BACKGROUND Serum protein induced by vitamin K absence or antagonist-Ⅱ(PIVKA-Ⅱ) is a promising biomarker for hepatocellular carcinoma(HCC) surveillance.AIM To identify the contributing factors related to the abnormal...BACKGROUND Serum protein induced by vitamin K absence or antagonist-Ⅱ(PIVKA-Ⅱ) is a promising biomarker for hepatocellular carcinoma(HCC) surveillance.AIM To identify the contributing factors related to the abnormal elevation of PIVKA-Ⅱ level and assess their potential influence on the performance of PIVKA-Ⅱ in detecting HCC.METHODS This study retrospectively enrolled in 784 chronic liver disease(CLD) patients and 267 HCC patients in Mengchao Hepatobiliary Hospital of Fujian Medical University from April 2016 to December 2019. Logistic regression and the area under the receiver operating characteristic curve(AUC) were used to evaluate the influencing factors and diagnostic performance of PIVKA-Ⅱ for HCC, respectively.RESULTS Elevated PIVKA-Ⅱ levels were independently positively associated with alcohol-related liver disease, serum alkaline phosphatase(ALP), and total bilirubin(TBIL) for CLD patients and aspartate aminotransferase(AST) and tumor size for HCC patients(all P < 0.05). Serum PIVKA-Ⅱ were significantly lower in patients with viral etiology, ALP ≤ 1 × upper limit of normal(ULN), TBIL ≤ 1 × ULN, and AST ≤ 1 × ULN than in those with nonviral disease and abnormal ALP, TBIL, or AST(all P < 0.05), but the differences disappeared in patients with early-stage HCC. For patients with TBIL ≤ 1 × ULN, the AUC of PIVKA-Ⅱ was significantly higher compared to that in patients with TBIL > 1 × ULN(0.817 vs 0.669, P = 0.015), while the difference between ALP ≤ 1 × ULN and ALP > 1 × ULN was not statistically significant(0.783 vs 0.729, P = 0.398). These trends were then more prominently perceived in subgroups of patients with viral etiology and HBV alone.CONCLUSION Serum PIVKA-Ⅱ has better performance in detecting HCC at an early stage for CLD patients with normal serum TBIL.展开更多
BACKGROUND Non-invasive evaluation for liver fibrosis is clinically important,especially in patients with undetectable hepatitis B virus(HBV)DNA treated with nucleoside analogs.AIM To clarify the monitoring power of h...BACKGROUND Non-invasive evaluation for liver fibrosis is clinically important,especially in patients with undetectable hepatitis B virus(HBV)DNA treated with nucleoside analogs.AIM To clarify the monitoring power of hepatitis B core-related antigen(HBcrAg)for hepatic histologic changes in patients with chronic hepatitis B(CHB)treated with entecavir.METHODS This prospective multicenter study used multiple ordinal and multivariate logistics regression analysis to assess variables associated with Ishak fibrosis score and regression for fibrosis regression,respectively,in 403 CHB patients,including 374 with entecavir for 72 weeks(291 underwent paired liver biopsy)and 29 as controls.RESULTS Level of HBcrAg correlated negatively with liver fibrosis staging(γ=-0.357,P<0.001)in hepatitis B e antigen(HBeAg)-positive patients,and positively with liver fibrosis staging in HBeAg-negative patients.Higher HBcrAg concentration was associated with younger age,HBeAg positive status,high HBV DNA loads,high level of hepatitis B surface antigen(HBsAg)and higher necroinflammation,but not with HBV genotype.Serum concentration of HBcrAg,basal core promoter/precore(BCP/PC)mutant,quantitation of HBsAg(qHBsAg)and platelet counts were independently associated with Ishak fibrosis score on multiple ordinal regression.HBV DNA was undetectable in 88.37%of patients treated with entecavir at week 72,while their level of HBcrAg was still detectable.A greater reduction in post-treatment HBcrAg concentration was associated with the regression of hepatic fibrosis and histological improvement.HBcrAg concentration>6.33 log IU/mL at baseline and logarithmic reduction>1.03 log IU/mL at week 72 were associated with a higher chance of regression of liver fibrosis and histological improvement,respectively.CONCLUSION HBcrAg level is associated with liver fibrosis progression.HBcrAg is an excellent monitor of hepatic histological changes,especially in CHB patients treated with nucleoside analogs.展开更多
Chronic liver disease(CLD)causes approximately 2.14 million(2.06-2.30)deaths annually,and;therefore,represents a heavy global health burden.[1]Currently,chronic hepatitis B(CHB),hepatitis C,alcohol-related liver disea...Chronic liver disease(CLD)causes approximately 2.14 million(2.06-2.30)deaths annually,and;therefore,represents a heavy global health burden.[1]Currently,chronic hepatitis B(CHB),hepatitis C,alcohol-related liver disease,and non-alcoholic liver disease(NAFLD)account for 29%,26%,25%,and 9%of cirrhosis-related deaths worldwide,respectively.[1]Although vaccination has resulted in reductions in the seroprevalence of hepatitis B surface antigen and the overall prevalence of liver-related mortality,CHB remains the principal cause of liver disease,especially in China.展开更多
Background and Aims: Occult HBV infection (OBI) in chil-dren has proven to be associated with their immune re-sponse to hepatitis B vaccine (HepB). This study aimed to investigate the effect of a booster HepB on OBI, ...Background and Aims: Occult HBV infection (OBI) in chil-dren has proven to be associated with their immune re-sponse to hepatitis B vaccine (HepB). This study aimed to investigate the effect of a booster HepB on OBI, which is rarely investigated. Methods: This study enrolled 236 ma-ternal HBsAg-positive children who were followed up annu-ally until 8 years of age and were hepatitis B surface antigen (HBsAg) negative. Of those 100 received a booster HepB be-tween 1 and 3 years of age (booster group), and 136 were never boosted (non-booster group). Serial follow-up data of children and baseline data of their mothers were collected and between-group differences were analyzed. Results: The incidence of OBI varied dynamically during follow-up, with 37.14% (78/210), 19.09% (42/220), 20.85% (44/211), 31.61% (61/193), 8.65% (18/208) and 12.71% (30/236) at 7 months, 1, 2, 3, 4, and 8 years of age. At 8 years of age, the negative conversion rate of HBV DNA in the booster group was significantly higher than that in non-booster group [57.89% (11/19) vs. 30.51% (18/59), p=0.032]. For chil-dren without OBI at 7 months old, the incidence of OBI in booster group was significantly lower than that in non-boost-er group [25.64% (10/39) vs. 67.74% (63/93), p<0.001]. Conclusions: The incidence of OBI in maternal HBsAg-positive children was high, serum HBV DNA in children with OBI was intermittently positive at low levels, and a booster HepB in infancy reduced the incidence of OBI in children with HBsAg-positive mothers.展开更多
Enterovirus A71(EV-A71) is the major pathogen responsible for the severe hand, foot and mouth disease worldwide, for which few effective antiviral drugs are presently available. Interferon-a(IFN-a) has been used in an...Enterovirus A71(EV-A71) is the major pathogen responsible for the severe hand, foot and mouth disease worldwide, for which few effective antiviral drugs are presently available. Interferon-a(IFN-a) has been used in antiviral therapy for decades;it has been reported that EV-A71 antagonizes the antiviral activity of IFN-a based on viral 2 Apro-mediated reduction of the interferon-alpha receptor 1(IFNAR1);however, the mechanism remains unknown. Here, we showed a significant increase in IFNAR1 protein induced by IFN-a in RD cells, whereas EV-A71 infection caused obvious downregulation of the IFNAR1 protein and blockage of IFN-a signaling. Subsequently, we observed that EV-A71 2 Apro inhibited IFNAR1 translation by cleavage of the eukaryotic initiation factor 4 GI(eIF4GI), without affecting IFNAR1 m RNA levels induced by IFN-a. The inhibition of IFNAR1 translation also occurred in puromycin-induced apoptotic cells when caspase-3 cleaved e IF4 GI. Importantly, we verified that 2 Aprocould activate cellular caspase-3, which was subsequently involved in e IF4 GI cleavage mediated by 2 Apro. Furthermore, inhibition of caspase-3 activation resulted in the partial restoration of IFNAR1 in cells transfected with 2 A or infected with EV-A71, suggesting the pivotal role of both viral 2 Aproand caspase-3 activation in the disturbance of IFN-a signaling. Collectively, we elucidate a novel mechanism by which cellular caspase-3 contributes to viral 2 Apro-mediated down-regulation of IFNAR1 at the translation level during EV-A71 infection, indicating that caspase-3 inhibition could be a potential complementary strategy to improve clinical anti-EV-A71 therapy with IFN-a.展开更多
Background and Aims:The poor outcomes of hepatocellular carcinoma(HCC)patients may be due to not only malignant tumors but also limited liver function.Therefore,as stated in major guidelines,only patients with relativ...Background and Aims:The poor outcomes of hepatocellular carcinoma(HCC)patients may be due to not only malignant tumors but also limited liver function.Therefore,as stated in major guidelines,only patients with relatively normal liver function(Child-Pugh A)would be referred for curative hepatectomy.Even so,the postsurgery survival rate of patients is still extremely poor.Direct curative resection may benefit most patients.This study aimed to improve the prognosis predicting accuracy of the Child-Pugh scoring system.Methods:This study included two cohorts:cohort A being composed of 613 HCC patients,with a 23-month median postsurgery follow-up time;and cohort B being composed of 554 tumor-free chronic liver disease patients.Kaplan-Meier test and Cox model were used for survival analysis.Independent-samples t test or one-way ANOVA was used to test the differences between different groups.Results:Serum prealbumin levels were found inversely correlated with worsening of flbrotic scores(r=-0.482,p<0.001).Lower levels of presurgery prealbumin was an independent factor of poor postsurgery prognosis in Child-Pugh A patients,with a hazard ratio of 0.731(p=0.001).By integrating prealbumin together with total bilirubin level,serum albumin concentration and prothrombin time,a modified liver disease prognosis scoring system was developed to define traditional Child-Pugh A HCC patients as Modified Child-Pugh MCP-1,MCP-2 and MCP-3,with median postsurgery overall survival times of 44.00,28.00 and 11.00 months respectively.Conclusions:Preoperative serum prealbumin is a valuable prognosis predicting biomarker for Child-Pugh A HCC patients who may be under consideration for curative resection.With serum prealbumin included as one of the parameters,the MCP scoring system might improve the postsurgery survival predicting accuracy for HCC patients.展开更多
Background and Aims: Non-invasive evaluation of liver nec-roinflammation in patients with chronic liver disease is an un-met need in clinical practice.The diagnostic accuracy of transient elastography-based liver stif...Background and Aims: Non-invasive evaluation of liver nec-roinflammation in patients with chronic liver disease is an un-met need in clinical practice.The diagnostic accuracy of transient elastography-based liver stiffness measurement(LSM)for liver fibrosis could be affected by liver necroinflam-mation,the latter of which could intensify stiffness of the liver.Such results have prompted us to explore the diagnosis potential of LSM for liver inflammation.Methods: Three cross-sectional cohorts of liver biopsy-proven chronic liver dis-ease patients were enrolled,including 1417 chronic hepatitis B(CHB)patients from 10 different medical centers,106 non-al-coholic steatohepatitis patients,and 143 patients with auto-immune-related liver diseases.Another longitudinal cohort of 14 entecavir treatment patients was also included.The re-ceiver operating characteristic(ROC)curve was employed to explore the diagnostic value of LSM.Results: In CHB patients,LSM value ascended with the increased severity of liver nec-roinflammation in patients with the same fibrosis stage.Such positive correlation between LSM and liver necroinflammation was also found in non-alcoholic steatohepatitis and autoim-mune-related liver diseases populations.Furthermore,the ROC curve exhibited that LSM could identify moderate and se-vere inflammation in CHB patients(area under the ROC curve as 0.779 and 0.838)and in non-alcoholic steatohepatitis pa-tients(area under the ROC curve as 0.826 and 0.871),respec-tively.Such moderate diagnostic value was also found in autoimmune-related liver diseases patients.In addition,in the longitudinal entecavir treated CHB cohort,a decline of LSM values was observed in parallel with the control of inflam-matory activity in liver.Conclusions: Our study implicates a diagnostic potential of LSM to evaluate the severity of liver necroinflammation in chronic liver disease patients.展开更多
Background and Aims:As a hepatocellular carcinoma biomarker,serum Golgi protein 73(GP73)is reportedly related to inflammation.Acute-on-chronic liver failure(ACLF)is characterized by severe systemic inflammation.In thi...Background and Aims:As a hepatocellular carcinoma biomarker,serum Golgi protein 73(GP73)is reportedly related to inflammation.Acute-on-chronic liver failure(ACLF)is characterized by severe systemic inflammation.In this study,we aimed to explore the association between the GP73 level and short-term mortality in patients with alcohol-associated liver disease-related ACLF(ALD-ACLF).Methods:This retrospective cohort study involved 126 Chinese adults with ALD-ACLF.Baseline serum GP73 level was measured using enzymelinked immunosorbent assay.Patients were followed-up for 90 d and outcomes were assessed.Data were analyzed using multivariate Cox regression and piecewise linear regression analyses.The predictive value of GP73 and classic models for the short-term prognosis of participants were evaluated and compared using receiver operating characteristic curves.Results:The serum GP73 level was independently associated with an increased mortality risk in patients with ALD-ACLF.Compared with the lowest tertile,the highest serum GP73 level predisposed patients with ALD-ACLF to a higher mortality risk in the fully adjusted model[at 28 days:hazard ratio(HR):4.29(0.99–18.54),p=0.0511;at 90 days:HR:3.52(1.15–10.79),p=0.0276].Further analysis revealed a positive linear association.GP73 significantly improved the accuracy of the Child-Turcotte-Pugh score,model for end-stage liver disease score,and model for end-stage liver diseasesodium score in predicting short-time prognosis of patients with ALD-ACLF.Conclusions:The serum GP73 level is a significant predictor of the subsequent risk of death in patients with ALD-ACLF.GP73 improved the predictive value of classic prognostic scores.展开更多
The pandemic of coronavirus disease 2019 has threatened humans for more than one and a half years.In particular,viral mutation like delta strain has led to third-or fourth-wave transmission among the countries in Asia...The pandemic of coronavirus disease 2019 has threatened humans for more than one and a half years.In particular,viral mutation like delta strain has led to third-or fourth-wave transmission among the countries in Asia,Europe,and North America.Although large-scale vaccination has been carried out in many countries,the incidence of reinfection and vaccine-past breakthrough infection is becoming an emerging challenge to humans worldwide.The related mechanisms underlying the reinfection and breakthrough infection remain unknown.In this review,we summarized the challenge and related reasons for severe acute respiratory syndrome coronavirus 2 reinfection and breakthrough infection.Simultaneously,we addressed some critical contents of the study in future.展开更多
Background and Aims:Natural vaginal delivery and breastfeeding favor the development of a strong immune system in infants,and the immune response of infants to vaccines is closely related to their immune system.This l...Background and Aims:Natural vaginal delivery and breastfeeding favor the development of a strong immune system in infants,and the immune response of infants to vaccines is closely related to their immune system.This large prospective cohort study aimed to explore the effects of delivery and feeding mode on infant’s immune response to hepatitis B vaccine(HepB).Methods:A total of 1,254 infants who completed the whole course of HepB immunization and whose parents were both HBsAg negative were enrolled from infants born in Jinchang City during 2018-2019 by cluster sampling method.Results:Twenty(1.59%)of the 1,254 infants were nonresponders to HepB.Among the other 1,234 infants,10.05%(124/1,234),81.69%(1,008/1,234)and 8.27%(102/1,234)of infants had low,medium,and high responses to HepB,respectively.Logistic regression analysis showed that cesarean section(OR:8.58,95%CI:3.11-23.65,p<0.001)and birth weight<3.18 kg(OR:5.58,95%CI:1.89-16.51,p=0.002)were independent risk factors for infant nonresponse to HepB,and cesarean section(OR:7.63,95%CI:4.64-12.56,p<0.001),formula feeding(OR:4.91,95%CI:1.47-16.45,p=0.001),maternal antiHBs negativity(OR:27.2,95%CI:10.67-69.35,p<0.001),paternal non-response history of HepB(OR:7.86,95%CI:2.22-27.82,p=0.014)and birth weight<3.22 kg(OR:4.00,95%CI:2.43-6.59,p<0.001)were independent risk factors for infant low response to HepB.In cases where birth weight and genetic factors are unmodifiable and maternal anti-HBs effects are controversial,it makes sense to enhance infant response by changing delivery and feeding patterns.Conclusions:Natural vaginal delivery and breastfeeding are beneficial to the infant’s immune response to HepB.展开更多
In the issue of Gastroenterology published October 2018,the article by Moon et al.1 demonstrated that screening patients with cirrhosis for hepatocellular carcinoma(HCC)by ultrasound scan(USS),measurement of serumα-f...In the issue of Gastroenterology published October 2018,the article by Moon et al.1 demonstrated that screening patients with cirrhosis for hepatocellular carcinoma(HCC)by ultrasound scan(USS),measurement of serumα-fetoprotein(AFP),each alone or in combination,was not associated with the decreased HCC-related mortality.In this matched case control study,all the study patients were registered in detail in the U.S.Department of Veterans Affairs.The study included 238 cases who died of HCC with cirrhosis,and the same number of matched controls with cirrhosis who had been enrolled in U.S.Department of Veterans Affairs care for the 4 years before the index date and alive at the time of their matched case's death.The study retrospectively collected each case's USS and AFP screening data for 4 years before the date of HCC diagnosis or the equivalent index date in controls.Authors found that there was no significant difference of frequency of routine screening between the cases and controls.Therefore,the authors interpreted these results as indicating that the routine screening would not reduce cancer-related mortality.展开更多
Circular RNAs(circRNAs)are involved in various biological processes and disease pathogenesis.However,only a small number of functional circRNAs have been identified among hundreds of thousands of circRNA species,partl...Circular RNAs(circRNAs)are involved in various biological processes and disease pathogenesis.However,only a small number of functional circRNAs have been identified among hundreds of thousands of circRNA species,partly because most current methods are based on circular junction counts and overlook the fact that a circRNA is formed from the host gene by backsplicing(BS).To distinguish the expression difference originating from BS or the host gene,we present differentially expressed back-splicing(DEBKS),a software program to streamline the discovery of differential BS events between two rRNA-depleted RNA sequencing(RNA-seq)sample groups.By applying to real and simulated data and employing RT-qPCR for validation,we demonstrate that DEBKS is efficient and accurate in detecting circRNAs with differential BS events between paired and unpaired sample groups.DEBKS is available at https://github.com/yangence/DEBKS as open-source software.展开更多
Dear Editor,Hepatitis B virus(HBV)infection remains a major cause of liver diseases worldwide,which affects approximately 250 million people globally(Yuen et al.2018).Individuals with chronic HBV infection are at high...Dear Editor,Hepatitis B virus(HBV)infection remains a major cause of liver diseases worldwide,which affects approximately 250 million people globally(Yuen et al.2018).Individuals with chronic HBV infection are at high risk of developing liver cirrhosis,and ultimately hepatocellular carcinoma(HCC).HBV is a Hepadnavirus DNA virus,which specifically infects and efficiently replicates in hepatocytes.It has been proposed for decades that HBV replicates preferentially in non-dividing quiescent hepatocytes(Ozer et al.1996).展开更多
On April 5,2022,United Kingdom(UK)reported 10 cases of severe acute hepatitis with unknown cause among children under 10 years old.The initial symptoms of these cases could date back to March 2022.A rapidly increasing...On April 5,2022,United Kingdom(UK)reported 10 cases of severe acute hepatitis with unknown cause among children under 10 years old.The initial symptoms of these cases could date back to March 2022.A rapidly increasing number of cases lasted for a month and the growth seems to be slightly slowing down in May.As of May 27,2022,the total number of children with acute hepatitis in UK reached to 222(UKHSA,2022a).European Union and European Economic Area reported 305 cases across 17 countries and none as epidemiologically linked as of May 31,2022(ECDC-WHO,2022).展开更多
COVID-19,caused by SARS-CoV-2,is the most consequential pandemic of this century.Since the outbreak in late 2019,animal models have been playing crucial roles in aiding the rapid development of vaccines/drugs for prev...COVID-19,caused by SARS-CoV-2,is the most consequential pandemic of this century.Since the outbreak in late 2019,animal models have been playing crucial roles in aiding the rapid development of vaccines/drugs for prevention and therapy,as well as understanding the pathogenesis of SARS-CoV-2 infection and immune responses of hosts.However,the current animal models have some deficits and there is an urgent need for novel models to evaluate the virulence of variants of concerns(VOC),antibodydependent enhancement(ADE),and various comorbidities of COVID-19.This review summarizes the clinical features of COVID-19 in different populations,and the characteristics of the major animal models of SARS-CoV-2,including those naturally susceptible animals,such as non-human primates,Syrian hamster,ferret,minks,poultry,livestock,and mouse models sensitized by genetically modified,AAV/adenoviral transduced,mouse-adapted strain of SARS-CoV-2,and by engraftment of human tissues or cells.Since understanding the host receptors and proteases is essential for designing advanced genetically modified animal models,successful studies on receptors and proteases are also reviewed.Several improved alternatives for future mouse models are proposed,including the reselection of alternative receptor genes or multiple gene combinations,the use of transgenic or knock-in method,and different strains for establishing the next generation of genetically modified mice.展开更多
基金Supported by the National Key Clinical Discipline,Fuzhou “14th Five-Year Plan” Clinical Key Specialty (laboratory medicine)the National Science Foundation of China,No. 82002587
文摘BACKGROUND Serum protein induced by vitamin K absence or antagonist-Ⅱ(PIVKA-Ⅱ) is a promising biomarker for hepatocellular carcinoma(HCC) surveillance.AIM To identify the contributing factors related to the abnormal elevation of PIVKA-Ⅱ level and assess their potential influence on the performance of PIVKA-Ⅱ in detecting HCC.METHODS This study retrospectively enrolled in 784 chronic liver disease(CLD) patients and 267 HCC patients in Mengchao Hepatobiliary Hospital of Fujian Medical University from April 2016 to December 2019. Logistic regression and the area under the receiver operating characteristic curve(AUC) were used to evaluate the influencing factors and diagnostic performance of PIVKA-Ⅱ for HCC, respectively.RESULTS Elevated PIVKA-Ⅱ levels were independently positively associated with alcohol-related liver disease, serum alkaline phosphatase(ALP), and total bilirubin(TBIL) for CLD patients and aspartate aminotransferase(AST) and tumor size for HCC patients(all P < 0.05). Serum PIVKA-Ⅱ were significantly lower in patients with viral etiology, ALP ≤ 1 × upper limit of normal(ULN), TBIL ≤ 1 × ULN, and AST ≤ 1 × ULN than in those with nonviral disease and abnormal ALP, TBIL, or AST(all P < 0.05), but the differences disappeared in patients with early-stage HCC. For patients with TBIL ≤ 1 × ULN, the AUC of PIVKA-Ⅱ was significantly higher compared to that in patients with TBIL > 1 × ULN(0.817 vs 0.669, P = 0.015), while the difference between ALP ≤ 1 × ULN and ALP > 1 × ULN was not statistically significant(0.783 vs 0.729, P = 0.398). These trends were then more prominently perceived in subgroups of patients with viral etiology and HBV alone.CONCLUSION Serum PIVKA-Ⅱ has better performance in detecting HCC at an early stage for CLD patients with normal serum TBIL.
基金Supported by Chinese Ministry of Science and Technology Grants the Major Science and Technology Special Project Fund Scheme,No.2013ZX10005002Beijing the Special Clinical Application Research and Translational Grants,No.Z151100004015221
文摘BACKGROUND Non-invasive evaluation for liver fibrosis is clinically important,especially in patients with undetectable hepatitis B virus(HBV)DNA treated with nucleoside analogs.AIM To clarify the monitoring power of hepatitis B core-related antigen(HBcrAg)for hepatic histologic changes in patients with chronic hepatitis B(CHB)treated with entecavir.METHODS This prospective multicenter study used multiple ordinal and multivariate logistics regression analysis to assess variables associated with Ishak fibrosis score and regression for fibrosis regression,respectively,in 403 CHB patients,including 374 with entecavir for 72 weeks(291 underwent paired liver biopsy)and 29 as controls.RESULTS Level of HBcrAg correlated negatively with liver fibrosis staging(γ=-0.357,P<0.001)in hepatitis B e antigen(HBeAg)-positive patients,and positively with liver fibrosis staging in HBeAg-negative patients.Higher HBcrAg concentration was associated with younger age,HBeAg positive status,high HBV DNA loads,high level of hepatitis B surface antigen(HBsAg)and higher necroinflammation,but not with HBV genotype.Serum concentration of HBcrAg,basal core promoter/precore(BCP/PC)mutant,quantitation of HBsAg(qHBsAg)and platelet counts were independently associated with Ishak fibrosis score on multiple ordinal regression.HBV DNA was undetectable in 88.37%of patients treated with entecavir at week 72,while their level of HBcrAg was still detectable.A greater reduction in post-treatment HBcrAg concentration was associated with the regression of hepatic fibrosis and histological improvement.HBcrAg concentration>6.33 log IU/mL at baseline and logarithmic reduction>1.03 log IU/mL at week 72 were associated with a higher chance of regression of liver fibrosis and histological improvement,respectively.CONCLUSION HBcrAg level is associated with liver fibrosis progression.HBcrAg is an excellent monitor of hepatic histological changes,especially in CHB patients treated with nucleoside analogs.
基金National S&T Major Project for Infectious Diseases(Nos.2017ZX10201201 and 2017ZX10302201)National Natural Science Foundation of China Grant(No.81902115)。
文摘Chronic liver disease(CLD)causes approximately 2.14 million(2.06-2.30)deaths annually,and;therefore,represents a heavy global health burden.[1]Currently,chronic hepatitis B(CHB),hepatitis C,alcohol-related liver disease,and non-alcoholic liver disease(NAFLD)account for 29%,26%,25%,and 9%of cirrhosis-related deaths worldwide,respectively.[1]Although vaccination has resulted in reductions in the seroprevalence of hepatitis B surface antigen and the overall prevalence of liver-related mortality,CHB remains the principal cause of liver disease,especially in China.
基金National Major Scientific and Technological Special Project during the Thirteenth Five-Year Plan Period(2017ZX10201201003).
文摘Background and Aims: Occult HBV infection (OBI) in chil-dren has proven to be associated with their immune re-sponse to hepatitis B vaccine (HepB). This study aimed to investigate the effect of a booster HepB on OBI, which is rarely investigated. Methods: This study enrolled 236 ma-ternal HBsAg-positive children who were followed up annu-ally until 8 years of age and were hepatitis B surface antigen (HBsAg) negative. Of those 100 received a booster HepB be-tween 1 and 3 years of age (booster group), and 136 were never boosted (non-booster group). Serial follow-up data of children and baseline data of their mothers were collected and between-group differences were analyzed. Results: The incidence of OBI varied dynamically during follow-up, with 37.14% (78/210), 19.09% (42/220), 20.85% (44/211), 31.61% (61/193), 8.65% (18/208) and 12.71% (30/236) at 7 months, 1, 2, 3, 4, and 8 years of age. At 8 years of age, the negative conversion rate of HBV DNA in the booster group was significantly higher than that in non-booster group [57.89% (11/19) vs. 30.51% (18/59), p=0.032]. For chil-dren without OBI at 7 months old, the incidence of OBI in booster group was significantly lower than that in non-boost-er group [25.64% (10/39) vs. 67.74% (63/93), p<0.001]. Conclusions: The incidence of OBI in maternal HBsAg-positive children was high, serum HBV DNA in children with OBI was intermittently positive at low levels, and a booster HepB in infancy reduced the incidence of OBI in children with HBsAg-positive mothers.
基金grants from Beijing Natural Science Foundation(No.19G10290)National Natural Science Foundation of China(No.81772184).
文摘Enterovirus A71(EV-A71) is the major pathogen responsible for the severe hand, foot and mouth disease worldwide, for which few effective antiviral drugs are presently available. Interferon-a(IFN-a) has been used in antiviral therapy for decades;it has been reported that EV-A71 antagonizes the antiviral activity of IFN-a based on viral 2 Apro-mediated reduction of the interferon-alpha receptor 1(IFNAR1);however, the mechanism remains unknown. Here, we showed a significant increase in IFNAR1 protein induced by IFN-a in RD cells, whereas EV-A71 infection caused obvious downregulation of the IFNAR1 protein and blockage of IFN-a signaling. Subsequently, we observed that EV-A71 2 Apro inhibited IFNAR1 translation by cleavage of the eukaryotic initiation factor 4 GI(eIF4GI), without affecting IFNAR1 m RNA levels induced by IFN-a. The inhibition of IFNAR1 translation also occurred in puromycin-induced apoptotic cells when caspase-3 cleaved e IF4 GI. Importantly, we verified that 2 Aprocould activate cellular caspase-3, which was subsequently involved in e IF4 GI cleavage mediated by 2 Apro. Furthermore, inhibition of caspase-3 activation resulted in the partial restoration of IFNAR1 in cells transfected with 2 A or infected with EV-A71, suggesting the pivotal role of both viral 2 Aproand caspase-3 activation in the disturbance of IFN-a signaling. Collectively, we elucidate a novel mechanism by which cellular caspase-3 contributes to viral 2 Apro-mediated down-regulation of IFNAR1 at the translation level during EV-A71 infection, indicating that caspase-3 inhibition could be a potential complementary strategy to improve clinical anti-EV-A71 therapy with IFN-a.
基金supported by the SZSM201612071the National S&T Major Project for Infectious Diseases(2017YFC0908100,2017ZX10302201,2017ZX10201201)the project from Beijing Municipal Science and Technology Commission(No.Z161100000116047)
文摘Background and Aims:The poor outcomes of hepatocellular carcinoma(HCC)patients may be due to not only malignant tumors but also limited liver function.Therefore,as stated in major guidelines,only patients with relatively normal liver function(Child-Pugh A)would be referred for curative hepatectomy.Even so,the postsurgery survival rate of patients is still extremely poor.Direct curative resection may benefit most patients.This study aimed to improve the prognosis predicting accuracy of the Child-Pugh scoring system.Methods:This study included two cohorts:cohort A being composed of 613 HCC patients,with a 23-month median postsurgery follow-up time;and cohort B being composed of 554 tumor-free chronic liver disease patients.Kaplan-Meier test and Cox model were used for survival analysis.Independent-samples t test or one-way ANOVA was used to test the differences between different groups.Results:Serum prealbumin levels were found inversely correlated with worsening of flbrotic scores(r=-0.482,p<0.001).Lower levels of presurgery prealbumin was an independent factor of poor postsurgery prognosis in Child-Pugh A patients,with a hazard ratio of 0.731(p=0.001).By integrating prealbumin together with total bilirubin level,serum albumin concentration and prothrombin time,a modified liver disease prognosis scoring system was developed to define traditional Child-Pugh A HCC patients as Modified Child-Pugh MCP-1,MCP-2 and MCP-3,with median postsurgery overall survival times of 44.00,28.00 and 11.00 months respectively.Conclusions:Preoperative serum prealbumin is a valuable prognosis predicting biomarker for Child-Pugh A HCC patients who may be under consideration for curative resection.With serum prealbumin included as one of the parameters,the MCP scoring system might improve the postsurgery survival predicting accuracy for HCC patients.
基金the National S&T Major Project for Infectious Diseases(2017ZX10201201,2017ZX10202202,2017ZX10302201 and 2017ZX10202203)the project from Beijing Municipal Science & Technology Commission(Z161100000116047)+1 种基金Project funded by China Postdoc-toral Science Foundation(2017M620544,2018T110014)Project funded by Shenzhen Municipal Health Commission(SZSM201612071)
文摘Background and Aims: Non-invasive evaluation of liver nec-roinflammation in patients with chronic liver disease is an un-met need in clinical practice.The diagnostic accuracy of transient elastography-based liver stiffness measurement(LSM)for liver fibrosis could be affected by liver necroinflam-mation,the latter of which could intensify stiffness of the liver.Such results have prompted us to explore the diagnosis potential of LSM for liver inflammation.Methods: Three cross-sectional cohorts of liver biopsy-proven chronic liver dis-ease patients were enrolled,including 1417 chronic hepatitis B(CHB)patients from 10 different medical centers,106 non-al-coholic steatohepatitis patients,and 143 patients with auto-immune-related liver diseases.Another longitudinal cohort of 14 entecavir treatment patients was also included.The re-ceiver operating characteristic(ROC)curve was employed to explore the diagnostic value of LSM.Results: In CHB patients,LSM value ascended with the increased severity of liver nec-roinflammation in patients with the same fibrosis stage.Such positive correlation between LSM and liver necroinflammation was also found in non-alcoholic steatohepatitis and autoim-mune-related liver diseases populations.Furthermore,the ROC curve exhibited that LSM could identify moderate and se-vere inflammation in CHB patients(area under the ROC curve as 0.779 and 0.838)and in non-alcoholic steatohepatitis pa-tients(area under the ROC curve as 0.826 and 0.871),respec-tively.Such moderate diagnostic value was also found in autoimmune-related liver diseases patients.In addition,in the longitudinal entecavir treated CHB cohort,a decline of LSM values was observed in parallel with the control of inflam-matory activity in liver.Conclusions: Our study implicates a diagnostic potential of LSM to evaluate the severity of liver necroinflammation in chronic liver disease patients.
基金supported by a grant from the Capital’s Funds for Health Improvement and Research,China(NO.2020-1-5031).
文摘Background and Aims:As a hepatocellular carcinoma biomarker,serum Golgi protein 73(GP73)is reportedly related to inflammation.Acute-on-chronic liver failure(ACLF)is characterized by severe systemic inflammation.In this study,we aimed to explore the association between the GP73 level and short-term mortality in patients with alcohol-associated liver disease-related ACLF(ALD-ACLF).Methods:This retrospective cohort study involved 126 Chinese adults with ALD-ACLF.Baseline serum GP73 level was measured using enzymelinked immunosorbent assay.Patients were followed-up for 90 d and outcomes were assessed.Data were analyzed using multivariate Cox regression and piecewise linear regression analyses.The predictive value of GP73 and classic models for the short-term prognosis of participants were evaluated and compared using receiver operating characteristic curves.Results:The serum GP73 level was independently associated with an increased mortality risk in patients with ALD-ACLF.Compared with the lowest tertile,the highest serum GP73 level predisposed patients with ALD-ACLF to a higher mortality risk in the fully adjusted model[at 28 days:hazard ratio(HR):4.29(0.99–18.54),p=0.0511;at 90 days:HR:3.52(1.15–10.79),p=0.0276].Further analysis revealed a positive linear association.GP73 significantly improved the accuracy of the Child-Turcotte-Pugh score,model for end-stage liver disease score,and model for end-stage liver diseasesodium score in predicting short-time prognosis of patients with ALD-ACLF.Conclusions:The serum GP73 level is a significant predictor of the subsequent risk of death in patients with ALD-ACLF.GP73 improved the predictive value of classic prognostic scores.
基金This work was supported by Emergency Key Program of Guangzhou Laboratory(EKPG21-30-4)National key research and development plan(2020YFC0860900).
文摘The pandemic of coronavirus disease 2019 has threatened humans for more than one and a half years.In particular,viral mutation like delta strain has led to third-or fourth-wave transmission among the countries in Asia,Europe,and North America.Although large-scale vaccination has been carried out in many countries,the incidence of reinfection and vaccine-past breakthrough infection is becoming an emerging challenge to humans worldwide.The related mechanisms underlying the reinfection and breakthrough infection remain unknown.In this review,we summarized the challenge and related reasons for severe acute respiratory syndrome coronavirus 2 reinfection and breakthrough infection.Simultaneously,we addressed some critical contents of the study in future.
基金This study was supported by grants from the Chinese Foundation for Hepatitis Prevention and Control(YGFK20180006).
文摘Background and Aims:Natural vaginal delivery and breastfeeding favor the development of a strong immune system in infants,and the immune response of infants to vaccines is closely related to their immune system.This large prospective cohort study aimed to explore the effects of delivery and feeding mode on infant’s immune response to hepatitis B vaccine(HepB).Methods:A total of 1,254 infants who completed the whole course of HepB immunization and whose parents were both HBsAg negative were enrolled from infants born in Jinchang City during 2018-2019 by cluster sampling method.Results:Twenty(1.59%)of the 1,254 infants were nonresponders to HepB.Among the other 1,234 infants,10.05%(124/1,234),81.69%(1,008/1,234)and 8.27%(102/1,234)of infants had low,medium,and high responses to HepB,respectively.Logistic regression analysis showed that cesarean section(OR:8.58,95%CI:3.11-23.65,p<0.001)and birth weight<3.18 kg(OR:5.58,95%CI:1.89-16.51,p=0.002)were independent risk factors for infant nonresponse to HepB,and cesarean section(OR:7.63,95%CI:4.64-12.56,p<0.001),formula feeding(OR:4.91,95%CI:1.47-16.45,p=0.001),maternal antiHBs negativity(OR:27.2,95%CI:10.67-69.35,p<0.001),paternal non-response history of HepB(OR:7.86,95%CI:2.22-27.82,p=0.014)and birth weight<3.22 kg(OR:4.00,95%CI:2.43-6.59,p<0.001)were independent risk factors for infant low response to HepB.In cases where birth weight and genetic factors are unmodifiable and maternal anti-HBs effects are controversial,it makes sense to enhance infant response by changing delivery and feeding patterns.Conclusions:Natural vaginal delivery and breastfeeding are beneficial to the infant’s immune response to HepB.
基金the National S&T Major Project for Infectious Diseases(No.20177X10201201)
文摘In the issue of Gastroenterology published October 2018,the article by Moon et al.1 demonstrated that screening patients with cirrhosis for hepatocellular carcinoma(HCC)by ultrasound scan(USS),measurement of serumα-fetoprotein(AFP),each alone or in combination,was not associated with the decreased HCC-related mortality.In this matched case control study,all the study patients were registered in detail in the U.S.Department of Veterans Affairs.The study included 238 cases who died of HCC with cirrhosis,and the same number of matched controls with cirrhosis who had been enrolled in U.S.Department of Veterans Affairs care for the 4 years before the index date and alive at the time of their matched case's death.The study retrospectively collected each case's USS and AFP screening data for 4 years before the date of HCC diagnosis or the equivalent index date in controls.Authors found that there was no significant difference of frequency of routine screening between the cases and controls.Therefore,the authors interpreted these results as indicating that the routine screening would not reduce cancer-related mortality.
基金supported by the Beijing Municipal Science and Technology Commission,China(Grant No.Z181100001518005)the Chinese Institute for Brain Research,Beijing,China to EY,the National Natural Science Foundation of China(Grant No.81873769)to CCthe Innovation Fund for Outstanding Doctoral Candidates of Peking University Health Science Center,China(Grant No.BMU2020BSS001)to ZL.
文摘Circular RNAs(circRNAs)are involved in various biological processes and disease pathogenesis.However,only a small number of functional circRNAs have been identified among hundreds of thousands of circRNA species,partly because most current methods are based on circular junction counts and overlook the fact that a circRNA is formed from the host gene by backsplicing(BS).To distinguish the expression difference originating from BS or the host gene,we present differentially expressed back-splicing(DEBKS),a software program to streamline the discovery of differential BS events between two rRNA-depleted RNA sequencing(RNA-seq)sample groups.By applying to real and simulated data and employing RT-qPCR for validation,we demonstrate that DEBKS is efficient and accurate in detecting circRNAs with differential BS events between paired and unpaired sample groups.DEBKS is available at https://github.com/yangence/DEBKS as open-source software.
基金This work was supported by the National S&T Major Project for Infectious Diseases of China(Nos.2017ZX10202202,2017ZX10202203)Beijing Natural Science Foundation(7182079).
文摘Dear Editor,Hepatitis B virus(HBV)infection remains a major cause of liver diseases worldwide,which affects approximately 250 million people globally(Yuen et al.2018).Individuals with chronic HBV infection are at high risk of developing liver cirrhosis,and ultimately hepatocellular carcinoma(HCC).HBV is a Hepadnavirus DNA virus,which specifically infects and efficiently replicates in hepatocytes.It has been proposed for decades that HBV replicates preferentially in non-dividing quiescent hepatocytes(Ozer et al.1996).
基金supported by grants from the Natural Science Foundation of China (No. 8214100646)Construction Project of Highlevel Technology Talents in Public Health (Discipline leader-01-12)
文摘On April 5,2022,United Kingdom(UK)reported 10 cases of severe acute hepatitis with unknown cause among children under 10 years old.The initial symptoms of these cases could date back to March 2022.A rapidly increasing number of cases lasted for a month and the growth seems to be slightly slowing down in May.As of May 27,2022,the total number of children with acute hepatitis in UK reached to 222(UKHSA,2022a).European Union and European Economic Area reported 305 cases across 17 countries and none as epidemiologically linked as of May 31,2022(ECDC-WHO,2022).
基金We are grateful for the support by the National Key R&D Program of China(2021YFC2301700)National Science and Technology Major Projects of Infectious Disease funds(2017ZX103304402)。
文摘COVID-19,caused by SARS-CoV-2,is the most consequential pandemic of this century.Since the outbreak in late 2019,animal models have been playing crucial roles in aiding the rapid development of vaccines/drugs for prevention and therapy,as well as understanding the pathogenesis of SARS-CoV-2 infection and immune responses of hosts.However,the current animal models have some deficits and there is an urgent need for novel models to evaluate the virulence of variants of concerns(VOC),antibodydependent enhancement(ADE),and various comorbidities of COVID-19.This review summarizes the clinical features of COVID-19 in different populations,and the characteristics of the major animal models of SARS-CoV-2,including those naturally susceptible animals,such as non-human primates,Syrian hamster,ferret,minks,poultry,livestock,and mouse models sensitized by genetically modified,AAV/adenoviral transduced,mouse-adapted strain of SARS-CoV-2,and by engraftment of human tissues or cells.Since understanding the host receptors and proteases is essential for designing advanced genetically modified animal models,successful studies on receptors and proteases are also reviewed.Several improved alternatives for future mouse models are proposed,including the reselection of alternative receptor genes or multiple gene combinations,the use of transgenic or knock-in method,and different strains for establishing the next generation of genetically modified mice.
