NATAP/DDW: Pioglitazone Treatment for

[Guest guest]

NATAP - www.natap.org

PILOT STUDY OF PIOGLITAZONE IN NONALCOHOLIC STEATOHEPATITIS

Reported by Jules Levin

Insulin resistance is common in patients with nonalcoholic steatohepatitis

(NASH) and may be involved in the pathogenesis of this disease. Promrat and

colleagues reported the results of pilot study at DDW (May, 2003) using

pioglitazone (insulin-sensitizing agent) in nondiabetic patients with histologic

features of NASH (non-alcoholic steatosis hepatitis).

The purpose of the study was to determine if 1 year of treatment with the

insulin sensitizing agent, pioglitazone, will reduce hepatic steatosis,

inflammation and fibrosis in patients with NASH.

Twenty patients (9 men) with biopsy-proven NASH without diabetes were treated

with 30 mg of pioglitazone daily for 48 weeks. Medical evaluation and liver

biopsy were performed before and at the end of treatment. Insulin sensitivity

was assessed by oral glucose tolerance test (OGTT) and frequently sampled

intravenous glucose tolerance test (FSIGT). Liver histology was scored for

degree

of steatosis, cellular injury, parenchymal and portal inflammation, Mallory

bodies and fibrosis.

Nine patients have completed 48 weeks of treatment. Serum ALT decreased in

all 9 and were normal in 7 (78%) at 48 wks; mean ALT decreasing from 90.6 to 34

U/L . Insulin sensitivity also improved with decreases in fasting insulin from

18.4 to 10.6 mIU/ml, C-peptide from 5.5 to 3.3ng/ml, and free fatty acids

from 815.8 to 597.5 mEQ/L..

Also improved were estimates of insulin sensitivity including QUICKI (0.32 to

0.34), HOMA-IR (Homeostasis model assessment- insulin resistance index) (3.72

to 2.50) and insulin sensitivity derived from FSIGT (1.18 to 2.65 x 10-4

min-1._U-1.ml-1).

End-of-treatment liver biopsies showed significant improvements in steatosis,

Mallory bodies and parenchymal inflammation. Fibrosis (0-4) improved from 2.3

to 1.8 P=0.10). Steatosis improved from 2.1 to 1.1 (p=0.02). Mallory bodies

(0-4) improved from 2.1 to 1.1 (p=0.04). Parenchial inflammation (0-4) improved

from 2.6 to 1.4 (p=0.05). Portal inflammation (0-4) improved from 2.0 to 1.8

p=0.58).

Five (56%) patients had improvements in at least three features of

steatohepatitis. None had worsening of liver histology or fibrosis. The main

side effect

of pioglitazone was weight gain, which averaged 3.5 kg. All patients had

increased total body fat by DEXA (31.7 to 33.7%, p=0.01), even among those who

lost weight.

The authors concluded that in non-diabetic patients with NASH, a 48-week

course of pioglitazone was associated with significant improvements in insulin

sensitivity, serum ALT and histologic features of NASH but induced gain in

adiposity.

Promrat K, Lutchman G, Kleiner DE, et al. Pilot study of pioglitazone in

nonalcoholic steatohepatitis. Gastroenterology. 2003;124:A-708. DDW Conference,

May 17-22, 2003, Orlando, FL [Abstract #334]

to get off this Email list reply with your Email address and unsubscribe in

the Subject.