Ursodeoxycholic acid or clofibrate in the treatment of non‐alcohol‐induced steatohepatitis: A pilot study

Non‐alcohol‐induced steatohepatitis (NASH) is characterized by elevated serum aminotransferase activities with hepatic steatosis, inflammation, and occasionally fibrosis that may progress to cirrhosis. No established treatment exists for this potentially serious disorder. Our aim was to conduct a pilot study to evaluate the safety and estimate the efficacy of ursodeoxycholic acid (UDCA) and clofibrate in the treatment of NASH. Forty patients were diagnosed with NASH based on a compatible liver biopsy with other causes of liver disease, including alcohol abuse, excluded by history, serum tests, and use of ultrasound. Twenty‐four patients received 13 to 15 mg/kg/d of UDCA for 12 months. Sixteen patients with hypertriglyceridemia were placed on clofibrate, 2 g/day for 12 months. Twenty‐five women and 15 men entered the study. Six of 40 patients (15%) withdrew because of side effects. Four additional patients were withdrawn because of noncompliance; one of them later required liver transplantation. In the UDCA group, the decreases in mean serum levels of alkaline phosphatase, alanine transaminase (ALT), and γ‐glutamyl transpeptidase (GGT) as well as histological grade of steatosis were significant. Among the patients treated with clofibrate, no change from baseline was found in mean ALT, aspartate transaminase (AST), GGT, bilirubin, triglycerides, and cholesterol, or in histological grade of steatosis, inflammation, or fibrosis after 12 months of treatment as compared with entry. Alkaline phosphatase activities decreased significantly from baseline. Despite the known lipid‐lowering effects of clofibrate, it did not appear to be of clinical benefit in the treatment of NASH in this 1‐year pilot study. However, treatment of NASH with UDCA for 12 months resulted in significant improvement in alkaline phosphatase, ALT, GGT, and hepatic steatosis. The possible benefit of UDCA therapy should be further investigated in the context of a randomized, controlled trial.

[1]  F. Perlík,et al.  [Ursodeoxycholic acid in the treatment of primary biliary cirrhosis]. , 1997, Casopis lekaru ceskych.

[2]  B. Neuschwander‐Tetri,et al.  Nonalcoholic steatohepatitis: an expanded clinical entity. , 1994, Gastroenterology.

[3]  C. Gluud,et al.  Hepatic effects of dietary weight loss in morbidly obese subjects. , 1991, Journal of hepatology.

[4]  F. Schaffner,et al.  Effect of weight reduction on hepatic abnormalities in overweight patients. , 1990, Gastroenterology.

[5]  I. Wanless,et al.  Fatty liver hepatitis (steatohepatitis) and obesity: An autopsy study with analysis of risk factors , 1990, Hepatology.

[6]  F. Heller,et al.  The rationale for using ursodeoxycholic acid in chronic liver disease. , 1990, Acta gastro-enterologica Belgica.

[7]  R. Hanson,et al.  The natural history of nonalcoholic steatohepatitis: A follow‐up study of forty‐two patients for up to 21 years , 1990, Hepatology.

[8]  Randall G. Lee,et al.  Nonalcoholic steatohepatitis: a study of 49 patients. , 1989, Human pathology.

[9]  K. Ishak,et al.  Alcohollike liver disease in nonalcoholics. A clinical and histologic comparison with alcohol-induced liver injury. , 1988, Gastroenterology.

[10]  K. Ishak,et al.  ALCOHOL-LIKE DISEASE IN NONALCOHOLICS , 1988 .

[11]  K. Kawagoe,et al.  Comparison between nonalcoholic steatohepatitis and alcoholic hepatitis. , 1987, The American journal of gastroenterology.

[12]  K. Eriksson,et al.  Nonalcoholic steatohepatitis in obesity: a reversible condition. , 2009, Acta medica Scandinavica.

[13]  T. Peters,et al.  Raised hepatic free fatty acids in a patient with acute fatty liver after gastric surgery for morbid obesity. , 1986, Journal of clinical pathology.

[14]  F. Schaffner,et al.  Nonalcoholic fatty liver disease. , 1986, Progress in liver diseases.

[15]  J. Schölmerich,et al.  Influence of Hydroxylation and Conjugation of Bile Salts on Their Membrane‐Damaging Properties‐Studies on Isolated Hepatocytes and Lipid Membrane Vesicles , 1984, Hepatology.

[16]  C. Gluud,et al.  Liver morphology in morbid obesity: a literature study. , 1984, International journal of obesity.

[17]  R. Komorowski,et al.  Hepatic Free Fatty Acids in Alcoholic Liver Disease and Morbid Obesity , 2007, Hepatology.

[18]  T. Peters,et al.  Biochemical analysis of hepatic lipid in alcoholic and diabetic and control subjects. , 1983, Clinical science.

[19]  J. Ludwig,et al.  Nonalcoholic steatohepatitis: Mayo Clinic experiences with a hitherto unnamed disease. , 1980, Mayo Clinic proceedings.

[20]  E. Smuckler,et al.  Lipid content in the liver of fatty metamorphosis of pregnancy. , 1975, The American journal of pathology.

[21]  D. Acosta,et al.  Injury produced by free fatty acids to lysosomes and mitochondria in cultured heart muscle and endothelial cells. , 1974, Atherosclerosis.

[22]  G. Korb,et al.  Five-year follow-up study of patients with nonalcoholic and nondiabetic fatty liver. , 1974, Acta hepato-gastroenterologica.

[23]  L. J. Duncan,et al.  Follow-up study of refractory obesity treated by fasting. , 1968, British medical journal.

[24]  D. Brown,et al.  The effect of ethyl α-p. Chlorophenoxyisobutyrate on ethanol-induced hepatic steatosis in the rat , 1966 .

[25]  D. Brown.  The effect of ethyl alpha-p. chlorophenoxyisobutyrate on ethanol-induced hepatic steatosis in the rat. , 1966, Metabolism: clinical and experimental.