Changes in nonalcoholic fatty liver disease and M2BPGi due to lifestyle intervention in primary healthcare

PLOS ONE RESEARCH ARTICLE Changes in nonalcoholic fatty liver disease and M2BPGi due to lifestyle intervention in primary healthcare Eun-Hee Nah ID1*, Yong Jun Choi1, Seon Cho2, Hyeran Park2, Suyoung Kim2, Eunjoo Kwon2, Han-Ik Cho3 1 Department of Laboratory Medicine, Chonnam National University Hwasun Hospital, Hwasun, South Korea, 2 Health Promotion Research Institute, Korea Association of Health Promotion, Seoul, South Korea, 3 MEDIcheck LAB, Korea Association of Health Promotion, Seoul, South Korea * a1111111111 a1111111111 a1111111111 a1111111111 a1111111111 OPEN ACCESS Citation: Nah E-H, Choi YJ, Cho S, Park H, Kim S, Kwon E, et al. (2024) Changes in nonalcoholic fatty liver disease and M2BPGi due to lifestyle intervention in primary healthcare. PLoS ONE 19(2): e0298151. https://doi.org/10.1371/journal. pone.0298151 Editor: Jee-Fu Huang, Kaohsiung Medical University Hospital, TAIWAN Received: September 4, 2023 Accepted: January 6, 2024 Published: February 29, 2024 Copyright: © 2024 Nah et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: All relevant data are within the manuscript and its Supporting Information files. Funding: The authors received no specific funding for this work. Competing interests: The authors have declared that no competing interests exist. Abstract Background A healthy lifestyle is the most important method for managing nonalcoholic fatty liver disease (NAFLD). Mac-2-binding protein glycosylated isomer (M2BPGi) has been suggested as a biomarker for NAFLD. This study aimed to determine the efficacy of personalized lifestyle interventions on NAFLD remission. Methods This single-arm intervention study recruited participants with NAFLD who underwent health checkups at seven health-promotion centers in five South Korean cities. Fatty liver diagnosis was based on ultrasonography (US). The 109 individuals were recruited for personalized lifestyle interventions of hypocaloric diets and exercise. The participants attended the lifestyle intervention programs once per month for the first 3 months, and once every 3 months for the subsequent 6 months. In addition to sessions through center visits, phone-based intervention and self-monitoring at 4-, 5-, 7-, and 8-month were provided during the 9-month intervention period. And phone-based self-monitoring were also provided monthly during the 3-month follow-up period. The primary outcome was NAFLD remission at month 12 as measured on US and magnetic resonance elastography. The secondary outcomes were the changes in metabolic factors and M2BPGi. Results The 108 individuals (62 males and 46 females; age 51.1±12.4 years, mean±standard deviation) were finally analyzed after the 12month intervention. Body mass index, waist circumference (WC), blood pressure, blood lipids (total cholesterol, triglycerides, and HDL-C), and fasting blood sugar levels were improved relative to baseline (all P<0.05). Fatty liver at or above the moderate grade according to US was decreased at month 12 relative to baseline (67.6% vs 50.9%) (P = 0.002). M2BPGi levels decreased during the 12-month study period (P<0.001). M2BPGi levels were moderately correlated with hepatic fat fraction by magnetic resonance imaging (r = 0.33, P = 0.05). WC (OR = 0.82, 95% CI = 0.67–1.00, P = 0.05) and PLOS ONE | https://doi.org/10.1371/journal.pone.0298151 February 29, 2024 1 / 14 PLOS ONE Changes in NAFLD and M2BPGi due to lifestyle intervention HDL-C (OR = 1.17, 95% CI = 1.03–1.32, P = 0.014) were associated with remission of fatty liver in the multivariate analysis. Conclusion The personalized lifestyle intervention was effective in improving fatty liver and metabolic factors, but not hepatic stiffness, in NAFLD. Trial registration ICTRP, cris.nih.go.kr (KCT0006380). Introduction The increasing prevalence of obesity and diabetes is resulting in nonalcoholic fatty liver disease (NAFLD) also becoming increasingly prevalent. Approximately 25% of the worldwide population was estimated to have NAFLD [1], affecting 60% of patients with diabetes [2] and 90% of people with obesity [3]. The spectrum of NAFLD ranges from simple steatosis to nonalcoholic steatohepatitis (NASH). Patients with NAFLD, and especially those with NASH, may eventually progress to fibrosis, leading to cirrhosis and hepatocellular carcinoma. The fibrosis stage of liver disease is known to be associated with the long-term outcomes in individuals with NAFLD [4, 5]. NAFLD development is related to lifestyle factors such as a high-calorie diet with reduced physical activity and exercise. Effectively treating NASH is required to interrupt the disease progression [6]. Lifestyle changes that focus on weight loss remain the cornerstone of NASH treatment [7]. Lifestyle interventions combined with a 10% decrease in body weight may improve the states of steatosis, inflammation, and even fibrosis [8]. Recent studies were conducted at a tertiary medical center and expert centers [8, 9]. Some studies used interventions that involved tightly controlled diets over short periods ranging several weeks to months [10– 12]. However, it is unlikely that participants can adhere to such diets for a long time to achieve NAFLD remission, and hence a community-based lifestyle modification program that could be applied in primary healthcare centers is needed. Imaging technologies such as ultrasonography (US), magnetic resonance imaging (MRI), and transient elastography have also been widely used for the assessment of liver steatosis and stiffness. Magnetic resonance elastography (MRE) has been demonstrated to show high diagnostic accuracy for liver fibrosis [13, 14]. An MRI-based technique of measuring the protondensity fat fraction (PDFF) was developed to measure the hepatic fat level. This technique can accurately measure the fat levels of all hepatic areas [15, 16]. However, considering its cost and need for MRI equipment, it is inappropriate to apply these techniques to periodic follow-ups of the degree of hepatic fat and fibrosis in individuals with NAFLD in primary healthcare. Therefore, simple, reliable, and noninvasive biomarkers also need to be identified for assessing the change in hepatic steatosis and fibrosis in NAFLD. This study aimed to determine the efficacy of personalized lifestyle interventions on NAFLD remission, and on the improvement of metabolic factors and Mac-2-binding protein glycosylated isomer (M2BPGi) in primary healthcare. Materials and methods Study design and participants This single-arm intervention study had a prospective multicenter design. Participants were recruited from among health examinees who underwent health checkups at seven health- PLOS ONE | https://doi.org/10.1371/journal.pone.0298151 February 29, 2024 2 / 14 PLOS ONE Changes in (...truncated)