Plasma transforming growth factor-beta 1 level and efficacy of alpha-tocopherol in patients with non-alcoholic steatohepatitis: a pilot study

Background: Non-alcoholic steatohepatitis is a distinct entity, characteriz ed by fatty change, lobular inflammation and fibrosis of the liver. Some ca ses of non-alcoholic steatohepatitis progress to cirrhosis, but it is not e asy to distinguish this disease from non-alcoholic fatty liver by non-invas ive examinations. No proven therapy for nonalcoholic steatohepatitis exists . Transforming growth factor-beta1 is implicated in the development of live r fibrosis, and is inhibited by alpha -tocopherol (vitamin E) in the liver. Therefore, in this study, the significance of the measurement of the level of plasma transforming growth factor-beta1 and the effect of a-tocopherol on the clinical course of non-alcoholic steatohepatitis were investigated. Methods: Twelve patients with non-alcoholic steatohepatitis and 10 patients with non-alcoholic fatty liver, with a diagnosis confirmed by liver biopsy , were studied. None of the patients had a history of alcohol abuse, habitu al medicine or malignant or inflammatory diseases. All patients were negati ve for hepatitis B, C and G virus. Patients were given dietary instruction for 6 months, and then alpha -tocopherot (300 mg/day) was given for 1 year. Blood chemistries, measurement of plasma transforming growth factor-beta1 level and liver biopsies were undertaken before and after the 1-year alpha -tocopherol treatment. Results: The serum alanine transaminase level decreased in non-alcoholic fa tty liver patients, but not in non-alcoholic steatohepatitis patients, afte r 6 months of dietary therapy. Although the serum alanine transaminase leve l in non-alcoholic steatohepatitis patients was reduced during the 1-year a lpha -tocopherol treatment, a-tocopherol had no effect on the serum alanine transaminase level in non-alcoholic fatty liver patients. The histological findings, such as steatosis, inflammation and fibrosis, of the non-alcohol ic steatohepatitis patients were improved after alpha -tocopherol treatment . The plasma transforming growth factor-beta1 level in non-alcoholic steato hepatitis patients was significantly elevated compared with that in non-alc oholic fatty liver patients and healthy controls, and decreased, accompanie d by an improvement in serum alanine transaminase level, with alpha -tocoph erol treatment. Conclusions: Our data suggest that the measurement of the level of plasma t ransforming growth factor-beta1 represents a possible method of distinguish ing between non-alcoholic steatohepatitis and non-alcoholic fatty liver. Lo ng-term alpha -tocopherol treatment may be safe and effective for non-alcoh olic steatohepatitis. A randomized, controlled, double-blind trial is neede d to confirm the full potential of alpha -tocopherol in the management of n on-alcoholic steatohepatitis.