Diagnostic value of FIB-4, aspartate aminotransferaseto-platelet ratio index and liver stiffness measurement in hepatitis B virus-infected patients with persistently normal alanine aminotransferase

AIM To assess the diagnostic value of FIB-4, aspartate aminotransferase-to-platelet ratio index(APRI), and liver stiffness measurement(LSM) in patients with hepatitis B virus infection who have persistently normal alanine transaminase(PNALT).METHODS We enrolled 245 patients with chronic hepatitis B: 95 in PNALT group, 86 in intermittently elevated alanine transaminase(PIALT1) group [alanine transaminase(ALT) within 1-2 × upper limit of normal value(ULN)], and 64 in PIALT2 group(ALT > 2 × ULN). All the patients received a percutaneous liver biopsy guided by ultrasonography. LSM, biochemical tests, and complete blood cell counts were performed.RESULTS The pathological examination revealed moderate inflammatory necrosis ratios of 16.81%(16/95), 32.56%(28/86), and 45.31%(28/64), and moderate liverfibrosis of 24.2%(23/95), 33.72%(29/86), and 43.75%(28/64) in the PNALT, PIALT1, and PIALT2 groups, respectively. The degrees of inflammation and liver fibrosis were significantly higher in the PIALT groups than in the PNALT group(P < 0.05). No significant difference was found in the areas under the curve(AUCs) between APRI and FIB-4 in the PNALT group; however, significant differences were found between APRI and LSM, and between FIB-4 and LSM in the PNALT group(P < 0.05 for both). In the PIALT1 and PIALT2 groups, no significant difference(P > 0.05) was found in AUCs for all comparisons(P > 0.05 for all). In the overall patients, a significant difference in the AUCs was found only between LSM and APRI(P < 0.05).CONCLUSION APRI and FIB-4 are not the ideal noninvasive hepatic fibrosis markers for PNALT patients. LSM is superior to APRI and FIB-4 in PNALT patients because of the influence of liver inflammation and necrosis.

Computed tomography vs liver stiffness measurement and magnetic resonance imaging in evaluating esophageal varices in cirrhotic patients:A systematic review and meta-analysis

BACKGROUND Computed tomography(CT),liver stiffness measurement(LSM),and magnetic resonance imaging(MRI)are non-invasive diagnostic methods for esophageal varices(EV)and for the prediction of high-bleeding-risk EV(HREV)in cirrhotic patients.However,the clinical use of these methods is controversial.AIM To evaluate the accuracy of LSM,CT,and MRI in diagnosing EV and predicting HREV in cirrhotic patients.METHODS We performed literature searches in multiple databases,including Pub Med,Embase,Cochrane,CNKI,and Wanfang databases,for articles that evaluated the accuracy of LSM,CT,and MRI as candidates for the diagnosis of EV and prediction of HREV in cirrhotic patients.Summary sensitivity and specificity,positive likelihood ratio and negative likelihood ratio,diagnostic odds ratio,and the areas under the summary receiver operating characteristic curves were analyzed.The quality of the articles was assessed using the quality assessment of diagnostic accuracy studies-2 tool.Heterogeneity was examined by Q-statistic test and I2 index,and sources of heterogeneity were explored using metaregression and subgroup analysis.Publication bias was evaluated using Deek’s funnel plot.All statistical analyses were conducted using Stata12.0,Meta Disc1.4,and Rev Man5.3.RESULTS Overall,18,17,and 7 relevant articles on the accuracy of LSM,CT,and MRI in evaluating EV and HREV were retrieved.A significant heterogeneity was observed in all analyses(P<0.05).The areas under the summary receiver operating characteristic curves of LSM,CT,and MRI in diagnosing EV and predicting HREV were 0.86(95%confidence interval[CI]:0.83-0.89),0.91(95%CI:0.88-0.93),and 0.86(95%CI:0.83-0.89),and 0.85(95%CI:0.81-0.88),0.94(95%CI:0.91-0.96),and 0.83(95%CI:0.79-0.86),respectively,with sensitivities of 0.84(95%CI:0.78-0.89),0.91(95%CI:0.87-0.94),and 0.81(95%CI:0.76-0.86),and 0.81(95%CI:0.75-0.86),0.88(95%CI:0.82-0.92),and 0.80(95%CI:0.72-0.86),and specificities of 0.71(95%CI:0.60-0.80),0.75(95%CI:0.68-0.82),and 0.82(95%CI:0.70-0.89),and 0.73(95%CI:0.66-0.80),0.87(95%CI:0.81-0.92),and 0.72(95%CI:0.62-0.80),respectively.The corresponding positive likelihood ratios were 2.91,3.67,and 4.44,and 3.04,6.90,and2.83;the negative likelihood ratios were 0.22,0.12,and 0.23,and 0.26,0.14,and 0.28;the diagnostic odds ratios were 13.01,30.98,and 19.58,and 11.93,49.99,and 10.00.CT scanner is the source of heterogeneity.There was no significant difference in diagnostic threshold effects(P>0.05)or publication bias(P>0.05).CONCLUSION Based on the meta-analysis of observational studies,it is suggested that CT imaging,a non-invasive diagnostic method,is the best choice for the diagnosis of EV and prediction of HREV in cirrhotic patients compared with LSM and MRI.

Clinical value of predictive models based on liver stiffness measurement in predicting liver reserve function of compensated chronic liver disease

BACKGROUND Assessment of liver reserve function(LRF)is essential for predicting the prognosis of patients with chronic liver disease(CLD)and determines the extent of liver resection in patients with hepatocellular carcinoma.AIM To establish noninvasive models for LRF assessment based on liver stiffness measurement(LSM)and to evaluate their clinical performance.METHODS A total of 360 patients with compensated CLD were retrospectively analyzed as the training cohort.The new predictive models were established through logistic regression analysis and were validated internally in a prospective cohort(132 patients).RESULTS Our study defined indocyanine green retention rate at 15 min(ICGR15)≥10%as mildly impaired LRF and ICGR15≥20%as severely impaired LRF.We constructed predictive models of LRF,named the mLPaM and sLPaM,which involved only LSM,prothrombin time international normalized ratio to albumin ratio(PTAR),age and model for end-stage liver disease(MELD).The area under the curve of the mLPaM model(0.855,0.872,respectively)and sLPaM model(0.869,0.876,respectively)were higher than that of the methods for MELD,albumin bilirubin grade and PTAR in the two cohorts,and their sensitivity and negative predictive value were the highest among these methods in the training cohort.In addition,the new models showed good sensitivity and accuracy for the diagnosis of LRF impairment in the validation cohort.CONCLUSION The new models had a good predictive performance for LRF and could replace the indocyanine green(ICG)clearance test,especially in patients who are unable to undergo ICG testing.

Early diagnostic value of liver stiffness measurement in hepatic sinusoidal obstruction syndrome induced by hematopoietic stem cell transplantation

Hematopoietic stem cell transplantation(HSCT)-sinusoidal obstruction syndrome(SOS),also known as veno-occlusive disease,is a clinical syndrome characterized by symptoms,such as right upper quadrant pain,jaundice,fluid retention,and hepatomegaly,and is caused by pre-treatment-related hepatotoxicity during the early stages after HSCT.Clinical diagnosis of HSCT-SOS is based on the revised Seattle or Baltimore standards.The revised standard by the European Society for Bone Marrow Transplantation in 2016 has good practicability and can be used in combination with these two standards.Eight studies have shown the value of liver stiffness measurement(LSM)in the early diagnosis of HSCT-SOS.Four studies investigated LSM specificity and sensitivity for the early diagnosis of HSCT-SOS.LSM can distinguish SOS from other post-HSCT complications,enabling a clear differential diagnosis.It has been shown that median LSM of patients with SOS is significantly higher than that of patients with other treatment-related liver complications(e.g.,acute cholecystitis,cholangitis,antifungal drug-related liver injury,liver graft-versus-host disease,isolated liver biochemical changes,and fulminant Epstein Barr virus related hepatitis reactivation).Therefore,the above data confirmed the utility of LSM and strongly suggested that LSM improves the positive predictive value of the SOS diagnostic clinical score after allogeneic HSCT.Early diagnosis of SOS is beneficial in preventing severe HSCT complications.

Liver Stiffness Measurement Is Useful to Predict Early Recurrence of Hepatocellular Carcinoma after Sustained Virological Responses by Direct Antiviral Agents in Patients with Hepatitis C

Background: Recently, increases in the risk of Hepatocellular carcinoma (HCC) recurrence in patients with hepatitis C virus (HCV) due to the administration of direct antivirals agents (DAA) have been reported. Methods: One hundred and nineteen patients who were treated with DAA and achieved sustained viral response (SVR) were prospectively followed-up for over two years by transient elastography with liver stiffness measurements (LSM). Fourteen out of 119 patients (12%) had a history of being treated for HCC by radiofrequency ablation or resection and achieved complete responses after previous HCC treatments before the initiation of DAA. HCC was diagnosed by contrast-enhanced computed tomography (CT) or enhanced magnetic resonance imaging (MR). CT or MR was performed before the DAA treatment and every 6 months after during the follow-up. LSM was performed at the initiation of DAA (LSM0), at 24 weeks after the start of DAA (LSM24), at 48 weeks after that (LSM48) and at 2 years after that (LSM2y). Results: LSM0, LSM24, LSM48 and LSM2y of 105 patients without HCC were 7.5 (3.027.0), 6.0 (2.5 - 31.6), 4.6 (2.6?- 25.2) and 4.4 (3.1 - 29.9) kPa, respectively, showing significant improvements. Three out of 105 patients (2.9%) subsequently developed HCC and their LSM showed improvements. Eight out of fourteen patients (57%) with a history of HCC treatments subsequently developed HCC recurrence. LSM0 in the eight patients with recurrence increasing from 12.1 to 27.0 kPa, LSM24 from 9.9 to 26.6 kPa and LSM48 from 9.6 to 18.0 kPa. On the other hand, the six other patients without recurrence had LSM values that were less than 12.0 kPa at last. Based on the ROC analysis, LSM0 15.4, LSM24 12.8 and LSM48 9.6 kPa were identified as cut-off values. Conclusion: HCV patients previously treated for HCC with high LSM values before and after DAA have an elevated risk of HCC recurrence, particularly LSM24 >12.8 kPa and LSM48 >9.6 kPa.

The diagnostic value of liver stiffness measurement combined with S index in the degree of hepatitis B liver fibrosis

Objective:To investigate the value of liver stiffness measurement(LSM)combined with S index in predicting the degree of liver fibrosis in hepatitis B patients.Methods:A total of 187 chronic hepatitis B patients who were admitted to the Department of Infection,the First Affiliated Hospital of Hainan Medical College from January 2019 to December 2021 were selected.General data were collected,blood routine,liver function,liver fibrosis and liver stiffness measurement were tested,and S index,APRI and FIB-4 index were calculated,and liver biopsy was performed.Results:According to the pathological results of liver puncture,The patients were divided into no significant fibrosis group(n=86),significant fibrosis group(n=71)and cirrhosis group(n=30).There were significant differences in age,PLT,GGT,ALB,S index,HA,LN and LSM levels among the three groups(P<0.05).There was a good correlation between S index and the degree of hepatic fibrosis(rs=0.738,P<0.001).The AUC of S index and LSM for the diagnosis of significant fibrosis in hepatitis B were 0.873 and 0.792,respectively.And the AUC of S index and LSM for the diagnosis of liver cirrhosis were 0.966 and 0.879,respectively.The AUC for the combined diagnosis of significant fibrosis and cirrhosis were 0.908 and 0.988,respectively.The AUROC of combined detection in the diagnosis of cirrhosis was higher than that of LSM,APRI and FIB-4(P<0.05).Conclusion:LSM combined with S index has certain application value in the diagnosis of liver fibrosis/cirrhosis in hepatitis B patients.

Liver stiffness and serum markers for excluding high-risk varices in patients who do not meet Baveno VI criteria

BACKGROUND The Baveno VI criteria for predicting esophageal varices, i.e., liver stiffness measurement (LSM)< 20 kPa and platelet (PLT) count > 150 × 109/L, identify patients who can safely avoid gastroscopy screening. However, they require further refinement. AIM To evaluate the utility of LSM and serum markers of liver fibrosis in ruling out high-risk varices (HRV) in patients who do not meet Baveno VI criteria. METHODS Data from 132 patients with hepatitis B virus (HBV)-related compensated liver cirrhosis who did not meet the Baveno VI criteria were retrospectively reviewed. MedCalc 15.8 was used to calculate receiver operating characteristic (ROC) curves, and the accuracy of LSM, PLT count, aspartate aminotransferase (AST)- to-PLT ratio index, Fibrosis-4, and the Lok index in predicting HRV were evaluated according to the area under each ROC curve (AUROC). The utility of LSM, PLT, and serum markers of liver fibrosis stratified by alanine transaminase (ALT) and total bilirubin (TBil) levels was evaluated for ruling out HRV. RESULTS In all patients who did not meet the Baveno VI criteria, the independent risk factors for HRV were LSM and ALT. Only the AUROC of Lok index was above 0.7 for predicting HRV, and at a cutoff value of 0.4531 it could further spare 24.2% of gastroscopies without missing HRVs. The prevalence of HRV was significantly lower in patients with ALT or TBil ≥ 2 upper limit of normal (ULN)(14.3%) than in patients with both ALT and TBil < 2 ULN (34.1%)(P = 0.018). In the 41 patients with ALT and TBil < 2 ULN, LSM had an AUROC for predicting HRV of 0.821. LSM < 20.6 kPa spared 39.0% of gastroscopies without missing HRVs. In the 91 patients with ALT or TBiL ≥ 2 ULN, the Lok index and PLT had AUROCs of 0.814 and 0.741, respectively. Lok index ≤ 0.5596 or PLT > 100 × 109/L further spared 39.6% and 43.9% of gastroscopies, respectively, without missing HRVs. CONCLUSION In HBV-related compensated cirrhosis patients who do not meet Baveno VI criteria, the LSM, PLT, or Lok index cutoff stratified by ALT and TBil accurately identifies more patients without HRV.

Study of detection times for liver stiffness evaluation by shear wave elastography

AIM: To investigate enough valid measurements (VMs) to assess liver fibrosis in chronic hepatitis B patients (CHB).

Non-invasive model for predicting high-risk esophageal varices based on liver and spleen stiffness

BACKGROUND Acute bleeding due to esophageal varices(EVs)is a life-threatening complication in patients with cirrhosis.The diagnosis of EVs is mainly through upper gastrointestinal endoscopy,but the discomfort,contraindications and complications of gastrointestinal endoscopic screening reduce patient compliance.According to the bleeding risk of EVs,the Baveno VI consensus divides varices into high bleeding risk EVs(HEVs)and low bleeding risk EVs(LEVs).We sought to identify a non-invasive prediction model based on spleen stiffness measurement(SSM)and liver stiffness measurement(LSM)as an alternative to EVs screening.AIM To develop a safe,simple and non-invasive model to predict HEVs in patients with viral cirrhosis and identify patients who can be exempted from upper gastrointestinal endoscopy.METHODS Data from 200 patients with viral cirrhosis were included in this study,with 140 patients as the modelling group and 60 patients as the external validation group,and the EVs types of patients were determined by upper gastrointestinal endoscopy and the Baveno Ⅵ consensus.Those patients were divided into the HEVs group(66 patients)and the LEVs group(74 patients).The effect of each parameter on HEVs was analyzed by univariate and multivariate analyses,and a noninvasive prediction model was established.Finally,the discrimination ability,calibration ability and clinical efficacy of the new model were verified in the modelling group and the external validation group.RESULTS Univariate and multivariate analyses showed that SSM and LSM were associated with the occurrence of HEVs in patients with viral cirrhosis.On this basis,logistic regression analysis was used to construct a prediction model:Ln[P/(1-P)]=-8.184-0.228×SSM+0.642×LSM.The area under the curve of the new model was 0.965.When the cut-off value was 0.27,the sensitivity,specificity,positive predictive value and negative predictive value of the model for predicting HEVs were 100.00%,82.43%,83.52%,and 100%,respectively.Compared with the four prediction models of liver stiffness-spleen diameter to platelet ratio score,variceal risk index,aspartate aminotransferase to alanine aminotransferase ratio,and Baveno VI,the established model can better predict HEVs in patients with viral cirrhosis.CONCLUSION Based on the SSM and LSM measured by transient elastography,we established a non-invasive prediction model for HEVs.The new model is reliable in predicting HEVs and can be used as an alternative to routine upper gastrointestinal endoscopy screening,which is helpful for clinical decision making.

Nationwide retrospective study of hepatitis B virological response and liver stiffness improvement in 465 patients on nucleos(t)ide analogue

BACKGROUND Hepatitis B virus(HBV)nucleos(t)ide analog(NA)therapy reduces liver disease but requires prolonged therapy to achieve hepatitis B surface antigen(HBsAg)loss.There is limited North American real-world data using non-invasive tools for fibrosis assessment and few have compared 1st generation NA or lamivudine(LAM)to tenofovir disoproxil fumarate(TDF).AIM To assess impact of NA on virological response and fibrosis regression using liver stiffness measurement(LSM)(i.e.,FibroScan®).METHODS Retrospective,observational cohort study from the Canadian HBV Network.Data collected included demographics,NA,HBV DNA,alanine aminotransferase(ALT),and LSM.Patients were HBV monoinfected patients,treatment naïve,and received 1 NA with minimum 1 year follow-up.RESULTS In 465(median 49 years,37%female,35%hepatitis B e antigen+at baseline,84%Asian,6%White,and 9%Black).Percentage of 64(n=299)received TDF and 166 were LAM-treated with similar median duration of 3.9 and 3.7 years,respectively.The mean baseline LSM was 11.2 kPa(TDF)vs 8.3 kPa(LAM)(P=0.003).At 5-year follow-up,the mean LSM was 7.0 kPa in TDF vs 6.7 kPa in LAM(P=0.83).There was a significant difference in fibrosis regression between groups(i.e.,mean-4.2 kPa change in TDF and-1.6 kPa in LAM,P<0.05).The last available data on treatment showed that all had normal ALT,but more TDF patients were virologically suppressed(<10 IU/mL)(n=170/190,89%)vs LAM-treated(n=35/58,60%)(P<0.05).None cleared HBsAg.CONCLUSION In this real-world North American study,approximately 5 years of NA achieves liver fibrosis regression rarely leads to HBsAg loss.

Letter to editor‘Non-invasive model for predicting high-risk esophageal varices based on liver and spleen stiffness’

predicting high-risk esophageal varices based on liver and spleen stiffness".Acute bleeding caused by esophageal varices is a life-threatening complication in patients with liver cirrhosis.Due to the discomfort,contraindications,and associated complications of upper gastrointestinal endoscopy screening,it is crucial to identify an imaging-based non-invasive model for predicting high-risk esophageal varices in patients with cirrhosis.

Changing liver stiffness predict regression in advanced fibrosis patients with chronic hepatitis B,but not in moderate fibrosis patients

Background and objective:Liver stiffness measurement(LSM)may effectively correlate to the presence of liver fibrosis,but it is controversial to use for the prediction of clinical outcomes.Therefore,we aimed to evaluate the predictive value of liver stiffness for the regression of liver fibrosis.Methods:In this study,we collected data from a clinical cohort of patients who are received anti-virus therapies for 48 weeks.180 naive chronic hepatitis B(CHB)patients,who received paired LSM and liver biopsy with pre-and post-treatments were analyzed.Two methods(FibroScan and iLivTouch)test LSM.Result:The area under the receiver operating characteristics curve(AUROC)of changing LSM for fibrosis regression is higher in advanced fibrosis patients(F5/6)than in moderate fibrosis patients(F3/4)in both FibroScan(0.719,95%CI,0.590–0.848;P=0.003;vs 0.617,95%CI,0.379–0.856,P=0.282)and iLivTouch(0.707,95%CI,0.567–0.847;P=0.011;vs 0.583,95%CI,0.422–0.744;P=0.377).A higher kappa value was received in advanced stage than in moderate stage both in FibroScan(0.392,P=0.001 vs 0.265,P=0.053)and iLivTouch(0.326,P=0.019 vs 0.030,P=0.833).Cut-off set as 4.10 kPa(sen,69.4%;spe,73.9%)in FibroScan,as 4.25 kPa(sen,56.8%;spe,72.2%)in iLivTouch.Conclusion:The changing LSM can be used for predicting the liver fibrosis regression in advanced stage of CHB patients.

LSM、PNI、Mayo评分对PBC相关肝硬化的预测价值

目的:探讨肝脏弹性硬度(liver stiffness measurements,LSM)、预后营养指数(prognostic nutritional index,PNI)、Mayo评分在原发性胆汁性胆管炎(primary biliary cholangitis,PBC)相关肝硬化中的预测价值。方法:收集2019年1月—2022年8月在南通大学附属南通第三医院住院诊治的239例PBC患者的临床资料,其中胆管炎组123例,肝硬化组116例。计算PNI、Mayo评分,采用多因素Logistic回归模型分析影响PBC患者病情进展的危险因素,ROC曲线评估其预测效能。结果:肝硬化组患者的碱性磷酸酶(alkaline phosphatase,ALP)、总胆汁酸(total bile acid,TBA)、肌酐(creatinine,Cr)、IgM、抗gp210抗体阳性率、LSM、Mayo评分均高于胆管炎组(均P<0.05);肝硬化组的PNI低于胆管炎组(P<0.05)。多因素Logistic回归分析结果显示,LSM、IgM、抗gp210抗体、PNI、Mayo评分是影响PBC患者肝硬化进程的独立危险因素(P<0.05)。Pearson相关性分析结果显示,LSM与Mayo评分呈正相关(r=0.224,P<0.001),PNI与Mayo评分呈负相关(r=-0.759,P<0.001)。LSM、PNI、Mayo评分的AUC分别为0.776、0.839、0.818,三者联合预测模型的AUC为0.914。结论:LSM、PNI、Mayo评分对PBC相关肝硬化有较好的预测价值,三者联合预测价值更高。

Spleen stiffness mirrors changes in portal hypertension after successful interferon-free therapy in chronic-hepatitis C virus patients

AIM To investigate changes in spleen stiffness measurements(SSMs) and other non-invasive tests(NITs) after treatment with direct-acting antivirals(DAAs) and identify predictors of SSM change after sustainedvirological response(SVR). METHODS We retrospectively analysed 146 advanced-chronic liver disease(ACLD) patients treated with DAA with available paired SSM at baseline and SVR24. Liver stiffness(LSM), spleen diameter(SD), platelet count(PLT) and liver stiffness-spleen diameter to platelet ratio score(LSPS) were also investigated. LSM ≥ 21 k Pa was used as a cut-off to rule-in clinically significant portal hypertension(CSPH). SSM reduction > 20% from baseline was defined as significant.RESULTS SSM significantly decreased at SVR24, in both patients with and without CSPH; in 44.8% of cases, SSM reduction was > 20%. LSPS significantly improved in the entire cohort at SVR24; SD and PLT changed significantly only in patients without CSPH. LSM significantly decreased in 65.7% of patients and also in 2/3 patients in whom SSM did not decrease. The independent predictor of decreased SSM was median relative change of LSM. CSPH persisted in 54.4% patients after SVR. Delta LSM and baseline SSM were independent factors associated with CSPH persistence.CONCLUSION SSM and other NITs significantly decrease after SVR, although differently according to the patient's clinical condition. SSM faithfully reflects changes in portal hypertension and could represent a useful NIT for the follow-up of these patients.

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.

Liver Stiffness Measurement Can Reflect the Active Liver Necroinflammation in Population with Chronic Liver Disease:A Real-world Evidence Study

Background and Aims: Non-invasive evaluation of liver nec-roinflammation in patients with chronic liver disease is an un-met need in clinical practice.The diagnostic accuracy of transient elastography-based liver stiffness measurement(LSM)for liver fibrosis could be affected by liver necroinflam-mation,the latter of which could intensify stiffness of the liver.Such results have prompted us to explore the diagnosis potential of LSM for liver inflammation.Methods: Three cross-sectional cohorts of liver biopsy-proven chronic liver dis-ease patients were enrolled,including 1417 chronic hepatitis B(CHB)patients from 10 different medical centers,106 non-al-coholic steatohepatitis patients,and 143 patients with auto-immune-related liver diseases.Another longitudinal cohort of 14 entecavir treatment patients was also included.The re-ceiver operating characteristic(ROC)curve was employed to explore the diagnostic value of LSM.Results: In CHB patients,LSM value ascended with the increased severity of liver nec-roinflammation in patients with the same fibrosis stage.Such positive correlation between LSM and liver necroinflammation was also found in non-alcoholic steatohepatitis and autoim-mune-related liver diseases populations.Furthermore,the ROC curve exhibited that LSM could identify moderate and se-vere inflammation in CHB patients(area under the ROC curve as 0.779 and 0.838)and in non-alcoholic steatohepatitis pa-tients(area under the ROC curve as 0.826 and 0.871),respec-tively.Such moderate diagnostic value was also found in autoimmune-related liver diseases patients.In addition,in the longitudinal entecavir treated CHB cohort,a decline of LSM values was observed in parallel with the control of inflam-matory activity in liver.Conclusions: Our study implicates a diagnostic potential of LSM to evaluate the severity of liver necroinflammation in chronic liver disease patients.

Liver Stiffness Measurement can Predict Liver Inflammation in Chronic Hepatitis B Patients with Normal Alanine Transaminase

Background and Aims:To determine whether liver stiffness measurement(LSM)indicates liver inflammation in chronic hepatitis B(CHB)with different upper limits of normal(ULNs)for alanine aminotransferase(ALT).Methods:We grouped 439 CHB patients using different ULNs for ALT:cohort I,≤40 U/L(439 subjects);cohort II,≤35/25 U/L(males/females;330 subjects);and cohort III,≤30/19 U/L(males/females;231 subjects).Furthermore,84 and 96 CHB patients with normal ALT(≤40 U/L)formed the external and prospective validation groups,respectively We evaluated the correlation between LSM and biopsy-confirmed liver inflammation,and determined diagnostic accuracy using area under the curve(AUC).A noninvasive LSM-based model was developed using multivariate logistic regression.Results:Fibrosis-adjusted LSM values significantly increased with increasing inflammation.The AUCs of LSM in cohorts I,II,and III were 0.799,0.796,and 0.814,respectively,for significant inflammation(A≥2)and 0.779,0.767,and 0.770,respectively,for severe inflammation(A=3).Cutoff LSM values in all cohorts for A≥2and A=3 were 6.3 and 7.5 kPa,respectively.Internal,external,and prospective validations showed high diagnostic accuracy of LSM for A≥2 and A=3,and no significant differences in AUCs among the four groups.LSM and globulin independently predicted A≥2.The AUC of an LSM-globulin model for A≥2 exceeded those of globulin,ALT,and AST,but was similar to that of LSM.Conclusions:LSM predicted liver inflammation and guided the indication of antiviral therapy for CHB in patients with normal ALT.

LSM值与APRI评估慢性肝病肝纤维化程度的临床研究

目的:探讨肝脏硬度测定(LSM)值、天门冬氨酸氨基转移酶(AST)与血小板(PLT)比值指数(APR I)用于评估慢性肝病肝纤维化程度的临床应用价值。方法:对94例慢性肝病患者肝活检当日或前一日作血常规、肝功能检测与瞬时弹性扫描(FS)检查。以肝活检结果为标准,比较LSM值与ARPI评估肝纤维化程度的接受者操作特征(ROC)曲线下面积(AUC),并比较相应的截断点值及其灵敏度和特异度。结果:应用LSM值与APR I区分显著肝纤维化(S≥2)的截断点分别为8.10 kPa、0.45,对应的AUC分别为0.85、0.67;两者区分早期肝硬化(S≥3)和肝硬化(S=4)的截断点分别为9.80 kPa、0.98与13.10 kPa、0.98,对应的AUC分别为0.96、0.66与0.97、0.72。在测定结果与肝纤维化程度相关性上,LSM值(r=0.64,P<0.05)比APR I(r=0.42,P<0.05)更明显。结论:应用LSM值和APR I评估慢性肝病肝纤维化程度时,以LSM值反映更为准确。

Performance of transient elastography in assessing liver fibrosis in patients with autoimmune hepatitis-primary biliary cholangitis overlap syndrome

AIM To investigate the performance of transient elastography(TE) for diagnosis of fibrosis in patients with autoimmune hepatitis-primary biliary cholangitis(AIHPBC) overlap syndrome.METHODS A total of 70 patients with biopsy-proven AIH-PBC overlap syndrome were included. Spearman correlation test was used to analyze the correlation of liver stiffness measurement(LSM) and fibrosis stage. Independent samples Student's t-test or one-way analysis of variance was used to compare quantitative variables. Receiver operating characteristics(ROC) curve was used to calculate the optimal cut-off values of LSM for predicting individual fibrosis stages. A comparison on the diagnostic accuracy for severe fibrosis was made between LSM and other serological scores.RESULTS Patients with AIH-PBC overlap syndrome had higher median LSM than healthy controls(11.3 ± 6.4 k Pa vs 4.3 ± 1.4 k Pa, P < 0.01). LSM was significantly correlated with fibrosis stage(r = 0.756, P < 0.01). LSM values increased gradually with an increased fibrosis stage. The areas under the ROC curves of LSM for stages F ≥ 2, F ≥ 3, and F4 were 0.837(95%CI: 0.729-0.914), 0.910(0.817-0.965), and 0.966(0.893-0.995), respectively. The optimal cut-off values of LSM for fibrosis stages F ≥ 2, F ≥ 3, and F4 were 6.55, 10.50, and 14.45 k Pa, respectively. LSM was significantly superior to fibrosis-4, glutaglumyl-transferase/platelet ratio, and aspartate aminotransferase-to-platelet ratio index scores in detecting severe fibrosis(F ≥ 3)(0.910 vs 0.715, P < 0.01; 0.910 vs 0.649, P < 0.01; 0.910 vs 0.616, P < 0.01, respectively).CONCLUSION TE can accurately detect hepatic fibrosis as a noninvasive method in patients with AIH-PBC overlap syndrome.

Effect of liver inflammation on accuracy of FibroScan device in assessing liver fibrosis stage in patients with chronic hepatitis B virus infection

BACKGROUND Transient elastography(FibroScan)is a new and non-invasive test,which has been widely recommended by the guidelines of chronic hepatitis B virus(HBV)management for assessing hepatic fibrosis staging.However,some confounders may affect the diagnostic accuracy of the FibroScan device in fibrosis staging.AIM To evaluate the diagnostic value of the FibroScan device and the effect of hepatic inflammation on the accuracy of FibroScan in assessing the stage of liver fibrosis in patients with HBV infection.METHODS The data of 416 patients with chronic HBV infection who accepted FibroScan,liver biopsy,clinical,and biological examination were collected from two hospitals retrospectively.Receiver operating characteristic(ROC)curves were used to analyze the diagnostic performance of FibroScan for assessing the stage of liver fibrosis.Any discordance in fibrosis staging by FibroScan and pathological scores was statistically analyzed.Logistic regression and ROC analyses were used to analyze the accuracy of FibroScan in assessing the stage of fibrosis in patients with different degrees of liver inflammation.A non-invasive model was constructed to predict the risk of misdiagnosis of fibrosis stage using FibroScan.RESULTS In the overall cohort,the optimal diagnostic values of liver stiffness measurement(LSM)using FibroScan for significant fibrosis(≥F2),severe fibrosis(≥F3),and cirrhosis(F4)were 7.3 kPa[area under the curve(AUC)=0.863],9.7 kPa(AUC=0.911),and 11.3 kPa(AUC=0.918),respectively.The rate of misdiagnosis of fibrosis stage using FibroScan was 34.1%(142/416 patients).The group of patients who showed discordance between fibrosis staging using FibroScan and pathological scores had significantly higher alanine aminotransferase and aspartate aminotransferase levels,and a higher proportion of moderate to severe hepatic inflammation,compared with the group of patients who showed concordance in fibrosis staging between the two methods.Liver inflammation activity over 2(OR=3.53)was an independent risk factor for misdiagnosis of fibrosis stage using FibroScan.Patients with liver inflammation activity≥2 showed higher LSM values using FibroScan and higher rates of misdiagnosis of fibrosis stage,whereas the diagnostic performance of FibroScan for different fibrosis stages was significantly lower than that in patients with inflammation activity<2(all P<0.05).A non-invasive prediction model was established to assess the risk of misdiagnosis of fibrosis stage using FibroScan,and the AUC was 0.701.CONCLUSION Liver inflammation was an independent risk factor affecting the diagnostic accuracy of FibroScan for fibrosis stage.A combination of other related noninvasive factors can predict the risk of misdiagnosis of fibrosis staging using FibroScan.