Hepatitis B Virus Infected Patients Research Articles

Circulating soluble CD36 as a novel biomarker for progression and prognosis of HBV-related liver diseases.

Our previous study suggested CD36 may be a positive regulator of hepatitis B virus (HBV) replication in vitro. Therefore, the present study aimed to investigate whether circulating soluble CD36 (sCD36) could serve as a diagnostic and prognostic biomarker for HBV-related liver diseases based on the clinic collected data. A total of 282 subjects were divided into healthy controls (HC, n = 47), chronic hepatitis B (CHB, n = 68), HBV-related liver cirrhosis (HBV-LC, n = 167). Soluble CD36 in plasma was measured by ELISA, and monocyte or platelet CD36 expression was determined by flow cytometry. There was a step-wise increase of sCD36 with the progression of chronic HBV infection, and it was the highest in the HBV- LC group with liver failure (1.50, IQR:1.04-2.00) as compared with HC (0.38, IQR:0.27-0.38), CHB (0.75, IQR:0.40-1.13), and HBV-LC without liver failure (1.02, IQR,0.61-1.35) group. Circulating sCD36 was not correlated with serum HBV DNA levels, but correlated with liver function parameters. Additionally, ROC analysis confirmed sCD36 could be used to predict liver failure for HBV-LC patients, which yielded an AUC of 0.775 with 71.0% sensitivity and 72.2% specificity. Multivariate logistic regression analysis revealed sCD36 is an independent risk factor in predicting liver failure. Moreover, plasma sCD36 in HBV-LC patients was significantly correlated with prognostic indices, including MELD, MELD-Na and CHILD-PUGH scores. On the other hand, CD36 expression on monocytes or platelets was positively correlated with plasma sCD36 levels, whereas they were not strongly associated with the disease severity. Circulating sCD36 could be used as a novel noninvasive biomarker for predicting liver failure and prognosis in chronic HBV infected patients.

Associations between Extracellular Matrix Protein 1 Gene Polymorphism and Progression of Liver Disease.

Background Our study aimed to investigate the relationship between extracellular matrix 1 (ECM1) gene polymorphism and progression of liver fibrosis in the Chinese population. Methods A total 656 patients with hepatitis B virus (HBV) infection and 298 healthy individuals of the Chinese Han population were recruited for a retrospective case-control study. Of the disease group, 104 cases had chronic hepatitis B (CHB), 266 had LC, and 286 had hepatocellular carcinoma (HCC). Subjects were frequency-matched according to age and gender. Polymorphisms of the ECM1 gene were examined using the MassARRAY SNP genotyping method. Results There were no associations between genotype and allele frequencies of ECM1 rs3737240 and rs13294 loci with the risk of CHB and CHB-related HCC. After adjustment for age, sex, smoking status, and drinking habits, the GT genotype was dramatically related to a reduced risk of chronic HBV infection in both non-HCC (OR = 0.68, 95% CI: 0.49-0.94) and total chronic HBV infection patients (OR = 0.75, 95% CI: 0.56-1.00). Haplotype analyses revealed twelve protective haplotypes against total chronic HBV infection and four against non-HCC chronic HBV infection. Conclusion ECM1 gene polymorphism in rs3834087 and rs3754217 loci is associated with a reduced risk of chronic HBV infection but not with liver fibrosis development and the occurrence of HCC.

Clinical, Laboratory and Virological Characteristics of Patients with Positive Hepatitis B Surface Antigen

Background and Aim: Globally, Hepatitis B virus (HBV) infection is a major health issue contributing to various diseases such as hepatocellular carcinoma (HCC) and liver cirrhosis. Virus replication complex interaction with host immune system response causes dynamic interplay leading to HBV infection. In developing countries, HBV infection plays a significant role in higher rates of morbidities and mortalities. The present study aimed to assess the clinical, laboratory, and virological characteristics of patients with positive HBV surface antigen. Methodology: This cross-sectional study was carried out on 182 positive HBV surface antigen (HBsAg) in the department of Medicine, Social Security Hospital, Multan Road Lahore from April 2021 to March 2022. All the patients with positive HBsAg and negative hepatitis C were enrolled. Patients with a history of chronic liver disease, acute hepatitis B infection, and antiviral therapy were excluded. All patients underwent CBC, liver function tests, clinical evaluation, and abdominal ultrasonography examination, HBV serological marker’s assessment, HBV transmission risk factors, and HBV-DNA quantitative detection. SPSS version 25 was used for data analysis. Results: Out of 182 HBV infected patients, there were 162 (89%) males and 20 (11%) females. The overall mean age was 38.6 ± 8.6 years. The most prevalent complaint and common findings was arthralgia and hepatomegaly with reported incidence of 32 (17.6%) and 16 (8.8%) respectively. Based on ultrasonography imaging results, the incidence of normal liver, coarse liver, splenomegaly, and cirrhosis were found in 81.3% (n=148), 12.6% (n=23), 5.9% (n=11), and 6.6% (n=12) respectively. Based on laboratory results, normal alanine aminotransferase, normal aspartate aminotransferase, reduced serum albumin, and low platelet count were found in 76.9%, 84.8%, 4.9%, and 10.2% respectively. Regarding laboratory, clinical, and imaging characteristics, HBV-DNA positive and negative had no significant differences. Conclusion: The present study found that HBV infected patient’s clinical manifestations were fatigue, bleeding gums, abdominal pain and fatigue. Majority of patients had normal liver on liver function tests and ultrasonographic examination. Most patients had negative HBV infection antigen. Based on comparisons made between HBV-DNA negative and positive, no substantial variations were reported on laboratory, clinical, and imaging characteristics. Keywords: HBV antigen, Virological characteristics, HBV

Frequency distribution of hepatitis B virus (HBV) genotypes in Iraqi patients

Infection with the hepatitis B virus can lead to asymptomatic carrier status, developing into severe chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Ten genotypes (A-J) and 46 sub-genotypes have been discovered. As a result, the current study was conducted to determine HBV genotypes in Iraqi patients. RT-PCR was used to determine the highest viral load in infected subjects and then used for screening HBV genotyping. The results showed that HBV genotype distribution among HBV infected patients was as follows: genotypes C, A, B, and D (8.5%, 5%, 4.3%, and 2.1%, respectively). In addition, the value of the viral load was higher with genotype C compared to A, B, and D HBV genotyping. This study concluded that mono-genotypes prevalent in patients infected with HBV and genotype C were more prevalent. In addition to the existence of a relationship between viral load and genotyping.

Prevalence of occult hepatitis B virus infection among patients receiving haemodialysis in Sana'a city

Occult hepatitis B virus infection (OBI) is a challenging entity. Due to the increase in invasive procedures, blood transfusions, and difficulties in diagnosing OBI, patients are more likely to acquire OBI. This cross-sectional study was conducted to assess the prevalence of OBI by hepatitis B virus (HBV)-DNA detection, the prevalence of HBV infection by total hepatitis B core antibody (HBcAb) detection, and the potential risk factors for HBV infection in patients receiving haemodialysis regularly. This study included 80 patients receiving haemodialysis regularly, without acute or chronic HBV infection. They were selected from the dialysis units in Sana'a city, Yemen from June 2016 to June 2017. Patients who were positive for hepatitis B surface antigen and hepatitis B surface antibody were excluded from this study. Blood samples were taken prior to each haemodialysis session, and serological markers of HBV were included. HBcAb was measured by enzyme-linked immunosorbent assay, and HBV-DNA was measured by polymerase chain reaction. HBV-DNA was detected in four patients (5%) and HBcAb was detected in 38 patients (47.5%). There was a significant association between HBV-DNA and HBcAb in patients receiving haemodialysis regularly. Patients who test positive for HBcAb should undergo additional HBV-DNA testing to allow accurate HBV screening and prevent infection of other patients.

Gender disparity and stigma experience of patients with chronic hepatitis B virus infection: A prospective cross-sectional study from a hospital in Nigeria.

Hepatitis B virus (HBV) infected persons often suffer stigma. Stigma can come from the society or be self-induced. This study assessed the gender differences and stigma experience of patients with HBV. Prospective cross-sectional design with a qualitative element using a pretested interviewer administered questionnaire and an in-depth oral interview of HBV infected patients. Quantitative data obtained were entered into SPSS version 20 and analyzed using simple descriptive and inferential statistics, while content analysis was used for the qualitative data. Total of 242 respondents answered the quantitative questionnaire. There were 142(58.7%) males and 100 (41.3%) females; age range was 18-72years with mean (SD) of 35.4(10.7) years. Overall stigma rate was 23.1%. Stigma resulted from a positive HBsAg test, and the experience was unaffected by other markers of HBV infection. Stigma was higher in the domain of disease transmission for both single and married respondents and was particularly higher among males than females. Stigma among females affected pre-marital engagements and also caused marital disharmony among married respondents. In-depth oral interview of 23 HBV infected respondents revealed that many exhibited self-stigma, had wrong knowledge of HBV infection modes, complications, and interpretation of HBV internet information which aggravated stigma reactions. Stigma of HBV is high and majorly in the domain of disease transmission. It is higher in males than females. Enlightenment campaign targeting singles and married couples and HBV infection modes is advocated.

Prevalence of Hepatitis B Virus and Latent Tuberculosis Coinfection in the United States.

Underlying chronic hepatitis B virus (HBV) infection increases the risk of drug-induced liver injury (DILI) when receiving tuberculosis therapies. Prevalence of HBV and latent tuberculosis infection (LTBI) coinfection is not well reported and no studies have evaluated testing patterns for and prevalence of HBV-LTBI coinfection in the United States. To evaluate patterns of HBV and LTBI testing and prevalence of HBV-LTBI coinfection in the United States. Retrospective cohort study. Quest Diagnostics clinical laboratory data, 2014-2020. Chronic HBV infection was defined as any combination of 2 positive HBV surface antigen, HBV e antigen, or detectable HBV DNA tests at least 6 months apart. LTBI was defined as a positive QuantiFERON-TB or T-SPOT.TB test without evidence of active tuberculosis infection. Testing patterns for chronic HBV infection and LTBI and prevalence of HBV-LTBI coinfection were evaluated from 2016 through 2020 and stratified by age, sex, and race and ethnicity. Among 89 259 patients with chronic HBV infection, 9508 (10.7%) were tested for LTBI, among whom prevalence of HBV-LTBI coinfection was 19.6%, more than twice the observed prevalence of LTBI in patients with no chronic HBV infection in our cohort. Among 394 817 LTBI patients, 127 414 (32.3%) were tested for HBV, among whom prevalence of HBV-LTBI coinfection was 1.5%, approximately 3 times higher than prevalence of HBV infection in patients with no LTBI. The HBV-LTBI coinfection prevalence was highest among Asian Americans and older individuals. The HBV-LTBI coinfection prevalence was likely underestimated because of suboptimal awareness and testing among at-risk populations. Among US individuals with chronic HBV infection or LTBI, prevalence of HBV-LTBI coinfection is substantial and highlights the need of testing for HBV-LTBI coinfection to mitigate risk of DILI associated with tuberculosis medications in patients with chronic HBV infection.

Discovery of Novel cccDNA Reducers toward the Cure of Hepatitis B Virus Infection.

Chronic hepatitis B virus (HBV) infection is a worldwide disease that causes thousands of deaths per year. Currently, there is no therapeutic that can completely cure already infected HBV patients due to the inability of humans to eliminate covalently closed circular DNA (cccDNA), which serves as the template to (re)initiate an infection even after prolonged viral suppression. Through phenotypic screening, we discovered xanthone series hits as novel HBV cccDNA reducers, and subsequent structure optimization led to the identification of a lead compound with improved antiviral activity and pharmacokinetic profiles. A representative compound 59 demonstrated good potency and oral bioavailability with no cellular toxicity. In an HBVcircle mouse model, compound 59 showed excellent efficacy in significantly reducing HBV antigens, DNA, and intrahepatic cccDNA levels.

Development and Validation of a Non-invasive Model to Predict Liver Histological Lesions in Chronic Hepatitis B Patients With Persistently Normal Alanine Aminotransferase and Detectable Viremia

BackgroundA critical and controversial issue is whether antiviral therapy should be recommended in chronic hepatitis B virus (HBV) infection patients with persistently normal alanine aminotransferase (PNALT) and detectable HBV DNA. The study aimed to develop a non-invasive model for predicting significant liver histological changes (SLHC), which is the histological indication for antiviral therapy in chronic hepatitis B (CHB) patients with PNALT and detectable HBV DNA.Methods398 chronic HBV infection patients with PNALT and detectable HBV DNA who underwent liver biopsy were divided into the estimation set (n = 256) and validation set (n = 142). A multivariate logistic regression model was developed to predict SLHC in the estimation set, and the diagnostic performance was further validated in the validation set.Results132 patients (33.2%) with PNALT and detectable HBV DNA had SLHC. Aspartate aminotransferase (AST), cholinesterase (ChE), and liver stiffness measurement (LSM) were identified as the independent predictors of SLHC. The AUROC of the SLHC index, which combined AST, ChE, and LSM, was 0.824 and 0.816 in the estimation and validation set, respectively, for the prediction of SLHC. Applying the SLHC index ≤ 0.15, the presence of SLHC could be excluded with high negative predictive value in the estimation set (93.2%) and in the validation set (90.2%). Applying the SLHC index ≥ 0.55, the presence of SLHC could be considered with high positive predictive value in the estimation set (79.2%) and in the validation set (76.5%).ConclusionThe SLHC index provides a high accuracy in predicting liver histological indication for antiviral therapy in CHB patients with PNALT and detectable HBV DNA.

Association of Serum 25(OH)D Deficiency with High Viral Load in HBV Infected Patients

Hepatitis B virus (HBV) is a significant public health concern, particularly in low-income countries. The host immune response plays an essential role in hepatitis B virus outcome, mainly orchestrated by cytokines and immune modulators molecules such as vitamin D. This study aimed to determine the levels of cytokines (IL-10), interferon-gamma (IFN-gamma), interferon-lambada (IFN-lambada), granzyme B, and vitamin D in Khartoum, Sudan, and to assess the association between them and variable HBV viral load as well as liver enzyme levels. A total of 174 participants were enrolled in the trial, with 100 HBV-infected patients (who were HIV and HCV negative) and 74 healthy volunteers. Patients’ HBV viral load, vitamin D levels, liver enzymes, and circulatory cytokines were measured. This study revealed a remarkable decrease in vitamin D levels in HBV infected patients with an elevation in levels of liver biomarkers. The level of IL-10 was significantly higher in patients than in apparently healthy controls (p-value <0.001). There was a positive correlation between IFN-ϒ, Granzyme B, and viral load. According to the findings of this study, there is a marked hypovitaminosis D among hepatitis B infected patients with a significant increase in IL-10, which may implicate the persistence of HBV infection. Moreover, HBV DNA levels were significantly associated with IFN- g and granzyme B levels.

Association of IRGM gene promoter polymorphisms with hepatitis B virus infection.

In response to intracellular pathogens, the autophagy gene IRGM plays an essential role in the innate immune response. Various identified IRGM gene risk loci are associated with several diseases but, so far, no study is available that shows the association of IRGM with hepatitis B virus (HBV) infection. We genotyped promoter variants (rs4958842, rs4958843, and rs4958846) of IRGM in HBV infected patients (551) and healthy controls (247) for their role in HBV infection. The genotyping was performed by applying methods developed in our laboratory and various biochemical parameters were assessed applying commercially available kits. Data analysis has shown that the mutant allele A of rs4958842 plays a role in the protection from HBV infection in various genetic models that includes allelic, co-dominant and dominant models with the respective statistical data: allelic (odds ratio [OR] = 0.61; 95% confidence interval [CI] = 0.48-0.78; p = 0.0003), co-dominant (OR = 0.52; 95% CI = 0.38-0.71; p = 0.0008) and dominant (OR = 0.51; 95% CI = 0.38-0.70, p = 0.0004). In chronic hepatitis B (CHB), protective association was observed in the allelic (OR = 0.48; 95% CI = 0.35-0.65, p = 0.0004), co-dominant (OR = 0.38; 95% CI = 0.26-0.54, p = 0.0004) and dominant (OR = 0.38; 95% CI = 0.26-0.54, p = 0.0002) models. Mutant allele C of rs49598843 was associated with the risk of CHB in co-dominant (OR = 1.52; 95% CI = 1.07-2.16, p = 0.04) and dominant (OR = 1.41; 95% CI = 1.00-2.00, p = 0.04) models. The mutant allele C of rs4958846 decreased the risk of HBV infection in allelic (OR = 0.74; 95% CI = 0.59-0.92, p = 0.01), dominant (OR = 0.72; 95% CI = 0.53-0.98, p = 0.05), homozygous (OR = 0.42; 95% CI = 0.24-0.74, p = 0.01) and recessive (OR = 0.42; 95% CI = 0.24-0.74, p = 0.0004) models. However, in the asymptomatic group, it was associated with the increased chance of HBV infection. Haplotypes, ATT (OR = 0.47; 95% CI = 0.33-0.68, p = 0.001) and GTC (OR = 0.68; 95% CI = 0.51-0.92, p = 0.01) protect, whereas GTT (OR = 2.01; 95% CI = 1.55-2.60, p < 0.0001) predisposes the individuals to HBV infection. All of these pvalues mentioned here were obtained after performing Bonferroni correction. In conclusion, our findings revealed that mutant allele A of rs4958842, mutant allele C of rs4958843 and rs4958846 were associated with hepatitis B virus infection in the North Indian population.

Hepatitis B core-related antigen serum levels are associated with significant liver fibrosis in treatment-naive chronic HBV infection patients.

Several hepatitis B virus (HBV) serum markers have been identified as risk factors for liver fibrosis in patients with chronic HBV infection, and several noninvasive fibrosis tests based on serum indexes are now used to identify the severity of liver fibrosis. We aimed to identify the relationship between hepatitis B core-related antigen (HBcrAg) serum levels and liver fibrosis in treatment-naive chronic HBV infection patients. A total of 246 treatment-naive chronic HBV infection patients were enrolled in this study. All of the patients underwent liver biopsies at baseline. Using the METAVIR fibrosis stages, there were 15, 140, 50, 26 and 15 patients in the F0, F1, F2, F3 and F4stages (METAVIR scoring system), respectively. The biochemical, serological and virological parameters were measured using standard laboratory procedures. The HBcrAg serum levels of the patients were examined via ELISA. HBcrAg serum levels of F2, F3 and F4stage patients were significantly higher than those of nonsignificant liver fibrosis patients (METAVIR F0-F1), but there were no significant differences among F2, F3 and F4stage patients. Serum HBcrAg (OR, 2.18; 95% confidence interval [CI], 1.51-3.16), albumin (ALB) (OR, 0.60; 95% CI, 0.41-0.87), prothrombin activity (PTA) (OR, 0.58; 95% CI, 0.40-0.83) and platelet (PLT) counts (OR, 0.38; 95% CI, 0.25-0.57) were associated with significant liver fibrosis (METAVIR F2-F4). The serum HBcrAg value enabled the correct identification of patients with significant fibrosis, with an area under the receiver operating characteristic curve of 0.81 (95% CI, 0.75-0.88). The APRI, FIB-4 index and ALBI score can identify significant liver fibrosis with an area under the ROC curve of 0.74 (95% CI, 0.66-0.81), 0.73 (95% CI, 0.65-0.80) and 0.63 (95% CI, 0.55-0.72), respectively. Compared with these three indexes, the accuracy rate of diagnosis of significant fibrosis based on HBcrAg was higher than that of the FIB-4 index (p=0.0479) and ALBI score (p=0.0030). HBcrAg, ALB, PTA serum levels and PLT counts were associated with significant liver fibrosis in treatment-naive chronic HBV infection patients. HBcrAg serum levels enabled the correct identification of patients with significant fibrosis (METAVIR F2-F4), and HBcrAg was moreeffective than the FIB-4 index and ALBI score.

Screening and Identification of HBV Epitopes Restricted by Multiple Prevalent HLA-A Allotypes.

Although host T cell immune responses to hepatitis B virus (HBV) have been demonstrated to have important influences on the outcome of HBV infection, the development of T cell epitope-based vaccine and T cell therapy and the clinical evaluation of specific T cell function are currently hampered markedly by the lack of validated HBV T cell epitopes covering broad patients. This study aimed to screen T cell epitopes spanning overall HBsAg, HBeAg, HBx and HBpol proteins and presenting by thirteen prevalent human leukocyte antigen (HLA)-A allotypes which gather a total gene frequency of around 95% in China and Northeast Asia populations. 187 epitopes were in silico predicted. Of which, 62 epitopes were then functionally validated as real-world HBV T cell epitopes by ex vivo IFN-γ ELISPOT assay and in vitro co-cultures using peripheral blood mononuclear cells (PBMCs) from HBV infected patients. Furthermore, the HLA-A cross-restrictions of each epitope were identified by peptide competitive binding assay using transfected HMy2.CIR cell lines, and by HLA-A/peptide docking as well as molecular dynamic simulation. Finally, a peptide library containing 105 validated epitopes which cross-binding by 13 prevalent HLA-A allotypes were used in ELISPOT assay to enumerate HBV-specific T cells for 116 patients with HBV infection. The spot forming units (SFUs) was significantly correlated with serum HBsAg level as confirmed by multivariate linear regression analysis. This study functionally validated 62 T cell epitopes from HBV main proteins and elucidated their HLA-A restrictions and provided an alternative ELISPOT assay using validated epitope peptides rather than conventional overlapping peptides for the clinical evaluation of HBV-specific T cell responses.

NTCP polymorphisms were associated with fibrosis development in patients with chronic HBV infection.

Sodium taurocholate cotransporting polypeptide has been identified as the hepatitis B virus (HBV) entry receptor. However, information regarding the role of sodium taurocholate cotransporting polypeptide variants in the development of HBV-related advanced cirrhosis and hepatocellular carcinoma is limited. Overall, 581 patients with chronic HBV infection were divided into the liver fibrosis or cirrhosis group based on the Fibrosis-4 index. Further, 183 patients with hepatocellular carcinoma were distributed into early/intermediate and advanced/end stage groups based on Barcelona Clinic Liver Cancer Staging approach. Three single nucleotide polymorphisms were genotyped by high resolution melting curve method. Serum biomarkers of liver function were detected, and hepatocellular carcinoma properties were collected as well. Subjects with GA+AA genotypes at the rs4646287 polymorphism site were associated with a significantly higher rate of fibrosis development (rs4646287 GA+AA genotypes were 13.7% and 20.0% in the non-fibrosis and fibrosis group, respectively; p = 0.038). There were no significant differences between sodium taurocholate cotransporting polypeptide polymorphisms and hepatocellular carcinoma progression. The GA+AA genotype carriers of rs7154439 had relatively high albumin levels (p = 0.035). The rs2296651 GA genotype carriers tended to have solitary tumor nodule and without metastasis (p = 0.004 and 0.015, respectively). Rs4646287 was associated with HBV-related fibrosis development. Sodium taurocholate cotransporting polypeptide polymorphisms were correlated with serum albumin level as well as hepatocellular carcinoma multifocality and metastasis. Therefore, integrating sodium taurocholate cotransporting polypeptide polymorphisms to a risk stratification algorithm may help clinicians manage the chronic HBV infection patients better.

Metabolically Improved Stem Cell Derived Hepatocyte-Like Cells Support HBV Life Cycle and Are a Promising Tool for HBV Studies and Antiviral Drug Screenings

More than 300 million people worldwide are diagnosed with a chronic hepatitis B virus (HBV) infection. Nucleos(t)ide viral polymerase inhibitors are available on the market and can efficiently treat patients with chronic HBV. However, life-long treatment is needed as covalently closed circular DNA (cccDNA) persists in the hepatocyte nucleus. Hence, there is a high demand for novel therapeutics that can eliminate cccDNA from the hepatocyte nucleus and cure chronically infected HBV patients. The gold standard for in vitro HBV studies is primary human hepatocytes (PHHs). However, alternatives are needed due to donor organ shortage and high batch-to-batch variability. Therefore, human pluripotent stem cell (hPSC)-derived hepatocyte-like cells (HLCs) are being explored as an in vitro HBV infection model. We recently generated hPSC lines that overexpress three transcription factors (HC3x) and that, upon differentiation in a high amino-acid supplemented maturation medium, generate a more mature hepatocyte progeny (HC3x-AA-HLCs). Here, we demonstrate that HBV can efficiently infect these HC3x-AA-HLCs, as was shown by the presence of HBV core (HBc) and surface antigens. A clear increasing release of HBV surface and e antigens was detected, indicating the formation of functional cccDNA. Moreover, back-titration of culture supernatant of HBV-infected HC3x-AA-HLCs on HepG2-NTCP cells revealed the production of novel infectious HBV particles. Additionally, an increasing number of HBc-positive HC3x-AA-HLCs over time suggests viral spreading is occurring. Finally, the HC3x-AA-HLC model was validated for use in antiviral drug studies using the nucleoside reverse-transcriptase inhibitor, lamivudine, and the HBV entry inhibitor, Myrcludex B.

Association of PD-L1 gene polymorphisms and circulating sPD-L1 levels with HBV infection susceptibility and related liver disease progression.

Soluble molecules of programmed death ligand 1 (sPD-L1) are known to modulate T-cell depletion, an important mechanism of hepatitis B virus (HBV) persistence and liver disease progression. In addition, PD-L1 polymorphisms in the 3'-UTR can influence PD-L1 expression and have been associated with cancer risk, although not definitively. The purpose of this study was to investigate the association of PD-L1 polymorphisms and circulating levels of sPD-L1 in HBV infection and live disease progression. In this study, five hundred fifty-one HBV infected patients of the three clinically well-defined subgroups chronic hepatitis B (CHB, n=186), liver cirrhosis (LC, n=142) and hepatocellular carcinoma (HCC, n=223) and 240 healthy individuals (HC) were enrolled. PD-L1 polymorphisms (rs2297136 and rs4143815) were genotyped by in-house validated ARMS assays. Logistic regression models were applied in order to determine the association of PD-L1 polymorphisms with HBV infection as well as with progression of related liver diseases. Plasma sPD-L1 levels were quantified by ELISA assays. The PD-L1 rs2297136 AA genotype was associated with HBV infection susceptibility (HBV vs. HC: OR=1.6; 95%CI=1.1-2.3; p=0.0087) and disease progression (LC vs. CHB: OR=1.8; 95%CI=1.1-2.9; p=0.018). Whereas, the rs2297136 GG genotype was a protective factor for HCC development. Plasma sPD-L1 levels were significantly high in HBV patients (p<0.0001) and higher in the LC followed by CHB and HCC groups. High sPD-L1 levels correlated with increased liver enzymes and with advanced liver disease progression (Child-pugh C>B>A, p<0.0001) and BCLC classification (BCLC D>C>B>A, p=0.031). We could, for the first time, conclude that PD-L1 rs2297136 polymorphism and plasma sPD-L1 protein levels associate with HBV infection and HBV-related liver disease progression.

Abstract PO-035: Knowledge, motivation, and mental health: Factors associated with adherence to Hepatitis B medication among underserved Asian Americans

Abstract Introduction: Chronic Hepatitis B (CHB) Virus disproportionately affects Asian Americans, where they represent 6% of the total United States (U.S.) population but make up 58% of Hepatitis B Virus (HBV)-linked hepatocellular carcinoma (HCC) cases. HBV is the leading risk factor for developing HCC. Vietnamese and Chinese Americans suffer from disproportionate amounts of HBV infections as they represent foreign born immigrants that have come from countries with endemic HBV levels. The consequences of non-adherence to medication among is increased virological failure and a higher risk of disease progression to CHB leading to conditions such as cirrhosis as well as HCC. Understanding what factors contribute to medication adherence can be crucial for providing appropriate support for maintaining long-term treatment adherence and sustaining a virological response through interventions and strategies for high-risk populations affected by HBV. This study aims to examine the sociodemographic and psychosocial predictors of low versus medium/high adherence to medication among a community-based sample of Chinese and Vietnamese HBV infected patients. Methods: Study participants were comprised of 382 Asian American CHB patients, including 298 (78.01%) Chinese Americans and 84 (21.99%) Vietnamese Americans. Study participants were recruited between March 2019 to March 2020 and were enrolled through multiple recruitment approaches in the Greater Philadelphia Area and New York City regions. This presentation reports data from the study baseline survey with measures that included medication adherence measured by the Morisksy Medication Adherence Scale, knowledge regarding HBV diagnosis, prevention and treatment, motivation of HBV medication treatment, self-efficacy about HBV medication treatment, depression, and socioeconomic status. Multivariable logistic regression model was used, controlling for recruitment source and clustering by site. Results: Multivariable logistic regression analysis revealed that with regards to sociodemographic predictors, living longer in the U.S. (OR=4.46; 95% CI: 1.23, 16.14; p=0.023), and greater English proficiency characterized as speaking English well or very well were associated with greater odds of medium/high medication adherence (OR=0.31; 95% CI: 0.10, 0.89; p=0.030). With regards to psychosocial predictors, greater knowledge about HBV diagnosis, prevention, and treatment was associated with greater odds of medication adherence (OR=1.46; 95% CI: 1.16, 1.83, p=0.025). Additionally, greater depression score was associated with lower odds of medium/high medication adherence (OR=0.88; 95% CI: 0.78, 0.98, p=0.025). Conclusion: The study findings suggested a need for intervention regarding medication treatment and tertiary prevention and management of CHB among underserved Asian Americans. Furthermore, the association between depression and medication adherence suggests the need for psychological interventions to enhance mental health outcomes and quality of life to potentially improve or maintain medication adherence. Citation Format: Aisha Bhimla, Lin Zhu, Wenyue Lu, Sarit Golub, Chibuzo Enemchukwu, Elizabeth Handorf, Yin Tan, Minhhuyen T. Nguyen, Min Qi Wang, Grace X Ma. Knowledge, motivation, and mental health: Factors associated with adherence to Hepatitis B medication among underserved Asian Americans [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PO-035.

Celiac Disease: Risk of Hepatitis B Infection.

The aim of our study was to assess the response to hepatitis B virus (HBV) vaccination and the risk of HBV infection in patients with celiac disease (CD). We performed a cross-sectional study using the National Health and Nutrition Examination Survey (NHANES) database (2009-2014) to assess the rate of HBV vaccination, immune response, and HBV infection risk in patients with and without CD. We also determined the rate of HBV infection via retrospective analysis of two cohorts: patients seen at Mayo Clinic (1998-2021), and a stable longitudinally observed cohort, the Rochester Epidemiology Project (REP; 2010-2020). Based on the NHANES data, the rate of HBV infection in the United States was 0.33% (95% confidence interval 0.25-0.41). Of 93 patients with CD, 46 (49%) were vaccinated for HBV and of the remaining 19,422 without CD, 10,228 (53%) were vaccinated. Twenty-two (48%) vaccinated patients with CD had HBV immunity and 4405 (43.07%) vaccinated patients without CD had HBV immunity, which was not statistically different. In NHANES data, there were no cases of HBV infection in patients with CD. During the study period, 3568 patients with CD were seen at Mayo Clinic and 3918 patients with CD were identified using the REP database. Of those patients with CD, only four (0.11%) at Mayo Clinic and nine (0.23%) of the REP patients had HBV infection. The rate of HBV vaccination and immunity was similar in individuals with and without CD. Predictably, no increased risk of HBV infection was detected in CD patients. These results do not support screening and revaccination practice for HBV immunity in patients with CD within the United States.

Effects of alcohol consumption on viral hepatitis B and C.

The liver is the main target organ for hepatitis viruses and the vital organ for alcohol metabolism. These two factors of viral hepatitis and alcohol abuse in combination can exert dual harmful actions, leading to enhanced damage to the liver. Epidemiological studies have revealed a higher prevalence of hepatitis C virus (HCV) infection among alcoholics than the general population. The interaction of alcohol with viral hepatitis [e.g., hepatitis B virus (HBV), HCV] and the underlying mechanisms are not fully understood. The effects of alcohol on viral hepatitis include promoted viral replication, weakened immune response, and increased oxidative stress. Clinically, alcohol abuse is correlated with an increased risk of developing end-stage liver cirrhosis and hepatocellular carcinoma in patients with chronic hepatitis B and C, suggesting that the combination of alcohol and HBV/HCV lead to more severe liver damage. The influence of mild to moderate alcohol drinking on the HBV-induced liver fibrosis, cirrhosis, and hepatocellular carcinoma among patients infected with HBV remains unclear. Unlike HBV infected patients, no safe level of alcohol intake has been established for patients with HCV. Even light to moderate alcohol use can exert a synergistic effect with viral hepatitis, leading to the rapid progression of liver disease. Furthermore, interferon-based therapy is less effective in alcohol drinkers than in control patients, even after abstinence from alcohol for a period of time. Therefore, abstaining from alcohol is highly recommended to protect the liver, especially in individuals with HBV/HCV infection, to improve the clinical efficacy of antiviral treatment and prevent the rapid progression of chronic viral hepatitis.

Study of the D-dimer, C-reactive protein, and autoantibodies markers among HBV infected patients in Babylon province, Iraq.

BackgroundHepatitis B can be defined as one of the dangerous diseases caused by the hepatitis B virus (HBV), which infects the liver and causes liver failure, cirrhosis, and death.AimsThis study aimed to evaluate the D-dimer, C-reactive protein (CRP), and autoantibodies markers among HBV-infected patients in Babylon province, Iraq, compared to a healthy control group.MethodsIn this cross-sectional study, all patients referred to GIT and liver centers in Merjan Medical City, Babylon, Iraq from January 2016 to January 2018 were screened for HBV infection by quantitative real-time polymerase chain reaction (qPCR). Antinuclear antibody (ANA), dsDNA, D-dimer, and CRP markers were examined using fluorescence technique in randomly selected patients and some healthy individuals as control group. Statistical analysis was performed using SPSS program.ResultsIn this study, 424 HBV patients from different areas of Babylon province, Iraq were enrolled. A total of 40 patients and 15 healthy participants were selected for evaluation of D-dimer, CRP, ANA, and dsDNA levels. The results of the distribution of HBV-infected patient by gender per area revealed that males accounted for a higher percentage than females in all parts of Babylon provinces. Also, a highly significant increase in serum levels was observed in the patients compared to the control subjects for all the studied parameters D-dimer, ANA, dsDNA, and CRP. Overall, 5.5% of HBV patients (3/40) had a positive ANA titer. None of the HBV patients had a positive dsDNA titer.ConclusionThis study showed that, HBV-infected patients had elevated levels of D-dimer and CRP compared to the control group. Also, the seropositivity titers of ANA and anti-dsDNA autoantibodies were low in Iraqi HBV patients.