Lifestyle intervention for morbid obesity: effects on liver steatosis, inflammation, and fibrosis

Abstract

The prevalence of obesity-related nonalcoholic fatty liver disease (NAFLD) is rising. NAFLD may result in nonalcoholic steatohepatitis (NASH), progressing to liver cirrhosis. Weight loss is recommended to treat obesity-related NASH. Lifestyle intervention may improve NASH; however, pertinent trials have so far focused on overweight patients, whereas patients with obesity are at highest risk of developing NAFLD. Furthermore, reports of effects on liver fibrosis are scarce. We evaluated the effect of lifestyle intervention on NAFLD in a real-life cohort of morbidly obese patients. In our observational study, 152 patients underwent lifestyle intervention, with a follow-up of 52 weeks. Noninvasive measures of obesity, metabolic syndrome, liver steatosis, liver damage, and liver fibrosis were analyzed. Treatment response in terms of weight loss was achieved in 85.1% of patients. Dysglycemia and dyslipidemia improved. The proportion of patients with fatty liver dropped from 98.1 to 54.3% ( P < 0.001). Weight loss >10% was associated with better treatment response ( P = 0.0009). Prevalence of abnormal serum transaminases fell from 81.0 to 50.5% ( P < 0.001). The proportion fibrotic patients, as determined by the NAFLD fibrosis score, dropped from 11.8 to 0% ( P < 0.05). Low serum levels of adiponectin correlated with degree of liver damage, i.e., serum liver transaminases ( r = -0,32, P < 0.05). Serum levels of adiponectin improved with intervention. In conclusion, lifestyle intervention effectively targeted obesity and the metabolic syndrome. Liver steatosis, damage and fibrosis were ameliorated in this real-life cohort of morbidly obese patients, mediated in part by changes in the adipokine profile. Patients with weight loss of >10% seemed to benefit most. NEW & NOTEWORTHY We demonstrate new evidence that lifestyle intervention is effective in treating NAFLD in the important group of patients with (morbid) obesity. Although current guidelines on the therapy of NASH recommend weight loss of 5-7%, weight reduction >10% may be favorable in morbid obesity. Serum levels of adipokines correlate with liver damage, which is indicative of their pathogenetic importance in human NASH. Our study adds to the limited body of evidence that NAFLD-associated liver fibrosis may resolve with lifestyle intervention.

Effectiveness of lifestyle interventions in NAFLD (nonalcoholic fatty liver disease) – how are clinical trials affected?

“…In the trial by Hohenester et al, a weight loss of more than 10% showed a significant decline of ALT serum levels and an improvement of hepatic steatosis. In contrast, weight loss <10% was overall less significantly efficient in order to achieve a 'complete hepatic response' (normal serum ALT values, improved FLI and NFS) at week 52 [3].…”

“…Thus, further studies, that use less resources could be important in the management of NASH. In a monocentric, single arm, interventional study by Hohenester et al, the effects of a formula diet on hepatic steatosis and fibrosis were determined in patients with morbid obesity in Germany [3]. The intervention consisted of calorie restriction to 800 kcal/day for 12 weeks, with a follow-up of 13 weeks on a normal, balanced meal.…”

<p>Sequential Matrix Metalloproteinase-1 Expression Triggered by Infiltrating Monocytic Lineage Cells Modulates Pathophysiological Aspects of Human Nonalcoholic Steatohepatitis</p>

“…It is well known that obesity or metabolic syndrome per see can be a significant risk factor of liver fibrosis. 43 Even though all non-NASH subjects exhibited normal liver function values, we have to be careful when dealing with the obtained results. Ideally, MMP-1 expression should be analyzed and compared between patients with NASH and simple steatosis without any inflammation or fibrosis, both of which are diagnosed by liver biopsy.…”

Efficacy and safety of anti-hepatic fibrosis drugs

“…Weight loss of 5% via caloric restriction has been shown to improve steatosis, weight loss of 5% to 7% resulted in improved inflammation, and a 7%-10% reduction in weight led to possible NAFLD/NASH remission and improved fibrosis[ 51 ]. Investigation by Hohenester et al [ 52 ], found that 11.8% of patients demonstrated liver fibrosis at baseline via NAFLD fibrosis score. Following weight loss, 0% of patients were fibrotic after 52 wk ( P < 0.05).…”