Noninvasive assessment of liver fibrosis with combined serum aminotransferase/platelet ratio index and hyaluronic acid in patients with chronic hepatitis B

AIM： To construct a noninvasive assessment model consisting of routine laboratory data to predict significant fibrosis and cirrhosis in patients with chronic hepatitis B （CHB）. METHODS： A total of 137 consecutive patients with CriB who underwent percutaneous liver biopsy were retrospectively analyzed. These patients were divided into two groups according to their aminotransferase （ALT） level. The sensitivity, specificity, positive predictive value （PPV）, negative predictive value （NPV）, the likelihood ratio （LR） of aminotransferase/platelet ratio index （APRI） ≥ 1.5 or 〈 1.5 in combination with different hyaluronic acid （HA） cut-off points were calculated for the presence of moderate to severe fibrosis/cirrhosis （fibrosis stages 2 and 4） and no to mild fibrosis/cirrhosis （fibrosis stages 0 and 1）. RESULTS： The APRI correlated with fibrosis stage in CriB patients. The APRI ≥1.5 in combination with a cut-off HA cut-off point 〉 300 ng/mL could detect moderate to severe fibrosis （stages 2-4） in Crib patients. The PPV was 93.7%, the specificity was 98.9%. The APRI 〈 1.5 in combination with different HA cut-off points could not detect no to mild fibrosis in CHB patients. CONCLUSION： The APRI ≥ 1.5 in combination with a HA cut-off point 〉 300 ng/mL can detect moderate to severe fibrosis （stages 2-4） in Crib patients.

Combined acoustic radiation force impulse, aminotransferase to platelet ratio index and Forns index assessment for hepatic fibrosis grading in hepatitis B

AIM: To investigate the combined diagnostic accuracy of acoustic radiation force impulse(ARFI), aspartate aminotransferase to platelet ratio index(APRI) and Forns index for a non-invasive assessment of liver fibrosis in patients with chronic hepatitis B(CHB). METHODS: In this prospective study, 206 patients had CHB with liver fibrosis stages F0-F4 classified by METAVIR and 40 were healthy volunteers were measured by ARFI, APRI and Forns index separately or combined as indicated. RESULTS: ARFI, APRI or Forns index demonstrated a significant correlation with the histological stage(all P < 0.001). According to the AUROC of ARFI and APRI for evaluating fibrotic stages more than F2, ARFI showed an enhanced diagnostic accuracy than APRI(P < 0.05). The combined measurement of ARFI and APRI exhibited better accuracy than ARFI alone when evaluating ≥ F2 fibrotic stage(Z = 2.77, P = 0.006). Combination of ARFI, APRI and Forns index did not obviously improve the diagnostic accuracy compared to the combination of ARFI and APRI(Z = 0.958, P = 0.338). CONCLUSION: ARFI + APRI showed enhanced diagnostic accuracy than ARFI or APRI alone for significant liver fibrosis and ARFI + APRI + Forns index shows the same effect with ARFI + APRI.

Prediction of hepatocellular carcinoma development by aminotransferase to platelet ratio index in primary biliary cholangitis

AIM To investigate the usefulness of aspartate aminotransferase to platelet ratio index(APRI) in predicting hepatocellular carcinoma(HCC) risk in primary biliary cholangitis(PBC).METHODS We identified PBC patients between 2000 and 2015 by searching the electronic medical database of a tertiary center. The hazard ratio(HR) of HCC with different risk factors was determined by Cox proportional hazards model. RESULTS One hundred and forty-four PBC patients were recru-ited. Patients were diagnosed at a median age of 57.8 years [interquartile range(IQR): 48.7-71.5 years), and 41(28.5%) patients had cirrhosis at baseline. The median follow-up duration was 6.9 years(range: 1.0-26.3 years). Twelve patients developed HCC, with an incidence rate of 10.6 cases per 1000 patient-years. The overall 5-, 10-and 15-year cumulative incidences of HCC were 2.3% 95%CI: 0%-4.8%), 8.4%(95%CI: 1.8%-14.5%) and 21.6%(6.8%-34.1%), respectively. Older age(HR = 1.07), cirrhosis(HR = 4.38) and APRI at 1 year after treatment(APRI-r1) > 0.54(HR = 3.94) were independent factors for HCC development. APRI-r1, when combined with treatment response, further stratified HCC risk(log rank P < 0.05). The area under receiver operating curve of APRI-r1 in predicting HCC was 0.77(95%CI: 0.64-0.88).CONCLUSION APRI-r1 can be used to predict the development of HCC in PBC patients. Combination of APRI-r1 with treatment response can further stratify the HCC risk.

Association between community-acquired pneumonia and platelet indices: A case-control study

Objective:To examine whether the platelet index would be applicable for the diagnosis of community-acquired pneumonia(CAP).Methods:In this study,64 CAP patients(the case group)and 68 healthy children(the control group)were included from 2017 to 2018.Baseline variables were recorded including total white blood cells,neutrophils,lymphocytes,red blood cells,platelet,mean platelet volume,platelet distribution width,erythrocyte sedimentation rate,and C-reactive protein,and compared between the case group and the control group.The cutoff value,sensitivity,and specificity of neutrophil-to-lymphocyte ratio,platelet,neutrophils,lymphocytes,and platelet larger cell ratio were calculated by receiver-operating characteristic curves.Results:The median platelet count of the case group and the control group were(411.09±67.40)mm3 and(334.48±78.15)mm3,respectively(P=0.000).The median neutrophil count of the case group was higher than that of the control group,while the lymphocyte level of the case group was lower.Differences in other variables including the mean platelet volume,platelet distribution width,C-reactive protein,and erythrocyte sedimentation rate were not statistically significant between the two groups.Conclusions:Due to the different levels of platelet,neutrophil and lymphocyte indices in the case and the control group,these indices can be used simultaneously for the diagnosis of CAP.

Improvement of hepatic fibrosis after tenofovir disoproxil fumarate switching to tenofovir alafenamide for three years

BACKGROUND Both tenofovir alafenamide(TAF)and tenofovir disoproxil fumarate(TDF)are the first-line treatments for chronic hepatitis B(CHB).We have showed switching from TDF to TAF for 96 weeks resulted in further alanine aminotransferase(ALT)improvement,but data remain lacking on the long-term benefits of TDF switching to TAF on hepatic fibrosis.AIM To assess the benefits of TDF switching to TAF for 3 years on ALT,aspartate aminotransferase(AST),and hepatic fibrosis improvement in patients with CHB.METHODS A single center retrospective study on 53 patients with CHB who were initially treated with TDF,then switched to TAF to determine dynamic patterns of ALT,AST,AST to platelet ratio index(APRI),fibrosis-4(FIB-4)scores,and shear wave elastography(SWE)reading improvement at switching week 144,and the associated factors.RESULTS The mean age was 55(28-80);45.3%,males;15.1%,clinical cirrhosis;mean baseline ALT,24.8;AST,25.7 U/L;APRI,0.37;and FIB-4,1.66.After 144 weeks TDF switching to TAF,mean ALT and AST were reduced to 19.7 and 21,respectively.From baseline to switching week 144,the rates of ALT and AST<35(male)/25(female)and<30(male)/19(female)were persistently increased;hepatic fibrosis was also improved by APRI<0.5,from 79.2%to 96.2%;FIB-4<1.45,from 52.8%to 58.5%,respectively;mean APRI was reduced to 0.27;FIB-4,to 1.38;and mean SWE reading,from 7.05 to 6.30 kPa after a mean of 109 weeks switching.The renal function was stable and the frequency of patients with glomerular filtration rate>60 mL/min was increased from 86.5%at baseline to 88.2%at switching week 144.CONCLUSION Our data confirmed that switching from TDF to TAF for 3 years results in not only persistent ALT/AST improvement,but also hepatic fibrosis improvement by APRI,FIB-4 scores,as well as SWE reading,the important clinical benefits of long-term hepatitis B virus antiviral treatment with TAF.

Golgi protein-73:A biomarker for assessing cirrhosis and prognosis of liver disease patients

BACKGROUND Reliable biomarkers of cirrhosis,hepatocellular carcinoma(HCC),or progression of chronic liver diseases are missing.In this context,Golgi protein-73(GP73)also called Golgi phosphoprotein-2,was originally defined as a resident Golgi type II transmembrane protein expressed in epithelial cells.As a result,GP73 expression was found primarily in biliary epithelial cells,with only slight detection in hepatocytes.However,in patients with acute or chronic liver diseases and especially in HCC,the expression of GP73 is significantly up-regulated in hepatocytes.So far,few studies have assessed GP73 as a diagnostic or prognostic marker of liver fibrosis and disease progression.AIM To assess serum GP73 efficacy as a diagnostic marker of cirrhosis and/or HCC or as predictor of liver disease progression.METHODS GP73 serum levels were retrospectively determined by a novel GP73 ELISA(QUANTA Lite®GP73,Inova Diagnostics,Inc.,Research Use Only)in a large cohort of 632 consecutive patients with chronic viral and non-viral liver diseases collected from two tertiary Academic centers in Larissa,Greece(n=366)and Debrecen,Hungary(n=266).Aspartate aminotransferase(AST)/Platelets(PLT)ratio index(APRI)was also calculated at the relevant time points in all patients.Two hundred and three patients had chronic hepatitis B,183 chronic hepatitis C,198 alcoholic liver disease,28 autoimmune cholestatic liver diseases,15 autoimmune hepatitis,and 5 with other liver-related disorders.The duration of follow-up was 50(57)mo[median(interquartile range)].The development of cirrhosis,liver decompensation and/or HCC during follow-up were assessed according to internationally accepted guidelines.In particular,the surveillance for the development of HCC was performed regularly with ultrasound imaging and alpha-fetoprotein(AFP)determination every 6 mo in cirrhotic and every 12 mo in non-cirrhotic patients.RESULTS Increased serum levels of GP73(>20 units)were detected at initial evaluation in 277 out of 632 patients(43.8%).GP73-seropositivity correlated at baseline with the presence of cirrhosis(96.4%vs 51.5%,P<0.001),decompensation of cirrhosis(60.3%vs 35.5%,P<0.001),presence of HCC(18.4%vs 7.9%,P<0.001)and advanced HCC stage(52.9%vs 14.8%,P=0.002).GP73 had higher diagnostic accuracy for the presence of cirrhosis compared to APRI score[Area under the curve(AUC)(95%CI):0.909(0.885-0.934)vs 0.849(0.813-0.886),P=0.003].Combination of GP73 with APRI improved further the accuracy(AUC:0.925)compared to GP73(AUC:0.909,P=0.005)or APRI alone(AUC:0.849,P<0.001).GP73 levels were significantly higher in HCC patients compared to non-HCC[22.5(29.2)vs 16(20.3)units,P<0.001)and positively associated with BCLC stage[stage 0:13.9(10.8);stage A:17.1(16.8);stage B:19.6(22.3);stage C:32.2(30.8);stage D:45.3(86.6)units,P<0.001]and tumor dimensions[very early:13.9(10.8);intermediate:19.6(18.4);advanced:29.1(33.6)units,P=0.004].However,the discriminative ability for HCC diagnosis was relatively low[AUC(95%CI):0.623(0.570-0.675)].Kaplan-Meier analysis showed that the detection of GP73 in patients with compensated cirrhosis at baseline,was prognostic of higher rates of decompensation(P=0.036),HCC development(P=0.08),and liver-related deaths(P<0.001)during follow-up.CONCLUSION GP73 alone appears efficient for detecting cirrhosis and superior to APRI determination.In combination with APRI,its diagnostic performance can be further improved.Most importantly,the simple GP73 measurement proved promising for predicting a worse outcome of patients with both viral and nonviral chronic liver diseases.

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.

Noninvasive assessment of hepatic fibrosis in Egyptian patients with chronic hepatitis C virus infection

AIM: To evaluate the accuracy of specific biochemical markers for the assessment of hepatic fibrosis in patients with chronic hepatitis C virus (HCV) infection. METHODS: One hundred and fifty-four patients with chronic HCV infection were included in this study; 124 patients were non-cirrhotic, and 30 were cirrhotic. The following measurements were obtained in all patients: serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin, total bilirubin, prothrombin time and concentration, complete blood count, hepatitis B surface antigen (HBsAg), HCVAb, HCV-RNA by quantitative polymerase chain reaction, abdominal ultrasound and ultrasonic-guided liver biopsy. The following ratios, scores and indices were calculated and compared with the results of the histopathological examination: AST/ALT ratio (AAR), age platelet index (API), AST to platelet ratio index (APRI), cirrhosis discriminating score (CDS), Pohl score, G teborg University Cirrhosis Index (GUCI). RESULTS: AAR, APRI, API and GUCI demonstrated good diagnostic accuracy of liver cirrhosis (80.5%, 79.2%, 76.6% and 80.5%, respectively); P values were: < 0.01, < 0.05, < 0.001 and < 0.001, respectively. Among the studied parameters, AAR and GUCI gave the highest diagnostic accuracy (80.5%) with cutoff values of 1.2 and 1.5, respectively. APRI, API and GUCI were significantly correlated with the stage of fibrosis (P < 0.001) and the grade of activity (P < 0.001, < 0.001 and < 0.005, respectively), while CDS only correlated significantly with the stage of fibrosis (P < 0.001) and not with the degree of activity (P > 0.05). In addition, we found significant correlations for the AAR, APRI, API, GUCI and Pohl score between the non-cirrhotic (F0, F1, F2, F3) and cirrhotic (F4) groups (P values: < 0.001, < 0.05, < 0.001, < 0.001 and < 0.005, respectively; CDS did not demonstrate significant correlation (P > 0.05). CONCLUSION: The use of AAR, APRI, API, GUCI and Pohl score measurements may decrease the need for liver biopsies in diagnosing cirrhosis, especially in Egypt, where resources are limited.

Validation of conventional non-invasive fibrosis scoring systems in patients with metabolic associated fatty liver disease

BACKGROUND Non-invasive fibrosis scores are not yet validated in the newly defined metabolic associated fatty liver disease(MAFLD).AIM To evaluate the diagnostic performance of four non-invasive scores including aspartate aminotransferase to platelet ratio index(APRI),fibrosis-4 index(FIB-4),body mass index,aspartate aminotransferase/alanine aminotransferase ratio,diabetes score(BARD),and nonalcoholic fatty liver disease fibrosis score(NFS)in patients with MAFLD.METHODS Consecutive patients with histologically confirmed MAFLD were included.The discrimination ability of different non-invasive scores was compared.RESULTS A total of 417 patients were included;156(37.4%)of them had advanced fibrosis(Metavir≥F3).The area under receiver operating characteristic curve of FIB-4,NFS,APRI,and BARD for predicting advanced fibrosis was 0.736,0.724,0.671,and 0.609,respectively.The area under receiver operating characteristic curve of FIB-4 and NFS was similar(P=0.523),while the difference between FIB-4 and APRI(P=0.001)and FIB-4 and BARD(P<0.001)was statistically significant.The best thresholds of FIB-4,NFS,APRI,and BARD for diagnosis of advanced fibrosis in MAFLD were 1.05,-2.1,0.42,and 2.A subgroup analysis showed that FIB-4,APRI,and NFS performed worse in the pure MAFLD group than in the hepatitis B virus-MAFLD group.CONCLUSION APRI and BARD scores do not perform well in MAFLD.The FIB-4 and NFS could be more useful,but a new threshold is needed.Novel non-invasive scoring systems for fibrosis are required for MAFLD.

Transient elastography: A non-invasive tool for assessing liver fibrosis in HIV/HCV patients

AIM: To assess the prevalence of advanced liver fibrosis (ALF) in human immunodeficiency virus (HIV), hepatitis C virus (HCV) and HIV/HCV patients using transient elastography, and to identify factors associated with ALF. METHODS: Between September 2008 and October 2009, 71 HIV mono-infected, 57 HIV/HCV co-infected and 53 HCV mono-infected patients on regular follow-up at our Center were enrolled in this study. Alcohol intake, the main parameters of liver function, presence of HCV-RNA, HIV-RNA, duration of highly active anti-retroviraltherapy (HAART) and CD4 cell count were recorded. ALF was defined as liver stiffness (LS) ≥ 9.5 kPa. To estimate liver fibrosis (LF) a further 2 reliable biochemical scores, aspartate aminotransferase platelet ratio index (APRI) and FIB-4, were also used. RESULTS: LS values of co-infected patients were higher than in either HIV or HCV mono-infected patients (χ 2M H = 4, P < 0.04). In fact, LS ≥ 9.5 was significantly higher in co-infected than in HIV and HCV mono-infected pa-tients (χ 2 = 5, P < 0.03). Also APRI and the FIB-4 index showed more LF in co-infected than in HIV mono-infect-ed patients (P < 0.0001), but not in HCV mono-infected patients. In HIV?HCV co-infected patients, the extent of LS was significantly associated with alcohol intake (P < 0.04) and lower CD4+ cell count (P < 0.02). In HCV pa-tients, LS was correlated with alcohol intake (P < 0.001) and cholesterol levels (P < 0.03). Body mass index, dia-betes, HCV-and HIV-viremia were not significantly cor-related with LS. In addition, 20% of co-infected patients had virologically unsuccessful HAART; in 50% compliance was low, CD4+ levels were < 400 cells/mm 3 and LS was > 9.5 kPa. There was no significant correlation between extent of LF and HAART exposure or duration of HAART exposure, in particular with specific dideoxynucleoside analogues. CONCLUSION: ALF was more frequent in co-infected than mono-infected patients. This result correlated with lower CD4 levels. Protective immunological effects of HAART on LF progression outweigh its hepatotoxic effects.

APRI as a predictor of early viral response in chronic hepatitis C patients

AIM:To evaluate the aspartate aminotransferase(AST) to platelet ratio index(APRI) as a predictive factor of early viral response in chronic hepatitis C naive patients.METHODS:We performed an ambispective case-control study.We enrolled chronic hepatitis C naive patients who were evaluated to start therapy with PEGylated interferon α-2b(1.5 μg/kg per week) and ribavirin(>75 kg:1200mg and <75kg:1000mg).Patients were allocated into two groups,group 1:Hepatitis C patients with early viral response(EVR),group 2:Patients without EVR.Odds ratio(OR) and 95% confi dence interval(CI) were calculated to assess the relationship between each risk factor and the EVR in both groups.RESULTS:During the study,80 patients were analyzed,45 retrospectively and 35 prospectively.The mean ± SD age of our subjects was 42.9 ± 12 years;weight 70 kg(±11.19),AST 64.6 IU/mL(±48.74),alanine aminotransferase(ALT) 76.3 IU/mL(±63.08) and platelets 209000 mill/mm3(±84 429).Fifty-five(68.8%) were genotype 1 and 25(31.3%) were genotype 2 or 3;the mean hepatitis C virus RNA viral load was 2 269 061 IU/mL(±7220266).In the univariate analysis,APRI was not associated with EVR [OR 0.61(95% CI 0.229-1.655,P=0.33)],and the absence of EVR was only associated with genotype 1 [OR 0.28(95% CI 0.08-0.94,P=0.034)].After adjustment in a logistic regression model,genotype 1 remains signifi cant.CONCLUSION:APRI was not a predictor of EVR in chronic hepatitis C;Genotype 1 was the only predictive factor associated with the absence of EVR in our patients.

Non-invasive strategies to predict post-hepatectomy liver failure

The ability to predict outcome in patients with cirrhosis remains a challenge for clinicians,particularly when intervention or operative management is required.The outcomes may be unpredictable and for individual patients,there is an imperative to be able to counsel them appropriately.A range of predictive scores have been generated and modified in order to facilitate these aims.