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)

Troglitazone maleate (Rezulin) has been associated with severe hepatotoxicity, which led to its withdrawal from the U.S. market in March 2000. Rosiglitazone maleate (Avandia) is being marketed as a safe alternative in the treatment of type 2 diabetes mellitus. We report a case of severe thiazolidinedione-induced cholestatic hepatitis in a 56-year-old female patient at a university hospital who was given rosiglitazone, 8 mg/day, after she developed milder hepatotoxicity while taking troglitazone. Rosiglitazone was discontinued, and the patient was treated with prednisone, azathioprine, and ursodiol. Clinical evaluation and liver biopsy were performed and liver function tests were monitored. After being switched from troglitazone to rosiglitazone the patient developed a severe cholestatic hepatitis with marked jaundice and moderate increases in serum alkaline phosphatase and gamma-glutamyltranspeptidase but only mild increases in serum aminotransferases. Discontinuation of rosiglitazone and treatment with prednisone, azathioprine, and ursodiol led to improvement, albeit with residual injury, dropout of intrahepatic bile ducts, and persisting elevations of serum alkaline phosphatase. Rosiglitazone is not always a safe alternative in patients who have had hepatotoxicity to troglitazone. It is important to monitor the serum alkaline phosphatase in addition to the serum aminotransferases in patients taking thiazolidinediones.
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PMID:Severe cholestatic hepatitis caused by thiazolidinediones: risks associated with substituting rosiglitazone for troglitazone. 1214 28

Past studies of the relation between hepatitis C virus (HCV) infection and type 2 diabetes conflict. The authors aimed to elucidate the relation by using a large community-based sample with a wide range of liver conditions. Between October 1997 and February 1998, 2,327 consecutive subjects (aged > or =35 years) were enrolled at the public health facility in Taiwan. Blood sugar, hepatitis B surface antigen, and antibody for HCV (anti-HCV) were tested. Abdominal sonography was performed on viral-hepatitis-positive subjects. In univariate analysis, older age, lower educational levels, sedentary work, body mass index of > or 25 kg/m2, and anti-HCV positivity were significantly associated with type 2 diabetes (p<0.05), but smoking, alcohol consumption, gender, and hepatitis B surface antigen status were not. In multivariate logistic regression, anti-HCV positivity was strongly associated with type 2 diabetes in subjects aged 35-49 years (odds ratio (OR)=3.3, 95% confidence interval (CI): 1.4, 8.0) and 50-64-years (OR=1.6, 95% CI: 1.1, 2.5). Sonographic evidence of fatty liver (OR=2.4, 95% CI: 1.2, 4.8) and chronic liver disease (OR=2.0, 95% CI: 1.0, 4.2) in anti-HCV-positive subjects was moderately associated with type 2 diabetes after age and gender adjustment. Data suggest that HCV infection is moderately associated with type 2 diabetes; the association was strongest for subjects aged 35-49 years and increased with severity of the liver condition.
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PMID:Community-based study of hepatitis C virus infection and type 2 diabetes: an association affected by age and hepatitis severity status. 1465

We report a singular clinical condition observed following a short duration treatment with sulphasalazine (SSZ) in a 64-year-old woman affected by psoriatic arthritis. Two weeks after starting treatment, a high degree, subcontinuous fever occurred, together with systemic discomfort, fatigue, headache, and ultimately a moderate wakefulness impairment. Upon admission to the hospital, a malar rash became evident. Modest notes of hepatotoxicity were also evident. All of the symptoms suddenly resolved after SSZ withdrawal. The markers of hepatitis become negative just 2 months later. It is interesting to note that after dismissal, in order to counteract the severe arthritic conditions and the presence of a type 2 diabetes, a combined therapy with methotrexate and cyclosporin had to be used, with no renal or hepatic side effects and remarkable therapeutic effects. No markers of autoimmunity were found in this patient. The chronology and the clinical events here described may confirm the hypothesis of a idiosyncratic reaction to SSZ, closely resembling a rare, sometimes irreversible, condition known as "the 3 week sulphasalazine syndrome".
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PMID:Abrupt occurrence of high fever and rash in a patient treated with sulphasalazine for psoriatic arthritis. 1497 71

Obesity, now an epidemic in the USA, northern Europe, and Italy, is associated with several co-morbidities that shorten life expectancy, in particular type 2 diabetes mellitus (T2DM), arterial hypertension, and hyperlipidemia. The impact of obesity on mortality is evident in all ages, and is especially strong in young persons. Obesity, especially visceral obesity, associated with a sedentary lifestyle, is among the strongest risk factors for T2DM, and a diagnosis of T2DM seems to increase linearly as a function of duration of obesity. The pathogenesis of T2DM is based on a dual defect, i.e. increased insulin resistance coupled with defective insulin release. The main abnormality in obesity is increased insulin resistance, while insulin release, even though defective compared with body needs, is usually abundant. The incidence of obesity among children aged 6-16 years is now even greater than that among adults: in Italy, figures up to 30% have been reported. As in adults, obesity is a cause, among children, of arterial hypertension, left ventricular hypertrophy, hyperlipidemia, non-alcoholic-steato hepatitis, sleep apnea syndrome (SAS), and orthopedic, psychological, and social problems. Together with an increase in body weight, there is an increase of visceral fat. Obesity in children has also led to a tremendous increase in the prevalence of impaired glucose tolerance (IGT); the percentages span from 25% in a multiethnic cohort in the USA, to 4% in Italian Caucasians. Management of obesity and of T2DM in children has to face the issue of poor compliance; there is consensus that dietary treatment of obese T2DM children is a failure, so that drugs are required; the only drug evaluated in a formal trial is metformin, that behaves in terms of efficacy and of minor side effects as in adults. In conclusion, obesity in children is not pure obesity, but is accompanied by co-morbidities that cluster to form the "metabolic syndrome" just like in the adults. If this epidemics continues and is not properly challenged, in the next decades we will face an epidemic of early cardiovascular morbidity and mortality.
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PMID:Type 2 diabetes mellitus is becoming the most common type of diabetes in school children. 1566 74

We describe a 52-year-old man with type 2 diabetes mellitus who developed cholestatic hepatitis in association with rosiglitazone use. Liver biopsy findings included dilated canaliculi, inspissated bile, intrahepatocellular bile pigment deposits, and enlarged xanthomatous Kupffer cells. The form of liver injury reported in this case differs markedly from those reported previously for rosiglitazone.
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PMID:Hepatic injury in a patient taking rosiglitazone. 1600 Sep 35

Troglitazone is a thiazolidinedione antidiabetic agent with insulin-sensitizing activities that was withdrawn from the market in 2000 due to its association with idiosyncratic hepatotoxicity. To address the suspected autoantibody production associated with troglitazone, we investigated autoantibodies in sera from patients with type II diabetes mellitus with troglitazone-induced liver dysfunction. Two female patients (47- and 70-year-old) ceased taking troglitazone (400 mg/day) after 23.5 and 16 weeks, respectively, due to increased serum ALT. Using two-dimensional electrophoresis and amino acid sequence analyses, aldolase B was identified as an autoantigen that reacted with antibodies in sera from both patients. The titer of anti-aldolase B remained high for several weeks after stopping troglitazone administration. The mean reactivity of autoantibodies to aldolase B determined by ELISA with sera of patients with chronic hepatitis (n = 40) and liver cirrhosis (n = 40) was significantly higher (p < 0.05 and p < 0.001, respectively) than with sera of healthy subjects (n = 80). These findings suggest that liver injury may cause the appearance of autoantibodies to aldolase B which may then aggravate the hepatitis. In addition, the anti-aldolase B titer might indicate the severity of liver dysfunction.
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PMID:Detection of autoantibody to aldolase B in sera from patients with troglitazone-induced liver dysfunction. 1611 20

Cryptogenic cirrhosis (CC) is diagnosed in 5-30% of cirrhotic patients overall and 7% of patients who undergo liver transplantation for cirrhosis. In our series of patients transplanted for CC, pre-transplant clinical and histological data and the post-transplant course were reexamined in an attempt to identify the aetiology. Among the 881 patients transplanted in our centre between 1987 and 2000, 28 patients with a median age of 46 yr (range: 18-69) at transplantation were initially classified as having CC. Two patients were excluded because of intense ischaemic lesions caused by chemoembolization prevented histological analysis of the native liver (n = 1) and because of cryptic HBV infection (n = 1). Among the remaining 26 patients, four groups were individualized: (i) patients with chronic inflammatory liver disease with autoimmune features (n = 14, 54%); (ii) patients with features suggestive of non-alcoholic fatty liver disease (n = 3, 11.5%); (iii); patients with incomplete septal cirrhosis (ISC) and vascular liver disease (n = 3), and (iv) patients with unresolved CC (n = 6, 23%). In the autoimmune liver disease group, the median International Autoimmune Hepatitis score was 12.5 (range: 11-19) after reevaluation and review of the post-transplantation course was helpful to confirm the diagnosis with the occurrence of active graft hepatitis in nine patients, with autoantibodies in five patients. The vascular group was characterized by lesions of obliterative portal venopathy and ISC in all native livers. Diagnosis of NAFLD was based on the clinical background of obesity and/or type 2 diabetes and the presence of steatosis or steatohepatitis in native livers and graft biopsies. A definite aetiological diagnosis can be achieved in the majority of patients initially diagnosed with CC. Autoimmune liver disease emerged as the main aetiology (14 of 26 patients, 54%) and frequently recurred on the grafted liver (nine cases). In all cases a precise diagnosis is obviously of practical interest for better management of post-transplant survey and treatment.
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PMID:Could post-liver transplantation course be helpful for the diagnosis of so called cryptogenic cirrhosis? 1710 Jul 32

Non-alcoholic liver steatosis is associated with metabolic syndrome and type 2 diabetes. The prevalence of this condition in type 2 diabetes is estimated to be between 28 and 55%. Non-alcoholic liver steatosis is not a benign disease because of its potential progression to liver fibrosis, cirrhosis and cancer. The Verona diabetes study, a population-based observational study, on 7148 type 2 diabetic patients after 5 years of follow-up has reported an increased risk of death from gastrointestinal diseases, particularly from chronic liver cirrhosis. Moreover, in the same population after 10 years of follow-up a higher risk of mortality from liver cancer was observed and this risk increased significantly in obese patients (body mass index >30 kg/m2). Of note is that obese diabetic patients suffer an even higher prevalence of non-alcoholic liver steatosis. In conclusion, the Verona diabetes study showed an increased risk of mortality from liver cirrhosis and liver cancer in type 2 diabetic patients. Diverse pathophysiological mechanisms can be responsible, i.e. higher alcohol consumption, hepatitis and others but, considering the high prevalence of non-alcoholic liver steatosis in these patients, it is plausible to hypothesize that non-alcoholic liver steatosis may play a significant role in predisposing the liver of diabetics to chronic diseases.
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PMID:Review article: type 2 diabetes and chronic liver disease in the Verona diabetes study. 1622 67

Changes in human behavior and lifestyle over the last century have resulted in a dramatic increase in the incidence of obesity, type 2 diabetes, and the metabolic syndrome. Differences in the reported overall prevalence of the metabolic syndrome, which is generally in the range of 10-30% depend on the diagnostic criteria and subjects of the study. Recently, Japanese criteria for diagnosis of the metabolic syndrome were defined. With these criteria, presence of visceral obesity is essential for the diagnosis and is simply determined by measurement of waist circumference. Reflecting a dramatic increase in the incidence of obesity and type 2 diabetes, the incidence of the metabolic syndrome is increasing in Japan as well as in Western countries, regardless of the criteria applied. Recently, the number of workers with elevated liver enzymes, in whom virus hepatitis, alcoholic liver disease, drug induced hepatitis, autoimmune hepatitis, and iron overload were ruled out as causal agents, has also be found to be increasing at workplace health checkups. Most of such workers have components of the metabolic syndrome and the presence of steatosis in the liver, this pathologic condition now being termed nonalcoholic fatty liver disease (NAFLD). In this review, we describe the relationship between NAFLD and the metabolic syndrome.
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PMID:Metabolic syndrome from the view point of public health: with special reference to nonalcoholic fatty liver disease. 1640 78

This study aimed to elucidate the relationship of type 2 diabetes, other known risk factors, and primary hepatocellular carcinoma (HCC) in countries with a high prevalence of hepatitis infection. We followed a prospective cohort of 54,979 subjects who participated in the Keelung Community-Based Integrated Screening program between 1999 and 2002. A total of 5,732 subjects with type 2 diabetes cases were identified at enrollment on the basis of fasting blood glucose level, and a total of 138 confirmed HCC cases were identified either through two-stage liver cancer screening or linkage with the National Cancer Registry. The independent effect of type 2 diabetes on the incidence of HCC and the interaction between type 2 diabetes and hepatitis infection or lipids profile were assessed using the Cox proportional hazards regression model. After controlling for age, sex, hepatitis B virus (HBV), hepatitis C virus (HCV), smoking, and alcohol consumption, the association between type 2 diabetes and incidence of HCC (excluding 33 prevalent cases identified at enrollment) was modified by HCV status and cholesterol level. The associations were only statistically significant (adjusted hazard ratio [HR] = 2.08 [1.03-4.18]) for being HCV negative and for having hypercholesterolemia (adjusted HR = 2.81 [1.20-6.55]). These statistically significant findings remained even excluding cases of diabetes newly diagnosed at enrollment. In conclusion, in an area with a high prevalence of hepatitis virus infection, type 2 diabetes increases the risk of developing HCC in those who are HCV negative or have a high level of total cholesterol.
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PMID:Type 2 diabetes and hepatocellular carcinoma: A cohort study in high prevalence area of hepatitis virus infection. 1713 79


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