Quantitative hepatitis B core antibody and quantitative hepatitis B surface antigen:Novel viral biomarkers for chronic hepatitis B management

The management of hepatitis B virus(HBV)infection now involves regular and appropriate monitoring of viral activity,disease progression,and treatment response.Traditional HBV infection biomarkers are limited in their ability to predict clinical outcomes or therapeutic effectiveness.Quantitation of HBV core antibodies(qAnti-HBc)is a novel non-invasive biomarker that may help with a variety of diagnostic issues.It was shown to correlate strongly with infection stages,hepatic inflammation and fibrosis,chronic infection exacerbations,and the presence of occult infection.Furthermore,qAnti-HBc levels were shown to be predictive of spontaneous or treatment-induced HBeAg and HBsAg seroclearance,relapse after medication termination,re-infection following liver transplantation,and viral reactivation in the presence of immunosuppression.qAnti-HBc,on the other hand,cannot be relied on as a single diagnostic test to address all problems,and its diagnostic and prognostic potential may be greatly increased when paired with qHBsAg.Commercial qAnti-HBc diagnostic kits are currently not widely available.Because many methodologies are only semi-quantitative,comparing data from various studies and defining universal cut-off values remains difficult.This review focuses on the clinical utility of qAnti-HBc and qHBsAg in chronic hepatitis B management.

Chronic hepatitis B and occult infection in chemotherapy patients-evaluation in oncology and hemato-oncology settings:The CHOICE study

BACKGROUND Reactivation of hepatitis B virus(HBV)infection is a well-known risk that can occur spontaneously or following immunosuppressive therapies,including cancer chemotherapy.HBV reactivation can cause significant morbidity and even mortality,which are preventable if at-risk individuals are identified through screening and started on antiviral prophylaxis.AIM To determine the prevalence of chronic HBV(CHB)and occult HBV infection(OBI)among oncology and hematology-oncology patients undergoing chemo-therapy.METHODS In this observational study,the prevalence of CHB and OBI was assessed among patients receiving chemotherapy.Serological markers of HBV infection[hepatitis B surface antigen(HBsAg)/anti-hepatitis B core antigen(HBc)]were evaluated for all patients.HBV DNA levels were assessed in those who tested negative for HBsAg but positive for total anti-HBc.RESULTS The prevalence of CHB in the study cohort was determined to be 2.3%[95%confidence interval(95%CI):1.0-4.2].Additionally,the prevalence of OBI among the study participants was found to be 0.8%(95%CI:0.2-2.3).CONCLUSION The findings of this study highlight the importance of screening for hepatitis B infection in oncology and hematology-oncology patients undergoing chemotherapy.Identifying individuals with CHB and OBI is crucial for implementing appropriate antiviral prophylaxis to prevent the reactivation of HBV infection,which can lead to increased morbidity and mortality.

Chronic Hepatitis B in Indian Americans: Lack of Screening and Poor Linkage to Care

Background: Chronic hepatitis B (CHB) is a major cause of liver-related morbidity and mortality in the United States (US) and globally. CHB disproportionately affects Asian Americans and many other immigrant minority populations, primarily owing to the high prevalence of CHB in their countries of origin. India is a country with a medium-to-high prevalence of hepatitis B (HB) (>2%) and has over 40 million people infected with hepatitis B virus (HBV), with more than 115,000 deaths annually from HBV-related complications. Indian Americans are one of the largest immigrant populations in the US but remain underdiagnosed and poorly linked to clinical care. We, therefore, assessed the HBV prevalence and evaluated the linkage-to-care (LTC) among Indian Americans to develop strategic plans to reduce the impact of HBV in the US. Methods: Between April 2022 and January 2024, serologic screening and surveys were provided to 328 Indian American adults (age 20 - 80) in New York City. All participants were tested for a triple panel consisting of hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), and hepatitis B core IgG antibody (anti-HBc). A survey was conducted on the subjects chronically infected with HBV regarding their histories of infection. Self-administered questionnaires were employed to evaluate demographic and epidemiologic characteristics. Results: Of 328 screened and evaluated (246 males and 82 females), 10 (3.0%) were HBV-infected, 222 (67.7%) were susceptible to HBV, and 96 (29.3%) were immune. The prevalence of chronic HBV varied between the age groups: 4.6% (age 20 - 40), 3.4% (age 41 - 60), and 1.7% (age 61 - 80). Of 10 chronically infected, only two subjects had been previously diagnosed but were not engaged in care. Conclusion: HBV disproportionately affects Asian Americans, primarily owing to immigration from parts of the world where the disease is endemic. Indian Americans belong to an intermediate-risk group, with an HBV prevalence of >2%, but remain underdiagnosed and poorly linked to care. Our pilot study on Indian American populations, the first of its kind, demonstrates a 3% prevalence of CHB, none of whom are linked to care. In addition, this population has a high percentage of unimmune subjects, creating a large reservoir for future infection. With the growing population of Indian Americans, our findings can be used to develop community-based strategies for HBV screenings and LTC that target high-risk groups.

Prediction model for hepatitis B e antigen seroconversion in chronic hepatitis B with peginterferon-alfa treated based on a responseguided therapy strategy

BACKGROUND Models for predicting hepatitis B e antigen(HBeAg)seroconversion in patients with HBeAg-positive chronic hepatitis B(CHB)after nucleos(t)ide analog treatment are rare.AIM To establish a simple scoring model based on a response-guided therapy(RGT)strategy for predicting HBeAg seroconversion and hepatitis B surface antigen(HBsAg)clearance.METHODS In this study,75 previously treated patients with HBeAg-positive CHB underwent a 52-week peginterferon-alfa(PEG-IFNα)treatment and a 24-wk follow-up.Logistic regression analysis was used to assess parameters at baseline,week 12,and week 24 to predict HBeAg seroconversion at 24 wk post-treatment.The two best predictors at each time point were used to establish a prediction model for PEG-IFNαtherapy efficacy.Parameters at each time point that met the corresponding optimal cutoff thresholds were scored as 1 or 0.RESULTS The two most meaningful predictors were HBsAg≤1000 IU/mL and HBeAg≤3 S/CO at baseline,HBsAg≤600 IU/mL and HBeAg≤3 S/CO at week 12,and HBsAg≤300 IU/mL and HBeAg≤2 S/CO at week 24.With a total score of 0 vs 2 at baseline,week 12,and week 24,the response rates were 23.8%,15.2%,and 11.1%vs 81.8%,80.0%,and 82.4%,respectively,and the HBsAg clearance rates were 2.4%,3.0%,and 0.0%,vs 54.5%,40.0%,and 41.2%,respectively.CONCLUSION We successfully established a predictive model and diagnosis-treatment process using the RGT strategy to predict HBeAg and HBsAg seroconversion in patients with HBeAg-positive CHB undergoing PEG-IFNαtherapy.

Factors Associated with Renal Impairment in Patients on Tenofovir for Chronic Hepatitis B in Yaoundé (Cameroon)

Background: Tenofovir (TFV) is widely used to treat patients with hepatitis B virus (HBV) infection. But kidney abnormalities are the main concern using this drug. Few studies have described the renal impairment due to the TFV in chronic hepatitis B (CHB) in Sub-Saharan Africa. The objective was to evaluate factors associated with renal impairment observed in patients on TFV for CHB. Method: It was a hospital based cross sectional prospective study carried out from June 2023 to July 2023 in Yaoundé (Cameroon) and included any patient treated with TFV for CHB during at least a period of 6 months. For each participant, we collected in the medical report socio-demographic data, clinical data, baseline creatinine, treatment information (type of TFV which was Disoproxil Fumarate (TDF) or Alafenamide (TAF), duration). Then, we collected blood samples to measure serum creatinine and phosphate levels and urine dipstick analysis. Factors associated with renal impairment were assessed with the Odds Ratio. A p value of Results: A total of 60 participants were included. The median age was 44 years [36-55] and median duration of TFV therapy was 17.5 months [11.7-25.7]. The prevalence of reduced eGFR (Conclusion: Kidney function was impaired in some patients receiving TFV for CHB. It should be monitored, particularly after 36 months and for those receiving TDF prodrug.

Liver histological changes in untreated chronic hepatitis B patients in indeterminate phase

BACKGROUND Studies with large size samples on the liver histological changes of indeterminate phase chronic hepatitis B(CHB)patients were not previously conducted.AIM To assess the liver histological changes in the indeterminate phase CHB patients using liver biopsy.METHODS The clinical and laboratory data of 1532 untreated CHB patients were collected,and all patients had least once liver biopsy from January 2015 to December 2021.The significant differences among different phases of CHB infection were compared with t-test,and the risk factors of significant liver histological changes were analyzed by the multivariate logistic regression analysis.RESULTS Among 1532 untreated CHB patients,814(53.13%)patients were in the indeterminate phase.Significant liver histological changes(defined as biopsy score≥G2 and/or≥S2)were found in 488/814(59.95%)CHB patients in the indete-rminate phase.Significant liver histological changes were significant differences among different age,platelets(PLTs),and alanine aminotransferase(ALT)subgroup in indeterminate patient.Multivariate logistic regression analysis indicated that age≥40 years old[adjust odd risk(aOR),1.44;95%confidence interval(CI):1.06-1.97;P=0.02],PLTs≤150×10^(9)/L(aOR,2.99;95%CI:1.85-4.83;P<0.0001),and ALT≥upper limits of normal(aOR,1.48;95%CI:1.08,2.05,P=0.0163)were independent risk factors for significant liver histological changes in CHB patients in the indeterminate phase.CONCLUSION Our results suggested that significant liver histological changes were not rare among the untreated CHB patients in indeterminate phase,and additional strategies are urgently required for the management of these patients.

Chronic active and atrophic gastritis as significant contributing factor to the development of gastric cystica profunda

Gastric cystica profunda(GCP)is an uncommon but underestimated gastric lesion.Its precancerous potential determines its significance.In addition to previous mucosa injury due to operations,biopsy or polypectomy,chronic active and atrophic gastritis may also lead to the development of GCPs.By carefully examining the stomach and taking biopsy samples from the susceptible regions,the stage of atrophy can be determined.Chronic atrophic gastritis is a risk factor for cancer evolvement and it can also contribute to GCPs formation.GCPs frequently occur close to early gastric cancers(EGCs)or EGC can arise from the cystic glands.Endoscopic resection is an effective and minimally invasive treat-ment in GCP.

Effect of viral hepatitis on type 2 diabetes:A Mendelian randomization study

BACKGROUND The effects of viral hepatitis(VH)on type 2 diabetes(T2D)remain controversial.AIM To analyze the causal correlation between different types of VH and T2D using Mendelian randomization(MR).METHODS Single nucleotide polymorphisms of VH,chronic hepatitis B(CHB),chronic hepatitis C(CHC)and T2D were obtained from the BioBank Japan Project,European Bioinformatics Institute,and FinnGen.Inverse variance weighted,MREgger,and weighted median were used to test exposure-outcome associations.The MR-Egger intercept analysis and Cochran’s Q test were used to assess horizontal pleiotropy and heterogeneity,respectively.Leave-one-out sensitivity analysis was used to evaluate the robustness of the MR analysis results.RESULTS The MR analysis showed no significant causal relationship between VH and T2D in Europeans[odds ratio(OR)=1.028;95%confidence interval(CI):0.995-1.062,P=0.101].There was a negative causal association between CHB and T2D among East Asians(OR=0.949;95%CI:0.931-0.968,P<0.001),while there was no significant causal association between CHC and T2D among East Asians(OR=1.018;95%CI:0.959-1.081,P=0.551).Intercept analysis and Cochran’s Q test showed no horizontal pleiotropy or heterogeneity(P>0.05).Sensitivity analysis showed that the results were robust.CONCLUSION Among East Asians,CHB is associated with a reduced T2D risk,but this association is limited by HBV load and cirrhosis.Although VH among Europeans and CHC among East Asians are not associated with the risk of T2D,focusing on blood glucose in patients with CHC is still relevant for the early detection of T2D induced by CHCmediated pathways of hepatic steatosis,liver fibrosis,and cirrhosis.

DETECTION OF PLASMA SOLUBLE INTERLEUKIN－2 RECEPTOR IN PATIENTS WITH SEVERE AND CHRONIC ACTIVE HEPATITIS B

Plasma levels of soluble interleukin-2 receptor (sIL-2R) in patients with chronic active hepatitis B (CAHB) or severe hepatitis B (SHB) were measured quantitatively by 'sandwich' ELISA with monoclonal antibodies in order to explore the change of sIL-2R levels, its clinical significance,and its relation to liver damage. The results showed that the plasma sIL-2R levels in patients with CAHB and SHB were much higher than those in normal controls (P < 0. 01 ), and the level ofplasma sIL-2R in patients with SHB was greatly higher than that in patients with CAHB. These results suggest that there is close relation between plasma level of sIL-2R, the clinical types of hepatitis B,and the severity of liver damage. In addition, there is no significant difference in plasma levels of sIL-2R between acute severe hepatitis B (ASHB), subacute severe hepatitis B (SASHB), and chronic severe hepatitis B (CSHB). No relation was found between sIL-2R level and hepatitis B virusreplication activity.

Decade of optimizing therapy with direct-acting antiviral drugs and the changing profile of patients with chronic hepatitis C

Chronic infection with the hepatitis C virus(HCV)remains a major health problem affecting approximately 58 million people worldwide.In the era of interferon(IFN)-based regimens,patients particularly infected with genotypes 1 and 4 achieved a low response rate.The implementation of direct-acting antivirals changed the landscape of HCV treatment.The increase in effectiveness provided us with the hope of eliminating HCV as a significant public threat by 2030.In the following years,there was an observed improvement in the treatment of HCV with genotype-specific regimens and highly effective pangenotypic options that are the most recent stage of the revolution.The optimization of therapy was accompanied by changes in the patient profile from the beginning of the IFN-free era over time.Patients treated with antiviral therapies were younger in successive periods,less burdened with comorbidities and comedications,more frequently treatment-naïve and had less advanced liver disease.Before the IFN-free era,specific subpopulations such as patients with HCV/HIV coinfection,those with a history of previous treatment,patients with renal impairment or with cirrhosis had lower chances for a virologic response.Currently,these populations should no longer be considered difficult to treat.Despite the high effectiveness of HCV therapy,there is a small percentage of patients with treatment failure.However,they can be effectively retreated with pangenotypic rescue regimens.

Antiviral treatment standards for hepatitis B:An urgent need for expansion

The present letter to the editor is related to the review with the title“Past,present,and future of long-term treatment for hepatitis B virus.”Chronic hepatitis B(CHB)represents an important and pressing public health concern.Timely identification and effective antiviral therapy hold the potential to reduce liver-related mortality attributable to chronic infection with hepatitis B virus(HBV)substantially.However,the current global treatment rates for CHB remain conspicuously low,with the excessively stringent treatment criteria advocated by national CHB guidelines being a contributing factor to these low rates.Nevertheless,recent strides in comprehending this malady and the emergence of novel antiviral agents prompt the imperative re-evaluation of treatment standards to extend the sphere of potential beneficiaries.An impending need arises for a novel paradigm for the classification of patients with CHB,the expansion of antiviral treatment eligibility for HBV-infected individuals,and even the streamlining of the diagnostic process for CHB to amplify cost-effectiveness and augment survival prospects.

Editorial:Metabolomics in chronic hepatitis C:Decoding fibrosis grading and underlying pathways

In the management of the growing population of hepatitis C virus-infected patients,a significant clinical challenge exists in determining the most effective methods for assessing liver impairment.The prognosis and treatment of chronic hepatitis C depend,in part,on the evaluation of histological activity,specifically cell necrosis and inflammation,and the extent of liver fibrosis.These parameters are traditionally obtained through a liver biopsy.However,liver biopsy presents both invasiveness and potential sampling errors,primarily due to inadequate biopsy size.To circumvent these issues,several non-invasive markers have been proposed as alternatives for diagnosing liver damage.Different imaging techniques and blood parameters as single markers or combined with clinical information are included.This Editorial discusses the identification of a set of six distinctive lipid metabolites in every fibrosis grade that appear to show a pronounced propensity to create clusters among patients who share the same fibrosis grade,thereby demonstrating enhanced efficacy in distinguishing between the different grades.

Baseline hepatocyte ballooning is a risk factor for adverse events in patients with chronic hepatitis B complicated with nonalcoholic fatty liver disease

BACKGROUND Although many studies have investigated the impact of chronic hepatitis B virus(HBV)infection and nonalcoholic fatty liver disease(NAFLD)on liver disease,few have investigated the relationship between nonalcoholic steatohepatitis(NASH)defined by liver pathology and the prognosis of chronic HBV infection.Most patients were followed up for a short time.This study aimed to further explore the impact of NAFLD and the pathological changes confirmed by liver pathology in patients with chronic HBV infection.AIM To study the effect of NAFLD confirmed using liver pathology on the outcomes of long-term serious adverse events[cirrhosis,hepatocellular carcinoma(HCC),and death]in patients with chronic hepatitis B(CHB)virus infection.METHODS We enrolled patients with chronic hepatitis B virus(HBV)infection who underwent liver biopsy at the Third People’s Hospital of Zhenjaing Affiliated Jiangsu University between January 2005 and September 2020.Baseline clinical and pathological data on liver pathology and clinical data at the end of follow-up were collected.Propensity score matching(PSM)was used to balance baseline parameters,Kaplan-Meier(K-M)survival analysis was used to evaluate the risk of clinical events,and Cox regression was used to analyze the risk factors of events.RESULTS Overall,456 patients with chronic HBV infection were included in the study,of whom 152(33.3%)had histologically confirmed NAFLD.The median follow-up time of the entire cohort was 70.5 mo.Thirty-four patients developed cirrhosis,which was diagnosed using ultrasound during the follow-up period.K-M survival analysis showed that NAFLD was not significantly associated with the risk of cirrhosis(log-rank test,P>0.05).Patients with CHB with fibrosis at baseline were more prone to cirrhosis(log-rank test,P=0.046).After PSM,multivariate analysis showed that diabetes mellitus,ballooning deformation(BD),and platelet(PLT)were independent risk factors for cirrhosis diagnosed using ultrasound(P<0.05).A total of 10 patients(2.2%)developed HCC,and six of these patients were in the combined NAFLD group.K-M survival analysis showed that the cumulative risk of HCC in the NAFLD group was significantly higher(log-rank test,P<0.05).Hepatocyte ballooning,and severe liver fibrosis were also associated with an increased risk of HCC(log-rank test,all P<0.05).Cox multivariate analysis revealed that hepatocyte ballooning,liver fibrosis,and diabetes mellitus were independent risk factors for HCC.CONCLUSION There was no significant correlation between chronic HBV infection and the risk of cirrhosis in patients with NAFLD.Diabetes mellitus,BD,and PLT were independent risk factors for liver cirrhosis.Patients with chronic HBV infection and NASH have an increased risk of HCC.BD,liver fibrosis,and diabetes mellitus are independent risk factors for HCC.

Chronic hepatitis B:New potential therapeutic drugs target

liverrelated morbidity and mortality worldwide.It impacts nearly 300 million people.The current treatment for chronic infection with the hepatitis B virus(HBV)is complex and lacks a durable treatment response,especially hepatitis B surface antigen(HBsAg)loss,necessitating indefinite treatment in most CHB patients due to the persistence of HBV covalently closed circular DNA(cccDNA).New drugs that target distinct steps of the HBV life cycle have been investigated,which comprise inhibiting the entry of HBV into hepatocytes,disrupting or silencing HBV cccDNA,modulating nucleocapsid assembly,interfering HBV transcription,and inhibiting HBsAg release.The achievement of a functional cure or sustained HBsAg loss in CHB patients represents the following approach towards HBV eradication.This review will explore the up-to-date advances in the development of new direct-acting anti-HBV drugs.Hopefully,with the combination of the current antiviral drugs and the newly developed direct-acting antiviral drugs targeting the different steps of the HBV life cycle,the ultimate eradication of CHB infection will soon be achieved.

Global trends in hepatitis C-related hepatocellular carcinoma mortality:A public database analysis(1999-2019)

BACKGROUND Hepatitis C is the leading cause of chronic liver disease worldwide and it significantly contributes to the burden of hepatocellular carcinoma(HCC).However,there are marked variations in the incidence and mortality rates of HCC across different geographical regions.With the advent of new widely available treatment modalities,such as direct-acting antivirals,it is becoming increasingly imperative to understand the temporal and geographical trends in HCC mortality associated with Hepatitis C.Furthermore,gender disparities in HCC mortality related to Hepatitis C are a crucial,yet underexplored aspect that adds to the disease's global impact.While some studies shed light on gender-specific trends,there is a lack of comprehensive data on global and regional mortality rates,particularly those highlighting gender disparities.This gap in knowledge hinders the development of targeted interventions and resource allocation strategies.DISCUSSION The results of our study show an overall decline in the mortality rates of patients with hepatitis C-related HCC over the last two decades.Notably,females exhibited a remarkable decrease in mortality compared to males.Regionally,East Asia and the Pacific displayed a significant decline in mortality,while Europe and Central Asia witnessed an upward trend.Latin America and the Caribbean also experienced an increase in mortality rates.However,no significant difference was observed in the Middle East and North Africa.North America exhibited a notable upward trend.South Asia and Sub-Saharan Africa significantly declined throughout the study period.This raises the hope of identifying areas for implementing more targeted resources.Despite some progress,multiple challenges remain in meeting the WHO 2030 goal of eliminating viral hepatitis[24].

Metabolomics in chronic hepatitis C:Decoding fibrosis grading and underlying pathways

BACKGROUND Chronic Hepatitis C(CHC)affects 71 million people globally and leads to liver issues such as fibrosis,cirrhosis,cancer,and death.A better understanding and prognosis of liver involvement are vital to reduce morbidity and mortality.The accurate identification of the fibrosis stage is crucial for making treatment decisions and predicting outcomes.Tests used to grade fibrosis include histological analysis and imaging but have limitations.Blood markers such as molecular biomarkers can offer valuable insights into fibrosis.AIM To identify potential biomarkers that might stratify these lesions and add information about the molecular mechanisms involved in the disease.METHODS Plasma samples were collected from 46 patients with hepatitis C and classified into fibrosis grades F1(n=13),F2(n=12),F3(n=6),and F4(n=15).To ensure that the identified biomarkers were exclusive to liver lesions(CHC fibrosis),healthy volunteer participants(n=50)were also included.An untargeted metabolomic technique was used to analyze the plasma metabolites using mass spectrometry and database verification.Statistical analyses were performed to identify differential biomarkers among groups.RESULTS Six differential metabolites were identified in each grade of fibrosis.This six-metabolite profile was able to establish a clustering tendency in patients with the same grade of fibrosis;thus,they showed greater efficiency in discriminating grades.CONCLUSION This study suggests that some of the observed biomarkers,once validated,have the potential to be applied as prognostic biomarkers.Furthermore,it suggests that liquid biopsy analyses of plasma metabolites are a good source of molecular biomarkers capable of stratifying patients with CHC according to fibrosis grade.

Lowering the threshold of alanine aminotransferase for enhanced identification of significant hepatic injury in chronic hepatitis B patients

BACKGROUND The clinical and histological features of chronic hepatitis B(CHB)patients who fall into the"grey zone(GZ)"and do not fit into conventional natural phases are unclear.AIM To explore the impact of varying the threshold of alanine aminotransferase(ALT)levels in identifying significant liver injury among GZ patients.METHODS This retrospective analysis involved a cohort of 1617 adult patients diagnosed with CHB who underwent liver biopsy.The clinical phases of CHB patients were determined based on the European Association for the Study of the Liver 2017 Clinical Practice Guidelines.GZ CHB patients were classified into four groups:GZ-A(HBeAg positive,normal ALT levels,and HBV DNA≤10^(7) IU/mL),GZ-B(HBeAg positive,elevated ALT levels,and HBV DNA<10^(4) or>10^(7) IU/mL),GZC(HBeAg negative,normal ALT levels,and HBV DNA≥2000 IU/mL),and GZ-D(HBeAg negative,elevated ALT levels,and HBV DNA≤2000 IU/mL).Significant hepatic injury(SHI)was defined as the presence of notable liver inflammation(≥G2)and/or significant fibrosis(≥S2).RESULTS The results showed that 50.22%of patients were classified as GZ,and 63.7%of GZ patients developed SHI.The study also found that lowering the ALT treatment thresholds to the American Association for the Study of Liver Diseases 2018 treatment criteria(35 U/L for men and 25 U/L for women)can more accurately identify patients with significant liver damage in the GZ phases.In total,the proportion of patients with ALT≤40 U/L who required antiviral therapy was 64.86%[(221+294)/794].When we lowered the ALT treatment threshold to the new criteria(30 U/L for men and 19 U/L for women),the same outcome was revealed,and the proportion of patients with ALT≤40 U/L who required antiviral therapy was 75.44%[(401+198)/794].Additionally,the proportion of SHI was 49.1%in patients under 30 years old and increased to 55.3%in patients over 30 years old(P=0.136).CONCLUSION These findings suggest the importance of redefining the natural phases of CHB and using new ALT treatment thresholds for better diagnosis and management of CHB patients in the GZ phases.

Tenofovir amibufenamide vs tenofovir alafenamide for treating chronic hepatitis B:A real-world study

BACKGROUND The efficacy and safety profile of tenofovir amibufenamide(TMF)in chronic hepatitis B(CHB)patients is not well-established.AIM To compare the efficacy and safety of TMF and tenofovir alafenamide(TAF)over a 48-wk period in patients with CHB.METHODS A total of 215 subjects meeting the inclusion criteria were enrolled and divided into two groups:TMF group(n=106)and the TAF group(n=109).The study included a comparison of virological response(VR):Undetectable hepatitis B virus DNA levels,alanine transaminase(ALT)normalization rates,renal function parameters,and blood lipid profiles.RESULTS At 24 and 48 wk,VR rates for the TMF group were 53.57%and 78.57%,respectively,compared with 48.31%and 78.65%for the TAF group(P>0.05).The VR rates were also similar in both groups among patients with low-level viremia,both hepatitis B e antigen(HBeAg)-positive and HBeAg-negative subgroups.The TMF cohort showed ALT normalization and renal safety profiles similar to the TAF group.There was a notable increase in total cholesterol levels in the TAF group(P=0.045),which was not observed in the TMF group(P>0.05).In patients with liver cirrhosis,both groups exhibited comparable VR and ALT normalization rates and renal safety profiles.However,the fibrosis 4 score at 48 wk showed a significant reduction in the TAF group as compared to the TMF group within the liver cirrhosis subgroup.CONCLUSION Our study found TMF is as effective as TAF in treating CHB and has a comparable safety profile.However,TAF may be associated with worsening lipid profiles.

Efficacy of a Chinese herbal formula on hepatitis B e antigenpositive chronic hepatitis B patients

BACKGROUND No guideline recommends antiviral therapy for hepatitis B e antigen(HBeAg)-positive chronic hepatitis B patients with persistently normal alanine aminotransferase levels and a high hepatitis B virus(HBV)DNA viral load.AIM To evaluate the feasibility and safety of a Chinese herbal formula as a therapeutic option for chronic HBV infection.METHODS In total,395 patients(30–65 years old)with confirmed HBeAg-positive chronic hepatitis B infection and persistently normal alanine aminotransferase were randomized to receive either Chinese herbal formula or placebo for 96 wk.Endpoints to evaluate therapeutic efficacy included:(1)HBV DNA levels decreased to less than 4 log10 IU/mL at weeks 48 and 96;and(2)HBeAg clearance and seroconversion rates at weeks 48 and 96.RESULTS HBV DNA levels≤4 log10 IU/mL were 10.05%at week 48 and 18.59%at week 96 in the treatment group.The HBeAg clearance and conversion rates were 8.54%and 8.04%at week 48 and 16.08%and 14.57%at week 96,respectively.However,HBV DNA levels≤4 log10 IU/mL were 2.55%and 2.55%at weeks 48 and 96,respectively,and the HBeAg clearance rates were 3.06%and 5.61%at weeks 48 and 96,respectively,in the control group.The quantitative hepatitis B surface antigen and HBeAg levels at baseline and changes during the treatment period as well as the alanine aminotransferase elevation at weeks 12 and 24 were strong predictors of HBeAg clearance.CONCLUSION High rates of HBV DNA reduction,HBeAg clearance and seroconversion could be achieved with Chinese herbal formula treatments,and the treatments were relatively safe for HBeAg-positive chronic hepatitis B-infected patients with persistently normal alanine aminotransferase.The ability of the compound to modulate host immune function probably contributed to this effect.

Fas/FasL and Complement Activation are Associated with Chronic Active Epstein-Barr Virus Hepatitis

Background and Aims:Chronic active Epstein-Barr virus hepatitis(CAEBVH)is a rare and highly lethal disease char-acterized by hepatitis and hepatomegaly.This study aimed to investigate the clinicopathological features and pathogenic mechanisms of CAEBVH.Methods:Ten patients with con-firmed Epstein-Barr virus hepatitis infection were enrolled.The clinicopathological characteristics of these patients were summarized and analyzed.Flow cytometry was utilized to detect peripheral blood immune cell phenotypes and whole exome sequencing was used to explore pathogenic genetic mechanisms.Lastly,immunohistochemical staining was em-ployed to verify pathogenic mechanisms.Results:Clinical features observed in all Epstein-Barr virus hepatitis patients included fever(7/10),splenomegaly(10/10),hepatomeg-aly(9/10),abnormal liver function(8/10),and CD8+T cell lymphopenia(6/7).Hematoxylin and eosin staining revealed lymphocytic infiltration in the liver.Positive Epstein-Barr vi-rus-encoded small RNA in-situ hybridization(EBER-ISH)of lymphocytes of liver tissues was noted.Whole exome se-quencing indicated that cytotoxic T lymphocytes and the complement system were involved.The expression of CD8,Fas,FasL,and Caspase-8 expression as well as apoptotic markers was enhanced in the Epstein-Barr virus hepatitis group relative to the controls(p<0.05).Lastly,Complement 1q and complement 3d expression,were higher in CAEBVH patients relative to controls(p<0.05).Conclusions:CAE-BVH patients developed fever,hepatosplenomegaly,and lymphadenopathy.Histopathological changes were a diffuse lymphocytic sinusoidal infiltrate with EBER-ISH positivity.Fas/FasL and complement activation were involved in CAE-BVH patients.