Controlled attenuation parameter for non-invasive assessment of hepatic steatosis in Chinese patients

AIM: To evaluate the performance of a novel non-invasive controlled attenuation parameter (CAP) to assess liver steatosis.

High value of controlled attenuation parameter predicts a poor antiviral response in patients with chronic hepatits B

BACKGROUND: Controlled attenuation parameter (CAP) is a non-invasive method for diagnosing hepatic steatosis based on vibration-controlled transient elastography. The objective of this study was to investigate the effect of high value of CAP on antiviral therapy in patients with chronic hepatitis B (CHB). METHODS: Patients with CHB receiving enticavir for initial antiviral therapy were studied; they were divided into the high CAP group and normal CAP group at baseline according to the CAP values. The effect of the antiviral therapy between the two groups were compared at week 12, 24 and 48. Patients with high CAP value at baseline were divided into three subgroups, mild, moderate and severe elevation; the therapeutic response were compared among patients with normal CAP and subgroups of patients with elevated CAP. RESULTS: A total of 153 patients were enrolled. Among them, 63 were in the high CAP group and 90 in the normal CAP group. Patients with high CAP had lower rates of ALT normalization and HBV DNA clearance in response to antiviral therapy compared with those with normal CAP at week 12, 24 and 48. Further analysis showed that the rate of ALT normalization in patients with mildly and moderately elevated CAP were significant lower than those with normal CAP at week 12 and 24; while the difference was not significant between the patients with normal CAP and those with severely elevated CAP. The rate of HBV DNA clearance was significantly lower in patients with severely elevated CAP compared with those with normal CAP at week 12, 24 and 48. CONCLUSION: CHB patients with high CAP had poor response to antiviral therapy.

Controlled attenuation parameter for evaluating liver steatosis in chronic viral hepatitis

AIM: To assess the performance of controlled attenuation parameter (CAP) in patients with chronic viral hepatitis.

Diagnostic value of controlled attenuation parameter for liver steatosis in patients with chronic hepatitis B

AIM: To study the diagnostic value of controlled attenuation parameter (CAP), evaluated by transient elastography, for liver steatosis in patients with chronic hepatitis B (CHB).

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.

Prospective study comparing hepatic steatosis assessment by magnetic resonance imaging and four ultrasound methods in 105 successive patients

BACKGROUND Non-alcoholic fatty liver disease(NAFLD)is becoming a major health problem,resulting in hepatic,metabolic and cardio-vascular morbidity.AIM To evaluate new ultrasonographic tools to detect and measure hepatic steatosis.METHODS We prospectively included 105 patients referred to our liver unit for NAFLD suspicion or follow-up.They underwent ultrasonographic measurement of liver sound speed estimation(SSE)and attenuation coefficient(AC)using Aixplorer MACH 30(Supersonic Imagine,France),continuous controlled attenuation parameter(cCAP)using Fibroscan(Echosens,France)and standard liver ultrasound with hepato-renal index(HRI)calculation.Hepatic steatosis was then classified according to magnetic resonance imaging proton density fat fraction(PDFF).Receiver operating curve(ROC)analysis was performed to evaluate the diagnostic performance in the diagnosis of steatosis.RESULTS Most patients were overweight or obese(90%)and had metabolic syndrome(70%).One third suffered from diabetes.Steatosis was identified in 85 patients(81%)according to PDFF.Twenty-one patients(20%)had advanced liver disease.SSE,AC,cCAP and HRI correlated with PDFF,with respective Spearman correlation coefficient of-0.39,0.42,0.54 and 0.59(P<0.01).Area under the receiver operating characteristic curve(AUROC)for detection of steatosis with HRI was 0.91(0.83-0.99),with the best cut-off value being 1.3(Se=83%,Sp=98%).The optimal cCAP threshold of 275 dB/m,corresponding to the recent EASL-suggested threshold,had a sensitivity of 72%and a specificity of 80%.Corresponding AUROC was 0.79(0.66-0.92).The diagnostic accuracy of cCAP was more reliable when standard deviation was<15 dB/m with an AUC of 0.91(0.83-0.98).An AC threshold of 0.42 dB/cm/MHz had an AUROC was 0.82(0.70-0.93).SSE performed moderately with an AUROC of 0.73(0.62-0.84).CONCLUSION Among all ultrasonographic tools evaluated in this study,including new-generation tools such as cCAP and SSE,HRI had the best performance.It is also the simplest and most available method as most ultrasound scans are equipped with this module.

Prevalence and predictors of nonalcoholic fatty liver disease in South Asian women with polycystic ovary syndrome

BACKGROUND Polycystic ovary disease(PCOS)may be a risk factor for nonalcoholic fatty liver disease(NAFLD)due to common pathogenetic pathways,including insulin resistance and obesity.Both PCOS and NAFLD are more severe in South Asian women.Data on NAFLD in South Asian women with PCOS are lacking.AIM To investigate prevalence and predictors of NAFLD and liver fibrosis in PCOS patients from South Asia.METHODS We conducted an observational routine screening program by means of transient elastography(TE)with associated controlled attenuation parameter(CAP).NAFLD was defined as CAP≥288 decibels per meter.Significant liver fibrosis(stage 2 and higher out of 4)was defined as TE measurement≥8.0 kilopascals.Elevated alanine aminotransferase(ALT)was defined as ALT>24 IU/L,as per upper limit of normal reported in South Asian women.Biochemical hyperandrogenism was defined as free androgen index>5.Predictors of NAFLD were determined by logistic regression analysis.RESULTS 101 PCOS patients(mean age 36.3 years)with no significant alcohol intake or viral hepatitis were included.Prevalence of NAFLD and significant liver fibrosis was 39.6% and 6.9%,respectively.Elevated ALT was observed in 40%and 11.5%of patients with and without NAFLD,respectively.After adjusting for duration of PCOS and insulin resistance measured by homeostasis model for assessment of insulin resistance,independent predictors of NAFLD were higher body mass index[adjusted odds ratio(aOR)1.30,95% confidence interval(CI):1.13-1.52],hyperandrogenism(aOR:5.32,95%CI:1.56-18.17)and elevated ALT(aOR:3.54,95%CI:1.10-11.47).Lifetime cardiovascular risk was higher in patients with NAFLD compared to those without NAFLD(0.31±0.11 vs 0.26±0.13).CONCLUSION Despite their young age,NAFLD diagnosed by TE with CAP is a frequent comorbidity in South Asian women with PCOS and is strongly associated with higher body mass index and hyperandrogenism.Non-invasive screening strategies could help early diagnosis and initiation of interventions,including counselling on weight loss,cardiovascular risk stratification and linkage to hepatology care where appropriate.

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

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

Non-alcoholic steatohepatitis in liver transplant recipients diagnosed by serum cytokeratin 18 and transient elastography:A prospective study

BACKGROUND Nonalcoholic fatty liver disease(NAFLD)and nonalcoholic steatohepatitis(NASH)seem common after liver transplantation.AIM To investigate incidence and predictors of NAFLD and NASH by employing noninvasive testing in liver transplant recipients,namely controlled attenuation parameter(CAP)and the serum biomarker cytokeratin 18(CK-18).We also evaluated the diagnostic accuracy of CK-18 and CAP compared to liver histology.METHODS We prospectively recruited consecutive adult patients who received liver transplant at the McGill University Health Centre between 2015-2018.Serial measurements of CK-18 and CAP were recorded.NAFLD and NASH were diagnosed by CAP≥270 dB/m,and a combination of CAP≥270 dB/m with CK-18>130.5 U/L,respectively.Incidences and predictors of NAFLD and NASH were investigated using survival analysis and Cox proportional hazards.RESULTS Overall,40 liver transplant recipients(mean age 57 years;70%males)were included.During a median follow-up of 16.8 mo(interquartile range 15.6-18.0),63.0%and 48.5%of patients developed NAFLD and NASH,respectively.On multivariable analysis,after adjusting for sex and alanine aminotransferase,body mass index was an independent predictor of development of NAFLD[adjusted hazard ratio(aHR):1.21,95%confidence interval(CI):1.04-1.41;P=0.01]and NASH(aHR:1.26,95%CI:1.06-1.49;P<0.01).Compared to liver histology,CAP had a 76%accuracy to diagnose NAFLD,while the accuracy of CAP plus CK-18 to diagnose NASH was 82%.CONCLUSION NAFLD and NASH diagnosed non-invasively are frequent in liver transplant recipients within the first 18 mo.Close follow-up and nutritional counselling should be planned in overweight patients.

Effect of Helicobacter pylori-eradication therapy on hepatic steatosis in patients with non-alcoholic fatty liver disease:a randomized–controlled pilot study

Background:Helicobacter pylori infection has been associated with insulin resistance and non-alcoholic fatty liver disease(NAFLD).This study was done to evaluate the effect of H.pylori-eradication therapy(HPET)in patients with NAFLD compared to standard management therapy(SMT).Methods:Eighty NAFLD patients with H.pylori co-infection were randomized into SMT(diet and exercise,n=36)and HPET(SMT plus amoxicillin,clarithromycin,and pantoprazole,n=44)groups.The controlled attenuation parameter(CAP),anthropometric parameters,liver enzymes,lipid profile,and glycemic parameters including homeostasis model assessment-insulin resistance(HOMA-IR)were measured and compared between two groups at the baseline and 24 weeks.Results:Sixty-four participants(SMT group[n=28]and HPET group[n=36])were included in amodified intention-to-treat analysis.Both the SMT group and the HPET group had a significant reduction in CAP scores at 24weeks(P=0.002 and P<0.001,respectively),but the change between the groups was insignificant(P=0.213).Successful eradication of H.pylori occurred in 68%of the HPET group and led to greater improvement in HOMA-IR at 24weeks compared to SMT or non-responder patients(P=0.007).The liver enzymes reduced significantly at 24weeks in both groups,but the changes between the groups were similar.The lipid parameters remained unchanged within the groups and between the groups at 24weeks.A significant increase in the levels of reduced glutathione was noted in the HPET group,but the change between the two groups was not statistically different.Conclusions:HPET was found to be comparable to SMT alone in reducing hepatic steatosis and liver enzymes at 24 weeks in NAFLD patients.However,successful eradication of H.pylori led to greater improvement in HOMA-IR(Trial registration CTRI/2017/05/008608).

Variable optical attenuators with ability to independently control two orthogonal linearly polarized light amplitudes

New techniques for controlling the amplitudes of two orthogonal linearly polarized light are presented. One is based on adjusting the DC voltage into a Mach–Zehnder modulator（MZM） to alter the amplitude of the light traveling on the slow axis of a fiber into the modulator with little changes in the fast-axis light amplitude.Another is based on adjusting the input DC voltages of a dual-polarization MZM operating in the reverse direction, which enables independent control of the two input orthogonal linearly polarized light amplitudes.Experimental results demonstrate that more than 30 dB difference in slow-and fast-axis light power can be obtained by controlling an MZM input DC voltage, and over 24 dB independent power adjustment for light traveling on the slow and fast axes into a dual-polarization MZM.

Temperature Insensitive Open Loop Attenuation Control of a Liquid Crystal Based VOA

A patent pending open-loop liquid crystal based variable optical attenuator is introduced. The temperature dependent performance is compensated through electric monitoring and adjustment utilizing liquid crystal's opto-electronic properties.

Advances in diagnostic ultrasound techniques for assessing liver steatosis in nonalcoholic fatty liver disease

The incidence of nonalcoholic fatty liver disease(NAFLD),a common chronic liver disease,is increasing yearly.With increasing degrees of liver steatosis,NAFLD can progress to varying degrees of hepatic fibrosis,cirrhosis,and even hepatocellular carcinoma(HCC),with a concomitant increase in the risk of metabolic syndrome and cardiovascular disease.Therefore,early diagnosis and accurate assessment of NAFLD are particularly significant.Although liver biopsy is regarded as the standard for evaluating the degree of hepatic steatosis in NAFLD,it is not frequently utilized due to its invasiveness.Ultrasound technology as a noninvasive diagnostic method has the advantages of operating simplicity and economy.It can effectively diagnose and assess the disease of NAFLD.This article mainly summarizes the current status and progress of research on the assessment of NAFLD and liver steatosis by two main types of ultrasound techniques,semi-quantitative and quantitative ultrasound,as well as other emerging techniques,and briefly describes the strengths and limitations of B-mode ultrasound,controlled attenuation parameters(CAP),and attenuation imaging(ATI)in this field.

Association between NAFLD and Risk of Colorectal Adenoma in Chinese Han Population

Background and Aims:Colorectal cancer is associated with non-alcoholic fatty liver disease(NAFLD)and other metabolic syndromes,such as obesity,abnormal blood glucose,and dyslipidemia.The relationship of NAFLD and colorectal adenoma,which is the precursor of colorectal cancer,is worthy of discussion.The aim of this study was to investigate the association between colorectal adenoma and NAFLD,colorectal adenoma and metabolic syndrome in a Chinese Han population.Methods:This retrospective study analyzed the relationship between NAFLD and colorectal adenoma in 1089 patients in Qingdao municipal hospital.Subjects were divided into a colorectal adenoma group(n=267)and a control group(n=822).NAFLD and the controlled attenuation parameter(CAP)value were determined by abdominal ultrasound and FibroScan.Results:Patients with NAFLD in the colorectal adenoma group and the control group represented 142 cases(53.2%)and 360 cases(43.8%),respectively.The mean CAP value in the colorectal adenoma group was significantly higher than that in the control group.The values of body mass index,triglyceride,high-density lipoprotein cholesterol,aspartate aminotransferase,fasting plasma glucose,and uric acid were also significantly higher in the colorectal adenoma group than in the control group.Multifactor logistic regression analysis showed that the sex,NAFLD,CAP,body mass index,triglyceride,aspartate aminotransferase,and fasting plasma glucose were significant risk factors for colorectal adenoma.Besides,NAFLD and CAP value were significant risk factors for colorectal adenoma in males but not in females.Conclusions:NAFLD and metabolic syndrome were tightly associated with the risk of colorectal adenoma in this Chinese Han population.The effect of NAFLD on colorectal adenoma was prominent in males rather than in females.

Discrepancies between Nonalcoholic and Metabolic-associated Fatty Liver Disease by Multiple Steatosis Assessment

Background and Aims:The redefinition of metabolic-as-sociated fatty liver disease(MAFLD)from nonalcoholic fat-ty liver disease(NAFLD)has caused a revolution in clinical practice,and the characteristics of patients with steatosis but not MAFLD remain unclear.The aims were to compare the diagnosis rate of MAFLD in NAFLD using different steato-sis methods and explore the features of non-MAFLD-NAFLD and MAFLD-non-NAFLD.Methods:A cross-sectional study enrolling consecutive individuals was conducted at three medical centers in southern China from January 2015 to September 2020.Steatosis was evaluated by liver biopsy or magnetic resonance imaging-based proton density fat frac-tion(MRI-PDFF),ultrasound,controlled attenuation param-eter(CAP),and fatty liver index(FLI).Fibrosis was assessed by the NAFLD fibrosis score,transient elastography,or shear wave elastography.Results:The study enrolled 14,985 Chi-nese adults.The agreement of MAFLD and NAFLD diagnoses were 83%for FLI,95%for ultrasound,94%for both CAP and MRI-PDFF,and 95%for liver biopsy.The body mass index,blood pressure and lipid levels among non-MAFLD-NAFLD pa-tients were similar metabolic parameters(p>0.05 for all),but not the alanine aminotransferase and the proportion of pa-tients with insulin resistance,which were significantly higher in non-MAFLD-NAFLD with significant fibrosis.Conclusions:The new MAFLD definition ruled out 5-17%of NAFLD cases.NAFLD and MAFLD-NAFLD involved more severe metabolic abnormalities than MAFLD and MAFLD-non-NAFLD.Non-MAFLD-NAFLD patients with significant fibrosis had more se-vere liver injury and increased glycemic dysregulation within the normal range.Attention should be paid to its progression.

Accuracy of non-invasive liver stiffness measurement and steatosis quantification in patients with severe and morbid obesity

Background:Vibration controlled transient elastography(VCTE)and controlled attenuation parameter(CAP™)have shown reliable performance predicting fibrosis and steatosis in normal-to overweight patients but have not been validated in severe to morbid obesity.This study aimed at determining the accuracy of VCTE,CAP™and the composite score FibroScan-AST(FAST)in patients with a body mass index(BMI)of≥35 kg/m^(2).Methods:Patients scheduled for bariatric-metabolic surgery underwent preoperative VCTE/CAP™measurement,and intraoperative liver biopsy.The feasibility and accuracy of VCTE,CAP™and the composite score FAST were retrospectively analysed to evaluate fibrosis,steatosis and active fibrotic non-alcoholic steatohepatitis[NASH+non-alcoholic fatty liver disease(NAFLD)activity score≥4+fibrosis grade≥2]using per protocol(PP)and intent to diagnose(ITD)calculation.Results:In total,170 patients(median BMI 44.4 kg/m²)were included in the study.Liver biopsy showed NASH,simple steatosis,and normal livers in 60.6%(n=103),28.8%(n=49),and 10.6%(n=18),respectively.VCTE and CAP™delivered reliable results in 90.6%(n=154/170)and 90.5%(n=134/148).The AUC(PP)of VCTE,CAP™,and FAST were 0.687(≥F2),0.786(≥F3),0.703(≥S2),0.738(S3),and 0.780(active fibrotic NASH).The AUC increased to 0.742(≥F2),0.842(≥F3),0.712(≥S2),0.780(S3),and 0.836(active fibrotic NASH)in patients below the median BMI of 44.4 kg/m².Conclusions:VCTE,CAP™and FAST show acceptable accuracy for the detection of fibrosis,steatosis and NASH in a real-life cohort of patients with obesity.Accuracy improves in patients with a BMI<44.4 kg/m^(2).