Sarcopenia in non-alcoholic fatty liver disease: Targeting the real culprit?

Abstract

Cleveland Clinic, Gastroenterology, Cleveland, OH, United StatesSee Article, pages xxx-xxxThere is exponential interest in non-alcoholic fatty liver disease(NAFLD) as a cause of chronic liver disease in the last decade[1]. The epidemic of obesity due to changes in life style and nutri-tional habits in Western countries has greatly contributed to therapid increase in prevalence of NAFLD. In addition to obesity,NAFLD is strongly associated with diabetes mellitus and insulinresistance that are believed to be a consequence of low physicalactivityand increased fat mass as well as the metabolic syndrome[2,3].The rst observation that a reduction in muscle tissue (betterknown as sarcopenia) could be involved in NAFLD came from theKorean Sarcopenic Obesity Study [4]. The authors found that indi-viduals with age-related sarcopenia which was associated withhigher body mass index (BMI) and fat mass had an increasedprevalence of NAFLD. By analyzing the same database, previousstudies had shown that, during aging, the increase in fat massand the decrease in muscle mass resulted in an increase in meta-bolic disorders [5]. Type 2 diabetes has also been found to beindependently associated with sarcopenia [6]. These studies haveled to the hypothesis that leptin and other adipocytokines fromthe adipose tissue increase muscle catabolism and consequentsarcopenia and reduced physical activity which, through a viciouscycle, results in increased fat accumulation and weight gain.In this issue of Journal of Hepatology, Lee and coworkers [7]provide further information on the relationship between sarcope-nia and NAFLD by analyzing the data from the Korea NationalHealth and Nutrition Examination Survey.The opportunity to derive data from this large populationstudy was based on the application of non-invasive scores, withan acceptable positive predictive index, for the diagnosis ofNAFLD. Dual-energy X-ray absorptiometry was used for theassessment of body composition to dene changes in musclemass. Sarcopenia was diagnosed using the skeletal muscle index(SMI) and dened as <1 standard deviation below the average of ayoung reference population.The key nding of this study was the strong associationbetween sarcopenia and NAFLD regardless of obesity or meta-bolic syndrome. Bothnon-obese and obese subjects showed a sig-nicantly increased prevalence of NAFLD when sarcopenia waspresent (non-obese non–sarcopenic: 4–14% vs. non–obese sar-copenic: 9–30%; p <0.001, and obese non–sarcopenic 50–72% vs.obese sarcopenic 61–83%; p <0.001). Similar results were foundwhen patients were stratied by the presence or absence ofmetabolic syndrome. Interestingly, the authors also examinedthe impact of regular exercise in patients with NAFLD and foundthat in obese subjects with preserved skeletal muscle mass, reg-ular exercise was associated with a reduced probability of NAFLD(46 vs. 55% p <0.001). Furthermore, among patients with NAFLD,the presence of sarcopenia was also independently associatedwith a higher probability of advanced liver brosis (evaluatedthrough brosis predictors).It is important to note that in the study by Lee, diagnosis ofsarcopenia was made using the SMI, a ratio of the appendicularskeletal muscle (ASM) and body weight (BW). SMI may decreasewhen the fat mass is enhanced, either for obesity or for aging, dueto the increase in body mass and therefore the absolute decreasein muscle tissue may be lower than indicated [8]. Recently how-ever, in a more limited group of patients, sarcopenia evaluatedusing computed tomographic (CT) scans, a method which allowsprecise quantication of muscle mass, was also reported to beassociated to the development of NASH or NASH and cirrhosis[9,10].An increasingly recognized limitation of body compositionmeasurements is the difculty of quantifying muscle mass withprecision [11,12]. A number of methods have been describedincluding DEXA and image analysis using CT or magnetic reso-nance imaging (MRI). A major limitation of CT and MRI despitetheir recognized accuracy in identifying skeletal muscle is dueto their cost and logistics in population studies. DEXA remainsthe best option and even though DEXA measures non-fat massand not muscle mass directly, appendicular non-fat, non-bonemass is predominantly skeletal muscle. Furthermore, the authorsacknowledge that muscle mass can be measured using DEXA butthe impact on quality of the muscle is not known. This isespecially relevant since in type 2 diabetes mellitus, an insulinresistant state, inter- and intra-myocellular fat are increased.Journal of Hepatology 2015 vol. xxx