Evaluation of Non-Invasive Markers of Liver Fibrosis in Chronic Hepatitis B Patients in a Sub-Saharan African Setting: Transient Elastography versus APRI, FIB4, GTT/Platelet Scores

Background: Non-invasive markers which use routine laboratory tests are less expensive and highly needed to assess and stage liver fibrosis in chronic hepatitis B patients in Sub-Saharan Africa. We aimed at evaluating liver fibrosis, using the Aspartate aminotransferase to Platelet Ratio Index (APRI), Fibrosis Index Based on 4 factors (FIB4), and Gamma-glutamyl transpeptidase to Platelet Ratio (GPR) in chronic hepatitis B patients with transient elastography as the reference so as to choose an alternative to transient elastography. Method: We carried out a cross-sectional study using the records of patients who attended the Douala General Hospital and Marie O Polyclinic Douala from 2012 to 2017. Non-invasive tests were compared with Transient Elastography. The Spearman coefficient was used to determine correlation. The sensitivity, specificity, positive predictive values and negative predictive values were used to get the optimal cut-off values. The diagnostic accuracy was estimated by calculating the area under the Receiver Operating Characteristic Curve (ROC). P Results: Of the 243 patient records studied, the median age or interquartile range (IQR) was 35 (29 - 42) years with a male predominance of 73.7%. More than 60% of the study population had normal transaminases. Significant fibrosis was found in 88 (36.2%) patients and 32 (13.7%) patients had cirrhosis. APRI had the best cut-off values and highest area under the ROC Curve, for significant fibrosis and cirrhosis with 0.55 (0.823 95% CI [0.769 - 0.869], P Conclusion: APRI, had the best diagnostic properties to detect liver fibrosis and cirrhosis in patients with Chronic Hepatitis B in Douala. The cut-off values are 0.55 and 0.65 for significant fibrosis and cirrhosis respectively.

Staging of liver fibrosis in chronic hepatitis B patients with a composite predictive model:A comparative study

AIM:To evaluate the efficacy of 6 noninvasive liver fibrosis models and to identify the most valuable model for the prediction of liver fibrosis stage in chronic hepatitis B(CHB) patients.METHODS:Seventy-eight CHB patients were consecutively enrolled in this study.Liver biopsy was performed and blood serum was obtained at admission.Histological diagnosis was made according to the METAVIR system.Significant fibrosis was defined as stage score ≥ 2,severe fibrosis as stage score ≥ 3.The diagnostic accuracy of 6 noninvasive liver fibrosis models,including serum aspartate aminotransferase(AST) to platelet ratio index(APRI),FIB-4,Forn's index,Fibrometer,Hepascore,and Shanghai Liver Fibrosis Group's index(SLFG),was investigated.RESULTS:The APRI,FIB-4 and Forn's index under receiver operating characteristic curve(AUROC) for sig-nificant fibrosis were 0.71,0.75 and 0.79,respectively,with a diagnosis accuracy of 67%,77% and 80%,respectively,and 0.80,0.87 and 0.86,respectively,under the AUROC for severe fibrosis.The Hepascore,SLFG,and Fibrometer were 0.80,0.83 and 0.85,respectively under the AUROC for significant fibrosis(P < 0.01).The diagnosis accuracy of Hepascore and SLFG was 86% and 88%,respectively.The Hepascore,SLFG,and Fibrometer were 0.95,0.93,and 0.94,respectively,under the AUROC for severe fibrosis(P < 0.01).CONCLUSION:The models containing direct serum markers have a better diagnostic value than those not containing direct serum markers.

Non-invasive assessment of liver fibrosis in chronic hepatitis B

The goal of this review is to provide a comprehensive picture of the role,clinical applications and future perspectives of the most widely used non-invasive techniques for the evaluation of hepatitis B virus(HBV)infection.During the past decade many non-invasive methods have been developed to reduce the need for liver biopsy in staging fibrosis and to overcome whenever possible its limitations,mainly:invasiveness,costs,low reproducibility,poor acceptance by patients.Elastographic techniques conceived to assess liver stiffness,in particular transient elastography,and the most commonly used biological markers will be assessed against their respective role and limitations in staging hepatic fibrosis.Recent evidence highlights that both liver stiffness and some bio-chemical markers correlatewith survival and major clinical end-points such as liver decompensation,development of hepatocellular carcinoma and portal hypertension.Thus the non-invasive techniques here discussed can play a major role in the management of patients with chronic HBV-related hepatitis.Given their prognostic value,transient elastography and some bio-chemical markers can be used to better categorize patients with advanced fibrosis and cirrhosis and assign them to different classes of risk for clinically relevant outcomes.Very recent data indicates that the combined measurements of liver and spleen stiffness enable the reliable prediction of portal hypertension and esophageal varices development.

Sequential algorithms combining non-invasive markers and biopsy for the assessment of liver fibrosis in chronic hepatitis B

AIM： To assess the performance of several noninvasive markers and of our recently proposed stepwise combination algorithms to diagnose significant fibrosis （F ≥ 2 by METAVIR） and cirrhosis （F4 by METAVIR） in chronic hepatitis B （CHB）.METHODS： One hundred and ten consecutive patients （80 males, 30 females, mean age： 42.6 ± 11.3） with CHB undergoing diagnostic liver biopsy were included. AST-to-Platelet ratio （APRI）, Forns＇ index, AST-to-ALT Ratio, Goteborg University Cirrhosis Index （GUCD, Hui＇s model and Fibrotest were measured on the day of liver biopsy. The performance of these methods and of sequential algorithms combining Fibrotest, APRI and biopsy was defined by positive （PPV） and negative （NPV） predictive values, accuracy and area under the curve （AUC）. RESULTS： PPV for significant fibrosis was excellent （100%） with Forns and high （〉 92%） with APR1, GUCI, Fibrotest and Hui. However, significant fibrosis could not be excluded by any marker （NPV 〈 65%）. Fibretest had the best PPV and NPV for cirrhosis （87% and 90%, respectively）. Fibrotest showed the best AUC for both significant fibrosis and cirrhosis （0.85 and 0.76, respectively）. Stepwise combination algorithms of APR1, Fibrotest and biopsy showed excellent performance （0.96 AUC, 100% NPV） for significant fibrosis and 0.95 AUC, 98% NPV for cirrhosis, with 50%-80% reduced need for liver biopsy. CONCLUSION： In CHB sequential combination of APRI, Fibrotest and liver biopsy greatly improves the diagnostic performance of the single non-invasive markers. Need for liver biopsy is reduced by 50%-80% but cannot be completely avoided. Non-invasive markers and biopsy should be considered as agonists and not antagonists towards the common goal of estimating liver fibrosis.

Effects of entecavir on inflammatory reaction, liver function and liver fibrosis in chronic hepatitis b patients

Objective:To observe the effect of entecavir on inflammatory reaction, liver function and liver fibrosis in patients with chronic hepatitis B.Method:A total of 100 patients with chronic hepatitis B admitted in our hospital from February 2015 to October 2016 were randomly divided into observation group (50 cases) and control group (50 cases). The control group were given reduced glutathione and compound glycyrrhizin and other conventional liver protection;the observation group received entecavir dispersible tablets based on the treatment of the control group. The changes of inflammatory factors, liver function and liver fibrosis indexes of patients in both groups were compared.Results:Before treatment, the difference in inflammatory factors, liver function indexes and liver fibrosis indexes between the two groups was not significant. After treatment, the TGF-β1, hs-CRP and TNF-α levels in both groups were significantly lower than those before treatment, in the observation group, TGF-β1 (144.94±36.21) μg/L, hs-CRP level (48.81±10.74) ng/L and TNF-α level (82.43±22.29) pg/mL were significantly lower than those in the control group, there was significant difference between the two groups. After treatment, ALT, and AST levels in both groups were significantly lower than before treatment, compared with before treatment, TBiL level after treatment was not significant. After treatment, the ALT level (35.71±17.81) U/L and AST level (38.82±14.51) U/L in observation group were significantly lower than those in the control group, while the TBiL level in the observation group were not significantly different from that in the control group. After treatment, the levels of HA (91.71 ± 20.81) μg/mL and IV-C (140.82 ± 48.51) μg/L and LN (73.02 ± 21.06) μg/mL in the observation group were significantly lower than those in the control group.Conclusion:Entecavir combined with conventional drug therapy can effectively improve the inflammatory state of patients with chronic hepatitis B, enhance liver function and reduce liver fibrosis.

Transient elastography and diffusion-weighted magnetic resonance imaging for assessment of liver fibrosis in children with chronic hepatitis C

BACKGROUND Chronic hepatitis C(CHC)is a health burden with consequent morbidity and mortality.Liver biopsy is the gold standard for evaluating fibrosis and assessing disease severity and prognostic purposes post-treatment.Noninvasive altern-atives for liver biopsy such as transient elastography(TE)and diffusion-weighted magnetic resonance imaging(DW-MRI)are critical needs.AIM To evaluate TE and DW-MRI as noninvasive tools for predicting liver fibrosis in children with CHC.METHODS This prospective cross-sectional study initially recruited 100 children with CHC virus infection.Sixty-four children completed the full set of investigations including liver stiffness measurement(LSM)using TE and measurement of apparent diffusion coefficient(ADC)of the liver and spleen using DW-MRI.Liver biopsies were evaluated for fibrosis using Ishak scoring system.LSM and liver and spleen ADC were compared in different fibrosis stages and correlation analysis was performed with histopathological findings and other laboratory parameters.RESULTS Most patients had moderate fibrosis(73.5%)while 26.5%had mild fibrosis.None had severe fibrosis or cirrhosis.The majority(68.8%)had mild activity,while only 7.8%had moderate activity.Ishak scores had a significant direct correlation with LSM(P=0.008)and were negatively correlated with both liver and spleen ADC but with no statistical significance(P=0.086 and P=0.145,respectively).Similarly,histopatho-logical activity correlated significantly with LSM(P=0.002)but not with liver or spleen ADC(P=0.84 and 0.98 respectively).LSM and liver ADC were able to significantly discriminate F3 from lower fibrosis stages(area under the curve=0.700 and 0.747,respectively)with a better performance of liver ADC.CONCLUSION TE and liver ADC were helpful in predicting significant fibrosis in children with chronic hepatitis C virus infection with a better performance of liver ADC.

Liver stiffness in hepatocellular carcinoma and chronic hepatitis patients:Hepatitis B virus infection and transaminases should be considered

BACKGROUND Liver condition is a crucial prognostic factor for patients with hepatocellular carcinoma(HCC),but a convenient and comprehensive method to assess liver condition is lacking.Liver stiffness(LS)measured by two-dimensional shear wave elastography may help in assessing liver fibrosis and liver condition.Chronic hepatitis B(CHB)is an important risk factor for HCC progression,but LS was found to be less reliable in assessing liver fibrosis following hepatitis viral eradication.We hypothesize that the status of hepatitis virus infection would affect the accuracy of LS in assessing the liver condition.AIM To test the feasibility and impact factors of using LS to assess liver condition in patients with HCC and CHB.METHODS A total of 284 patients were retrospectively recruited and classified into two groups on the basis of serum CHB virus hepatitis B virus(HBV)-DNA levels[HBV-DNA≥100.00 IU/mL as Pos group(n=200)and<100.00 IU/mL as Neg group(n=84)].Correlation analyses and receiver operating characteristic analyses were conducted to evaluate the relationship between LS and liver condition.RESULTS A significant correlation was found between LS and most of the parameters considered to have the ability to evaluate liver condition(P<0.05).When alanine aminotransferase(ALT)concentrations were normal(≤40 U/L),LS was correlated with liver condition indices(P<0.05),but the optimal cutoff of LS to identify a Child-Pugh score of 5 was higher in the Neg group(9.30 kPa)than the Pos group(7.40 kPa).When ALT levels were elevated(>40 U/L),the correlations between LS and liver condition indices were not significant(P>0.05).CONCLUSION LS was significantly correlated with most liver condition indices in patients with CHB and HCC.However,these correlations varied according to differences in HBV-DNA and transaminase concentrations.

Liver histological changes in untreated chronic hepatitis B patients in indeterminate phase

BACKGROUND Studies with large size samples on the liver histological changes of indeterminate phase chronic hepatitis B(CHB)patients were not previously conducted.AIM To assess the liver histological changes in the indeterminate phase CHB patients using liver biopsy.METHODS The clinical and laboratory data of 1532 untreated CHB patients were collected,and all patients had least once liver biopsy from January 2015 to December 2021.The significant differences among different phases of CHB infection were compared with t-test,and the risk factors of significant liver histological changes were analyzed by the multivariate logistic regression analysis.RESULTS Among 1532 untreated CHB patients,814(53.13%)patients were in the indeterminate phase.Significant liver histological changes(defined as biopsy score≥G2 and/or≥S2)were found in 488/814(59.95%)CHB patients in the indete-rminate phase.Significant liver histological changes were significant differences among different age,platelets(PLTs),and alanine aminotransferase(ALT)subgroup in indeterminate patient.Multivariate logistic regression analysis indicated that age≥40 years old[adjust odd risk(aOR),1.44;95%confidence interval(CI):1.06-1.97;P=0.02],PLTs≤150×10^(9)/L(aOR,2.99;95%CI:1.85-4.83;P<0.0001),and ALT≥upper limits of normal(aOR,1.48;95%CI:1.08,2.05,P=0.0163)were independent risk factors for significant liver histological changes in CHB patients in the indeterminate phase.CONCLUSION Our results suggested that significant liver histological changes were not rare among the untreated CHB patients in indeterminate phase,and additional strategies are urgently required for the management of these patients.

Quantitative Assessment of Liver Fibrosis by Elastography in Patients with Chronic Liver Disease: A Cross-Sectional Study in Lomé (Togo)

Aim: To describe the two-dimensional elastographic profile according to the Shearwave (2D-SWE) technique in patients with chronic liver disease in Lom. Materials and method: Cross-sectional, descriptive study conducted over seven month at the Autel dElie Clinic in Lom, from January to August 2022, on adult patients with chronic liver disease who underwent abdominal ultrasound coupled with two-dimensional elastography. Results: The sample size was 54 patients. The mean age of the patients was 33 12 years, with extremes of 18 and 66 years. Patients aged 30 years or less accounted for 48.1% (n = 26). All patients (n = 54) had at least one transaminase assay with a mean of 69.3 78.3 IU/l (AST) and 59.3 82.8 IU/l (ALT). There was no statistically significant association between the biological parameters and the presence of fibrosis. Viral liver disease was the main cause, accounting for 81.5% (n = 44) of cases, with no significant association with the degree of fibrosis. Ultrasound revealed a dysmorphic liver (57.4%;n = 31) and portal hypertension (18.5%, n = 10). Fibrosis stages F1, F2 and F4 accounted for (48.1%, n = 26), (24.1%, n = 13) and (13%, n = 7) of cases respectively. Liver dysmorphia was significantly associated with the presence of fibrosis (p = 0.012) and portal hypertension was significantly associated with the degree of fibrosis (p = 0.0063). Conclusion: Assessment of liver fibrosis in patients with chronic liver disease using 2D-SWE elastography is essential for patient follow-up.

An-Luo-Hua-Xian Pill Improves the Regression of Liver Fibrosis in Chronic Hepatitis B Patients Treated with Entecavir

Background and Aims:Chronic hepatitis B(CHB)can cause liver fibrosis and lead to cirrhosis and cancer.As the effectiveness of antiviral therapy to reverse liver fibrosis is limited,We aimed to evaluate the effect of An-Luo-Hua-Xian pill(ALHX)on fibrosis regression in CHB patients treated with entecavir(ETV).Methods:Treatment-naïve patients with CHB were randomly treated with ETV alone or combined with ALHX(ETV+ALHX)between October 1,2013 and December 31,2020.Demographic,laboratory,and liver histology data before and after 78 weeks of treatment were collected.The Ishak fibrosis score(F)was used and fibrosis regression required a decrease in F of≥1 after treatment.Results:A total of 780 patients were enrolled,and 394 with a second liver biopsy after treatment were included in the per-protocol population,132 in ETV group and 262 in ETV+ALHX group.After 78 weeks of treatment,the fibrosis regression rate in the ETV+ALHX group was significantly higher than that of the ETV group at baseline F≥3 patients:124/211(58.8%)vs.45/98(45.9%),p=0.035.The percentage of patients with a decreased liver stiffness measurement(LSM)was higher in the ETV+ALHX group:156/211(73.9%)vs.62/98(63.%),p=0.056.Logistic regression analysis showed that ETV combined with ALHX was associated with fibrosis regression[odds ratio(OR)=1.94,p=0.018],and a family history of hepatocellular carcinoma was on the contrary.(OR=0.41,p=0.031).Conclusions:ETV combined with ALHX increased liver fibrosis regression in CHB patients.

Evaluation of the diagnostic efficacy of noninvasive diagnosis in patients with chronic viral hepatitis B complicated with nonalcoholic fatty liver disease and significant liver fibrosis

Objective:To evaluate the diagnostic efficacy of chronic viral hepatitis B(CHB)with significant liver fibrosis(S2)in patients with nonalcoholic fatty liver disease(NAFLD)by using noninvasive diagnosis and their combined models,and to explore their clinical features.Methods:A total of 104 inpatients with CHB diagnosed and complicated with NAFLD(hepatic steatosis suggested by liver biopsy)were retrospectively collected from January 2018 to January 2023 in the Affiliated Hospital of Traditional Chinese Medicine of Xinjiang Medical University.Liver biopsy was performed in all patients.General data,laboratory test results,liver hardness(LSM),FIB-4,APRI,GGT/PLT,AST/PLT and other results of patients were collected and grouped according to different fibrosis stages(S)to explore the clinical and pathological characteristics of patients with<S2 and S2 stages.Receiver operating characteristic curve was used to evaluate the diagnostic value of LSM,FIB-4,APRI,GGT/PLT,AST/PLT and their combined models in patients with significant liver fibrosis in CHB patients with NAFLD.Results:Among the 104 patients,there were 55 patients had S1 fibrosis,32 patients had S2 fibrosis,11 patients had S3 fibrosis and 6 patients had S4 fibrosis.Patients had<S2 fibrosis,ALT 33.75±17.15 U/L,AST 24.00(19.77,29.00)U/L,inflammation above G2 stage accounted for 92.72%,GGT/PLT 0.07(0.10,0.15),AST/PLT 0.09(0.10,0.15),LSM 8.70(6.80,10.10)kPa,FIB-41.07±0.51,APRI 0.26(0.22,0.28).In patients S2 fibrosis,ALT 42.14±21.39 U/L,AST 29.04(24.00,40.32)U/L,inflammation above G2 stage accounted for 97.95%,GGT/PLT 0.15(0.10,0.28),AST/PLT 0.14(0.10,0.26),GGT/PLT 0.15(0.10,0.28),AST/PLT 0.14(0.10,0.26).LSM 11.80(8.50,16.65)kPa,FIB-41.39±0.72,APRI 0.35(0.26,0.66),the difference between the two groups was statistically significant(P<0.05).The area under the receiver operator characteristic curves of the subjects of LSM,FIB-4,APRI,GGT/PLT and AST/PLT were 0.716,0.623,0.669,0.644 and 0.669(P<0.05),respectively.In the combined model,the area under the receiver operator characteristic curves of LSM combined with FIB-4,LSM combined with APRI,LSM combined with GGT/PLT and LSM combined with AST/PLT were 0.712,0.719,0.715 and 0.719,respectively(P<0.05).Conclusion:Although the currently commonly used Noninvasive diagnosis of liver fibrosis has certain diagnostic efficacy for significant liver fibrosis in CHB complicated with NAFLD,it cannot replace liver biopsy.Noninvasive Diagnosis can be used as an auxiliary method for regular clinical evaluation of liver biopsy.

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.

Effectiveness and safety of tenofovir amibufenamide in chronic hepatitis B patients

This letter to the editor relates to the study entitled“Tenofovir amibufenamide vs tenofovir alafenamide for treating chronic hepatitis B:A real-world study”,which was recently published by Peng et al.Hepatitis B virus infection represents a significant health burden worldwide and can lead to cirrhosis and even liver cancer.The antiviral drugs currently used to treat patients with chronic hepatitis B infection still have many side effects,so it is crucial to identify safe and effective drugs to inhibit viral replication.

Calcitriol attenuates liver fibrosis through hepatitis C virus nonstructural protein 3-transactivated protein 1-mediated TGF β1/Smad3 and NF-κB signaling pathways

BACKGROUND Hepatic fibrosis is a serious condition,and the development of hepatic fibrosis can lead to a series of complications.However,the pathogenesis of hepatic fibrosis remains unclear,and effective therapy options are still lacking.Our group identified hepatitis C virus nonstructural protein 3-transactivated protein 1(NS3TP1) by suppressive subtractive hybridization and bioinformatics analysis,but its role in diseases including hepatic fibrosis remains undefined.Therefore,additional studies on the function of NS3TP1 in hepatic fibrosis are urgently needed to provide new targets for treatment.AIM To elucidate the mechanism of NS3TP1 in hepatic fibrosis and the regulatory effects of calcitriol on NS3TP1.METHODS Twenty-four male C57BL/6 mice were randomized and separated into three groups,comprising the normal,fibrosis,and calcitriol treatment groups,and liver fibrosis was modeled by carbon tetrachloride(CCl4).To evaluate the level of hepatic fibrosis in every group,serological and pathological examinations of the liver were conducted.TGF-β1 was administered to boost the in vitro cultivation of LX-2 cells.NS3TP1,α-smooth muscle actin(α-SMA),collagen I,and collagen Ⅲ in every group were examined using a Western blot and real-time quantitative polymerase chain reaction.The activity of the transforming growth factor beta 1(TGFβ1)/Smad3 and NF-κB signaling pathways in each group of cells transfected with pcDNA-NS3TP1 or siRNA-NS3TP1 was detected.The statistical analysis of the data was performed using the Student’s t test.RESULTS NS3TP1 promoted the activation,proliferation,and differentiation of hepatic stellate cells(HSCs)and enhanced hepatic fibrosis via the TGFβ1/Smad3 and NF-κB signaling pathways,as evidenced by the presence of α-SMA,collagen I,collagen Ⅲ,p-smad3,and p-p65 in LX-2 cells,which were upregulated after NS3TP1 overexpression and downregulated after NS3TP1 interference.The proliferation of HSCs was lowered after NS3TP1 interference and elevated after NS3TP1 overexpression,as shown by the luciferase assay.NS3TP1 inhibited the apoptosis of HSCs.Moreover,both Smad3 and p65 could bind to NS3TP1,and p65 increased the promoter activity of NS3TP1,while NS3TP1 increased the promoter activity of TGFβ1 receptor I,as indicated by coimmunoprecipitation and luciferase assay results.Both in vivo and in vitro,treatment with calcitriol dramatically reduced the expression of NS3TP1.Calcitriol therapy-controlled HSCs activation,proliferation,and differentiation and substantially suppressed CCl4-induced hepatic fibrosis in mice.Furthermore,calcitriol modulated the activities of the above signaling pathways via downregulation of NS3TP1.CONCLUSION Our results suggest that calcitriol may be employed as an adjuvant therapy for hepatic fibrosis and that NS3TP1 is a unique,prospective therapeutic target in hepatic fibrosis.

Baseline metabolites could predict responders with hepatitis B virus-related liver fibrosis for entecavir or combined with FuzhengHuayu tablet

BACKGROUND After receiving entecavir or combined with FuzhengHuayu tablet(FZHY)treatment,some sufferers with hepatitis B virus(HBV)-related liver fibrosis could achieve a histological improvement while the others may fail to improve even worsen.Serum metabolomics at baseline in these patients who were effective in treatment remain unclear.AIM To explore baseline serum metabolites characteristics in responders.METHODS A total of 132 patients with HBV-related liver fibrosis and 18 volunteers as healthy controls were recruited.First,all subjects were divided into training set and validation set.Second,the included patients were subdivided into entecavir responders(E-R),entecavir no-responders(E-N),FZHY+entecavir responders(FR),and FZHY+entecavir no-responders(F-N)following the pathological histological changes after 48 wk’treatments.Then,Serum samples of all subjects before treatment were tested by high performance liquid chromatographytandem mass spectrometry(LC-MS)high-performance LC-MS.Data processing was conducted using multivariate principal component analysis and orthogonal partial least squares discriminant analysis.Diagnostic tests of selected differential metabolites were used for Boruta analyses and logistic regression.RESULTS As for the intersection about differential metabolic pathways between the groups E-R vs E-N and F-R vs F-N,results showed that 4 pathways including linoleic acid metabolism,aminoacyl-tRNA biosynthesis,cyanoamino acid metabolism,alanine,aspartate and glutamate metabolism were screened out.As for the differential metabolites,these 7 intersected metabolites including hydroxypropionic acid,tyrosine,citric acid,taurochenodeoxycholic acid,benzoic acid,2-Furoic acid,and propionic acid were selected.CONCLUSION Our findings showed that 4 metabolic pathways and 7 differential metabolites had potential usefulness in clinical prediction of the response of entecavir or combined with FZHY on HBV fibrotic liver.

Editorial:Metabolomics in chronic hepatitis C:Decoding fibrosis grading and underlying pathways

In the management of the growing population of hepatitis C virus-infected patients,a significant clinical challenge exists in determining the most effective methods for assessing liver impairment.The prognosis and treatment of chronic hepatitis C depend,in part,on the evaluation of histological activity,specifically cell necrosis and inflammation,and the extent of liver fibrosis.These parameters are traditionally obtained through a liver biopsy.However,liver biopsy presents both invasiveness and potential sampling errors,primarily due to inadequate biopsy size.To circumvent these issues,several non-invasive markers have been proposed as alternatives for diagnosing liver damage.Different imaging techniques and blood parameters as single markers or combined with clinical information are included.This Editorial discusses the identification of a set of six distinctive lipid metabolites in every fibrosis grade that appear to show a pronounced propensity to create clusters among patients who share the same fibrosis grade,thereby demonstrating enhanced efficacy in distinguishing between the different grades.

Baseline hepatocyte ballooning is a risk factor for adverse events in patients with chronic hepatitis B complicated with nonalcoholic fatty liver disease

BACKGROUND Although many studies have investigated the impact of chronic hepatitis B virus(HBV)infection and nonalcoholic fatty liver disease(NAFLD)on liver disease,few have investigated the relationship between nonalcoholic steatohepatitis(NASH)defined by liver pathology and the prognosis of chronic HBV infection.Most patients were followed up for a short time.This study aimed to further explore the impact of NAFLD and the pathological changes confirmed by liver pathology in patients with chronic HBV infection.AIM To study the effect of NAFLD confirmed using liver pathology on the outcomes of long-term serious adverse events[cirrhosis,hepatocellular carcinoma(HCC),and death]in patients with chronic hepatitis B(CHB)virus infection.METHODS We enrolled patients with chronic hepatitis B virus(HBV)infection who underwent liver biopsy at the Third People’s Hospital of Zhenjaing Affiliated Jiangsu University between January 2005 and September 2020.Baseline clinical and pathological data on liver pathology and clinical data at the end of follow-up were collected.Propensity score matching(PSM)was used to balance baseline parameters,Kaplan-Meier(K-M)survival analysis was used to evaluate the risk of clinical events,and Cox regression was used to analyze the risk factors of events.RESULTS Overall,456 patients with chronic HBV infection were included in the study,of whom 152(33.3%)had histologically confirmed NAFLD.The median follow-up time of the entire cohort was 70.5 mo.Thirty-four patients developed cirrhosis,which was diagnosed using ultrasound during the follow-up period.K-M survival analysis showed that NAFLD was not significantly associated with the risk of cirrhosis(log-rank test,P>0.05).Patients with CHB with fibrosis at baseline were more prone to cirrhosis(log-rank test,P=0.046).After PSM,multivariate analysis showed that diabetes mellitus,ballooning deformation(BD),and platelet(PLT)were independent risk factors for cirrhosis diagnosed using ultrasound(P<0.05).A total of 10 patients(2.2%)developed HCC,and six of these patients were in the combined NAFLD group.K-M survival analysis showed that the cumulative risk of HCC in the NAFLD group was significantly higher(log-rank test,P<0.05).Hepatocyte ballooning,and severe liver fibrosis were also associated with an increased risk of HCC(log-rank test,all P<0.05).Cox multivariate analysis revealed that hepatocyte ballooning,liver fibrosis,and diabetes mellitus were independent risk factors for HCC.CONCLUSION There was no significant correlation between chronic HBV infection and the risk of cirrhosis in patients with NAFLD.Diabetes mellitus,BD,and PLT were independent risk factors for liver cirrhosis.Patients with chronic HBV infection and NASH have an increased risk of HCC.BD,liver fibrosis,and diabetes mellitus are independent risk factors for HCC.

Noninvasive models for assessment of liver fibrosis in patients with chronic hepatitis B virus infection

There are approximately 240 million patients with chronic hepatitis B virus(HBV) infection worldwide. Up to 40% of HBV-infected patients can progress to liver cirrhosis, hepatocellular carcinoma or chronic end-stage liver disease during their lifetime. This, in turn, is responsible for around 650000 deaths annually worldwide. Repeated hepatitis flares may increase the progression of liver fibrosis, making the accurate diagnosis of the stage of liver fibrosis critical in order to make antiviral therapeutic decisions for HBV-infected patients. Liver biopsy remains the "gold standard" for diagnosing liver fibrosis. However, this technique has recently been challenged by the development of several novel noninvasive tests to evaluate liver fibrosis, including serum markers, combined models and imaging techniques. In addition, the cost and accessibility of imaging techniques have been suggested as additional limitations for invasive assessment of liver fibrosis in developing countries. Therefore, a noninvasive assessment model has been suggested to evaluate liver fibrosis, specifically in HBVinfected patients, owing to its high applicability, interlaboratory reproducibility, wide availability for repeated assays and reasonable cost. The current review aims to present the status of knowledge in this new and exciting field, and to highlight the key points in HBVinfected patients for clinicians.

Is the neutrophil to lymphocyte ratio associated with liver fibrosis in patients with chronic hepatitis B?

AIM: To determine the association between the neutrophil to lymphocyte(N/L) ratio and the degree of liver fibrosis in patients with chronic hepatitis B(CHB) infection. METHODS: Between December 2011 and February 2013, 129 consecutive CHB patients who were admitted to the study hospitals for histological evaluation of chronic hepatitis B-related liver fibrosis were included in this retrospective study. The patients were divided into two groups based on the fibrosis score: individuals with a fibrosis score of F0 or F1 were included in the "no/minimal liver fibrosis" group, whereas patients with a fibrosis score of F2, F3, or F4 were included in the "advanced liver fibrosis" group. The Statistical Package for Social Sciences 18.0 for Windows was used to analyze the data. A P value of < 0.05 was accepted as statistically significant.RESULTS: Three experienced and blinded pathologists evaluated the fibrotic status and inflammatory activity of 129 liver biopsy samples from the CHB patients. Following histopathological examination, the "no/minimal fibrosis" group included 79 individuals, while the "advanced fibrosis" group included 50 individuals. Mean(N/L) ratio levels were notably lower in patients with advanced fibrosis when compared with patients with no/minimal fibrosis. The mean value of the aspartate aminotransferase-platelet ratio index was markedly higher in cases with advanced fibrosis compared to those with no/minimal fibrosis.CONCLUSION: Reduced levels of the peripheral blood N/L ratio were found to give high sensitivity, specificity and predictive values in CHB patients with significant fibrosis. The prominent finding of our research suggests that the N/L ratio can be used as a novel noninvasive marker of fibrosis in patients with CHB.

Inflammation and fibrosis in chronic liver diseases including nonalcoholic fatty liver disease and hepatitis C

At present chronic liver disease(CLD),the third commonest cause of premature death in the United Kingdom is detected late,when interventions are ineffective,resulting in considerable morbidity and mortality.Injury to the liver,the largest solid organ in the body,leads to a cascade of inflammatory events.Chronic inflammation leads to the activation of hepatic stellate cells that undergo transdifferentiation to become myofibroblasts,the main extra-cellular matrix producing cells in the liver;over time increased extra-cellular matrix production results in the formation of liver fibrosis.Although fibrogenesis may be viewed as having evolved as a“wound healing”process that preserves tissue integrity,sustained chronic fibrosis can become pathogenic culminating in CLD,cirrhosis and its associated complications.As the reference standard for detecting liver fibrosis,liver biopsy,is invasive and has an associated morbidity,the diagnostic assessment of CLD by non-invasive testing is attractive.Accordingly,in this review the mechanisms by which liver inflammation and fibrosis develop in chronic liver diseases are explored to identify appropriate and meaningful diagnostic targets for clinical practice.Due to differing disease prevalence and treatment efficacy,disease specific diagnostic targets are required to optimally manage individual CLDs such as non-alcoholic fatty liver disease and chronic hepatitis C infection.To facilitate this,a review of the pathogenesis of both conditions is also conducted.Finally,the evidence for hepatic fibrosis regression and the mechanisms by which this occurs are discussed,including the current use of antifibrotic therapy.