Plasma transforming growth factor-beta1 level and efficacy of alpha-tocopherol in patients with non-alcoholic steatohepatitis: a pilot study.
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.
Hasegawa
T
T
Second Department of Medicine, Asahikawa Medical College, Asahikawa, Japan.
Yoneda
M
M
Nakamura
K
K
Makino
I
I
Terano
A
A
D000328:Adult; D000410:Alanine Transaminase / Q000378:metabolism; D000469:Alkaline Phosphatase / Q000378:metabolism; D001219:Aspartate Aminotransferases / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D005234:Fatty Liver / Q000097:blood / Q000178:diet therapy / Q000188:drug therapy; D005260:Female; D006505:Hepatitis / Q000097:blood* / Q000178:diet therapy / Q000188:drug therapy / Q000201:enzymology; D006801:Humans; D008103:Liver Cirrhosis / Q000188:drug therapy; D008297:Male; D010865:Pilot Projects; D016212:Transforming Growth Factor beta / Q000097:blood*; D053773:Transforming Growth Factor beta1; D014280:Triglycerides / Q000097:blood; D024502:alpha-Tocopherol / Q000627:therapeutic use*; D005723:gamma-Glutamyltransferase / Q000378:metabolism
C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D014280:Triglycerides; D002784:Cholesterol; D005723:gamma-Glutamyltransferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase; D024502:alpha-Tocopherol