Original Article Clinical and pathological features of sarcopenia-related indices in patients with non-alcoholic fatty liver disease Yuya Seko, Naoki Mizuno, Shinya Okishio, Aya Takahashi, Seita Kataoka, Keiichiroh Okuda, Mitsuhiro Furuta, Masashi Takemura, Hiroyoshi Taketani, Atsushi Umemura, Taichiro Nishikawa, Kanji Yamaguchi, Michihisa Moriguchi and Yoshito Itoh Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto Background: Sarcopenia is diagnosed with the skeletal mus- cle index (SMI) or the sarcopenia index (SI). We previously re- ported that the ratio of skeletal muscle mass to body fat mass (SF ratio) was a novel index of sarcopenia in patients with non- alcoholic fatty liver disease (NAFLD). The aim of this retrospec- tive study was to evaluate sarcopenia with these indices in patients with NAFLD. Methods: One hundred and fifty-six consecutive patients with biopsy-proven NAFLD and alanine aminotransferase (ALT) >40 IU/L were enrolled. Liver function and body composition were evaluated in 121 patients after 12 months. We evaluated the relationship between histological findings, changes in liver function, and the SMI, SI, and SF ratio. Results: Of the 156 patients enrolled, 13.5% and 26.3% were di- agnosed with sarcopenia with the SMI and SI. In patients with hepatic fibrosis stage <2, the SI and the SF ratio were signifi- cantly greater than in patients with fibrosis stage ≥2. There was no difference in SMI between groups. In the cohort assessed at baseline and 12 months later, transaminase activity and SMI decreased significantly, and the SF ratio increased over time. A multivariate analysis revealed the presence of the PNPLA3 G allele and an increase in SF ratio (odds ratio, 7.406) as predictive factors of ALT reduction >30% from baseline. Conclusions: Due to the high prevalence of obesity, we should consider both skeletal muscle mass and body fat mass in the di- agnosis and treatment of NAFLD. The SF ratio could be a useful index in sarcopenic NAFLD. Key words: NAFLD, PNPLA3, sarcopenia, SF ratio, SI INTRODUCTION S ARCOPENIA IS NOW a common problem not only for elderly people, but also for people with diseases such as renal disease, inflammatory disease, malignant tu- mors and chronic liver disease, including non-alcoholic fatty liver disease (NAFLD). Sarcopenia, characterized by a loss of skeletal muscle mass, muscle strength, and func- tion, affects clinical outcomes, including quality of life, infection rate, and survival in patients with cirrhosis. 1–3 In European populations, approximately 0.5–1.0% of skeletal muscle mass is lost per year after the age of 30 years, and up to 60% of patients with end-stage liver disease had sarcopenia. 4 Non-alcoholic fatty liver disease is currently the most common liver disease worldwide, af- fecting an estimated 25% of the adult population, 5 and is the most common indication for liver transplantation. 6 It is a disease covering a wide spectrum, ranging from non- alcoholic fatty liver (NAFL), which is usually a benign con- dition, to non-alcoholic steatohepatitis (NASH), which can sometimes lead to liver cirrhosis or hepatocellular car- cinoma without significant alcohol consumption. 7,8 The prevalence of NAFLD is increasing rapidly in Asian coun- tries because of westernized dietary patterns and a lack of exercise. Recently, sarcopenia has become known as a novel risk factor for the development of NAFLD. 9 A clear mechanism underlying the relationship between NAFLD and sarcopenia remains unknown, but insulin resistance (IR) and systemic inflammation could play a key role. In- sulin resistance facilitates lipolysis and leads to free fatty acid (FFA) flux in liver. Excessive FFA also inhibits the growth hormone/insulin growth factor-1 axis, which Correspondence: Dr Yuya Seko, Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan. Email: yuyaseko@koto.kpu-m.ac.jp Conflict of interest: The authors have no conflict of interest. Financial support: None declared. Received 19 December 2018; revision 17 January 2019; accepted 29 January 2019. Hepatology Research 2019 doi: 10.1111/hepr.13321 1 © 2019 The Japan Society of Hepatology