AIM To build a regional database of chronic patients to define the clinical epidemiology of hepatitis B virus(HBV)-infected patients in the Tuscan public health care system.METHODS This study used a cross-sectional co...AIM To build a regional database of chronic patients to define the clinical epidemiology of hepatitis B virus(HBV)-infected patients in the Tuscan public health care system.METHODS This study used a cross-sectional cohort design. We evaluated chronic viral hepatitis patients with HBV referred to the outpatient services of 16 hospital units. Information in the case report forms included main demographic data, blood chemistry data, viral hepatitis markers, instrumental evaluations, and eligibility for treatment or ongoing therapy and liver transplantation. RESULTS Of 4015 chronic viral hepatitis patients, 1096(27.3%) were HBV infected. The case report form was correctly completed for only 833 patients(64% males, 36% females; mean age 50.1 ± 15.4). Of these HBV-infected patients, 73% were Caucasian, 21% Asian, 4% Central African, 1% North African and 1% American. Stratifying patients by age and nationality, we found that 21.7% of HBV-infected patients were aged < 34 years(only 2.8% were Italian). The most represented routes of transmission were nosocomial/dental procedures(23%), mother-to-child(17%) and sexual transmission(12%). The most represented HBV genotypes were D(72%) and A(14%). Of the patients, 24.7% of patients were HBe Ag positive, and 75.3% were HBe Ag negative. Of the HBV patients 7% were anti-HDV positive. In the whole cohort, 26.9% were cirrhotic(35.8% aged < 45 years), and 47% were eligible for or currently undergoing treatment, of whom 41.9 % were cirrhotic. CONCLUSION Only 27.3% of chronic viral hepatitis patients were HBV infected. Our results provide evidence of HBV infection in people aged < 34 years, especially in the foreign population not protected by vaccination. In our cohort of patients, liver cirrhosis was also found in young adults.展开更多
BACKGROUND Disease-related single nucleotide polymorphisms(SNPs)based genetic risk score(GRS)has been proven to provide independent inherited risk other than family history in multiple cancer types.AIM To evaluate the...BACKGROUND Disease-related single nucleotide polymorphisms(SNPs)based genetic risk score(GRS)has been proven to provide independent inherited risk other than family history in multiple cancer types.AIM To evaluate the potential of GRS in the prediction of pancreatic cancer risk.METHODS In this case-control study(254 cases and 1200 controls),we aimed to evaluate the association between GRS and pancreatic ductal adenocarcinoma(PDAC)risk in the Chinese population.The GRS was calculated based on the genotype information of 18 PDAC-related SNPs for each study subject(personal genotyping information of the SNPs)and was weighted by external odd ratios(ORs).RESULTS GRS was significantly different in cases and controls(1.96±3.84 in PDACs vs 1.09±0.94 in controls,P<0.0001).Logistic regression revealed GRS to be associated with PDAC risk[OR=1.23,95%confidence interval(CI):1.13-1.34,P<0.0001].GRS remained significantly associated with PDAC(OR=1.36,95%CI:1.06-1.74,P=0.015)after adjusting for age and sex.Further analysis revealed an association of increased risk for PDAC with higher GRS.Compared with low GRS(<1.0),subjects with high GRS(2.0)were 99%more likely to have PDAC(OR:1.99,95%CI:1.30-3.04,P=0.002).Participants with intermediate GRS(1.0-1.9)were 39%more likely to have PDAC(OR:1.39,95%CI:1.03-1.84,P=0.031).A positive trend was observed(P trend=0.0006).CONCLUSION GRS based on PDAC-associated SNPs could provide independent information on PDAC risk and may be used to predict a high risk PDAC population.展开更多
Objective: To determine the frequency of anti-HCV antibody positivity in patients with nonliver disease complaints, to explore whether anti-HCV positive patients had been properly advised and visited hepatologists for...Objective: To determine the frequency of anti-HCV antibody positivity in patients with nonliver disease complaints, to explore whether anti-HCV positive patients had been properly advised and visited hepatologists for further assessments, and to investigate their clinical characteristics as well as the HCV treatment status.Methods: A hospital based survey of nonliver disease patients with anti-HCV positive and their attending physicians was conducted to determine: 1.were the patients adequately advised of the implication of anti-HCV positive finding; 2.to what extent the patients were aware of potential chronic liver disease associated with HCV infection and whether they sought for further assessments and care of hepatologists.Results: A total of 295 294 non-liver disease patients were tested for anti-HCV antibody, and 2 778 of them were found to be positive(0.94%).However, only 45.10%(1 253/2 778) of the anti-HCV antibody(+) patients were referred to hepatologists and received HCV RNA test.In addition, 34.10%(312/915) and 1.42%(13/915) of them had already advanced to cirrhosis and hepatocellular carcinoma(HCC), respectively.Further analysis showed that the patients who declined antiviral therapy were older, with lower education and lower income, possessed poorer knowledge on the risk of chronic hepatitis C, and had more severe liver diseases.Surprisingly, 65% of the surveyed physicians did not know the genotype-guided treatment duration suggested by the guidelines.Alarmingly, 22% of the surveyed physicians did not know the standard assays for the diagnosis of HCV infection.Conclusions: Our findings highlight the challenge and hidden enormous burden of chronic HCV infection among patients with non-liver disease complaints in China.展开更多
Background and Aims:Tenofovir amibufenamide(TMF)is a novel phosphoramidated prodrug of tenofovir with nonin-ferior efficacy and better bone and renal safety to tenofovir disoproxil fumarate(TDF)in 48 weeks of treatmen...Background and Aims:Tenofovir amibufenamide(TMF)is a novel phosphoramidated prodrug of tenofovir with nonin-ferior efficacy and better bone and renal safety to tenofovir disoproxil fumarate(TDF)in 48 weeks of treatment.Here,we update 96-week comparison results.Methods:Patients with chronic hepatitis B were assigned(2:1)to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks.The virological suppression was defined as HBV DNA levels<20 IU/mL at week 96.Safety was evaluated thoroughly with focusing on bone,renal,and metabolic pa-rameters.Results:Virological suppression rates at week 96 were similar between TMF and TDF group in both HBeAg-positive and HBeAg-negative populations.Noninferior efficacy was maintained in the pooled population,while it was first achieved in patients with HBV DNA≥7 or 8 log10 IU/mL at baseline.Non-indexed estimated glomerular filtration rate for renal safety assessment was adopted,while a smaller decline of which was seen in the TMF group than in the TDF group(p=0.01).For bone mineral density,patients receiv-ing TMF displayed significantly lower reduction levels in the densities of spine,hip,and femur neck at week 96 than those receiving TDF.In addition,the lipid parameters were stable after week 48 in all groups while weight change still showed the opposite trend.Conclusions:TMF maintained similar efficacy at week 96 compared with TDF with continued superior bone and renal safety profiles(NCT03903796).展开更多
Background and Aims:Numerous studies have explored the important role of N6-methyladenosine(m^(6)A)in cancer.Nonetheless,the interaction between m^(6)A and long noncoding RNAs(lncRNAs)is poorly investigated.Herein,we ...Background and Aims:Numerous studies have explored the important role of N6-methyladenosine(m^(6)A)in cancer.Nonetheless,the interaction between m^(6)A and long noncoding RNAs(lncRNAs)is poorly investigated.Herein,we systematically analyzed the role and prognostic value of m^(6)A-related lncRNAs in hepatocellular carcinoma(HCC).Methods:The m^(6)A-related lncRNAs were identified based on the correlation coefficients with m^(6)A-related genes in HCC from The Cancer Genome Atlas.Subsequently,a novel risk score model was determined using the least absolute shrinkage and selection operator Cox regression analyses.Univariate and multivariate Cox analyses were used to identify independent prog-nostic factors for overall survival(OS)of HCC;thereafter,a prognostic nomogram was constructed.Results:A total of 259 lncRNAs showed significant correlations with m^(6)A in HCC,while 29 lncRNAs had prognostic significance.Further,six critical m^(6)A-related lncRNAs(NRAV,SNHG3,KDM4A-AS1,AC074117.1,AC025176.1,and AL031985.3)were screened out to construct a novel risk score model which classified HCC patients into high-and low-risk groups.Survival analy-ses revealed that patients in the high-risk group exhibited worse OS,both in the training and validation groups.The risk score was also identified as an independent prognostic factor of OS,and a nomogram was established and verified with superior prediction capacity.Besides,the risk score signifi-cantly correlated with the expression of immune checkpoint genes and immune subtypes.Conclusions:These findings indicated the significant role of m^(6)A-related lncRNAs in HCC and the potential application of the novel risk score model for prognostic prediction.展开更多
Background:It is well established that obesity is a disease of sustained low-grade inflammation.However,it is currently unknown if obesity plays a role in the clinical manifestations and prognosis of severe acute resp...Background:It is well established that obesity is a disease of sustained low-grade inflammation.However,it is currently unknown if obesity plays a role in the clinical manifestations and prognosis of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infected patients.In this study,we aimed to investigate whether obesity played a role in clinical manifestations and prognosis in patients infected with SARS-CoV-2.Methods:This is a retrospective multicenter clinical study.A total of 96 patients hospitalized with SARS-CoV-2 infection were enrolled from Dongguan People’s Hospital,Nanfang hospital and the First Affiliated Hospital of Xiamen University between 23 January and 14 February 2020.Demographic and clinical data were extracted from medical records.Acute respiratory distress syndrome(ARDS)was defined as oxygenation index(PaO2/FiO2)≤300 mmHg.We grouped patients through the body mass index(BMI).Associations were examined using the t test,χ2 test and multivariate logistic forward regression test.Results:Patients with BMI<24 were significantly younger(P=0.025)with lower creatine kinase(P=0.013),lower diastolic pressure blood(P=0.035),lower serum creatinine(P=0.012),lower lactate dehydrogenase(P=0.001)and higher platelet count(P=0.002).The BMI level was 20.78±3.15 in patients without pneumonia compared with the patients with pneumonia(23.81±3.49,P=0.001).For patients without ARDS,an average BMI level of 22.65±3.53 was observed,significantly lower than patients with ARDS(24.57±3.59,P=0.022).The mean BMI was 22.35±3.56 in patients experienced with relieving the clinical symptoms or stable condition by radiographic tests,lower than patients with disease exacerbation with 24.89±3.17(P=0.001).In addition,lymphocyte count(r=−0.23,P=0.027)and platelet count(r=−0.44,P<0.001)were negatively correlated with BMI.While hemoglobin(r=0.267,P=0.008),creatine kinase(r=0.331,P=0.001),serum creatinine(r=0.424,P<0.001)and lactate dehydrogenase(r=0.343,P=0.001)were significantly positive correlated with BMI.Multivariate analysis showed that older age(OR=1.046,P=0.009)and BMI≥24(OR=1.258,P=0.005)were independent risk factors associated ICU admission while BMI≥24(OR=4.219,P=0.007)was independent risk factor associated with radiographic disease exacerbation.Conclusions:Our study found BMI was significantly associated with clinical manifestations and prognosis of patients with SARS-CoV-2 infection.For patients with increased risk,clinicians should intervene promptly to avoid disease progression.展开更多
Background and aim:Real-world data on the effectiveness and safety of treatment with the direct-acting antiviral agent-based regimen are limited on the Chinese mainland.The aim of this study was to conduct a multicent...Background and aim:Real-world data on the effectiveness and safety of treatment with the direct-acting antiviral agent-based regimen are limited on the Chinese mainland.The aim of this study was to conduct a multicenter,prospective,real-world study of ombitasvir/paritaprevir/ritonavir(OBT/PTV/r)combined with dasabuvir(DSV)in hepatitis C virus(HCV)genotype 1b-infected non-cirrhotic or compensated cirrhotic Chinese adult patients.Materials and methods:Genotype 1b-infected patients were enrolled at eight sites in China.Patients received 25/150/100 mg of OBT/PTV/r once daily combined with 250 mg of DSV twice daily for 8 weeks or 12 weeks.Sustained virological response at 12 weeks post-treatment(SVR12)and the incidence of adverse events were assessed.We have also evaluated the effect of intensive questioning of patients who were overdue for SVR12 testing.Intention-to-treat(ITT)and modified ITT(mITT)populations were used in the analysis.Results:One hundred forty patients were included,among whom 90.0%(126/140)were newly diagnosed,9.3%(13/140)had compensated cirrhosis,92.9%(130/140)received 12 weeks of treatment,and 7.1%(10/140)received 8 weeks of treatment.In the mITT population,the virological response rate at week 4 was 96.4%(108/112),and at the end of treatment was 100%(102/102).Among these patients,139 patients completed 12 weeks of treatment,and 73 patients were followed-up.All followed-up patients achieved SVR12.There was no adverse event-related discontinuation.Serious adverse events during treatment were reported in two(1.4%)patients,and none were considered to be drug-related.Sixty-six(47.1%)patients did not return to receive the HCV RNA test at 12 weeks post-treatment.Conclusions:The rate of SVR12 was consistent with Phase III clinical studies.OBT/PTV/r combined with DSV showed effectiveness in Chinese adult patients,and both tolerability and safety profile were favorable.However,patient compliance should be further improved in the real world.展开更多
Evaluation of the extent and progression of liver fibrosis and cirrhosis is of critical importance in the management and prognosis of patients with chronic hepatitis B.Due to the limitation of liver biopsy,non-invasiv...Evaluation of the extent and progression of liver fibrosis and cirrhosis is of critical importance in the management and prognosis of patients with chronic hepatitis B.Due to the limitation of liver biopsy,non-invasive methods,especially liver stiffness measurement (LSM) by vibration controlled transient elastography,have been developed and widely applied for liver fibrosis assessment.LSM aims to reduce,but not to substitute,the need for liver biopsy for fibrosis/cirrhosis diagnosis.While LSM may have potential utility in monitoring treatment response,its applications in prediction of liver complications in terms of portal hypertension and esophageal varices,as well as disease prognosis,have been gradually validated.Here,we review the latest clinical applications of LSM in patients with chronic hepatitis B.展开更多
I nterleukin （I L）-21, a cytokine produced by activated CD4＋ T cells, has broad pleiotropic actions that affect the functions of a variety of lymphoid cells. The roles of IL-21 in modulating immunity to infections ...I nterleukin （I L）-21, a cytokine produced by activated CD4＋ T cells, has broad pleiotropic actions that affect the functions of a variety of lymphoid cells. The roles of IL-21 in modulating immunity to infections are currently being defined. Notably, IL-21-mediated cellular and humoral immune responses play an important role in determining the outcome of viral infection. This article reviews the current knowledge on the critical role of IL-21 in hepatitis B virus （HBV） infection. As a competent intermediary, IL-21 derived from virus-specific CD4＋ T cells plays key roles in sustaining CD8＋ T cells and promoting B-cell responses that are essential for effective viral control. However, as a mediator of inflammation, I L-21 is also involved in the development of HBV-induced liver cirrhosis and exacerbating liver injury. Overall, the current data point to IL-21 as an immunomodulatory cytokine in HBV infection. Immunotherapeutic strategies aimed at optimizing the beneficial effects of IL-21 in HBV infection may prove to be a rigorous challenge in the future, as they should foster the strengths of IL-21 while circumventing potential drawbacks.展开更多
Background and Aims:Hepatitis B surface antigen(HBsAg)loss is seldom achieved with nucleos(t)ide analog(NA)therapy in chronic hepatitis B patients but may be enhanced by switching to finite pegylated-interferon(Peg-IF...Background and Aims:Hepatitis B surface antigen(HBsAg)loss is seldom achieved with nucleos(t)ide analog(NA)therapy in chronic hepatitis B patients but may be enhanced by switching to finite pegylated-interferon(Peg-IFN)alfa-2a.We assessed HBsAg loss with 48-and 96-week Peg-IFN alfa-2a in chronic hepatitis B patients with partial response to a previous NA.Methods:Hepatitis B e antigen(HBeAg)-positive patients who achieved HBeAg loss and hepatitis B virus DNA<200 IU/mL with previous adefovir,lamivudine or entecavir treatment were randomized 1:1 to receive Peg-IFN alfa-2a for 48(n=153)or 96 weeks(n=150).The primary endpoint of this study was HBsAg loss at end of treatment.The ClinicalTrials.gov identifier is NCT01464281.Results:At the end of 48 and 96 weeks'treatment,14.4%(22/153)and 20.7%(31/150)of patients,respectively,who switched from NA to Peg-IFN alfa-2a cleared HBsAg.Rates were similar irrespective of prior NA or baseline HBeAg seroconversion.Among those who cleared HBsAg by the end of 48 and 96 weeks'treatment,77.8%(14/18)and 71.4%(20/28),respectively,sustained HBsAg loss for a further 48 weeks.Baseline HBsAg<1500 IU/mL and week 24 HBsAg<200 IU/mL were associated with the highest rates of HBsAg loss at the end of both 48-and 96-week treatment(51.4%and 58.7%,respectively).Importantly,extending treatment from 48 to 96 weeks enabled 48.3%(14/29)more patients to achieve HBsAg loss.Conclusions:Patients on long-term NA who are unlikely to meet therapeutic goals can achieve high rates of HBsAg loss by switching to Peg-IFN alfa-2a.HBsAg loss rates may be improved for some patients by extending treatment from 48 to 96 weeks,although the differences in our study cohort were not statistically significant.Baseline and on-treatment HBsAg may predict HBsAg loss with Peg-IFN alfa-2a.展开更多
Background and Aims:Only a small percentage of chronic hepatitis B(CHB)patients effectively respond to treatment with pegylated-interferon alpha(PegIFNα)or nucleos(t)ide analogues(NUCs).We aimed to detect the correla...Background and Aims:Only a small percentage of chronic hepatitis B(CHB)patients effectively respond to treatment with pegylated-interferon alpha(PegIFNα)or nucleos(t)ide analogues(NUCs).We aimed to detect the correlations of complement regulators-associated single-nucleotide polymorphisms(SNPs)with treatment response of hepatitis B e antigen(HBeAg)-positive CHB patients.Methods:A total of 1,763 HBeAg-positive CHB patients were enrolled,894 received PegIFNαfor at least 48 weeks and were followed up for 24 weeks,and 869 received NUCs for 104 weeks.For each patient,nine SNPs in genes encoding for complement regulators were determined and genotyped.To assess the cumulative effect of numerous SNPs,a polygenic score(PGS)was utilized.The correlations of SNPs and PGS with the levels of combined response(CR)and hepatitis B s antigen(HBsAg)loss were also investigated.Results:In PegIFNα-treated patients,an intronic SNP of CD55,rs28371597,was strongly related to CR,and the CR rate in rs28371597_GG genotype carriers was only approximately half that of rs28371597_GT/TT genotype carriers(20.29%vs.37.10%,p=2.00×10^(−3)).A PGS incorporating CD55_rs28371597 and two additional SNPs,CFB_rs12614 and STAT4_rs7574865,which had been considered as predictors for PegIFNαtreatment response before,was strongly correlated with the levels of CR(ptrend=7.94×10^(−6))and HBsAg loss(p-trend=9.40×10^(−3))in PegIFNα-treated patients.In NUCs-treated individuals,however,none of the nine SNPs were shown to be significantly linked to CHB treatment response.Conclusions:CD55_rs28371597 is a promising biomarker for predicting CHB patients’responsiveness to PegIFNαtherapy.The updated PGS may be used for optimizing CHB treatment.展开更多
Type 1 diabetes mellitus （T1D） is an immune-mediated disease. The autoreactive T cells in T1D patients attack and destroy their own pancreatic cells. In order to systematically investigate the potential autoreactive...Type 1 diabetes mellitus （T1D） is an immune-mediated disease. The autoreactive T cells in T1D patients attack and destroy their own pancreatic cells. In order to systematically investigate the potential autoreactive T cell receptors （TCRs）, we used a high-throughput immune repertoire sequencing technique to profile the spectrum of TCRs in individual T1D patients and controls. We sequenced the T cell repertoire of nine T1D patients, four type 2 diabetes （T2D） patients,and six nondiabetic controls. The diversity of the T cell repertoire in T1D patients was significantly decreased in comparison with T2D patients （P = 7.0E-08 for CD4＋ T cells, P = 1.4E-04 for CD8＋ T cells） and nondiabetic controls （P = 2.7E-09 for CD4＋ T cells, P = 7.6E-06 for CD8 ＋ T cells）. Moreover, T1D patients had significantly more highly-expanded T cell clones than T2D patients （P = 5.2E-06 for CD4＋ T cells, P = 1.9E-07 for CD8＋ T cells） and nondiabetic controls （P = 1.7E-07 for CD4＋ T cells, P =Y3E-03 for CD8＋ T cells）. Furthermore, we iden- tified a group of highly-expanded T cell receptor clones that are shared by more than two TID patients. Although further validation in larger cohorts is needed, our data suggest that T cell receptor diversity measurements may become a valuable tool in investigating diabetes, such as using the diversity as an index to distinguish different types of diabetes.展开更多
Background:Hepatocellular carcinoma(HCC)is one of the most common cancers worldwide and is prevalent in East Asia.Although genome-wide association studies(GWASs)of HCC have identified 23 risk regions,the susceptibilit...Background:Hepatocellular carcinoma(HCC)is one of the most common cancers worldwide and is prevalent in East Asia.Although genome-wide association studies(GWASs)of HCC have identified 23 risk regions,the susceptibility genes underlying these associa-tions largely remain unclear.To identify novel candidate genes for HCC,we conducted liver single-tissue and cross-tissue transcrip-tomewide association studies(TWASs)in two populations of East Asia.Methods:GWAS summary statistics of 2,514 subjects(1,161 HCC cases and 1,353 controls)from the Chinese Qidong cohort and 161,323 subjects(2,122 HCC cases and 159,201 controls)from the BioBank Japan project were used to conduct TWAS analysis.The single-tissue and cross-tissue TWAS approaches were both used to detect the association between susceptible genes and the risk of HCC.TWAS identified genes were further annotated by Metascape,UALCAN,GEPIA2,and DepMap.Results:We identified 22 novel genes at 16 independent loci significantly associated with HCC risk after Bonferroni correction.Of these,13 genes were located in novel regions.Besides,we found 83 genes overlapped in the Chinese and Japanese cohorts with P<0.05,of which,three genes(NUAK2,HLA-DQA1,and ATP6V1G2)were discerned by both single-tissue and cross-tissue TWAS approaches.Among the genes identified through TWAS,a significant proportion of them exhibit a credible role in HCC biology,such as FAM96B,HSPA5,POLRMT,MPHOSPH10,and RABL2A.HLA-DQA1,NUAK2,and HSPA5 associated with the process of carcinogenesis in HCC as previously reported.Conclusions:Our findings highlight the value of leveraging the gene expression data to identify new candidate genes beyond the GWAS associations and could further provide a genetic insight for the biology of HCC.展开更多
文摘AIM To build a regional database of chronic patients to define the clinical epidemiology of hepatitis B virus(HBV)-infected patients in the Tuscan public health care system.METHODS This study used a cross-sectional cohort design. We evaluated chronic viral hepatitis patients with HBV referred to the outpatient services of 16 hospital units. Information in the case report forms included main demographic data, blood chemistry data, viral hepatitis markers, instrumental evaluations, and eligibility for treatment or ongoing therapy and liver transplantation. RESULTS Of 4015 chronic viral hepatitis patients, 1096(27.3%) were HBV infected. The case report form was correctly completed for only 833 patients(64% males, 36% females; mean age 50.1 ± 15.4). Of these HBV-infected patients, 73% were Caucasian, 21% Asian, 4% Central African, 1% North African and 1% American. Stratifying patients by age and nationality, we found that 21.7% of HBV-infected patients were aged < 34 years(only 2.8% were Italian). The most represented routes of transmission were nosocomial/dental procedures(23%), mother-to-child(17%) and sexual transmission(12%). The most represented HBV genotypes were D(72%) and A(14%). Of the patients, 24.7% of patients were HBe Ag positive, and 75.3% were HBe Ag negative. Of the HBV patients 7% were anti-HDV positive. In the whole cohort, 26.9% were cirrhotic(35.8% aged < 45 years), and 47% were eligible for or currently undergoing treatment, of whom 41.9 % were cirrhotic. CONCLUSION Only 27.3% of chronic viral hepatitis patients were HBV infected. Our results provide evidence of HBV infection in people aged < 34 years, especially in the foreign population not protected by vaccination. In our cohort of patients, liver cirrhosis was also found in young adults.
文摘BACKGROUND Disease-related single nucleotide polymorphisms(SNPs)based genetic risk score(GRS)has been proven to provide independent inherited risk other than family history in multiple cancer types.AIM To evaluate the potential of GRS in the prediction of pancreatic cancer risk.METHODS In this case-control study(254 cases and 1200 controls),we aimed to evaluate the association between GRS and pancreatic ductal adenocarcinoma(PDAC)risk in the Chinese population.The GRS was calculated based on the genotype information of 18 PDAC-related SNPs for each study subject(personal genotyping information of the SNPs)and was weighted by external odd ratios(ORs).RESULTS GRS was significantly different in cases and controls(1.96±3.84 in PDACs vs 1.09±0.94 in controls,P<0.0001).Logistic regression revealed GRS to be associated with PDAC risk[OR=1.23,95%confidence interval(CI):1.13-1.34,P<0.0001].GRS remained significantly associated with PDAC(OR=1.36,95%CI:1.06-1.74,P=0.015)after adjusting for age and sex.Further analysis revealed an association of increased risk for PDAC with higher GRS.Compared with low GRS(<1.0),subjects with high GRS(2.0)were 99%more likely to have PDAC(OR:1.99,95%CI:1.30-3.04,P=0.002).Participants with intermediate GRS(1.0-1.9)were 39%more likely to have PDAC(OR:1.39,95%CI:1.03-1.84,P=0.031).A positive trend was observed(P trend=0.0006).CONCLUSION GRS based on PDAC-associated SNPs could provide independent information on PDAC risk and may be used to predict a high risk PDAC population.
基金partly supported by the grants from the National Natural Science Foundation of China(81470856,81772923,31470263 and 81360001)
文摘Objective: To determine the frequency of anti-HCV antibody positivity in patients with nonliver disease complaints, to explore whether anti-HCV positive patients had been properly advised and visited hepatologists for further assessments, and to investigate their clinical characteristics as well as the HCV treatment status.Methods: A hospital based survey of nonliver disease patients with anti-HCV positive and their attending physicians was conducted to determine: 1.were the patients adequately advised of the implication of anti-HCV positive finding; 2.to what extent the patients were aware of potential chronic liver disease associated with HCV infection and whether they sought for further assessments and care of hepatologists.Results: A total of 295 294 non-liver disease patients were tested for anti-HCV antibody, and 2 778 of them were found to be positive(0.94%).However, only 45.10%(1 253/2 778) of the anti-HCV antibody(+) patients were referred to hepatologists and received HCV RNA test.In addition, 34.10%(312/915) and 1.42%(13/915) of them had already advanced to cirrhosis and hepatocellular carcinoma(HCC), respectively.Further analysis showed that the patients who declined antiviral therapy were older, with lower education and lower income, possessed poorer knowledge on the risk of chronic hepatitis C, and had more severe liver diseases.Surprisingly, 65% of the surveyed physicians did not know the genotype-guided treatment duration suggested by the guidelines.Alarmingly, 22% of the surveyed physicians did not know the standard assays for the diagnosis of HCV infection.Conclusions: Our findings highlight the challenge and hidden enormous burden of chronic HCV infection among patients with non-liver disease complaints in China.
文摘Background and Aims:Tenofovir amibufenamide(TMF)is a novel phosphoramidated prodrug of tenofovir with nonin-ferior efficacy and better bone and renal safety to tenofovir disoproxil fumarate(TDF)in 48 weeks of treatment.Here,we update 96-week comparison results.Methods:Patients with chronic hepatitis B were assigned(2:1)to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks.The virological suppression was defined as HBV DNA levels<20 IU/mL at week 96.Safety was evaluated thoroughly with focusing on bone,renal,and metabolic pa-rameters.Results:Virological suppression rates at week 96 were similar between TMF and TDF group in both HBeAg-positive and HBeAg-negative populations.Noninferior efficacy was maintained in the pooled population,while it was first achieved in patients with HBV DNA≥7 or 8 log10 IU/mL at baseline.Non-indexed estimated glomerular filtration rate for renal safety assessment was adopted,while a smaller decline of which was seen in the TMF group than in the TDF group(p=0.01).For bone mineral density,patients receiv-ing TMF displayed significantly lower reduction levels in the densities of spine,hip,and femur neck at week 96 than those receiving TDF.In addition,the lipid parameters were stable after week 48 in all groups while weight change still showed the opposite trend.Conclusions:TMF maintained similar efficacy at week 96 compared with TDF with continued superior bone and renal safety profiles(NCT03903796).
基金supported in part by grants from the GuangdongGuang-dong Natural Science Foundation(Nos.2015A030313038,2015A030312013)Science and Technology Program of Guangzhou City(No.201607010024)Guangdong Key Laboratory of Liver Disease Research(No.2017B030314027).
文摘Background and Aims:Numerous studies have explored the important role of N6-methyladenosine(m^(6)A)in cancer.Nonetheless,the interaction between m^(6)A and long noncoding RNAs(lncRNAs)is poorly investigated.Herein,we systematically analyzed the role and prognostic value of m^(6)A-related lncRNAs in hepatocellular carcinoma(HCC).Methods:The m^(6)A-related lncRNAs were identified based on the correlation coefficients with m^(6)A-related genes in HCC from The Cancer Genome Atlas.Subsequently,a novel risk score model was determined using the least absolute shrinkage and selection operator Cox regression analyses.Univariate and multivariate Cox analyses were used to identify independent prog-nostic factors for overall survival(OS)of HCC;thereafter,a prognostic nomogram was constructed.Results:A total of 259 lncRNAs showed significant correlations with m^(6)A in HCC,while 29 lncRNAs had prognostic significance.Further,six critical m^(6)A-related lncRNAs(NRAV,SNHG3,KDM4A-AS1,AC074117.1,AC025176.1,and AL031985.3)were screened out to construct a novel risk score model which classified HCC patients into high-and low-risk groups.Survival analy-ses revealed that patients in the high-risk group exhibited worse OS,both in the training and validation groups.The risk score was also identified as an independent prognostic factor of OS,and a nomogram was established and verified with superior prediction capacity.Besides,the risk score signifi-cantly correlated with the expression of immune checkpoint genes and immune subtypes.Conclusions:These findings indicated the significant role of m^(6)A-related lncRNAs in HCC and the potential application of the novel risk score model for prognostic prediction.
基金This work was supported by the grants from the Major Science and Technology Special Project of China(2017ZX09304016,2017ZX10302201004008)the National Natural Science Foundation of China(81971949)the Clinical Research Startup Program of Southern Medical University by High-level University Construction Funding of Guangdong Provincial Department of Education(LC2016PY003).
文摘Background:It is well established that obesity is a disease of sustained low-grade inflammation.However,it is currently unknown if obesity plays a role in the clinical manifestations and prognosis of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infected patients.In this study,we aimed to investigate whether obesity played a role in clinical manifestations and prognosis in patients infected with SARS-CoV-2.Methods:This is a retrospective multicenter clinical study.A total of 96 patients hospitalized with SARS-CoV-2 infection were enrolled from Dongguan People’s Hospital,Nanfang hospital and the First Affiliated Hospital of Xiamen University between 23 January and 14 February 2020.Demographic and clinical data were extracted from medical records.Acute respiratory distress syndrome(ARDS)was defined as oxygenation index(PaO2/FiO2)≤300 mmHg.We grouped patients through the body mass index(BMI).Associations were examined using the t test,χ2 test and multivariate logistic forward regression test.Results:Patients with BMI<24 were significantly younger(P=0.025)with lower creatine kinase(P=0.013),lower diastolic pressure blood(P=0.035),lower serum creatinine(P=0.012),lower lactate dehydrogenase(P=0.001)and higher platelet count(P=0.002).The BMI level was 20.78±3.15 in patients without pneumonia compared with the patients with pneumonia(23.81±3.49,P=0.001).For patients without ARDS,an average BMI level of 22.65±3.53 was observed,significantly lower than patients with ARDS(24.57±3.59,P=0.022).The mean BMI was 22.35±3.56 in patients experienced with relieving the clinical symptoms or stable condition by radiographic tests,lower than patients with disease exacerbation with 24.89±3.17(P=0.001).In addition,lymphocyte count(r=−0.23,P=0.027)and platelet count(r=−0.44,P<0.001)were negatively correlated with BMI.While hemoglobin(r=0.267,P=0.008),creatine kinase(r=0.331,P=0.001),serum creatinine(r=0.424,P<0.001)and lactate dehydrogenase(r=0.343,P=0.001)were significantly positive correlated with BMI.Multivariate analysis showed that older age(OR=1.046,P=0.009)and BMI≥24(OR=1.258,P=0.005)were independent risk factors associated ICU admission while BMI≥24(OR=4.219,P=0.007)was independent risk factor associated with radiographic disease exacerbation.Conclusions:Our study found BMI was significantly associated with clinical manifestations and prognosis of patients with SARS-CoV-2 infection.For patients with increased risk,clinicians should intervene promptly to avoid disease progression.
基金This work was supported by a grant for clinical investigation from Key Projects of Guangdong Science and Technology Plan of China(2014B020212025).
文摘Background and aim:Real-world data on the effectiveness and safety of treatment with the direct-acting antiviral agent-based regimen are limited on the Chinese mainland.The aim of this study was to conduct a multicenter,prospective,real-world study of ombitasvir/paritaprevir/ritonavir(OBT/PTV/r)combined with dasabuvir(DSV)in hepatitis C virus(HCV)genotype 1b-infected non-cirrhotic or compensated cirrhotic Chinese adult patients.Materials and methods:Genotype 1b-infected patients were enrolled at eight sites in China.Patients received 25/150/100 mg of OBT/PTV/r once daily combined with 250 mg of DSV twice daily for 8 weeks or 12 weeks.Sustained virological response at 12 weeks post-treatment(SVR12)and the incidence of adverse events were assessed.We have also evaluated the effect of intensive questioning of patients who were overdue for SVR12 testing.Intention-to-treat(ITT)and modified ITT(mITT)populations were used in the analysis.Results:One hundred forty patients were included,among whom 90.0%(126/140)were newly diagnosed,9.3%(13/140)had compensated cirrhosis,92.9%(130/140)received 12 weeks of treatment,and 7.1%(10/140)received 8 weeks of treatment.In the mITT population,the virological response rate at week 4 was 96.4%(108/112),and at the end of treatment was 100%(102/102).Among these patients,139 patients completed 12 weeks of treatment,and 73 patients were followed-up.All followed-up patients achieved SVR12.There was no adverse event-related discontinuation.Serious adverse events during treatment were reported in two(1.4%)patients,and none were considered to be drug-related.Sixty-six(47.1%)patients did not return to receive the HCV RNA test at 12 weeks post-treatment.Conclusions:The rate of SVR12 was consistent with Phase III clinical studies.OBT/PTV/r combined with DSV showed effectiveness in Chinese adult patients,and both tolerability and safety profile were favorable.However,patient compliance should be further improved in the real world.
基金This study was funded by the National Science and Technology Major Project(2013ZX10002004 to YPC)the Dean's Fund of Nanfang Hospital(2015C022 to XEL)
文摘Evaluation of the extent and progression of liver fibrosis and cirrhosis is of critical importance in the management and prognosis of patients with chronic hepatitis B.Due to the limitation of liver biopsy,non-invasive methods,especially liver stiffness measurement (LSM) by vibration controlled transient elastography,have been developed and widely applied for liver fibrosis assessment.LSM aims to reduce,but not to substitute,the need for liver biopsy for fibrosis/cirrhosis diagnosis.While LSM may have potential utility in monitoring treatment response,its applications in prediction of liver complications in terms of portal hypertension and esophageal varices,as well as disease prognosis,have been gradually validated.Here,we review the latest clinical applications of LSM in patients with chronic hepatitis B.
基金The authors express their sincere thanks to Drs Xiaoyong Zhang and Chris Kafai Li for their critical comments. This work was supported by the Major Science and Technology Special Project of China （2008ZX10002-004, 2012ZX10002-003 and 2011CB946100） and the National Natural Science Foundation of China （81270025）.
文摘I nterleukin （I L）-21, a cytokine produced by activated CD4＋ T cells, has broad pleiotropic actions that affect the functions of a variety of lymphoid cells. The roles of IL-21 in modulating immunity to infections are currently being defined. Notably, IL-21-mediated cellular and humoral immune responses play an important role in determining the outcome of viral infection. This article reviews the current knowledge on the critical role of IL-21 in hepatitis B virus （HBV） infection. As a competent intermediary, IL-21 derived from virus-specific CD4＋ T cells plays key roles in sustaining CD8＋ T cells and promoting B-cell responses that are essential for effective viral control. However, as a mediator of inflammation, I L-21 is also involved in the development of HBV-induced liver cirrhosis and exacerbating liver injury. Overall, the current data point to IL-21 as an immunomodulatory cytokine in HBV infection. Immunotherapeutic strategies aimed at optimizing the beneficial effects of IL-21 in HBV infection may prove to be a rigorous challenge in the future, as they should foster the strengths of IL-21 while circumventing potential drawbacks.
基金The authors would like to thank the patients and their families for their contribution to this studyThis study was supported by the National Science and Technology Major Project of China(2008ZX10002-006,2012ZX10002007001,2017ZX10202203-007,2017ZX10202203-008)+2 种基金the National Natural Science Foundation of China(81171561,30972584)This study was also supported in part by Shanghai Roche Pharmaceuticals LtdWriting assistance was provided by Stefanie Chuah,from Mudskipper Business Ltd,funded by F Hoffmann-La Roche
文摘Background and Aims:Hepatitis B surface antigen(HBsAg)loss is seldom achieved with nucleos(t)ide analog(NA)therapy in chronic hepatitis B patients but may be enhanced by switching to finite pegylated-interferon(Peg-IFN)alfa-2a.We assessed HBsAg loss with 48-and 96-week Peg-IFN alfa-2a in chronic hepatitis B patients with partial response to a previous NA.Methods:Hepatitis B e antigen(HBeAg)-positive patients who achieved HBeAg loss and hepatitis B virus DNA<200 IU/mL with previous adefovir,lamivudine or entecavir treatment were randomized 1:1 to receive Peg-IFN alfa-2a for 48(n=153)or 96 weeks(n=150).The primary endpoint of this study was HBsAg loss at end of treatment.The ClinicalTrials.gov identifier is NCT01464281.Results:At the end of 48 and 96 weeks'treatment,14.4%(22/153)and 20.7%(31/150)of patients,respectively,who switched from NA to Peg-IFN alfa-2a cleared HBsAg.Rates were similar irrespective of prior NA or baseline HBeAg seroconversion.Among those who cleared HBsAg by the end of 48 and 96 weeks'treatment,77.8%(14/18)and 71.4%(20/28),respectively,sustained HBsAg loss for a further 48 weeks.Baseline HBsAg<1500 IU/mL and week 24 HBsAg<200 IU/mL were associated with the highest rates of HBsAg loss at the end of both 48-and 96-week treatment(51.4%and 58.7%,respectively).Importantly,extending treatment from 48 to 96 weeks enabled 48.3%(14/29)more patients to achieve HBsAg loss.Conclusions:Patients on long-term NA who are unlikely to meet therapeutic goals can achieve high rates of HBsAg loss by switching to Peg-IFN alfa-2a.HBsAg loss rates may be improved for some patients by extending treatment from 48 to 96 weeks,although the differences in our study cohort were not statistically significant.Baseline and on-treatment HBsAg may predict HBsAg loss with Peg-IFN alfa-2a.
基金supported by the National Science and Technology Major Project (No.2017ZX10202202 to JS and DKJ and 2018ZX10301202 to JH and DKJ)the Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program (No.2017BT01S131 to JH,JS and DKJ)+5 种基金the General Programs from the National Natural Science Foundation of China (No.81472618 to DKJ,81670535 to DKJ,and 81802833 to HC)the General Program from the Natural Science Foundation of Guangdong Province (No.2019A1515011423 to DKJ)the Key-Area Research and Development Program of Guangdong Province (No.2019B020227004 to DKJ)the Innovative Research Team Project of Guangxi Province (No.2017GXNSFGA198002 to DKJ)the Dean Fund of Nanfang Hospital,Southern Medical University (No.2018Z005 to DKJ)the Grant for Recruited Talents to Start Scientific Research from Nanfang Hospital,and the Outstanding Youth Development Scheme of Nanfang Hospital,Southern Medical University (No.2017J001 to DKJ).
文摘Background and Aims:Only a small percentage of chronic hepatitis B(CHB)patients effectively respond to treatment with pegylated-interferon alpha(PegIFNα)or nucleos(t)ide analogues(NUCs).We aimed to detect the correlations of complement regulators-associated single-nucleotide polymorphisms(SNPs)with treatment response of hepatitis B e antigen(HBeAg)-positive CHB patients.Methods:A total of 1,763 HBeAg-positive CHB patients were enrolled,894 received PegIFNαfor at least 48 weeks and were followed up for 24 weeks,and 869 received NUCs for 104 weeks.For each patient,nine SNPs in genes encoding for complement regulators were determined and genotyped.To assess the cumulative effect of numerous SNPs,a polygenic score(PGS)was utilized.The correlations of SNPs and PGS with the levels of combined response(CR)and hepatitis B s antigen(HBsAg)loss were also investigated.Results:In PegIFNα-treated patients,an intronic SNP of CD55,rs28371597,was strongly related to CR,and the CR rate in rs28371597_GG genotype carriers was only approximately half that of rs28371597_GT/TT genotype carriers(20.29%vs.37.10%,p=2.00×10^(−3)).A PGS incorporating CD55_rs28371597 and two additional SNPs,CFB_rs12614 and STAT4_rs7574865,which had been considered as predictors for PegIFNαtreatment response before,was strongly correlated with the levels of CR(ptrend=7.94×10^(−6))and HBsAg loss(p-trend=9.40×10^(−3))in PegIFNα-treated patients.In NUCs-treated individuals,however,none of the nine SNPs were shown to be significantly linked to CHB treatment response.Conclusions:CD55_rs28371597 is a promising biomarker for predicting CHB patients’responsiveness to PegIFNαtherapy.The updated PGS may be used for optimizing CHB treatment.
基金supported by the National Natural Science Foundation of China(Grant Nos.31200688,81470136,31401145,and 81372507)support from the International S&T Cooperation Program of China(Grant No.2014DFA31050)
文摘Type 1 diabetes mellitus （T1D） is an immune-mediated disease. The autoreactive T cells in T1D patients attack and destroy their own pancreatic cells. In order to systematically investigate the potential autoreactive T cell receptors （TCRs）, we used a high-throughput immune repertoire sequencing technique to profile the spectrum of TCRs in individual T1D patients and controls. We sequenced the T cell repertoire of nine T1D patients, four type 2 diabetes （T2D） patients,and six nondiabetic controls. The diversity of the T cell repertoire in T1D patients was significantly decreased in comparison with T2D patients （P = 7.0E-08 for CD4＋ T cells, P = 1.4E-04 for CD8＋ T cells） and nondiabetic controls （P = 2.7E-09 for CD4＋ T cells, P = 7.6E-06 for CD8 ＋ T cells）. Moreover, T1D patients had significantly more highly-expanded T cell clones than T2D patients （P = 5.2E-06 for CD4＋ T cells, P = 1.9E-07 for CD8＋ T cells） and nondiabetic controls （P = 1.7E-07 for CD4＋ T cells, P =Y3E-03 for CD8＋ T cells）. Furthermore, we iden- tified a group of highly-expanded T cell receptor clones that are shared by more than two TID patients. Although further validation in larger cohorts is needed, our data suggest that T cell receptor diversity measurements may become a valuable tool in investigating diabetes, such as using the diversity as an index to distinguish different types of diabetes.
基金supported by the National Natural Science Foundation of China[grant number:82272312]the 100 Top Talent Programs of Sun Yat-sen University[grant number:58000-12230029]the Shenzhen-Hong Kong-Macao Science and Technology Project(Category C project)[grant number:SGDX20220530111403024].
文摘Background:Hepatocellular carcinoma(HCC)is one of the most common cancers worldwide and is prevalent in East Asia.Although genome-wide association studies(GWASs)of HCC have identified 23 risk regions,the susceptibility genes underlying these associa-tions largely remain unclear.To identify novel candidate genes for HCC,we conducted liver single-tissue and cross-tissue transcrip-tomewide association studies(TWASs)in two populations of East Asia.Methods:GWAS summary statistics of 2,514 subjects(1,161 HCC cases and 1,353 controls)from the Chinese Qidong cohort and 161,323 subjects(2,122 HCC cases and 159,201 controls)from the BioBank Japan project were used to conduct TWAS analysis.The single-tissue and cross-tissue TWAS approaches were both used to detect the association between susceptible genes and the risk of HCC.TWAS identified genes were further annotated by Metascape,UALCAN,GEPIA2,and DepMap.Results:We identified 22 novel genes at 16 independent loci significantly associated with HCC risk after Bonferroni correction.Of these,13 genes were located in novel regions.Besides,we found 83 genes overlapped in the Chinese and Japanese cohorts with P<0.05,of which,three genes(NUAK2,HLA-DQA1,and ATP6V1G2)were discerned by both single-tissue and cross-tissue TWAS approaches.Among the genes identified through TWAS,a significant proportion of them exhibit a credible role in HCC biology,such as FAM96B,HSPA5,POLRMT,MPHOSPH10,and RABL2A.HLA-DQA1,NUAK2,and HSPA5 associated with the process of carcinogenesis in HCC as previously reported.Conclusions:Our findings highlight the value of leveraging the gene expression data to identify new candidate genes beyond the GWAS associations and could further provide a genetic insight for the biology of HCC.
