Gamma-glutamyl transferase and cardiovascular risk in nonalcoholic fatty liver disease:The Gut and Obesity Asia initiative

BACKGROUND Gamma-glutamyl transferase(GGT)is associated with the risk of cardiovascular disease(CVD)in the general population.AIM To identify the association of baseline GGT level and QRISK2 score among patients with biopsy-proven nonalcoholic fatty liver disease(NAFLD).METHODS This was a retrospective study involving 1535 biopsy-proven NAFLD patients from 10 Asian centers in 8 countries using data collected by the Gut and Obesity in Asia(referred to as“GO ASIA”)workgroup.All patients with available baseline GGT levels and all 16 variables for the QRISK2 calculation(QRISK2-2017;developed by researchers at the United Kingdom National Health Service;https://qrisk.org/2017/;10-year cardiovascular risk estimation)were included and compared to healthy controls with the same age,sex,and ethnicity.Relative risk was reported.QRISK2 score>10%was defined as the high-CVD-risk group.Fibrosis stages 3 and 4(F3 and F4)were considered advanced fibrosis.RESULTS A total of 1122 patients(73%)had complete data and were included in the final analysis;314(28%)had advanced fibrosis.The median age(interquartile range[IQR])of the study population was 53(44-60)years,532(47.4%)were females,and 492(43.9%)were of Chinese ethnicity.The median 10-year CVD risk(IQR)was 5.9%(2.6-10.9),and the median relative risk of CVD over 10 years(IQR)was 1.65(1.13-2.2)compared to healthy individuals with the same age,sex,and ethnicity.The high-CVD-risk group was significantly older than the low-risk group(median[IQR]:63[59-67]vs 49[41-55]years;P<0.001).Higher fibrosis stages in biopsy-proven NAFLD patients brought a significantly higher CVD risk(P<0.001).Median GGT level was not different between the two groups(GGT[U/L]:Median[IQR],high risk 60[37-113]vs low risk 66[38-103],P=0.56).There was no correlation between baseline GGT level and 10-year CVD risk based on the QRISK2 score(r=0.02).CONCLUSION The CVD risk of NAFLD patients is higher than that of healthy individuals.Baseline GGT level cannot predict CVD risk in NAFLD patients.However,advanced fibrosis is a predictor of a high CVD risk.

Validation model of fibrosis-8 index score to predict significant fibrosis among patients with nonalcoholic fatty liver disease

BACKGROUND Identifying hepatic fibrosis is crucial for nonalcoholic fatty liver disease(NAFLD)management.The fibrosis-8(FIB-8)score,recently developed by incorporating four additional variables into the fibrosis-4(FIB-4)score,showed better performance in predicting significant fibrosis in NAFLD.AIM To validate the FIB-8 score in a biopsy-proven NAFLD cohort and compare the diagnostic performance of the FIB-8 and FIB-4 scores and NAFLD fibrosis score(NFS)for predicting significant fibrosis.METHODS We collected the data of biopsy-proven NAFLD patients from three Asian centers in three countries.All the patients with available variables for the FIB-4 score(age,platelet count,and aspartate and alanine aminotransferase levels)and FIB-8 score(the FIB-4 variables plus 4 additional parameters:The body mass index(BMI),albumin to globulin ratio,gamma-glutamyl transferase level,and presence of diabetes mellitus)were included.The fibrosis stage was scored using nonalcoholic steatohepatitis CRN criteria,and significant fibrosis was defined as at least fibrosis stage 2.RESULTS A total of 511 patients with biopsy-proven NAFLD and complete data were included for validation.Of these 511 patients,271(53.0%)were female,with a median age of 51(interquartile range:41,58)years.The median BMI was 29(26.3,32.6)kg/m2,and 268(52.4%)had diabetes.Among the 511 NAFLD patients,157(30.7%)had significant fibrosis(≥F2).The areas under the receiver operating characteristic curves of the FIB-8 and FIB-4 scores and NFS for predicting significant fibrosis were 0.774,0.743,and 0.680,respectively.The FIB-8 score demonstrated significantly better performance for predicting significant fibrosis than the NFS(P=0.001)and was also clinically superior to FIB-4,although statistical significance was not reached(P=0.073).The low cutoff point of the FIB-8 score for predicting significant fibrosis of 0.88 showed 92.36%sensitivity,and the high cutoff point of the FIB-8 score for predicting significant fibrosis of 1.77 showed 67.51%specificity.CONCLUSION We demonstrated that the FIB-8 score had significantly better performance for predicting significant fibrosis in NAFLD patients than the NFS,as well as clinically superior performance vs the FIB-4 score in an Asian population.A novel simple fibrosis score comprising commonly accessible basic laboratories may be beneficial to use for an initial assessment in primary care units,excluding patients with significant liver fibrosis and aiding in patient selection for further hepatologist referral.

Pharmacological Therapeutics:Current Trends for Metabolic Dysfunction-associated Fatty Liver Disease(MAFLD)

Metabolic dysfunction-associated fatty liver disease(MAFLD)is a new term from nonalcoholic fatty liver disease(NAFLD)and is a positive diagnosis based on histopathology,imaging,or blood biomarkers.MAFLD is one of the common causes of liver dysfunction worldwide,likely due to the increase in metabolic syndrome as well as the high burden of disease and its relationship to other extrahepatic conditions.However,effective pharmacological therapeutic agents are still lacking;current management largely focuses on weight reduction and lifestyle modification.The purpose of this review was to summarize the updated evidence of novel therapies targeting different pathogenetic pathways in MAFLD.

Nonalcoholic fatty liver disease(NAFLD)among older adults

Nonalcoholic fatty liver disease(NAFLD)is now the leading cause of liver disease,and its prevalence is expected to increase in the future due to the increasing prevalence of obesity and an increasing aging population.With increases in longevity,NAFLD has emerged as a growing public health concern worldwide.NAFLD is a multisystem disease that has a strong association with metabolic risk factors.The presence of NAFLD increases the risks of liver‐and cardiovascular‐related mortality.Many studies have found age to be an additional risk factor for advanced fibrosis,which is associated with adverse outcomes.The identification of high‐risk older persons using noninvasive methods is a key step in community management.Limitations in the diagnostic performance of current assessment methods have been encountered.This review provides an update on the new terminology that has changed from NAFLD to metabolic‐associated fatty liver disease(MAFLD),and the epidemiology,clinical characteristics,noninvasive assessment,and prognosis of older persons with NAFLD.