TY - JOUR
T1 - Meta-analysis
T2 - Insulin sensitizers for the treatment of non-alcoholic steatohepatitis
AU - Rakoski, M. O.
AU - Singal, A. G.
AU - Rogers, M. A M
AU - Conjeevaram, H.
PY - 2010/11
Y1 - 2010/11
N2 - Non-alcoholic fatty liver disease generally has a benign course; however, patients with non-alcoholic steatohepatitis (NASH) may progress to cirrhosis and hepatocellular carcinoma. Currently, there is a lack of consensus about optimal NASH treatment. Aim To assess the efficacy of insulin-sensitizing agents on histological and biochemical outcomes in randomized control trials of biopsy-proven NASH. Methods Multiple online databases and conference abstracts were searched. Random effects meta-analyses were performed, with assessment for heterogeneity and publication bias. Results Nine trials were included; five trials using thiazolidinediones (glitazones), three using metformin and one trial using both drugs. There was no publication bias. Compared with controls, glitazones resulted in improved steatosis (WMD = 0.57, 95% CI 0.36-0.77, P = <0.001), hepatocyte ballooning (WMD = 0.36, 95% CI 0.24-0.49, P < 0.001) and ALT (WMD = 16.4, 95% CI 7.7-25.0, P < 0.001), but not inflammation (P = 0.09) or fibrosis (P = 0.11). In patients without diabetes, glitazones significantly improved all histological and biochemical outcomes, most importantly including fibrosis (WMD = 0.29, 95% CI 0.078-0.51, P = 0.008). Metformin failed to improve any pooled outcome. Conclusions Treatment of NASH with glitazones, but not metformin, demonstrates a significant histological and biochemical benefit, especially in patients without diabetes. Additional studies are needed to investigate long-term outcomes of glitazone therapy in patients without diabetes.
AB - Non-alcoholic fatty liver disease generally has a benign course; however, patients with non-alcoholic steatohepatitis (NASH) may progress to cirrhosis and hepatocellular carcinoma. Currently, there is a lack of consensus about optimal NASH treatment. Aim To assess the efficacy of insulin-sensitizing agents on histological and biochemical outcomes in randomized control trials of biopsy-proven NASH. Methods Multiple online databases and conference abstracts were searched. Random effects meta-analyses were performed, with assessment for heterogeneity and publication bias. Results Nine trials were included; five trials using thiazolidinediones (glitazones), three using metformin and one trial using both drugs. There was no publication bias. Compared with controls, glitazones resulted in improved steatosis (WMD = 0.57, 95% CI 0.36-0.77, P = <0.001), hepatocyte ballooning (WMD = 0.36, 95% CI 0.24-0.49, P < 0.001) and ALT (WMD = 16.4, 95% CI 7.7-25.0, P < 0.001), but not inflammation (P = 0.09) or fibrosis (P = 0.11). In patients without diabetes, glitazones significantly improved all histological and biochemical outcomes, most importantly including fibrosis (WMD = 0.29, 95% CI 0.078-0.51, P = 0.008). Metformin failed to improve any pooled outcome. Conclusions Treatment of NASH with glitazones, but not metformin, demonstrates a significant histological and biochemical benefit, especially in patients without diabetes. Additional studies are needed to investigate long-term outcomes of glitazone therapy in patients without diabetes.
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U2 - 10.1111/j.1365-2036.2010.04467.x
DO - 10.1111/j.1365-2036.2010.04467.x
M3 - Article
C2 - 20955440
AN - SCOPUS:78249262957
SN - 0269-2813
VL - 32
SP - 1211
EP - 1221
JO - Alimentary Pharmacology and Therapeutics
JF - Alimentary Pharmacology and Therapeutics
IS - 10
ER -