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 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.

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.

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.

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.

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.

Clinical study of standard residual liver volume and transient elastography in predicting poor prognosis of patients after hemihepatectomy

BACKGROUND Liver cancer resection,especially in patients with hemihepatectomy or extended hemihepatectomy,often leads to poor prognosis,such as liver insufficiency and even liver failure and death,because the standard residual liver volume(SRLV)cannot be fully compensated after surgery.AIM To explore the risk factors of poor prognosis after hemihepatectomy for hepatocellular carcinoma and evaluate the application value of related prognostic approaches.METHODS The clinical data of 35 patients with primary liver cancer in Nantong Third People's Hospital from February 2016 to July 2020 were retrospectively analyzed.The receiver operating characteristic curve was created using medcac19.0.4 to compare the critical values of the SRLV in different stages of liver fibrosis after hemihepatectomy with those of liver dysfunction after hemihepatectomy.It was constructed by combining the Child-Pugh score to evaluate its application value in predicting liver function compensation.RESULTS The liver stiffness measure(LSM)value and SRLV were associated with liver dysfunction after hemihepatectomy.Logistic regression analysis showed that an LSM value≥25 kPa[odds ratio(OR)=6.254,P<0.05]and SRLV≤0.290 L/m^(2)(OR=5.686,P<0.05)were independent risk factors for postoperative liver dysfunction.The accuracy of the new liver reserve evaluation model for predicting postoperative liver function was higher than that of the Child-Pugh score(P<0.05).CONCLUSION SRLV and LSM values can be used to evaluate the safety of hemihepatectomy.The new liver reserve evaluation model has good application potential in the evaluation of liver reserve function after hemihepatectomy.

Non-invasive assessment of esophageal varices:Status of today

With increasing burden of compensated cirrhosis,we desperately need noninvasive methods for assessment of clinically significant portal hypertension.The use of liver and spleen stiffness measurement helps in deferring unnecessary endoscopies for low risk esophageal varices.This would reduce cost and patient discomfort.However,these special techniques may not be feasible at remote areas where still we need only biochemical parameters.More prospective studies validating the non-invasive risk prediction models are definitely needed.

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.

Evaluation of controlled attenuation parameter in assessing hepatic steatosis in patients with autoimmune liver diseases

BACKGROUND Hepatic steatosis commonly occurs in some chronic liver diseases and may affect disease progression.AIM To investigate the performance of controlled attenuation parameter(CAP)for the diagnosis of hepatic steatosis in patients with autoimmune liver diseases(AILDs).METHODS Patients who were suspected of having AILDs and underwent liver biopsy were consistently enrolled.Liver stiffness measurement(LSM)and CAP were performed by transient elastography.The area under the receiver operating characteristic(AUROC)curve was used to evaluate the performance of CAP for diagnosing hepatic steatosis compared with biopsy.RESULTS Among 190 patients with biopsy-proven hepatic steatosis,69 were diagnosed with autoimmune hepatitis(AIH),18 with primary biliary cholangitis(PBC),and 27 with AIH-PBC overlap syndrome.The AUROCs of CAP for the diagnosis of steatosis in AILDS were 0.878(0.791-0.965)for S1,0.764(0.676-0.853)for S2,and 0.821(0.716-0.926)for S3.The CAP value was significantly related to hepatic steatosis grade(P<0.001).Among 69 patients with AIH,the median CAP score was 205.63±47.36 dB/m for S0,258.41±42.83 dB/m for S1,293.00±37.18 dB/m for S2,and 313.60±27.89 dB/m for S3.Compared with patients with nonalcoholic fatty liver disease(NAFLD)presenting with autoimmune markers,patients with AIH concomitant with NAFLD were much older and had higher serum IgG levels and LSM values.CONCLUSION CAP can be used as a noninvasive diagnostic method to evaluate hepatic steatosis in patients with AILDs.Determination of LSM combined with CAP may help to identify patients with AIH concomitant with NAFLD from those with NAFLD with autoimmune phenomena.

Shear wave velocity is a useful marker for managing nonalcoholic steatohepatitis

AIM:To investigate whether a noninvasive measurement of tissue strain has a potential usefulness for management of nonalcoholic steatohepatitis(NASH).METHODS:In total 26 patients,23 NASHs and 3 normal controls were enrolled in this study.NASH was staged based on Brunt criterion.At a region of interest(ROI),a shear wave was evoked by implementing an acoustic radiation force impulse(ARFI),and the propagation velocity was quantif ied.RESULTS:Shear wave velocity(SWV) could be reproducibly quantified at all ROIs in all subjects except for 4 NASH cases,in which a reliable SWV value was not calculated at several ROIs.An average SWV of 1.34 ± 0.26 m/s in fibrous stage 0-1 was significantly slower than 2.20 ± 0.74 m/s and 2.90 ± 1.01 m/s in stages 3 and 4,respectively,but was not significantly different from 1.79 ± 0.78 m/s in stage 2.When a cutoff value was set at 1.47 m/s,receiver operating characteristic analysis showed significance to dissociate stages 3 and 4 from stage 0-1(P=0.0092) with sensitivity,specificity and area under curve of 100%,75% and 94.2%,respectively.In addition,the correlation between SWV and hyaluronic acid was significant(P<0.0001),while a tendency toward negative correlation was observed with serum albumin(P=0.053).CONCLUSION:The clinical implementation of ARFI provides noninvasive repeated evaluations of liver stiffness at an arbitrary position,which has the potential to shed new light on NASH management.

Non-invasive tests for the prediction of primary hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is one of the most common malignancies in the world and it is one of the main complications of cirrhosis and portal hypertension.Even in the presence of a well-established follow-up protocol for cirrhotic patients,to date poor data are available on predictive markers for primary HCC occurrence in the setting of compensated advanced chronic liver disease patients(cACLD).The gold standard method to evaluate the prognosis of patients with cACLD,beyond liver fibrosis assessed with histology,is the measurement of the hepatic venous pressure gradient(HVPG).An HVPG≥10 mmHg has been related to an increased risk of HCC in cACLD patients.However,these methods are burdened by additional costs and risks for patients and are mostly available only in referral centers.In the last decade increasing research has focused on the evaluation of several,simple,non-invasive tests(NITs)as predictors of HCC development.We reviewed the currently available literature on biochemical and ultrasound-based scores developed for the noninvasive evaluation of liver fibrosis and portal hypertension in predicting primary HCC.We found that the most reliable methods to assess HCC risk were the liver stiffness measurement,the aspartate aminotransferase to platelet ratio index score and the fibrosis-4 index.Other promising NITs need further investigations and validation for different liver disease aetiologies.

Transient elastography in chronic hepatitis B: An Asian perspective

Transient elastography (TE) is a new non-invasive tool for assessing liver stiffness, which is correlated with the histologic stage of liver fibrosis. Many studies have reported a good accuracy of TE in predicting signif icant fibrosis and an optimal accuracy in predicting cirrhosis. Furthermore, the potential role of TE in screening the general population has also been proven. TE thus helps physicians to decide treatment strategies, predict prog-nosis, and monitor disease progression in patients with chronic liver disease and to screen the general popula-tion to identify high risk patients with potential liver disease. However, most data on the clinical roles of TE have been gathered in European patients with chronic hepatitis C (CHC), because TE was first developed in France. Accordingly, much data on the usefulness of TE in patients with CHC has accumulated. Recently, however, vigorous efforts have been made to apply TEto patients with chronic hepatitis B (CHB), and TE has also proved to have acceptable accuracy in diagnosing liver fibrosis and cirrhosis in these patients. Thus, we focused on TE in the Asian population with CHB in comparison with the European population with CHC and found that the diagnostic performance and cutoff values were different between the 2 populations possibly as a result of several different confounders between Asian and European populations (the etiology of chronic liver disease, histologic features, major fluctuation in alanine aminotransferase levels, and the prevalence of high body mass index and metabolic syndrome). Therefore, further studies tailored to the Asian population with CHB should be performed before the widespread application of TE in Asian populations with CHB.

Shear wave elastography may be sensitive and more precise than transient elastography in predicting significant fibrosis

BACKGROUND Noninvasive measurements including transient elastography(TE)and twodimensional shear wave elastography(SWE)have been used clinically instead of liver biopsy for regular assessment of liver fibrosis in chronic hepatitis B(CHB)patients.AIM To investigate the diagnostic efficiency of SWE compared to TE by assessing independent influencing factors and performance for diagnosing significant fibrosis based on our cohort of treatment-naive CHB patients.METHODS Fifty-four treatment-naive CHB patients who underwent liver biopsy to determine whether to initiate antiviral therapy were enrolled.SWE,TE,serum tests and liver biopsy were performed for all participants.The fibrosis-4 and aspartate aminotransferase to platelet ratio index scores were also calculated.Potential independent influencing factors on SWE and TE values were analyzed.Based on liver pathology results,the agreement and correlation were determined,and a comparison of the two methods was performed.RESULTS There were 27 cases(50%)of mild fibrosis(F0-F2)and 27(50%)cases of significant fibrosis(F3-F6);fibrosis was assessed with the Ishak scoring system.Multivariate linear regression analyses revealed that the fibrosis stage was the only factor that affected the SWE values(P<0.001),whereas the total bilirubin level(P=0.013)and fibrosis stage(P=0.037)were independent factors that affected TE values.Orthogonal partial least squares discriminant analysis showed that the number of independent factors(VIP>1)was higher for TE than SWE.Bland-Altman analysis showed satisfactory agreement between liver stiffness measurements(LSMs)of SWE and TE.Both SWE and TE could significantly discriminate significant fibrosis from mild fibrosis(P<0.001).SWE exhibited a higher correlation with LSMs of liver fibrosis than TE(r=0.65 and 0.50,P<0.001).The diagnostic performance of SWE was better than that of TE for significant fibrosis(F>2).The areas under the receiver operating characteristic curves of SWE and TE were 0.786 and 0.714,respectively.The optimal LSM cutoff values of SWE and TE were 9.05 kPa and 8.15 kPa,respectively.CONCLUSION Compared to the TE value,the SWE value was less affected by other factors.SWE may be more sensitive and precise than TE in predicting significant fibrosis(>F2)in CHB patients.

Update of liver fibrosis and steatosis with transient elastography (Fibroscan)

Background:Assessment of liver fibrosis and steatosis is now almost indispensable in most of the chronic liver diseases in order to determine prognosis and need for treatment,and to monitor disease progression and response to treatment.Liver biopsy is limited by its invasiveness and patient acceptability.Transient elastography(TE;Fibroscan)is a non-invasive tool with satisfactory accuracy and reproducibility to estimate liver fibrosis.Aims&Methods:To review the existing evidence concerning the clinical applications of TE in major liver diseases,including chronic hepatitis B and-C,non-alcoholic fatty liver disease(NAFLD),alcoholic liver disease,primary biliary cirrhosis and primary sclerosing cholangitis.Results:As alanine aminotransferase(ALT)is one of the major confounding factors of liver stiffness in chronic hepatitis B,an ALT-based algorithm has been developed and higher liver stiffness measurements(LSM)cut-off values for different stages of liver fibrosis should be used in patients with elevated ALT levels up to five times the upper limit of normal.Furthermore,falsely-high LSM results up to the cirrhotic range may occur during ALT flare.TE is also useful predicting patient prognosis in the development of hepatocellular carcinoma(HCC),portal hypertension,postoperative complications in HCC patients and survival.Unfortunately,failed acquisition of TE is common in obese patients.Furthermore,obese patients may have higher LSM results,even in the same stage of liver fibrosis.To better evaluate NAFLD a new XL probe,with a larger probe with lower ultrasound frequency and deeper penetration,increases the success rate of TE in obese patients.The median LSM value with the XL probe was found to be lower than that by the conventional M probe,hence cut-off values were approximately 1.2 to 1.3 kilopascals lower than those of the M probe,suggesting its adoption.Studies reveal that a novel ultrasonic controlled attenuation parameter is potentially useful to detect and quantify hepatic steatosis non-invasively.Conclusion:TE is a non-invasive,accurate and reproducible test of liver fibrosis and possibly hepatic steatosis and has been validated in a wide spectrum of liver diseases.TE is also useful to predict patient outcomes.

Non-invasive tests for the prediction of post-hepatectomy liver failure in the elderly

Post-hepatectomy liver failure(PHLF)is associated with great morbidity and mortality after resection of hepatocellular carcinoma.Previous studies have underlined that advanced age could be a potential factor influencing post-operative complications and long-term survival.In the past,candidates for resection were based on the Child-Pugh classification,the predictive value of which was rather low.The selection of patients undergoing resection in Western countries is based on the assessment of portal hypertension(PH),which is clinically assessed by measurement of the hepatic venous pressure gradient,an invasive and costly process.Thus,there have been several attempts to identify the best non-invasive test(NIT)to accurately predict PHLF.Most biochemical NITs for the prediction of PHLF are focused on evaluation of underlying liver cirrhosis and PH.Amongst them,FIB-4,which also includes the patient's age,seems to have more robust supporting results.In Europe and the USA.,the most tested and reliable NIT for predicting PHLF is the evaluation of liver stiffness measurement,which is also influenced by age.Imaging parameters are promising tools which are used only in specialized centers however,and when available.Liver volume parameters,as well as contrast-enhanced data,demonstrate good accuracy in predicting PHLF.In this scenario,the evaluation of sarcopenia and bone mineral density through contextual imaging allows the delineation of PHLF in at-risk elderly patients.Further studies focused on parameters for the evaluation of PHLF in elderly patients are needed.