Outcome Of Hepatitis B Virus Infection Research Articles

The Association of IFNL4 Gene Polymorphisms with Hepatitis B Virus (HBV) Infection in the Northern Region of Pará, Brazil

It is heavily suggested that one IFNL4 gene polymorphism, rs12979860 (T/C), exerts influence on the outcome of HBV infection, with the rs12979860-T allele being classified as a risk predictor, and the rs12979860-C allele being classified as a protective one. This study investigated whether the rs12979860 IFNL4 gene polymorphism presented any association with the clinical severity for HBV carriers in an admixed population in Northern Brazil. A total of 69 samples were investigated from infected people from the city of Belém-Pará. The rs12979860-T allele was positively associated with HBV infection, suggesting a higher risk of chronicity. This research’s importance is that the polymorphism influence was investigated in a population of HBV carriers with a heterogeneous genetic profile, formed through the extensive admixture of different ethnic groups, including Europeans, Africans, and Natives with indigenous heritage. This analysis is particularly important since highly mixed populations do not always follow the same association patterns previously established by studies using populations classified as more genetically homogeneous, due to a different formation process.

Association of HLA-G 3'UTR polymorphisms with hepatitis B virus infection in Tunisian population.

Hepatitis B virus (HBV) infection is a major public health burden. The mechanisms of immune evasion during chronic HBV (CHB) infection are poorly understood. Human leukocyte antigen (HLA)-G, an immune checkpoint molecule, plays a crucial role in the tolerance mechanisms of various infectious diseases. The 3' untranslated region (3'UTR), including the HLA-G + 3142 C > G polymorphism (rs1063320) and the 14-pb Ins/Del (rs66554220) has been strongly suggested to influence HLA-G expression. This study conducted a case-control analysis to evaluate the potential correlation between the HLA-G + 3142 C > G polymorphism and HBV infection outcome in a Tunisian cohort. The HLA-G + 3142 C > G polymorphism was analysed by PCR-RFLP in 242 patients with chronic HBV infection (116 males and 126 females), 241 healthy controls (116 males and 125 females), and 100 spontaneously resolved subjects (52 males and 48 females). Patients with chronic HBV infection showed a higher frequency of the + 3142G allele compared to healthy controls and spontaneously resolved subjects (p = 0.001 and p = 0.002, respectively). An association between the + 3142G allele and high HBV DNA levels was observed when HBV patients were stratified based on their HBV DNA levels (p = 0.016). Furthermore, the dominant model (GG + GC vs CC) was associated with liver function parameters, including AST, ALT, and high HBV DNA levels (p = 0.04, p < 0.001 and p = 0.002, respectively). However, there was no significant association found between this polymorphism and the fibrosis stage (p = 0.32). The haplotype analysis, using a subset of previously published data on the HLA-G 14-pb Ins/Del polymorphism, revealed an association between the Ins/G haplotype and chronic HBV infection (H1: InsG, p < 0.001). Our findings suggest that the + 3142G allele is a risk factor for the persistence and progression of HBV infection, while the + 3142C allele serves as a protective allele associated with the spontaneous resolution of the infection. Additionally, the HLA-G 3'UTR haplotype Ins/G is associated with chronic HBV infection in the Tunisian population.

Genetic variations underlying Gilbert syndrome and HBV infection outcomes: a cross-sectional study.

Background: Constant cellular damage causes a poor prognosis of hepatitis B virus (HBV) infection. Accumulating evidence indicates the cytoprotective properties of bilirubin. Here, we investigated the association of UDP glucuronosyltransferase family 1 member A1 (UGT1A1), the genetic cause of Gilbert syndrome (GS), a common condition of mild unconjugated bilirubinemia, with HBV infection outcomes. Methods: Patients (n = 2,792) with unconjugated hyperbilirubinemia were screened for HBV infection and host UGT1A1 variations in Ruijin Hospital from January 2015 to May 2023, and those with confirmed HBV exposure were included. The promoter/exons/adjacent intronic regions of UGT1A1 were sequenced. HBV infection outcomes were compared between hosts with wild-type and variant-type UGT1A1. The effect magnitudes of UGT1A1 variations were evaluated using three classification approaches. Results: In total, 175 patients with confirmed HBV exposure were recruited for final analysis. Age, gender, level of HBV serological markers, and antiviral treatment were comparable between UGT1A1 wild-type and disease-causing variation groups. Five known disease-causing mutations (UGT1A1*28, UGT1A1*6, UGT1A1*27, UGT1A1*63, and UGT1A1*7) were detected. The incidence of cirrhosis or hepatocellular carcinoma (LC/HCC) was significantly lower in UGT1A1 variant hosts than in UGT1A1 wild-type hosts (13.14% vs. 78.95%, p < 0.0001). The rarer the UGT1A1 variation a patient possessed, the higher the age at which LC/HCC was diagnosed (R = 0.34, p < 0.05). In contrast, patients without cirrhosis achieving HBsAg clearance were identified only in the UGT1A1 variant group (12.32% vs. 0%). Conclusion: The findings of this study provide insights into the association between preexisting genetically mild bilirubin elevation and viral infection outcome. We showed that the accumulation of UGT1A1 variants or the rarity of the variation is associated with a better prognosis, and the effect magnitude correlates with UGT1A1 deficiency. This study demonstrates the therapeutic potential of host UGT1A1 variations underlying GS against HBV infection outcomes.

Host and HBV Interactions and Their Potential Impact on Clinical Outcomes.

Hepatitis B virus (HBV) is a challenge for global health services, affecting millions and leading thousands to end-stage liver disease each year. This comprehensive review explores the interactions between HBV and the host, examining their impact on clinical outcomes. HBV infection encompasses a spectrum of severity, ranging from acute hepatitis B to chronic hepatitis B, which can potentially progress to cirrhosis and hepatocellular carcinoma (HCC). Occult hepatitis B infection (OBI), characterized by low HBV DNA levels in hepatitis B surface antigen-negative individuals, can reactivate and cause acute hepatitis B. HBV genotyping has revealed unique geographical patterns and relationships with clinical outcomes. Moreover, single nucleotide polymorphisms (SNPs) within the human host genome have been linked to several clinical outcomes, including cirrhosis, HCC, OBI, hepatitis B reactivation, and spontaneous clearance. The immune response plays a key role in controlling HBV infection by eliminating infected cells and neutralizing HBV in the bloodstream. Furthermore, HBV can modulate host metabolic pathways involved in glucose and lipid metabolism and bile acid absorption, influencing disease progression. HBV clinical outcomes correlate with three levels of viral adaptation. In conclusion, the clinical outcomes of HBV infection could result from complex immune and metabolic interactions between the host and HBV. These outcomes can vary among populations and are influenced by HBV genotypes, host genetics, environmental factors, and lifestyle. Understanding the degrees of HBV adaptation is essential for developing region-specific control and prevention measures.

Sex-differences in the association of interleukin-10 and interleukin-12 variants with the progression of hepatitisB virus infection in Caucasians.

Interleukin (IL)-10 and IL-12 contribute to immune responses against hepatitisB virus (HBV) infection. Polymorphisms in the IL-10 and IL-12A genes might affect the clinical outcome of HBV infection. We evaluated the association of IL-10 rs1800896 and rs3024490, and IL-12A rs568408 and rs2243115 with the progression of HBV infection and development of severe liver disease stages in a white European population. A total of 636 white European patients with chronic HBV infection, 239 individuals with spontaneous HBV surface antigen seroclearance, and 254 healthy controls were enrolled. The chronic HBV infection group included patients with hepatitisB envelope antigen (HBeAg) negative chronic hepatitisB (n=255), with HBeAg positive chronic hepatitisB (n=99) and with HBeAg negative HBV infection (n=228). A total of 104 chronically infected patients were diagnosed with liver cirrhosis. Serum levels of cytokines were measured in patients with HBV infection (n=195) and in healthy controls (n=160). In adjusted multivariate analysis, the IL-10 rs1800896 AG/GG genotypes were significantly associated with an increased probability of HBV surface antigen seroclearance (OR=1.75, 95% CI 1.04-2.94, p=0.034), with an increased likelihood of HBeAg negative chronic infection (OR=1.93, 95% CI 1.05-3.54, p=0.034) and with increased serum cytokines levels in female patients. In contrast, the IL-12A rs568408 AG/AA genotypes were independently associated with an increased risk to develop liver cirrhosis, with an OR of 1.90 (95% CI 1.07-3.39, p=0.029) in male patients. The current study shows a sex-related association of the IL-10 single-nucleotide polymorphism rs1800896 and IL-12A single-nucleotide polymorphism rs568408 with different stages of HBV infection and with HBV-related liver cirrhosis in white European patients.

Hepatitis B virus genotypes influence clinical outcomes: A review.

Hepatitis B virus (HBV) is a hepatotropic virus that affects approximately 296 million people worldwide. A crucial step to HBV replication is the transcription of its infectious DNA from its viral RNA intermediate. The production of the RNA intermediate hinges on reverse transcription, and therefore the lack of proofreading in that process commonly yields mutants and has led to nine well-described genotypes (A-I) and over 30 known sub-genotypes of the virus. The influence of genotype on HBV infection outcomes, which include fibrosis progression, cirrhosis, and hepatocellular carcinoma (HCC), remain uncertain. This review aims to analyze the influence of HBV genotype on the risk of development of these outcomes. The response to current and future HBV therapies is considered. Further study of larger and more diverse samples will hopefully resolve outstanding uncertainties.

Immune response and treatment targets of chronic hepatitis B virus infection: innate and adaptive immunity.

Chronic hepatitis B virus (HBV) infection is a major global public health risk that threatens human life and health, although the number of vaccinated people has increased. The clinical outcome of HBV infection depends on the complex interplay between viral replication and the host immune response. Innate immunity plays an important role in the early stages of the disease but retains no long-term immune memory. However, HBV evades detection by the host innate immune system through stealth. Therefore, adaptive immunity involving T and B cells is crucial for controlling and clearing HBV infections that lead to liver inflammation and damage. The persistence of HBV leads to immune tolerance owing to immune cell dysfunction, T cell exhaustion, and an increase in suppressor cells and cytokines. Although significant progress has been made in HBV treatment in recent years, the balance between immune tolerance, immune activation, inflammation, and fibrosis in chronic hepatitis B remains unknown, making a functional cure difficult to achieve. Therefore, this review focuses on the important cells involved in the innate and adaptive immunity of chronic hepatitis B that target the host immune system and identifies treatment strategies.

Role of host immunity and HBx among inactive chronic hepatitis B patients in a highly endemic region

The hepatitis B virus (HBV) infection has a wide range, from fulminant hepatitis to inactive chronic hepatitis B (ICB) infection. The present study evaluated critical factors in the outcomes of HBV infection in a highly endemic region of Iran (approximately 12% HBV positive). The expression of seven genes involved in host immunity (Foxp3, T-bet, ROR-γt, AKT, CREB, IL-28/or IFN-λ2, and IL-28R) and HBx for viral activities were evaluated using real-time PCR, TaqMan method. A total of 58 subjects were randomly chosen, including 28 ICB and 30 healthy controls (HCs) from the Esfandiar district, South Khorasan province, Iran. The expression index of Foxp3 and ROR-γt was moderately up-regulated in ICBs but did not statistically significant. T-bet expression in ICB patients was significantly higher than in HCs (p = 0.004).Furthermore, evaluating two signalling pathways in Th activation and cell survival showed that the CREB pathway was significantly up-regulated in ICB patients compared to HCs (p = 0.006), but the AKT did not differ. In innate immune responses, the IL-28/or IFN-λ2 expression in ICB patients was significantly higher than in the HCs (p = 0.02). Surprisingly, only one ICB patient disclosed HBx expression, which shows deficient virus activity in these patients. The ICB condition seems to result from host immune pressure on HBV activities, up-regulation of T-bet and IFN-λ. The high expression of CREB may prevent Kupffer's pro-inflammatory reactions in the liver. Whereas the absence of HBx expression in ICB patients and, consequently, the inactivity of HBV may also confirm such immune pressure.

Polymorphism Analysis of Interleukin-18 and Interleukin-37 Genes in Hepatitis B Infections with Different Outcomes: A Preliminary Report from an Iranian Population.

Given the vital role of cytokines in influencing the outcomes of hepatitis B virus (HBV) infections, this study aimed to investigate the association between polymorphisms of interleukin (IL)-18 and IL-37 and the outcomes of HBV infection. In this study, we enrolled 300 subjects with chronic HBV infection, including those with cirrhosis/hepatocellular carcinoma (C/HCC), chronic active hepatitis B (CAH) infection, or asymptomatic carriers (AC), and 58 individuals whose infection was spontaneously cleared (SC). Genomic DNA was extracted, and IL-18/IL-37 genotyping was performed using PCR-RFLP and ARMS-PCR. The frequency of genotypes and alleles of IL-18 single nucleotide polymorphisms (SNPs) at positions rs1946519, rs1946518, and rs187238 and IL-37 at position rs4241122 were not statistically different among the four studied groups (P>0.05). Furthermore, the frequency of different haplotypes was similar among the studied groups (P>0.05). Polymorphisms of IL-18 SNPs at positions rs1946519, rs1946518, and rs187238 and variation of IL-37 at position rs4241122 do not appear to influence the outcome of HBV infection.

Fecal Microbiota Transplantation Alters the Outcome of Hepatitis B Virus Infection in Mice.

The susceptibility of mice to hepatitis B virus (HBV) infection depends on their genetic background. The gut microbiota modulates the antiviral immune response in the liver and plays a protective role against HBV infection. However, whether HBV infection outcomes depend on the gut microbiota remains unclear. In this study, we assessed the gut microbiota composition in naïve BALB/c and C57BL/6 mice using 16S rRNA gene sequencing. The gut microbiota in BALB/c mice was depleted using broad-spectrum antibiotics (ABX) and then reconstituted with fecal microbiota from naïve BALB/c or C57BL/6 mice to evaluate the effect of fecal microbiota transplantation (FMT) on the outcomes of and immune response to HBV infection. We found that HBV infection outcomes and the gut microbiota composition differed between BALB/c and C57BL/6 mice. Commensal bacteria from the fecal microbiota selectively colonized the guts of ABX-treated BALB/c mice. Mice receiving fecal microbiota from BALB/c or C57BL/6 mice displayed different HBV infection outcomes. The fecal microbiota from C57BL/6 mice induced immune tolerance in the liver and prolonged HBV infection. In conclusion, HBV infection outcomes in mice are determined by the host genetic background and gut microbiota composition. Reconstitution of the gut microbiota by FMT can alter the susceptibility to HBV infection in mice.

Alinity m, a Random-Access System, for Hepatitis B Virus DNA Quantification in Plasma and Whole Blood Collected on Dried Blood Spots.

ABSTRACTThe International Liver Association recommends the use of accurate and sensitive molecular methods for determination of hepatitis B virus (HBV) DNA levels in plasma or serum of chronic HBsAg carriers. The level of HBV replication represents the strongest predictive biomarker associated with disease progression and long-term outcome of chronic HBV infection. The purpose of this study was to evaluate the ability to the new Alinity m System to detect and quantify HBV DNA in plasma and whole blood collected on dried blood spots (DBS). Paired plasma and DBS samples from patients chronically infected with various HBV genotypes were tested in parallel for HBV DNA detection and quantification. There is a linear relationship between HBV DNA levels measured in plasma samples using the Alinity m HBV assay and the Xpert HBV viral load assay, used for comparison. A slight deviation (0.03 ± 0.31 log IU/mL) was observed within the quantitative range. In DBS, HBV DNA levels closely correlated with levels measured in plasma. All patients had detectable and quantifiable HBV DNA by DBS testing, except for one patient with a plasma HBV DNA level above 2,000 IU/mL. In conclusion, the newly developed real-time PCR-based assay Alinity m HBV assay can correctly detect HBV DNA in DBS, especially for patients with blood HBV DNA levels above 2,000 IU/mL, and also accurately quantify HBV DNA in plasma samples.IMPORTANCE Hepatitis B virus is one of the most prevalent blood-borne viruses affecting the liver and causing acute and chronic hepatitis. Only a small proportion of people with HBV infection are diagnosed. HBV DNA measurement is critical in clinical practice for the diagnosis and treatment decisions of patients requiring antiviral therapy. Dried blood spot (DBS) collection provides a simple, practical, and acceptable alternative to venous blood collection, especially in community settings. We have demonstrated high sensitivity and specificity for HBV DNA detection in DBS compared to plasma samples, especially when using clinically relevant cutoffs of 2,000 and 20,000 IU/mL. Results support the use of DBS in community-based settings.

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.

Hepatitis B Virus-Specific Cellular Immunity Contributes to the Outcome of Occult Hepatitis B Virus Infection.

There is little known of immunologic factors leading to the occurrence of occult HBV infection (OBI). Specific cellular immune response to hepatitis B virus (HBV) core/pol peptides was compared between blood donor populations, including 37 OBIs, 53 chronic HBV infections (CHB), 47 resolved infections, and 56 non-infected controls, respectively. The rate of CD4+/CD8+ T cell proliferation in OBI or CHB carriers was higher than in HBV resolved and non-infected individuals (P < 0.05). The intensity of IFN-γ-secretion T-cell response of OBI carriers was highest, followed by CHB and resolved infections, and non-infected individuals (P < 0.05). The frequency of intracellular IFN-γ and IL-17A CD4+/CD8+ and IL-21 CD4+ T-cell responses was significantly higher in resolved infections than in OBI or CHB carriers (P < 0.05), while the level of extracellular IL-17A of peripheral blood mononuclear cells (PBMCs) was higher in OBI and CHB carriers than in resolved infections (P < 0.01). The frequency of intracellular IL-10 CD4+ T-cell response in CHB, OBI, and resolved infections was higher than in HBV non-infected individuals (P < 0.01). Intracellular IL-10 CD8+ T cell and extracellular IL-10 T-cell responses were higher in CHB than in OBI (P = 0.012) or HBV resolved infections (P < 0.01). In conclusion, the higher level of effective T-cell response with IFN-γ, IL-17A, and IL-21 contributes to resolved infection outcome, while higher levels of suppressive T-cell response with IL-10 result in HBV chronicity. OBI is an intermediary status between HBV resolved and chronic infections, in which IL-21 effector and IL-10 suppressor T-cell responses play an important role in directing the outcome of HBV infection.

Evaluation of Some Haematological Parameters in the Management of HBV Infection Treatment Outcome in Delta State, Nigeria

Aims: To evaluate Hepatitis B virus (HBV) infection treatment outcome using the levels of white blood cells, haemoglobin, platelets counts and other red cell indices of HBV positive treatment naïve, on treatment at 3- and 6-months subjects attending gastro-enterology clinic in Federal Medical Centre Asaba, Delta State, Nigeria&#x0D; Study Design: Cross-Sectional and longitudinal study.&#x0D; Place and Duration of Study: Federal Medical Centre Asaba (FMC) and Iykenson Medical and Diagnostic Co. Ltd, Awka. Federal Medical Centre, Asaba, between August 2019 and September 2020.&#x0D; Methodology: A total of one hundred and fifteen (115) adults aged 22 – 64 years participated in this study. The study sites for this work comprised of Federal Medical Centre Asaba (FMC) and Iykenson Medical and Diagnostic Co. Ltd, Awka. The cross-sectional study consists of fifty (50) confirmed hepatitis B negative subjects as negative controls whereas, the follow-up study consists sixty-five (65) treatment naïve HBV positive subjects which were followed-up at three and six months on treatment with tenovofir respectively. Four (4) of the participants (two in three months post treatment and two six months post treatment) dropped-out of the research due to time constraint. Blood samples were collected from the subjects in EDTA bottles and were used for the analysis of white blood cell (WBC count), haemoglobin concentration, packed cell volume (PCV), mean cell volume (MCV), mean cell haemoglobin (MCH), mean cell haemoglobin concentration (MCHC) and platelet count (PLT). Statistical Package for social Science (SPSS) software version 26 was used in the analysis of data and P&lt;.05 was considered statistically significant.&#x0D; Results: There were no significant difference (P&gt;.05) in neutrophil, lymphocyte, eosinophil and monocyte in the study population among the four groups whereas, the level of total white blood cell counts was significantly lower in the HBV naïve, one month post treatment and three-month post treatment when compared with the control group. The levels of haemoglobin, packed cell volume, mean cell volume, mean cell haemoglobin and mean cell haemoglobin concentration were significantly lower in the HBV naïve, three months on treatment and six-months on treatment when compared with the control group (P&lt;.05).&#x0D; Conclusion: In conclusion, it is possible that HBV infection has effect on iron metabolism and production of haematological precursor cells which are reflected in low levels of haemoglobin, PCV, MCV, MCH and MCHC as such these parameters could be used as co – markers to viral load in monitoring the treatment outcome of HBV infection in Nigeria.

A Systematic Review of T Cell Epitopes Defined from the Proteome of Hepatitis B Virus.

Hepatitis B virus (HBV) infection remains a worldwide health problem and no eradicative therapy is currently available. Host T cell immune responses have crucial influences on the outcome of HBV infection, however the development of therapeutic vaccines, T cell therapies and the clinical evaluation of HBV-specific T cell responses are hampered markedly by the lack of validated T cell epitopes. This review presented a map of T cell epitopes functionally validated from HBV antigens during the past 33 years; the human leukocyte antigen (HLA) supertypes to present these epitopes, and the methods to screen and identify T cell epitopes. To the best of our knowledge, a total of 205 CD8+ T cell epitopes and 79 CD4+ T cell epitopes have been defined from HBV antigens by cellular functional experiments thus far, but most are restricted to several common HLA supertypes, such as HLA-A0201, A2402, B0702, DR04, and DR12 molecules. Therefore, the currently defined T cell epitope repertoire cannot cover the major populations with HLA diversity in an indicated geographic region. More researches are needed to dissect a more comprehensive map of T cell epitopes, which covers overall HBV proteome and global patients.

Prognostic impact of hepatitis B virus infection in patients with primary cervical cancer.

BackgroundHepatitis B virus (HBV) infection has been associated with an increased risk of a few malignancies. However, the prognostic impact of HBV infection remains unclear in cervical cancer.ObjectiveTo explore the association between HBV infection and survival outcomes of patients with primary cervical cancer, using overall survival (OS) and disease‐free survival (DFS) as primary endpoints.MethodsThis analysis was performed retrospectively with newly diagnosed cervical cancer patients admitted to the Department of Gynecologic Oncology at the Sun Yat‐sen Memorial Hospital of Sun Yat‐sen University from June 2013 to October 2019, who were enrolled and followed up. The Kaplan–Meier method and Cox proportional hazard analysis were used to examine the performance of HBV infection in predicting OS and DFS.ResultsPatients were followed up for a median of 37.17 months (95% CI, 34.69–39.65). Among the 695 patients, 87 (12.5%) were serologically positive for hepatitis B surface antigen (HBsAg), and 276 (39.7%) had a prior history of HBV infection. There was no significant difference between HBsAg‐positive group and HBsAg‐negative patients concerning OS or DFS. Multivariate analysis showed prior HBV infection was an independent favorable prognosticator for OS (HR, 0.335; 95% CI, 0.153–0.0.734; p = 0.006) and DFS (HR, 0.398; 95% CI, 0.208–0.691; p = 0.002).ConclusionWe provide the first clinical evidence that suggests prior HBV infection as an independent favorable prognostic factor for patients with primary cervical cancer.

Значення генотипів вірусу гепатиту В у клінічній практиці

Інфекція, спричинена вірусом гепатиту В (HBV), як і раніше, залишається глобальною проблемою охорони здоров’я і характеризується високим рівнем захворюваності та смертності. У процесі реплікації вірусу накопичуються численні мутації, які протягом філогенезу призводять до появи генотипів і субгенотипів HBV. На сьогодні налічується 10 різних генотипів HBV (A-J). Вони мають різне географічне поширення з досить вираженим переважанням тих чи інших генотипів залежно від регіону. В Україні, як і в інших європейських країнах, відзначається переважання генотипів A і D. Велика кількість досліджень вказує на те, що генотип HBV впливає на природний перебіг захворювання, схильність до хронізації, ймовірність сероконверсії HBeAg і відповідь на терапію пегільованим інтерфероном альфа. У даному літературному огляді узагальнені результати наукових досліджень, присвячених вивченню впливу генотипів HBV на природний перебіг захворювання. Наводяться дані про географічне поширення генотипів HBV в Україні та світі, аргументується важливість визначення генотипів HBV з точки зору їх впливу на перебіг та наслідки HBV-інфекції.

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.

IL-10 -1082 A/G (rs1800896) Polymorphism is Effective in Clearing Hepatitis B Virus Infection

Background: Hepatitis B Virus (HBV) is a universal health challenge all around the world. Several factors like viral load, genetic characteristics, age, sex, and immune status contribute to variable clinical outcomes of HBV infection. The sequels of HBV infection vary remarkably among persons ranging from the spontaneous deletion of infection to persistent infection. Objective: The present study aimed to evaluate the association of single nucleotide polymorphisms IL10-1082 with HBV clearance. Methods: Sixty subjects with Chronic Hepatitis B (CHB) infection and 60 subjects who spontaneously recovered HBV were enrolled in the study. The IL-10-1082 polymorphisms were determined by Polymerase Chain Reaction with Restriction Fragment Length Polymorphism (PCR–RFLP). Results: The clearance of HBV infection demonstrated a significant association with IL-10-1082 polymorphisms in the GG genotype (P = 0.03), while there was no association with other genotypes. Reduced risk of chronic hepatitis B infection was associated with IL-10-1082 GG (OR: 2.33, 95% CI: 1.07 - 5.09). Besides, IL-10-1082 A/G alleles did not differ clearly between the two study groups (P = 0.07) Conclusions: The IL-10-1082 polymorphisms may be associated with a reduced risk of CHB infection and recovery after HBV infection.

Modeling reveals no direct role of the extent of HBV DNA integrations on the outcome of infection

Hepatitis B virus (HBV) with its high prevalence and death toll is one of the most important infectious diseases to study. Yet, there is very little progress in the development of within-host models for HBV, which has subsequently hindered our understanding of this virus. The uncertainty around the proliferation of infected hepatocytes has been studied but never in association with other important biological continuous events such as integrations and superinfections. This is despite the fact that these processes affect the diversity and composition of infected cell population in the liver and an improved understanding of the cellular composition will undoubtedly assist in strategizing against this viral infection. Here, we developed novel mathematical models that incorporate these key biological processes and analyzed them both analytically and numerically. Unaffected by the extent of integrated DNA (IDNA), the outcome of HBV infection was primarily dictated by the balance between processes generating and killing infected hepatocytes containing covalent closed circular DNA (cccDNA). The superinfection was found to be a key process in the spread of HBV infection as its exclusion could not reproduce experimentally observed composition of infected hepatocytes at peak of acute HBV infection, a stage where our model predicts that infected hepatocytes most likely carry both cccDNA and IDNA. Our analysis further suggested the existence of some form of selective advantage of infected hepatocytes containing only IDNA to explain the viral dynamics observed during antiviral treatment and the transition from peak to acute infection. Finally, the fine line between liver destruction and resolution of acute HBV infection was found to be highly influenced by the fate of cccDNA during cellular proliferation.