PT - JOURNAL ARTICLE AU - Eduardo Vilar-Gomez AU - Shaminie J. Athinarayanan AU - Rebecca N. AdamS AU - Sarah J. Hallberg AU - Nasir H. Bhanpuri AU - Amy L. McKenzie AU - Wayne W. Campbell AU - James P. McCarter AU - Stephen D. Phinney AU - Jeff S. Volek AU - Naga Chalasani TI - Post-hoc analyses of Surrogate Markers of Non-Alcoholic Fatty Liver Disease (NAFLD) and Liver Fibrosis in Patients with Type 2 Diabetes in a Digitally-Supported Continuous Care Intervention: An Open Label, Non-Randomized, Controlled Study AID - 10.1101/293548 DP - 2018 Jan 01 TA - bioRxiv PG - 293548 4099 - http://biorxiv.org/content/early/2018/11/21/293548.short 4100 - http://biorxiv.org/content/early/2018/11/21/293548.full AB - Objective One-year of comprehensive continuous care intervention (CCI) through nutritional ketosis improves HbA1c, body weight and liver enzymes among type 2 diabetes (T2D) patients. Here, we report the effect of the CCI on surrogate scores of non-alcoholic fatty liver disease (NAFLD) and liver fibrosis.Methods This was a non-randomized longitudinal study, including adults with T2D who were self-enrolled to the CCI (n=262) or to receive usual care (UC, n=87) during one year. A NAFLD liver fat score [N-LFS] > −0.640 defined the presence of fatty liver. A NAFLD fibrosis score [NFS] of > 0.675 identified subjects with advanced fibrosis. Changes in N-LFS and NFS at one year were the main endpoints.Results At baseline, NAFLD was present in 95% of patients in the CCI and 90% of patients in the UC. At one year, weight loss of > 5% was achieved in 79% of patients in the CCI vs. 19% of patients in UC (P<0.001). N-LFS mean score was reduced in the CCI group (−1.95±0.22, P<0.001) whereas it was not changed in the UC (0.47±0.41, P=0.26) (CCI vs. UC, P<0.001). NFS was reduced in the CCI group (−0.65±0.06, P<0.001) compared with UC (0.26±0.11, P=0.02) (P<0.001 between two groups). In the CCI group, the percentage of individuals with a low probability of advanced fibrosis increased from 18% at baseline to 33% at 1 year (P<0.001).Conclusions One year of a digitally-supported CCI significantly improved surrogates of NAFLD and advanced fibrosis in patients with type 2 diabetes.DATA SHARING Data sets and statistical code used for the current study are available from the corresponding author on reasonable request.Article Summary Strengths and limitations of this studyThis study highlights the beneficial effect of the CCI on NAFLD in high risk patients with T2DThis study also identifies positive associations between glycemic improvements and improvements in ALT levelsThe assessment of resolution of steatosis and fibrosis is limited by the sensitivity and specificity of the non-invasive markers used in the studyThe patients were restricted in their carbohydrate intake and monitored for their nutritional ketosis state, but dietary energy, macronutrient and micronutrient intakes were not assessed.AbbreviationsCCIcontinuous care intervention;UCusual care;NAFLDnon-alcoholic fatty liver disease;;N-LFSnon-alcoholic liver fatty score;NFSnon-alcoholic fatty liver disease fibrosis score;CLDchronic liver disease;HCChepatocellular carcinoma;T2Dtype 2 diabetes;NASHnonalcoholic steatohepatitis;BMIbody mass index;LCHFlow-carbohydrate high-fat;ALTalanine aminotransferase;ASTaspartate aminotransferase;IHLCintrahepatic lipid content;ADAAmerican Diabetes Association;BHBbeta-hydroxybutyrate;CLIAclinical laboratory improvement amendments;ITTintention-to-treat;MIMmultiple imputation methods;WLweight loss;EOTend-of-treatment;HDLhigh density lipoprotein;RCTrandomized controlled trial;LCDlow-carbohydrate diet;KDketogenic diet;HFDhigh-fat diet