The clinical significance of slightly to moderately increased liver transaminase values in asymptomatic patients

Mathiesen, Ulrik; Franzén, LE; Frydén, Aril; Foberg, U; Bodemar, Göran

doi:10.1097/00042737-199904000-00025

Cited by 60 publications

(69 citation statements)

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“…Alanine aminotransferase is, however, commonly used as a surrogate of non-alcoholic liver steatosis and is considered to be a clinically relevant variable [4,19,20]. The concentration of ASAT which is more associated with alcohol consumption was increased in the same proportion of patients in the three genetic groups [2,18].…”

Section: Discussionmentioning

confidence: 99%

Association between microsomal triglyceride transfer protein gene polymorphism and the biological features of liver steatosis in patients with Type II diabetes

Touzet²,

et al. 2000

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The term non-alcoholic steatohepatitis (NASH) describes liver disease histologically similar to alcoholic liver disease occurring in patients without any history of excessive alcohol consumption [1,2]. Two main histological criteria are necessary for the diagnosis of NASH: fatty degeneration and inflammation or fibrosis. The latter criteria distinguishes NASH from simple steatosis which has a non-progressive course [3]. In western countries, NASH is a major cause of increased liver enzymes, next to alcohol consumption and hepatitis C [2]. It is frequently associated with obesity (40 %), Type II diabetes (20 %) and hyperlipidaemia (20 %) We therefore assessed the association between a functional polymorphism in the promoter region of MTP gene (±493 G/T) and the biological features of steatohepatitis in Type II diabetic patients. Methods. We studied 271 patients with Type II diabetes. Determination of ±493 G/T polymorphism was made by PCR-RFLP. Increased liver enzymes were used as surrogates of liver steatosis and alanine aminotransferase concentration was the outcome variable for the multivariate analysis. Liver ultrasonography was available for a subgroup of patients with newly diagnosed diabetes.Results. The proportion of patients with increased alanine aminotransferase was higher in GG than in GT and TT subgroups (23 %, 11 % and 6 %, respectively, p = 0.01). Additionally, patients with high alanine aminotransferase concentrations were more likely to be young (p = 0.01), male (p = 0.001), obese (p = 0.04) and have low HDL-cholesterol (p = 0.01).In multivariate analysis, the MTP genotype was independently associated with alanine aminotransferase concentration (p = 0.0023) as well as sex and body mass index but not HDL-cholesterol. Conclusion/interpretation. The ±493 G/T MTP gene polymorphism is associated with biological surrogates of steatohepatitis in patients with Type II diabetes. The G allele which is responsible for a decrease in MTP gene transcription is prone to increase the intrahepatic triglycerides content, conferring by this a genetic susceptibility for steatohepatitis. [Diabetologia (2000) 43: 995±999]

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Section: Discussionmentioning

confidence: 99%

Association between microsomal triglyceride transfer protein gene polymorphism and the biological features of liver steatosis in patients with Type II diabetes

Touzet²,

et al. 2000

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“…A diagnostic workup was performed including physical examination, laboratory investigations, and liver biopsy. 12 One hundred and forty-four patients were diagnosed with hepatic steatosis without any other concomitant liver disease or medication associated with fatty infiltration of the liver. Seven of these subjects reported at baseline current or previous average weekly alcohol consumption Ն 140 g and were excluded from follow-up.…”

Section: Methodsmentioning

confidence: 99%

Long-term follow-up of patients with NAFLD and elevated liver enzymes

Ekstedt¹,

Franzén

Mathiesen³

et al. 2006

Hepatology

2,078

1,714

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Nonalcoholic fatty liver disease (NAFLD) is the most common cause of elevated liver enzymes in patients of developed countries. We determined the long-term clinical and histological courses of such patients. In a cohort study, 129 consecutively enrolled patients diagnosed with biopsyproven NAFLD were reevaluated. Survival and causes of death were compared with a matched reference population. Living NAFLD patients were offered repeat liver biopsy and clinical and biochemical investigation. Mean follow-up (SD) was 13.7 (1.3) years. Mortality was not increased in patients with steatosis. Survival of patients with nonalcoholic steatohepatitis (NASH) was reduced (P ‫؍‬ .01). These subjects more often died from cardiovascular (P ‫؍‬ .04) and liver-related (P ‫؍‬ .04) causes. Seven patients (5.4%) developed end-stage liver disease, including 3 patients with hepatocellular carcinoma. The absence of periportal fibrosis at baseline had a negative predictive value of 100% in predicting liver-related complications. At follow-up, 69 of 88 patients had diabetes or impaired glucose tolerance. Progression of liver fibrosis occurred in 41%. These subjects more often had a weight gain exceeding 5 kg (P ‫؍‬ .02), they were more insulin resistant (P ‫؍‬ .04), and they exhibited more pronounced hepatic fatty infiltration (P ‫؍‬ .03) at follow-up. In conclusion, NAFLD with elevated liver enzymes is associated with a clinically significant risk of developing end-stage liver disease. Survival is lower in patients with NASH. Most NAFLD patients will develop diabetes or impaired glucose tolerance in the long term. Progression of liver fibrosis is associated with more pronounced insulin resistance and significant weight gain. (HEPATOLOGY 2006;44:865-873.)

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“…NAFLD is perhaps the most common of all liver disorders. [17][18][19][20][21][22][23] Wanless and Lentz 24 found steatosis in 70% of obese and 35% of lean patients and NASH in 18.5% of obese and 2.7% of lean patients in a consecutive autopsy study. Among obese patients, the prevalence of class 1 NAFLD (simple steatosis) is about 60%, whereas NASH is found in 20% to 25% and 2% to 3% have cirrhosis.…”

Section: Clinical Aspectsmentioning

confidence: 98%