Gastroenterology

Gastroenterology

Volume 114, Issue 2, February 1998, Pages 311-318
Gastroenterology

Liver, Pancreas, and Biliary Tract
Increased hepatic iron concentration in nonalcoholic steatohepatitis is associated with increased fibrosis,☆☆,

https://doi.org/10.1016/S0016-5085(98)70482-2Get rights and content

Abstract

Background & Aims: Nonalcoholic steatohepatitis (NASH) is a chronic liver disease that occasionally progresses to cirrhosis but usually has a benign course. The aim of this study was to investigate the role of the hemochromatosis mutation Cys282Tyr in development of the mild hepatic iron overload found in some patients with NASH and its association with hepatic damage in these patients. Methods: Fifty-one patients with NASH were studied. The presence of the Cys282Tyr mutation was tested in all patients, and the data were analyzed with respect to the histological grade of steatosis, inflammation, Perls' staining, hepatic iron concentration (HIC), and serum iron indices. Results: Thirty-one percent of patients with NASH were either homozygous or heterozygous for the Cys282Tyr mutation. This mutation was significantly associated with Perls' stain grade (P < 0.005), HIC (P < 0.005), and transferrin saturation percentage (P < 0.005) but not with serum ferritin levels. Linear regression analysis showed that increased hepatic iron (Perls' stain or HIC) had the greatest association with the severity of fibrosis (P < 0.0001). Conclusions: The Cys282Tyr mutation is responsible for most of the mild iron overload found in NASH and thus has a significant association with hepatic damage in these patients. Heterozygosity for the hemochromatosis gene mutation therefore cannot always be considered benign.

GASTROENTEROLOGY 1998;114:311-318

Section snippets

Patients

Fifty-one patients in whom NASH was diagnosed were studied. The diagnosis of NASH was made on the basis of the presence of predominantly macrovesicular steatosis with lobular inflammation. The presence of Mallory's bodies and hepatic fibrosis was not considered essential for the diagnosis. No patient had a family history of hemochromatosis, and no patient was diagnosed or treated as having hemochromatosis after initial investigation and liver biopsy, because no patient fitted the accepted

General characteristic of the cohort of NASH patients studied

The main laboratory and histological features of the 51 patients with NASH studied are summarized in Table 1. The HIC of the patients with NASH ranged from 1 to 81 mmol/g dry wt. The men with NASH (51%) tended to be younger and have higher hepatic iron stores than the women. For this reason, results in Table 1 are presented for each sex. In this group of patients with NASH, in support of our clinical impression, 62% (26 of 42) had serum ferritin levels of >300 mmol/L, whereas only 22% (9 of 41)

Discussion

Most previous publications on NASH have not commented on iron stores in the liver. This study has confirmed that many patients with NASH have elevated serum ferritin levels at presentation (62%), although their TS results are usually normal. It also demonstrates that most patients with NASH with stainable hepatic iron stores have 1 or 2 copies of the Cys282Tyr mutation. Furthermore, increased hepatic iron stores may be a major determinant of fibrosis in patients with NASH.

The recognition of

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    Supported by a Program Grant from the National Health and Medical Research Council of Australia. Graeme A. Macdonald is a National Health and Medical Research Council of Australia Medical Postgraduate Scholar. Elizabeth C. Jazwinska is a Senior Research Fellow of the Gastroenterological Society of Australia.

    ☆☆

    Address requests for reprints to: Lawrie W. Powell, M.D., Ph.D., Queensland Institute of Medical Research, The Bancroft Centre, P.O. Royal Brisbane Hospital, Brisbane, Queensland, Australia 4029.

    Drs. George and Goldwurm contributed equally to this work.

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