Interaction between Lifestyle Changes and PNPLA3 Genotype in NAFLD Patients during the COVID-19 Lockdown

Abstract

The coronavirus disease 2019 (COVID-19) lockdown dramatically changed people’s lifestyles. Diet, physical activity, and the PNPLA3 gene are known risk factors for non-alcoholic fatty liver disease (NAFLD). Aim: To evaluate changes in metabolic and hepatic disease in NAFLD patients after the COVID-19 lockdown. Three hundred and fifty seven NAFLD patients were enrolled, all previously instructed to follow a Mediterranean diet (MD). Anthropometric, metabolic, and laboratory data were collected before the COVID-19 lockdown in Italy and 6 months apart, along with ultrasound (US) steatosis grading and information about adherence to MD and physical activity (PA). In 188 patients, PNPLA3 genotyping was performed. After the lockdown, 48% of patients gained weight, while 16% had a worsened steatosis grade. Weight gain was associated with poor adherence to MD (p = 0.005), reduced PA (p = 0.03), and increased prevalence of PNPLA3 GG (p = 0.04). At multivariate analysis (corrected for age, sex, MD, PA, and PNPLA3 GG), only PNPLA3 remained independently associated with weight gain (p = 0.04), which was also associated with worsened glycemia (p = 0.002) and transaminases (p = 0.02). During lockdown, due to a dramatic change in lifestyles, half of our cohort of NAFLD patients gained weight, with a worsening of metabolic and hepatologic features. Interestingly, the PNPLA3 GG genotype nullified the effect of lifestyle and emerged as an independent risk factor for weight gain, opening new perspectives in NAFLD patient care.

Intrahepatic Fat Content and COVID-19 Lockdown in Adults with NAFLD and Metabolic Syndrome

“…By comparing pre- and post-lockdown periods, participants in the IIFC group showed a significant increase in body weight, systolic and diastolic blood pressure, fasting glycemia, ALT, GGT, intrahepatic fat content by NMR, fatty liver index, and hepatic steatosis index. Current findings are in line with a previous study in Italy which found that, after lockdown, participants worsened steatosis from mild to moderate or severe, and experienced an increase in body weight and an increase in fasting glycemia compared to the pre-lockdown period [ 31 ]. Another previous study carried out in participants living in European countries found that the high level of social isolation paved the way for people to live unhealthy lifestyles or have work as an exacerbator of existing metabolic problems [ 24 ].…”

“…Another previous study carried out in participants living in European countries found that the high level of social isolation paved the way for people to live unhealthy lifestyles or have work as an exacerbator of existing metabolic problems [ 24 ]. In the current study, an increase in body weight was found, similar to other previous studies where weight gain occurred [ 31 , 32 , 33 , 34 ]. The first and most effective treatment for MetS and NAFLD is weight loss, achieved by diet and physical exercise [ 35 ].…”

Impact of COVID-19 Lockdown on Non-Alcoholic Fatty Liver Disease and Insulin Resistance in Adults: A before and after Pandemic Lockdown Longitudinal Study

“…The study by Cinque et al [59] shows how changes in lifestyle with changes in diet and physical activity are risk factors for the development of cardio-metabolic diseases [59,60], parameters that were also observed in our study.…”

Non-alcoholic fatty liver disease and COVID-19: Harmless companions or disease intensifier?

“…In an Italian cohort study, 48% of 357 NAFLD patients gained weight during lockdown, and this weight gain was associated with abandonment of a Mediterranean diet and decreased physical activity in univariate analysis and various multivariate models. Interestingly, in PNPLA3-GG polymorphism patients, this genotype represented the only favoring factor for weight gain[ 75 ]. A Japanese study examined 973 patients with health checks in 2018 and 2020.…”