Safety and immunogenicity of COVID-19 vaccination among liver transplant recipients in China

To the Editor:During the ongoing coronavirus disease 2019(COVID-19)pan-demic globally,patients with chronic liver diseases(CLD),par-ticularly cirrhosis,hepatobiliary malignancies,candidates for liver transplantation(LT),and immunosuppressed LT recipients appear to be at increased risk of infections,which leads to an increase in mortality[1-6].Apart from physical distancing,quarantine and isolation,vaccination is crucial for the restraining of the epidemic and the protection from severe acute respiratory syndrome coron-avirus 2(SARS-CoV-2)infection and aggravation of COVID-19[7,8].A recent prospective,multicenter,open-label study in China has demonstrated the safety of inactivated whole-virion SARS-CoV-2 vaccines in patients with CLD.

Endoscopic Ruler for varix size measurement:A multicenter pilot study

BACKGROUND We invented Endoscopic Ruler,a new endoscopic device to measure the size of varices in patients with cirrhosis and portal hypertension.AIM To assess the feasibility and safety of Endoscopic Ruler,and evaluate the agreement on identifying large oesophageal varices(OV)between Endoscopic Ruler and the endoscopists,as well as the interobserver agreement on diagnosing large OV using Endoscopic Ruler.METHODS We prospectively and consecutively enrolled patients with cirrhosis from 11 hospitals,all of whom got esophagogastroduodenoscopy(EGD)with Endoscopic Ruler.The primary study outcome was a successful measurement of the size of varices using Endoscopic Ruler.The secondary outcomes included adverse events,operation time,the agreement of identifying large OV between the objective measurement of Endoscopic Ruler and the empirical reading of endoscopists,together with the interobserver agreement on diagnosing large OV by Endoscopic Ruler.RESULTS From November 2020 to April 2022,a total of 120 eligible patients with cirrhosis were recruited and all of them underwent EGD examinations with Endoscopic Ruler successfully without any adverse event.The median operation time of Endoscopic Ruler was 3.00 min[interquartile range(IQR):3.00 min].The kappa value between Endoscopic Ruler and the endoscopists while detecting large OV was 0.52,demonstrating a moderate agreement.The kappa value for diagnosing large OV using Endoscopic Ruler among the six independent observers was 0.77,demonstrating a substantial agreement.CONCLUSION The data demonstrates that Endoscopic Ruler is feasible and safe for measuring the size of varices in patients with cirrhosis and portal hypertension.Endoscopic Ruler is potential to promote the clinical practice of the two-grade classification system of OV.

Noncontrast-enhanced MRI-based Noninvasive Score for Portal Hypertension(CHESS1802):An International Multicenter Study

Background and Aims:This study aimed to determine the performance of the non-invasive score using noncontrastenhanced MRI(CHESS-DIS score)for detecting portal hy-pertension in cirrhosis.Methods:In this international multicenter,diagnostic study(ClinicalTrials.gov,NCT03766880),patients with cirrhosis who had hepatic venous pressure gradient(HVPG)measurement and noncontrast-enhanced MRI were prospectively recruited from four university hospitals in China(n=4)and Turkey(n=1)between December 2018 and April 2019.A cohort of patients was retrospectively recruited from a university hospital in Italy between March 2015 and November 2017.After segmentation of the liver on fat-suppressed T1-weighted MRI maps,CHESS-DIS score was calculated automatically by an in-house developed code based on the quantification of liver surface nodularity.Results:A total of 149 patients were included,of which 124 were from four Chinese hospitals(training cohort)and 25 were from two international hospitals(validation cohort).A positive correlation between CHESS-DIS score and HVPG was found with the correlation coefficients of 0.36(p<0.0001)and 0.55(p<0.01)for the training and validation cohorts,respectively.The area under the receiver operating characteristic curve of CHESS-DIS score in detection of clinically significant portal hypertension(CSPH)was 0.81 and 0.9 in the training and validation cohorts,respectively.The intra-class correlation coefficients for assessing the inter-and intra-observer agreement were 0.846 and 0.841,respectively.Conclusions:A non-invasive score using noncontrast-enhanced MRI was developed and proved to be significantly correlated with invasive HVPG.Besides,this score could be used to detect CSPH in patients with cirrhosis.

Portal hypertension in nonalcoholic fatty liver disease: Challenges and perspectives

Nonalcoholic fatty liver disease(NAFLD)has become the most common chronic liver disease worldwide.NAFLD‐related cirrhosis is often complicated by portal hypertension(PHT).Recent evidence showed that portal venous pressure(PVP)starts to rise in the early stages of NAFLD,even in absence of advanced fibrosis or cirrhosis.However,the precise pathological mechanisms of this process are still poorly understood.Lipid accumulation,hepatocellular ballooning,sinusoidal endothelial cell dysfunction,capillarization,microthrombosis,increased angiogenesis,and pericellular fibrosis may all be involved in the early development of increased PVP in NAFLD.Direct measurement of PHT is invasive and impractical in noncirrhotic NAFLD individuals and may also underestimate its severity.Thus,the development and validation of noninvasive and more accurate measurements,including new serum biomarkers,scoring models,and imaging techniques(such as ultrasonography,elastography,and magnetic resonance imaging),are urgently needed.Owing to the increasing morbidity,challenges in the prevention and management of PHT in NAFLD are unprecedented.This review article aims to briefly discuss these challenges and summarizes the mechanisms,diagnosis,and emerging therapies for PHT in people with NAFLD.

Meta-analysis of the immunogenicity of standard and booster SARS-CoV-2 vaccination in patients with chronic liver disease and post-liver transplantation

Aims:Patients with liver disease may exhibit higher infection rates and mortality rates from coronavirus disease 2019(COVID-19)than healthy individuals,and vaccination against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is an effective prevention strategy.This metaanalysis aimed to assess the effectiveness and safety of SARS-CoV-2 vaccines in patients with chronic liver disease(CLD)and post-liver transplantation(LT).Methods:The PubMed,Embase,and Cochrane databases were searched.A random-effects model meta-analysis was used to determine the seropositivity rates of SARS-CoV-2 antibodies,odds ratio(OR)compared with healthy controls(HC),risk ratio(RR)between the booster and standard vaccination regimen,and the rate of adverse reactions(ADR).Results:In the standard vaccination regimen analysis,17 controlled articles were included for effectiveness analysis,and six articles for ADR analysis.The pooled seropositivity rates of SARS-CoV-2 antibodies in patients with CLD and post-LT were 93.3%(95%confidence interval[CI]:89.0%-97.6%)and 69.1%(95%CI:63.0%-75.3%),respectively.Both rates were lower than those in HC(p<0.001).The differences remained significant after sorting by detection interval,vaccine type,antibody type,or CLD type.LT recipients showed much lower seropositivity rates of antibodies than patients with CLD(69.1%vs.93.3%)or HC(OR:0.055).The pooled total ADR rate of patients was 24.0%(95%CI:16.2%-31.8%).In the booster vaccination regimen analysis,11 prospective studies were enrolled,and the seropositivity rates of antibodies after the booster dose were increased by 27%compared with those of the standard vaccination regimen(RR:1.27,95%CI:1.15-1.41,p<0.001).Conclusion:Patients with CLD and post-LT can gain protection against COVID-19 from standard vaccines,demonstrating a potentially weaker immunogenic response than HC.Booster vaccines can compensate for this deficiency.Therefore,patients with CLD and post-LT should be prioritized for receiving the COVID-19 booster vaccine.

Tolerance and acceptance of hepatic venous pressure gradient measurement in cirrhosis(CHESS1904):An international multicenter study

Aim:To determine the tolerance and acceptance of hepatic venous pressure gradient(HVPG)measurements in patients with liver cirrhosis.Methods:This prospective international multicenter study included 271 patients with cirrhosis who were scheduled to undergo HVPG measurement between October 2019 and June 2020.Data related to the tolerance and acceptance of HVPG measurements were collected using descriptive questionnaires.Results:HVPG measurements were technically successful in all 271 patients,with 141(52.0%)undergoing HVPG measurement alone.The complication rate was 0.4%.Postoperative pain was significantly lower than preoperative expected pain(p<0.001)and intraoperative pain(p<0.001),and intraoperative pain was also significantly lower than preoperative expected pain(p=0.036).No,mild,moderate,severe,and intolerable discomfort scores were reported by 36.9%,44.6%,11.1%,6.3%,and 0.4%of these patients,respectively,during HVPG measurement and by 54.6%32.5%,11.4%,1.5%,and 0%,respectively,after HVPG measurement.Of these patients,39.5%had little understanding and 10%had no understanding of the value of HVPG measurement,with 35.1%and 4.1%regarding HVPG measurements as being of little or no help,respectively.Most patients reported that they would definitely(15.5%),probably(46.9%),or possibly(29.9%)choose to undergo additional HVPG measurements again,and 62.7%regarded the cost of the procedure as acceptable.Conclusion:HVPG measurement was safe and well‐tolerated in patients with cirrhosis,but patient education and communication are warranted to improve the acceptance of this procedure.

Transforming one organ into another to overcome challenges in tissue engineering

Tissue engineering(TE)is promising for the regeneration of failed organs.However,immune rejection,shortage of seed cells,and unintegrated blood vessels restrict the development and clinical application of TE.The last factor is the most challenging and intractable.Harnessing the mature blood vessel network in existing dispensable organs could be a powerful approach to effectively overcome the obstacles.After being remodeled to harbor an immunosuppressive and proregenerative niche,these potential target organs can be transformed into other organs with specific physiological functions,compensating the latter's failed native functions.Organ transformation,such as a hepatized spleen,represents an effective and encouraging TE strategy.In this review,we discuss the current development and obstacles of TE and its feasibility and superiority in organ transformation.