Primary hepatic leiomyosarcoma is a very rare disease,accounting for less than 1%of all primary hepatic malignancies[1].As a malignant tumor of the smooth muscle,it originates in the hepatic blood vessels,bile ducts o...Primary hepatic leiomyosarcoma is a very rare disease,accounting for less than 1%of all primary hepatic malignancies[1].As a malignant tumor of the smooth muscle,it originates in the hepatic blood vessels,bile ducts or round ligaments of the liver[2,3].The clinical manifestations are nonspecific,and tumors are usually asymptomatic until they are relatively large in size.Primary hepatic leiomyosarcoma is characterized by a relatively poor prognosis and aggressive metastatic potential[3].The specific etiology and pathogenesis of primary hepatic leiomyosarcoma are still unclear.Several studies indicated that primary hepatic leiomyosarcoma might be related to acquired immune deficiency syndrome[4],Epstein-Barr virus[5],immunosuppression after organ transplantation[6],hepatitis virus[7,8],Hodgkin’s lymphoma[9]and other medical histories.Here,we present a case of primary hepatic leiomyosarcoma.展开更多
Objective:To evaluate the effectiveness of direct-acting antivirals(DAAs)in patients with chronic hepatitis C,assess changes in liver function and hepatic fibrosis following treatment,and identify independent predicto...Objective:To evaluate the effectiveness of direct-acting antivirals(DAAs)in patients with chronic hepatitis C,assess changes in liver function and hepatic fibrosis following treatment,and identify independent predictors of treatment failure.Methods:This retrospective cohort study included patients who received DAA therapy at Hospital Kuala Lumpur between January 2020 and December 2023.Sustained virologic response(SVR)was assessed at least 12 weeks post-treatment by reverse transcription-polymerase chain reaction for hepatitis C virus(HCV)RNA.Demographic,clinical,and laboratory data were collected and analyzed.Multiple logistic regression analysis was performed to identify independent predictors of treatment failure.Results:A total of 335 patients in the study.The overall SVR rate was 89%.After achieving SVR,significant improvements were observed in liver enzyme levels and non-invasive liver fibrosis scores,whereas the overall Model for End-Stage Liver Disease(MELD)scores remained unchanged.Significant independent predictors of treatment failure included non-compliance with DAA therapy[adjusted odds ratio(aOR)68.3;95%confidence interval(95%CI)16.3-285.0;P<0.001],treatment with sofosbuvir/velpatasvir(aOR 6.1;95%CI 1.4-26.5;P=0.015),MELD score of 10-15(aOR 4.6;95%CI 1.1-18.2;P=0.031),HCV genotype 3 infection(aOR 4.5;95%CI 1.1-17.6;P=0.031),and elevated serum total bilirubin level(aOR 1.1;95%CI 1.0-1.1;P=0.003).Conclusions:DAA therapy yielded a high SVR rate,and treatment failure was strongly associated with non-adherence to therapy and advanced liver disease.These findings underscore the necessity of adherence support,early diagnosis,and individualized clinical management to optimize treatment outcomes in patients with chronic hepatitis C.展开更多
Advanced age impairs bone fracture healing;the underlying mechanism of this phenomenon remains unknown.We determined that apolipoprotein E(ApoE)increases with age and causes poor fracture healing.After deletion of hep...Advanced age impairs bone fracture healing;the underlying mechanism of this phenomenon remains unknown.We determined that apolipoprotein E(ApoE)increases with age and causes poor fracture healing.After deletion of hepatic ApoE expression(ΔApoE),24-month-oldΔApoE mice displayed a 95%reduction in circulating ApoE levels and significantly improved fracture healing.ApoE treatment of aged BMSCs inhibited osteoblast differentiation in tissue culture models;RNA-seq,Western blot,immunofluorescence,and RT-PCR analyses indicated that the Wnt/β-catenin pathway is the target of this inhibition.Indeed,we showed that ApoE had no effect on cultures with stabilizedβ-catenin levels.Next,we determined that Lrp4 serves as the osteoblast cell surface receptor to ApoE,as expression of Lrp4 is required in ApoE-based inhibition of Wnt/β-catenin signaling and osteoblast differentiation.Importantly,we validated this ApoE-Lrp4-Wnt/β-catenin molecular mechanism in human osteoblast differentiation.Finally,we identified an ApoE-neutralizing antibody(NAb)and used it to treat aged,wildtype mice 3 days after fracture surgery resulting in fracture calluses with 35%more bone deposition.Our work here identifies novel liver-to-bone cross-talk and a noninvasive,translatable therapeutic intervention for aged bone regeneration.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)is a major type of liver cancer worldwide.In advanced stages,portal vein tumor thrombosis(PVTT)and jaundice are common,whereas obstructive jaundice(OJ)is relatively rare.Both co...BACKGROUND Hepatocellular carcinoma(HCC)is a major type of liver cancer worldwide.In advanced stages,portal vein tumor thrombosis(PVTT)and jaundice are common,whereas obstructive jaundice(OJ)is relatively rare.Both conditions markedly reduce survival and increase therapeutic complexity.Recently,hepatic artery infusion chemotherapy(HAIC)in combination with targeted immunotherapy has shown promise for advanced HCC.CASE SUMMARY We report a 47-year-old male with advanced HCC complicated by PVTT and OJ,who was admitted with marked jaundice of the skin and sclera.Imaging revealed a large hepatic mass(14.5 cm×11.3 cm)in the right lobe with associated portal vein tumor thrombus.The tertiary bile duct was only mildly dilated,making percutaneous transhepatic cholangiography drainage infeasible.The patient underwent reduced-dose HAIC,which resulted in significant tumor shrinkage and marked reduction in serum bilirubin.This improvement enabled sequential treatment with lenvatinib and camrelizumab.After six cycles,both liver function and alphafetoprotein levels improved.The patient achieved a progression-free survival of 20 months and an overall survival of 29 months.CONCLUSION HAIC can treat high-bilirubin HCC with PVTT and OJ,allowing for subsequent targeted immunotherapy.展开更多
Hepatitis E virus(HEV)is the primary cause of acute viral hepatitis globally and is prevalent in many developing countries.Serological epidemiology studies[1,2]suggest that approximately onethird of the global populat...Hepatitis E virus(HEV)is the primary cause of acute viral hepatitis globally and is prevalent in many developing countries.Serological epidemiology studies[1,2]suggest that approximately onethird of the global population has been infected with HEV.There are an estimated 20 million new cases of HEV infection worldwide annually.World Health Organization(WHO)reported that HEV caused approximately 44000 deaths in 2015,which accounted for3.3%of deaths from viral hepatitis[3,4].Clinically,most cases of acute hepatitis E have a self-limiting course.However,co-infection with other viruses can increase the risk of acute or subacute liver failure.Hepatitis B virus(HBV)and HEV are highly prevalent in many regions worldwide,and these areas have high rates of coinfection with both viruses.The rate of co-infection with HEV among patients with chronic hepatitis B(CHB)is high,resulting in more severe health outcomes and a significantly elevated risk of liver failure and death.展开更多
Hepatitis B virus(HBV)infection is a global health concern.The current sequen-tial endpoints for the treatment of HBV infection include viral suppression,hepatitis B e antigen(HBeAg)seroconversion,functional cure,and ...Hepatitis B virus(HBV)infection is a global health concern.The current sequen-tial endpoints for the treatment of HBV infection include viral suppression,hepatitis B e antigen(HBeAg)seroconversion,functional cure,and covalently closed circular DNA(cccDNA)clearance.Serum hepatitis B core-related antigen(HBcrAg)is an emerging HBV marker comprising three components:HBeAg,hepatitis B core antigen,and p22cr.It responds well to the transcriptional activity of cccDNA in the patient's liver and is a promising alternative marker for serolo-gical testing.There is a strong correlation,and a decrease in its level corresponds to sustained viral suppression.In patients with chronic hepatitis B(CHB),serum HBcrAg levels are good predictors of HBeAg seroconversion(both spontaneous and after antiviral therapy),particularly in HBeAg-positive patients.Both low baseline HBcrAg levels and decreasing levels early in antiviral therapy favored HBsAg seroconversion,which may serve as a good surrogate option for treatment endpoints.In this review,we summarize the role of serum HBcrAg in the treat-ment of CHB.Therefore,long-term continuous monitoring of serum HBcrAg levels contributes to the clinical management of patients with CHB and optimizes the choice of treatment regimen,making it a promising marker for monitoring HBV cure.展开更多
To the Editor:Hepatitis caused by the hepatitis C virus(HCV)infection has a long course,insidious onset,and slow progression.Patients with hepatitis C are often in the late stages by the time of diagnoses.The long-ter...To the Editor:Hepatitis caused by the hepatitis C virus(HCV)infection has a long course,insidious onset,and slow progression.Patients with hepatitis C are often in the late stages by the time of diagnoses.The long-term chronic damage caused by HCV leads to impaired liver function,portal hypertension,liver fibrosis,cirrhosis and even hepatocellular carcinoma(HCC)[1,2].Therefore,it is imperative to improve the diagnosis and treatment of hepatitis C.In 2016,World Health Organization(WHO)set the goal of“eliminating viral hep-atitis as a public health hazard by 2030”.Some associations intro-duced guidelines for hepatitis C screening and treatment.After a period of effort,in 2020,the number of people receiving treatment for chronic HCV infection had significantly increased compared to the number in 2015,and the HCV-related mortality rate had de-creased.Nevertheless,nearly 80%of infected individuals have not been timely diagnosed and treated[3,4].Like many other coun-tries,China still faces a significant gap in achieving the goal of hep-atitis C elimination,and some literature indicated limited public awareness and high medication costs might slow the progress of policy implementation[5-7].How to effectively improve the diag-nosis and treatment of hepatitis C has garnered widespread global attention.展开更多
BACKGROUND For decades,hepatitis A virus(HAV)has been a leading cause of acute hepatitis among children and was less prevalent among adults.However,recently a paradigm shift has been observed in the epidemiology of HA...BACKGROUND For decades,hepatitis A virus(HAV)has been a leading cause of acute hepatitis among children and was less prevalent among adults.However,recently a paradigm shift has been observed in the epidemiology of HAV,as evident by cases of acute hepatitis due to HAV among adults.AIM To estimate frequency of HAV in acute viral hepatitis and compare characteristics in HAV and hepatitis E virus(HEV)infection.METHODS This was a trend analysis conducted at Aga Khan University Hospital Karachi(Sindh,Pakistan)from February 2024 to May 2024.Individuals aged 18 years and older diagnosed with acute viral hepatitis attributed to hepatotropic viruses in 2024 were reviewed.To compare the trend patients admitted with acute hepatitis during 2019-2023 were also reviewed.Data regarding clinical and laboratory parameters were recorded.The yearly trend of acute hepatitis due to HAV and HEV was analyzed,and comparative analysis was done between HAV and HEV cases among adults.RESULTS A total of 396 patients were found to have acute hepatitis during our study duration.HAV was diagnosed in 234 patients(59%)while 157 patients(39.6%)were found to have acute HEV infection.Additionally,acute hepatitis B virus infection was identified in 3 patients(0.7%),whereas acute hepatitis C virus infection was found in 2(0.5%)cases of acute hepatitis.Yearly trends showed increasing occurrence of HAV infection among adults over last 5 years.The patients with acute HAV were younger than patients with HEV(28 years±8 years vs 30 years±8 years;P<0.01).Higher levels of total bilirubin were seen in HEV infection,while higher levels of alanine transaminase were seen in HAV infection.However,a higher proportion of acute liver failure(ALF),coagulopathy,and mortality were observed in HEV.CONCLUSION An increase in acute hepatitis A cases among adults shows less severity than hepatitis E,highlighting the need for better sanitation,hygiene,and adult hepatitis A vaccination programs.展开更多
The highly conserved human leukocyte antigen-A2(HLA-A2)-restricted epitope NS3-1073 represents a promising candidate for a therapeutic vaccine against hepatitis C virus(HCV).In this study,we engineered a set of fusion...The highly conserved human leukocyte antigen-A2(HLA-A2)-restricted epitope NS3-1073 represents a promising candidate for a therapeutic vaccine against hepatitis C virus(HCV).In this study,we engineered a set of fusion proteins based on the artificial self-assembling peptide(SAP),which were expressed in Escherichia coli and spontaneously self-assembled into nanosized particles displaying HCV epitopes,including NS3-1073.To enhance immunogenicity,we incorporated the T helper epitope PADRE into the construct.Alpha-helical linkers were introduced between SAP and the epitopes to facilitate proper protein folding.Notably,a helical linker with a high supercoiling propensity enabled soluble expression of the fusion protein containing both the NS3-1073 and PADRE epitopes,allowing purification of the in vivo-formed nanoparticles by metal affinity chromatography.Human dendritic cells derived from peripheral blood monocytes showed robust activation in response to the fusion proteins and preferentially stimulated T lymphocytes toward a Th1-biased immune response.In mice,immunization with nanoparticles carrying NS3-1073 induced splenocyte proliferation in response to in vitro stimulation with a mixture of NS3 peptides.These results demonstrate that recombinant nanoparticle-based carriers presenting the NS3-1073 epitope can be produced in bacterial systems and hold strong potential as a foundation for a therapeutic HCV vaccine.展开更多
Objective:To assess the knowledge and attitudes of the general population regarding hepatitis B virus(HBV)infection,their association with sociodemographic factors,and the community’s willingness to pay for hepatitis...Objective:To assess the knowledge and attitudes of the general population regarding hepatitis B virus(HBV)infection,their association with sociodemographic factors,and the community’s willingness to pay for hepatitis B vaccination.Methods:This cross-sectional study was conducted from January to March 2025 in Ho Chi Minh City,Vietnam.A self-administered questionnaire was distributed to 1098 adults who were recruited via nonprobability convenience sampling.Descriptive analysis was conducted to calculate the frequencies and percentages of the categorical variables.A Chi-square test was carried out to explore the association between the independent and categorical dependent variables.Results:A total of 926 complete questionnaires were returned and included in the analysis.Among the participants,524(56.6%)exhibited good knowledge about HBV infection and vaccination,while 651(70.3%)showed positive attitudes toward the issues of interest.The factors associated with knowledge and attitudes were household incomes,health insurance,family history of HBV infection,vaccination intention,reasons for nonvaccination,sources of HBV information,and awareness of immunization programs and vaccination sites.Conclusions:Although most participants had limited knowledge of HBV symptoms and transmission,their attitudes toward vaccination remained positive.Targeted national strategies and intervention initiatives are needed since public awareness and attitudes toward the condition greatly impact intervention success.展开更多
Liver is prone to viral infection.Viral hepatitis can be roughly divided into hepatitis A,B,C,D and E.Accurate diagnosis of viral hepatitis is crucial for accurate treatments.Different types of biomarkers,including no...Liver is prone to viral infection.Viral hepatitis can be roughly divided into hepatitis A,B,C,D and E.Accurate diagnosis of viral hepatitis is crucial for accurate treatments.Different types of biomarkers,including non-invasive biomarkers have been explored for the diagnosis of viral hepatitis.With the fast development of multi-omics technology,non-invasive biomarkers can be detected from blood,saliva,urine,stool,and other body fluids.The advantages of non-invasive biomarkers are:1)non-invasive;2)convenient to test and 3)repeatable.The application of non-invasive biomarkers significantly improves the diagnostic accuracy of viral hepatitis.The non-invasive biomarkers can be sugars,proteins,nucleic acids,and even microorganisms.In this review,we summarized recent advances in identifying non-invasive biomarkers using multi-omics technology and discussed their potential diagnostic values for viral hepatitis.展开更多
Objective: To explore the impact of high-quality nursing on the nursing effect of patients with hepatic encephalopathy, and provide a basis for optimizing clinical nursing plans. Methods: A total of 80 patients with h...Objective: To explore the impact of high-quality nursing on the nursing effect of patients with hepatic encephalopathy, and provide a basis for optimizing clinical nursing plans. Methods: A total of 80 patients with hepatic encephalopathy admitted to a hospital from April 2023 to April 2024 were selected and randomly divided into a conventional group (37 cases, receiving conventional nursing) and an observation group (43 cases, receiving high-quality nursing) using a blind selection method. The incidence of complications, nursing satisfaction, changes in quality of life (SF-36 scale) and liver function indicators (ALT, AST, TBIL, ALB) before and after nursing were compared between the two groups. Results: The incidence of complications in the observation group (6.98%) was significantly lower than that in the conventional group (24.32%), and the nursing satisfaction (97.67%) was significantly higher than that in the conventional group (81.08), with statistically significant differences (p < 0.05);after nursing, the scores of each dimension and total score of the SF-36 scale, and the improvement range of liver function indicators in the observation group were significantly better than those in the conventional group, with statistically significant differences (p < 0.05). Conclusion: High-quality nursing can effectively reduce the risk of complications in patients with hepatic encephalopathy, improve nursing satisfaction and quality of life, and enhance liver function, which has important clinical promotion value.展开更多
Background:Liver failure(LF)is a disorder with a high mortality rate and large resource costs.In regions where liver transplantation resources are limited,artificial liver support systems(ALS)such as selective plasma ...Background:Liver failure(LF)is a disorder with a high mortality rate and large resource costs.In regions where liver transplantation resources are limited,artificial liver support systems(ALS)such as selective plasma exchange with dialysis(PED)may serve as a bridge to transplantation or hepatic recovery.This retrospective study aimed to evaluate the clinical outcomes,biochemical parameters,and prognostic factors associated with PED therapy in patients with hepatitis B-related acute-on-chronic liver failure(ACLF).Methods:This was a single-center,retrospective,observational cohort study.A total of 63 consecutive patients with HBV-related ACLF who received PED treatment between January 2020 and December 2022 were analyzed.Patients who underwent liver transplantation(n=11)were included in the survival group,as PED successfully functioned as a bridge to transplantation.The study was approved by the Institutional Review Board and informed consent was obtained.Variables with P<0.10 in univariate analysis were included in a stepwise binary logistic regression model to identify independent predictors of 3-month mortality.Results:Significant improvements in biochemical parameters,including MELD score,INR,TBIL,and blood ammonia,were observed following PED treatment(P<0.05).The overall 3-month mortality rate was 38.10%(24/63).No significant difference in mortality was found between HBeAg-positive patients(15/40,37.50%)and HBeAg-negative patients(9/23,39.13%)(P>0.05).In univariate analysis,3-month mortality was significantly associated with HBV DNA load(P<0.001),ALT(P=0.020),TBIL(P=0.036),DBIL(P=0.009),Cl^(-)(P<0.001),CO_(2)CP(P=0.011),INR(P=0.044),and blood ammonia reduction(P=0.033).However,the MELD score showed no significant association in univariate analysis(P=0.896).By multivariate binary logistic regression analysis,blood ammonia reduction(OR:0.85;95%CI:0.72-0.98;P=0.035)and MELD score(OR:1.12;95%CI:1.01-1.25;P=0.028)were identified as independent predictors of 3-month mortality in all patients.Conclusion:PED treatment was associated with improved biochemical parameters in patients with hepatitis B-related ACLF.Higher blood ammonia reduction was associated with improved survival.In multivariate analysis,blood ammonia reduction and MELD score were independent predictors of 3-month mortality.However,due to the limitations of this single-center,retrospective,observational study,further prospective controlled studies comparing PED with standard medical therapy or conventional plasma exchange are needed to establish the definitive role of PED in mortality reduction.展开更多
Diabetes is accompanied by oxidative damage,inflammation,and disorder of metabolic profiles.Dietary procyanidins have been reported to alleviate symptoms of diabetes,however,the underlying mechanism through which proc...Diabetes is accompanied by oxidative damage,inflammation,and disorder of metabolic profiles.Dietary procyanidins have been reported to alleviate symptoms of diabetes,however,the underlying mechanism through which procyanidins impact liver metabolic function remains unclear.Here,the effects of p eanut skin procyanidins(PSP)on oxidative stress,inflammatory injury,and dysregulated metabolism in the liver of diabetic mice were evaluated.The results showed that PSP r educed the accumulation of cholesterol and alleviated oxidative stress and inflammatory response in the liver.Moreover,PSP enhanced i nsulin signaling by increasing hepatic protein expression of insulin receptor substrate 1/phosphatidylinositol-3-kinase/protein kinase B.Untargeted metabolomics revealed that PSP altered bile acid biosynthesis,alpha linolenic acid and linoleic acid,arachidonic acid,and glycolipid metabolism in the liver.This study reveals positive effects of PSP in alleviating liver dysfunction in diabetic mice.展开更多
OBJECTIVE:To elucidate the therapeutic efficacy and mechanism of action of Chaihu Guizhi Ganjiang decoction(柴胡桂枝干姜汤,CGGD)in autoimmune hepatitis.METHODS:CGGD components and potential target genes were extracted...OBJECTIVE:To elucidate the therapeutic efficacy and mechanism of action of Chaihu Guizhi Ganjiang decoction(柴胡桂枝干姜汤,CGGD)in autoimmune hepatitis.METHODS:CGGD components and potential target genes were extracted from previously published databases.The autoimmune hepatitis(AIH)-related regulatory genes were obtained from the Dis Ge NET database.Intersections were taken,and enrichment analyses were performed on the extracted data.Concanavalin A(Con A)-induced AIH model mice were treated with CGGD via gavage.The results of network pharmacological analysis were experimentally validated.RESULTS:Network pharmacology revealed 228 genes at the intersection of AIH and CGGD.Kyoto Encyclopedia of Genes and Genomes analysis revealed that CGGD primarily regulates the phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)signaling pathway and cellular metabolism in AIH.Gene Ontology enrichment analysis revealed that CGGD modulates inflammation through transcription factor-mediated signaling pathways.As predicted,CGGD attenuated Con A-induced AIH in a dose-dependent manner by activating the PI3K/AKT signaling pathway.Histopathological assessment confirmed the protective effects of CGGD against Con Ainduced AIH.Further investigation revealed that CGGD regulated the T helper cell 17(Th17)/regulatory T cell(Treg)balance by modulating the PI3K/Akt/nuclear factor kappa-B(NF-κB)pathway.CONCLUSIONS:This study demonstrated the therapeutic effect of CGGD on AIH through a combination of network pharmacological prediction and experimental validation.Its mechanism of action involves PI3K/Akt/NF-κB-mediated regulation of Th17/Treg cells.展开更多
Each hepatitis virus—Hepatitis A,B,C,D,E,and G—poses a distinct scenario to the patient and clinician alike.Since the discovery of each virus,extensive knowledge regarding epidemiology,virologic properties,and the n...Each hepatitis virus—Hepatitis A,B,C,D,E,and G—poses a distinct scenario to the patient and clinician alike.Since the discovery of each virus,extensive knowledge regarding epidemiology,virologic properties,and the natural clinical and immunologic history of acute and chronic infections has been generated.Basic discoveries about host immunologic responses to acute and chronic viral infections,combined with virologic data,has led to vaccines to prevent Hepatitis A,B,and E and highly efficacious antivirals for Hepatitis B and C.These therapeutic breakthroughs are transforming the fields of hepatology,transplant medicine in general,and public and global health.Most notably,there is even an ambitious global effort to eliminate chronic viral hepatitis within the next decade.While attainable,there are many barriers to this goal that are being actively investigated in basic and clinical labs on the local,national,and international scales.Herein,we discuss pertinent clinical information and recent organizational guidelines for each of the individual hepatitis viruses while also synthesizing this information with the latest research to focus on exciting future directions for each virus.展开更多
Drug-induced autoimmune-like hepatitis(DI-ALH)is an increasingly recognized phenotype within the spectrum of drug-induced liver injury.Several drugs,including nitrofurantoin,minocycline,hydralazine,methyldopa and infl...Drug-induced autoimmune-like hepatitis(DI-ALH)is an increasingly recognized phenotype within the spectrum of drug-induced liver injury.Several drugs,including nitrofurantoin,minocycline,hydralazine,methyldopa and infliximab,have a well-documented capacity to induce DI-ALH.Distinguishing DI-ALH from classic de novo autoimmune hepatitis(AIH)can be challenging due to overlapping clinical,biochemical,and serological features.Accurate distinction from classic AIH is crucial,as management and prognosis differ.While some DIALH cases resolve spontaneously after drug withdrawal,others show persistent or worsening liver injury.Histological studies have shown that fibrosis and cirrhosis are more prevalent in classic AH.Unfortunately,there are no pathognomic clinical,biochemical or immunological features that reliably distinguish DI-ALH from classic AIH.However,most patients with DI-ALH do not relapse after corticosteroid withdrawal,in contrast to the high relapse rate observed in classic AIH.Most patients respond well to corticosteroids,and once liver tests normalize,biochemical parameters should be monitored,and long-term immunosuppression should not be indicated.However,DI-ALH is not exempt from risk of relapse,underscoring the need for long-term follow-up.Most patients with DIALH have a favorable prognosis;however,although rare,cases of cirrhosis and,in exceptional instances,acute liver failure have been reported.International collaborative studies are needed to further characterize DI-ALH.In this review,we update current controversies,present emerging concepts,and outline future challenges in the diagnosis and management of this complex condition learned so far.展开更多
BACKGROUND Existing assessment systems for chronic hepatitis B(CHB)-associated liver fibrosis(LF)exhibit insufficient accuracy,thereby requiring further improvements.AIM To investigate the association of LF staging wi...BACKGROUND Existing assessment systems for chronic hepatitis B(CHB)-associated liver fibrosis(LF)exhibit insufficient accuracy,thereby requiring further improvements.AIM To investigate the association of LF staging with hepatitis B core antibody(HBcAb),hepatitis B virus DNA(HBV-DNA),and hepatitis B surface antigen(HBsAg)in patients with CHB.METHODS We selected 120 patients with CHB receiving treatment in Hangzhou Linping District First People’s Hospital from January 2020 to June 2024.Participants were allocated into the mild(F0-F1,n=52)and moderate-to-severe groups(F2-F4,n=68)following the rigorous LF staging criteria.HBcAb,HBV-DNA,and HBsAg concentrations were measured.Pearson correlations were employed to examine the correlations of HBcAb with HBV-DNA and HBsAg,whereas Spearman correlation analysis was conducted to identify the associations of the three with LF staging.Receiver operating characteristic(ROC)curves were further used to analyze the performance of these biomarkers in diagnosing LF stages.Furthermore,binary logistic regression analysis was conducted to determine the association of these three with LF progression in CHB.RESULTS Markedly increased HBcAb and notably decreased HBV-DNA and HBsAg were observed in moderate-to-severe cases vs their mild counterparts.A positive correlation was observed between HBV-DNA and HBsAg,whereas both markers were inversely associated with HBcAb.Moreover,LF staging exhibited a significant positive correlation with HBcAb and an inverse connection with HBVDNA and HBsAg.The receiver operating characteristic analysis revealed area under the curve values of 0.715,0.799,and 0.662 for HBcAb,HBV-DNA,and HBsAg in diagnosing LF staging,respectively.Combining these markers improved the area under the curve to 0.851.The final analysis identified HBcAb as promoting fibrosis advancement(odds ratio=2.765),whereas HBVDNA demonstrated protective properties(odds ratio=0.247).CONCLUSION HBcAb is negatively correlated with HBV-DNA and HBsAg but positively associated with LF staging.All three markers are valuable in assessing LF staging,and their combined use presents the highest diagnostic efficacy.Importantly,a high HBcAb/low HBV-DNA profile markedly increased fibrosis progression risks in CHB-affected individuals.展开更多
An estimated 3%-4%of people are living with the hepatitis B virus(HBV),and without treatment,the risk of developing cirrhosis and hepatocellular cancer(HCC)is an omnipresent threat.Prevention of HCC is a major challen...An estimated 3%-4%of people are living with the hepatitis B virus(HBV),and without treatment,the risk of developing cirrhosis and hepatocellular cancer(HCC)is an omnipresent threat.Prevention of HCC is a major challenge,as the association between viral suppression and HCC risk reduction is multifactorial,involving the progressive depletion of hepatocytes through covalently closed circular DNA integration,as well as the prevention of liver fibrosis and cirrhosis.Despite effective and cheap antiviral treatment capable of suppressing HBV replication and thereby cirrhosis and HCC,the current indications for therapy need revision and more research to expand the gamut and treat more infected people.In this review,we discuss the possible expansion of antiviral treatment in chronic hepatitis B to prevent cirrhosis and,importantly,HCC.展开更多
BACKGROUND The relationship between hepatitis B surface antigen(HBsAg)concentrations,hepatitis B virus(HBV)DNA levels,and hepatic function in individuals with chronic hepatitis B(CHB)remains incompletely characterized...BACKGROUND The relationship between hepatitis B surface antigen(HBsAg)concentrations,hepatitis B virus(HBV)DNA levels,and hepatic function in individuals with chronic hepatitis B(CHB)remains incompletely characterized.AIM To examine the association of serum HBsAg concentrations with HBV DNA levels and hepatic function parameters in patients with CHB.METHODS A total of 110 individuals with CHB admitted to Kunming Third People’s Hospital between January 2023 and January 2025 were enrolled as the observation group,whereas 70 age-and sex-matched healthy individuals served as the control group.Fasting peripheral venous blood(5 mL)was collected from all participants.Serum HBsAg and HBV DNA levels(in the observation group),along with hepatic function markers,including total bilirubin(TBIL),aspartate aminotransferase(AST),and alanine aminotransferase(ALT),were measured in both groups.Pearson correlation analysis was used to assess the association between serum HBsAg levels and HBV DNA,TBIL,AST,and ALT levels in patients with CHB.Receiver operating characteristic(ROC)curve analysis was conducted to determine optimal cutoff values of HBsAg for predicting high viral load(HBV DNA≥10^(5) IU/mL)and significant liver injury(ALT≥2×upper limit of normal[ULN]).RESULTS HBsAg levels differed significantly across CHB phases:Immune tolerance(IT)phase(4.62±1.51 lgIU/mL),immune clearance(IC)phase(3.84±1.16 lgIU/mL),low replication(LR)phase(2.99±0.66 lgIU/mL),and HBV e antigen-negative hepatitis(ENH)phase(3.40±0.69 lgIU/mL).Corresponding HBV DNA levels were highest in the IT phase(7.41±1.83 log copies/mL),followed by the IC phase(6.03±1.92 log copies/mL),ENH phase(3.89±1.23 log copies/mL),and LR phase(2.55±1.00 log copies/mL).All hepatic function parameters in patients with CHB were significantly elevated compared to the healthy controls.Pearson correlation analysis showed significant positive associations between serum HBsAg levels and HBV DNA,TBIL,AST,and ALT levels.ROC analysis revealed that an HBsAg cutoff>4.09 lgIU/mL predicted HBV DNA≥105 IU/mL(high viral load)with 88.57%sensitivity,78.67%specificity,and an area under the curve(AUC)of 0.868(P<0.001),while a cutoff>4.07 lgIU/mL predicted ALT≥2×ULN(significant liver injury)with 69.70%sensitivity,90.91%specificity,and an AUC of 0.821(P<0.001).CONCLUSION Serum HBsAg,a noninvasive serological marker,holds significant clinical value in CHB management by aiding in the stratification of viral burden and the prediction of hepatic impairment.展开更多
文摘Primary hepatic leiomyosarcoma is a very rare disease,accounting for less than 1%of all primary hepatic malignancies[1].As a malignant tumor of the smooth muscle,it originates in the hepatic blood vessels,bile ducts or round ligaments of the liver[2,3].The clinical manifestations are nonspecific,and tumors are usually asymptomatic until they are relatively large in size.Primary hepatic leiomyosarcoma is characterized by a relatively poor prognosis and aggressive metastatic potential[3].The specific etiology and pathogenesis of primary hepatic leiomyosarcoma are still unclear.Several studies indicated that primary hepatic leiomyosarcoma might be related to acquired immune deficiency syndrome[4],Epstein-Barr virus[5],immunosuppression after organ transplantation[6],hepatitis virus[7,8],Hodgkin’s lymphoma[9]and other medical histories.Here,we present a case of primary hepatic leiomyosarcoma.
文摘Objective:To evaluate the effectiveness of direct-acting antivirals(DAAs)in patients with chronic hepatitis C,assess changes in liver function and hepatic fibrosis following treatment,and identify independent predictors of treatment failure.Methods:This retrospective cohort study included patients who received DAA therapy at Hospital Kuala Lumpur between January 2020 and December 2023.Sustained virologic response(SVR)was assessed at least 12 weeks post-treatment by reverse transcription-polymerase chain reaction for hepatitis C virus(HCV)RNA.Demographic,clinical,and laboratory data were collected and analyzed.Multiple logistic regression analysis was performed to identify independent predictors of treatment failure.Results:A total of 335 patients in the study.The overall SVR rate was 89%.After achieving SVR,significant improvements were observed in liver enzyme levels and non-invasive liver fibrosis scores,whereas the overall Model for End-Stage Liver Disease(MELD)scores remained unchanged.Significant independent predictors of treatment failure included non-compliance with DAA therapy[adjusted odds ratio(aOR)68.3;95%confidence interval(95%CI)16.3-285.0;P<0.001],treatment with sofosbuvir/velpatasvir(aOR 6.1;95%CI 1.4-26.5;P=0.015),MELD score of 10-15(aOR 4.6;95%CI 1.1-18.2;P=0.031),HCV genotype 3 infection(aOR 4.5;95%CI 1.1-17.6;P=0.031),and elevated serum total bilirubin level(aOR 1.1;95%CI 1.0-1.1;P=0.003).Conclusions:DAA therapy yielded a high SVR rate,and treatment failure was strongly associated with non-adherence to therapy and advanced liver disease.These findings underscore the necessity of adherence support,early diagnosis,and individualized clinical management to optimize treatment outcomes in patients with chronic hepatitis C.
基金supported by a Borden Scholars awardDuke Claude D.Pepper Older Americans Independence Center Pilot Award(P30AG028716)by the NIH/NIA(R01AG081393)。
文摘Advanced age impairs bone fracture healing;the underlying mechanism of this phenomenon remains unknown.We determined that apolipoprotein E(ApoE)increases with age and causes poor fracture healing.After deletion of hepatic ApoE expression(ΔApoE),24-month-oldΔApoE mice displayed a 95%reduction in circulating ApoE levels and significantly improved fracture healing.ApoE treatment of aged BMSCs inhibited osteoblast differentiation in tissue culture models;RNA-seq,Western blot,immunofluorescence,and RT-PCR analyses indicated that the Wnt/β-catenin pathway is the target of this inhibition.Indeed,we showed that ApoE had no effect on cultures with stabilizedβ-catenin levels.Next,we determined that Lrp4 serves as the osteoblast cell surface receptor to ApoE,as expression of Lrp4 is required in ApoE-based inhibition of Wnt/β-catenin signaling and osteoblast differentiation.Importantly,we validated this ApoE-Lrp4-Wnt/β-catenin molecular mechanism in human osteoblast differentiation.Finally,we identified an ApoE-neutralizing antibody(NAb)and used it to treat aged,wildtype mice 3 days after fracture surgery resulting in fracture calluses with 35%more bone deposition.Our work here identifies novel liver-to-bone cross-talk and a noninvasive,translatable therapeutic intervention for aged bone regeneration.
文摘BACKGROUND Hepatocellular carcinoma(HCC)is a major type of liver cancer worldwide.In advanced stages,portal vein tumor thrombosis(PVTT)and jaundice are common,whereas obstructive jaundice(OJ)is relatively rare.Both conditions markedly reduce survival and increase therapeutic complexity.Recently,hepatic artery infusion chemotherapy(HAIC)in combination with targeted immunotherapy has shown promise for advanced HCC.CASE SUMMARY We report a 47-year-old male with advanced HCC complicated by PVTT and OJ,who was admitted with marked jaundice of the skin and sclera.Imaging revealed a large hepatic mass(14.5 cm×11.3 cm)in the right lobe with associated portal vein tumor thrombus.The tertiary bile duct was only mildly dilated,making percutaneous transhepatic cholangiography drainage infeasible.The patient underwent reduced-dose HAIC,which resulted in significant tumor shrinkage and marked reduction in serum bilirubin.This improvement enabled sequential treatment with lenvatinib and camrelizumab.After six cycles,both liver function and alphafetoprotein levels improved.The patient achieved a progression-free survival of 20 months and an overall survival of 29 months.CONCLUSION HAIC can treat high-bilirubin HCC with PVTT and OJ,allowing for subsequent targeted immunotherapy.
基金supported by a grant from the Zhejiang Province Traditional Chinese Medicine Science and Technology Plan Project(2019ZB101)。
文摘Hepatitis E virus(HEV)is the primary cause of acute viral hepatitis globally and is prevalent in many developing countries.Serological epidemiology studies[1,2]suggest that approximately onethird of the global population has been infected with HEV.There are an estimated 20 million new cases of HEV infection worldwide annually.World Health Organization(WHO)reported that HEV caused approximately 44000 deaths in 2015,which accounted for3.3%of deaths from viral hepatitis[3,4].Clinically,most cases of acute hepatitis E have a self-limiting course.However,co-infection with other viruses can increase the risk of acute or subacute liver failure.Hepatitis B virus(HBV)and HEV are highly prevalent in many regions worldwide,and these areas have high rates of coinfection with both viruses.The rate of co-infection with HEV among patients with chronic hepatitis B(CHB)is high,resulting in more severe health outcomes and a significantly elevated risk of liver failure and death.
基金Supported by The Chongqing Talents Project,No.cstc2021ycjh-bgzxm0150The First Batch of Key Disciplines on Public Health in Chongqing,The Health Commission of Chongqing,No.2022(72)+1 种基金The Remarkable Innovation-Clinical Research Project,The Second Affiliated Hospital of Chongqing Medical UniversityThe Scientific and Technological Research Program of Chongqing Municipal Education Commission,the Second Affiliated Hospital of Chongqing Medical University,No.KJZD-K202300404.
文摘Hepatitis B virus(HBV)infection is a global health concern.The current sequen-tial endpoints for the treatment of HBV infection include viral suppression,hepatitis B e antigen(HBeAg)seroconversion,functional cure,and covalently closed circular DNA(cccDNA)clearance.Serum hepatitis B core-related antigen(HBcrAg)is an emerging HBV marker comprising three components:HBeAg,hepatitis B core antigen,and p22cr.It responds well to the transcriptional activity of cccDNA in the patient's liver and is a promising alternative marker for serolo-gical testing.There is a strong correlation,and a decrease in its level corresponds to sustained viral suppression.In patients with chronic hepatitis B(CHB),serum HBcrAg levels are good predictors of HBeAg seroconversion(both spontaneous and after antiviral therapy),particularly in HBeAg-positive patients.Both low baseline HBcrAg levels and decreasing levels early in antiviral therapy favored HBsAg seroconversion,which may serve as a good surrogate option for treatment endpoints.In this review,we summarize the role of serum HBcrAg in the treat-ment of CHB.Therefore,long-term continuous monitoring of serum HBcrAg levels contributes to the clinical management of patients with CHB and optimizes the choice of treatment regimen,making it a promising marker for monitoring HBV cure.
基金supported by a grant from the R&D Program of China(2022YFC2304500).
文摘To the Editor:Hepatitis caused by the hepatitis C virus(HCV)infection has a long course,insidious onset,and slow progression.Patients with hepatitis C are often in the late stages by the time of diagnoses.The long-term chronic damage caused by HCV leads to impaired liver function,portal hypertension,liver fibrosis,cirrhosis and even hepatocellular carcinoma(HCC)[1,2].Therefore,it is imperative to improve the diagnosis and treatment of hepatitis C.In 2016,World Health Organization(WHO)set the goal of“eliminating viral hep-atitis as a public health hazard by 2030”.Some associations intro-duced guidelines for hepatitis C screening and treatment.After a period of effort,in 2020,the number of people receiving treatment for chronic HCV infection had significantly increased compared to the number in 2015,and the HCV-related mortality rate had de-creased.Nevertheless,nearly 80%of infected individuals have not been timely diagnosed and treated[3,4].Like many other coun-tries,China still faces a significant gap in achieving the goal of hep-atitis C elimination,and some literature indicated limited public awareness and high medication costs might slow the progress of policy implementation[5-7].How to effectively improve the diag-nosis and treatment of hepatitis C has garnered widespread global attention.
文摘BACKGROUND For decades,hepatitis A virus(HAV)has been a leading cause of acute hepatitis among children and was less prevalent among adults.However,recently a paradigm shift has been observed in the epidemiology of HAV,as evident by cases of acute hepatitis due to HAV among adults.AIM To estimate frequency of HAV in acute viral hepatitis and compare characteristics in HAV and hepatitis E virus(HEV)infection.METHODS This was a trend analysis conducted at Aga Khan University Hospital Karachi(Sindh,Pakistan)from February 2024 to May 2024.Individuals aged 18 years and older diagnosed with acute viral hepatitis attributed to hepatotropic viruses in 2024 were reviewed.To compare the trend patients admitted with acute hepatitis during 2019-2023 were also reviewed.Data regarding clinical and laboratory parameters were recorded.The yearly trend of acute hepatitis due to HAV and HEV was analyzed,and comparative analysis was done between HAV and HEV cases among adults.RESULTS A total of 396 patients were found to have acute hepatitis during our study duration.HAV was diagnosed in 234 patients(59%)while 157 patients(39.6%)were found to have acute HEV infection.Additionally,acute hepatitis B virus infection was identified in 3 patients(0.7%),whereas acute hepatitis C virus infection was found in 2(0.5%)cases of acute hepatitis.Yearly trends showed increasing occurrence of HAV infection among adults over last 5 years.The patients with acute HAV were younger than patients with HEV(28 years±8 years vs 30 years±8 years;P<0.01).Higher levels of total bilirubin were seen in HEV infection,while higher levels of alanine transaminase were seen in HAV infection.However,a higher proportion of acute liver failure(ALF),coagulopathy,and mortality were observed in HEV.CONCLUSION An increase in acute hepatitis A cases among adults shows less severity than hepatitis E,highlighting the need for better sanitation,hygiene,and adult hepatitis A vaccination programs.
基金supported by the Russian Science Foundation(Grant No.24-25-20087 to V.K.)。
文摘The highly conserved human leukocyte antigen-A2(HLA-A2)-restricted epitope NS3-1073 represents a promising candidate for a therapeutic vaccine against hepatitis C virus(HCV).In this study,we engineered a set of fusion proteins based on the artificial self-assembling peptide(SAP),which were expressed in Escherichia coli and spontaneously self-assembled into nanosized particles displaying HCV epitopes,including NS3-1073.To enhance immunogenicity,we incorporated the T helper epitope PADRE into the construct.Alpha-helical linkers were introduced between SAP and the epitopes to facilitate proper protein folding.Notably,a helical linker with a high supercoiling propensity enabled soluble expression of the fusion protein containing both the NS3-1073 and PADRE epitopes,allowing purification of the in vivo-formed nanoparticles by metal affinity chromatography.Human dendritic cells derived from peripheral blood monocytes showed robust activation in response to the fusion proteins and preferentially stimulated T lymphocytes toward a Th1-biased immune response.In mice,immunization with nanoparticles carrying NS3-1073 induced splenocyte proliferation in response to in vitro stimulation with a mixture of NS3 peptides.These results demonstrate that recombinant nanoparticle-based carriers presenting the NS3-1073 epitope can be produced in bacterial systems and hold strong potential as a foundation for a therapeutic HCV vaccine.
基金funded by Vietnam National University Ho Chi Minh City(VNU-HCM)under grant number 36-2025-44-02.
文摘Objective:To assess the knowledge and attitudes of the general population regarding hepatitis B virus(HBV)infection,their association with sociodemographic factors,and the community’s willingness to pay for hepatitis B vaccination.Methods:This cross-sectional study was conducted from January to March 2025 in Ho Chi Minh City,Vietnam.A self-administered questionnaire was distributed to 1098 adults who were recruited via nonprobability convenience sampling.Descriptive analysis was conducted to calculate the frequencies and percentages of the categorical variables.A Chi-square test was carried out to explore the association between the independent and categorical dependent variables.Results:A total of 926 complete questionnaires were returned and included in the analysis.Among the participants,524(56.6%)exhibited good knowledge about HBV infection and vaccination,while 651(70.3%)showed positive attitudes toward the issues of interest.The factors associated with knowledge and attitudes were household incomes,health insurance,family history of HBV infection,vaccination intention,reasons for nonvaccination,sources of HBV information,and awareness of immunization programs and vaccination sites.Conclusions:Although most participants had limited knowledge of HBV symptoms and transmission,their attitudes toward vaccination remained positive.Targeted national strategies and intervention initiatives are needed since public awareness and attitudes toward the condition greatly impact intervention success.
文摘Liver is prone to viral infection.Viral hepatitis can be roughly divided into hepatitis A,B,C,D and E.Accurate diagnosis of viral hepatitis is crucial for accurate treatments.Different types of biomarkers,including non-invasive biomarkers have been explored for the diagnosis of viral hepatitis.With the fast development of multi-omics technology,non-invasive biomarkers can be detected from blood,saliva,urine,stool,and other body fluids.The advantages of non-invasive biomarkers are:1)non-invasive;2)convenient to test and 3)repeatable.The application of non-invasive biomarkers significantly improves the diagnostic accuracy of viral hepatitis.The non-invasive biomarkers can be sugars,proteins,nucleic acids,and even microorganisms.In this review,we summarized recent advances in identifying non-invasive biomarkers using multi-omics technology and discussed their potential diagnostic values for viral hepatitis.
基金Chongqing Vocational Education Teaching Reform Research Project,Exploration and Practice of Psychological Education System in Higher Vocational Colleges from the Perspective of Fostering Morality and Cultivating People(Project No.:Z2241421)。
文摘Objective: To explore the impact of high-quality nursing on the nursing effect of patients with hepatic encephalopathy, and provide a basis for optimizing clinical nursing plans. Methods: A total of 80 patients with hepatic encephalopathy admitted to a hospital from April 2023 to April 2024 were selected and randomly divided into a conventional group (37 cases, receiving conventional nursing) and an observation group (43 cases, receiving high-quality nursing) using a blind selection method. The incidence of complications, nursing satisfaction, changes in quality of life (SF-36 scale) and liver function indicators (ALT, AST, TBIL, ALB) before and after nursing were compared between the two groups. Results: The incidence of complications in the observation group (6.98%) was significantly lower than that in the conventional group (24.32%), and the nursing satisfaction (97.67%) was significantly higher than that in the conventional group (81.08), with statistically significant differences (p < 0.05);after nursing, the scores of each dimension and total score of the SF-36 scale, and the improvement range of liver function indicators in the observation group were significantly better than those in the conventional group, with statistically significant differences (p < 0.05). Conclusion: High-quality nursing can effectively reduce the risk of complications in patients with hepatic encephalopathy, improve nursing satisfaction and quality of life, and enhance liver function, which has important clinical promotion value.
基金supported by Beijing Gandan Xiangzhao Charity Foundation(iGandanF-1082022-RGG023).
文摘Background:Liver failure(LF)is a disorder with a high mortality rate and large resource costs.In regions where liver transplantation resources are limited,artificial liver support systems(ALS)such as selective plasma exchange with dialysis(PED)may serve as a bridge to transplantation or hepatic recovery.This retrospective study aimed to evaluate the clinical outcomes,biochemical parameters,and prognostic factors associated with PED therapy in patients with hepatitis B-related acute-on-chronic liver failure(ACLF).Methods:This was a single-center,retrospective,observational cohort study.A total of 63 consecutive patients with HBV-related ACLF who received PED treatment between January 2020 and December 2022 were analyzed.Patients who underwent liver transplantation(n=11)were included in the survival group,as PED successfully functioned as a bridge to transplantation.The study was approved by the Institutional Review Board and informed consent was obtained.Variables with P<0.10 in univariate analysis were included in a stepwise binary logistic regression model to identify independent predictors of 3-month mortality.Results:Significant improvements in biochemical parameters,including MELD score,INR,TBIL,and blood ammonia,were observed following PED treatment(P<0.05).The overall 3-month mortality rate was 38.10%(24/63).No significant difference in mortality was found between HBeAg-positive patients(15/40,37.50%)and HBeAg-negative patients(9/23,39.13%)(P>0.05).In univariate analysis,3-month mortality was significantly associated with HBV DNA load(P<0.001),ALT(P=0.020),TBIL(P=0.036),DBIL(P=0.009),Cl^(-)(P<0.001),CO_(2)CP(P=0.011),INR(P=0.044),and blood ammonia reduction(P=0.033).However,the MELD score showed no significant association in univariate analysis(P=0.896).By multivariate binary logistic regression analysis,blood ammonia reduction(OR:0.85;95%CI:0.72-0.98;P=0.035)and MELD score(OR:1.12;95%CI:1.01-1.25;P=0.028)were identified as independent predictors of 3-month mortality in all patients.Conclusion:PED treatment was associated with improved biochemical parameters in patients with hepatitis B-related ACLF.Higher blood ammonia reduction was associated with improved survival.In multivariate analysis,blood ammonia reduction and MELD score were independent predictors of 3-month mortality.However,due to the limitations of this single-center,retrospective,observational study,further prospective controlled studies comparing PED with standard medical therapy or conventional plasma exchange are needed to establish the definitive role of PED in mortality reduction.
基金supported by the project of National Natural Science Foundation of China(32272331 and 82560638)Guizhou Provincial Science and Technology Projects(Qiankehe[2024]youth 326)+1 种基金Zunyi Science and Technology Projects(Zunshikehe HZ zi 2024312 hao)Guizhou Provincial Health Commission Science and Technology Fund(gzwkj2025-512).
文摘Diabetes is accompanied by oxidative damage,inflammation,and disorder of metabolic profiles.Dietary procyanidins have been reported to alleviate symptoms of diabetes,however,the underlying mechanism through which procyanidins impact liver metabolic function remains unclear.Here,the effects of p eanut skin procyanidins(PSP)on oxidative stress,inflammatory injury,and dysregulated metabolism in the liver of diabetic mice were evaluated.The results showed that PSP r educed the accumulation of cholesterol and alleviated oxidative stress and inflammatory response in the liver.Moreover,PSP enhanced i nsulin signaling by increasing hepatic protein expression of insulin receptor substrate 1/phosphatidylinositol-3-kinase/protein kinase B.Untargeted metabolomics revealed that PSP altered bile acid biosynthesis,alpha linolenic acid and linoleic acid,arachidonic acid,and glycolipid metabolism in the liver.This study reveals positive effects of PSP in alleviating liver dysfunction in diabetic mice.
基金Supported by the Nanjing Health Science and Technology Key Medical Science and Technology Development Program:Mechanism of Action of the Modified Si-Miao Powder with Sanguisorba Carbonisata in Regulating Microbiota and Microecology for the Treatment of Recurrent Vulvovaginal Candidiasis(ZKX22039)。
文摘OBJECTIVE:To elucidate the therapeutic efficacy and mechanism of action of Chaihu Guizhi Ganjiang decoction(柴胡桂枝干姜汤,CGGD)in autoimmune hepatitis.METHODS:CGGD components and potential target genes were extracted from previously published databases.The autoimmune hepatitis(AIH)-related regulatory genes were obtained from the Dis Ge NET database.Intersections were taken,and enrichment analyses were performed on the extracted data.Concanavalin A(Con A)-induced AIH model mice were treated with CGGD via gavage.The results of network pharmacological analysis were experimentally validated.RESULTS:Network pharmacology revealed 228 genes at the intersection of AIH and CGGD.Kyoto Encyclopedia of Genes and Genomes analysis revealed that CGGD primarily regulates the phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)signaling pathway and cellular metabolism in AIH.Gene Ontology enrichment analysis revealed that CGGD modulates inflammation through transcription factor-mediated signaling pathways.As predicted,CGGD attenuated Con A-induced AIH in a dose-dependent manner by activating the PI3K/AKT signaling pathway.Histopathological assessment confirmed the protective effects of CGGD against Con Ainduced AIH.Further investigation revealed that CGGD regulated the T helper cell 17(Th17)/regulatory T cell(Treg)balance by modulating the PI3K/Akt/nuclear factor kappa-B(NF-κB)pathway.CONCLUSIONS:This study demonstrated the therapeutic effect of CGGD on AIH through a combination of network pharmacological prediction and experimental validation.Its mechanism of action involves PI3K/Akt/NF-κB-mediated regulation of Th17/Treg cells.
文摘Each hepatitis virus—Hepatitis A,B,C,D,E,and G—poses a distinct scenario to the patient and clinician alike.Since the discovery of each virus,extensive knowledge regarding epidemiology,virologic properties,and the natural clinical and immunologic history of acute and chronic infections has been generated.Basic discoveries about host immunologic responses to acute and chronic viral infections,combined with virologic data,has led to vaccines to prevent Hepatitis A,B,and E and highly efficacious antivirals for Hepatitis B and C.These therapeutic breakthroughs are transforming the fields of hepatology,transplant medicine in general,and public and global health.Most notably,there is even an ambitious global effort to eliminate chronic viral hepatitis within the next decade.While attainable,there are many barriers to this goal that are being actively investigated in basic and clinical labs on the local,national,and international scales.Herein,we discuss pertinent clinical information and recent organizational guidelines for each of the individual hepatitis viruses while also synthesizing this information with the latest research to focus on exciting future directions for each virus.
文摘Drug-induced autoimmune-like hepatitis(DI-ALH)is an increasingly recognized phenotype within the spectrum of drug-induced liver injury.Several drugs,including nitrofurantoin,minocycline,hydralazine,methyldopa and infliximab,have a well-documented capacity to induce DI-ALH.Distinguishing DI-ALH from classic de novo autoimmune hepatitis(AIH)can be challenging due to overlapping clinical,biochemical,and serological features.Accurate distinction from classic AIH is crucial,as management and prognosis differ.While some DIALH cases resolve spontaneously after drug withdrawal,others show persistent or worsening liver injury.Histological studies have shown that fibrosis and cirrhosis are more prevalent in classic AH.Unfortunately,there are no pathognomic clinical,biochemical or immunological features that reliably distinguish DI-ALH from classic AIH.However,most patients with DI-ALH do not relapse after corticosteroid withdrawal,in contrast to the high relapse rate observed in classic AIH.Most patients respond well to corticosteroids,and once liver tests normalize,biochemical parameters should be monitored,and long-term immunosuppression should not be indicated.However,DI-ALH is not exempt from risk of relapse,underscoring the need for long-term follow-up.Most patients with DIALH have a favorable prognosis;however,although rare,cases of cirrhosis and,in exceptional instances,acute liver failure have been reported.International collaborative studies are needed to further characterize DI-ALH.In this review,we update current controversies,present emerging concepts,and outline future challenges in the diagnosis and management of this complex condition learned so far.
文摘BACKGROUND Existing assessment systems for chronic hepatitis B(CHB)-associated liver fibrosis(LF)exhibit insufficient accuracy,thereby requiring further improvements.AIM To investigate the association of LF staging with hepatitis B core antibody(HBcAb),hepatitis B virus DNA(HBV-DNA),and hepatitis B surface antigen(HBsAg)in patients with CHB.METHODS We selected 120 patients with CHB receiving treatment in Hangzhou Linping District First People’s Hospital from January 2020 to June 2024.Participants were allocated into the mild(F0-F1,n=52)and moderate-to-severe groups(F2-F4,n=68)following the rigorous LF staging criteria.HBcAb,HBV-DNA,and HBsAg concentrations were measured.Pearson correlations were employed to examine the correlations of HBcAb with HBV-DNA and HBsAg,whereas Spearman correlation analysis was conducted to identify the associations of the three with LF staging.Receiver operating characteristic(ROC)curves were further used to analyze the performance of these biomarkers in diagnosing LF stages.Furthermore,binary logistic regression analysis was conducted to determine the association of these three with LF progression in CHB.RESULTS Markedly increased HBcAb and notably decreased HBV-DNA and HBsAg were observed in moderate-to-severe cases vs their mild counterparts.A positive correlation was observed between HBV-DNA and HBsAg,whereas both markers were inversely associated with HBcAb.Moreover,LF staging exhibited a significant positive correlation with HBcAb and an inverse connection with HBVDNA and HBsAg.The receiver operating characteristic analysis revealed area under the curve values of 0.715,0.799,and 0.662 for HBcAb,HBV-DNA,and HBsAg in diagnosing LF staging,respectively.Combining these markers improved the area under the curve to 0.851.The final analysis identified HBcAb as promoting fibrosis advancement(odds ratio=2.765),whereas HBVDNA demonstrated protective properties(odds ratio=0.247).CONCLUSION HBcAb is negatively correlated with HBV-DNA and HBsAg but positively associated with LF staging.All three markers are valuable in assessing LF staging,and their combined use presents the highest diagnostic efficacy.Importantly,a high HBcAb/low HBV-DNA profile markedly increased fibrosis progression risks in CHB-affected individuals.
文摘An estimated 3%-4%of people are living with the hepatitis B virus(HBV),and without treatment,the risk of developing cirrhosis and hepatocellular cancer(HCC)is an omnipresent threat.Prevention of HCC is a major challenge,as the association between viral suppression and HCC risk reduction is multifactorial,involving the progressive depletion of hepatocytes through covalently closed circular DNA integration,as well as the prevention of liver fibrosis and cirrhosis.Despite effective and cheap antiviral treatment capable of suppressing HBV replication and thereby cirrhosis and HCC,the current indications for therapy need revision and more research to expand the gamut and treat more infected people.In this review,we discuss the possible expansion of antiviral treatment in chronic hepatitis B to prevent cirrhosis and,importantly,HCC.
文摘BACKGROUND The relationship between hepatitis B surface antigen(HBsAg)concentrations,hepatitis B virus(HBV)DNA levels,and hepatic function in individuals with chronic hepatitis B(CHB)remains incompletely characterized.AIM To examine the association of serum HBsAg concentrations with HBV DNA levels and hepatic function parameters in patients with CHB.METHODS A total of 110 individuals with CHB admitted to Kunming Third People’s Hospital between January 2023 and January 2025 were enrolled as the observation group,whereas 70 age-and sex-matched healthy individuals served as the control group.Fasting peripheral venous blood(5 mL)was collected from all participants.Serum HBsAg and HBV DNA levels(in the observation group),along with hepatic function markers,including total bilirubin(TBIL),aspartate aminotransferase(AST),and alanine aminotransferase(ALT),were measured in both groups.Pearson correlation analysis was used to assess the association between serum HBsAg levels and HBV DNA,TBIL,AST,and ALT levels in patients with CHB.Receiver operating characteristic(ROC)curve analysis was conducted to determine optimal cutoff values of HBsAg for predicting high viral load(HBV DNA≥10^(5) IU/mL)and significant liver injury(ALT≥2×upper limit of normal[ULN]).RESULTS HBsAg levels differed significantly across CHB phases:Immune tolerance(IT)phase(4.62±1.51 lgIU/mL),immune clearance(IC)phase(3.84±1.16 lgIU/mL),low replication(LR)phase(2.99±0.66 lgIU/mL),and HBV e antigen-negative hepatitis(ENH)phase(3.40±0.69 lgIU/mL).Corresponding HBV DNA levels were highest in the IT phase(7.41±1.83 log copies/mL),followed by the IC phase(6.03±1.92 log copies/mL),ENH phase(3.89±1.23 log copies/mL),and LR phase(2.55±1.00 log copies/mL).All hepatic function parameters in patients with CHB were significantly elevated compared to the healthy controls.Pearson correlation analysis showed significant positive associations between serum HBsAg levels and HBV DNA,TBIL,AST,and ALT levels.ROC analysis revealed that an HBsAg cutoff>4.09 lgIU/mL predicted HBV DNA≥105 IU/mL(high viral load)with 88.57%sensitivity,78.67%specificity,and an area under the curve(AUC)of 0.868(P<0.001),while a cutoff>4.07 lgIU/mL predicted ALT≥2×ULN(significant liver injury)with 69.70%sensitivity,90.91%specificity,and an AUC of 0.821(P<0.001).CONCLUSION Serum HBsAg,a noninvasive serological marker,holds significant clinical value in CHB management by aiding in the stratification of viral burden and the prediction of hepatic impairment.
