Regular physical exercise significantly improved measures of nonalcoholic fatty liver disease independently of dietary changes, according to a meta-analysis of randomized clinical trials published in the October issue of Clinical Gastroenterology and Hepatology.
“On the basis of the current findings, physical activity should be recommended not only in combination with dietary changes but also independently as an effective approach to manage NAFLD,” wrote Lorenzo Orci, MD, and his associates at the University of Geneva. “We propose that the level of evidence surrounding the specific role of physical activity in the management of NAFLD is now sufficient to be awarded a grade of Ia.”
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Nonalcoholic fatty liver disease, “the hepatic manifestation of metabolic syndrome,” affects at least one in four U.S. adults and 15%-35% of individuals in Europe, the Middle East, China, and Japan, the researchers noted. Dietary changes are the cornerstone of NAFLD management, and there is less evidence for how physical exercise affects liver fat content. Therefore, the researchers searched MEDLINE, Embase, and the Cochrane databases from inception through October 2015 to find randomized trials of the impact of physical activity on markers of liver steatosis and liver inflammation in patients diagnosed with NAFLD, obesity, type 2 diabetes, or metabolic syndrome. This approach yielded 28 trials with data from more than 1,600 patients. Only two trials were multicenter, 13 required participants to have an NAFLD diagnosis, four focused on type 2 diabetes, and most of the rest included sedentary obese patients without requiring a diagnosis of NAFLD, the researchers said (Clin Gastroenterol Hepatol. 2016 May 4. doi: 10.1016/j.cgh.2016.04.036).
After researchers accounted for dietary changes, physical activity led to a significant drop in intrahepatic lipid content with a standardized mean difference of –0.69 compared with controls (95% confidence interval, –0.90 to –0.48; P less than .0001). “Because effect sizes such as standard mean difference [SMD] are difficult to interpret, the translation of such a statistical measure into a clinically relevant notion has been the focus of research for more than a decade,” the investigators added. “A commonly used interpretation was proposed by Cohen, who suggested that SMDs of 0.2, 0.5, and 0.8 correspond to small, moderate, and large effect sizes, respectively. By using this rule of thumb, our results indicate that physical activity exerts a moderate-to-large impact on the reduction of intrahepatic lipid content.”
Exercise reduced liver fat content even more in pediatric patients (SMD, –0.75; 95% CI, –0.1 to –0.5; P less than .0001) and in patients who had been specifically diagnosed with NAFLD (SMD, –0.86; 95% CI, –1.26 to –0.46; P less than .0001). Patients with the highest baseline body mass index also seemed to benefit more than patients with lower baseline BMI (P = .04). Indeed, exercise reduced BMI itself by a weighted mean difference of 0.8 (95% CI, –1.22 to 0.38; P less than .001), the researchers noted. Exercise intensity did not seem to affect the likelihood of benefit. There was a trend toward a greater effect of aerobic over resistance training (P = .06), and few studies examined the effects of combining both types of exercise.
The multivariable analysis also linked physical activity to an average 3.30 IU/L drop in alanine aminotransferase levels (95% CI, –5.57 to –1.04) and to a 4.9 IU/L decrease in aspartate aminotransferase levels (95% CI, –8.68 to –1.02). The investigators were unable to assess the long-term effects of physical exercise, nor its effects on hepatic fibrosis or inflammation, they noted. Nonetheless, the moderate to large effect size “provides strong evidence for the recommendation of physical activity as an effective intervention in the treatment of NAFLD,” they concluded. “Physical activity is also associated with an improvement in blood levels of aminotransferases and is particularly beneficial in patients presenting with severe obesity at baseline.”
The work was funded by the Ligue Genevoise contre le Cancer and the Dr Henri Dubois-Ferrière/Dinu Lipatti Foundation and by the Swiss National Science Foundation. The investigators had no disclosures.