Plasma transforming growth factor‐β1 level and efficacy of α‐tocopherol in patients with non‐alcoholic steatohepatitis: a pilot study

Abstract

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‐β1 is implicated in the development of liver fibrosis, and is inhibited by α‐tocopherol (vitamin E) in the liver. Therefore, in this study, the significance of the measurement of the level of plasma transforming growth factor‐β1 and the effect of α‐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 α‐tocopherol (300 mg/day) was given for 1 year. Blood chemistries, measurement of plasma transforming growth factor‐β1 level and liver biopsies were undertaken before and after the 1‐year α‐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 α‐tocopherol treatment, α‐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 α‐tocopherol treatment. The plasma transforming growth factor‐β1 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 α‐tocopherol treatment. Conclusions: lOur data suggest that the measurement of the level of plasma transforming growth factor‐β1 represents a possible method of distinguishing between non‐alcoholic steatohepatitis and non‐alcoholic fatty liver. Long‐term α‐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 α‐tocopherol in the management of non‐alcoholic steatohepatitis.