Plasma transforming growth factor-beta1 level and efficacy of alpha-tocopherol in patients with non-alcoholic steatohepatitis: a pilot study

Aliment Pharmacol Ther. 2001 Oct;15(10):1667-72. doi: 10.1046/j.1365-2036.2001.01083.x.


Background: Non-alcoholic steatohepatitis is a distinct entity, characterized by fatty change, lobular inflammation and fibrosis of the liver. Some cases of non-alcoholic steatohepatitis progress to cirrhosis, but it is not easy to distinguish this disease from non-alcoholic fatty liver by non-invasive examinations. No proven therapy for non-alcoholic steatohepatitis exists. Transforming growth factor-beta1 is implicated in the development of liver 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 alpha-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, habitual medicine or malignant or inflammatory diseases. All patients were negative for hepatitis B, C and G virus. Patients were given dietary instruction for 6 months, and then alpha-tocopherol (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 fatty liver patients, but not in non-alcoholic steatohepatitis patients, after 6 months of dietary therapy. Although the serum alanine transaminase level in non-alcoholic steatohepatitis patients was reduced during the 1-year alpha-tocopherol treatment, alpha-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-alcoholic steatohepatitis patients were improved after alpha-tocopherol treatment. The plasma transforming growth factor-beta1 level in non-alcoholic steatohepatitis patients was significantly elevated compared with that in non-alcoholic fatty liver patients and healthy controls, and decreased, accompanied by an improvement in serum alanine transaminase level, with alpha-tocopherol treatment.

Conclusions: Our data suggest that the measurement of the level of plasma transforming growth factor-beta1 represents a possible method of distinguishing between non-alcoholic steatohepatitis and non-alcoholic fatty liver. Long-term alpha-tocopherol treatment may be safe and effective for non-alcoholic steatohepatitis. A randomized, controlled, double-blind trial is needed to confirm the full potential of alpha-tocopherol in the management of non-alcoholic steatohepatitis.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alanine Transaminase / metabolism
  • Alkaline Phosphatase / metabolism
  • Aspartate Aminotransferases / metabolism
  • Body Weight / drug effects
  • Cholesterol / blood
  • Fatty Liver / blood
  • Fatty Liver / diet therapy
  • Fatty Liver / drug therapy
  • Female
  • Hepatitis / blood*
  • Hepatitis / diet therapy
  • Hepatitis / drug therapy
  • Hepatitis / enzymology
  • Humans
  • Liver Cirrhosis / drug therapy
  • Male
  • Pilot Projects
  • Transforming Growth Factor beta / blood*
  • Transforming Growth Factor beta1
  • Triglycerides / blood
  • alpha-Tocopherol / therapeutic use*
  • gamma-Glutamyltransferase / metabolism


  • TGFB1 protein, human
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta1
  • Triglycerides
  • Cholesterol
  • gamma-Glutamyltransferase
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • Alkaline Phosphatase
  • alpha-Tocopherol