Alpha-1 antitrypsin deficiency and Pi^(*)Z allele as important co-factors in the development of liver fibrosis

BACKGROUND Alpha-1 antitrypsin deficiency(AATD)is a codominant autosomal hereditary condition that predisposes patients to the development of lung and/or liver disease,and Pi*Z allele is the most clinically relevant mutation.AIM To evaluate the impact of clinical parameters and AATD phenotypes,particularly the Pi*Z allele,in liver fibrosis.METHODS Cross-sectional cohort study including consecutive patients with AATD followed in Pulmonology or Hepatology consultation.RESULTS Included 69 patients,49.3%had Pi*MZ phenotype and 10.1%Pi*ZZ.An age≥55 years,age at diagnosis≥41 years and AAT at diagnosis<77 mg/dL predicted a nonalcoholic fatty liver disease fibrosis score(NFS)not excluding advanced fibrosis[area under the curve(AUC)=0.840,P<0.001;AUC=0.836,P<0.001;AUC=0.681,P=0.025].An age≥50 years and age at diagnosis≥41 years predicted a fibrosis-4 index of moderate to advanced fibrosis(AUC=0.831,P<0.001;AUC=0.795,P<0.001).Patients with hypertension,type 2 diabetes mellitus(DM),dyslipidaemia,metabolic syndrome,and regular alcohol consumption were more likely to have a NFS not excluding advanced fibrosis(P<0.001,P=0.002,P=0.008,P<0.001,P=0.033).Patients with at least one Pi*Z allele and type 2 DM were 8 times more likely to have liver stiffness measurement≥7.1 kPa(P=0.040).CONCLUSION Risk factors for liver disease in AATD included an age≥50 years,age at diagnosis≥41 years,metabolic risk factors,regular alcohol consumption,at least one Pi*Z allele,and AAT value at diagnosis<77 mg/dL.We created an algorithm for liver disease screening in AATD patients to use in primary care,selecting those to be referred to Hepatology consultation.

Screening for metabolic dysfunction-associated fatty liver disease:Time to discard the emperor’s clothes of normal liver enzymes?

Metabolic dysfunction-associated fatty liver disease(MAFLD)is the most prevalent chronic liver condition worldwide.Current liver enzyme-based screening methods have limitations that may missed diagnoses and treatment delays.Regarding Chen et al,the risk of developing MAFLD remains elevated even when alanine aminotransferase levels fall within the normal range.Therefore,there is an urgent need for advanced diagnostic techniques and updated algorithms to enhance the accuracy of MAFLD diagnosis and enable early intervention.This paper proposes two potential screening methods for identifying individuals who may be at risk of developing MAFLD:Lowering these thresholds and promoting the use of noninvasive liver fibrosis scores.

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.

Validation of conventional non-invasive fibrosis scoring systems in patients with metabolic associated fatty liver disease

BACKGROUND Non-invasive fibrosis scores are not yet validated in the newly defined metabolic associated fatty liver disease(MAFLD).AIM To evaluate the diagnostic performance of four non-invasive scores including aspartate aminotransferase to platelet ratio index(APRI),fibrosis-4 index(FIB-4),body mass index,aspartate aminotransferase/alanine aminotransferase ratio,diabetes score(BARD),and nonalcoholic fatty liver disease fibrosis score(NFS)in patients with MAFLD.METHODS Consecutive patients with histologically confirmed MAFLD were included.The discrimination ability of different non-invasive scores was compared.RESULTS A total of 417 patients were included;156(37.4%)of them had advanced fibrosis(Metavir≥F3).The area under receiver operating characteristic curve of FIB-4,NFS,APRI,and BARD for predicting advanced fibrosis was 0.736,0.724,0.671,and 0.609,respectively.The area under receiver operating characteristic curve of FIB-4 and NFS was similar(P=0.523),while the difference between FIB-4 and APRI(P=0.001)and FIB-4 and BARD(P<0.001)was statistically significant.The best thresholds of FIB-4,NFS,APRI,and BARD for diagnosis of advanced fibrosis in MAFLD were 1.05,-2.1,0.42,and 2.A subgroup analysis showed that FIB-4,APRI,and NFS performed worse in the pure MAFLD group than in the hepatitis B virus-MAFLD group.CONCLUSION APRI and BARD scores do not perform well in MAFLD.The FIB-4 and NFS could be more useful,but a new threshold is needed.Novel non-invasive scoring systems for fibrosis are required for MAFLD.

Liver Fibrosis Scoring Systems as Novel Tools for Predicting Recurrent Cardiovascular Events in Patients with a Prior Cardiovascular Event

Objective:Regarding the secondary prevention of cardiovascular disease(CVD),there is great interest in preventing recurrent cardiovascular events(RCVEs).The prognostic importance of liver fibrosis scores(LFSs)has previously been reported in variousCVDs.We hypothesized that LFSs might also be useful predictors for RCVEs in patients with prior cardiovascular events(CVEs).Herein,we aimed to evaluate the associations of LFSs with RCVEs in a large,real-world cohort of coronary artery disease(CAD)patients with a prior CVE.Methods:In this multicenter prospective study,6527 consecutive patients with angiography-diagnosed CAD who had experienced a prior CVE(acute coronary syndrome,stroke,percutaneous coronary intervention,or coronary artery bypass grafting)were enrolled.LFSs were computed according to the published formulas:non-alcoholic fatty liver disease fibrosis score(NFS)includes age,body mass index(BMI),impaired fasting glycemia or diabetes mellitus(DM),aspartate aminotransferase(AST)/alanine aminotransferase(ALT)ratio,platelets,and albumin;fibrosis-4(FIB-4)includes age,AST,ALT,and platelets;Forns score includes age,gamma-glutamyltransferase(GGT),and platelets;BARD includes BMI,AST/ALT ratio,and DM;GGT/platelet ratio includes GGT and platelets;AST/ALT ratio includes AST and ALT;and AST/platelet ratio index includes AST and platelets.The originally reported cutoffs were used for the categorization of low-,intermediate-,and high-score subgroups.All patients were followed up for the occurrence of RCVEs(comprising cardiovascular death,non-fatal myocardial infarction,and stroke).Cox and Poisson regression analyses were used to assess the relationship of baseline LFSs with the risk of RCVE.Results:During a mean follow-up of(54.67±18.80)months,532(8.2%)RCVEs were recorded.Intermediate and high NFS,FIB-4,Forns,and BARD scores were independently associated with an increased risk of RCVE(hazard ratios ranging from 1.42 to 1.75 for intermediate scores and 1.35 to 2.52 for high scores).In the subgroup analyses of sex,age,BMI,DM,and hypertension status,the increased risk of RCVEs with high LFSs(NFS,FIB-4,Forns,and BARD)was maintained across the different subgroups(all P<0.05).Conclusion:This study showed that LFSs are indeed independently associated with RCVEs,suggesting that LFSs may be used as novel tools for risk stratification in CAD patients with a prior CVE.

Metabolic Dysfunction-associated Fatty Liver Disease is Associated with Greater Impairment of Lung Function than Nonalcoholic Fatty Liver Disease

Background and Aims:We compared lung function parameters in nonalcoholic fatty liver disease(NAFLD)and metabolic dysfunction-associated fatty liver disease(MAFLD),and examined the association between lung function parameters and fibrosis severity in MAFLD.Methods:In this cross-sectional study,we randomly recruited 2,543 middle-aged individuals from 25 communities across four cities in China during 2016 and 2020.All participants received a health check-up including measurement of anthropometric parameters,biochemical variables,liver ultrasonography,and spirometry.The severity of liver disease was assessed by the fibrosis(FIB)-4 score.Results:The prevalence of MAFLD was 20.4%(n=519)and that of NAFLD was 18.4%(n=469).After adjusting for age,sex,adiposity measures,smoking status,and significant alco-hol intake,subjects with MAFLD had a significantly lower predicted forced vital capacity(FVC,88.27±17.60%vs.90.82±16.85%,p<0.05)and lower 1 s forced expiratory volume(FEV1,79.89±17.34 vs.83.02±16.66%,p<0.05)than those with NAFLD.MAFLD with an increased FIB-4 score was significantly associated with decreased lung function.For each 1-point increase in FIB-4,FVC was diminished by 0.507(95%CI:-0.840,-0.173,p=0.003),and FEV1 was diminished by 0.439(95%CI:-0.739,-0.140,p=0.004).The results remained unchanged when the statistical analyses was performed separately for men and women.Conclusions:MAFLD was significantly asso-ciated with a greater impairment of lung function param-eters than NAFLD.