Clinical Advances in Liver, Pancreas, and Biliary TractRandomized, Placebo-Controlled Trial of Pioglitazone in Nondiabetic Subjects With Nonalcoholic Steatohepatitis
Section snippets
Materials and Methods
We recruited patients for the randomized, double-blind, placebo-controlled trial between November 25, 2002, and March 31, 2006, from the Queen's Medical Centre in Nottingham and from Derby City General Hospital (see Supplementary diagram online at www.gastrojournal.org). The study was approved by the Nottingham Joint Ethics Committee. (National Research Register Document: N0192119052; ISRCTN: 10319160.) Takeda Pharmaceuticals UK provided the pioglitazone and placebo tablets for this
Results
Baseline characteristics were similar for the 2 groups except for lower alkaline phosphatase and fasting insulin levels in the pioglitazone-treated group (Table 2, Table 3, Table 4). Although the mean γ-glutamyltransferase (GGT) level appears higher in the pioglitazone group, the 2 study groups were not significantly different in this respect.
Discussion
This was a randomized controlled trial evaluating a pharmacologic treatment for NASH in exclusively nondiabetic subjects. We have shown that treatment with pioglitazone 30 mg over a 12-month period reduced the degree of steatosis, hepatocellular injury, lobular inflammation, Mallory–Denk bodies, and fibrosis. Although hepatic steatosis improved in the placebo group, hepatocellular injury (representing ballooning degeneration, apoptosis, and drop-out hepatocytes) worsened during the study
References (41)
- et al.
Nonalcoholic steatohepatitis: association of insulin resistance and mitochondrial abnormalities
Gastroenterology
(2001) - et al.
NASH and insulin resistance: insulin hypersecretion and specific association with the insulin resistance syndrome
Hepatology
(2002) - et al.
Pioglitazone prevents early-phase hepatic fibrogenesis caused by carbon tetrachloride
Biochem Biophys Res Commun
(2002) - et al.
Nonalcoholic steatohepatitis: summary of an AASLD Single Topic Conference
Hepatology
(2003) - et al.
Metformin in non-alcoholic steatohepatitis
Lancet
(2001) - et al.
Nonalcoholic steatohepatitis: a proposal for grading and staging the histological lesions
Am J Gastroenterol
(1999) Liver biopsy size matters in hepatitis C: bigger is better
Hepatology
(2003)- et al.
Nonalcoholic fatty liver disease: a spectrum of clinical and pathological severity
Gastroenterology
(1999) - et al.
Is weight reduction an effective therapy for nonalcoholic fatty liver?A systematic review
Am J Med
(2003) - et al.
Liver fibrosis in overweight patients
Gastroenterology
(2000)
Clinical and histologic spectrum of nonalcoholic fatty liver disease associated with normal ALT values
Hepatology
The histological course of nonalcoholic fatty liver disease: a longitudinal study of 103 patients with sequential liver biopsies
J Hepatol
A pilot study of a thiazolidinedione, troglitazone, in nonalcoholic steatohepatitis
Am J Gastroenterol
Improved nonalcoholic steatohepatitis after 48 weeks of treatment with the PPAR-gamma ligand rosiglitazone
Hepatology
ACRP30/adiponectin: an adipokine regulating glucose and lipid metabolism
Trends Endocrinol Metab
Leptin and liver fibrosis: a matter of fat
Gastroenterology
Hypoadiponectinemia and NASH: cause or effect?
Gastroenterology
Interim results of a pilot study demonstrating the early effects of the PPAR-gamma ligand rosiglitazone on insulin sensitivity, aminotransferases, hepatic steatosis and body weight in patients with non-alcoholic steatohepatitis
J Hepatol
Pioglitazone treatment increases whole body fat but not total body water in patients with non-alcoholic steatohepatitis
J Hepatol
The natural history of nonalcoholic fatty liver disease: a population-based cohort study
Gastroenterology
Cited by (0)
Takeda Pharmaceuticals UK provided the pioglitazone and placebo tablets for this investigator-initiated study. Jonathan Webber has received funding from Takeda, Novo, Sanofi-Aventis, and Pfizer to attend meetings. Investigator conflicts of interests were disclosed to study participants.