Current status of drug therapy for chronic hepatitis B

In this editorial,we comment on the article by Meng et al.Chronic hepatitis B(CHB)is a significant global health problem,particularly in developing countries.Hepatitis B virus(HBV)infection is one of the most important risk factors for cirrhosis and hepatocellular carcinoma.Prevention and treatment of HBV are key measures to reduce complications.At present,drug therapy can effectively control virus replication and slow disease progression,but completely eliminating the virus remains a challenge.Anti-HBV treatment is a long-term process,and there are many kinds of antiviral drugs with different mechanisms of action,it is essential to evaluate the safety and efficacy of these drugs to reduce side effects and improve patients’compliance.We will summarize the current status of CHB drug treatment,hoping to provide a reference for the selection of clinical antiviral drugs.

Gut microbiota shifts in hepatitis B-related portal hypertension after transjugular intrahepatic portosystemic shunt:Mechanistic and clinical implications

In this article,we provide commentary on the recent article by Zhao et al.We focus on the shifts in the gut microbiota of patients with hepatitis B virus(HBV)-associated cirrhosis/portal hypertension(PH)following transjugular intrahepatic portosystemic shunt(TIPS)and the implications for understanding the mechanisms,diagnosis,and treatment.By comparing the gut microbiota composition and dynamic changes before and after TIPS in patients with and without hepatic encephalopathy,the authors found an increase in non-probiotic bacteria in those who developed hepatic encephalopathy post-TIPS,with Morganella species present only in the hepatic encephalopathy group.The gut microbiota changes post-TIPS among patients without the occurrence of hepatic encephalopathy suggest potential therapeutic benefits through prophylactic microbiome therapies.Furthermore,the specific gut microbiota alterations may hold promise to predict the risk of hepatic encephalopathy in individuals undergoing TIPS for HBVrelated PH.Despite these promising findings,future studies are needed to address limitations,including a small sample size,a relatively short evaluation period for gut microbiota alterations,the absence of data on dynamic alterations in gut microbiota post-TIPS and their correlation with blood ammonia levels,and the lack of validation in animal models.In conclusion,Zhao et al's study has shed new light on the link of gut microbiota with post-TIPS hepatic encephalopathy,potentially through the intricate gut-liver axis,and has important clinical implications for improving the management of patients with HBV-related PH.

Antiviral therapy for hepatitis B virus infection is beneficial for the prognosis hepatocellular carcinoma

In this editorial,we comment on the article by Mu et al,published in the recent issue of the World Journal of Gastrointestinal Oncology.We pay special attention to the immune tolerance mechanism caused by hepatitis B virus(HBV)infection,the pathogenesis of hepatocellular carcinoma(HCC),and the role of antiviral therapy in treating HCC related to HBV infection.HBV infection leads to systemic innate immune tolerance by directly inhibiting pattern recognition receptor recognition and antiviral signaling pathways,as well as by inhibiting the immune functions of macrophages,natural killer cells and dendritic cells.In addition,HBV leads to an immunosuppressive cascade by expressing inhibitory molecules to induce exhaustion of HBV-specific cluster of differentiation 8+T cells,ultimately leading to long-term viral infection.The loss of immune cell function caused by HBV infection ultimately leads to HCC.Long-term antiviral therapy can improve the prognosis of patients with HCC and prevent tumor recurrence and metastasis.

Rising incidence of acute hepatitis A among adults and clinical characteristics in a tertiary care center of Pakistan

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.

Exploring the performance of large language models on hepatitis B infection-related questions:A comparative study

BACKGROUND Patients with hepatitis B virus(HBV)infection require chronic and personalized care to improve outcomes.Large language models(LLMs)can potentially provide medical information for patients.AIM To examine the performance of three LLMs,ChatGPT-3.5,ChatGPT-4.0,and Google Gemini,in answering HBV-related questions.METHODS LLMs’responses to HBV-related questions were independently graded by two medical professionals using a four-point accuracy scale,and disagreements were resolved by a third reviewer.Each question was run three times using three LLMs.Readability was assessed via the Gunning Fog index and Flesch-Kincaid grade level.RESULTS Overall,all three LLM chatbots achieved high average accuracy scores for subjective questions(ChatGPT-3.5:3.50;ChatGPT-4.0:3.69;Google Gemini:3.53,out of a maximum score of 4).With respect to objective questions,ChatGPT-4.0 achieved an 80.8%accuracy rate,compared with 62.9%for ChatGPT-3.5 and 73.1%for Google Gemini.Across the six domains,ChatGPT-4.0 performed better in terms of diagnosis,whereas Google Gemini demonstrated excellent clinical manifestations.Notably,in the readability analysis,the mean Gunning Fog index and Flesch-Kincaid grade level scores of the three LLM chatbots were significantly higher than the standard level eight,far exceeding the reading level of the normal population.CONCLUSION Our results highlight the potential of LLMs,especially ChatGPT-4.0,for delivering responses to HBV-related questions.LLMs may be an adjunctive informational tool for patients and physicians to improve outcomes.Nevertheless,current LLMs should not replace personalized treatment recommendations from physicians in the management of HBV infection.

C-X-C chemokine receptor type 5+CD8+T cells as immune regulators in hepatitis Be antigen-positive chronic hepatitis B under interferonalpha treatment

BACKGROUND C-X-C chemokine receptor type 5(CXCR5)^(+)CD8^(+)T cells represent a unique immune subset with dual roles,functioning as cytotoxic cells in persistent viral infections while promoting B cell responses.Despite their importance,the specific role of CXCR5^(+)CD8^(+)T cells in chronic hepatitis B(CHB),particularly during interferon-alpha(IFN-α)treatment,is not fully understood.This study aims to elucidate the relationship between CXCR5^(+)CD8^(+)T cells and sustained serologic response(SR)in patients undergoing 48 weeks of pegylated IFN-α(peg-IFN-α)treatment for CHB.AIM To elucidate the relationship between CXCR5^(+)CD8^(+)T cells and sustained SR in patients undergoing 48 weeks of peg-IFN-αtreatment for CHB.METHODS This study enrolled 60 patients with hepatitis Be antigen(HBeAg)-positive CHB undergoing 48 weeks of peg-IFN-αtreatment.Participants were assessed for eligibility based on criteria such as persistent HBsAg-positive status for at least six months,HBeAb-negative,hepatitis B virus DNA levels exceeding 2×10^(4) copies/mL,and alanine aminotransferase(ALT)levels between 2 and 10 times the upper limit of normal.Blood samples were collected at baseline and at weeks 12,24,48,and a 24-week treatment-free follow-up(week 72)to measure serum interleukin(IL)-21 concentration via ELISA and to analyze CXCR5 and programmed death-ligand 1(PD-L1)expression on CD8^(+)T cells by flow cytometry,CXCR5 is a chemokine receptor that directs immune cells to specific tissues,while PD-L1 is a protein that regulates immune responses by inhibiting T cell activity.RESULTS Patients with CHB exhibited significantly lower levels of circulating CXCR5^(+)CD8^(+)T cells compared to healthy controls(P<0.01).Notably,CXCR5^(+)CD8^(+)T cells were prominently expressed in patients who achieved sustained SR compared to non-SR(NSR).A significant correlation was observed between CXCR5 and PD-L1 expression(r=-0.189,P=0.002).However,there was no significant correlation between serum IL-21 levels and CXCR5+CD8+lymphocytes(r=-0.03,P=0.625)or serum ALT levels(r=0.026,P=0.678).CONCLUSION The enhanced expression of CXCR5^(+)CD8^(+)T cells in patients achieving HBeAg seroconversion during IFN-αtreatment suggests that these cells play a crucial role in antiviral immune responses against hepatitis B.This study highlights the potential of CXCR5^(+)CD8^(+)T cells as immune regulators in CHB,which may inform future therapeutic strategies to optimize antiviral treatments.

Hepatitis B core-related antigen as a promising serological marker for monitoring hepatitis B virus cure

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.

Timing of post-vaccination tests in infants born to mothers with chronic hepatitis B virus infection

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.

Clinical features of abnormalα-fetoprotein in 15 patients with chronic viral hepatitis B after treatment with antiviral drugs

BACKGROUND Liver function of chronic hepatitis B(CHB)patients is essentially normal after treatment with antiviral drugs.In rare cases,persistently abnormally elevatedα-fetoprotein(AFP)is seen in CHB patients following long-term antiviral treatment.However,in the absence of imaging evidence of liver cancer,a reasonable expla-nation for this phenomenon is still lacking.AIM To explore the causes of abnormal AFP in patients with CHB who were not diag-nosed with liver cancer.METHODS From November 2019 to May 2023,15 patients with CHB after antiviral treatment and elevated AFP were selected.Clinical data and quality indicators related to laboratory testing,imaging data,and pathological data were obtained through inpatient medical records.RESULTS All patients had increased AFP and significantly elevated IgG.Cancer was excluded by imaging examination.Only four patients had elevated alanine ami-notransferase,10 had elevated aspartate aminotransferase,nine had elevated total bilirubin,and two had antinuclear antibodies.The liver biopsy and histopatho-logical examination indicated that 14 patients had rosette,moderate,or higher interfacial inflammation,lymphocyte infiltration,and severe hepatic fibers(11 cases),which was consistent with the pathological features of autoimmune hepa-titis(AIH).After 8-12 week of hormone therapy,the levels of AFP and IgG,and liver function returned to normal(P<0.05).CONCLUSION For patients with CHB and elevated AFP after antiviral treatment,autoimmune hepatitis should be considered.CHB with AIH is clinically insidious and difficult to detect,and prone to progression to cirrhosis.Liver puncture pathological examination should be performed when necessary to confirm diagnosis.

Trends of alkaline phosphatase to prealbumin ratio in patients with hepatitis B linked to hepatocellular carcinoma development

BACKGROUND Chronic hepatitis B often progresses silently toward hepatocellular carcinoma(HCC),a leading cause of mortality worldwide.Early detection of HCC is crucial,yet challenging.AIM To investigate the role of dynamic changes in alkaline phosphatase to prealbumin ratio(APR)in hepatitis B progression to HCC.METHODS Data from 4843 patients with hepatitis B(January 2015 to January 2024)were analyzed.HCC incidence rates in males and females were compared using the log-rank test.Data were evaluated using Kaplan–Meier analysis.The Linear Mixed-Effects Model was applied to track the fluctuation of APR levels over time.Furthermore,Joint Modeling of Longitudinal and Survival data was employed to investigate the temporal relationship between APR and HCC risk.RESULTS The incidence of HCC was higher in males.To ensure the model’s normality assumption,this study applied a logarithmic transformation to APR,yielding ratio.Ratio levels were higher in females(t=5.26,P<0.01).A 1-unit increase in ratio correlated with a 2.005-fold higher risk of HCC in males(95%CI:1.653-2.431)and a 2.273-fold higher risk in females(95%CI:1.620-3.190).CONCLUSION Males are more prone to HCC,while females have higher APR levels.Despite no baseline APR link,rising APR indicates a higher HCC risk.

Hepatitis B virus infection and its treatment in Eastern Ethiopia

Hepatitis B virus(HBV)infection causes acute and chronic hepatitis,compensated and decompensated cirrhosis,and hepatocellular carcinoma worldwide.The actual status of HBV infection and its treatment in certain regions of Asian and African countries,including Ethiopia,has not been well-documented thus far.Antiviral therapy for HBV infection can prevent the progression of HBV-related liver diseases and decrease the HBV-related symptoms,such as abdominal symp-toms,fatigue,systemic symptoms and others.In Eastern Ethiopia,HBV-infected patients with cirrhosis were found to be positive for the HBV e antigen and to have a higher viral load than those without cirrhosis.Notably,54.4%of patients practiced khat chewing and 18.1%consumed excessive amounts of alcohol.Teno-fovir disoproxil fumarate effectively suppressed HBV DNA in those infected with HBV.It is important to elucidate the actual status of HBV infection in Eastern Ethiopia to eliminate HBV infection worldwide by 2030.HBV vaccination and the educational programs for Health Science students that provide practical strategies could help to reduce HBV infection in Eastern Ethiopia.

Prevalence of cardiometabolic co-morbidities in patients with vs persons without chronic hepatitis B: The FitLiver cohort study

BACKGROUND Chronic hepatitis B(CHB)affects>300 million people worldwide.The combi-nation of CHB and cardiometabolic co-morbidities increases the risk of liver-related morbidity and mortality.However,international guidelines for CHB treatment do not provide recommendations for follow-up examinations or treatment of patients with CHB and cardiometabolic comorbidities.In studies investigating cardiometabolic co-morbidity in patients with CHB,inconsistent findings have been observed,and both lower and higher prevalence of car-diometabolic co-morbidities compared to the general population have been re-ported.It is unclear whether patients with CHB living in Denmark have an increased prevalence of cardiometabolic co-morbidities.We examined patients with CHB and age-,sex-,body mass index(BMI)-,and country-of-birth matched comparison group.Defining cardiometabolic co-morbidity:Obesity(BMI>25 kg/m2/abnormal waist-to-hip ratio),metabolic dysfunction-associated steatotic liver disease(MASLD),hypercholesterolemia(total-cholesterol>5 mmol/L/statin use),hypertension(systolic≥135 mmHg/diastolic≥85 mmHg/antihypertensive medication)and type 2 diabetes(T2D)(2-hour oral glucose tolerance test glucose>11.1 mmol/L/HbA1c>48 mmol/mol/antidiabetic medication).Physical activity was evaluated using maximal oxygen consumption(VO2max),activity monitors,and a questionnaire.RESULTS We included 98 patients with CHB and 49 persons in the comparison group.The two groups were well-matched,showing no significant differences in age,sex,BMI,country-of-birth,education,or employment.Among patients with CHB,the following prevalence of cardiometabolic co-morbidity was found:77%were obese,45%had MASLD,38%had hypercholesterolemia,26%had hypertension,and 7%had T2D,which did not differ significantly from the comparison group,apart from lower prevalence of hemoglobin A1c(HbA1c)≥48 mmol/L or known T2D.Both groups had low VO2max of 27 mL/kg/minute in the patients with CHB and 30 mL/kg/minute in the comparison group,and the patients with CHB had a shorter self-assessed sitting time.CONCLUSION The patients with CHB and the comparison group were well-matched and had a similar prevalence of car-diometabolic comorbidities.Furthermore,both groups had low levels of physical fitness.

Evaluating the scope of human leukocyte antigen polymorphisms influencing hepatitis B virus-related liver cancer and cirrhosis through multi-clustering analysis

Hepatitis B virus remains a major cause of cirrhosis and hepatocellular carcinoma,with genetic polymorphisms and mutations influencing immune responses and disease progression.Nguyen et al present novel findings on specific human leukocyte antigen(HLA)alleles,including rs2856718 of HLA-DQ and rs3077 and rs9277535 of HLA-DP,which may predispose individuals to cirrhosis and liver cancer,based on multi-clustering analysis.Here,we discuss the feasibility of this approach and identify key areas for further investigation,aiming to offer insights for advancing clinical practice and research in liver disease and related cancers.

Hepatitis B virus infection and metabolic dysfunction associated steatotic liver disease:Rising pandemic with complex interaction

Due to sedentary lifestyle and rising prevalence of obesity,patients with general population and those who are infected with chronic hepatitis B are found to have metabolic dysfunction associated steatotic liver disease(MASLD).Both chronic hepatitis B virus(HBV)infection and MASLD can damage hepatocytes in their own way,but concomitant HBV-MASLD has its own clinical implications.Cherry on top is the presence of diabetes mellitus,hypertension or obesity which added more chances of unfavorable outcomes in these patients.In this article,we co-mment on the article by Wang et al published in the recent issue.This article provides a comprehensive overview of the complex interaction between HBV-MASLD,HBV alone and MASLD alone patients.We discuss key findings from recent studies,including the promising outcomes observed in patients with concurrent HBV and MASLD,warrants further research.The insights presented here offer renewed understanding of this complex interaction.

Alterations in the gut microbiome after transjugular intrahepatic portosystemic shunt in patients with hepatitis B virus-related portal hypertension

BACKGROUND Gut microbiota(GM)affects the progression and response to treatment in liver diseases.The GM composition is diverse and associated with different etiologies of liver diseases.Notably,alterations in GM alterations are observed in patients with portal hypertension(PH)secondary to cirrhosis,with hepatitis B virus(HBV)infection being a major cause of cirrhosis in China.Thus,understanding the role of GM alterations in patients with HBV infection-related PH is essential.AIM To evaluate GM alterations in patients with HBV-related PH after transjugular intrahepatic portosystemic shunt(TIPS)placement.METHODS This was a prospective,observational clinical study.There were 30 patients(with a 100%technical success rate)recruited in the present study.Patients with esophagogastric variceal bleeding due to HBV infection-associated PH who underwent TIPS were enrolled.Stool samples were obtained before and one month after TIPS treatment,and GM was analyzed using 16S ribosomal RNA amplicon sequencing.RESULTS One month after TIPS placement,8 patients developed hepatic encephalopathy(HE)and were assigned to the HE group;the other 22 patients were assigned to the non-HE group.There was no substantial disparity in the abundance of GM at the phylum level between the two groups,regardless of TIPS treatment(all,P>0.05).However,following TIPS placement,the following results were observed:(1)The abundance of Haemophilus and Eggerthella increased,whereas that of Anaerostipes,Dialister,Butyricicoccus,and Oscillospira declined in the HE group;(2)The richness of Eggerthella,Streptococcus,and Bilophila increased,whereas that of Roseburia and Ruminococcus decreased in the non-HE group;and(3)Members from the pathogenic genus Morganella appeared in the HE group but not in the non-HE group.CONCLUSION Intestinal microbiota-related synergism may predict the risk of HE following TIPS placement in patients with HBVrelated PH.Prophylactic microbiome therapies may be useful for preventing and treating HE after TIPS placement.

Current perspectives of viral hepatitis

Viral hepatitis represents a major danger to public health,and is a globally leading cause of death.The five liver-specific viruses:Hepatitis A virus,hepatitis B virus,hepatitis C virus,hepatitis D virus,and hepatitis E virus,each have their own unique epidemiology,structural biology,transmission,endemic patterns,risk of liver complications,and response to antiviral therapies.There remain few options for treatment,in spite of the increasing prevalence of viral-hepatitiscaused liver disease.Furthermore,chronic viral hepatitis is a leading worldwide cause of both liver-related morbidity and mortality,even though effective treatments are available that could reduce or prevent most patients’complications.In 2016,the World Health Organization released its plan to eliminate viral hepatitis as a public health threat by the year 2030,along with a discussion of current gaps and prospects for both regional and global eradication of viral hepatitis.Today,treatment is sufficiently able to prevent the disease from reaching advanced phases.However,future therapies must be extremely safe,and should ideally limit the period of treatment necessary.A better understanding of pathogenesis will prove beneficial in the development of potential treatment strategies targeting infections by viral hepatitis.This review aims to summarize the current state of knowledge on each type of viral hepatitis,together with major innovations.

Perioperative remedial antiviral therapy in hepatitis B virus-related hepatocellular carcinoma resection:How to achieve a better outcome

BACKGROUND Although the benefits of antiviral therapy for hepatitis B virus(HBV)-related hepatocellular carcinoma(HCC)have been proven,researchers have not con-firmed the differences in patient outcomes between patients who received preoperative antiviral therapy for a period of time(at least 24 wk)and patients who received remedial antiviral therapy just before radical resection for HBV-related HCC.AIM To investigate the efficacy of perioperative remedial antiviral therapy in patients with HBV-related HCC.METHODS A retrospective study of patients who underwent radical resection for HBV-related HCC at the First Affiliated Hospital of Xi’an Jiaotong University from January 2016 to June 2019 was conducted.Considering the history of antiviral therapy,patients were assigned to remedial antiviral therapy and preoperative antiviral therapy groups.RESULTS Kaplan–Meier analysis revealed significant differences in overall survival(P<0.0001)and disease-free survival(P=0.035)between the two groups.Multivariate analysis demonstrated that a history of preoperative antiviral treatment was independently related to improved survival(hazard ratio=0.27;95%confidence interval:0.08-0.88;P=0.030).CONCLUSION In patients with HBV-related HCC,it is ideal to receive preoperative long-term antiviral therapy,which helps patients tolerate more extensive hepatectomy;however,remedial antiviral therapy,which reduces preoperative HBV-DNA levels to less than 4 Log10 copies DNA/mL,can also result in improved outcomes.

Risk of hepatitis B virus reactivation in oncological patients treated with tyrosine kinase inhibitors:A case report and literature analysis

Hepatitis B virus(HBV)reactivation(HBVr)represents a severe and potentially life-threatening condition,and preventive measures are available through blood test screening or prophylactic therapy administration.The assessment of HBVr traditionally considers factors such as HBV profile,including hepatitis B surface antigen(HBsAg)and antibody to hepatitis B core antigen,along with type of medication(chemotherapy;immunomodulants).Nevertheless,consideration of possible patient’s underlying tumor and the specific malignancy type(solid or hematologic)plays a crucial role and needs to be assessed for decision-making process.

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.

Subclinical hepatitis E virus genotype 1 infection:The concept of“dynamic human reservoir”

Hepatitis E virus(HEV)is hyperendemic in South Asia and Africa accounting for half of total Global HEV burden.There are eight genotypes of HEV.Among them,the four common ones known to infect humans,genotypes 1 and 2 are prevalent in the developing world and genotypes 3 and 4 are causing challenge in the industrialized world.Asymptomatic HEV viremia in the general population,especially among blood donors,has been reported in the literature worldwide.The clinical implications related to this asymptomatic viremia are unclear and need further exploration.Detection of viremia due to HEV genotype 1 infection,apparently among healthy blood donors is also reported without much knowledge about its infection rate.Similarly,while HEV genotype 3 is known to be transmitted via blood transfusion in humans and has been subjected to screening in many European nations,instances of transmission have also been documented albeit without significant clinical consequences.Epidemiology of HEV genotype 1 in endemic areas often show waxing and waning pattern.Occasional sporadic occurrence of HEV infection interrupted by outbreaks have been frequently seen.In absence of known animal reservoir,where HEV exists in between outbreak is a mystery that needs further exploration.However,occurrence of asymptomatic HEV viremia due to HEV genotype 1 during epidemiologically quiescent period may explain that this phenomenon may act as a dynamic reservoir.Since HEV genotype 1 infection cannot cause chronicity,subclinical transient infection and transmission of virus might be the reason it sustains in interepidemic period.This might be the similar phenomenon with SARS COVID-19 corona virus infection which is circulating worldwide in distinct phases with peaks and plateaus despite vaccination against it.In view of existing evidence,we propose the concept of“Dynamic Human Reservoir.”Quiescent subclinical infection of HEV without any clinical consequences and subsequent transmission may contribute to the existence of the virus in a community.The potential for transmitting HEV infection by asymptomatic HEV infected individuals by fecal shedding of virus has not been reported in literature.This missing link may be a key to Pandora's box in understanding epidemiology of HEV infection in genotype 1 predominant region.