Prevalence and risk factors for impaired renal function among Asian patients with nonalcoholic fatty liver disease

Background:Nonalcoholic fatty liver disease(NAFLD)is associated with impaired renal function,and both diseases often occur alongside other metabolic disorders.However,the prevalence and risk factors for impaired renal function in patients with NAFLD remain unclear.The objective of this study was to identify the prevalence and risk factors for renal impairment in NAFLD patients.Methods:All adults aged 18-70 years with ultrasound-diagnosed NAFLD and transient elastography examination from eight Asian centers were enrolled in this prospective study.Liver fibrosis and cirrhosis were assessed by FibroScan-aspartate aminotransferase(FAST),Agile 3+and Agile 4 scores.Impaired renal function and chronic kidney disease(CKD)were defined by an estimated glomerular filtration rate(eGFR)with value of<90 mL/min/1.73 m^(2) and<60 mL/min/1.73 m^(2),respectively,as estimated by the CKD-Epidemiology Collaboration(CKD-EPI)equation.Results:Among 529 included NAFLD patients,the prevalence rates of impaired renal function and CKD were 37.4%and 4.9%,respectively.In multivariate analysis,a moderate-high risk of advanced liver fibrosis and cirrhosis according to Agile 3+and Agile 4 scores were independent risk factors for CKD(P<0.05).Furthermore,increased fasting plasma glucose(FPG)and blood pressure were significantly associated with impaired renal function after controlling for the other components of metabolic syndrome(P<0.05).Compared with patients with normoglycemia,those with prediabetes[FPG≥5.6 mmol/L or hemoglobin A1c(HbA1c)≥5.7%]were more likely to have impaired renal function(P<0.05).Conclusions:Agile 3+and Agile 4 are reliable for identifying NAFLD patients with high risk of CKD.Early glycemic control in the prediabetic stage might have a potential renoprotective role in these patients.

Split-dose vs same-day reduced-volume polyethylene glycol electrolyte lavage solution for morning colonoscopy

AIM:To compare same-day whole-dose vs split-dose of 2-litre polyethylene glycol electrolyte lavage solution(PEG-ELS)plus bisacodyl for colon cleansing for morning colonoscopy.METHODS:Consecutive adult patients undergoing morning colonoscopy were allocated into two groups i.e.,same-day whole-dose or split-dose of 2-litre PEGELS.Investigators and endoscopists were blinded to the allocation.All patients completed a questionnaire that was designed by Aronchick and colleagues to assess the tolerability of the bowel preparation regime used.In addition,patients answered an ordinal fivevalue Likert scale question on comfort level during bowel preparation.Endoscopists graded the quality of bowel preparation using the Boston bowel preparation scale(BBPS).In addition,endoscopists gave an overall grading of the quality of bowel preparation.Cecal intu-bation time,withdrawal time,total colonoscopy time,adenoma detection rate and number of adenomas detected for each patient were recorded.Sample size was calculated using an online calculator for binary outcome non-inferiority trial.Analyses was based upon intent-to-treat.Significance was assumed at P-value<0.05.RESULTS:Data for 295 patients were analysed.Mean age was 62.0±14.4 years old and consisted of 50.2%male.There were 143 and 152 patients in the split-dose and whole-dose group,respectively.Splitdose was as good as whole-dose for quality of bowel preparation.The total BBPS score was as good in the split-dose group compared to the whole-dose group[6(6-8)vs 6(6-7),P=0.038].There was no difference in cecal intubation rate,cecal intubation time,withdrawal time,total colonoscopy time and adenoma detection rate.Median number of adenoma detected was marginally higher in the split-dose group[2(1-3)vs 1(1-2),P=0.010].Patients in the whole-dose group had more nausea(37.5%vs 25.2%,P=0.023)and vomiting(16.4%vs 8.4%,P=0.037),and were less likely to complete the bowel preparation(94.1%vs 99.3%,P=0.020).Patients in the split-dose group were less likely to refuse the same bowel preparation regime(6.3%vs 13.8%,P=0.033)and less likely to want to try another bowel preparation regime(53.8%vs 78.9%,P<0.001).CONCLUSION:Splitting reduced-volume PEG-ELS for morning colonoscopy is as effective as taking the whole dose on the same morning but is better tolerated and preferred by patients.

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.

An international Delphi consensus statement on metabolic dysfunction-associated fatty liver disease and risk of chronic kidney disease

Background:With the rising global prevalence of fatty liver disease related to metabolic dysfunction,the association of this common liver condition with chronic kidney disease(CKD)has become increasingly evident.In 2020,the more inclusive term metabolic dysfunction-associated fatty liver disease(MAFLD)was proposed to replace the term non-alcoholic fatty liver disease(NAFLD).The observed association between MAFLD and CKD and our understanding that CKD can be a consequence of underlying metabolic dysfunction support the notion that individuals with MAFLD are at higher risk of having and developing CKD compared with those without MAFLD.However,to date,there is no appropriate guidance on CKD in individuals with MAFLD.Furthermore,there has been little attention paid to the link between MAFLD and CKD in the Nephrology community.Methods and Results:Using a Delphi-based approach,a multidisciplinary panel of 50 international experts from 26 countries reached a consensus on some of the open research questions regarding the link between MAFLD and CKD.Conclusions:This Delphi-based consensus statement provided guidance on the epidemiology,mechanisms,management and treatment of MAFLD and CKD,as well as the relationship between the severity of MAFLD and risk of CKD,which establish a framework for the early prevention and management of these two common and interconnected diseases.

Hepatocyte apoptosis fragment product cytokeratin-18 M30 level and non-alcoholic steatohepatitis risk diagnosis:an international registry study

Background:Liver biopsy for the diagnosis of non-alcoholic steatohepatitis(NASH)is limited by its inherent invasiveness and possible sampling errors.Some studies have shown that cytokeratin-18(CK-18)concentrations may be useful in diagnosing NASH,but results across studies have been inconsistent.We aimed to identify the utility of CK-18 M30 concentrations as an alternative to liver biopsy for non-invasive identification of NASH.Methods:Individual data were collected from 14 registry centers on patients with biopsy-proven non-alcoholic fatty liver disease(NAFLD),and in all patients,circulating CK-18 M30 levels were measured.Individuals with a NAFLD activity score(NAS)≥5 with a score of≥1 for each of steatosis,ballooning,and lobular inflammation were diagnosed as having definite NASH;individuals with a NAS≤2 and no fibrosis were diagnosed as having non-alcoholic fatty liver(NAFL).Results:A total of 2571 participants were screened,and 1008(153 with NAFL and 855 with NASH)were finally enrolled.Median CK-18 M30 levels were higher in patients with NASH than in those with NAFL(mean difference 177 U/L;standardized mean difference[SMD]:0.87[0.69–1.04]).There was an interaction between CK-18 M30 levels and serum alanine aminotransferase,body mass index(BMI),and hypertension(P<0.001,P=0.026 and P=0.049,respectively).CK-18 M30 levels were positively associated with histological NAS in most centers.The area under the receiver operating characteristics(AUROC)for NASH was 0.750(95%confidence intervals:0.714–0.787),and CK-18 M30 at Youden’s index maximum was 275.7 U/L.Both sensitivity(55%[52%–59%])and positive predictive value(59%)were not ideal.Conclusion:This large multicenter registry study shows that CK-18 M30 measurement in isolation is of limited value for non-invasively diagnosing NASH.

The role of B cells in metabolic(dysfunction)-associated fatty liver disease

Metabolic(dysfunction)-associated fatty liver disease(MAFLD;formerly known as non-alcoholic fatty liver disease)is the most common liver disorder,affecting around one-third of the population worldwide(1).MAFLD is a heterogeneous disease with a spectrum of liver pathologies that spans from hepatic lipid accumulation(steatosis)to chronic inflammation(steatohepatitis),which can progress to cirrhosis and hepatocellular carcinoma.It is impacted by a myriad of factors,including metabolic health,biological and chronological age,genetics and epigenetics(2-4).However,only a proportion(5-40%)of patients develop liver inflammation or steatohepatitis(5).This transition is a cardinal feature of progressive liver disease,which is the precursor to the development of the hepatic and extra-hepatic outcomes.