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
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
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
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
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
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
Viral hepatitis,secondary to infection with hepatitis A,B,C,D,and E viruses,are a major public health problem and an important cause of morbidity and mortality.Despite the huge medical advances achieved in recent year...Viral hepatitis,secondary to infection with hepatitis A,B,C,D,and E viruses,are a major public health problem and an important cause of morbidity and mortality.Despite the huge medical advances achieved in recent years,there are still points of conflict concerning the pathogenesis,immune response,development of new and more effective vaccines,therapies,and treatment.This review focuses on the most important research topics that deal with issues that are currently being solved,those that remain to be solved,and future research directions.For hepatitis A virus we will address epidemiology,molecular surveillance,new susceptible populations as well as environmental and food detections.In the case of hepatitis B virus,we will discuss host factors related to disease,diagnosis,therapy,and vaccine improvement.On hepatitis C virus,we will focus on pathogenesis,immune response,direct action antivirals treatment in the context of solid organ transplantation,issues related to hepatocellular carcinoma development,direct action antivirals resistance due to selection of resistanceassociated variants,and vaccination.Regarding hepatitis D virus,we describe diagnostic methodology,pathogenesis,and therapy.Finally,for hepatitis E virus,we will address epidemiology(including new emerging species),diagnosis,clinical aspects,treatment,the development of a vaccine,and environmental surveillance.展开更多
In this review the current overall knowledge on hepatitis A,B,C,D,and E will be discussed.These diseases are all characterized by liver inflammation but have significant differences in distribution,transmission routes...In this review the current overall knowledge on hepatitis A,B,C,D,and E will be discussed.These diseases are all characterized by liver inflammation but have significant differences in distribution,transmission routes,and outcomes.Hepatitis B virus and hepatitis C virus are transmitted by exposure to infected blood,and in addition to acute infection,they can cause chronic hepatitis,which in turn can evolve into cirrhosis.It is estimated that more than 300 million people suffer from chronic hepatitis B or C worldwide.Hepatitis D virus,which is also transmitted by blood,only affects hepatitis B virus infected people,and this dual infection results in worse liver-related outcomes.Hepatitis A and E spread via the fecal-oral route,which corresponds mainly to the ingestion of food or water contaminated with infected stools.However,in developed countries hepatitis E is predominantly a zoonosis.Although hepatitis A virus and hepatitis E virus are usually responsible for a self-limiting hepatitis,a serious,rarely fatal illness is also possible,and in immunosuppressed patients,such as organ transplant recipients,hepatitis E virus infection can become chronic.The description of goals achieved,unresolved issues,and the latest research on this topic may make it possible to speculate on future scenarios in the world of viral hepatitis.展开更多
This review aims to summarize the current evidence on the treatment of viral hepatitis,focusing on its clinical management.Also,future treatment options and areas of potential research interest are detailed.PubMed and...This review aims to summarize the current evidence on the treatment of viral hepatitis,focusing on its clinical management.Also,future treatment options and areas of potential research interest are detailed.PubMed and Scopus databases were searched for primary studies published within the last ten years.Keywords included hepatitis A virus,hepatitis B virus(HBV),hepatitis C virus,hepatitis D virus(HDV),hepatitis E virus,and treatment.Outcomes reported in the studies were summarized,tabulated,and synthesized.Significant advances in viral hepatitis treatment were accomplished,such as the advent of curative therapies for hepatitis C and the development and improvement of hepatitis A,hepatitis B,and hepatitis E vaccination.Drugs that cure hepatitis B,going beyond viral suppression,are so far unavailable;however,targeted antiviral drugs against HBV(immunomodulatory therapies and gene silencing technologies)are promising approaches to eradicating the virus.Ultimately,high vaccination coverage and large-scale test-and-treat programmes with high screening rates may eliminate viral hepatitis and mitigate their burden on health systems.The development of curative hepatitis C treatment renewed the enthusiasm for curing hepatitis B,albeit further investigation is required.Novel therapeutic options targeting HDV life cycle are currently under clinical investigation.展开更多
Hepatitis C virus (HCV) elimination by 2030, using direct-acting antiviraltreatments, has been promoted by the World Health Organization. Thisachievement is not attainable, however, particularly after the 2020 pandemi...Hepatitis C virus (HCV) elimination by 2030, using direct-acting antiviraltreatments, has been promoted by the World Health Organization. Thisachievement is not attainable, however, particularly after the 2020 pandemic ofthe coronavirus disease 2019. Consequently, the more realistic objective ofeliminating HCV from population segments for which targeted strategies ofprevention and treatment are easily attained has been promoted in Europe, as avalid alternative. The underlying idea is that micro-elimination will ultimatelylead to macro-elimination. The micro-elimination strategy may target differentspecific populations and at-risk groups. Different settings, including prisons andhospitals, have also been identified as micro-elimination scenarios. In addition,dedicated micro-elimination strategies have been designed that are tailored at thegeographical level according to HCV epidemiology and individual country’sincome. The main elements of a valid and successful micro-elimination project arereliable epidemiological data and active involvement of all the stakeholders.Community involvement represents another essential component for a successfulprogram.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
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 Hepatitis D virus-hepatitis B virus(HDV-HBV)co-infection accelerates liver disease progression and increases the risk of hepatocellular carcinoma,but the immunopathogenic mechanism of its combination with a...BACKGROUND Hepatitis D virus-hepatitis B virus(HDV-HBV)co-infection accelerates liver disease progression and increases the risk of hepatocellular carcinoma,but the immunopathogenic mechanism of its combination with autoimmune hepatitis(AIH)has not been clarified.This study reveals for the first time that HDV may induce AIH through abnormalities in immunoregulation in two specific cases.This is the first report of HDV-HBV co-infected patients who did not receive interferon therapy and achieved serological conversion and histological remission by combining antiviral(entecavir)with immunosuppression(prednisone+azathioprine)therapy,providing new evidence of the mechanism of this complex disease.CASE SUMMARY A 40-year-old female developed malaise and jaundice with an alanine aminotransferase/aspartate aminotransferase>20 upper limit of normal(ULN),total bilirubin:97.20μmol/L,immunoglobulin G(IgG)47.1 g/L(>3×ULN),HDV RNA 1.6×10^(7)copies/mL and liver biopsy showed G3S4.Tenofovir alafenamide combined with prednisone and azathioprine was administered,and three months later the Child-Turcotte-Pugh class C was reduced to class B and IgG decreased to 13.62 g/L.Another 58-year-old male complained of pain in the liver area,antinuclear antibody was 1:320,IgG 22.6 g/L(>1.3×ULN),and liver biopsy showed G2S3.Entecavir was administered in combination with prednisone and azathioprine,and after 3 months,liver function returned to normal,and IgG reduced to 14.22 g/L.CONCLUSION Patients with HDV-HBV co-infection combined with AIH can achieve clinical remission following combination therapy,and the study of immunomodulatory mechanisms should be emphasized.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
Immunoprophylaxis is routinely recommended for infants born to mothers with hepatitis B virus(HBV)infection within the first 12-24 hours.Detection of he-patitis B surface antibody(HBsAb)resulting from hepatitis B immu...Immunoprophylaxis is routinely recommended for infants born to mothers with hepatitis B virus(HBV)infection within the first 12-24 hours.Detection of he-patitis B surface antibody(HBsAb)resulting from hepatitis B immunoglobulin administered at birth may be perceived as a real vaccine response.This makes it difficult to detect HBV infection.For this reason,it is recommended that infants born to hepatitis B surface antigen positive mothers and who received immunop-rophylaxis at birth should have HBsAb testing when they are 9-15 months old.展开更多
According to the World Health Organization,an estimated 58 million people worldwide are chronically infected with hepatitis C virus(HCV),yet only about 20%have been formally diagnosed.Traditional laboratory–based ant...According to the World Health Organization,an estimated 58 million people worldwide are chronically infected with hepatitis C virus(HCV),yet only about 20%have been formally diagnosed.Traditional laboratory–based antibody and RNA assays require infrastructure and trained personnel,limiting their uptake in resource-limited and hard-to-reach settings.The OraQuick HCV self-test(HCVST)is the first World Health Organization-prequalified HCVST,which delivers results in 20-40 min via an easy-to-use gum-swab format.Field evaluations report a sensitivity of about 97%–98%and a specificity of about 99%–100%that are comparable with those of blood-based lateral-flow assays(e.g.,Alere Truline,SD Bioline).Usability studies demonstrated an acceptability rate of over 90%and a correct self-test completion rate of over 85%in key populations.HCVST with the Ora-Quick HCVST kit provides a practical,evidence-based approach to closing diagnostic gaps,particularly among underserved or stigmatized populations.To maximize the public health impact,programs should integrate self-testing into national screening algorithms,ensure linkage to RNA confirmation and treatment,and consider economic and operational contexts.展开更多
BACKGROUND Whether rtS106C+H126Y+D134E/rtS106C+H126Y+D134E+L269I(rtCYE/rtCYEI)mutations in the hepatitis B virus(HBV)reverse-transcriptase(RT)region are associated with tenofovir disoproxil fumarate(TDF)resistance is ...BACKGROUND Whether rtS106C+H126Y+D134E/rtS106C+H126Y+D134E+L269I(rtCYE/rtCYEI)mutations in the hepatitis B virus(HBV)reverse-transcriptase(RT)region are associated with tenofovir disoproxil fumarate(TDF)resistance is controversial.AIM To evaluate the presence of the rtCYE/rtCYEI mutations in a large cohort of Chinese patients with chronic HBV infection.METHODS A total of 28236 patients who underwent drug resistance testing at the Fifth Medical Center of Chinese PLA General Hospital from 2007 to 2019 were enrolled.All patients received nucleoside/nucleotide analogues(NAs)therapy,and serum samples were collected for sequence analysis of the HBV RT domain with mutation analysis.RESULTS The detection rates of a single mutation of rtS106C,rtH126Y,rtD134E,and rtL269I were 8.21%,3.20%,2.55%and 61.49%in 23718 genotype C patients,and 1.31%,1.76%,0.21%,and 92.33%in 4266 genotype B patients,respectively.The combined mutations of rtCYE/rtCYEI were only detected in 12 genotype C patients,accounting for 0.042%of all patients.These 12 patients had received NA treatments except TDF before testing.Among them,6 patients had coexisting rtCYE/rtCYEI and lamivudine-resistance mutations,and 2 patients had coexisting rtCYE/rtCYEI and adefovir-resistance mutations.Compared with the wild-type(WT)strain,the replication capacity of rtCYE/rtCYEI mutants from representative patients decreased by 41.1%-71.8%,and TDF susceptibility reduced by less than 2-fold,but rtCYEI+rtA181V/N236T mutants exhibited a 6.2-/9.9-fold decrease in TDF susceptibility.Molecular modeling showed that rtCYE/rtCYEI mutants had a slight decrease in binding energy to TDF compared to the WT strain.In the clinic,emergence of the rtCYE/rtCYEI mutations was not specifically associated with TDF treatment.CONCLUSION HBV rtCYE/rtCYEI mutations have a limited effect on TDF susceptibility and are not sufficient to cause TDF resistance.展开更多
Background:Hepatitis E virus(HEV)may induce acute self-limiting illnesses or persistent infections.Chronic hepatitis E frequently occurs in immunocompromised persons,including organ transplant recipients,HIV-positive ...Background:Hepatitis E virus(HEV)may induce acute self-limiting illnesses or persistent infections.Chronic hepatitis E frequently occurs in immunocompromised persons,including organ transplant recipients,HIV-positive patients,and those with hematological malignancies.It poses a risk of liver fibrosis and cirrhosis.Data sources:Relevant articles published till September 2024 were located using Pub Med searches.The further search terms utilized were:“immunocompromised”,“solid organ transplant”,“HIV”,“hematological malignancy”,and“hepatitis E virus”.A manual search of references from pivotal articles extended further publications.The search parameters encompass publications in English.Results:The epidemiology,clinical manifestations,diagnostic measures,and therapeutic modalities of chronic hepatitis E were discussed.Immunocompromised individuals who are infected with HEV are at an increased risk of developing chronic infections,which may progress to liver fibrosis and cirrhosis.Current understanding of HEV is still limited,and there is no medicine that specifically targets hepatitis E.Consequently,the prevention and management of hepatitis E continue to present a significant challenge.Conclusions:Chronic hepatitis E patients need special attention in clinical practice.The relevant risk factors must be identified to facilitate accurate diagnosis and the implementation of more effective preventive measures,thereby enhancing the monitoring,treatment,and prevention of immunocompromised individuals.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
Chronic hepatitis B(CHB)continues to contribute to worldwide morbidity and mortality significantly.Scientists,clinicians,pharmaceutical companies,and health organizations have dedicated substantial Intellectual and mo...Chronic hepatitis B(CHB)continues to contribute to worldwide morbidity and mortality significantly.Scientists,clinicians,pharmaceutical companies,and health organizations have dedicated substantial Intellectual and monetary resources to finding a cure,increasing immunization rates,and reducing the global burden of CHB.National and international health-related organizations including the center for disease control,the national institute of health,the American Association for the study of liver disease(AASLD),The European association for the study of the Liver(EASL),The Asia Pacific association for the study of the Liver(APASL)and the world health organization release periodic recommendations for disease prevention and treatment.Our review of the most recent guidelines by EASL,AASLD,APASL,and Taiwan Association for the Study of the Liver revealed that an overwhelming majority of cited studies were published before 2018.We reviewed Hepatitis B-related literature published 2018 onwards to identify recent developments and current barriers that will likely direct future efforts towards eradicating hepatitis B.The breakthrough in our understanding of the hepatitis B virus life cycle and resulting drug development is encouraging with significant room for further progress.Data from high-risk populations,most vulnerable to the devastating effects of hepatitis B infection and reactivation remain sparse.Utilization of systems approach,optimization of experimental models,identification and validation of next-generation biomarkers,and precise modulation of the human immune response will be critical for future innovation.Within the foreseeable future,new treatments will likely complement conventional therapies rather than replace them.Most Importantly,pragmatic management of CHB related population health challenges must be prioritized to produce real-world results.展开更多
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 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.
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.
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.
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.
文摘Viral hepatitis,secondary to infection with hepatitis A,B,C,D,and E viruses,are a major public health problem and an important cause of morbidity and mortality.Despite the huge medical advances achieved in recent years,there are still points of conflict concerning the pathogenesis,immune response,development of new and more effective vaccines,therapies,and treatment.This review focuses on the most important research topics that deal with issues that are currently being solved,those that remain to be solved,and future research directions.For hepatitis A virus we will address epidemiology,molecular surveillance,new susceptible populations as well as environmental and food detections.In the case of hepatitis B virus,we will discuss host factors related to disease,diagnosis,therapy,and vaccine improvement.On hepatitis C virus,we will focus on pathogenesis,immune response,direct action antivirals treatment in the context of solid organ transplantation,issues related to hepatocellular carcinoma development,direct action antivirals resistance due to selection of resistanceassociated variants,and vaccination.Regarding hepatitis D virus,we describe diagnostic methodology,pathogenesis,and therapy.Finally,for hepatitis E virus,we will address epidemiology(including new emerging species),diagnosis,clinical aspects,treatment,the development of a vaccine,and environmental surveillance.
文摘In this review the current overall knowledge on hepatitis A,B,C,D,and E will be discussed.These diseases are all characterized by liver inflammation but have significant differences in distribution,transmission routes,and outcomes.Hepatitis B virus and hepatitis C virus are transmitted by exposure to infected blood,and in addition to acute infection,they can cause chronic hepatitis,which in turn can evolve into cirrhosis.It is estimated that more than 300 million people suffer from chronic hepatitis B or C worldwide.Hepatitis D virus,which is also transmitted by blood,only affects hepatitis B virus infected people,and this dual infection results in worse liver-related outcomes.Hepatitis A and E spread via the fecal-oral route,which corresponds mainly to the ingestion of food or water contaminated with infected stools.However,in developed countries hepatitis E is predominantly a zoonosis.Although hepatitis A virus and hepatitis E virus are usually responsible for a self-limiting hepatitis,a serious,rarely fatal illness is also possible,and in immunosuppressed patients,such as organ transplant recipients,hepatitis E virus infection can become chronic.The description of goals achieved,unresolved issues,and the latest research on this topic may make it possible to speculate on future scenarios in the world of viral hepatitis.
文摘This review aims to summarize the current evidence on the treatment of viral hepatitis,focusing on its clinical management.Also,future treatment options and areas of potential research interest are detailed.PubMed and Scopus databases were searched for primary studies published within the last ten years.Keywords included hepatitis A virus,hepatitis B virus(HBV),hepatitis C virus,hepatitis D virus(HDV),hepatitis E virus,and treatment.Outcomes reported in the studies were summarized,tabulated,and synthesized.Significant advances in viral hepatitis treatment were accomplished,such as the advent of curative therapies for hepatitis C and the development and improvement of hepatitis A,hepatitis B,and hepatitis E vaccination.Drugs that cure hepatitis B,going beyond viral suppression,are so far unavailable;however,targeted antiviral drugs against HBV(immunomodulatory therapies and gene silencing technologies)are promising approaches to eradicating the virus.Ultimately,high vaccination coverage and large-scale test-and-treat programmes with high screening rates may eliminate viral hepatitis and mitigate their burden on health systems.The development of curative hepatitis C treatment renewed the enthusiasm for curing hepatitis B,albeit further investigation is required.Novel therapeutic options targeting HDV life cycle are currently under clinical investigation.
文摘Hepatitis C virus (HCV) elimination by 2030, using direct-acting antiviraltreatments, has been promoted by the World Health Organization. Thisachievement is not attainable, however, particularly after the 2020 pandemic ofthe coronavirus disease 2019. Consequently, the more realistic objective ofeliminating HCV from population segments for which targeted strategies ofprevention and treatment are easily attained has been promoted in Europe, as avalid alternative. The underlying idea is that micro-elimination will ultimatelylead to macro-elimination. The micro-elimination strategy may target differentspecific populations and at-risk groups. Different settings, including prisons andhospitals, have also been identified as micro-elimination scenarios. In addition,dedicated micro-elimination strategies have been designed that are tailored at thegeographical level according to HCV epidemiology and individual country’sincome. The main elements of a valid and successful micro-elimination project arereliable epidemiological data and active involvement of all the stakeholders.Community involvement represents another essential component for a successfulprogram.
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.
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.
基金Supported by Xinjiang“Tianshan Talents”Medical and Health High-Level Talent Training Program-Young and Middle-Aged Backbone Medical Talents.
文摘BACKGROUND Hepatitis D virus-hepatitis B virus(HDV-HBV)co-infection accelerates liver disease progression and increases the risk of hepatocellular carcinoma,but the immunopathogenic mechanism of its combination with autoimmune hepatitis(AIH)has not been clarified.This study reveals for the first time that HDV may induce AIH through abnormalities in immunoregulation in two specific cases.This is the first report of HDV-HBV co-infected patients who did not receive interferon therapy and achieved serological conversion and histological remission by combining antiviral(entecavir)with immunosuppression(prednisone+azathioprine)therapy,providing new evidence of the mechanism of this complex disease.CASE SUMMARY A 40-year-old female developed malaise and jaundice with an alanine aminotransferase/aspartate aminotransferase>20 upper limit of normal(ULN),total bilirubin:97.20μmol/L,immunoglobulin G(IgG)47.1 g/L(>3×ULN),HDV RNA 1.6×10^(7)copies/mL and liver biopsy showed G3S4.Tenofovir alafenamide combined with prednisone and azathioprine was administered,and three months later the Child-Turcotte-Pugh class C was reduced to class B and IgG decreased to 13.62 g/L.Another 58-year-old male complained of pain in the liver area,antinuclear antibody was 1:320,IgG 22.6 g/L(>1.3×ULN),and liver biopsy showed G2S3.Entecavir was administered in combination with prednisone and azathioprine,and after 3 months,liver function returned to normal,and IgG reduced to 14.22 g/L.CONCLUSION Patients with HDV-HBV co-infection combined with AIH can achieve clinical remission following combination therapy,and the study of immunomodulatory mechanisms should be emphasized.
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Immunoprophylaxis is routinely recommended for infants born to mothers with hepatitis B virus(HBV)infection within the first 12-24 hours.Detection of he-patitis B surface antibody(HBsAb)resulting from hepatitis B immunoglobulin administered at birth may be perceived as a real vaccine response.This makes it difficult to detect HBV infection.For this reason,it is recommended that infants born to hepatitis B surface antigen positive mothers and who received immunop-rophylaxis at birth should have HBsAb testing when they are 9-15 months old.
文摘According to the World Health Organization,an estimated 58 million people worldwide are chronically infected with hepatitis C virus(HCV),yet only about 20%have been formally diagnosed.Traditional laboratory–based antibody and RNA assays require infrastructure and trained personnel,limiting their uptake in resource-limited and hard-to-reach settings.The OraQuick HCV self-test(HCVST)is the first World Health Organization-prequalified HCVST,which delivers results in 20-40 min via an easy-to-use gum-swab format.Field evaluations report a sensitivity of about 97%–98%and a specificity of about 99%–100%that are comparable with those of blood-based lateral-flow assays(e.g.,Alere Truline,SD Bioline).Usability studies demonstrated an acceptability rate of over 90%and a correct self-test completion rate of over 85%in key populations.HCVST with the Ora-Quick HCVST kit provides a practical,evidence-based approach to closing diagnostic gaps,particularly among underserved or stigmatized populations.To maximize the public health impact,programs should integrate self-testing into national screening algorithms,ensure linkage to RNA confirmation and treatment,and consider economic and operational contexts.
基金Supported by The National Natural Science Foundation of China,No.82470632.
文摘BACKGROUND Whether rtS106C+H126Y+D134E/rtS106C+H126Y+D134E+L269I(rtCYE/rtCYEI)mutations in the hepatitis B virus(HBV)reverse-transcriptase(RT)region are associated with tenofovir disoproxil fumarate(TDF)resistance is controversial.AIM To evaluate the presence of the rtCYE/rtCYEI mutations in a large cohort of Chinese patients with chronic HBV infection.METHODS A total of 28236 patients who underwent drug resistance testing at the Fifth Medical Center of Chinese PLA General Hospital from 2007 to 2019 were enrolled.All patients received nucleoside/nucleotide analogues(NAs)therapy,and serum samples were collected for sequence analysis of the HBV RT domain with mutation analysis.RESULTS The detection rates of a single mutation of rtS106C,rtH126Y,rtD134E,and rtL269I were 8.21%,3.20%,2.55%and 61.49%in 23718 genotype C patients,and 1.31%,1.76%,0.21%,and 92.33%in 4266 genotype B patients,respectively.The combined mutations of rtCYE/rtCYEI were only detected in 12 genotype C patients,accounting for 0.042%of all patients.These 12 patients had received NA treatments except TDF before testing.Among them,6 patients had coexisting rtCYE/rtCYEI and lamivudine-resistance mutations,and 2 patients had coexisting rtCYE/rtCYEI and adefovir-resistance mutations.Compared with the wild-type(WT)strain,the replication capacity of rtCYE/rtCYEI mutants from representative patients decreased by 41.1%-71.8%,and TDF susceptibility reduced by less than 2-fold,but rtCYEI+rtA181V/N236T mutants exhibited a 6.2-/9.9-fold decrease in TDF susceptibility.Molecular modeling showed that rtCYE/rtCYEI mutants had a slight decrease in binding energy to TDF compared to the WT strain.In the clinic,emergence of the rtCYE/rtCYEI mutations was not specifically associated with TDF treatment.CONCLUSION HBV rtCYE/rtCYEI mutations have a limited effect on TDF susceptibility and are not sufficient to cause TDF resistance.
基金supported by grants from the National Natural Science Foundation of China(82272396)Gusu Health Project of Suzhou(GSWS2022076 and GSWS2023004)。
文摘Background:Hepatitis E virus(HEV)may induce acute self-limiting illnesses or persistent infections.Chronic hepatitis E frequently occurs in immunocompromised persons,including organ transplant recipients,HIV-positive patients,and those with hematological malignancies.It poses a risk of liver fibrosis and cirrhosis.Data sources:Relevant articles published till September 2024 were located using Pub Med searches.The further search terms utilized were:“immunocompromised”,“solid organ transplant”,“HIV”,“hematological malignancy”,and“hepatitis E virus”.A manual search of references from pivotal articles extended further publications.The search parameters encompass publications in English.Results:The epidemiology,clinical manifestations,diagnostic measures,and therapeutic modalities of chronic hepatitis E were discussed.Immunocompromised individuals who are infected with HEV are at an increased risk of developing chronic infections,which may progress to liver fibrosis and cirrhosis.Current understanding of HEV is still limited,and there is no medicine that specifically targets hepatitis E.Consequently,the prevention and management of hepatitis E continue to present a significant challenge.Conclusions:Chronic hepatitis E patients need special attention in clinical practice.The relevant risk factors must be identified to facilitate accurate diagnosis and the implementation of more effective preventive measures,thereby enhancing the monitoring,treatment,and prevention of immunocompromised individuals.
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.
文摘Chronic hepatitis B(CHB)continues to contribute to worldwide morbidity and mortality significantly.Scientists,clinicians,pharmaceutical companies,and health organizations have dedicated substantial Intellectual and monetary resources to finding a cure,increasing immunization rates,and reducing the global burden of CHB.National and international health-related organizations including the center for disease control,the national institute of health,the American Association for the study of liver disease(AASLD),The European association for the study of the Liver(EASL),The Asia Pacific association for the study of the Liver(APASL)and the world health organization release periodic recommendations for disease prevention and treatment.Our review of the most recent guidelines by EASL,AASLD,APASL,and Taiwan Association for the Study of the Liver revealed that an overwhelming majority of cited studies were published before 2018.We reviewed Hepatitis B-related literature published 2018 onwards to identify recent developments and current barriers that will likely direct future efforts towards eradicating hepatitis B.The breakthrough in our understanding of the hepatitis B virus life cycle and resulting drug development is encouraging with significant room for further progress.Data from high-risk populations,most vulnerable to the devastating effects of hepatitis B infection and reactivation remain sparse.Utilization of systems approach,optimization of experimental models,identification and validation of next-generation biomarkers,and precise modulation of the human immune response will be critical for future innovation.Within the foreseeable future,new treatments will likely complement conventional therapies rather than replace them.Most Importantly,pragmatic management of CHB related population health challenges must be prioritized to produce real-world results.
