Gastroenterology

Gastroenterology

Volume 123, Issue 1, July 2002, Pages 134-140
Gastroenterology

Clinical–Liver, Pancreas, and Biliary Tract
Expanding the natural history of nonalcoholic steatohepatitis: From cryptogenic cirrhosis to hepatocellular carcinoma

https://doi.org/10.1053/gast.2002.34168Get rights and content

Abstract

Background & Aims: Nonalcoholic steatohepatitis (NASH) may progress to cirrhosis; whether NASH plays also a role in the development of hepatocellular carcinoma (HCC) is unknown. Methods: Among 641 cirrhosis-associated HCCs, we retrospectively identified 44 patients with cryptogenic cirrhosis (CC). Of these, 23 were actively followed up and were compared in a case-control study with viral- and alcohol-associated HCC. Family and personal history of diabetes, hypertension, coronary heart disease, dyslipidemia, obesity, and biochemical data were compared between groups. Iron status and presence of mutations in the HFE gene of familiar hemochromatosis were also determined. Results: Family history was not different in relation to etiology. The prevalence of obesity and diabetes was significantly higher in patients with CC. Although liver function was similar, CC patients had higher glucose, cholesterol, and triglyceride plasma levels, increased parameters of insulin resistance, and lower aminotransferase levels. Iron status and prevalence of mutations in the HFE gene did not differ. Logistic regression analysis identified in sequence hypertriglyceridemia, diabetes, and normal aminotransferases as independent factors associated with HCC arising in CC. Conclusions: Features suggestive of NASH are more frequently observed in HCC arising in patients with CC than in age- and sex-matched HCC patients of well-defined viral or alcoholic etiology. HCC may represent a late complication of NASH-related cirrhosis.

GASTROENTEROLOGY 2002;123:134-140

Section snippets

Patients

Among 786 white patients with HCC superimposed to liver cirrhosis identified from our Liver Unit registry since 1990, 641 had been submitted to an extensive investigation as part of a diagnostic workup aimed at evaluation for liver transplantation, hepatic resection, or nonsurgical treatment of HCC. In these patients, sufficient data were available to establish the etiology of liver disease.

The clinical history and laboratory data had failed to identify any recognizable cause in 46 patients who

Results

The prevalence of CC in 641 patients with HCC was 6.9%, compared with 54.9% in patients with HCV-related cirrhosis, 16.2% in patients with HBV-related cirrhosis, and 12.9% in patients with postalcoholic cirrhosis. The remaining patients (7.6%) had cirrhosis of mixed etiology (contemporary presence of HBV and/or HCV and/or alcohol). Only a small proportion of patients had hemochromatosis or primary biliary cirrhosis (1.4%). Patients with CC and HCC were older in comparison with the entire

Discussion

This study demonstrates that features suggestive of the metabolic syndrome,9 including type 2 diabetes, obesity, dyslipidemia, and insulin resistance, are observed more frequently in patients with HCC superimposed on cirrhosis of unknown etiology than in carefully matched control patients. Our data are consistent with the existence of a metabolic disorder leading first to fatty liver and then to HCC via NASH, fibrosis, and cirrhosis.

There is a broad consensus that NASH patients share many of

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    Address requests for reprints to: Elisabetta Bugianesi, M.D, Department of Gastroenterology, Ospedale S. Giovanni Battista, Corso Bramante 88, 10126 Torino, Italy. e-mail: [email protected]; fax: (39) 011-633-5927.

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