Chronic Hepatitis B Infection Research Articles

The Association Between Weight Loss and Hepatitis B Surface Antigen Seroclearence in Chronic Hepatitis B Patients

Background: In chronic hepatitis B (CHB) patients, hepatitis B surface antigen (HBsAg) seroclearance is the main target of therapy and is rarely observed. Objectives: This study aimed to investigate the factors affecting HBsAg loss by focusing especially on the relationship between weight loss and HBsAg loss. Methods: This study was designed retrospectively to assess HBsAg status and clinical and laboratory findings in CHB patients, as well as cross-sectionally to evaluate lifestyle factors. A total of 5600 hepatitis B (HB) infection patients who were treated or followed between 2008 and 2020 were evaluated retrospectively. In the HBsAg loss group, 94 CHB patients were examined based on exclusion criteria, and 95 patients without HBsAg loss were matched as controls. Patient data and laboratory findings were retrieved from patient files. All participants were surveyed using a questionnaire developed by the authors, which inquired about the lifestyle characteristics of CHB patients. The questionnaire covered topics such as the use of herbal products, coffee consumption, medication history, antiviral treatment, concurrent diseases, weight changes, and patient demographics. Statistical analysis was performed using SPSS version 25.0. The Student's t-test was used to compare quantitative variables, while the chi-square test was used for categorical variables. A paired samples t-test was used to compare dependent samples. The statistical significance level was set at a p value less than 0.05. Results: The basal mean hepatitis B virus (HBV) DNA level was significantly lower in the HBsAg loss group (P < 0.001). The prevalence of hyperlipidemia comorbidity (P = 0.008) and moderate/severe hepatosteatosis (P < 0.05) was significantly higher in the HBsAg loss group compared to the non-HBsAg loss group. Prior to HBsAg loss, 44 (47%) patients in the HBsAg loss group experienced weight loss, whereas only 22 (23%) patients in the non-HBsAg group had a history of weight loss (P < 0.001). Conversely, the incidence of weight gain was significantly lower in the HBsAg loss group (P = 0.001). A paired samples t-test was conducted to compare the baseline and last period body mass index (BMI) means of the HBsAg loss group, revealing a statistically significant decrease in mean BMI in the last period (P < 0.001). Conclusions: Weight loss was significantly associated with HBsAg seroclearance in patients with CHB infection. Conversely, weight gain was associated with HBsAg persistence.

Chronic Hepatitis B in Women of Childbearing Age and Pregnant Women in China: A Cross-Sectional Study.

Pregnant women and women of childbearing age were enrolled in our study and their knowledge about the Hepatitis B virus (HBV) and chronic hepatitis B (CHB) was evaluated. A questionnaire was distributed to every woman in the cross-sectional study. The questionnaire was answered by all participants before they received health education and advice about HBV and CHB from the doctors visited. Data collected from all answers were analyzed using the χ2 test and logistic regression models. A total of 206 pregnant women and women of childbearing age with CHB infection were enrolled in the study during their first visit to the Infectious Diseases Clinic of the Third Affiliated Hospital of Guangzhou Medical University. Some women of childbearing age (40.8%) and pregnant women with CHB infection (30.6%) still believed HBV could be transmitted through diet and/or mosquito bites. Some women of childbearing age and pregnant women with CHB infection had limited knowledge of the prevention of HBV transmission (111 of 206, 53.9%). Women with higher levels of education had more knowledge about HBV (senior middle school, P = 0.02; university, P <0.01). The majority of participants were willing to take antiviral medicine to decrease the mother-to-child transmission (MTCT) rate of HBV. Some women of childbearing age and/or pregnant women with CHB infection have relatively limited knowledge about HBV or CHB. This situation contributes to the timeliness, or lack thereof, of these women with CHB to see a doctor and receive antiviral therapy. As a result, the morbidity and mortality of HBV-related complications could increase along with the rate of MTCT of HBV.

Furanocoumarins promote proteasomal degradation of viral HBx protein and down-regulate cccDNA transcription and replication of hepatitis B virus

Nucleot(s)ide analogues, the current antiviral treatments against chronic hepatitis B (CHB) infection, are non-curative due to their inability to eliminate covalently closed circular DNA (cccDNA) from the infected hepatocytes. Preclinical studies have shown that coumarin derivatives can effectively reduce the HBV DNA replication. We evaluated the antiviral efficacy of thirty new coumarin derivatives in cell culture models for studying HBV. Furanocoumarins Fc-20 and Fc-31 suppressed the levels of pre-genomic RNA as well as cccDNA, and reduced the secretion of virions, HBsAg and HBeAg. The antiviral efficacies of Fc-20 and Fc31 improved further when used in combination with the hepatitis B antiviral drug Entecavir. There was a marked reduction in the intracellular HBx level in the presence of these furanocoumarins due to proteasomal degradation resulting in the down-regulation of HBx-dependent viral genes. Importantly, both Fc-20 and Fc-31 were non-cytotoxic to cells even at high concentrations. Further, our molecular docking studies confirmed a moderate to high affinity interaction between furanocoumarins and viral HBx via residues Ala3, Arg26 and Lys140. These data suggest that furanocoumarins could be developed as a new therapeutic for CHB infection.

Predictors of Significant Histological Hepatic Abnormality in Treatment-Naive Patients Infected with HBeAg-Negative Chronic Hepatitis B.

This study aimed to determine the predictors for significant hepatic abnormality (SHA), a treatment indication, by assessing demographic, laboratory, and radiological results of chronic hepatitis B (CHB) patients who underwent liver biopsy. In this retrospective study, individuals with untreated hepatitis B e-antigen (HBeAg)-negative CHB infection were enrolled. Multivariate analysis modeling was conducted with parameters identified as predictors for SHA in univariate analysis. Optimal threshold levels for variables to predict SHA in patients with chronic hepatitis B were determined based on receiver operating characteristic (ROC) curve analysis. A total of 566 patients with untreated chronic hepatitis B were included in the cohort; 61% (345/566) were male, and the median age was 41 years (interquartile range [IQR]=34-50). Notably, 36.9% (209/566) had SHA. In the multivariate analysis, utilizing different models, age, gender, HBV-DNA, LDL, ALT, and platelet count were identified as the most reliable predictors for SHA in CHB patients. For predicting SHA, the area under the ROC curve values of HBV-DNA, AST, and ALT were 0.704 (sensitivity=62.8%, specificity=76.2%; p<0.0001), 0.747 (sensitivity=51.9%, specificity=88.9%; p<0.0001), and 0.737 (sensitivity=68.6%, specificity=68.4%; p<0.0001), respectively. In our study, age, male gender, ALT, AST, HBV-DNA, LDL cholesterol, platelet count, and FIB-4 score were independent predictors of SHA in HBeAg-negative chronic hepatitis B. The most sensitive parameters for SHA were LDL and ALT. The most specific parameters were age, AST, and APRI score. SHA may occur in patients with high HBV-DNA levels, even if ALT values are normal in HBeAg-negative patients.

The novel mechanism facilitating chronic hepatitis B infection: immunometabolism and epigenetic modification reprogramming.

Hepatitis B Virus (HBV) infections pose a global public health challenge. Despite extensive research on this disease, the intricate mechanisms underlying persistent HBV infection require further in-depth elucidation. Recent studies have revealed the pivotal roles of immunometabolism and epigenetic reprogramming in chronic HBV infection. Immunometabolism have identified as the process, which link cell metabolic status with innate immunity functions in response to HBV infection, ultimately contributing to the immune system's inability to resolve Chronic Hepatitis B (CHB). Within hepatocytes, HBV replication leads to a stable viral covalently closed circular DNA (cccDNA) minichromosome located in the nucleus, and epigenetic modifications in cccDNA enable persistence of infection. Additionally, the accumulation or depletion of metabolites not only directly affects the function and homeostasis of immune cells but also serves as a substrate for regulating epigenetic modifications, subsequently influencing the expression of antiviral immune genes and facilitating the occurrence of sustained HBV infection. The interaction between immunometabolism and epigenetic modifications has led to a new research field, known as metabolic epigenomics, which may form a mutually reinforcing relationship with CHB. Herein, we review the recent studies on immunometabolism and epigenetic reprogramming in CHB infection and discuss the potential mechanisms of persistent HBV infection. A deeper understanding of these mechanisms will offer novel insights and targets for intervention strategies against chronic HBV infection, thereby providing new hope for the treatment of related diseases.

Association of chronic hepatitis B infection with hepatic steatosis and injury in nonalcoholic fatty liver disease children

BackgroundThe influence of chronic hepatitis B infection (CBI) on hepatic steatosis, necroinflammation, and fibrosis in nonalcoholic fatty liver disease (NAFLD) population was unclear. We aimed to investigate the effect of CBI on hepatic steatosis and assess the association between NAFLD co-existed CBI and hepatic injury in NAFLD pediatric population.MethodsConsecutive hospitalized children with biopsy-proven NAFLD with or without CBI were included. Hepatic steatosis, necroinflammation and fibrosis were evaluated by NASH CRN system and/or METAVIR scoring system, appropriately. Using multivariate logistic analysis, we identified variables associated with hepatic steatosis and liver injury.ResultsOf 223 biopsy-proven NAFLD children, 161 were NAFLD without CBI, and 62 were NAFLD co-existed CBI. Grouped by mild, moderate and severe hepatic steatosis, there was an inverse association between CBI and the severity of hepatic steatosis [odd ratio (OR) 0.037, 95% confidence interval (CI) 0.014–0.098]. In addition, we explored the relationship between CBI and hepatic necroinflammation and fibrosis in NAFLD children. Hepatic necroinflammation and fibrosis, respectively, were divided into two groups according to severity. And CBI was positively associated with hepatic necroinflammation (OR 6.125, 95%CI 1.958–19.158). However, there was no statistically independent association between CBI and significant hepatic fibrosis.ConclusionsCBI was inverse associated with the grade of steatosis and positively associated with severe hepatic necroinflammation, and does not appear to affect significant hepatic fibrosis in pediatric NAFLD children.

Porto-sinusoidal vascular disorder in chronic HBV: A significant coexistence not to be overlooked

Porto-sinusoidal vascular disorder (PSVD) encompasses a group of liver diseases with vascular abnormalities that can cause portal hypertension in the absence of cirrhosis. The new diagnostic criteria allow for coexistence with other liver diseases, however its relationship with chronic hepatitis B (CHB) remains unclear. This study aimed to assess HBV prevalence in a PSVD cohort and evaluate its clinical impact. This retrospective study was conducted on patients with PSVD at Hospital Clínic Barcelona. HBV serology was evaluated, and patients were categorized into HBV chronic infection, past infection, or no HBV exposure. Clinical characteristics and outcomes were compared. We included 155 patients with PSVD. Prevalence of CHB and past HBV infection in patients with PSVD was higher than in the general population (5.8% vs. 0.5%, p <0.0001 and 20% vs. 9.1%, p <0.0001, respectively). Patients with CHB had a significant delay in PSVD diagnosis compared to those without CHB (11 [5-25] vs. 1 [0-3] years, p= 0.002) and had a more advanced disease (MELD score 12 [9-17] vs. 9 [7-11], p= 0.012) at the time of PSVD diagnosis. The clinical evolution of PSVD in patients with CHB was marked by a significantly higher transplantation rate at the last follow-up (33% vs. 4.1%, p= 0.001). Recognizing the coexistence of PSVD and CHB is important for timely diagnosis and optimal management, highlighting the potential benefits of specialized care for potentially improved outcomes. The new diagnostic criteria for porto-sinusoidal vascular disorder (PSVD) allow for coexistence with other liver diseases. The results of the present study highlight, for the first time, a non-negligible prevalence of chronic hepatitis B in the PSVD population that was previously unknown. Coexistence may challenge and delay the PSVD diagnosis and is associated with a more unfavorable clinical course. Our findings will increase awareness of this coexistence and improve PSVD diagnosis and management. Furthermore, the data will encourage new studies to determine the prevalence and clinical behavior of other chronic liver diseases that coexist with PSVD.

Detection of serum large and middle hepatitis B virus surface proteins: A novel potential diagnostic and prognostic biomarker for chronic hepatitis B

BackgroundThe significance of large (LHB) and middle (MHB) HBV surface proteins in chronic hepatitis B (CHB) remains uncertain. This study investigates the role of LHB and MHB in different infection phases and liver diseases. MethodsSerum samples from 217 patients with HBV chronic infection, CHB, liver cirrhosis (LC), and hepatocellular carcinoma (HCC) were subjected to quantification of LHB and MHB using ELISA. ResultsPositive correlations were observed among LHB, MHB, and LHB/HBsAg, with HBV serum markers including HBsAg, HBeAg, and HBV DNA. (P < 0.0001). In HBeAg-positive chronic infection, LHB and MHB were higher than in HBeAg-positive CHB (P < 0.01). In HBeAg-negative chronic infection, LHB and MHB were lower than in HBeAg-negative CHB (P < 0.01). ROC analysis identified LHB and MHB as potential discriminators of CHB and chronic infection. LC and HCC exhibited lower LHB, MHB, and MHB/HBsAg than CHB (P < 0.05). Multivariate analysis found that age and the MHB/HBsAg serve as independent factors for the progression of CHB to end stage of liver disease. ConclusionsLHB and MHB emerge as novel biomarkers distinguishing chronic infection and CHB. MHB/HBsAg shows promise as a predictor for CHB progression.

A Narrative Review on the Specific Pattern of HBV Genotype in Bangladesh: Clinical Implications for Management.

Bangladesh's unique epidemiological landscape presents an intriguing puzzle. This South Asian nation, with its complex sociodemographic and environmental factors, is home to a diverse array of hepatitis-B virus (HBV) genotypes, identified as Genotype C, with Genotypes D and A also making a significant contribution to the viral landscape. Reviewing such insights is necessary not only to underscore the country's regional diversity in HBV strains but also to bring into focus the clinical implications these genetic variations may have on disease progression and management. A thorough database search covered various sources using relevant keywords like "Hepatitis B virus genotypes", "HBV genotypes in Bangladesh", and "HBV clinical implications". The review synthesized findings and analyzed HBV genotype prevalence and clinical implications in Bangladesh. Genotypes C and D collectively represent 82% of chronic hepatitis-B infection (CHB) cases in Bangladesh, underscoring their regional prevalence. The geographic context is pivotal in understanding HBV infection dynamics and disease progression in this area. Notably, genotype C and the presence of A1762T/G1764A mutations appear to have a distinct impact on disease development, potentially affecting the immune response in CHB patients. This highlights the need for tailored management approaches in this specific region. Further research is vital to confirm and elaborate on these findings, particularly in relation to how these mutations influence the host's immune response. In summary, studies on HBV genotypes in Bangladesh stress the need for genotype-specific clinical considerations and more research to improve diagnostics and therapies. Raihan R, Akbar SMF. A Narrative Review on the Specific Pattern of HBV Genotype in Bangladesh: Clinical Implications for Management. Euroasian J Hepato-Gastroenterol 2023;13(2):152-158.

Prognostic Significance of Alpha-Fetoprotein in Staging of Chronic Hepatitis B Infection

Background Ascertaining the stage of chronic hepatitis-B infection (CHBI) remains one of the major predicaments to effective therapeutic decision. There is pressing need to forestall dearth of such reliable biomarker(s). Despite the promising tendency of alpha-fetoprotein (AFP), it has not been assessed in staging CHBI.ObjectiveThis study was to determine the prognosis of serum AFP as a biomarker for staging CHBI. MethodsParticipants were grouped into three based on their hepatitis-B envelope antigen (HBeAg) status and alanine aminotransferase (ALT) level. By denoting HbeAg(+) as (EP), HbeAg(-) as (EN), elevated ALT as (H) and normal ALT as (I), the stages were EPH, ENH and ENI. AFP was assayed, One-way ANOVA, Multivariate linear regression and area under curve were adopted for the analysis. ResultsAFP was significantly elevated, (P &lt; 0.05) in EPH, which equally has the highest prevalence of elevated AFP (64.7%). After adjusting for confounding factors, odds ratio was 1.438 (95% CI, 0.62–1.948), while area under the curve for predicting EPH was (0.828, 95% CI, 0.778 –0.895).ConclusionsThe finding of elevated AFP in CHBI is an independent prognostic marker of EPH. It is often associated with necroinflammation; thus, it is a reliable indicator for treatment initiation.Rwanda J Med Health Sci 2023;6(3):355-366

Real-World Epidemiology, Treatment Patterns, and Disease Burden of Chronic Hepatitis B and HDV Co-Infection in South Korea.

Long-term complications of chronic hepatitis B (CHB) viral infection, such as cirrhosis, hepatocellular carcinoma (HCC), and liver failure, cause a large disease burden. This study aimed to describe the epidemiology, clinical outcomes, and treatment patterns of CHB infection and co-infection with hepatitis Dvirus (HDV) in South Korea. The retrospective, observational study used existing data from the Health Insurance Review and Assessment Service (HIRA) database. Confirmed cases of (CHB) and HBV/HDV co-infection were identified between 2013 and 2019. Hepatitis C virus co-infections and acute HBV infections were excluded. Incident cases diagnosed between 2015 and 2018 with no prior disease history up to 2years were included. Patient characteristics, clinical outcomes, economic burden, and healthcare-resource utilization were described. The estimated 7-year prevalence of CHB and HBV/HDV co-infection were 0.9% and 0.0024%, respectively. The prevalence was higher among 45-54years old (CHB: 1.6%, HBV/HDV: 0.0049%) and males (1.1%, 0.0035%). The 5-year cumulative incidences of compensated cirrhosis, decompensated cirrhosis, HCC, and liver transplantation were 13.3%, 7.1%, 8.4%, and 0.7%, respectively. Hyperlipidemia (40.6%), hypertension (23.5%), and peptic ulcer (23.7%) were the more prevalent comorbidities. Among CHB patients, 48.1% received≥1 prescribed anti-HBV drug including interferon or nucleos(t)ide analogues and 64.4% had≥1 hospitalization compared to 80.4% and 79.4% HBV/HDV patients. Estimated total healthcare costs for CHB and HBV/HDV were US$786million and $62million, respectively. These findings provide insights to the epidemiology, clinical burden, treatment patterns, and healthcare costs of CHB and HBV/HDV co-infection in South Korea.

Unraveling the Complexity of Atypical Serological Profiles in Chronic Hepatitis B: Insights Into Disease Dynamics and Clinical Implications.

Introduction Chronic hepatitis B (CHB) continues to be a significant global public health problem. Conventional serological markers play a pivotal role in diagnosing and prognosticating CHB, but atypical serological profiles deviating from established norms pose challenges. Methods A cohort of 35 CHB patients who did not receive an antiviral treatment with atypical serological markers was followed for five years (2017-2022). Demographics, serological parameters, and changes were documented. Serological parameters and serum viral loads (hepatitis B virus (HBV)-deoxyribonucleic acid (DNA) levels) were assayed at the central laboratory during their routine follow-ups. Three groups of atypical serological markers are defined: hepatitis B surface antigen (HBsAg) and hepatitis B surface antibody (anti-HBs) positivity; hepatitis B e antigen(HBeAg) and anti-hepatitis B e-antigen (anti-HBe) positivity; and isolated core (anti-hepatitis B core (anti-HBc) immunoglobulin G (IgG)) positivity. Patients with concomitant HBsAg and anti-HBs were also stratified into seroreversion groups. Changes in serological markers and HBV-DNA levels across the study period were documented and evaluated at the end of the study period. Statistical analysis was conducted using the Kruskal-Wallis test and IBM SPSS Statistics software for Windows, Version 23.0 (IBM Corp., Armonk, NY, USA). Results In a cohort of 35 patients with atypical hepatitis B serology, demographic analysis revealed that 51.4% (n=18) were female and 48.6% (n=17) were male, with a mean age of 45.7 years. Educational distribution showed that 45.7% (n=16) completed primary education, 22.8% (n=8) had a high school education, and 31.5% (n=11) held university degrees. Among these patients, 10 displayed the concurrent presence of HBsAg and anti-HBs, with 60% (n=6) being female. Serum HBV-DNA was detectable in all cases. After five years, 60% (n=6) exhibited seroconversion from HBsAg to anti-HBs, particularly notable in females (66.7%). These patients showed lower HBsAg titers and serum HBV-DNA levels (p = 0.048, p = 0.036). A subset of 15 patients demonstrated simultaneous HBeAg and anti-HBe positivity. The HBeAg seropositivity waned over time, with 40% (n=6) and 26.7% (n=4) females and males, respectively, retaining positivity by the fifth year. During this period, serum HBV-DNA levels decreased. The remaining five patients sustained HBeAg and anti-HBe positivity. Among 10 patients solely positive for anti-HBc IgG, three had concurrent HBV-DNA positivity. Strikingly, three patients with negative HBV-DNA developed anti-HBs positivity after five years. Conclusion The complexity of CHB infection demands a comprehensive understanding. Atypical serological profiles suggest distinct disease stages, immune response variations, and viral mutations. This study enhances comprehension of viral replication, immune responses, and disease progression, potentially guiding tailored therapeutic strategies.

Hepatitis B virus infection in patients with Wilson disease: A large retrospective study.

Wilson disease (WD) is the most common genetic metabolic liver disease. Some studies have shown that comorbidities may have important effects on WD. Data on hepatitis B virus (HBV) infection in patients with WD are limited. To investigate the prevalence and clinical impact of HBV infection in patients with WD. The clinical data of patients with WD were analyzed retrospectively, and the data of patients with concurrent WD and HBV infection were compared with those of patients with isolated WD. Among a total of 915 WD patients recruited, the total prevalence of current and previous HBV infection was 2.1% [95% confidence interval (CI): 1.2%-3.0%] and 9.2% (95%CI: 7.3%-11.1%), respectively. The main finding of this study was the identification of 19 patients with concurrent WD and chronic hepatitis B (CHB) infection. The diagnosis of WD was missed in all but two patients with CHB infection. The mean delay in the diagnosis of WD in patients with concurrent WD and CHB infection was 32.5 mo, which was significantly longer than that in patients with isolated WD (10.5 mo). The rates of severe liver disease and mortality in patients with concurrent WD and CHB infection were significantly higher than those in patients with isolated WD (63.1% vs 19.3%, P = 0.000 and 36.8% vs 4.1%, P < 0.001, respectively). Binary logistic regression analysis revealed a significantly higher risk of severe liver disease at the diagnosis of WD in patients with current HBV infection [odds ratio (OR) = 7.748; 95%CI: 2.890-20.774; P = 0.000)] or previous HBV infection (OR = 5.525; 95%CI: 3.159-8.739; P = 0.000) than in patients with isolated WD. The total prevalence of current HBV infection in patients with WD was 2.1%. The diagnosis of WD in CHB patients is usually missed. HBV infection is an independent risk factor for severe liver disease in WD patients. The diagnosis of WD should be ruled out in some patients with CHB infection.

Antiviral therapy substantially reduces HCC risk in patients with chronic hepatitis B infection in the indeterminate phase.

HCC risk in chronic hepatitis B (CHB) is higher in the indeterminate phase compared with the inactive phase. However, it is unclear if antiviral therapy reduces HCC risk in this population. We aimed to evaluate the association between antiviral therapy and HCC risk in the indeterminate phase. We analyzed 855 adult (59% male), treatment-naïve patients with CHB infection without advanced fibrosis in the indeterminate phase at 14 centers (USA, Europe, and Asia). Inverse probability of treatment weighting (IPTW) was used to balance the treated (n = 405) and untreated (n = 450) groups. The primary outcome was HCC development. The mean age was 46±13 years, the median alanine transaminase was 38 (interquartile range, 24-52)U/L, the mean HBV DNA was 4.5±2.1log 10 IU/mL, and 20% were HBeAg positive. The 2 groups were similar after IPTW. After IPTW (n = 819), the 5-, 10-, and 15-year cumulative HCC incidence was 3%, 4%, and 9% among treated patients (n = 394) versus 3%, 15%, and 19%, among untreated patients (n = 425), respectively ( p = 0.02), with consistent findings in subgroup analyses for age >35 years, males, HBeAg positive, HBV DNA>1000IU/mL, and alanine transaminase<upper limit of normal. In multivariable Cox proportional hazards analysis adjusted for age, sex, HBeAg, HBV DNA, alanine transaminase, diabetes, and platelets, antiviral therapy remained an independent predictor of reduced HCC risk (adjusted HR = 0.3, 95% CI: 0.1-0.6, p = 0.001). Antiviral therapy reduces HCC risk by 70% among patients with indeterminate-phase CHB. These data have important implications for the potential expansion of CHB treatment criteria.

Comparison of the optimized direct spectrophotometric serum prolidase enzyme activity assay method with the currently used spectrophotometric assay methods and liver fibrosis indexes to distinguish the early stages of liver fibrosis in patients with chronic hepatitis B infection.

The aim of this study was to optimize the currently used direct spectrophotometric serum prolidase enzyme activity (SPEA) assay method and compare its diagnostic accuracy with current precipitation and direct spectrophotometric assay methods, AST-to-ALT ratio, age platelet index, AST-to-platelet ratio index, cirrhosis discriminate score, Doha score, FIB-4, FibroQ, fibrosis index, Goteborg University Cirrhosis Index , King's score, and Pohl score for distinguishing Ishak F0 from F1-F3 in patients with chronic hepatitis B (CHB) infection. Liver biopsy results from 112 patients were included in this study. The SPEA values were 529(292-794) U/L, 671(486-927) U/L, and 1077(867-1399) U/L with the precipitation, current, and optimized direct spectrophotometric assay methods, respectively. According to multivariate logistic regression analysis optimized direct spectrophotometric SPEA was the only statistically significant parameter to predict the early stages of liver fibrosis. Optimized direct spectrophotometric SPEA assay method could be used to distinguish early stages of liver fibrosis in patients with CHB infection instead of the currentlyused spectrophotometric SPEA assay methods and other evaluated liver fibrosis indexes.

Dysregulation of T Cell Differentiation and the IL17A(+)Foxp3(+)Treg Subset in Chronic Hepatitis B Patients with Hepatitis Flare.

The regulatory T (Treg) and T helper 17 (Th17) cells modulate the immune response in chronic hepatitis B virus (HBV) infection by promoting immune tolerance and restricting liver damage or stimulating inflammatory response and rendering hepatocyte injury. These cells act through signaling transcription factors and secreting cytokines. We aimed to observe the percentages of Treg, Th17 cells, and their messenger RNA (mRNA) level of forkhead box protein 3 (Foxp3) and retinoid orphan receptor γt (RORγt) in the chronic hepatitis B (CHB)-infected group and CHB patients with hepatitis flare (HF). We recruited 103 participants, including 88 CHB-infected cases and 15 healthy controls (HCs) in Ho Chi Minh City. CHB cases were enrolled into two groups: HBeAg+ CHB infection (e+CHBI; n = 42) and HF (including 20 mild HF and 26 severe HF [sHF]). The Foxp3(+)Treg and Th17 cells were measured by flow cytometry. The mRNA levels of Foxp3 and RORγt were analyzed by real-time polymerase chain reaction. The percentages of Foxp3(+)Treg, of Th17, and the Foxp3(+)Treg/Th17 ratio were significantly higher in the sHF compared to the e+CHBI group. The sHF and e+CHBI groups had significantly higher mRNA levels of Foxp3 and RORγt compared to the HC group. Furthermore, a special subset, interleukin 17A(+)Foxp3(+)Treg cells, were observed with a significantly higher percentage in the sHF compared to the e+CHBI group. This finding revealed the contributions of this new subset on the severe flare cases. Our results explained the diversity of T cells and their subsets in the immune response in CHB. This subset should be further investigated as a specific tool in HBV immune response.

Evaluation of bone mineral density in tenofovir disoproxil fumarate-treated patients with chronic hepatitis B

Aim: Evaluate the impact of Tenofovir Disoproxil Fumarate (TDF) treatment on bone mineral density (BMD) for patients with chronic hepatitis B (CHB) with Dual X-ray absorptiometry (DEXA) and the Fracture Risk Assessment Tool (FRAX) score. Material and Methods: A total of 38 CHB patients treated with TDF were included in this retrospective study. To estimate BMD, DEXA, demographic details, and laboratory values were examined in patients. The BMD measurements were compared after dividing the patients into 3 groups as normal BMD, osteopenic, and osteoporotic. FRAX scores (before and after DEXA) were calculated. Results: Twenty-one of the 38 (55.3%) cases of CHB infection were male, the median age was 51 (min-max: 29-71) years, and seven patients (18.4%) were over 60 years of age. The median TDF duration was median 6 (min-max: 3-13) years. Osteopenia, defined by DEXA results, was found in 17 patients (44.7%) at the lumbar spine site, 11 (28.9%) at the femoral neck, and 10 (26.3%) at the total hip. Osteoporosis was detected in six patients (15.8%) at the lumbar spine site. Pre-DEXA FRAX score and post-DEXA FRAX score were calculated. Only one patient (1/33, 3%) had a score over the intervention threshold, by post-DEXA FRAX score. None of the patients classified as low risk based on the pre-DEXA FRAX score had a post-DEXA FRAX score above the intervention threshold. When the TDF duration, serum phosphorus level, vitamin D levels, and ALP levels were compared, no significant differences were found between the groups. Conclusion: There are concerns about the negative effects of TDF used in CHB infection on BMD. However, BMD loss may not increase as the duration of TDF use increases. FRAX score is useful in identifying to risk of osteoporotic fracture. FRAX score can also eliminate the need for DEXA in most CHB cases. The FRAX score should be used in clinical practice to determine cases at risk.

Effect modification of hepatitis B viral load on the association between metabolic risk factors and hepatic steatosis.

It is not clear if chronic hepatitis B (CHB) infection potentiates the severity of hepatic steatosis (HS) in patients with metabolic risk factors. We tested for the effect modification of hepatitis B viral load on the association between metabolic risk factors and HS. In this retrospective cross-sectional study, we included adult subjects, who had non-cirrhotic nonalcoholic fatty liver disease and CHB infection with positive hepatitis B envelope antibody. We reported descriptive statistics, stratified by detectable and undetectable hepatitis B viral load, by Kruskal-Wallis Rank Sum Test and chi-square. We reported coefficients of two multivariate regression predicting odds of HS > stage 2, testing for interaction between metabolic risk factors and hepatitis B viral load. When controlled for age, sex, and hepatitis B treatment, the odds of HS > stage 2 increased significantly by 77% for each additional metabolic risk factor [odds ratio (OR) 1.77, 95% confidence interval (CI): 1.20-2.69, P=0.005]. The odds of HS > stage 2 was not associated with detectable hepatitis B viral load (OR 1.00, 95% CI: 0.83-1.19, P=0.986). The association between the odds of HS > stage 2 and metabolic risk factors did not significantly change as hepatitis B viral load increased [ratio of odds ratio (ROR) 1.01, 95% CI: 0.94-1.08, P=0.839]. Our study does not find evidence of effect modification of hepatitis B viral load on the association between metabolic risk factors and HS in non-cirrhotic and hepatitis B envelope antibody positive patients with CHB viral infection. It suggests that the odds of HS in CHB infected patients is affected by metabolic risk factors and not by hepatitis B viremia.

Splenic Marginal Zone Lymphoma in a Chronic Hepatitis B Patient: A Rare Case Report and a Literature Review

BACKGROUND: Hepatitis B virus (HBV) is an important global public health problem with significant morbidity and mortality. Chronic HBV infection is a dynamic process with the risk of progression to cirrhosis and hepatic carcinoma (HCC). Although HCC is currently the main concern for diagnosed chronic hepatitis B (CHB), these patients are also considered in high risk for developing B-cell non-Hodgkin lymphoma (B-NHL). The increased risk for B-NHL is well- documented in chronic hepatitis C patients, while in HBV patients are still subject of studies and the most common form of B-NHL reported in these studies is diffuse large B-cell lymphoma (DLBCL). CASE REPORT: We are reporting the case of a patient with chronic HBV infection complicated with a rare type of B-NHL, a splenic marginal zone lymphoma (SMZL) and through a literature review aim to assess the importance of being aware of the increased risk of lymphoproliferative disorders in chronic HBV patients, asses the role of laboratory follow-up for the early diagnose of this complication, and also recommend testing for HBV infection in all patients diagnosed with B-NHL not only in DLBCL forms but also in rare forms like SMZL. CONCLUSION: CHB infection has an increased risk for B-NHL not only for the aggressive DLBCL form which is the most common form encountered but also for SMZL which is a rare indolent form of B-NHL with a better prognosis. Laboratory monitoring has a great value to the early detection of B-cell clonal expansion. In all SMZL, patients are recommended screening for HBV, because treatment with antivirals may regress lymphoma and also prevent reactivation of HBV in case of chemotherapy, especially rituximab.

Impact of advanced practice providers on characteristics and quality of care of patients with chronic hepatitis B.

Advanced practice providers (APP) may be able to play a role in improving the linkage to care in patients with chronic hepatitis B (CHB), but data are limited. To compare management of patients with CHB under APP-assisted versus physician-only care METHODS: This retrospective analysis identified patients with CHB infection from Optum's de-identified Clinformatics® Data Mart Database (2003-2021) using ICD-9/ICD-10 codes. We compared the proportion of patients with CHB who had adequate evaluation for treatment (defined as ALT, HBV DNA, ± HBeAg), and the proportion of treatment-eligible patients with CHB who received treatment between APP versus physician-only care. We included 42,140 eligible patients (mean age: 51.9 ± 15.1; 56.1% male). Overall, 34.3% received APP care with increasing utilisation over time. Compared to physician-only care, patients who also received APP care were more likely to have viral co-infection, and more likely to have been seen by a specialist (72.1%). Overall, 62.8% and 56.2% of treatment-eligible patients based on AASLD and EASL guidelines, respectively, received treatment. APP care patients were more likely to be treated (AASLD adjusted HR: 1.18, 95%CI: 1.03-1.34; EASL adjusted HR:1.24, 95%CI: 1.09-1.41) after adjustment for age, sex, race/ethnicity, viral dual infection, baseline cirrhosis/liver cancer, number of HBV DNA and alanine aminotransferase measurements, and physician provider type. Treatment-eligible patients with CHB receiving APP care were more likely to receive antiviral therapy. APP care may help to expand the pool of providers for patients with CHB, and to improve current suboptimal treatment rates.