson's disease, 18 with extrahepatic autoimmune disorders, and in 48 healthy controls. Anti-ASL was found in 16% of AIH and 23% of PBC patients by DDI and in 14% of AIH, 23% of PBC and 20% of HBV patients by WB. No argininosuccinate was present in the urine of four anti-ASL+ patients tested, excluding an inhibition of enzymatic activity by anti-ASL. The addition of anti-ASL+ serum to human fibroblast cultures induced a significant increase in ASL activity. ASL is a new autoantigen in liver disease and its clinical relevance warrants further investigation.
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PMID:Argininosuccinate lyase: a new autoantigen in liver disease. 984 57

Little information is available on acute liver failure (ALF) in the United States. We gathered demographic data retrospectively for a 2-year period from July 1994 to June 1996 on all cases of ALF from 13 hospitals (12 liver transplant centers). Data on the patients included age, hepatic coma grade on admission, presumed cause, transplantation, and outcome. Among 295 patients, 74 (25%) survived spontaneously, 121 (41%) underwent transplantation, and 99 (34%) died without undergoing transplantation. Ninety-two of 121 patients (76%) survived 1 year after transplantation. Acetaminophen overdose was the most frequent cause (60 patients; 20%), followed by cryptogenic/non A non B non C (NANBNC; 15%), idiosyncratic drug reactions (12%), hepatitis B (10%), and hepatitis A (7%). Spontaneous survival rates were highest for patients with acetaminophen overdose (57%) and hepatitis A (40%) and lowest for those with Wilson's disease (no survivors of 18 patients). The transplantation rate was highest for Wilson's disease (17 of 18 patients; 94%) and lowest for autoimmune hepatitis (29%) and acetaminophen overdose (12%). Age did not differ between survivors and nonsurvivors, perhaps reflecting a selection bias for patients transferred to liver transplant centers. Coma grade on admission was not a significant determinant of outcome, but showed a trend toward affecting both survival and transplantation rate. These findings on retrospectively studied patients from the United States differ from those previously gathered in the United Kingdom and France, highlighting the need for further study of trends in each country.
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PMID:Etiology and outcome for 295 patients with acute liver failure in the United States. 987 98

Conflicting results have been reported on the usefulness of histochemistry for copper in the diagnosis of Wilson's Disease (W.D.). In spite of the high number of methods proposed in the literature, no-one has shown to have the characteristics typical of a good histochemical method: high sensitivity associated with high specificity. On this basis, it seemed of interest to evaluate, in a large series of patients with W.D., the diagnostic value of the most commonly used histochemical methods for copper (rhodanine, orcein and Timm's method). To this end, 74 liver needle biopsies from patients affected by W.D., 39 males and 35 females, aged 4-60 years (mean age 28.5 years), were stained with rhodanine (R), orcein (O) and Timm's (T) methods. On the basis of the histological picture, liver biopsies were subdivided in four evolutive stages: stage I = steatosis; stage II = interface hepatitis; stage III = bridging fibrosis; stage IV = cirrhosis. In stage I, histochemistry for copper was positive in 11 out of 21 cases: 6 cases were T+; 1 case R+ and 2 cases O+; 2 cases were T+, R+, O+. In stage II, 11 out of 14 cases were positive for copper staining: 4 T+, 2 R+ and 2 O+; 3 cases were contemporary positives for T, R, O. In stage III, 22 out of 25 cases resulted positive: 8 T+, 3 R+ and 1 O+; 10 cases were positives, in the mean time, for more of one method. In stage IV, 12 of 14 cases were positives: 5 T+, 2 R+, 2 O+ and 3 cases were contemporaneously positives for multiple methods. Our data show that: 1) the percentage of positivity obtained using three histochemical methods for copper is higher than using only one method. From a practical point of view, it is mandatory to utilize, in clinical practice, multiple histochemical stains in order to increase the diagnostic utility of histochemistry for copper; 2) the Timm's method appears to be the most sensitive method for the demonstration of copper in all stages of W.D.; 3) even though hepatic copper already abounds in the early stages of W.D., this pool of intrahepatic copper is not yet demonstrable with any of the three histochemical techniques utilized.
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PMID:[Multiple histochemical methods in the diagnosis of Wilson's disease. (Presentation of 74 cases and review of the literature)]. 1022 Sep 97

At routine determination of serum activities of transaminases (aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT) increased levels are frequently found. An algorithm may be used in the analysis of elevated transaminase levels: after elimination of the most frequent causes of hepatitis (alcoholic hepatitis, chronic hepatitis B and C) and some rare conditions (autoimmune hepatitis, alpha 1-antitrypsin deficiency, haemochromatosis and Wilson's disease), the diagnosis will often be nonalcoholic steatohepatitis. Although nonalcoholic steatohepatitis is considered a stable disease, recent literature shows a progression to cirrhosis in 8-17%. So far, no effective therapeutic strategies are available for nonalcoholic steatohepatitis.
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PMID:[Management of asymptomatic elevated serum aminotransferase levels, particularly in nonalcoholic steatohepatitis]. 1032 Dec 58


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