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.

Histopathological differences utilizing the nonalcoholic fatty liver disease activity score criteria in diabetic(type 2 diabetes mellitus) and non-diabetic patients with nonalcoholic fatty liver disease

AIM: To study clinical and histopathological features of nonalcoholic fatty liver disease(NAFLD) in patients with and without type 2 diabetes mellitus(T2DM) using updated nonalcoholic steatohepatitis clinical research network(NASH-CRN) grading system.METHODS: We retrospectively analyzed data of 235 patients with biopsy proven NAFLD with and without T2 DM.This database was utilized in the previously published study comparing ethnicity outcomes in NAFLD by the same corresponding author.The pathology database from University of Chicago was utilized for enrolling consecutive patients who met the criteria for NAFLD and their detailed clinical and histopathology findings were obtained for comparison.The relevant clinical profile of patients was collected from the Electronic Medical Records around the time of liver biopsy and the histology was read by a single well-trained histopathologist.The updated criteria for type 2 diabetes have been utilized for analysis.Background data of patients with NASH and NAFLD has been included.The mean differences were compared using χ2 and t-test along with regression analysis to evaluate the predictors of NASH and advanced fibrosis.RESULTS: Patients with NAFLD and T2 DM were significantly older(49.9 vs 43.0,P < 0.01),predominantly female(71.4 vs 56.3,P < 0.02),had higher rate of metabolic syndrome(88.7 vs 36.4,P < 0.01),had significantly higher aspartate transaminase(AST)/alanine transaminase(ALT) ratio(0.94 vs 0.78,P < 0.01) and Fib-4 index(1.65 vs 1.06,P < 0.01) as markers of NASH,showed higher mean NAFLD activity score(3.5 vs 3.0,P = 0.03) and higher mean fibrosis score(1.2 vs 0.52,P < 0.01) compared to patients with NAFLD without T2 DM.Furthermore,advanced fibrosis(32.5 vs 12.0,P < 0.01) and ballooning(27.3 vs 13.3,P < 0.01) was significantly higher among patients with NAFLD and T2 DM compared to patients with NAFLD without T2 DM.On multivariate analysis,T2 DM was independently associated with NASH(OR = 3.27,95%CI: 1.43-7.50,P < 0.01) and advanced fibrosis(OR = 3.45,95%CI: 1.53-7.77,P < 0.01) in all patients with NAFLD.There was a higher rate of T2DM(38.1 vs 19.4,P < 0.01) and cirrhosis(8.3 vs 0.0,P = 0.01) along with significantly higher mean Bilirubin(0.71 vs 0.56,P = 0.01) and AST(54.2 vs 38.3,P < 0.01) and ALT(78.7 vs 57.0,P = 0.01) level among patients with NASH when compared to patients with steatosis alone.The mean platelet count(247 vs 283,P < 0.01) and high-density lipoprotein cholesterol level(42.7 vs 48.1,P = 0.01) was lower among patients with NASH compared to patients with steatosis.CONCLUSION: Patients with NAFLD and T2 DM tend to have more advanced stages of NAFLD,particularly advanced fibrosis and higher rate of ballooning than patients with NAFLD without T2 DM.

Peripheral Artery Disease and Risk of Fibrosis Deterioration in Nonalcoholic Fatty Liver Disease:A Prospective Investigation

Objective Liver fibrosis is an important predictor of mortality in nonalcoholic fatty liver disease(NAFLD).Peripheral artery disease(PAD)and liver fibrosis share many common metabolic dysfunctions.We aimed to explore the association between PAD and risk of fibrosis deterioration in NAFLD patients.Methods The study recruited 1,610 NAFLD patients aged≥40 years from a well-defined community at baseline in 2010 and followed up between August 2014 and May 2015.Fibrosis deterioration was defined as the NAFLD fibrosis score(NFS)status increased to a higher category at the follow-up visit.PAD was defined as an ankle-brachial index of<0.90 or>1.40.Results During an average of 4.3 years’follow-up,618 patients progressed to a higher NFS category.PAD was associated with 92%increased risk of fibrosis deterioration[multivariable-adjusted odds ratio(OR):1.92,95%confidence interval(CI):1.24,2.98].When stratified by baseline NFS status,the OR for progression from low to intermediate or high NFS was 1.74(95%CI:1.02,3.00),and progression from intermediate to high NFS was 2.24(95%CI:1.05,4.80).There was a significant interaction between PAD and insulin resistance(IR)on fibrosis deterioration(P for interaction=0.03).As compared with non-PAD and non-IR,the coexistence of PAD and IR was associated with a 3.85-fold(95%CI:2.06,7.18)increased risk of fibrosis deterioration.Conclusion PAD is associated with an increased risk of fibrosis deterioration in NAFLD patients,especially in those with IR.The coexistence of PAD and IR may impose an interactive effect on the risk of fibrosis deterioration.

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.

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.

Genetic background in nonalcoholic fatty liver disease: A comprehensive review

In the Western world, nonalcoholic fatty liver disease(NAFLD) is considered as one of the most significant liver diseases of the twenty-first century. Its development is certainly driven by environmental factors, but it is also regulated by genetic background. The role of heritability has been widely demonstratedby several epidemiological, familial, and twin studies and case series, and likely reflects the wide interindividual and inter-ethnic genetic variability in systemic metabolism and wound healing response processes. Consistent with this idea, genome-wide association studies have clearly identified Patatin-like phosholipase domain-containing 3 gene variant I148 M as a major player in the development and progression of NAFLD. More recently, the transmembrane 6 superfamily member 2 E167 K variant emerged as a relevant contributor in both NAFLD pathogenesis and cardiovascular outcomes. Furthermore, numerous casecontrol studies have been performed to elucidate the potential role of candidate genes in the pathogenesis and progression of fatty liver, although findings are sometimes contradictory. Accordingly, we performed a comprehensive literature search and review on the role of genetics in NAFLD. We emphasize the strengths and weaknesses of the available literature and outline the putative role of each genetic variant in influencing susceptibility and/or progression of the disease.

LC-MS-based lipidomic analysis in distinguishing patients with nonalcoholic steatohepatitis from nonalcoholic fatty liver

Background: Nonalcoholic fatty liver disease(NAFLD) is one of the main liver diseases, and its pathologic profile includes nonalcoholic fatty liver(NAFL) and nonalcoholic steatohepatitis(NASH). However, there is no reliable non-invasive parameter in distinguishing NASH from NAFL in clinical practice. The present study was to find a non-invasive way to differentiate these two categories of NAFLD via lipidomic analysis. Methods: Lipidomic analysis was used to determine the changes of lipid moieties in blood from 20 NAFL and 10 NASH patients with liver biopsy. Liver histology was evaluated after hematoxylin and eosin staining and Masson’s trichrome staining. The profile of lipid metabolites in correlation with steatosis, inflammation, hepatocellular necroptosis, fibrosis, and NAFLD activity score(NAS) was analyzed. Results: Compared with NAFL patients, NASH patients had higher degree of steatosis, ballooning degeneration, lobular inflammation. A total of 434 different lipid molecules were identified, which were mainly composed of various phospholipids and triacylglycerols. Many lipids, such as phosphatidylcholine(PC)(P-22:0/18:1), sphingomyelin(SM)(d14:0/18:0), SM(d14:0/24:0), SM(d14:0/22:0), phosphatidylethanolamine(PE)(18:0/22:5), PC(O-22:2/12:0), and PC(26:1/11:0) were elevated in the NASH group compared to those in the NAFL group. Specific analysis revealed an overall lipidomic profile shift from NAFL to NASH, and identified valuable lipid moieties, such as PCs [PC(14:0/18:2), PE(18:0/22:5) and PC(26:1/11:0)] or plasmalogens [PC(O-22:0/0:0), PC(O-18:0/0:0), PC(O-16:0/0:0)], which were significantly altered in NASH patients. In addition, PC(14:0/18:2), phosphatidic acid(18:2/24:4) were positively correlated with NAS;whereas PC(18:0/0:0) was correlated positively with fibrosis score. Conclusions: The present study revealed overall lipidomic profile shift from NAFL to NASH, identified valuable lipid moieties which may be non-invasive biomarkers in the categorization of NAFLD. The correlations between lipid moieties and NAS and fibrosis scores indicate that these lipid biomarkers may be used to predict the severity of the disease.

Real Time Elastography is an Easy Tool for Diagnosis of Liver Fibrosis in Non-Alcoholic Fatty Liver Disease

Background: Non-alcoholic fatty liver disease (NAFLD) has emerged a major challenge and become the leading indication for liver transplantation. We aimed to assess the applicability and performance of real-time elastography (RTE) in diagnosis of liver fibrosis in patients with NAFLD compared with NAFLD fibrosis score (NFS) and FIB-4 index. Patients and Methods: A prospective case-control study was conducted on 260 subjects attended Hepatology, Gastroenterology and Infectious diseases and Internal Medicine departments in Benha University Hospital from Marsh 20, 2018, to September 1, 2019 and divided into group I included 200 cases with NAFLD and group II included 60 healthy control subjects. Results: There was statistically significant increase in FIB-4 scores between two groups (1.39 ± 1.02 and -0.75 ± 0.32 respectively with p < 0.001), also there was statistically significant increase in NAFLD fibrosis score mean ± SD between two groups (-1.74 ± 1.17 and -2.75 ± 0.91 respectively with p < 0.001). Fibrosis stages in NAFLD patients significantly higher than in control group diagnosed by RTE (P = 0.001). There was an agreement between RTE and FIB-4 index (93%) and NAFLD fibrosis score (86%). Diagnostic performance of RTE in advanced liver fibrosis ≥ F3 was assessed in comparing with FIB-4 index show sensitivity 90%, specificity 93.3%, PPV 60%, NPV 98.8% and accuracy 93% with AUC0.917 (p = 0.001) and in comparing with NAFLD fibrosis score sensitivity 52.6%, specificity 93.8%, PPV 66.7%, NPV 98.4% and accuracy 86% with AUC 0.732 (p = 0.002). Conclusion: Real time elastography could be valuable in diagnosis of fibrosis in NAFLD especially in cases more than F3 score.

NAFLD fibrosis score:A prognostic predictor for mortality and liver complications among NAFLD patients

AIM:To study whether the severity of liver fibrosis estimated by the nonalcoholic fatty liver disease(NAFLD) fibrosis score can predict all-cause mortality,cardiac complications,and/or liver complications of patients with NAFLD over long-term follow-up.METHODS:A cohort of well-characterized patients with NAFLD diagnosed during the period of 1980-2000 was identified through the Rochester Epidemiology Project.The NAFLD fibrosis score(NFS) was used to separate NAFLD patients with and without advanced liver fibrosis.We used the NFS score to classify the probability of fibrosis as <-1.5 for low probability,>-1.5 to < 0.67 for intermediate probability,and > 0.67 for high probability.Primary endpoints included allcause death and cardiovascular-and/or liver-related mortality.From the 479 patients with NAFLD assessed,302 patients(63%) greater than 18 years old were included.All patients were followed,and medical charts were reviewed until August 31,2009 or the date when the first primary endpoint occurred.By using a standardized case record form,we recorded a detailed history and physical examination and the use of statins and metformin during the follow-up period.RESULTS:A total of 302/479(63%) NAFLD patients(mean age:47 ± 13 year) were included with a followup period of 12.0 ± 3.9 year.A low probability of advanced fibrosis(NFS <-1.5 at baseline) was found in 181 patients(60%),while an intermediate or high probability of advanced fibrosis(NSF >-1.5) was found in 121 patients(40%).At the end of the follow-up period,55 patients(18%) developed primary endpoints.A total of 39 patients(13%) died during the follow-up.The leading causes of death were non-hepatic malignancy(n = 13/39;33.3%),coronary heart disease(CHD)(n = 8/39;20.5%),and liver-related mortality(n = 5/39;12.8%).Thirty patients had new-onset CHD,whereas 8 of 30 patients(27%) died from CHD-related causes during the follow-up.In a multivariate analysis,a higher NFS at baseline and the presence of new-onset CHD were significantly predictive of death(OR = 2.6 and 9.2,respectively;P < 0.0001).Our study showed a significant,graded relationship between the NFS,as classified into 3 subgroups(low,intermediate and high probability of liver fibrosis),and the occurrence of primary endpoints.The use of metformin or simvastatin for at least 3 mo during the follow-up was associated with fewer deaths in patients with NAFLD(OR = 0.2 and 0.03,respectively;P < 0.05).Additionally,the rate of annual NFS change in patients with an intermediate or high probability of advanced liver fibrosis was significantly lower than those patients with a low probability of advanced liver fibrosis(0.06 vs 0.09,P = 0.004).The annual NFS change in patients who died was significantly higher than those in patients who survived(0.14 vs 0.07,P = 0.03).At the end of the follow-up,we classified the patients into 3 subgroups according to the progression pattern of liver fibrosis by comparing the NFS at baseline to the NFS at the end of the followup period.Most patients were in the stable-fibrosis(60%) and progressive-fibrosis(37%) groups,whereas only 3% were in the regressive fibrosis.CONCLUSION:A higher NAFLD fibrosis score at baseline and a new onset of CHD were significantly predictive of death in patients with NAFLD.

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.

Machine Learning Technology for Evaluation of Liver Fibrosis, Inflammation Activity and Steatosis (LIVERFASt^TM)

Using the latest available artificial intelligence (AI) technology, an advanced algorithm LIVERFAStTM has been used to evaluate the diagnostic accuracy of machine learning (ML) biomarker algorithms to assess liver damage. Prevalence of NAFLD (Nonalcoholic fatty liver disease) and resulting NASH (nonalcoholic steatohepatitis) are constantly increasing worldwide, creating challenges for screening as the diagnosis for NASH requires invasive liver biopsy. Key issues in NAFLD patients are the differentiation of NASH from simple steatosis and identification of advanced hepatic fibrosis. In this prospective study, the staging of three different lesions of the liver to diagnose fatty liver was analyzed using a proprietary ML algorithm LIVERFAStTM developed with a database of 2862 unique medical assessments of biomarkers, where 1027 assessments were used to train the algorithm and 1835 constituted the validation set. Data of 13,068 patients who underwent the LIVERFAStTM test for evaluation of fatty liver disease were analysed. Data evaluation revealed 11% of the patients exhibited significant fibrosis with fibrosis scores 0.6 - 1.00. Approximately 7% of the population had severe hepatic inflammation. Steatosis was observed in most patients, 63%, whereas severe steatosis S3 was observed in 20%. Using modified SAF (Steatosis, Activity and Fibrosis) scores obtained using the LIVERFAStTM algorithm, NAFLD was detected in 13.41% of the patients (Sx > 0, Ay 0). Approximately 1.91% (Sx > 0, Ay = 2, Fz > 0) of the patients showed NAFLD or NASH scorings while 1.08% had confirmed NASH (Sx > 0, Ay > 2, Fz = 1 - 2) and 1.49% had advanced NASH (Sx > 0, Ay > 2, Fz = 3 - 4). The modified SAF scoring system generated by LIVERFAStTM provides a simple and convenient evaluation of NAFLD and NASH in a cohort of Southeast Asians. This system may lead to the use of noninvasive liver tests in extended populations for more accurate diagnosis of liver pathology, prediction of clinical path of individuals at all stages of liver diseases, and provision of an efficient system for therapeutic interventions.

代谢相关脂肪性肝病及其严重程度与结直肠癌的相关性

目的 探讨代谢相关脂肪性肝病(metabolic associated fatty liver disease,MAFLD)及其严重程度和肝纤维化程度与结直肠癌(colorectal cancer,CRC)的关系。方法 选取美国国家健康与营养调查(National Health and Nutrition Examination Survey,NHANES)数据库中2017-2018年同时具有肝脏超声瞬时弹性成像结果和“是否患有CRC”调查问卷(MCQ-230)结果的4 365例20岁以上的成年人作为研究对象,根据是否患CRC将研究对象分为CRC组和非CRC组(对照组)。比较CRC组与对照组一般资料及MAFLD患者数目之间的差异,将研究对象根据肝脏超声瞬时弹性成像结果及FIB-4无创肝纤维化评分进行肝脂肪变性严重程度和肝纤维化程度分层,分为无/轻度脂肪肝组和中重度脂肪肝组,非进展期肝纤维化组和进展期肝纤维化组,采用Logistic回归分析MAFLD及其严重程度和肝纤维化程度与CRC的相关性。结果 年龄、BMI、腰围、高血压史、糖尿病史、代谢综合征(metabolic syndrome,MetS)、MAFLD、TG、CRP、HbA1c、CAP、肝脏硬度值(E值)、FIB-4是CRC的危险因素(P<0.05),MAFLD是CRC的独立危险因素(OR=2.510,95%CI:1.045~6.032,P=0.040),在对肝脂肪变性严重程度和肝纤维化程度进一步分层后,中重度脂肪肝与FIB-4提示的进展期肝纤维化是CRC的独立危险因素(P<0.05),然而,肝脏超声瞬时弹性成像提示的进展期肝纤维化与CRC的风险差异无统计学意义(P>0.05)。结论 MAFLD及其严重程度和肝纤维化程度与CRC密切相关,且MAFLD及其严重程度和FIB-4提示的肝纤维化程度是CRC发生的独立危险因素。

非酒精性脂肪性肝病肝纤维化程度与心脏左心室改变的关系

目的探讨非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)肝纤维化程度与心脏左心室结构和功能的关系。方法收集2022年6月~2023年4月新疆医科大学第二附属医院收治的NAFLD患者411例,将NAFLD患者通过FIB-4无创肝纤维化评分系统进行分层,分为进展期纤维化组(n=138)和非进展期纤维化组(n=273),选择同期就诊的腹部超声检查正常的151例患者为对照组,分析NAFLD患者肝纤维化严重程度与心脏左心室结构和功能的关系。结果NAFLD患者肝纤维化是心脏舒张功能受限的危险因素(P<0.05),且肝纤维化程度越重,心脏舒张功能受限越重。结论NAFLD肝纤维化程度与心脏左心室舒张功能受限显著相关,与心脏左心室结构改变可能相关。

Estimating steatosis and fibrosis: Comparison of acoustic structure quantification with established techniques

AIM:To compare ultrasound-based acoustic structure quantification(ASQ) with established non-invasive techniques for grading and staging fatty liver disease.METHODS:Type 2 diabetic patients at risk of nonalcoholic fatty liver disease(n = 50) and healthy volunteers(n = 20) were evaluated using laboratory analysis and anthropometric measurements, transient elastography(TE), controlled attenuation parameter(CAP), proton magnetic resonance spectroscopy(1H-MRS; only available for the diabetic cohort), and ASQ.ASQ parameters mode, average and focal disturbance(FD) ratio were compared with:(1) the extent of liver fibrosis estimated from TE and nonalcoholic fatty liver disease(NAFLD) fibrosis scores; and(2) the amount of steatosis, which was classified according to CAP values.RESULTS:Forty-seven diabetic patients(age 67.0±8.6 years;body mass index 29.4±4.5 kg/m2)with reliable CAP measurements and all controls(age 26.5±3.2 years;body mass index 22.0±2.7 kg/m2)were included in the analysis.All ASQ parameters showed differences between healthy controls and diabetic patients(P<0.001,respectively).The ASQ FD ratio(logarithmic)correlated with the CAP(r=-0.81,P<0.001)and 1H-MRS(r=-0.43,P=0.004)results.The FD ratio[CAP<250 d B/m:107(102-109),CAP between 250 and 300 d B/m:106(102-114);CAP between 300 and 350 d B/m:105(100-112),CAP≥350 d B/m:102(99-108)]as well as mode and average parameters,were reduced in cases with advanced steatosis(ANOVA P<0.05).However,none of the ASQ parameters showed a significant difference in patients with advanced fibrosis,as determined by TE and the NAFLD fibrosis score(P>0.08,respectively).CONCLUSION:ASQ parameters correlate with steatosis,but not with fibrosis in fatty liver disease.Steatosis estimation with ASQ should be further evaluated in biopsy-controlled studies.

Validation of Non-invasive Fibrosis Scores for Predicting Advanced Fibrosis in Metabolic-associated Fatty Liver Disease

Background and Aims:Metabolic-associated fatty liver disease(MAFLD)is a newly proposed terminology from 2020;yet,the applicability of conventional noninvasive fi-brosis models is still unknown for it.We aimed to evaluate the performance of conventional noninvasive fibrosis scores in MAFLD.Methods:The NHANES 2017-2018 datasets were used to compare the performances of different non-invasive fibrosis scores in MAFLD,including the aspartate aminotransferase(AST)to platelet ratio index(APRI),body mass index(BMI)-AST/alanine aminotransferase(ALT)ratio and diabetes score(BARD),fibrosis-4 index(FIB-4),and NAFLD fibrosis score(NFS).Moreover,Asian patients with biopsy-proven MAFLD were enrolled to further validate the findings.Results:A total of 2,622 participants in the Na-tional Health and Nutrition Examination Survey(NHANES)cohort and 293 patients with MAFLD in the Asian cohort were included.Patients in the Asian cohort had a lower BMI and higher liver enzymes(p<0.001).The area under the receiver operating characteristic curve(AUROC)of NFS was the largest in the NHANES cohort and Asian cohorts(0.679 and 0.699,respectively).The AUROC of NFS was followed by APRI,FIB-4,and BARD in the NHANES cohort(0.616,0.601,and 0.589,respectively).In the Asian cohort,the AUROC of APRI,FIB-4,and BARD for predicting advanced fibrosis were 0.625,0.683,and 0.615,respectively.The performance of FIB-4 was better in the Asian cohort than that in the NHANES cohort.Conclusions:NFS is better for predicting advanced fibrosis in MAFLD.FIB-4 can be an al-ternative choice for MAFLD with high liver enzymes when NFS is unavailable.Novel efficient noninvasive fibrosis scor-ing systems are highly required for patients with MAFLD.

代谢相关脂肪性肝病无创肝纤维化评分与急性冠状动脉综合征的相关性研究

目的:探讨代谢相关脂肪性肝病(metabolic associated fatty liver disease,MAFLD)患者的无创肝纤维化评分(non-invasive hepatic fibrosis score,NFS)与急性冠状动脉综合征(acute coronary syndromes,ACS)的相关性以及NFS对MAFLD患者发生ACS的预测价值。方法:选取2021年1月至2021年12月,在首都医科大学附属北京安贞医院,住院治疗具有明确影像学诊断脂肪肝并符合代谢性脂肪性肝病诊断标准的患者421例(超声诊断脂肪肝368例,CT诊断脂肪肝53例)。其中ACS组198例,包括不稳定心绞痛129例,非ST段抬高型心肌梗死32例, ST段抬高型心肌梗死37例,非ACS组223例。计算每名研究对象的NFS,并以是否发生ACS为因变量,进行Logistic回归分析,分析MAFLD患者发生ACS的危险因素。同时绘制受试者工作特征(ROC)曲线,探讨NFS对于MAFLD患者发生ACS的预测价值。结果:MAFLD合并ACS组的BMI,收缩压,空腹血糖,LDL-C,HbA1c,AST, ALT,谷氨酰转肽酶(GGT)均高于非ACS组(P <0.05),多因素Logistic回归分析结果显示, NFS (OR=1.680,95%CI:1.174~2.403,P <0.05)、空腹血糖(OR=1.191,95%CI:1.068~1.329,P <0.05),合并高血压病史(OR=1.738,95%CI:1.097~2.754,P <0.05)是MAFLD患者发生ACS的危险因素。以ACS作为因变量进行ROC曲线分析结果显示, NFS判断MAFLD患者发生ACS的曲线下面积为0.75。结论:对于MAFLD人群,NFS与ACS的发生相关,临床上可以通过NFS评分识别ACS的高危患者,并通过加强相关危险因素的管理以预防ACS的发生。

消脂清肝方辨证加减治疗代谢相关脂肪性肝病的临床观察

目的:探究消脂清肝方辨证加减对代谢相关脂肪性肝病(MAFLD)患者脂代谢、抗氧化能力及肝纤维化的影响。方法:选取2020年6月至2023年2月辽宁中医药大学附属医院收治的MAFLD患者85例作为研究对象,按照随机数字表法随机为对照组(n=42)和观察组(n=43)。对照组饮食控制和运动指导治疗,观察组在对照组基础给予消脂清肝方辨证加减治疗,2组均连续治疗1个月。比较2组患者临床疗效、中医证候积分、脂代谢、抗氧化能力和肝纤维化指标。结果:观察组临床总有效率为90.70%,较对照组的71.43%显著提高(P>0.05);与治疗前比较,2组患者治疗后各项中医证候积分均显著下降,观察组较对照组更明显(P<0.05);三酰甘油(TG)、胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、肝脏硬度值和脂肪衰减值均下降,高密度脂蛋白胆固醇(HDL-C)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)水平均明显升高,且观察组优于对照组(P<0.05)。结论:MAFLD患者应用消脂清肝方辨证加减治疗,疗效显著,可有效改善脂代谢指标,提高抗氧化能力,减轻肝纤维化程度。

内脏脂肪面积预测非酒精性脂肪性肝病患者严重程度的价值

目的分析非酒精性脂肪性肝病(NAFLD)患者内脏脂肪面积的变化,探讨内脏脂肪面积预测NAFLD患者严重程度的临床价值。方法回顾性分析2019年10月至2021年10月在南京中医药大学附属医院就诊的198例NAFLD患者的临床资料。通过磁共振质子密度脂肪分数判断肝脏脂肪变性程度,其中轻度60例、中度52例、重度36例。选自同期50例健康体检者作为对照组。通过Sperman相关分析评价肝功能、血脂、NAFLD纤维化评分(NFS)与内脏脂肪面积的关系,创建内脏脂肪面积和NFS受试者工作特征(ROC)曲线,探讨内脏脂肪面积预测NAFLD患者严重程度的评估效能。结果NAFLD患者的内脏脂肪面积高于对照组(F=43.413,P<0.05),与疾病严重程度成正比。相关性分析结果显示,NAFLD患者内脏脂肪面积与NFS(r=0.293,P<0.05)、肝脂肪变程度(r=0.697,P<0.05)等呈正相关,与年龄、身体质量指数无明显相关性。ROC曲线分析结果显示,内脏脂肪面积预测轻、中、重度NAFLD患者的曲线下面积分别为0.870、0.867和0.835,对应的最佳截断点分别为80 cm^(2)、95 cm^(2)和105.95 cm^(2)。内脏脂肪面积预测轻、中度NAFLD效能优于NFS(Z=3.987,P<0.001;Z=2.253,P=0.024);NFS预测重度NAFLD效能优于内脏脂肪面积(Z=2.274,P=0.023)。结论NAFLD患者内脏脂肪面积水平明显升高,可作为辅助诊断轻、中度NAFLD的潜在指标。

强肝胶囊对非酒精性脂肪性肝病患者胰岛素抵抗指数和肝纤维化评分的影响

目的观察强肝胶囊对非酒精性脂肪性肝病(NAFLD)患者肝纤维化评分和胰岛素抵抗指数的影响。方法选取2014年8月-2015年7月在上海市第八人民医院就诊的NAFLD患者85例,随机分为治疗组(n=45)和对照组(n=40)。治疗组给予强肝胶囊,对照组给予多烯磷脂酰胆碱胶囊,2组疗程均为24周。观察2组治疗前后血清转氨酶(AST、ALT)、稳态模型胰岛素抵抗指数(HOMA-IR)以及NAFLD肝纤维化评分(NAFLDFS)的变化。计量资料组间比较采用成组t检验,组内治疗前后比较采用配对t检验;计数资料组间比较采用χ2检验。结果 2组治疗后ALT、AST水平均较同组治疗前明显改善,差异均有统计学意义(P值均<0.05);与治疗前比,治疗组HOMA-IR、NAFLDFS治疗后均明显下降,差异均有统计学意义(3.58±0.85 vs 2.48±0.78,t=6.40,P<0.05;-1.78±1.24 vs-2.35±0.98,t=2.40,P<0.05)。2组间治疗后比较,治疗组HOMA-IR、NAFLDFS较对照组显著下降,差异均有统计学意义(2.48±0.78 vs 3.09±0.89,t=3.36,P<0.01;-2.35±0.98 vs-1.48±1.08,t=3.80,P<0.01)。整个疗程未见明显不良反应。结论强肝胶囊不仅能降低血清转氨酶水平,还可改善胰岛素抵抗和减轻NAFLD患者肝纤维化程度。

下丘脑STAT3在非酒精性脂肪性肝病大鼠发病中的作用及降脂颗粒的干预

目的:观察非酒精性脂肪肝大鼠下丘脑STAT3蛋白表达和组成性激活的改变,以及中药降脂颗粒对其干预作用.方法:高脂饲料制备非酒精性脂肪肝大鼠模型,待造模成功后将大鼠随机分为模型对照组(n=10)、辛伐他汀组(n=10)、降脂颗粒组(n=10),每日进行ig药物干预,4wk,并设空白对照组(n=8).比色法检测血清TG、TC;HE染色观察观察肝组织脂肪变和炎症;Westernblot检测下丘脑磷酸化STAT3蛋白表达,EMSA检测下丘脑STAT3的组成性激活状态.结果:磷酸化STAT3蛋白表达及其组成性激活在非酒精性脂肪肝大鼠均明显降低,降脂颗粒用药组及辛伐他汀组能下调大鼠血清TG(0.54±0.09mmol/L,0.68±0.08mmol/Lvs0.84±0.09mmol/L,均P<0.05)、TC(1.85±0.31mmol/L,2.08±0.30mmol/Lvs2.84±0.30mmol/L,均P<0.05)水平,减轻肝脂肪变(2.26±0.52,2.57±0.67vs3.10±0.57,均P<0.05)和炎症程度(0.68±0.67,0.95±0.6vs1.52±0.71,均P<0.05);上调下丘脑组织磷酸化STAT3蛋白表达及其组成性激活.结论:STAT3在非酒精性脂肪肝大鼠下丘脑组织表达和激活明显下降,中药降脂颗粒对非酒精性脂肪肝有很好的治疗作用,并可上调STAT3的表达和组成性激活.