Serum IP-10 increase correlated with PEG-IFNαresponse in nucleot(s)ide analogs-treated patients with chronic hepatitis B

Background and aims:To investigate the association between serum IP-10 and HBsAg levels in chronic hepatitis B(CHB)patients previously treated with nucleot(s)ide analogs(NAs)followed by combined treatment with an NA and pegylated interferon alpha(PEG-IFNα).Methods:Ninety-nine patients with serum levels of HBsAg<3000 IU/mL and HBV DNA<20 IU/mL who received prior NA treatment were enrolled.Participants were administered either NA monotherapy(NA group)or combination therapy with PEG-IFNα(Add-on group).Laboratory indicators and IP-10 levels were assessed in serial peripheral blood samples collected at 12-and 24-week intervals.The outcome of this study was a loss or>1 log10 IU/mL decline in serum HBsAg.Results:After 48 weeks of antiviral therapy,none of the 27 NA group patients and 15 of the 72 Add-on group patients achieved HBsAg loss.Baseline serum HBsAg and IP-10 levels were equivalent across both groups.The combination treatment led to a decrease in serum HBsAg levels and an early increase in IP-10 levels.Furthermore,a moderate increase in IP-10 levels at weeks 12 or 24 was correlated with loss and decline of HBsAg in the Add-on group.Receiver operating characteristic curve and regression analyses demonstrated that a moderate increase in serum IP-10 levels at weeks 12 or 24 was predictive of HBsAg loss and decline in the Add-on group(p<0.05).Conclusion:An early and moderate increase in the serum IP-10 level was correlated with responses to PEG-IFNαamong patients with CHB treated with NAs.

A New Prognostic Model Covering All Stages of Intrahepatic Cholangiocarcinoma

Background and Aims:Intrahepatic cholangiocarcinoma(ICC)is the second most common primary hepatic malignancy that causes a poor survival.We aimed to identify its prognostic factors and to develop a nomogram that will predict survival of ICC patients among all stages.Methods:A total of 442 patients with pathology-proven ICC registered at the Fifth Medical Center of PLA General Hospital between July 2007 and December 2019 were enrolled.Subjects were followed for survival status until June 30,2020.A prognostic model visualized as a nomogram was constructed in the training cohort using multivariate cox model,and was then validated in the validation cohort.Results:The median age was 55 years.With a median follow-up of 50.4 months,337 patients died.The median survival was 11.6 months,with 1-,3-and 5-year survival rates of 48.3%,22.7%and 16.2%,respectively.Factors associated with overall survival were multiple tumors,lymph node involvement,vascular invasion,distant metastasis,decreased albumin,elevated lactate dehydrogenase(LDH),decreased iron,elevated fi-brinogen,elevated CA125 and elevated CA19-9.A nomo-gram predicting survival of ICC patients at the time of di-agnosis achieved a Harrel’s c-statistic of 0.758,significantly higher than the 0.582 of the TNM stage alone.Predicted median survivals of those within the low,mid and high-risk subgroups were 35.6,12.1 and 6.2 months,respectively.Conclusions:A nomogram based on imaging data and serum biomarkers at diagnosis showed good ability to predict survival in patients with all stages of ICC.Further studies are needed to validate the prognostic capability of our new model.

Skewed CD39/CD73/adenosine pathway contributes to B-cell hyperactivation and disease progression in patients with chronic hepatitis B

Background:The mechanisms underlying B-cell hyperactivation in patients with chronic hepatitis B virus(HBV)infection remain largely undefined.The present study assessed the clinical characteristics of the CD39/CD73/adenosine pathway in patients with chronic hepatitis B(CHB).Methods:We examined CD39 and CD73 expression and adenosine production by B-cells from 202 HBV-infected patients.B-cell-activation phenotypes were assessed by flow cytometry after CpG+CD40 ligand stimulation with or without blockade and activation of the adenosine pathway.Results:CD39 and CD73 expression on circulating B-cells was decreased in CHB patients with high HBV DNA,HBeAg positivity,high HBsAg levels,and active liver inflammation,and was hierarchically restored in complete responders according to HBeAg seroconversion or HBsAg reduction.However,CD39 and CD73 expression on activated memory and tissue-like memory B-cell subsets in complete responders was not increased despite effective antiviral treatments.Furthermore,CD39 and CD73 expression on intra-hepatic B-cells was decreased in inflammatory livers.In vitro,B-cells from CHB patients showed a markedly reduced capacity to generate CD39/CD73-dependent extracellular adenosine and expressed increased levels of activation markers after adenosine-production blockade.Contrastingly,metformin significantly reduced activation-marker expression via regulating AMP-activated protein kinase.Conclusions:The skewed CD39 and CD73 expression on B-cells was associated with a high viral burden,liver inflammation,and antiviral efficacy in CHB patients,and the skewed CD39/CD73/adenosine pathway contributed to B-cell hyperactivation.Regulation of the CD39/CD73/adenosine pathway using metformin may represent a therapeutic option to reverse HBVinduced immune pathogenesis.

Hepatic sinusoidal obstruction syndrome due to tacrolimus in a liver-transplantation recipient

Introduction Hepatic sinusoidal obstruction syndrome(HSOS)is a hepatic vascular disease characterized by injury of the endothelial cells in the sinusoidal hepatic and interlobular veins,intra-hepatic congestion,liver dysfunction,and portal hypertension[1].In Western countries,HSOS is often associated with myeloablative regimens used for hematopoietic stem-cell transplantation,while,in China,it is often associated with oral intake of Gynura segetum plants that contain pyrrolidine alkaloids[2].In addition,new-onset HSOS after solid-organ transplantation has received increasing attention[3-8].