BACKGROUND After receiving entecavir or combined with FuzhengHuayu tablet(FZHY)treatment,some sufferers with hepatitis B virus(HBV)-related liver fibrosis could achieve a histological improvement while the others may ...BACKGROUND After receiving entecavir or combined with FuzhengHuayu tablet(FZHY)treatment,some sufferers with hepatitis B virus(HBV)-related liver fibrosis could achieve a histological improvement while the others may fail to improve even worsen.Serum metabolomics at baseline in these patients who were effective in treatment remain unclear.AIM To explore baseline serum metabolites characteristics in responders.METHODS A total of 132 patients with HBV-related liver fibrosis and 18 volunteers as healthy controls were recruited.First,all subjects were divided into training set and validation set.Second,the included patients were subdivided into entecavir responders(E-R),entecavir no-responders(E-N),FZHY+entecavir responders(FR),and FZHY+entecavir no-responders(F-N)following the pathological histological changes after 48 wk’treatments.Then,Serum samples of all subjects before treatment were tested by high performance liquid chromatographytandem mass spectrometry(LC-MS)high-performance LC-MS.Data processing was conducted using multivariate principal component analysis and orthogonal partial least squares discriminant analysis.Diagnostic tests of selected differential metabolites were used for Boruta analyses and logistic regression.RESULTS As for the intersection about differential metabolic pathways between the groups E-R vs E-N and F-R vs F-N,results showed that 4 pathways including linoleic acid metabolism,aminoacyl-tRNA biosynthesis,cyanoamino acid metabolism,alanine,aspartate and glutamate metabolism were screened out.As for the differential metabolites,these 7 intersected metabolites including hydroxypropionic acid,tyrosine,citric acid,taurochenodeoxycholic acid,benzoic acid,2-Furoic acid,and propionic acid were selected.CONCLUSION Our findings showed that 4 metabolic pathways and 7 differential metabolites had potential usefulness in clinical prediction of the response of entecavir or combined with FZHY on HBV fibrotic liver.展开更多
Metabonomics has recently been widely used todiscover the pathogenesis and find potential metabolic markers with high sensitivity and specificity. Furthermore, it develops new diagnosis and treatment methods, increase...Metabonomics has recently been widely used todiscover the pathogenesis and find potential metabolic markers with high sensitivity and specificity. Furthermore, it develops new diagnosis and treatment methods, increases early phase diagnosis rates of certain diseases and provides a new basis for targeted therapy. This review mainly analyzes the research progress of the metabonomics of hepatitis B virus(HBV)-related hepatic diseases, hoping to discover some potential metabolic markers for identification of HBVrelated hepatic diseases from other etiologies and for HBV-related hepatitis, liver cirrhosis and hepatocellular carcinoma. This can contribute to early discovery, diagnosis and treatment, eventually increasing the survival rate of HBV-related hepatic diseases.展开更多
Background:Hepatitis B virus-related acute-on-chronic liver failure(HBV-ACLF)has a high short-term mortality.However,the treatment progression for HBV-ACLF in China in the past decade has not been well characterized.T...Background:Hepatitis B virus-related acute-on-chronic liver failure(HBV-ACLF)has a high short-term mortality.However,the treatment progression for HBV-ACLF in China in the past decade has not been well characterized.The present study aimed to determine whether the HBV-ACLF treatment has significantly improved during the past decade.Methods:This study retrospectively compared short-term(28/56 days)survival rates of two different nationwide cohorts(cohort I:2008-2011 and cohort II:2012-2015).Eligible HBV-ACLF patients were enrolled retrospectively.Patients in the cohorts I and II were assigned either to the standard medical therapy(SMT)group(cohort I-SMT,cohort II-SMT)or artificial liver support system(ALSS)group(cohort IALSS,cohort II-ALSS).Propensity score matching analysis was conducted to eliminate baseline differences,and multivariate logistic regression analysis was used to explore the independent factors for 28-day survival.Results:Short-term(28/56 days)survival rates were significantly higher in the ALSS group than those in the SMT group(P<0.05)and were higher in the cohort II than those in the cohort I(P<0.001).After propensity score matching,short-term(28/56 days)survival rates were higher in the cohort II than those in the cohort I for both SMT(60.7%vs.53.0%,50.0%vs.39.8%,P<0.05)and ALSS(66.1%vs.56.5%,53.0%vs.44.4%,P<0.05)treatments.The 28-day survival rate was higher in patients treated with nucleos(t)ide analogs than in patients without such treatments(P=0.046).Multivariate logistic regression analysis revealed that ALSS(OR=0.962,95%CI:0.951-0.973,P=0.038),nucleos(t)ide analogs(OR=0.927,95%CI:0.871-0.983,P=0.046),old age(OR=1.028,95%CI:1.015-1.041,P<0.001),total bilirubin(OR=1.002,95%CI:1.001-1.003,P=0.004),INR(OR=1.569,95%CI:1.044-2.358,P<0.001),COSSH-ACLF grade(OR=2.683,95%CI:1.792-4.017,P<0.001),and albumin(OR=0.952,95%CI:0.924-0.982,P=0.002)were independent factors for 28-day mortality.Conclusions:The treatment for patients with HBV-ACLF has improved in the past decade.展开更多
The Editor welcomes submissions for possible publication in the Letters to the Editor section. Letters commenting on an article published in the Journal or other interesting pieces will be considered if they are recei...The Editor welcomes submissions for possible publication in the Letters to the Editor section. Letters commenting on an article published in the Journal or other interesting pieces will be considered if they are received within 6 weeks of the time the article was published. Authors of the article being commented on will be given an opportunity to offer a timely response to the letter. Authors of letters will be notified that the letter has been received. Unpublished letters cannot be returned.展开更多
While presenting biological characteristics of vaccinia virus and laboratory-acquired infections during related research processes, this paper focuses on benefits and risks of vaccinia virus immunization in relation t...While presenting biological characteristics of vaccinia virus and laboratory-acquired infections during related research processes, this paper focuses on benefits and risks of vaccinia virus immunization in relation to laboratory-acquired infections, describes characteristics and the adaptation of vaccinia virus vaccine, analyses the role vaccinia virus immunization plays in the prevention and control of laboratory-acquired infections, and finally proposes solutions and countermeasures to further promote and implement immune control strategies. The problem related to immune strategy and laboratory- acquired infections which is being raised, analyzed and explored plays an active and instructive role in vaccinia virus related researches and laboratory- acquired infections, and also helps to recommend and develop relevant immune strategy for future vaccine control of such infections.展开更多
Objective:The aim of the present study was to explore the potential biomarkers and pathways in hepatitis B virus(HBV)-related hepatocellular carcinoma(HCC)using bioinformatic analyses.Methods:GSE14520,a whole-genome e...Objective:The aim of the present study was to explore the potential biomarkers and pathways in hepatitis B virus(HBV)-related hepatocellular carcinoma(HCC)using bioinformatic analyses.Methods:GSE14520,a whole-genome expression profile dataset of HBV-related HCC,was downloaded from the gene expression omnibus database.Data of HCC patients from The Cancer Genome Atlas(TCGA)database were used as the validation cohort.展开更多
BACKGROUND: Few comprehensive reviews on the pa- thogenesis of hepatitis C virus (HCV)-related liver diseases have been presented to the present. This article was to re- view the pathogenesis and treatment of HCV-rela...BACKGROUND: Few comprehensive reviews on the pa- thogenesis of hepatitis C virus (HCV)-related liver diseases have been presented to the present. This article was to re- view the pathogenesis and treatment of HCV-related liver diseases. DATA SOURCES: Data presented here are mostly taken from Japanese studies. RESULTS: HCV infection is characterized by persistent in- flammation of the liver and frequent development of hepa- tocellular carcinoma (HCC) in most cases. These charac- teristic evidences could be explained by immunological al- terations and oxidative stress in the hepatocyte caused by HCV infection. Interferon (IFN) treatment is carried out, at present, not only for the elimination of infected HCV for the treatment of chronic liver diseases, but also for both the prevention of HCC and the treatment of advanced HCC with chemotherapy. The treatment for oxidative stress is al- so important for non-responders to IFN. CONCLUSION: It is important to understand the pathoge- nesis of HCV-related liver diseases for a successful treat- ment.展开更多
Background and aims:Hepatocellular carcinoma(HCC),which is prevalent worldwide and has a high mortality rate,needs to be effectively diagnosed.We aimed to evaluate the significance of plasma microRNA-15a/16-1(miR-15a/...Background and aims:Hepatocellular carcinoma(HCC),which is prevalent worldwide and has a high mortality rate,needs to be effectively diagnosed.We aimed to evaluate the significance of plasma microRNA-15a/16-1(miR-15a/16)as a biomarker of hepatitis B virus-related HCC(HBV-HCC)using the machine learning model.This study was the first large-scale investigation of these two miRNAs in HCC plasma samples.Methods:Using quantitative polymerase chain reaction,we measured the plasma miR-15a/16 levels in a total of 766 participants,including 74 healthy controls,335 with chronic hepatitis B(CHB),47 with compensated liver cirrhosis,and 310 with HBV-HCC.The diagnostic performance of miR-15a/16 was examined using a machine learning model and compared with that of alpha-fetoprotein(AFP).Lastly,to validate the diagnostic efficiency of miR-15a/16,we performed pseudotemporal sorting of the samples to simulate progression from CHB to HCC.Results:Plasma miR-15a/16 was significantly decreased in HCC than in all control groups(P<0.05 for all).In the training cohort,the area under the receiver operating characteristic curve(AUC),sensitivity,and average precision(AP)for the detection of HCC were higher for miR-15a(AUC=0.80,67.3%,AP=0.80)and miR-16(AUC=0.83,79.0%,AP=0.83)than for AFP(AUC=0.74,61.7%,AP=0.72).Combining miR-15a/16 with AFP increased the AUC to 0.86(sensitivity 85.9%)and the AP to 0.85 and was significantly superior to the other markers in this study(P<0.05 for all),as further demonstrated by the detection error tradeoff curves.Moreover,miR-15a/16 impressively showed potent diagnostic power in early-stage,small-tumor,and AFP-negative HCC.A validation cohort confirmed these results.Lastly,the simulated follow-up of patients further validated the diagnostic efficiency of miR-15a/16.Conclusions:We developed and validated a plasma miR-15a/16-based machine learning model,which exhibited better diagnostic performance for the early diagnosis of HCC compared to that of AFP.展开更多
Background:As a large,prospective,multicenter study-based prognostic score for hepatitis B virus-related acute-on-chronic liver failure(HBV-ACLF),the Chinese group on the study of severe hepatitis B-acute-on-chronic l...Background:As a large,prospective,multicenter study-based prognostic score for hepatitis B virus-related acute-on-chronic liver failure(HBV-ACLF),the Chinese group on the study of severe hepatitis B-acute-on-chronic liver failure score(COSSH-ACLFs),has been approved by some foreign scholars;however,its predictive value needs to be verified.This study investigated the predictive value of COSSH-ACLFs for short-term prognosis in Chinese patients with HBV-ACLF.Methods:This retrospective cohort study included 751 patients with HBV-ACLF admitted to the Fifth Medical Center of Chinese PLA General Hospital between January 2011 and December 2014.Spearman method was used to assess the correlation of COSSHACLFs with classical scores.Different COX multivariate regression models were used to confirm the relationship between COSSHACLFs and short-term prognosis in patients with HBV-ACLF,and stratified analysis was used to further verify the stability of this relationship.We compared the predictive powers of COSSH-ACLFs and other classical scores using area under the receiver operating characteristic curve(AUROC)and Z-test.Results:A total of 975 patients with HBV-ACLF were screened,and 751 were analyzed(623 male and 128 female).COSSH-ACLFs was the highest in patients with end-stage ACLF,followed by those with middle-and early-stage ACLF(H=211.8,P<0.001).In the fully adjusted model,COX multivariate regression analysis revealed that COSSH-ACLFs(as a continuous variable)was independently and positively correlated with mortality risk in patients with HBV-ACLF at 28 days(hazard ratio[HR]:1.37[1.22,1.53],P<0.001)and 90 days(HR:1.43[1.29,1.58],P<0.001).The same trend could be observed in the crude model and minimally adjusted model.The AUROCs of COSSH-ACLFs for 28-day and 90-day prognoses in patients with HBV-ACLF were 0.807 and 0.792,respectively,indicating a stronger predictive accuracy than those of classic models.Conclusions:COSSH-ACLFs,with a superior predictive accuracy compared with other classical scores,can strongly predict shortterm prognosis in Chinese patients with HBV-ACLF.展开更多
Background The long-term effectiveness and safety of lamivudine in patients with decompensated hepatitis B virus-related cirrhosis are still not clear. The present study attempted to describe the clinical outcomes of ...Background The long-term effectiveness and safety of lamivudine in patients with decompensated hepatitis B virus-related cirrhosis are still not clear. The present study attempted to describe the clinical outcomes of lamivudine therapy in these special patients over three years. Methods This study was a retrospective, controlled cohort study which involved 153 patients with decompensated hepatitis B virus-related cJrrhosJs. Of these, 86 patients received lamJvudJne 100 mg daily accompanied with general internal treatment, and the other 67 were given general internal treatment only. Significant clinical responses were recorded after years of antiviral treatment. Results The patients in both groups were matched in terms of age, sex and laboratory results at baseline. After years of therapy, the Child-Pugh-Turcotte scores and laboratory values of the patients receiving lamivudine were remarkably improved compared to the patients in the control group. The mortality rate and the incidence of cirrhosis-related complications were much lower in the lamivudine group than in the control group. Genotypic resistance tyrosine, methionine, aspartate, aspartate mutations developed in 26.7 percent of the patients during 3-year lamivudine treatment, and cirrhosis-related death and the hepatocellular carcinoma were more likely to occur in patients with these mutations than in the other patients who were treated with lamivudine. Conclusions Continuous long-term lamivudine treatment in patients with decompensated hepatitis B virus-related cirrhosis delays clinical progression, and significantly improves hepatic function and prognosis. However, the use of a retrospective control cohort precludes drawin（~ definitive conclusions.展开更多
Objective： To evaluate the clinical efficacy and safety of Yinchen Zhufu Decoction（茵陈术附汤, YCZFD） in the treatment of acute-on-chronic liver failure caused by hepatitis B virus（HBV-ACLF） with cold pattern in ...Objective： To evaluate the clinical efficacy and safety of Yinchen Zhufu Decoction（茵陈术附汤, YCZFD） in the treatment of acute-on-chronic liver failure caused by hepatitis B virus（HBV-ACLF） with cold pattern in Chinese medicine（CM）. Methods： This is a multi-center randomized controlled trial of integrative treatment of CM and Western medicine（WM） for the management of HBV-ACLF patients. A total of 200 HBV-ACLF patients with cold pattern were equally randomly assigned to receive YCZFD and WM（integrative treatment） or WM conventional therapy alone respectively for 4 weeks. The primary end point was the mortality for HBV-ACLF patients. Secondary outcome measures included Model for End-Stage Liver disease（MELD） score, liver biochemical function, coagulation function and complications. Adverse events during treatment were reported. Results： The mortality was decreased 14.28% in the integrative treatment group compared with WM group（χ^2=6.156, P=0.013）. The integrative treatment was found to significantly improve the MELD score（t=2.353, P=0.020）. There were statistically significant differences in aspartate transaminase, total bilirubin, indirect bilirubin, direct bilirubin and prothrombin time between the two groups（P〈0.05 or P〈0.01）. The complications of ascites（χ^2=9.033, P=0.003） and spontaneous bacteria peritonitis（χ^2=4.194, P=0.041） were improved significantly in the integrative treatment group. No serious adverse event was reported. Conclusions： The integrative treatment of CM and WM was effective and safe for HBV-ACLF patients with cold pattern in CM. The Chinese therapeutic principle ＂treating cold pattern with hot herbs＂ remains valuable to the clinical therapy.（Trial registration No. Chi CTR-TRC-10000766）展开更多
Objective To explore the possible role and clinical implications of myeloid-derived suppressor cells(MDSC)in the peripheral blood of patients with hepatitis B virus(HBV)-related acute-on-chronic liver failure(HBVACLF)...Objective To explore the possible role and clinical implications of myeloid-derived suppressor cells(MDSC)in the peripheral blood of patients with hepatitis B virus(HBV)-related acute-on-chronic liver failure(HBVACLF).Methods A total of 25 HBV-ACLF patients展开更多
Objective To analyze the serum keratin 18(K18)level of patients with hepatitis B virus(HBV)-related acute-on-chronic liver failure(HBV-ACLF)and its correlation with prognosis.Methods From December 2012 to October 2014...Objective To analyze the serum keratin 18(K18)level of patients with hepatitis B virus(HBV)-related acute-on-chronic liver failure(HBV-ACLF)and its correlation with prognosis.Methods From December 2012 to October 2014,120 patients who visited Fuzhou Infectious Diseases Hospital and were diagnosed with HBV-ACLF were enrolled,and 20 chronic hepatitis B(CHB)pa-展开更多
More than 90%of cases of hepatocellular carcinoma(HCC)occurs in patients with cirrhosis,of which hepatitis B virus and hepatitis C virus are the leading causes,while the tumor less frequently arises in autoimmune live...More than 90%of cases of hepatocellular carcinoma(HCC)occurs in patients with cirrhosis,of which hepatitis B virus and hepatitis C virus are the leading causes,while the tumor less frequently arises in autoimmune liver diseases.Advances in understanding tumor immunity have led to a major shift in the treatment of HCC,with the emergence of immunotherapy where therapeutic agents are used to target immune cells rather than cancer cells.Regulatory T cells(Tregs)are the most abundant suppressive cells in the tumor microenvironment and their presence has been correlated with tumor progression,invasiveness,as well as metastasis.Tregs are characterized by the expression of the transcription factor Foxp3 and various mechanisms ranging from cell-to-cell contact to secretion of inhibitory molecules have been implicated in their function.Notably,Tregs amply express checkpoint molecules such as cytotoxic T lymphocyte-associated antigen 4 and programmed cell-death 1 receptor and therefore represent a direct target of immune checkpoint inhibitor(ICI)immunotherapy.Taking into consideration the critical role of Tregs in maintenance of immune homeostasis as well as avoidance of autoimmunity,it is plausible that targeting of Tregs by ICI immunotherapy results in the development of immune-related adverse events(irAEs).Since the use of ICI becomes common in oncology,with an increasing number of new ICI currently under clinical trials for cancer treatment,the occurrence of irAEs is expected to dramatically rise.Herein,we review the current literature focusing on the role of Tregs in HCC evolution taking into account their opposite etiological function in viral and autoimmune chronic liver disease,and we discuss their involvement in irAEs due to the new immunotherapies.展开更多
AIM: To longitudinally investigate cytokine gene expression and protein levels in Th17 and Treg cells, to observe T-cell phenotypes during hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACHBLF) and to...AIM: To longitudinally investigate cytokine gene expression and protein levels in Th17 and Treg cells, to observe T-cell phenotypes during hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACHBLF) and to analyze changes in Th17 and Treg phenotypes during disease progression.展开更多
AIM： To explore the relationship between DNA methyltransferase 1 （DNMT1） and hepatitis B virus （HBV）-related hepatocellular carcinoma （HCC） and its biological significance in primary HCC. METHODS： We carried o...AIM： To explore the relationship between DNA methyltransferase 1 （DNMT1） and hepatitis B virus （HBV）-related hepatocellular carcinoma （HCC） and its biological significance in primary HCC. METHODS： We carried out an immunohistochemical examination of DNMT1 in both HCC and paired nonneoplastic liver tissues from Chinese subjects. DNMT1 mRNA was further examined in HCC cell lines by real-time PCR. We inhibited DNMT1 using siRNA and detected the effect of depletion of DNMT1 on cell proliferation ability and cell apoptosis in the HCC celt line SMMC-7721. RESULTS： DNMT1 protein expression was increased in HCCs compared to histologically normal nonneoplastic liver tissues and the incidence of DNMT1 immunoreactivity in HCCs correlated significantly with poor tumor differentiation （P = 0.014）. There were more cases with DNMT1 overexpression in HCC with HBV （42.85%） than in HCC without HBV （28.57%）. However, no significant difference in DNMT1 expression was found in HBV-positive and HBV-negative cases in the Chinese HCC group. There was a trend that DNMT1 RNA expression increased more in HCC cell lines than in pericarcinoma cell lines and normal liver cell lines. In addition, we inhibited DNMT1 using siRNA in the SMMC-7721 HCC cell line and found depletion of DNMT1 suppressed cells growth independent of expression of proliferating cell nuclear antigen （PCNA）, even in HCC cell lines where DNMT1 was stably decreased. CONCLUSION： The findings implied that DNMT1 plays a key role in HBV-retated hepatocellular tumorigenesis. Depletion of DNMT1 mediates growth suppression in SMMC-7721 cells.展开更多
AIM To investigate gender-specific liver estrogen receptor(ER) expression in normal subjects and patients with hepatitis C virus(HCV)-related cirrhosis and hepatocellular carcinoma(HCC).METHODS Liver tissues from norm...AIM To investigate gender-specific liver estrogen receptor(ER) expression in normal subjects and patients with hepatitis C virus(HCV)-related cirrhosis and hepatocellular carcinoma(HCC).METHODS Liver tissues from normal donors and patients diagnosed with HCV-related cirrhosis and HCV-related HCC were obtained from the NIH Liver Tissue and Cell Distribution System. The expression of ER subtypes, ERα and ERβ, were evaluated by Western blotting and real-time RT-PCR. The subcellular distribution of ERα and ERβ was further determined in nuclear and cytoplasmic tissue lysates along with the expression ofinflammatory [activated NF-κB and IκB-kinase(IKK)] and oncogenic(cyclin D1) markers by Western blotting and immunohistochemistry. The expression of ERα and ERβ was correlated with the expression of activated NF-κB, activated IKK and cyclin D1 by Spearman's correlation. RESULTS Both ER subtypes were expressed in normal livers but male livers showed significantly higher expression of ERα than females(P < 0.05). We observed significantly higher m RNA expression of ERα in HCV-related HCC liver tissues as compared to normals(P < 0.05) and ERβ in livers of HCV-related cirrhosis and HCV-related HCC subjects(P < 0.05). At the protein level, there was a significantly higher expression of nuclear ERα in livers of HCV-related HCC patients and nuclear ERβ in HCV-related cirrhosis patients as compared to normals(P < 0.05). Furthermore, we observed a significantly higher expression of phosphorylated NF-κB and cyclin D1 in diseased livers(P < 0.05). There was a positive correlation between the expression of nuclear ER subtypes and nuclear cyclin D1 and a negative correlation between cytoplasmic ER subtypes and cytoplasmic phosphorylated IKK in HCV-related HCC livers. These findings suggest that dysregulated expression of ER subtypes following chronic HCVinfection may contribute to the progression of HCVrelated cirrhosis to HCV-related HCC.CONCLUSION Gender differences were observed in ERα expression in normal livers. Alterations in ER subtype expression observed in diseased livers may influence genderrelated disparity in HCV-related pathogenesis.展开更多
Background： The ^13C urea breath test （^13C-UBT） is the gold standard for detecting Helicobacterpylori infection. H. pylori pathogenesis in patients with hepatitis B virus （HBV） and related diseases remains obscu...Background： The ^13C urea breath test （^13C-UBT） is the gold standard for detecting Helicobacterpylori infection. H. pylori pathogenesis in patients with hepatitis B virus （HBV） and related diseases remains obscure. We used ^13C-UBT to detect H. p.vlori infection in patients with chronic HBV infection, HBV-related cirrhosis, HBV-related hepatic carcinoma, and other chronic hepatic diseases. Methods： A total of 131 patients with chronic hepatitis B （HB）, 179 with HBV-related cirrhosis, 103 with HBV-related hepatic carcinoma, 45 with HBV-negative hepatic carcinoma, and 150 controls were tested for H. pylori infection using ^13C-UBT. We compared H. pylori infection rate, liver function, complications of chronic hepatic disease, serum HBV-DNA, serum alpha-fetoprotein （AFP）, and portal hypertensive gastropathy （PHG） incidence among groups. Results： HBV-related cirrhosis was associated with the highest H. pylori infection rate （79.3%）. H. pylori infection rate in chronic HB was significantly higher than in the HBV-negative hepatic carcinoma and control groups （P 〈 0.001 ）. 11. pylori infection rate in patients with HBV-DNA ≥10^3 copies/ml was significantly higher than in those with HBV-DNA 〈103 copies/ml （76.8% vs. 52.4%, P 〈 0.001）. Prothrombin time （21.3 ± 3.5 s vs. 18.8 ±4.3 s）, total bilirubin （47.3±12.3 μmol/L vs. 26.6±7.9 μmol/L）, aspartate aminotransferase （ 184.5 ±37.6 U/L vs. 98.4 ± 23.5 U/L）, blood ammonia （93.4 ± 43.6 μmol/L vs. 35.5 ± 11.7 μmol/L）, and AFP （203.4±62.6 μg/L vs. 113.2± 45.8 μg/L） in the ^13C-UBT-positive group were significantly higher than in the ^13C-UBT-negative group （P 〈 0.01）. The incidence rates of esophageal fundus variceal bleeding （25.4% vs. 16.0%）, ascites （28.9% vs. 17.8%）, and hepatic encephalopathy （24.8% vs. 13.4%） in the ^13C-UBT-positive group were significantly higher than in the 13C-UBT-negative group （P 〈 0.01 ）. The percentages of patients with liver function in Child-Pugh Grade C （29.6% vs. 8.1%） and PHG （43.0% vs. 24.3%） in the ^13C-UBT-positive group were significantly higher than in the ^13C-UBT-negative group （P 〈 0.05）. Conclusions： It is possible that H. pylori infection could increase liver damage caused by HBV. 1t. pylori eradication should be performed in patients with complicating H. pylori infection to delay hepatic disease progression.展开更多
On the basis of real-world clinical data,the study aimed to explore the effect and mechanisms of the treatment plan of“traditional Chinese medicine(TCM)regulating liver regeneration.”A total of 457 patients with HBV...On the basis of real-world clinical data,the study aimed to explore the effect and mechanisms of the treatment plan of“traditional Chinese medicine(TCM)regulating liver regeneration.”A total of 457 patients with HBV-related liver failure were retrospectively collected.The patients were divided into three groups:the modern medicine control group(MMC group),patients treated with routine medical treatment;the control group combining traditional Chinese and Western medicine(CTW),patients treated with routine medical treatment plus the common TCM formula;and the treatment group of“TCM regulating liver regeneration”(RLR),patients treated with both routine medical treatment and the special TCM formula of RLR.After 8 weeks of treatment,the mortality of patients in the RLR group(12.31%)was significantly lower than those in the MMC(50%)and CTW(29.11%)groups.Total bilirubin level significantly decreased and albumin increased in the RLR group when compared with the MMC and CTW groups(P<0.05).In addition,there were significant differences in the expression of several cytokines related to liver regeneration in the RLR group compared with the MMC group.RLR treatment can decrease jaundice,improve liver function,and significantly reduce the mortality in patients with HBV-related liver failure.The mechanism may be related to the role of RLR treatment in influencing cytokines related to liver regeneration.展开更多
Background and Objective:Hepatocellular carcinoma(HCC)poses a significant global health burden and ranks as the fifth most prevalent cancer on a global scale.Hepatitis C virus(HCV)infection remains one of the major ri...Background and Objective:Hepatocellular carcinoma(HCC)poses a significant global health burden and ranks as the fifth most prevalent cancer on a global scale.Hepatitis C virus(HCV)infection remains one of the major risk factors for HCC development.HCC is a heterogeneous disease,and the development of HCC caused by HCV is intricate and involves various factors,including genetic susceptibility,viral factors,immune response due to chronic inflammation,alcohol abuse,and metabolic dysfunction associated with fatty liver disease.In this review,we provide a comprehensive and updated review of research on the genetics and epigenetic mechanisms implicated in developing HCC associated with HCV infection.We also discuss the potential translational implications,including novel biomarkers and drugs for treatment.Methods:A comprehensive literature search was conducted in June 2023 in PubMed and Embase databases.Key Content and Findings:Recent findings indicate that a variety of genetic and epigenetic processes are involved in the pathogenesis and continue to exist even after the complete elimination of HCV.The deregulation of the epigenome has been identified as a significant factor in the deletrious effects of liver disease,especially during the initial stages when genetic alterations are uncommon.The enduring“epigenetic memory”of gene expression is believed to be regulated by epigenetic mechanisms,indicating that alterations caused by HCV infection continue to exist and are linked to the risk of development of liver cancer even after successful treatment.Systems biology analytical methods will be required to delineate the magnitude and significance of both genetic and epigenomic alterations in tumor evolution.Conclusions:By facilitating a more profound understanding of these aspects,this will ultimately foster the advancement of novel therapies and ultimately improve outcomes for patients.展开更多
基金Supported by National Science and Technology Major Project,No.2014ZX10005001 and No.2018ZX10302204National Natural Science Foundation of China,No.81730109 and No.82274305+2 种基金Shanghai Key Specialty of Traditional Chinese Clinical Medicine,No.shslczdzk01201China Postdoctoral Science Foundation,No.2022M722162Siming Youth Fund of Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,No.SGKJ-202104.
文摘BACKGROUND After receiving entecavir or combined with FuzhengHuayu tablet(FZHY)treatment,some sufferers with hepatitis B virus(HBV)-related liver fibrosis could achieve a histological improvement while the others may fail to improve even worsen.Serum metabolomics at baseline in these patients who were effective in treatment remain unclear.AIM To explore baseline serum metabolites characteristics in responders.METHODS A total of 132 patients with HBV-related liver fibrosis and 18 volunteers as healthy controls were recruited.First,all subjects were divided into training set and validation set.Second,the included patients were subdivided into entecavir responders(E-R),entecavir no-responders(E-N),FZHY+entecavir responders(FR),and FZHY+entecavir no-responders(F-N)following the pathological histological changes after 48 wk’treatments.Then,Serum samples of all subjects before treatment were tested by high performance liquid chromatographytandem mass spectrometry(LC-MS)high-performance LC-MS.Data processing was conducted using multivariate principal component analysis and orthogonal partial least squares discriminant analysis.Diagnostic tests of selected differential metabolites were used for Boruta analyses and logistic regression.RESULTS As for the intersection about differential metabolic pathways between the groups E-R vs E-N and F-R vs F-N,results showed that 4 pathways including linoleic acid metabolism,aminoacyl-tRNA biosynthesis,cyanoamino acid metabolism,alanine,aspartate and glutamate metabolism were screened out.As for the differential metabolites,these 7 intersected metabolites including hydroxypropionic acid,tyrosine,citric acid,taurochenodeoxycholic acid,benzoic acid,2-Furoic acid,and propionic acid were selected.CONCLUSION Our findings showed that 4 metabolic pathways and 7 differential metabolites had potential usefulness in clinical prediction of the response of entecavir or combined with FZHY on HBV fibrotic liver.
基金Supported by Liaoning Natural Science Foundation of China,No.2013B003
文摘Metabonomics has recently been widely used todiscover the pathogenesis and find potential metabolic markers with high sensitivity and specificity. Furthermore, it develops new diagnosis and treatment methods, increases early phase diagnosis rates of certain diseases and provides a new basis for targeted therapy. This review mainly analyzes the research progress of the metabonomics of hepatitis B virus(HBV)-related hepatic diseases, hoping to discover some potential metabolic markers for identification of HBVrelated hepatic diseases from other etiologies and for HBV-related hepatitis, liver cirrhosis and hepatocellular carcinoma. This can contribute to early discovery, diagnosis and treatment, eventually increasing the survival rate of HBV-related hepatic diseases.
基金supported by grants from the Science&Technology Key Program of Zhejiang China(2017C03051)the National Science&Technology Major Project of China(2017ZX10203201)。
文摘Background:Hepatitis B virus-related acute-on-chronic liver failure(HBV-ACLF)has a high short-term mortality.However,the treatment progression for HBV-ACLF in China in the past decade has not been well characterized.The present study aimed to determine whether the HBV-ACLF treatment has significantly improved during the past decade.Methods:This study retrospectively compared short-term(28/56 days)survival rates of two different nationwide cohorts(cohort I:2008-2011 and cohort II:2012-2015).Eligible HBV-ACLF patients were enrolled retrospectively.Patients in the cohorts I and II were assigned either to the standard medical therapy(SMT)group(cohort I-SMT,cohort II-SMT)or artificial liver support system(ALSS)group(cohort IALSS,cohort II-ALSS).Propensity score matching analysis was conducted to eliminate baseline differences,and multivariate logistic regression analysis was used to explore the independent factors for 28-day survival.Results:Short-term(28/56 days)survival rates were significantly higher in the ALSS group than those in the SMT group(P<0.05)and were higher in the cohort II than those in the cohort I(P<0.001).After propensity score matching,short-term(28/56 days)survival rates were higher in the cohort II than those in the cohort I for both SMT(60.7%vs.53.0%,50.0%vs.39.8%,P<0.05)and ALSS(66.1%vs.56.5%,53.0%vs.44.4%,P<0.05)treatments.The 28-day survival rate was higher in patients treated with nucleos(t)ide analogs than in patients without such treatments(P=0.046).Multivariate logistic regression analysis revealed that ALSS(OR=0.962,95%CI:0.951-0.973,P=0.038),nucleos(t)ide analogs(OR=0.927,95%CI:0.871-0.983,P=0.046),old age(OR=1.028,95%CI:1.015-1.041,P<0.001),total bilirubin(OR=1.002,95%CI:1.001-1.003,P=0.004),INR(OR=1.569,95%CI:1.044-2.358,P<0.001),COSSH-ACLF grade(OR=2.683,95%CI:1.792-4.017,P<0.001),and albumin(OR=0.952,95%CI:0.924-0.982,P=0.002)were independent factors for 28-day mortality.Conclusions:The treatment for patients with HBV-ACLF has improved in the past decade.
文摘The Editor welcomes submissions for possible publication in the Letters to the Editor section. Letters commenting on an article published in the Journal or other interesting pieces will be considered if they are received within 6 weeks of the time the article was published. Authors of the article being commented on will be given an opportunity to offer a timely response to the letter. Authors of letters will be notified that the letter has been received. Unpublished letters cannot be returned.
基金supported by the National Health and Family Planning Commission(201302006)
文摘While presenting biological characteristics of vaccinia virus and laboratory-acquired infections during related research processes, this paper focuses on benefits and risks of vaccinia virus immunization in relation to laboratory-acquired infections, describes characteristics and the adaptation of vaccinia virus vaccine, analyses the role vaccinia virus immunization plays in the prevention and control of laboratory-acquired infections, and finally proposes solutions and countermeasures to further promote and implement immune control strategies. The problem related to immune strategy and laboratory- acquired infections which is being raised, analyzed and explored plays an active and instructive role in vaccinia virus related researches and laboratory- acquired infections, and also helps to recommend and develop relevant immune strategy for future vaccine control of such infections.
文摘Objective:The aim of the present study was to explore the potential biomarkers and pathways in hepatitis B virus(HBV)-related hepatocellular carcinoma(HCC)using bioinformatic analyses.Methods:GSE14520,a whole-genome expression profile dataset of HBV-related HCC,was downloaded from the gene expression omnibus database.Data of HCC patients from The Cancer Genome Atlas(TCGA)database were used as the validation cohort.
文摘BACKGROUND: Few comprehensive reviews on the pa- thogenesis of hepatitis C virus (HCV)-related liver diseases have been presented to the present. This article was to re- view the pathogenesis and treatment of HCV-related liver diseases. DATA SOURCES: Data presented here are mostly taken from Japanese studies. RESULTS: HCV infection is characterized by persistent in- flammation of the liver and frequent development of hepa- tocellular carcinoma (HCC) in most cases. These charac- teristic evidences could be explained by immunological al- terations and oxidative stress in the hepatocyte caused by HCV infection. Interferon (IFN) treatment is carried out, at present, not only for the elimination of infected HCV for the treatment of chronic liver diseases, but also for both the prevention of HCC and the treatment of advanced HCC with chemotherapy. The treatment for oxidative stress is al- so important for non-responders to IFN. CONCLUSION: It is important to understand the pathoge- nesis of HCV-related liver diseases for a successful treat- ment.
基金supported by Research and Development Planned Project in Key Areas of Guangdong Province(No.2019B110233002)National Natural Science Foundation of China(No.12171494 and 11931019)+3 种基金Natural Science Foundation of Guangdong Province,China(No.2022A1515011540)Guangdong Province Key Laboratory of Computational Science at the Sun Yat-sen University(No.2020B1212060032)Joint Key Projects of City and Hospital of Guangzhou Science and Technology(No.202201020422)General Planned Project of Guangzhou Science and Technology(No.202201010950).
文摘Background and aims:Hepatocellular carcinoma(HCC),which is prevalent worldwide and has a high mortality rate,needs to be effectively diagnosed.We aimed to evaluate the significance of plasma microRNA-15a/16-1(miR-15a/16)as a biomarker of hepatitis B virus-related HCC(HBV-HCC)using the machine learning model.This study was the first large-scale investigation of these two miRNAs in HCC plasma samples.Methods:Using quantitative polymerase chain reaction,we measured the plasma miR-15a/16 levels in a total of 766 participants,including 74 healthy controls,335 with chronic hepatitis B(CHB),47 with compensated liver cirrhosis,and 310 with HBV-HCC.The diagnostic performance of miR-15a/16 was examined using a machine learning model and compared with that of alpha-fetoprotein(AFP).Lastly,to validate the diagnostic efficiency of miR-15a/16,we performed pseudotemporal sorting of the samples to simulate progression from CHB to HCC.Results:Plasma miR-15a/16 was significantly decreased in HCC than in all control groups(P<0.05 for all).In the training cohort,the area under the receiver operating characteristic curve(AUC),sensitivity,and average precision(AP)for the detection of HCC were higher for miR-15a(AUC=0.80,67.3%,AP=0.80)and miR-16(AUC=0.83,79.0%,AP=0.83)than for AFP(AUC=0.74,61.7%,AP=0.72).Combining miR-15a/16 with AFP increased the AUC to 0.86(sensitivity 85.9%)and the AP to 0.85 and was significantly superior to the other markers in this study(P<0.05 for all),as further demonstrated by the detection error tradeoff curves.Moreover,miR-15a/16 impressively showed potent diagnostic power in early-stage,small-tumor,and AFP-negative HCC.A validation cohort confirmed these results.Lastly,the simulated follow-up of patients further validated the diagnostic efficiency of miR-15a/16.Conclusions:We developed and validated a plasma miR-15a/16-based machine learning model,which exhibited better diagnostic performance for the early diagnosis of HCC compared to that of AFP.
文摘Background:As a large,prospective,multicenter study-based prognostic score for hepatitis B virus-related acute-on-chronic liver failure(HBV-ACLF),the Chinese group on the study of severe hepatitis B-acute-on-chronic liver failure score(COSSH-ACLFs),has been approved by some foreign scholars;however,its predictive value needs to be verified.This study investigated the predictive value of COSSH-ACLFs for short-term prognosis in Chinese patients with HBV-ACLF.Methods:This retrospective cohort study included 751 patients with HBV-ACLF admitted to the Fifth Medical Center of Chinese PLA General Hospital between January 2011 and December 2014.Spearman method was used to assess the correlation of COSSHACLFs with classical scores.Different COX multivariate regression models were used to confirm the relationship between COSSHACLFs and short-term prognosis in patients with HBV-ACLF,and stratified analysis was used to further verify the stability of this relationship.We compared the predictive powers of COSSH-ACLFs and other classical scores using area under the receiver operating characteristic curve(AUROC)and Z-test.Results:A total of 975 patients with HBV-ACLF were screened,and 751 were analyzed(623 male and 128 female).COSSH-ACLFs was the highest in patients with end-stage ACLF,followed by those with middle-and early-stage ACLF(H=211.8,P<0.001).In the fully adjusted model,COX multivariate regression analysis revealed that COSSH-ACLFs(as a continuous variable)was independently and positively correlated with mortality risk in patients with HBV-ACLF at 28 days(hazard ratio[HR]:1.37[1.22,1.53],P<0.001)and 90 days(HR:1.43[1.29,1.58],P<0.001).The same trend could be observed in the crude model and minimally adjusted model.The AUROCs of COSSH-ACLFs for 28-day and 90-day prognoses in patients with HBV-ACLF were 0.807 and 0.792,respectively,indicating a stronger predictive accuracy than those of classic models.Conclusions:COSSH-ACLFs,with a superior predictive accuracy compared with other classical scores,can strongly predict shortterm prognosis in Chinese patients with HBV-ACLF.
文摘Background The long-term effectiveness and safety of lamivudine in patients with decompensated hepatitis B virus-related cirrhosis are still not clear. The present study attempted to describe the clinical outcomes of lamivudine therapy in these special patients over three years. Methods This study was a retrospective, controlled cohort study which involved 153 patients with decompensated hepatitis B virus-related cJrrhosJs. Of these, 86 patients received lamJvudJne 100 mg daily accompanied with general internal treatment, and the other 67 were given general internal treatment only. Significant clinical responses were recorded after years of antiviral treatment. Results The patients in both groups were matched in terms of age, sex and laboratory results at baseline. After years of therapy, the Child-Pugh-Turcotte scores and laboratory values of the patients receiving lamivudine were remarkably improved compared to the patients in the control group. The mortality rate and the incidence of cirrhosis-related complications were much lower in the lamivudine group than in the control group. Genotypic resistance tyrosine, methionine, aspartate, aspartate mutations developed in 26.7 percent of the patients during 3-year lamivudine treatment, and cirrhosis-related death and the hepatocellular carcinoma were more likely to occur in patients with these mutations than in the other patients who were treated with lamivudine. Conclusions Continuous long-term lamivudine treatment in patients with decompensated hepatitis B virus-related cirrhosis delays clinical progression, and significantly improves hepatic function and prognosis. However, the use of a retrospective control cohort precludes drawin（~ definitive conclusions.
基金Supported by the Ministry of Science and Technology of China,through its National Key Projects for Basic Research(No.2007CB512607)National Eleventh Five-year Great Science and Technology Project(No.2008ZX10005-007)
文摘Objective： To evaluate the clinical efficacy and safety of Yinchen Zhufu Decoction（茵陈术附汤, YCZFD） in the treatment of acute-on-chronic liver failure caused by hepatitis B virus（HBV-ACLF） with cold pattern in Chinese medicine（CM）. Methods： This is a multi-center randomized controlled trial of integrative treatment of CM and Western medicine（WM） for the management of HBV-ACLF patients. A total of 200 HBV-ACLF patients with cold pattern were equally randomly assigned to receive YCZFD and WM（integrative treatment） or WM conventional therapy alone respectively for 4 weeks. The primary end point was the mortality for HBV-ACLF patients. Secondary outcome measures included Model for End-Stage Liver disease（MELD） score, liver biochemical function, coagulation function and complications. Adverse events during treatment were reported. Results： The mortality was decreased 14.28% in the integrative treatment group compared with WM group（χ^2=6.156, P=0.013）. The integrative treatment was found to significantly improve the MELD score（t=2.353, P=0.020）. There were statistically significant differences in aspartate transaminase, total bilirubin, indirect bilirubin, direct bilirubin and prothrombin time between the two groups（P〈0.05 or P〈0.01）. The complications of ascites（χ^2=9.033, P=0.003） and spontaneous bacteria peritonitis（χ^2=4.194, P=0.041） were improved significantly in the integrative treatment group. No serious adverse event was reported. Conclusions： The integrative treatment of CM and WM was effective and safe for HBV-ACLF patients with cold pattern in CM. The Chinese therapeutic principle ＂treating cold pattern with hot herbs＂ remains valuable to the clinical therapy.（Trial registration No. Chi CTR-TRC-10000766）
文摘Objective To explore the possible role and clinical implications of myeloid-derived suppressor cells(MDSC)in the peripheral blood of patients with hepatitis B virus(HBV)-related acute-on-chronic liver failure(HBVACLF).Methods A total of 25 HBV-ACLF patients
文摘Objective To analyze the serum keratin 18(K18)level of patients with hepatitis B virus(HBV)-related acute-on-chronic liver failure(HBV-ACLF)and its correlation with prognosis.Methods From December 2012 to October 2014,120 patients who visited Fuzhou Infectious Diseases Hospital and were diagnosed with HBV-ACLF were enrolled,and 20 chronic hepatitis B(CHB)pa-
文摘More than 90%of cases of hepatocellular carcinoma(HCC)occurs in patients with cirrhosis,of which hepatitis B virus and hepatitis C virus are the leading causes,while the tumor less frequently arises in autoimmune liver diseases.Advances in understanding tumor immunity have led to a major shift in the treatment of HCC,with the emergence of immunotherapy where therapeutic agents are used to target immune cells rather than cancer cells.Regulatory T cells(Tregs)are the most abundant suppressive cells in the tumor microenvironment and their presence has been correlated with tumor progression,invasiveness,as well as metastasis.Tregs are characterized by the expression of the transcription factor Foxp3 and various mechanisms ranging from cell-to-cell contact to secretion of inhibitory molecules have been implicated in their function.Notably,Tregs amply express checkpoint molecules such as cytotoxic T lymphocyte-associated antigen 4 and programmed cell-death 1 receptor and therefore represent a direct target of immune checkpoint inhibitor(ICI)immunotherapy.Taking into consideration the critical role of Tregs in maintenance of immune homeostasis as well as avoidance of autoimmunity,it is plausible that targeting of Tregs by ICI immunotherapy results in the development of immune-related adverse events(irAEs).Since the use of ICI becomes common in oncology,with an increasing number of new ICI currently under clinical trials for cancer treatment,the occurrence of irAEs is expected to dramatically rise.Herein,we review the current literature focusing on the role of Tregs in HCC evolution taking into account their opposite etiological function in viral and autoimmune chronic liver disease,and we discuss their involvement in irAEs due to the new immunotherapies.
基金Supported by Grants from Shanghai Natural Science Fund,No.09ZR1400500National Natural Science Foundation of China No.30972600Shanghai Health Bureau Fund,No.2012092
文摘AIM: To longitudinally investigate cytokine gene expression and protein levels in Th17 and Treg cells, to observe T-cell phenotypes during hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACHBLF) and to analyze changes in Th17 and Treg phenotypes during disease progression.
基金Supported by National Natural Science Foundation of China,No.30470950
文摘AIM： To explore the relationship between DNA methyltransferase 1 （DNMT1） and hepatitis B virus （HBV）-related hepatocellular carcinoma （HCC） and its biological significance in primary HCC. METHODS： We carried out an immunohistochemical examination of DNMT1 in both HCC and paired nonneoplastic liver tissues from Chinese subjects. DNMT1 mRNA was further examined in HCC cell lines by real-time PCR. We inhibited DNMT1 using siRNA and detected the effect of depletion of DNMT1 on cell proliferation ability and cell apoptosis in the HCC celt line SMMC-7721. RESULTS： DNMT1 protein expression was increased in HCCs compared to histologically normal nonneoplastic liver tissues and the incidence of DNMT1 immunoreactivity in HCCs correlated significantly with poor tumor differentiation （P = 0.014）. There were more cases with DNMT1 overexpression in HCC with HBV （42.85%） than in HCC without HBV （28.57%）. However, no significant difference in DNMT1 expression was found in HBV-positive and HBV-negative cases in the Chinese HCC group. There was a trend that DNMT1 RNA expression increased more in HCC cell lines than in pericarcinoma cell lines and normal liver cell lines. In addition, we inhibited DNMT1 using siRNA in the SMMC-7721 HCC cell line and found depletion of DNMT1 suppressed cells growth independent of expression of proliferating cell nuclear antigen （PCNA）, even in HCC cell lines where DNMT1 was stably decreased. CONCLUSION： The findings implied that DNMT1 plays a key role in HBV-retated hepatocellular tumorigenesis. Depletion of DNMT1 mediates growth suppression in SMMC-7721 cells.
基金Supported by Cancer Sucks,Bixby,Oklahoma Research grantto Kaul R
文摘AIM To investigate gender-specific liver estrogen receptor(ER) expression in normal subjects and patients with hepatitis C virus(HCV)-related cirrhosis and hepatocellular carcinoma(HCC).METHODS Liver tissues from normal donors and patients diagnosed with HCV-related cirrhosis and HCV-related HCC were obtained from the NIH Liver Tissue and Cell Distribution System. The expression of ER subtypes, ERα and ERβ, were evaluated by Western blotting and real-time RT-PCR. The subcellular distribution of ERα and ERβ was further determined in nuclear and cytoplasmic tissue lysates along with the expression ofinflammatory [activated NF-κB and IκB-kinase(IKK)] and oncogenic(cyclin D1) markers by Western blotting and immunohistochemistry. The expression of ERα and ERβ was correlated with the expression of activated NF-κB, activated IKK and cyclin D1 by Spearman's correlation. RESULTS Both ER subtypes were expressed in normal livers but male livers showed significantly higher expression of ERα than females(P < 0.05). We observed significantly higher m RNA expression of ERα in HCV-related HCC liver tissues as compared to normals(P < 0.05) and ERβ in livers of HCV-related cirrhosis and HCV-related HCC subjects(P < 0.05). At the protein level, there was a significantly higher expression of nuclear ERα in livers of HCV-related HCC patients and nuclear ERβ in HCV-related cirrhosis patients as compared to normals(P < 0.05). Furthermore, we observed a significantly higher expression of phosphorylated NF-κB and cyclin D1 in diseased livers(P < 0.05). There was a positive correlation between the expression of nuclear ER subtypes and nuclear cyclin D1 and a negative correlation between cytoplasmic ER subtypes and cytoplasmic phosphorylated IKK in HCV-related HCC livers. These findings suggest that dysregulated expression of ER subtypes following chronic HCVinfection may contribute to the progression of HCVrelated cirrhosis to HCV-related HCC.CONCLUSION Gender differences were observed in ERα expression in normal livers. Alterations in ER subtype expression observed in diseased livers may influence genderrelated disparity in HCV-related pathogenesis.
文摘Background： The ^13C urea breath test （^13C-UBT） is the gold standard for detecting Helicobacterpylori infection. H. pylori pathogenesis in patients with hepatitis B virus （HBV） and related diseases remains obscure. We used ^13C-UBT to detect H. p.vlori infection in patients with chronic HBV infection, HBV-related cirrhosis, HBV-related hepatic carcinoma, and other chronic hepatic diseases. Methods： A total of 131 patients with chronic hepatitis B （HB）, 179 with HBV-related cirrhosis, 103 with HBV-related hepatic carcinoma, 45 with HBV-negative hepatic carcinoma, and 150 controls were tested for H. pylori infection using ^13C-UBT. We compared H. pylori infection rate, liver function, complications of chronic hepatic disease, serum HBV-DNA, serum alpha-fetoprotein （AFP）, and portal hypertensive gastropathy （PHG） incidence among groups. Results： HBV-related cirrhosis was associated with the highest H. pylori infection rate （79.3%）. H. pylori infection rate in chronic HB was significantly higher than in the HBV-negative hepatic carcinoma and control groups （P 〈 0.001 ）. 11. pylori infection rate in patients with HBV-DNA ≥10^3 copies/ml was significantly higher than in those with HBV-DNA 〈103 copies/ml （76.8% vs. 52.4%, P 〈 0.001）. Prothrombin time （21.3 ± 3.5 s vs. 18.8 ±4.3 s）, total bilirubin （47.3±12.3 μmol/L vs. 26.6±7.9 μmol/L）, aspartate aminotransferase （ 184.5 ±37.6 U/L vs. 98.4 ± 23.5 U/L）, blood ammonia （93.4 ± 43.6 μmol/L vs. 35.5 ± 11.7 μmol/L）, and AFP （203.4±62.6 μg/L vs. 113.2± 45.8 μg/L） in the ^13C-UBT-positive group were significantly higher than in the ^13C-UBT-negative group （P 〈 0.01）. The incidence rates of esophageal fundus variceal bleeding （25.4% vs. 16.0%）, ascites （28.9% vs. 17.8%）, and hepatic encephalopathy （24.8% vs. 13.4%） in the ^13C-UBT-positive group were significantly higher than in the 13C-UBT-negative group （P 〈 0.01 ）. The percentages of patients with liver function in Child-Pugh Grade C （29.6% vs. 8.1%） and PHG （43.0% vs. 24.3%） in the ^13C-UBT-positive group were significantly higher than in the ^13C-UBT-negative group （P 〈 0.05）. Conclusions： It is possible that H. pylori infection could increase liver damage caused by HBV. 1t. pylori eradication should be performed in patients with complicating H. pylori infection to delay hepatic disease progression.
基金The present study was financially supported by the National Natural Science Foundation of China(Nos.81973669,81703912,and 81603484)the financial support of the Research Project for Practice Development of National TCM Clinical Research Bases(JDZX2015172)Program of Hanmin Li Famous and Old TCM master’Inheritance Studio.
文摘On the basis of real-world clinical data,the study aimed to explore the effect and mechanisms of the treatment plan of“traditional Chinese medicine(TCM)regulating liver regeneration.”A total of 457 patients with HBV-related liver failure were retrospectively collected.The patients were divided into three groups:the modern medicine control group(MMC group),patients treated with routine medical treatment;the control group combining traditional Chinese and Western medicine(CTW),patients treated with routine medical treatment plus the common TCM formula;and the treatment group of“TCM regulating liver regeneration”(RLR),patients treated with both routine medical treatment and the special TCM formula of RLR.After 8 weeks of treatment,the mortality of patients in the RLR group(12.31%)was significantly lower than those in the MMC(50%)and CTW(29.11%)groups.Total bilirubin level significantly decreased and albumin increased in the RLR group when compared with the MMC and CTW groups(P<0.05).In addition,there were significant differences in the expression of several cytokines related to liver regeneration in the RLR group compared with the MMC group.RLR treatment can decrease jaundice,improve liver function,and significantly reduce the mortality in patients with HBV-related liver failure.The mechanism may be related to the role of RLR treatment in influencing cytokines related to liver regeneration.
基金National Health and Medical Research Council of Australia(NHMRC)Program and Investigator Grants(2008983,1053206,and 1149976,to M.E.)Project and Ideas Grants(1107178 and 1108422,2001692,to M.E.).
文摘Background and Objective:Hepatocellular carcinoma(HCC)poses a significant global health burden and ranks as the fifth most prevalent cancer on a global scale.Hepatitis C virus(HCV)infection remains one of the major risk factors for HCC development.HCC is a heterogeneous disease,and the development of HCC caused by HCV is intricate and involves various factors,including genetic susceptibility,viral factors,immune response due to chronic inflammation,alcohol abuse,and metabolic dysfunction associated with fatty liver disease.In this review,we provide a comprehensive and updated review of research on the genetics and epigenetic mechanisms implicated in developing HCC associated with HCV infection.We also discuss the potential translational implications,including novel biomarkers and drugs for treatment.Methods:A comprehensive literature search was conducted in June 2023 in PubMed and Embase databases.Key Content and Findings:Recent findings indicate that a variety of genetic and epigenetic processes are involved in the pathogenesis and continue to exist even after the complete elimination of HCV.The deregulation of the epigenome has been identified as a significant factor in the deletrious effects of liver disease,especially during the initial stages when genetic alterations are uncommon.The enduring“epigenetic memory”of gene expression is believed to be regulated by epigenetic mechanisms,indicating that alterations caused by HCV infection continue to exist and are linked to the risk of development of liver cancer even after successful treatment.Systems biology analytical methods will be required to delineate the magnitude and significance of both genetic and epigenomic alterations in tumor evolution.Conclusions:By facilitating a more profound understanding of these aspects,this will ultimately foster the advancement of novel therapies and ultimately improve outcomes for patients.
