Chronic Hepatitis B Virus Patients Research Articles

HBV-RNA, Quantitative HBsAg, Levels of HBV in Peripheral Lymphocytes and HBV Mutation Profiles in Chronic Hepatitis B.

A comprehensive characterization of chronic HBV (CHB) patients is required to guide therapeutic decisions. The cumulative impact of classical and novel biomarkers on the clinical categorization of these patients has not been rigorously assessed. We determined plasma HBV-RNA and HBsAg levels, HBV in peripheral lymphocytes (PBMCs) and HBV mutation profiles in CHB patients. Patient demographics (n = 139) and classical HBV biomarkers were determined during a clinical routine. HBV-RNA in plasma and HBV-DNA in PBMCs were determined by RT-PCR. HBsAg levels were determined using Architect. In samples with HBV-DNA viral load >1000 IU/mL, genotype mutations in precore (PC), basal core promoter (BCP), HBsAg and Pol regions were determined by sequencing. Most patients (n = 126) were HBeAg-negative (HBeAgNeg) with significantly lower levels of HBV-RNA, HBV-DNA and HBsAg compared to HBeAg-positive (HBeAgPos) patients (p < 0.05). HBV genotype D prevailed (61/68), and >95% had BCP/PC mutations. Escape mutations were identified in 22.6% (13/63). HBeAgNeg patients with low levels of HBsAg (log IU ≤ 3) were older and were characterized by undetectable plasma HBV-DNA and undetectable HBV-RNA but not undetectable HBV-DNA in PBMCs compared to those with high HBsAg levels. In >50% of the studied HBeAgNeg patients (66/126), the quantitation of HBsAg and HBV-RNA may impact clinical decisions. In conclusion, the combined assessment of classical and novel serum biomarkers, especially in HBeAgNeg patients, which is the largest group of CHB patients in many regions, may assist in clinical decisions. Prospective studies are required to determine the real-time additive clinical advantage of these biomarkers.

Elevated coffee consumption is associated with a lower risk of elevated liver fibrosis biomarkers in patients treated for chronic hepatitis B (ANRS CO22 Hepather cohort)

Patients chronically infected with hepatitis B virus (HBV) are at high risk of liver fibrosis, cirrhosis and liver cancer, despite recent therapeutic advances. It is therefore crucial to find non-pharmaceutical options for liver fibrosis prevention in this population. Using cross-sectional data from the ANRS CO22 Hepather cohort, we aimed to identify socio-demographic and modifiable risk factors for significant fibrosis in chronic HBV patients. Logistic regression or Firth's penalized maximum likelihood logistic regression (according to outcome prevalence) multivariable models were used to test for associations between explanatory variables and significant fibrosis, as assessed by three non-invasive markers: aspartate aminotransferase to platelet ratio index (APRI), FIB-4, and gamma glutamyltransferase to platelet ratio (GPR). Analyses were stratified by HBV treatment status. The study population comprised 2065 untreated and 1727 treated chronic HBV patients. Elevated coffee consumption was consistently associated with a lower risk of elevated fibrosis biomarkers in all three treated-participant models, suggesting a dose-response relationship (adjusted odds ratios for ≥3 cups/day versus 0 cups/day: 0.16, 0.35 and 0.62, p≤0.002, according to APRI, FIB-4 and GPR, respectively). Other modifiable risk factors included tobacco and alcohol use. Elevated coffee consumption was consistently associated with a lower risk of significant liver fibrosis, as assessed by three non-invasive markers in treated chronic HBV patients. This result can be immediately used in real-world situations, as increasing coffee consumption may be beneficial for patients at risk of advanced liver disease.

Novel X gene point mutations in chronic hepatitis B and HBV related cirrhotic patients.

HBx is a multifunctional modulator viral protein with key roles in various biological processes such as signal transduction, transcription, proliferation, and cell apoptosis. Also, HBx has an important role in the progression of cirrhosis and hepatocellular carcinoma (HCC). This study aimed to determine mutations in X gene, enhancer II (EnhII), and basal core promoter (BCP) of genotype D of Hepatitis B Virus (HBV) in cirrhotic and chronic HBV patients. This cross-sectional study was performed on 68 cases with chronic HBV (cHBV) and 50 cases with HBV related cirrhosis. Serum samples were obtained for genomic DNA extraction. Semi-nested PCR was used to amplify the HBx region. Point mutations in the HBx region were detected by sequencing. Novel mutations were detected, including C1491G, C1500T, G1613T, and G1658T in the N-terminal of the X gene. The frequency of C1481T/G1479A, T1498C, C1500T, G1512A, A1635T, C1678T, A1727T, and A1762T/ G1764A/ C1773T was significantly higher in cirrhotic patients compared to chronically HBV infected ones. A higher rate of A1635T, C1678T, A1727T, A1762T, G1764A, and C1773T was observed in cirrhotic patients. Our findings showed that the frequency of mutations in the basal-core promoter, enhancer II, and regulatory region of the HBx gene was more seen in cirrhotic patients than in chronic HBV cases. Novel mutations were detected in the HBx gene, causing amino acid substitutions; however, the clinical impact of these novel mutations is yet to be cleared.

Serum levels of IL-12, IL-18, and IL-21 are indicators of viral load in patients chronically infected with HBV.

This study explored the correlation between interleukins (IL)-12, IL-18, and IL-21 and the viral load in patients with chronic hepatitis B virus (HBV). A total of 142 patients were consecutively enrolled. All were hepatitis B surface antigen (HBsAg)-positive for >6 months and did not receive drug therapy. An ELISA kit was used to test the IL-12, IL-18, IL-21, and acetylcholinesterase (AchE) levels in serum samples from chronic HBV patients and healthy control groups. The amounts of IL-12 and IL-18 were highest in the 5-6log10 (high viral load) group, while IL-21 was highest in the 3-4log10 (low viral load) group. Also, the IL-21 amount was decreased in the HBsAg+/HBeAg/HBcAb+ group, and IL-12, IL-18, and IL-21 were decreased in the normal alanine aminotransferase (ALT) group compared to the abnormal ALT group. These data suggested that IL-12, IL-18, and IL-21 serum levels were positively correlated with disease progression and could reflect disease severity for different HBV-DNA loads. Detection of IL-12, IL-18, and IL-21 levels was found to be helpful for evaluating the degree of liver cell damage and predicting the progression of hepatitis.

The Measurement of 25-Hydroxyvitamin-D in Chronic HBV Patients Using LC-MS/MS.

Vitamin D deficiency is universal among patients with chronic liver disease. Vitamin D may be involved in the regulation of immune function of chronic hepatitis B and related to disease progression. The study was a cross-sectional study. The level of vitamin 25(OH)D was detected in patients with chronic hepatitis B, hepatitis B cirrhosis, hepatitis B cancer, and healthy groups by isotope dilution liquid chromatography tandem mass spectrometry (LC-MS/MS). At the same time, the clinical data, biochemical indexes, and T lymphocyte subsets were collected to study the relationship between vitamin 25(OH)D deficiency and clinical indexes of hepatitis B patients. The prevalence of vitamin D deficiency (< 20 ng/mL) was higher in patients with liver cancer group (96.97%, 10.59 ± 3.06 ng/mL) and cirrhosis group (93.18%, 11.85 ± 2.66 ng/mL) than in the healthy group (76.92%, 16.38 ± 5.53 ng/mL) and chronic hepatitis B group (77.83%, 15.06 ± 4.91 ng/mL). There were significant differences in vitamin 25(OH)D levels between the cirrhosis groups and the healthy groups, the liver cancer groups and the healthy groups, the hepatitis B cirrhosis groups and the chronic hepatitis B groups, the liver cancer groups and the chronic hepatitis B groups (p < 0.05). There was no significant difference in vitamin 25 (OH)D level between liver cancer group and hepatitis B cirrhosis group, healthy group and chronic hepatitis B group (p > 0.05). Vitamin 25(OH)D level was correlated with age (r = -0.24, p = 0.015), lymphocyte (r = 0.24, p = 0.015), hemoglobin (r = 0.28, p = 0.005), platelet (r = 0.27, p = 0.006), PTA (r = 0.33, p = 0.001), albumin (r = 0.30, p = 0.002), prealbumin (r = 0.39, p = 0.001), cholinesterase (r = 0.29, p = 0.003), CD3+ (r = 0.20, p = 0.04), CD3+ CD8+ (r = 0.20, p = 0.04), CD45+ (r = 0.24, p = 0.017), but none correlated with liver function and HBV-DNA. Vitamin D deficiency existed in patients with hepatitis B, which was related to the clinical progress of hepatitis B and may be involved in the regulation of immune function in patients with chronic HBV infection.

Diagnostic Value of hTERT mRNA and in Combination With AFP, AFP-L3%, Des-γ-carboxyprothrombin for Screening of Hepatocellular Carcinoma in Liver Cirrhosis Patients HBV or HCV-Related.

Diagnosis of hepatocellular carcinoma (HCC) in early-stage, to give an effective treatment option and improve quality of life for cancer patients, is an important medical mission globally. Combination of AFP with some biomarkers may be more supportive in both diagnosis and screening of HCC, but the range value of these markers can be applied as daily markers were unclearly. In some studies, human telomerase reverse transcriptase (hTERT mRNA) was reported as an advantage marker to diagnose cancer. The present study identified serum of 340 patients that were infected chronic hepatitis B virus or hepatitis C virus and divided in 2 groups including Hepatocellular carcinoma (HCC) and liver cirrhosis (LC) to measure their values of hTERT mRNA, AFP, AFP-L3%, and DCP, as well as combination of them. As a result, the concentration of hTERT mRNA, AFP, AFP-L3%, and DCP in HCC groups were significantly higher than that in LC group (P < .01). For detecting HCC, hTERT mRNA had sensitivity of 88% and specificity of 96% (at the cutoff value of 31.5 copies/mL), AFP sensitivity of 73% and specificity of 92% (at the cutoff value of 5.1 ng/mL), AFP-L3% sensitivity of 69% and specificity of 90% (at the cutoff value of 1.05%), DCP sensitivity of 82% and specificity of 92% (at the cutoff value of 29.01 mAU/mL). The largest area under the curve (AUC) of combination hTERT mRNA with DCP was 0.932 (sensitivity of 98.2% and specificity of 88.2%). New combination of DCP with hTERT mRNA gave a useful choice for screening of HCC in chronic HBV or HCV patients associated liver cirrhosis.

Association of serum 25-hydroxyvitamin D3 levels and insulin resistance with viral load and degree of liver fibrosis in Egyptian chronic HBV patients: a case-control study.

Aim of the studyTo assess serum 25-hydroxyvitamin D3 level and insulin resistance (IR) in hepatitis B virus (HBV) patients compared with controls and to evaluate the correlation with HBV viral load, severity of liver disease and degree of liver fibrosis.Material and methodsA case-control study. Sixty HBV patients and 60 controls were enrolled. Chemiluminescence was used to determine 25-hydroxyvitamin D3 levels. Insulin resistance was evaluated using the homeostasis model assessment method. Polymerase chain reaction was used to quantify HBV viral loads. Severity of liver disease was assessed by Child-Pugh scores. Transient elastography was used to evaluate the degree of liver fibrosis.Results25-Hydroxyvitamin D3 deficiency is more prevalent among HBV patients compared to controls. 25-Hydroxyvitamin D3 levels declined considerably as viral load rose (p < 0.001). 25-Hydroxyvitamin D3 level declined as liver fibrosis progressed (34.0 ±0.0 ng/ml in F1 vs. 12.67 ±8.0 ng/ml in F4) and the severity of the disease increased (22.75 ±6.36 ng/ml in Child A vs. 5.50 ±0.58 ng/ml in Child C). Insulin resistance is more prevalent among HBV patients compared to controls and it appeared to deteriorate progressively with boosting of the viral load, degree of fibrosis and severity of liver disease (p < 0.001).ConclusionsHBV patients had significantly lower 25-hydroxyvitamin D3 levels compared to healthy individuals and HBV infection is associated with IR. 25-Hydroxyvitamin D3 deficiency and IR were associated with HBV viral loads, severity of liver disease, and degree of liver fibrosis.

Current Progress in the Development of Hepatitis B Virus Capsid Assembly Modulators: Chemical Structure, Mode-of-Action and Efficacy.

Hepatitis B virus (HBV) is a major causative agent of human hepatitis. Its viral genome comprises partially double-stranded DNA, which is complexed with viral polymerase within an icosahedral capsid consisting of a dimeric core protein. Here, we describe the effects of capsid assembly modulators (CAMs) on the geometric or kinetic disruption of capsid construction and the virus life cycle. We highlight classical, early-generation CAMs such as heteroaryldihydropyrimidines, phenylpropenamides or sulfamoylbenzamides, and focus on the chemical structure and antiviral efficacy of recently identified non-classical CAMs, which consist of carboxamides, aryl ureas, bithiazoles, hydrazones, benzylpyridazinones, pyrimidines, quinolines, dyes, and antimicrobial compounds. We summarize the therapeutic efficacy of four representative classical compounds with data from clinical phase 1 studies in chronic HBV patients. Most of these compounds are in phase 2 trials, either as monotherapy or in combination with approved nucleos(t)ides drugs or other immunostimulatory molecules. As followers of the early CAMs, the therapeutic efficacy of several non-classical CAMs has been evaluated in humanized mouse models of HBV infection. It is expected that these next-generation HBV CAMs will be promising candidates for a series of extended human clinical trials.

Late presentation of chronic HBV and HCV patients seeking first time specialist care in Spain: a 2-year registry review

Chronic viral hepatitis infection affects an estimated 325 million people globally. People who initiate treatment after significant disease progression face increased risk of severe liver complications and death. Data are scarce on the characteristics and risk factors of people who present late to care in Spain and globally. Data were collected from January 2018 to December 2019 to report late presentation (LP) to specialist care at 11 large university hospitals in Spain to assess related risk factors using a multivariable logistic regression model. 2290 (CHB = 505, CHC = 1785) patients were analysed, with 581 (25.2%) presenting late. Hepatitis C patients more frequently reported LP compared to hepatitis B patients (28.1% vs 15.0%; p < 0.001). Older age (p < 0.001), being male (p < 0.001), being Spanish-born (p < 0.001), and having an unknown origin of referral (p = 0.08) were associated with a higher likelihood of LP. Advanced liver disease was identified in 533 (23%) patients and late-stage liver disease in 124 (5.4%). LP, including with irreversible liver damage, to viral hepatitis specialist care is frequent in Spain, despite being a country with unrestricted treatment access. Initiatives to reduce LP should specifically target men, older individuals, foreign-born populations for CHB, and Spanish nationals for CHC.

Evaluation of antiviral treatment for hepatitis B with tenofovir and entecavir at the viral hepatitis outpatient clinic of the tropical medicine research center in Rondônia / Avaliação do tratamento antiviral da hepatite B com tenofovir e entecavir no ambulatório de hepatites virais do centro de pesquisa em medicina tropical de Rondônia

The emergence of treatment-resistant strains has been an obstacle in antiviral treatment of hepatitis B, which is carried out when the disease evolves to the chronic phase. In 2017, the Ministry of Health limited the therapeutic arsenal to the use of Tenofovir and Entecavir, due to their greater effectiveness and genetic barrier. However, there are no comparative studies of the antiviral activity of these two drugs in the state of Rondônia; such studies would improve the treatment of this disease. Thus, the objective of this study is to evaluate the therapeutic response of hepatitis B patients treated with Entecavir and Tenofovir at state of Rondônia. Patient data were analyzed in medical records containing information about the treatment used and the evolution of each patient’s clinical condition. The tests observed are those that detect HBV DNA to assess viral load, HBV serological markers and liver transaminases, to monitor the evolution of the disease. As a result, the samplings and correlations carried out in this study indicated that the efficacy of both Entecavir and Tenofovir was satisfactory in view of the different profiles of chronic HBV patients evaluated, since they reduced the viral load and normalized transaminases. The data obtained may help to understand the profile and therapeutic response of patients infected with the HBV virus who are treated with Tenofovir and Entecavir, as well as to disseminate pharmacoepidemiological data.

Identification and Mapping of HBsAg Loss-Related B-Cell Linear Epitopes in Chronic HBV Patients by Peptide Array.

Identification of immunogenic targets against hepatitis B virus (HBV)-encoded proteins will provide crucial advances in developing potential antibody therapies. In this study, 63 treatment-naïve patients with chronic HBV infection and 46 patients who achieved hepatitis B surface antigen loss (sAg loss) following antiviral treatment were recruited. Moreover, six patients who transitioned from the hepatitis B e antigen-positive chronic infection phase (eAg+CInf) to the hepatitis phase (eAg+CHep) were enrolled from real-life clinical practice. Additionally, telbivudine-treated eAg+CHep patients and relapsers or responders from an off-treatment cohort were longitudinally studied. The frequencies and function of B cells were assessed by flow cytometry. We devised a peptide array composed of 15-mer overlapping peptides of HBV-encoded surface (S), core (C), and polymerase (P) proteins and performed a screening on B-cell linear epitopes with sera. Naïve B cells and plasmablasts were increased, whereas total memory, activated memory (AM), and atypical memory (AtM) B cells were reduced in sAg- patients compared with sAg+ patients. Importantly, longitudinal observations found that AtM B cells were associated with successful treatment withdrawal. Interestingly, we identified six S-specific dominant epitopes (S33, S34, S45, S76, S78, and S89) and one C-specific dominant epitope (C37) that reacted with the majority of sera from sAg- patients. Of note, more B-cell linear epitopes were detected in CHep patients with alanine aminotransferase (ALT) flares than in nonflare CInf patients, and five B-cell linear epitopes (S4, S5, S10, S11, and S68) were overwhelmingly recognized by ALT flare patients. The recognition rates of epitopes on C and P proteins were significantly increased in CHep patients relative to CInf patients. Strikingly, a statistically significant elevation in the number of positive epitopes was observed when ALT nonflare patients shifted into the flare phase. Moreover, S76 identified at baseline was confirmed to be associated with a complete response after 48 weeks of telbivudine therapy. Taken together, we identified several functional cure-related B-cell linear epitopes of chronic HBV infection, and these epitopes may serve as vaccine candidates to elicit neutralizing antibodies to treat HBV infection.

GAS5 rs2067079 and miR-137 rs1625579 functional SNPs and risk of chronic hepatitis B virus infection among Egyptian patients

Hepatitis B virus (HBV) infection is a significant health issue worldwide.. We attempted to fulfill the molecular mechanisms of epigenetic and genetic factors associated with chronic HBV (CHBV). Expression levels of the lncRNA growth arrest-specific 5 (GAS5) and miR-137 and their corresponding SNPs, rs2067079 (C/T) and rs1625579 (G/T) were analyzed in 117 CHBV patients and 120 controls to investigate the probable association between these biomarkers and CHBV pathogenesis in the Egyptian population. Serum expression levels of GAS5 and miR-137 were significantly down-regulated in cases vs controls. Regarding GAS5 (rs2067079), the mutant TT genotype showed an increased risk of CHBV (p < 0.001), while the dominant CC was a protective factor (p = 0.004). Regarding miR-137 rs1625579, the mutant genotype TT was reported as a risk factor for CHBV (p < 0.001) and the normal GG genotype was a protective factor, p < 0.001. The serum GAS5 was significantly higher in the mutant TT genotype of GAS5 SNP as compared to the other genotypes (p = 0.007). Concerning miR-137 rs1625579, the mutant TT genotype was significantly associated with a lower serum expression level of miR-137 (p = 0.018). We revealed the dysregulated expression levels of GAS5 and miR-137 linked to their functioning SNPs were associated with CHBV risk and might act as potential therapeutic targets.

Comparative expression of pro-inflammatory and apoptotic biosignatures in chronic HBV-infected patients with and without liver cirrhosis

The interplay of immune mediators is paramount to optimal host anti-viral immune responses, especially against chronic hepatitis B virus (HBV) infection. Here, we investigated the dynamic changes in host immune responses in chronic HBV-infected individuals with and without liver cirrhosis by examining the signatures of apoptosis and plasma levels of pro-inflammatory cytokines, chemokines, and cytotoxic proteins. A total of 40 chronic HBV patients with and without liver cirrhosis were studied for plasma levels of immune mediators, and signatures of apoptosis in peripheral blood mononuclear cells (PBMCs). The intracellular concentrations of reactive oxygen species (ROS) in patients with chronic HBV with liver cirrhosis was relatively higher as compared to chronic HBV patients. The onset of apoptosis was sustained due to ongoing liver inflammation in concert with plasma TNF-α and IL-6 levels. Plasma VEGF was upregulated among chronic HBV patients with liver cirrhosis, whereas CCL2, CCL5 and granzyme B levels were down-regulated. High levels of ROS, IL-6 and TNF-α correlated with ongoing inflammation among chronic HBV patients with liver cirrhosis, which likely attributed to the expression of biosignatures of apoptosis and activation in immune cells.

S1190 Hepatic Fibrosis Improvement Does Not Differ Between Type of Antiviral Therapy in Chronic Hepatitis B Patients

Introduction: Chronic Hepatitis B infection (HBV) is the most common viral hepatitis infection worldwide. HBV can result in progressive liver injury culminating in significant inflammation and fibrosis. The aim of this study is to assess the effectiveness of various antiviral therapies on hepatic fibrosis in chronic HBV infection using noninvasive markers in a community setting. Methods: A retrospective study was conducted in chronic HBV patients seen at the Liver Associates of Texas Hepatology clinics in Houston, Texas, seen from 1/2018 to 5/2021. Epidemiological and clinical data of HBV patients treated with entecavir, tenofovir disoproxil fumarate, or tenofovir alafenamide were analyzed. APRI and FIB-4 scores, which are noninvasive markers of fibrosis, were calculated for all patients at baseline (before treatments) and 6 months post sustained virologic response (SVR). A repeated measures ANOVA analysis was used to assess fibrosis trends between the three treatments and within a single treatment group. Results: A total of 123 patients were reviewed. 64.2% of patients were male, with the mean age of 54.0 years. The ethnic breakdown was: 56.9% Asian, 24.4% African-American, 8.1% White, 4.9% Hispanic, 0.8% Native Hawaiian/Pacific Islander, and 4.9% Unknown. 85 patients received treatment, with 20 patients receiving entecavir, 29 tenofovir alafenamide, and 36 tenofovir disoproxil fumarate. Both APRI and FIB-4 scores showed a statistically significant difference from before treatment to 6 months post treatment independent of treatment type(APRI: p= 0.035; FIB-4: p= 0.037). Post-hoc analysis showed a statistical significant decrease from baseline to 5 months post initiation of treatment for both APRI (Mean difference = 0.229, pbonferroni = 0.035) and FIB4 (mean difference = 0.168, pbonferroni = 0.037). There was no statistical significant interactions between treatment type and FIB4 or APRI scores. Conclusion: This study demonstrated that in patients with Hepatitis B, there was a statistically significant improvement in hepatic fibrosis within 6 months of antiviral therapy initiation and that there is no significant difference in using any of the three types of antiviral treatments: entecavir, tenofovir disoproxil fumarate, or tenofovir alafenamide in this population of HBV patients.Figure 1.: Title: APRI scores over time in patients treated with Entecavir, Viread, and Vemlidy. Legend: Blue = entecavir. Gray = tenofovir alafenamide, Yellow = tenofovir disoproxil fumarate.Table 1.: GIST characteristics of patients with both abscess and GIST.

S1248 Renal Function Among Patients With Chronic Hepatitis B Virus Infection Receiving Antiviral Therapy

Introduction: Hepatitis B virus infection continues to be one of the most significant public health concerns globally. An estimated 250 million people are chronically infected with this disease worldwide. There are two groups of therapies currently approved for the treatment of this pathology: pegylated interferons and nucleos(t)ides analogs. Entecavir, tenofovir disoproxil fumarate, or tenofovir alafenamide are considered the first-line therapies for the treatment of adults with immune-active, chronic HBV infection. The primary aim of our study was to determine if tenofovir alafenamide is less nephrotoxic than entecavir or tenofovir disoproxil fumarate in Chronic HBV patients. Methods: A retrospective case control study was conducted at Liver Associates of Texas Hepatology clinics in Houston, Texas. Included were patients treated with HBV between December 2017- May 2021. All patients underwent laboratory and serologic testing. Creatinine clearance and EGFR values were recorded in all patients receiving either tenofovir disoproxil, tenofovir alafenamide, or entecavir at two-time points: baseline (before or at diagnosis) and 3 years after treatment. A two-way repeated-measures ANOVA test was used to compare creatinine clearance and EGFR of the treatment groups over time. Results: 94 patients were included in this study. 54 were Asian, 23 African American, 8 White, 6 Hispanic, and 3 unspecified. The mean age was 54 years old (± 13) and 63 patients were male. 22 patients received entecavir, 39 tenofovir disoproxil, and 33 tenofovir alafenamide. In our population, there was no statistical difference in the creatinine clearance at baseline vs 3 years follow-up (p = 0.548) independent of treatment type (table 1). Furthermore, no significant interaction was found between treatment groups and creatinine clearance over time (p = 0.725). Regarding EGFR, there was also no statistical difference in this lab parameter at baseline vs 3 years follow-up (p = 0.292) irrespective of the treatment received, and no significant interaction between treatment groups and EGFR (p = 0.457). Furthermore, no significant differences were found between treatment group in creatinine clearance (p=0.770) or EGFR (p= 0.835) irrespective of time. Conclusion: In our population, there was no statistically significant difference in renal function as assessed by creatinine clearance and EGFR, among patients with chronic hepatitis B virus infection after 3 years of follow-up irrespective of the type of treatment.Table 1.: Patient Characteristics at different levels of Alpha feto Protein a- Median and Inter quartile range b- Mean and standard deviation.Figure 1.: Association of B12 deficiency and NAFLD as well as NAFLD Complications

Association Analysis of Genetic Variants of Sodium Taurocholate Co-Transporting Polypeptide NTCP Gene (SLC10A1) and HBV Infection Status in a Cohort of Egyptian Patients

Background: Single nucleotide polymorphisms (SNPs) in the SLC10A1 gene, coding for a functional receptor of hepatitis B virus (HBV), sodium taurocholate co-transporting polypeptide (NTCP), may influence the susceptibility, outcome, and disease course of HBV infection in some populations. Aim: to determine the prevalence of SNPs of the NTCP gene, rs2296651 and rs943277, and their relationship with chronic HBV infection in a group of Egyptian patients. Methods: One hundred and thirty seven patients with HBV and 65 healthy controls were enrolled, and the patients were divided into two groups; group I chronic HBV infection (68 patients with normal ALT and minimal or no liver necroinflammation or fibrosis) and group II chronic hepatitis B (69 patients with elevated ALT and moderate or severe liver necroinflammation). They were subjected to full history taking, clinical examination, laboratory investigations, abdominal ultrasound, and liver stiffness measurement using both Echosens® Fibroscan and acoustic radiation force impulse (ARFI). A real time PCR TaqMan 5′ allelic discrimination assay was applied to detect the SNPs in the NTCP gene, rs2296651 and rs943277. Results: On studying the rs2296651 variant, all controls and patients had genotype GG without any significant association with HBV infection or disease progression. However, the rs943277 variant in all controls and 98% of patients had genotype GA, except for two chronic HBV infection patients who had genotype AA, but no significant difference between patients and controls was found. The non-invasive methods for liver fibrosis assessment ARFI, AST/platelet’s ratio (APRI), and fibrosis-4 score (FIB-4) could predict the stages of fibrosis in agreement with Fibroscan with AUCOR 0.8, 0.79, and 0.76, respectively. Conclusion: These findings may suggest that there is no relation between these SNPs of the NTCP gene and the susceptibility or chronicity of HBV infection in the Egyptian population. We also suggest that the use of the non-invasive methods for liver fibrosis assessment, ARFI, FIB-4, and APRI, may decrease the need for liver biopsies in the prediction of significant hepatic fibrosis in chronic HBV patients.

The Prevalence and Serological Association of Hepatitis D Virus Genotypes in Taiwan.

Hepatitis Delta Virus (HDV) is an RNA virus that requires the presence of hepatitis B surface antigen (HBsAg) to propagate into hepatocytes, with Genotype I being more prevalent globally. However, the prevalence of HDV genotypes in Taiwan is unknown. Accordingly, a cohort including 24 chronic HBV patients who received nucleos(t)ides (NUCs) between January 2002 and July 2018 was used to determine HDV genotypes and genotype specific serological association in chronic HBV carriers. HDV-positive genotypes in 18/24 (75%) males and 6/24 (25%) females were identified among chronic HBV patients. Viremia was lower in HDV-IV patients than in patients affected with other HDV genotypes (1.34 log10 copies/mL vs. 3.30 log10 copies/mL; p = 0.009). A logistics regression analysis revealed that HDV-IV was inversely proportional to HDV RNA (odds ratio [OR]/95% confidence intervals [CI]: 0.370/0.164–0.830; p = 0.017). The serologic association study indicated lower levels of creatinine (p = 0.047) and HDV-RNA (p = 0.009) in the HDV-IV group than the non-HDV-IV group but did not indicate any significant differences in the AST, ALT, bilirubin levels or other laboratory test factors. The three genotypes evident in Taiwan were HDV-I (4/24, 16.7%), HDV-II (6/24, 25.0%), and HDV-IV (14/24, 58.3%), and HDV-IV is the predominant HDV genotype in Taiwan. These results anticipate a clear understanding of HDV genotype serological association in chronic HBV carriers.

A Therapeutic Hepatitis B Virus DNA Vaccine Induces Specific Immune Responses in Mice and Non-Human Primates

Despite the availability of an effective prophylactic vaccine for more than 30 years, nearly 300 million people worldwide are chronically infected with the hepatitis B virus (HBV), leading to 1 death every 30 s mainly from viral hepatitis-related cirrhosis and liver cancer. Chronic HBV patients exhibit weak, transient, or dysfunctional CD8+ T-cell responses to HBV, which contrasts with high CD8+ T-cell responses seen for resolvers of acute HBV infection. Therefore, a therapeutic DNA vaccine was designed, expressing both HBV core and polymerase proteins, and was sequence optimized to ensure high protein expression and secretion. Although the vaccine, administered intramuscularly via electroporation, had no effect on plasma viral parameters in a mouse model of persistent HBV infection, it did induce robust HBV-specific immune responses in healthy and adeno-associated hepatitis B virus (AAV-HBV) infected mice as well as in healthy non-human primates.

MiR-155 T/A (rs767649) and miR-146a A/G (rs57095329) single nucleotide polymorphisms as risk factors for chronic hepatitis B virus infection among Egyptian patients.

Genetic variants in microRNAs (miRNAs) can alter the miRNAs expression and/or function, accordingly, affecting the related biological pathways and disease risk. Dysregulation of miR-155 and miR-146a expression levels has been well-described in viral hepatitis B (HBV). In the current study, we aimed to assess rs767649 T/A and rs57095329 A/G polymorphisms in miR-155, and miR-146a genes, respectively, as risk factors for Chronic HBV (CHBV) in the Egyptian population. Also, we aimed to do in silico analysis to investigate the molecules that primarily target these miRNAs. One hundred patients diagnosed as CHBV and one hundred age and sex-matched controls with evidence of past HBV infection were genotyped for miR-155 (rs767649) and miR-146a (rs57095329) using real-time polymerase chain reaction. The rs767649 AT and AA genotypes in CHBV patients confer four folds and ten folds risk respectively, as compared to control subjects [(AOR = 4.245 (95%CI 2.009–8.970), p<0.0001) and AOR = 10.583 (95%CI 4.012–27.919), p<0.0001, respectively)]. The rs767649 A allele was associated with an increased risk of developing CHBV (AOR = 2.777 (95%CI 1.847–4.175), p<0.0001). There was a significant difference in the frequency of rs57095329 AG and GG genotypes in CHBV patients compared to controls. AG and GG genotypes showed an increase in the risk of developing CHBV by about three and six folds respectively [AOR = 2.610 (95%CI 1.362–5.000), p = 0.004] and [AOR = 5.604 (95%CI 2.157–14.563), p<0.0001].We concluded that rs57095329 and rs767649 SNPs can act as potential risk factors for the development of CHBV in the Egyptian population.

Analysis of risk factors for drug resistant mutations in the reverse transcriptase region in chronic hepatitis B virus-infected patients

Objective: To analyze the risk factors that may affect the mutations in the reverse transcriptase region in chronic hepatitis B virus-infected patients. Methods: 678 hospitalized cases with chronic HBV infection who underwent HBV RT testing at Tianjin Second People's Hospital from January 1, 2016 to December 31, 2016 were collected retrospectively. Among them, 417 cases were diagnosed with chronic hepatitis B, 219 cases with liver cirrhosis and 42 cases with primary liver cancer. There were 268 cases of non-use of any antiviral therapy, 138 cases of discontinuation of antiviral drugs for 6 months or more, and 272 cases of continuous antiviral therapy. HBV genotyping and RT region mutation sites were detected by direct sequencing. The risk factors that may affect the drug resistant mutation in the HBV RT mutation, including age, genotype, antiviral drug selection and medication time, hepatitis B virus infection, and biochemical markers were analyzed by univariate analysis to screen out independent risk factors. Results: Among 678 HBV-infected cases, 290 cases (42.8%) were detected with RT-region mutation. Among them, the pre-existing drug resistant rate was 6.72%, and the drug resistant mutation rate was 23.19% in treated patients. The drug resistant mutation rate of patients with continuous antiviral therapy was 66.18%. Gene mutations highest rate for 1 ~ 5 years was 27.14% in chronic HBV patients treated with antiviral therapy. Logistic regression analysis of the factors that had led to HBV mutation showed that old age, the selection of nucleoside drugs at the beginning of treatment and medication time were the main factors affecting HBV RT mutations. Conclusion: Abnormal ALT level, HBV genotype, HBV DNA quantitative level are the main factors influencing non-drug resistant mutations. Age over 60 years old, and long-term use of low-barrier nucleoside drugs are high-risk groups for HBV resistant. Therefore, HBV resistant monitoring should be strengthened.