Non-alcoholic steatohepatitis: a common cause of progressive chronic liver injury?

AIM: To investigate the natural history of patients with non-alcoholic steatohepatitis by means of a prospective histological study. METHODS: One thousand five hundred and seventy one patients underwent liver biopsy at the Western Infirmary in Glasgow during the 10 year period 1985 to 1994. All biopsies were reported by a single pathologist: 62 were confirmed as having non-alcoholic steatohepatitis and prospective follow up was conducted in 1999. Repeat liver biopsy was carried out where appropriate to assess disease progression. RESULTS: Initial biopsy scores for the 62 patients (20 men; mean age at biopsy, 52 years) showed a mean of 1.85, 1.39, and 0.5 for necroinflammation, fibrosis, and iron stores, respectively. Forty six were traceable and invited for review, and 26 attended (six men; mean age at initial biopsy, 49.9 years) at a mean of 8.7 years after the initial liver biopsy. No patients had symptoms or signs of chronic liver disease. Four patients had normal liver function tests, one had cirrhosis; the remaining 21 were invited to have a repeat biopsy. Seven patients agreed, a mean 8.2 years after the initial biopsy, and repeat biopsy scores showed no significant difference over this time period, with mean scores of 1.71 (initial score, 2.14), 1.43 (initial score, 0.71), and 0.14 (initial score, 0) for necroinflammation, fibrosis, and iron stores, respectively. CONCLUSION: In this series of patients with non-alcoholic steatohepatitis, with a mean clinical follow up of 8.7 years, and a histological follow up of 8.2 years, there was no evidence of progressive chronic liver injury.

The role of iron and haemochromatosis gene mutations in the progression of liver disease in chronic hepatitis C.

BACKGROUND: Chronic hepatitis C virus (HCV) infection is frequently associated with elevated markers of iron stores. Recessively inherited mutations in the HFE gene are responsible for iron accumulation in most cases of hereditary haemochromatosis and may have a role in HCV infection. They may also be associated with progressive liver fibrosis although this remains controversial. AIMS: To assess the prevalence of HFE mutations in Scottish HCV infected patients and to explore the effect of the carrier state on serum and liver iron stores, and the severity of liver disease. PATIENTS: A total of 164 patients with antibodies to HCV who underwent liver biopsy were assessed prospectively. METHODS: Each patient was screened for HFE mutations (Cys282Tyr and His63Asp). Iron markers were assessed in serum (ferritin, transferrin saturation) and on liver biopsy (stainable iron, liver iron concentration (LIC) and hepatic iron index). RESULTS: There were 67 (41%, 26 Cys282Tyr, 33 His63Asp, eight compound) heterozygotes. Forty four (28%) patients had elevated serum iron markers, 24 (15%) had stainable liver iron, and five (3%) had elevated LICs. Carriage of HFE mutations was not associated with any clinical, biochemical, virological, or pathological features, including accumulation of liver iron. Elevated serum iron markers were associated with male sex, increased alcohol consumption, and increased liver inflammation and fibrosis. Patients with elevated LICs were older, acquired HCV infection earlier, and had more liver inflammation. CONCLUSIONS: Patients with chronic HCV infection frequently have elevated serum iron markers although elevated LICs are uncommon. Elevated serum iron studies and LICs occur in patients with more severe liver disease. Carriage of HFE mutations, although frequently observed in these HCV infected patients, does not have a role in the accumulation of iron or the progression of liver disease in HCV infection.