Effect of alcohol consumption on liver stiffness measured by transient elastography

AIM:To determine the evolution of transient elastography(TE) in patients with alcoholic liver disease according to alcohol cessation or continuation.METHODS:We retrospectively selected in our local database all patients who had two TE between June 2005 and November 2010 with chronic alcohol excessive consumption and excluded those with associated cause of liver disease.TE was performed at least one week apart by senior operator.TE examinations with less than ten successful measures or with an interquartile range above 30% were excluded.We retrospectively reviewed file of all patients to include only patient followed up by trained addictologist and for which definite information on alcohol consumption was available.Concomitant biological parameters [aspartate amino transferase(AST),alanine amino transferase and gamma-glutamyl transpeptidase(GGT)] within 4 wk of initial and final TE were recorded.Putative fibrosis score according to initial and final TE were determined with available cut-off for alcoholic liver disease and hepatitis C.Initial and final putative fibrosis score were compared according to alcohol consumption during follow-up.RESULTS:During the study period 572 patients had TE examination for alcoholic liver disease and 79 of them had at least two examinations.Thirty-seven patients met our criteria with a median follow-up of 32.5 wk.At the end of the study,13(35%) were abstinent,and 24(65%) relapsers.Eight patients had liver biopsy during follow-up.TE decreased significantly during follow-up in 85% of abstinent patients [median(range):-4.9(-6.1,-1.9)],leading to a modification of the putative fibrosis stage in 28%-71% of patient according to different cut-off value.In relapsers TE increased in 45% and decreased in 54% of patient.There was no statistical difference between initial and final TE in relapsers.In the overall population,using 22.6 kPa as cut-off for cirrhosis,4 patients had cirrhosis at initial TE and 3 patients had cirrhosis at final TE.Using 19.5 kPa as cut-off for cirrhosis,7 patients had cirrhosis at initial TE and 5 patients had cirrhosis at final TE.Using 12.5 kPa as cut-off for cirrhosis,16 patients had cirrhosis at initial TE and 15 patients had cirrhosis at final TE.Evolution of biological data was in accordance with the relapse or abstinent status:abstinence ratio(duration of abstinence/duration follow-up) was correlated with AST ratio(r =-0.465,P = 0.007) and GGT ratio(r =-0.662,P<0.0001).GGT was correlated with initial(r = 0.488,P = 0.002) and final TE(r = 0.49,P<0.005).Final TE was correlated with AST(r = 0.362,P<0.05).Correlation between TE ratio and AST ratio(r = 0.44,P = 0.01) revealed that TE varied proportionally to AST for all patients irrespective of their alcohol status.The same relationship was observed between TE ratio and GGT ratio(r = 0.65,P<0.0001).Evolution of TE was significantly correlated with the ratio of time of abstinence to observation time(r =-0.387,P = 0.016) and the evolution of liver enzymes.CONCLUSION:TE significantly decreased with abstinence.Results of TE in alcoholic liver disease cannot be interpreted without taking into account alcohol consumption and liver enzymes.

Clinical application of liver stiffness measurement using transient elastography in chronic liver disease from longitudinal perspectives

Accurate determination of the presence and degree of fibrosis in liver is of great importance, because the prognosis and management strategies for chronic liver disease depend mainly on these factors. To date, liver biopsy (LB) remains the "gold standard" for assessing the severity of liver fibrosis; however, LB is often limited by its invasiveness, sampling error, and intra/ inter-observer variability in histological interpretation. Furthermore, repeated LB examinations within a short time interval are indeed ineligible in a real clinical practice. Thus, due to the pressing need for non-invasive surrogates for liver fibrosis, transient elastography (TE),as a novel ultrasound based technology, has allowed a noninvasive measurement of liver stiffness and has gained in popularity over recent years. In the past few years, additional roles for transient TE beyond the initial purpose of a non-invasive surrogate for LB have included the prediction of the most two critical consequences of fibrosis progression: the development of portal hypertension-related complications and hepatocellular carcinoma. This indicates that the role of transient TE is not merely limited to reducing the need for LB, but transient TE can enable the establishment of tailored management strategies by providing more detailed prognostic information. In particular, under the concept in which the clinical course of liver fibrosis is dynamic and bidirectional, especially when appropriate intervention is commenced, transient TE can be used to track the dynamic changes in fibrotic burden during antiviral or antifibrotic treatment. This review discussed extended applications of transient TE in prediction of the development of real clinical endpoints from a longitudinal perspective.

Increased osteopontin and liver stiffness measurement by transient elastography in biliary atresia

AIM: To analyze plasma osteopontin levels and liver stiffness using transient elastography in postoperative biliary atresia (BA) children compared with healthy controls. METHODS: Thirty children with postoperative BA and 10 normal controls were enrolled. The patients were categorized into two groups according to their jaundicestatus. Plasma levels of osteopontin were determined using commercially available enzyme-linked immunosorbent assay. Liver stiffness was measured by using transient elastography (Fibroscan). Ten validated Fibroscan measurements were performed in each patient and control with the result expressed in kilopascals (kPa). RESULTS: Plasma osteopontin was significantly elevated in BA children compared with that of healthy controls (47.0 ± 56.4 ng/mL vs 15.1 ± 15.0 ng/mL, P = 0.01). The liver stiffness measurement was markedly elevated in the patients with BA compared with that of controls (26.9 ± 24.6 kPa vs 3.9 ± 0.7 kPa, P = 0.001). Subgroup analysis showed that the BA patients with jaundice had more pronounced plasma osteopontin levels than those without jaundice (87.1 ± 61.6 ng/mL vs 11.9 ± 6.1 ng/mL, P = 0.001). Furthermore, the mean liver stiffness was significantly greater in the jaundiced BA patients compared with non-jaundiced patients (47.7 ± 21.8 kPa vs 8.7 ± 3.0 kPa, P = 0.001). Additionally, plasma osteopontin was positively related to serum total bilirubin (r = 0.64, P < 0.001). There was also a correlation between plasma osteopontin and liver stiffness values (r = 0.60, P < 0.001). CONCLUSION: High plasma osteopontin positively correlated with degree of hepatic fibrosis and could be used as a biochemical parameter reflecting disease severity in postoperative BA children.

Increased liver stiffness in alcoholic liver disease:Differentiating fibrosis from steatohepatitis

AIM:To test if inflammation also interferes with liver stiffness (LS) assessment in alcoholic liver disease (ALD) and to provide a clinical algorithm for reliable fibrosis assessment in ALD by FibroScan (FS).METHODS:We first performed sequential LS analysis before and after normalization of serum transaminases in a learning cohort of 50 patients with ALD admitted for alcohol detoxification. LS decreased in almost all patients within a mean observation interval of 5.3 d. Six patients (12%) would have been misdiagnosed with F3and F4 fibrosis but LS decreased below critical cut-off values of 8 and 12.5 kPa after normalization of trans-aminases. RESULTS:Of the serum transaminases,the decrease in LS correlated best with the decrease in glutamic oxaloacetic transaminase (GOT). No significant chang-es in LS were observed below GOT levels of 100 U/L. After establishing the association between LS and GOT levels,we applied the rule of GOT < 100 U/L for reliable LS assessment in a second validation cohort of 101 patients with histologically confi rmed ALD. By ex-cluding those patients with GOT > 100 U/L at the time of LS assessment from this cohort,the area under the receiver operating characteristic (AUROC) for cirrhosis detection by FS improved from 0.921 to 0.945 while specificity increased from 80% to 90% at a sensitivity of 96%. A similar AUROC could be obtained for lower F3 fibrosis stage if LS measurements were restricted to patients with GOT < 50 U/L. Histological grading of inflammation did not further improve the diagnostic accuracy of LS.CONCLUSION:Coexisting steatohepatitis markedly increases LS in patients with ALD independent of fibrosis stage. Postponing cirrhosis assessment by FS during alcohol withdrawal until GOT decreases to < 100 U/mL signif icantly improves the diagnostic accuracy.

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.

Comparison of the liver stiffness measurement by transient elastography with the liver biopsy

AIM: To compare the liver stiffness (LS) measurement by transient elastography (TE) to the liver biopsy (LB)-considered the "gold standard" in the evaluation of patients with chronic hepatitis C. METHODS: During a period of 12 mo, we evaluated 199 consecutive patients with chronic hepatitis due to hepatitis C virus (HCV), in which LB and LS assessments (by means of TE) were performed during the same session. RESULTS: Out of 199 patients, a valid measurement of the LS could not be obtained in 8. The mean value of LS in the cohort of 191 valid measurements was 8.45 ± 4.96 kPa, ranging from 2.3 to 38 kPa. The mean value of LS in patients with signifi cant fi brosis at biopsy (161 patients with F ≥ 2 according to Metavir) was 9.02 ± 5.15 kPa, significantly higher than in patients with no or mild fi brosis (30 patients with F < 2 Metavir): 5.39 ± 1.81 kPa (P < 0.0001). For a cut- off value of 6.8 kPa, the LS had a PPV of 98%, a NPV of 30.1%, a sensitivity of 59.6% and a specificity of 93.3% for the presence of signifi cant fi brosis (at least F2 Metavir), with a diagnostic performance of 77.3% (AUROC 0.773). Using this cut-off value, we reached the best discrimination between absence of fibrosis/ mild fibrosis (F < 2 Metavir) and the presence ofmoderate to severe fi brosis (F ≥ 2 Metavir). CONCLUSION: In patients with chronic hepatitis due to HCV, a cut-off value of 6.8 kPa measured by TE can differentiate between significant fibrosis and absent or mild fi brosis, with a PPV of 98%, a NPV of 30.1%, a sensitivity of 59.6%, a specificity of 93.3%, and a diagnostic performance of 77.3%.

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.

Transient elastography improves detection of liver cirrhosis compared to routine screening tests

AIM:To investigate the diagnostic significance oftransient elastography(TE) in a daily routine clinical setting in comparison to clinical signs,laboratory parameters and ultrasound.METHODS:TE,ultrasound,laboratory parameters and cutaneous liver signs were assessed in 291 consecutive patients with chronic liver disease of various aetiologies who underwent liver biopsy in daily routine.RESULTS:Sensitivity of TE for the detection of liver cirrhosis was 90.4%,compared to 80.1% for ultrasound,58.0% for platelet count and 45.1% for cutaneous liver signs(P < 0.0001 for comparisons with histology).AUROC for TE was 0.760(95%CI:0.694-0.825).Combination of TE with ultrasound increased sensitivity to 96.1% and AUROC to 0.825(95%CI:0.768-0.882).TE correlated with laboratory parameters of cirrhosis progression like albumin(r =-0.43),prothrombin time(r =-0.44),and bilirubin(r = 0.34; P < 0.001 for each).Particularly,in patients with Child Pugh score A or normal platelet count TE improved sensitivity for the detection of liver cirrhosis compared to ultrasound by 14.1%(P < 0.04) and 16.3%(P < 0.02),respectively.CONCLUSION:Transient elastography is superior to routine diagnostic tests allowing detection of liver cirrhosis in additional 10%-16% of patients with chronic liver disease that would have been missed by clinical examinations.

Normal liver stiffness: a study in living donors with normal liver histology

AIM: To define the normal range of liver stiffness(LS) values using transient elastography in living-related liver transplantation candidate donors with normal liver histology. METHODS: LS was measured using Fibroscan in 50(16 women, 34 men) healthy potential donors(mean age 28.4 ± 5.9 years) who were being evaluated for liver donation for their relatives at the National Liver Institute, Menoufeya University, Egypt. All potential donors had normal liver tests and were negative for hepatitis B or C virus infection. Abdominal ultrasounds showed normal findings. None of the subjects had diabetes, hypertension, renal impairment, heart disease, or body mass index > 30 kg/m2. All subjects had normal liver histology upon liver biopsy. They all donated the right lobe of their liver with successful outcomes.RESULTS: The mean LS was 4.3 ± 1.2 k Pa(range: 1.8-7.1 k Pa). The 5th and 95 th percentiles of normal LS were 2.6 k Pa and 6.8 k Pa, respectively, with a median of 4 k Pa; the interquartile range was 0.6 ± 0.4. LS measurements were not significantly different between men and women(4.4 ± 1.1 k Pa vs 3.9 ± 1.3 k Pa) and did not correlate with age. However, stiffness values were significantly lower in subjects with a body mass index < 26 kg/m2 compared to those with an index ≥ 26 kg/m2(4.0 ± 1.1 k Pa vs 4.6 ± 1.2 k Pa; P <0.05). There were no differences in hospital stay or postoperative bilirubin, albumin,alanine and aspartate transaminases, or creatinine levels(at discharge) between donors with livers stiffness ≤ 4 k Pa and those with stiffness > 4 k Pa. CONCLUSION: Healthy donors with normal liver histology have a median LS of 4 k Pa. Stiffness values are elevated relative to increase in body mass index.

Does pressure cause liver cirrhosis? The sinusoidal pressure hypothesis

Independent of their etiology, all chronic liver diseases ultimately lead to liver cirrhosis, which is a majorhealth problem worldwide. The underlying molecular mechanisms are still poorly understood and no efficient treatment strategies are available. This paper introduces the sinusoidal pressure hypothesis(SPH), which identifies an elevated sinusoidal pressure(SP) as cause of fibrosis. SPH has been mainly derived from recent studies on liver stiffness. So far, pressure changes have been exclusively seen as a consequ-ence of cirrhosis. According to the SPH, however, an elevated SP is the major upstream event that initiates fibrosis via biomechanic signaling by stretching of perisinusoidal cells such as hepatic stellate cells or fibroblasts(SPH part?Ⅰ: initiation). Fibrosis progression is determined by the degree and time of elevated SP. The SPH predicts that the degree of extracellular matrix eventually matches SP with critical thresholds > 12 mmH g and > 4 wk. Elevated arterial flow and final arterialization of the cirrhotic liver represents the self-perpetuating key event exposing the low-pressure-organ to pathologically high pressures(SPH part?Ⅱ: perpetuation). It also defines the "point of no return" where fibrosis progression becomes irreversible. The SPH is able to explain the macroscopic changes of cirrhotic livers and the uniform fibrotic response to various etiologies. It also opens up new views on the role of fat and disease mechanisms in other organs. The novel concept will hopefully stimulate the search for new treatment strategies.

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.

Longitudinal assessment of liver stiffness by transient elastography for chronic hepatitis C patients

BACKGROUND Liver fibrosis is a common pathway of liver injury and is a feature of most chronic liver diseases.Fibrosis progression varies markedly in patients with hepatitis C virus(HCV).Liver stiffness has been recommended as a parameter of fibrosis progression/regression in patients with HCV.AIM To investigate changes in liver stiffness measured by transient elastography(TE)in a large,racially diverse cohort of United States patients with chronic hepatitis C(CHC).METHODS We evaluated the differences in liver stiffness between patients treated with direct-acting antiviral(DAA)therapy and untreated patients.Patients had≥2 TE measurements and no prior DAA exposure.We used linear regression to measure the change in liver stiffness between first and last TE in response to treatment,controlling for age,sex,race,diabetes,smoking status,human immunodeficiency virus status,baseline alanine aminotransferase,and baseline liver stiffness.Separate regression models analyzed the change in liver stiffness as measured by kPa,stratified by cirrhosis status.RESULTS Of 813 patients,419(52%)initiated DAA treatment.Baseline liver stiffness was 12 kPa in 127(16%).Median time between first and last TE was 11.7 and 12.7 mo among treated and untreated patients,respectively.There was no significant change in liver stiffness observed over time in either the group initiating DAA treatment(0.016 kPa/month;CI:-0.051,0.084)or in the untreated group(0.001 kPa/mo;CI:-0.090,0.092),controlling for covariates.A higher baseline kPa score was independently associated with decreased liver stiffness.CONCLUSION DAA treatment was not associated with a differential change in liver stiffness over time in patients with CHC compared to untreated 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.

CEUS and Fibroscan in non-alcoholic fatty liver disease and non-alcoholic steatohepatitis

AIM: To determine intra-hepatic blood flow and liver stiffness in patients with non-alcoholic fatty liver disease(NAFLD) and non-alcoholic steatohepatitis (NASH) using contrast-enhanced ultrasound and fibroscan.METHODS: This prospective study included 15 patients with NAFLD, 17 patients with NASH and 16 healthy controls.In each patient, real-time ultrasound was used to locate the portal vein (PV) and the right liver lobe, and 5 mL of SonoVue? was then injected intravenous in a peripheral vein of the left arm over a 4-s span. Digital recording was performed for 3 min thereafter. The recording was subsequently retrieved to identify an area of interest in the PV area and in the right liver parenchyma(LP) to assess the blood flow by processing the data using dedicated software (Qontrast?, Bracco, Italy).The following parameters were evaluated: percentage of maximal contrast activity (Peak%), time to peak (TTP, s), regional blood volume (RBV, cm3), regional blood flow (RBF, cm3/s) and mean transit time (MTT, s).At 24-48 h post-injection, liver stiffness was evaluated using Fibroscan and measured in kPa. The statistical evaluation was performed using Student’s t test.RESULTS: In the PV, the Peak%, RBV and RBF were significantly reduced in the NAFLD and NASH patientscompared with the controls (Peak%: NAFLD 26.3 ± 6.6,NASH 28.1 ± 7.3 vs controls 55.8 ± 9.9, P < 0.001;RBV: NAFLD 4202.3 ± 3519.7, NASH 3929.8 ± 1941.3vs controls 7473 ± 3281, P < 0.01; RBF: NAFLD 32.5± 10.8, NASH 32.7 ± 12.1 vs controls 73.1 ± 13.9, P< 0.001). The TTP in the PV was longer in both patient groups but reached statistical significance only in the NASH patients compared with the controls (NASH 79.5± 37.8 vs controls 43.2 ± 30, P < 0.01). In the LP,the Peak%, RBV and RBF were significantly reduced in the NAFLD and NASH patients compared with the controls (Peak%: NAFLD 43.2 ± 7.3, NASH 41.7 ± 7.7 vs controls 56.6 ± 6.3, P < 0.001; RBV: NAFLD 4851.5± 2009, NASH 5069.4 ± 2292.5 vs controls 6922.9 ±2461.5, P < 0.05; RBF: NAFLD 55.7 ± 10.1, NASH 54.5 ± 12.1 vs controls 75.9 ± 10.5, P < 0.001). The TTP was longer in both patient groups but did not reach statistical significance. The MTT in both the PV and LP in the NAFLD and NASH patients was not different from that in the controls. Liver stiffness was significantly increased relative to the controls only in the NASH patients(NASH: 6.4 ± 2.2 vs controls 4.6 ± 1.5, P < 0.05).CONCLUSION: Blood flow derangement within the liver present not only in NASH but also in NAFLD suggests that a vascular flow alteration precedes liver fibrosis development.

Diagnostic accuracy of transient elastography (Fibro Scan) in detection of esophageal varices in patients with cirrhosis: A meta-analysis

AIM To investigate the diagnostic accuracy of Fibro Scan(FS) in detecting esophageal varices(EV) in cirrhotic patients.METHODS Through a systemic literature search of multiple databases, we reviewed 15 studies using endoscopy as a reference standard, with the data necessary to calculate pooled sensitivity(SEN) and specificity(SPE), positive and negative LR, diagnostic odds ratio(DOR) and area under receiver operating characteristics(AUROC). The quality of the studies was rated by the Quality Assessment of Diagnostic Accuracy studies-2 tool. Clinical utility of FS for EV was evaluated by a Fagan plot. Heterogeneity was explored using meta-regression and subgroup analysis. All statistical analyses were conducted via Stata12.0, MetaD isc1.4 and RevM an5.RESULTS In 15 studies(n = 2697), FS detected the presence of EV with the summary sensitivities of 84%(95%CI: 81.0%-86.0%), specificities of 62%(95%CI: 58.0%-66.0%), a positive LR of 2.3(95%CI: 1.81-2.94), a negative LR of 0.26(95%CI: 0.19-0.35), a DOR of 9.33(95%CI: 5.84-14.92) and an AUROC of 0.8262. FS diagnosed the presence of large EV with the pooled SEN of 0.78(95%CI: 75.0%-81.0%), SPE of 0.76(95%CI: 73.0%-78.0%), a positive and negative LR of 3.03(95%CI: 2.38-3.86) and 0.30(95%CI: 0.23-0.39) respectively, a summary diagnostic OR of 10.69(95%CI: 6.81-16.78), and an AUROC of 0.8321. A meta-regression and subgroup analysis indicated different etiology could serve as a potential source of heterogeneity in the diagnosis of the presence of EV group. A Deek's funnel plot suggested a low probability for publication bias.CONCLUSION Using FS to measure liver stiffness cannot provide high accuracy for the size of EV due to the various cutoff and different etiologies. These limitations preclude widespread use in clinical practice at this time; therefore, the results should be interpreted cautiously given its SEN and SPE.

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.

Non-invasive diagnosis of hepatitis B virus-related cirrhosis

Chronic hepatitis B(CHB)infection is a major public health problem associated with significant morbidity and mortality worldwide.Twenty-three percent of patients with CHB progress naturally to liver cirrhosis,which was earlier thought to be irreversible.However,it is now known that cirrhosis can in fact be reversed by treatment with oral anti-nucleotide drugs.Thus,early and accurate diagnosis of cirrhosis is important to allow an appropriate treatment strategy to be chosen and to predict the prognosis of patients with CHB.Liver biopsy is the reference standard for assessment of liver fibrosis.However,the method is invasive,and is associated with pain and complications that can be fatal.In addition,intra-and inter-observer variability compromises the accuracy of liver biopsy data.Only small tissue samples are obtained and fibrosis is heterogeneous in such samples.This confounds the two types of observer variability mentioned above.Such limitations have encouraged development of non-invasive methods for assessment of fibrosis.These include measurements of serum biomarkers of fibrosis;and assessment of liver stiffness via transient elastography,acoustic radiation force impulse imaging,real-time elastography,or magnetic resonance elastography.Although significant advances have been made,most work to date has addressed the diagnostic utility of these techniques in the context of cirrhosis caused by chronic hepatitis C infection.In the present review,we examine the advantages afforded by use of non-invasive methods to diagnose cirrhosis in patients with CHB infections and the utility of such methods in clinical practice.

Correlation between Fibroscan and laboratory tests in non-alcoholic fatty liver disease/non-alcoholic steatohepatitis patients for assessing liver fibrosis

BACKGROUND Non-alcoholic fatty liver disease(NAFLD) is a spectrum of disease ranging from simple steatosis to non-alcoholic steatohepatitis(NASH), through to advanced fibrosis and cirrhosis. Many patients with NAFLD remain undiagnosed and recognizing those at risk is very crucial. Although liver biopsy is the gold standard method for diagnosing and staging NAFLD, non-invasive imaging and lab modalities are also very promising in diagnosing these diseases.AIM To explore some of these non-invasive modalities in this context and assess how they hold up in terms of making a diagnosis while avoiding an invasive procedure like a liver biopsy.METHODS This study was conducted on NAFLD/NASH patients(n = 73) who underwent Fibroscan examinations at Saint George Hospital University Medical Center over 17 mo in order to assess liver fibrosis. Obtained Fibroscan results were correlated to laboratory tests and calculated aspartate transaminase(AST)/alanine transaminase(ALT) ratio, AST platelet ratio index(APRI) score and Fibrosis-4 score.RESULTS A significant age difference was observed across fibrosis stages of investigated patients. The mean stiffness score was 9.48 ± 11.77 KPa. A significant negative correlation was observed between ALT, AST, Albumin, gamma-glutamyl transferase, cholesterol, LDL, HDL, triglycerides, and ALP when compared across fibrosis stages. On the other hand, a significant positive correlation was found between Bilirubin, PT INR, partial thromboplastin time, glucose, and Platelet count when compared across fibrosis stages, in addition to AST/ALT ratio, APRI, and Fib-4 scores.CONCLUSION This study showed that Ultrasound alone is not efficient in the assessment of advancement of liver disease. Furthermore, the high positive relation between AST/ALT ratio, APRI and Fib-4 scores with fibrosis stages in NAFLD patients suggests that they could be used clinically in combination with Fibroscan to predict significant fibrosis and cirrhosis and to avoid liver biopsy.

Predicting liver function after hemihepatectomy in patients with hepatocellular carcinoma using different modalities

In response to Dr.Yue et al's study on prognostic factors for post-hemihep-atectomy outcomes in hepatocellular carcinoma(HCC)patients,this critical review identifies methodological limitations and proposes enhancements for future research.While the study identifies liver stiffness measure and standard residual liver volume as potential predictors,concerns regarding small sample size,reliance on biochemical markers for safety assessment,and inadequate ad-justment for confounding variables are raised.Recommendations for rigorous methodology,including robust statistical analysis,consideration of confounding factors,and selection of outcome measures with clinical components,are proposed to strengthen prognostic assessments.Furthermore,validation of novel evaluation models is crucial for enhancing clinical applicability and advancing understanding of postoperative outcomes in patients with HCC undergoing hem-ihepatectomy.

肝组织炎症对FibroScan诊断慢性乙型肝炎患者肝纤维化的影响

目的探讨肝组织学炎症对瞬时弹性扫描仪(FS)诊断慢性乙型肝炎患者肝纤维化的影响。方法应用FS对124名慢性乙型肝炎患者进行肝穿刺前肝脏弹性测量值(LSM)的测定,采用肝穿刺活组织病理诊断技术进行肝纤维化分期(S)和炎症分级(G)。对同一肝纤维化分期不同肝组织炎症分级组间LSM进行比较,并对各肝纤维化分期中LSM与肝组织炎症分级进行相关性分析。结果肝组织纤维化逐渐发展伴随肝炎症程度加重,如肝纤维化S1期患者中以G1为主(81.8%),S2期以G2为主(54.2%),S3期以G3为主(47.4%),S4期以G3、G4为主(40%,33.4%),S1～S4每一纤维化分期水平上,不同炎症分级LSM差异均具有统计学意义(P<0.05),且LSM与不同炎症分级之间均呈显著正相关(P<0.01)。结论肝组织炎症程度是影响FS诊断的一个重要因素,炎症活动程度加重可使LSM增加。