Burden and impacts of chronic hepatitis B infection in rural Senegal: study protocol of a cross-sectional survey in the area of Niakhar (AmBASS ANRS 12356)

IntroductionThough Senegal has one of the highest estimated prevalence rates of chronic hepatitis B virus (HBV) infection worldwide, epidemiological data in the general population are lacking and consequences of the infection remain undocumented. The ANRS-12356 AmBASS study aims at evaluating the health and socioeconomic burden of chronic HBV infection at the individual, household and population level. Its specific objectives are (1) to document the epidemiology of chronic HBV infection, including prevalence and risk factors; (2) to assess the acceptability of home-based testing and first clinic visit; (3) to investigate the repercussions of chronic HBV infection on living conditions; and (4) to estimate the public health impact of chronic HBV infection at the population level and the feasibility of a decentralised model of HBV test and treat.Methods and analysisThis multidisciplinary cross-sectional survey includes a twofold data collection: (1) home-based screening using dried blood spot (DBS) sampling and collection of sociodemographic, economic and behavioural data, and (2) additional clinical and biological data collection in chronic HBV carriers at the first clinic visit. The prevalence of chronic HBV infection will be estimated in the general population and in key subgroups. Risk factors for HBV acquisition in children will be explored using case-control analysis. HBV burden will be assessed through comparisons of health and economic outcomes between households affected by the disease versus non-affected households. Last, an economic evaluation will assess costs and health benefits of scaling-up HBV care.Ethics and disseminationThis study was approved by the Senegalese National Ethical Committee for Research in Health, and received authorisation from the Senegalese Ministry of Health and the French Commission on Information Technology and Liberties (Senegalese Protocol Number: SEN17/15). The study results will be presented in peer-review journals, international conferences and at a workshop with national stakeholders in order to contribute to the design of programmes to address the HBV pandemic.Trial registration numberNCT03215732; Pre-results.

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Cross-sectional study of chronic hepatitis B virus infection in Rwandan high-risk groups: unexpected findings on prevalence and its determinants

BMJ Open ◽

10.1136/bmjopen-2021-054039 ◽

2021 ◽

Vol 11 (12) ◽

pp. e054039

Author(s):

Justine Umutesi ◽

Carolina Klett-Tammen ◽

Sabin Nsanzimana ◽

G Krause ◽

J J Ott

Keyword(s):

Chronic Hepatitis ◽

High Risk ◽

Hepatitis B ◽

Risk Groups ◽

Cross Sectional Study ◽

Hbv Infection ◽

Cross Sectional ◽

Chronic Hbv Infection ◽

Chronic Hepatitis B Virus ◽

Chronic Hbv

ObjectivesUsing secondary data from 208 079 Rwandans, we determined the prevalence of chronic hepatitis B virus (HBV) infection among high-risk groups and its demographic, geographical and health-related determinants.DesignIn this cross-sectional study, we obtained and analysed data from a national hepatitis B vaccination and screening campaign conducted in Rwanda in 2017. We performed logistic regression to examine associations between chronic HBV infection and related factors such as risk status and geographical characteristics.SettingIndividuals were sampled nationally in all 30 districts across 4 provinces and the city of Kigali and all prisons in Rwanda.ParticipantsThe study involves 208 079 individuals at high risk including prisoners and other high-risk groups (oHRG).Main outcomeThe primary outcome for our study was hepatitis B surface antigens (HBsAg) prevalence.FindingsFrom 208 079 adults participants, 206 517 (99.2%) had valid HBsAg results, 4.3% of 64 944 prisoners and 4.0% of 140 985 oHRG were HBV positive. The prevalence was higher in Northern Province 5.1%, (95% CI 4.8 to 5.4). In multivariate analysis, the odds of infection decreased with increasing age, and hepatitis C antibody positivity reduced the odds for chronic HBV (OR 0.58, 95% CI 0.52 to 0.66 and OR 0.74, 95% CI 0.62 to 0.89 among oHRG and prisoners, respectively). In addition, being female was associated with lower odds of HBV (OR 0.70, 95% CI 0.66 to 0.74 and OR 0.80, 95% CI 0.65 to 0.98 among oHRG and prisoners, respectively).ConclusionWe found that individuals below 55 years of age and individuals who belong to high-risk groups (ie, sex workers, injection drug users, men who have sex with men, etc) have a higher probability of chronic HBV infection. Infection with chronic hepatitis C virus was not correlated with chronic HBV infection in our study population. Potential explanations include differential routes of transmission, specific immunological and pathophysiological factors or different effects of health prevention and control programmes.

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Clinical Value of Plasma Secreted Frizzled-Related Protein 4 in the Chronic Hepatitis B Virus Infection: A Cross-Sectional Study

Hepatitis Monthly ◽

10.5812/hepatmon.116525 ◽

2021 ◽

Vol 21 (7) ◽

Author(s):

Miao Cheng ◽

Zhe Zhu ◽

Shuyuan Ye ◽

Junfeng Chen ◽

Xunjun Dong ◽

...

Keyword(s):

Chronic Hepatitis ◽

Hepatitis B ◽

Chronic Hepatitis B ◽

Cross Sectional Study ◽

Hbv Infection ◽

Clinical Value ◽

Cross Sectional ◽

Chronic Hbv Infection ◽

Chronic Hepatitis B Virus ◽

Chronic Hbv

Background: Secreted frizzled-related protein 4 (sFRP4) is elevated in hepatocellular carcinoma (HCC) patients, suggesting that it can be served as a candidate marker for diagnosing HCC. However, little is known about its role in the different stages of chronic hepatitis B virus (HBV) infection. Objectives: This study was conducted to explore the clinical value of plasma sFRP4 in the different stages of chronic HBV infection. Methods: A total of 303 patients with chronic HBV infection were enrolled in this cross-sectional study. They were classified into the chronic hepatitis B (CHB), liver cirrhosis (LC), HCC, and acute-on-chronic liver failure (ACLF) groups on admission. Additionally, 30 healthy subjects were included in the healthy control (HC) group. The clinical value of plasma sFRP4 in the different stages of chronic HBV infection was analyzed. Results: There were 54, 85, 105, 59, and 30 cases in the CHB, LC, HCC, ACLF, and HC groups, respectively. ACLF group had the highest plasma sFRP4 levels compared to the CHB, LC, and HCC groups (all P < 0.001), followed by the HCC and LC groups. LC and HCC groups were found with up-regulated sFRP4 than the CHB group (all P < 0.05). High levels of plasma sFRP4 were recognized as an independent risk factor for distinguishing patients with ACLF from patients with CHB and LC [adjusted odds ratio (OR):1.005, 95% confidence interval (CI): 1.000 - 1.010, P = 0.043], with the area under the receiver operating characteristic curve (AUC) of 0.790 (95% CI: 0.726 - 0.844, P < 0.001). However, in patients with ACLF, plasma sFRP4 levels in the deteriorated group were higher than in the improved group, with a marginally significant difference (P = 0.071). The AUC for predicting the 90 days prognosis in patients with ACLF was 0.640 (P = 0.064). Conclusions: Plasma sFRP4 might be a biomarker to reflect the progression of chronic HBV infection. However, it was not significantly related to the prognosis in patients with ACLF; we did not find this, which may be due to the small sample size.

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Association of STAT3 and STAT4 polymorphisms with susceptibility to chronic hepatitis B virus infection and risk of hepatocellular carcinoma: a meta-analysis

Bioscience Reports ◽

10.1042/bsr20190783 ◽

2019 ◽

Vol 39 (6) ◽

Cited By ~ 4

Author(s):

Han Shi ◽

Hongyan He ◽

Suvash Chandra Ojha ◽

Changfeng Sun ◽

Juan Fu ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Chronic Hepatitis ◽

Hepatitis B Virus ◽

Hepatitis B ◽

Chronic Hepatitis B ◽

Meta Analysis ◽

Hbv Infection ◽

Chronic Hbv Infection ◽

B Virus ◽

Chronic Hbv

Abstract Background: It has been reported that polymorphisms of signal transducer and activator of transcription (STAT) 3 and STAT4 might be associated with susceptibility to hepatitis B virus (HBV) infection and risk of chronic hepatocellular carcinoma (HCC). Owing to limitation of sample size and inconclusive results, we conducted a meta-analysis to clarify the association. Methods: We identified relevant studies by a systematic search of Medline/PubMed, Embase, Web of Science and the Cochrane Library up to 20 February 2019. The strength of the association measured by odds ratios (OR) with 95% confidence intervals (CIs) was studied. All the statistical analyses were conducted based on Review Manager 5.3 software. Results: A total of 5242 cases and 2717 controls from five studies were included for the STAT3 polymorphism, 5902 cases and 7867 controls from nine studies for the STAT4 polymorphism. Our results suggested that STAT3 rs1053004 polymorphism was a significant risk factor of chronic HBV infection (C vs. T: OR = 1.17, 95% CI: 1.07–1.29, PA=0.0007; CC + CT vs. TT: OR = 1.38, 95% CI: 1.09–1.76, PA=0.008). Validation with all the genetic models revealed that rs7574865 polymorphism of STAT4 gene was closely associated with chronic HBV infection (PA<0.01) and chronic hepatitis B (CHB)-related HCC (PA<0.05). Meanwhile, the authenticity of the above meta-analysis results was confirmed by trial sequential analysis (TSA). Conclusions: The meta-analysis showed that STAT3 rs1053004 polymorphism may be the risk for developing chronic HBV infection but not associated with HCC. The present study also indicates that STAT4 rs7574865 polymorphism increased the risk of chronic HBV infection and HCC.

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Serum pentraxin 3 as a biomarker of hepatocellular carcinoma in chronic hepatitis B virus infection

Scientific Reports ◽

10.1038/s41598-020-77332-3 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Huan Deng ◽

Xiude Fan ◽

Xiaoyun Wang ◽

Lu Zeng ◽

Kun Zhang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Chronic Hepatitis ◽

Early Stage ◽

Hbv Infection ◽

Healthy Controls ◽

Pentraxin 3 ◽

Chronic Hbv Infection ◽

Chronic Hepatitis B Virus ◽

B Virus ◽

Chronic Hbv

AbstractBiomarkers for early diagnosis of hepatocellular carcinoma (HCC) are needed in chronic hepatitis B virus (HBV) infection, a leading cause of HCC. We evaluated whether measurement of serum pentraxin 3 (PTX3) could improve diagnosis of HCC in chronic HBV infection. Data from patients with HBV-related chronic hepatitis (n = 159), cirrhosis (n = 99) and HCC (n = 107), and healthy controls (n = 151) were analyzed. Serum PTX3 concentration was measured by immunoassay. Area under the receiver operating characteristic curve (AUC) was applied to assess diagnostic accuracy. PTX3 levels were significantly higher in HBV patients than in healthy controls (P < 0.001) and in HCC than in chronic hepatitis (P < 0.001) or cirrhosis patients (P < 0.001). PTX3 was an independent risk factor of HCC [odds ratio (OR) 1.617, P < 0.001] and could distinguish HCC in chronic HBV infection [cutoff 9.231 ng/mL, AUC 0.929 with 95% confidence interval (CI) of 0.898–0.953], including α-fetoprotein (AFP) negative [cutoff 8.985 ng/mL, AUC (95%CI) 0.947 (0.908–0.973)] and early-stage HCC [cutoff 9.359 ng/mL, AUC (95%CI) 0.920 (0.885–0.947)]. Combination of PTX3 with AFP improved the discrimination of early HCC from chronic HBV infection [AUC (95%CI) 0.948 (0.918–0.970)]. In short, PTX3 measurement could identify HCC, including AFP-negative and early-stage HCC, in chronic HBV infection.

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Influence of universal HBV vaccination on chronic HBV infection in Italy: Results of a cross-sectional multicenter study

Journal of Medical Virology ◽

10.1002/jmv.24873 ◽

2017 ◽

Vol 89 (12) ◽

pp. 2138-2143 ◽

Cited By ~ 9

Author(s):

Evangelista Sagnelli ◽

Tommaso Stroffolini ◽

Caterina Sagnelli ◽

Filomena Morisco ◽

Nicola Coppola ◽

...

Keyword(s):

Multicenter Study ◽

Hbv Infection ◽

Cross Sectional ◽

Chronic Hbv Infection ◽

Hbv Vaccination ◽

Chronic Hbv

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Soluble immune markers in the different phases of chronic hepatitis B virus infection

Scientific Reports ◽

10.1038/s41598-019-50729-5 ◽

2019 ◽

Vol 9 (1) ◽

Author(s):

Steffen B. Wiegand ◽

Bastian Beggel ◽

Anika Wranke ◽

Elmira Aliabadi ◽

Jerzy Jaroszewicz ◽

...

Keyword(s):

Chronic Hepatitis ◽

Hepatitis B Virus ◽

Hepatitis B ◽

Hbeag Seroconversion ◽

Hbv Infection ◽

Immune Markers ◽

Chronic Hbv Infection ◽

Chronic Hepatitis B Virus ◽

B Virus ◽

Chronic Hbv

Abstract Chronic hepatitis B virus (HBV) infection may follow four different consecutive phases, which are defined by virology as well as biochemical markers and differ in terms of prognosis and need for antiviral treatment. Currently, host responses reflected by immune markers are not considered in this definition. We aimed to study soluble immune markers and their distribution in different phases of chronic HBV infection. In this cross-sectional retrospective study, we investigated a panel of 14 soluble immune markers (SIM) including CXCL10 in 333 patients with chronic HBV infection. In a small cohort of HBeAg positive patients we analyzed SIM before and after HBeAg seroconversion and compared seroconverters to patients with unknown outcome. Significant differences were documented in the levels of several SIM between the four phases of chronic HBV infection. The most pronounced difference among all investigated SIM was observed for CXCL10 concentrations with highest levels in patients with hepatitis. TGF-β and IL-17 revealed different levels between HBeAg negative patients. HBeAg positive patients with HBeAg seroconversion presented higher amounts of IL-12 before seroconversion compared to HBeAg positive patients with unknown follow up. SIM such as CXCL10 but also IL-12, TGF-β and IL-17 may be useful markers to further characterize the phase of chronic HBV infection.

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Chronic hepatitis B virus infection and total and cause-specific mortality: a prospective cohort study of 0.5 million people

BMJ Open ◽

10.1136/bmjopen-2018-027696 ◽

2019 ◽

Vol 9 (4) ◽

pp. e027696 ◽

Cited By ~ 4

Author(s):

Jiahui Si ◽

Canqing Yu ◽

Yu Guo ◽

Zheng Bian ◽

Ruogu Meng ◽

...

Keyword(s):

Chronic Hepatitis ◽

Cohort Study ◽

Hepatitis B Virus ◽

Hepatitis B ◽

Hbv Infection ◽

Chronic Hbv Infection ◽

Chronic Hepatitis B Virus ◽

B Virus ◽

Specific Mortality ◽

Chronic Hbv

ObjectivesChronic hepatitis B virus (HBV) infection is associated with a higher risk of liver diseases. Substantial uncertainty remains, however, about the associations of HBV infection with mortality from extrahepatic causes, especially from subtypes of cardiovascular diseases. We prospectively examined the association of chronic HBV infection with total and cause-specific mortality.DesignPopulation-based prospective cohort study.SettingChina Kadoorie Biobank in which participants from 10 geographically diverse areas across China were enrolled between 2004 and 2008.Participants475 801 participants 30–79 years of age without reporting major chronic diseases at baseline were enrolled. Hepatitis B surface antigen (HBsAg) was tested using an on-site rapid test strip at baseline.Primary and secondary outcome measuresTotal and cause-specific mortality.ResultsA total of 35 822 deaths were recorded during ~10 years of follow-up. In multivariable-adjusted analyses, compared with HBsAg-negative participants, HBsAg-positive participants had an increased risk of total mortality (HR=2.01, 95% CI: 1.91 to 2.12), which was higher in men (HR=2.16, 95% CI: 2.01 to 2.31) than in women (HR=1.74, 95% CI: 1.60 to 1.90). Presence of HBsAg was associated with increased mortality from liver cancer (1339 deaths, HR=13.95, 95% CI: 12.46 to 15.62), infections (410 deaths, HR=10.30, 95% CI: 8.21 to 12.94), digestive diseases (688 deaths, HR=6.83, 95% CI: 5.49 to 8.50), intracerebral haemorrhage (4077 deaths, HR=1.38, 95% CI: 1.14 to 1.68) and ischaemic heart diseases (4624 deaths, HR=1.31, 95% CI: 1.09 to 1.58). The positive association between HBsAg status and risk of death was stronger in participants younger than 50 years, smokers, physically active or non-hypertensive participants.ConclusionsAmong Chinese adults, chronic HBV infection was associated with increased mortality from a range of hepatic and extrahepatic diseases.

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Studies on Mutual Relationship between Anti-HBx and sFas, IL-10 or IL-12 in Sera of Cases with Chronic Hepatitis B Infection

Infection International ◽

10.1515/ii-2017-0075 ◽

2014 ◽

Vol 3 (2) ◽

pp. 49-53

Author(s):

Ai-kun Ding ◽

Li-wei Guo ◽

Yong-kong Wang ◽

Wei Liu ◽

Cheng Li ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Cirrhosis ◽

Chronic Hepatitis ◽

Hepatitis B ◽

Chronic Hepatitis B ◽

Sandwich Elisa ◽

Hbv Infection ◽

Mutual Relationship ◽

Chronic Hbv Infection ◽

Chronic Hbv

Abstract Objective To study the mutual relationship between anti-HBx and IL-10, IL-12 or soluble Fas (sFas) in sera of patients with chronic HBV infection and to explore the importance of anti-HBx detection as well as its role in the development of chronic HBV infection. Methods Total of 90 cases with chronic HBV infection were randomly selected, including 10 of asymptomatic carriers (ASC), 28 of chronic hepatitis B (CHB), 26 of liver cirrhosis (LC) and 26 patients of hepatocellular carcinoma (HCC). Their clinical data and blood samples were collected, and serum was prepared and stored at -73℃. Anti-HBx was detected with an indirect ELISA established in our earlier research, and levels of IL-10, IL-12 and Fas were determined with commercial double-antibody sandwich ELISA kits. The mutual relationship between anti-HBx and IL-10, IL-12 or sFas in serum were analyzed with the software SPSS 20.0. Results All levels of IL-10, IL-12 and sFas in peripheral blood showed a rising trend with development of chronic HBV infection. The levels of IL-10 in ASC, CHB, LC and HCC groups were 13.93 ± 14.40 ng/L, 39.38 ± 20.77 ng/L, 69.06 ± 46.37 ng/L and 62.82 ± 23.42 ng/L, respectively, levels of IL-12 in the 4 groups were 15.64 ± 23.04 ng/L, 68.50 ± 23.14 ng/L, 76.83 ± 12.82 ng/L and 83.74 ± 24.88 ng/L, respectively, and levels of sFas were 58.17 ± 77.42 ng/L, 179.88 ± 104.36 ng/L, 249.22 ± 107.80 ng/L and 252.98 ± 87.65 ng/L, respectively. Twenty-seven out of 90 patients showed a positive result for anti-HBx detection, including 1 in ASC, 4 in CHB, 12 in LC and 10 in HCC group. The levels of IL-10, IL-12 and sFas were higher in anti-HBx positive group than in negative group. Statistical analysis demonstrated significant differences of IL-10 and IL-12 between the two groups (P < 0.05), but the differences of sFas had no statistical significance (P = 0.094). Conclusions Anti-HBx antibody is not protective, and is closely related to IL-10, IL-12 and sFas. It may be an important serum indicator for aggravation from chronic hepatitis B to liver cirrhosis or hepatocellular carcinoma in patients with chronic HBV infection.

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Assessment of liver fibrosis in children with chronic HBV infection by non!invasive methods

Modern pediatrics. Ukraine ◽

10.15574/sp.2021.118.19 ◽

2021 ◽

pp. 19-24

Author(s):

V.S. Berezenko ◽

◽

O.M. Tkalik ◽

M.B. Dyba ◽

V.V. Krat ◽

...

Keyword(s):

Chronic Hepatitis ◽

Liver Fibrosis ◽

Shear Wave ◽

Shear Wave Elastography ◽

Hbv Infection ◽

Fibrosis Stage ◽

Chronic Hbv Infection ◽

Positive Chronic Hepatitis ◽

Apri Score ◽

Chronic Hbv

Purpose — to assess liver fibrosis in children with chronic HBV infection with nonEinvasive methods: instrumental (shear wave elastography) and serological (APRI score). Materials and methods. 70 children with HCV aged 2–17 years were examined. The stage of liver fibrosis was determined by the APRI index and the method of shear wave elastography. Results. The majority (82.8%; n=58) of children were diagnosed with HBeAgEpositive HBV infection: HBeAg-positive chronic hepatitis occurred in 54.3% (n=38) of children, HBeAg-positive chronic infection in 28.6% (n=20). 15.7% (n=11) of children had HBeAg-negative chronic infection, and only one (1.4%) patient had HBeAg-negative chronic hepatitis. According to the results of shear wave elastography, in 64.3% (n=45) the stage of liver fibrosis F0-1 was diagnosed; in 35.7% (n=25) — stage of fibrosis >F2. According to APRI score, 63.0% (n=44) had liver fibrosis F0-1, and liver fibrosis stage >F2 was diagnosed in 37.2% (n=26). According to liver elastography, 42.0% of patients with HBeAg-positive chronic hepatitis were diagnosed with liver fibrosis stage >F2. According to APRI score, almost 66% (n=46) of children with HBeAg-positive chronic hepatitis had progressive liver fibrosis >F2. According to the correlation analysis results, a direct correlation was found between liver enzymes levels and APRI score — ALT (τ=0.67; p<0.05), AST (τ=0.72; p<0.05) and GGT (τ=0.26; p<0.05). Conclusions. Most children with chronic HBV infection had stage F0-1 liver fibrosis according to both elastography and APRI score (64% and 63%, respectively). Elastography fibrosis stage >F2 was diagnosed in 42% of HBeAg-positive chronic hepatitis, while APRI index fibrosis stage >F2 was diagnosed in 66% of patients with HBeAg-positive chronic hepatitis. Thus, the results of the liver fibrosis evaluation according to the liver elastography and APRI score in children with chronic HBV infection are similar and can be used in clinical practice to select patients who require antiviral therapy. The APRI score depends on the activity of hepatitis and its use in children with HBeAg-positive chronic hepatitis has certain limitations. The research was carried out in accordance with the principles of the Helsinki declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interest was declared by the authors. Key words: children, chronic HBV infection, fibrosis, shear wave elastography, APRI.

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Distinct Bile Acid Profiles in Patients With Chronic Hepatitis B Virus Infection Reveal Metabolic Interplay Between Host, Virus and Gut Microbiome

Frontiers in Medicine ◽

10.3389/fmed.2021.708495 ◽

2021 ◽

Vol 8 ◽

Author(s):

Zeyu Sun ◽

Chenjie Huang ◽

Yixian Shi ◽

Rusha Wang ◽

Jun Fan ◽

...

Keyword(s):

Chronic Hepatitis ◽

Bile Acid ◽

Hepatitis B Virus ◽

Hepatitis B ◽

Gut Microbiome ◽

Hbv Infection ◽

Healthy Controls ◽

Chronic Hbv Infection ◽

B Virus ◽

Chronic Hbv

Hepatitis B virus (HBV) can hijack the host bile acids (BAs) metabolic pathway during infection in cell and animal models. Additionally, microbiome was known to play critical role in the enterohepatic cycle of BAs. However, the impact of HBV infection and associated gut microbiota on the BA metabolism in chronic hepatitis B (CHB) patients is unknown. This study aimed to unveil the distinct BA profiles in chronic HBV infection (CHB) patients with no or mild hepatic injury, and to explore the relationship between HBV, microbiome and BA metabolism with clinical implications.Methods: Serum BA profiles were compared between CHB patients with normal ALT (CHB-NALT, n = 92), with abnormal ALT (CHB-AALT, n = 34) and healthy controls (HCs, n = 28) using UPLC-MS measurement. Hepatic gene expression in CHB patients were explored using previously published transcriptomic data. Fecal microbiome was compared between 30 CHB-NALT and 30 HCs using 16S rRNA sequencing, and key microbial function was predicted by PICRUSt analysis.Results: Significant higher percentage of conjugated BAs and primary BAs was found in CHB patients even without apparent liver injury. Combinatory BA features can discriminate CHB patients and HCs with high accuracy (AUC = 0.838). Up-regulation of BA importer Na+ taurocholate co-transporting peptide (NTCP) and down-regulation of bile salt export pump (BSEP) was found in CHB-NALT patients. The microbial diversity and abundance of Lactobacillus, Clostridium, Bifidobacterium were lower in CHB-NALT patients compared to healthy controls. Suppressed microbial bile salt hydrolases (BSH), 7-alpha-hydroxysteroid dehydrogenase (hdhA) and 3-dehydro-bile acid Delta 4, 6-reductase (BaiN) activity were found in CHB-NALT patients.Conclusion: This study provides new insight into the BA metabolism influenced both by HBV infection and associated gut microbiome modulations, and may lead to novel strategy for clinical management for chronic HBV infection.

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