In the study by Ziegler-Sagi et al.,99 orlistat reportedly improved ALT and steatosis by US, but its effect on liver histology could not be evaluated because the majority of patients did not undergo

a follow-up liver biopsy. However, in the study by Harrison et al.,100 orlistat did not improve body weight or liver histology. The best evidence for weight loss as a means to improve liver histology in NASH comes from a trial that randomized 31 obese persons with NASH to intensive lifestyle changes (diet, behaviour modification and 200 minutes a week of moderate physical activity for 48 weeks) selleckchem versus structured basic education alone.101 The intensive arm had 9.3% weight loss (versus 0.2% in the dietary counseling alone arm) and led to an improvement in steatosis, necrosis and inflammation, but not fibrosis. Importantly, participants with ≥ 7% weight loss had significant improvement

in steatosis, lobular inflammation, ballooning, and NAFLD Activity Score (NAS).101 There was a similar pattern in the study by Harrison et al.,100 where participants who lost > 5% body weight improved steatosis, whereas individuals with ≥ 9% weight loss had significant improvement in steatosis, lobular inflammation, ballooning, and NAS. A number of recent studies used MR spectroscopy to assess changes Selleckchem ABT-263 in hepatic fat in response to lifestyle modification. The results from these studies using a variety of interventions, either by diet alone81, 83, 84, 89, 92, 93 or in combination with OSBPL9 different exercise prescriptions,82, 85-88, 92, 94 have consistently reported a significant reduction in liver fat by an average of ∼40% (ranging from 20% to 81%). The degree of hepatic fat reduction was proportional to the intensity of the lifestyle intervention and generally required

a body weight loss between ∼5 to 10%.82, 88, 92 The effect of exercise without dietary modification on hepatic steatosis was investigated in four studies using MR spectroscopy.102-105 Exercise programs consisted of 2-3 sessions a week of 30-60 minutes over a period of 6 to 12 weeks. In all but one study101 liver fat content diminished without a significant change in body weight. Recommendations 16. Weight loss generally reduces hepatic steatosis, achieved either by hypocaloric diet alone or in conjunction with increased physical activity. (Strength – 1, Evidence – A) 17. Loss of at least 3-5% of body weight appears necessary to improve steatosis, but a greater weight loss (up to 10%) may be needed to improve necroinflammation. (Strength – 1, Evidence – B) 18. Exercise alone in adults with NAFLD may reduce hepatic steatosis but its ability to improve other aspects of liver histology remains unknown. (Strength – 1, Evidence – B) Several studies investigated the effect of metformin on aminotransferases and liver histology in patients with NASH. Early small, open-label studies demonstrated a reduction in insulin resistance and aminotransferases106-108 but no significant improvement in liver histology.