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A controlled trial of gemfibrozil in the treatment of patients with nonalcoholic steatohepatitis
Correspondence
A controlled trial of gemfibrozil in the treatment of patients with nonalcoholic steatohepatitis To the Editor, We read with interest the review article by James & Day (1) about non-alcoholic steatohepatitis (NASH). We agree that, as mentioned in the article, NASH is a progressive necroinflammatory liver disease which is frequently seen in clinical practice (2-6). Although a few drugs have been tested in patients with NASH, there is currently no accepted form of medical therapy (7). We recently reported the beneficial effects of gemfibrozil in the treatment of patients with NASH (an oral presentation: “A controlled trial of gemfibrozil in the treatment of nonalcoholic steatohepatitis” at the international Association for the Study of the Liver (IASL) in Chicago, 46 November 1998). In this trial, we have assessed the effects of gemfibrozil on NASH. We prospectively studied 46 patients (37 male, 9 female; mean age 42.728.6 years, range 2664 years) with NASH who had persistently (>6 months) elevated serum transaminase levels (ALT and/or AST). The diagnosis of NASH was based on histological examination Patients were excluded if they had an ethanol intake of more than 20 g/day, known associated medications, and other liver diseases. A simple, computer-generated, random-number list was prepared. The code was kept in an opaque, sealed envolope. The treatment group (19 male, 4 female; mean age 41.626.6 years, range 26 54 years) took gemfibrozil 600 mg/day orally for 4 weeks and the control group (18 male, 5 female; mean age 43.82 10.7 years, range 28-64 years) was without treatment. Serum levels of ALT, AST. GGT, triglyceride, and body mass index (BMI) were measured initially and at the end of 4 weeks. In both groups, mean serum alkaline phosphatase and bilirubin levels were in the normal range. The statistical analysis were performed by using the two-tailed paired ttest and Wilcoxon-Mann-Whitney test. Biochemical and clinical data in the gemfibrozil and control groups are shown in Table 1. Seventeen patients (74%) in the gemfibrozil group showed a decrease in ALT value versus seven patients (30%) in the control group. Mean serum ALT, AST, and GGT levels were significantly decreased in the gemfibrozil group in comparison with control (-25.4%?32.6% vs 9.1%?39.3%, p
TABLE
1
Biochemical groups
and
clinical
data
in gemfibrozil
(G) and
control
Measurement (normal values)
Gemfibrozil
group
Control
G’
G2
C’
C2
ALT (542 IU/l) AST (5-37 IU/l) GGT (O-42 IU/l) Triglyceride (60-l 70 mg/dl) BMI
72.0-r-37.0
49.7+28.2a,e
76.4t35.3d
76.7224.9
49.1220.4
38.9?20.2b,”
46.3?20.gd
53.5236.3
55.6k34.7
40.7-+30.4’,e
64.1?40.5d
65.1239.8
229’141
153?90”
2131t11gd
199r95
28.223.1
28.0+3.5d
28.3?3.4d
28.3k3.1
Gi , C’: Entry. G2, C2: 4 weeks later. a: p
384
(C)
vs
6.3%? 17.4%, p
References 1. James OFW, Day CI? Non-alcoholic steatohepatitis (NASH): a disease of emerging identity and importance. J Hepdtol 1998; 29: 4955501. 2. Adler M, Schaffner E Fatty liver hepatitis and cirrhosis in obese patients. Am J Med 1979; 67: 811-6. 3. Ludwig J, Viggiano TR, McGill DB, Ott BJ. Nonalcoholic steatohepatitis. Mayo Clinic experiences with a hitherto unnamed disease. Mayo Clin Proc 1980; 55: 4348. 4. Diehl AM, Goodman Z, Ishak KG. Alcohol-like liver disease in non-alcoholics. A clinical and histologic comparison with alcohol-induced liver injury. Gastroenterology 1988; 95: 105662. 5. Bacon BR, Farahvash MJ, Janney CG, Neuschwander-Tetri BA. Nonalcoholic steatohepatitis: an expanded clinical entity. Gastroenterology 1994: 107: 110339. 6. Byron D, Minuk GY. Profile of an urban hospital-based practice. Hepatology 1996: 24: 813-5. 7. Laurin J, Lindor KD, Crippin SJ, Gossard A, Gores GJ, Ludwig J, et al. Ursodeoxycholic acid or clofibrate in the treatment of non-alcohol-induced steatohepatitis: a pilot study. Hepatology 1996; 23: 146447. 8. Lombardi B. Considerations on the pathogenesis of fatty liver. Lab Invest 1966; 15: l-20. 9. Dianzani MU. Hepatotoxicology. In: Meeks RG, Harrison SD, Bull RJ, editors. Biochemical Aspects of Fatty Liver. Boca Raton: CRC; 1991. p. 327-99. 10 Kissebah AH, Alfarsi S. Adams PW, Seed M, Folkard J, Wynn V, et al. Transport kinetics of plasma free fatty acids, very low density lipoprotein triglycerides and apoprotein in patients with hypertriglyceridemia. Effects of 2,2-diemthyl, 5-(2,5-xylyloxy) valeric acid therapy. Diabetologia 1976: 24: 199-218. 11 Kesaniemi YA, Grundy SM. Influence of gemfibrozil and clofibrate on metabolism of cholesterol and plasma triglyceride in man. JAMA 1984; 251: 2241-6.
A controlled trial of gemfibrozil in the treatment of patients with nonalcoholic steatohepatitis To the Editor, We read with interest the review article by James & Day (1) about non-alcoholic steatohepatitis (NASH). We agree that, as mentioned in the article, NASH is a progressive necroinflammatory liver disease which is frequently seen in clinical practice (2-6). Although a few drugs have been tested in patients with NASH, there is currently no accepted form of medical therapy (7). We recently reported the beneficial effects of gemfibrozil in the treatment of patients with NASH (an oral presentation: “A controlled trial of gemfibrozil in the treatment of nonalcoholic steatohepatitis” at the international Association for the Study of the Liver (IASL) in Chicago, 46 November 1998). In this trial, we have assessed the effects of gemfibrozil on NASH. We prospectively studied 46 patients (37 male, 9 female; mean age 42.728.6 years, range 2664 years) with NASH who had persistently (>6 months) elevated serum transaminase levels (ALT and/or AST). The diagnosis of NASH was based on histological examination Patients were excluded if they had an ethanol intake of more than 20 g/day, known associated medications, and other liver diseases. A simple, computer-generated, random-number list was prepared. The code was kept in an opaque, sealed envolope. The treatment group (19 male, 4 female; mean age 41.626.6 years, range 26 54 years) took gemfibrozil 600 mg/day orally for 4 weeks and the control group (18 male, 5 female; mean age 43.82 10.7 years, range 28-64 years) was without treatment. Serum levels of ALT, AST. GGT, triglyceride, and body mass index (BMI) were measured initially and at the end of 4 weeks. In both groups, mean serum alkaline phosphatase and bilirubin levels were in the normal range. The statistical analysis were performed by using the two-tailed paired ttest and Wilcoxon-Mann-Whitney test. Biochemical and clinical data in the gemfibrozil and control groups are shown in Table 1. Seventeen patients (74%) in the gemfibrozil group showed a decrease in ALT value versus seven patients (30%) in the control group. Mean serum ALT, AST, and GGT levels were significantly decreased in the gemfibrozil group in comparison with control (-25.4%?32.6% vs 9.1%?39.3%, p
TABLE
1
Biochemical groups
and
clinical
data
in gemfibrozil
(G) and
control
Measurement (normal values)
Gemfibrozil
group
Control
G’
G2
C’
C2
ALT (542 IU/l) AST (5-37 IU/l) GGT (O-42 IU/l) Triglyceride (60-l 70 mg/dl) BMI
72.0-r-37.0
49.7+28.2a,e
76.4t35.3d
76.7224.9
49.1220.4
38.9?20.2b,”
46.3?20.gd
53.5236.3
55.6k34.7
40.7-+30.4’,e
64.1?40.5d
65.1239.8
229’141
153?90”
2131t11gd
199r95
28.223.1
28.0+3.5d
28.3?3.4d
28.3k3.1
Gi , C’: Entry. G2, C2: 4 weeks later. a: p
384
(C)
vs
6.3%? 17.4%, p
References 1. James OFW, Day CI? Non-alcoholic steatohepatitis (NASH): a disease of emerging identity and importance. J Hepdtol 1998; 29: 4955501. 2. Adler M, Schaffner E Fatty liver hepatitis and cirrhosis in obese patients. Am J Med 1979; 67: 811-6. 3. Ludwig J, Viggiano TR, McGill DB, Ott BJ. Nonalcoholic steatohepatitis. Mayo Clinic experiences with a hitherto unnamed disease. Mayo Clin Proc 1980; 55: 4348. 4. Diehl AM, Goodman Z, Ishak KG. Alcohol-like liver disease in non-alcoholics. A clinical and histologic comparison with alcohol-induced liver injury. Gastroenterology 1988; 95: 105662. 5. Bacon BR, Farahvash MJ, Janney CG, Neuschwander-Tetri BA. Nonalcoholic steatohepatitis: an expanded clinical entity. Gastroenterology 1994: 107: 110339. 6. Byron D, Minuk GY. Profile of an urban hospital-based practice. Hepatology 1996: 24: 813-5. 7. Laurin J, Lindor KD, Crippin SJ, Gossard A, Gores GJ, Ludwig J, et al. Ursodeoxycholic acid or clofibrate in the treatment of non-alcohol-induced steatohepatitis: a pilot study. Hepatology 1996; 23: 146447. 8. Lombardi B. Considerations on the pathogenesis of fatty liver. Lab Invest 1966; 15: l-20. 9. Dianzani MU. Hepatotoxicology. In: Meeks RG, Harrison SD, Bull RJ, editors. Biochemical Aspects of Fatty Liver. Boca Raton: CRC; 1991. p. 327-99. 10 Kissebah AH, Alfarsi S. Adams PW, Seed M, Folkard J, Wynn V, et al. Transport kinetics of plasma free fatty acids, very low density lipoprotein triglycerides and apoprotein in patients with hypertriglyceridemia. Effects of 2,2-diemthyl, 5-(2,5-xylyloxy) valeric acid therapy. Diabetologia 1976: 24: 199-218. 11 Kesaniemi YA, Grundy SM. Influence of gemfibrozil and clofibrate on metabolism of cholesterol and plasma triglyceride in man. JAMA 1984; 251: 2241-6.