Course Of CHB Research Articles

Liver Fibrosis in the Natural Course of Chronic Hepatitis B Viral Infection: A Systematic Review with Meta-Analysis.

Quantitative data are limited on the natural course of liver fibrosis in patients with chronic HBV infection (CHB). To estimate the prevalence of fibrosis status including non-fibrosis, significant fibrosis, advanced fibrosis, and cirrhosis throughout the natural course of CHB. We searched Cochrane library, EMBASE, PubMed, SCOPUS, Web of Science, and ScienceDirect from January 1993 to November 2019 for studies with histologic data on liver fibrosis in CHB natural course. CHB course was defined based on current criteria for identifying infection phases as recommended by international clinical practice guidelines, including the HBeAg-positive immune-tolerant, HBeAg-positive immune-active, HBeAg-negative immune-inactive, HBeAg-negative immune-reactive, and HBsAg-negative phases. Pooled prevalence rate of fibrosis status at each phase was obtained from random-effect meta-analyses. Thirty-three studies with 9,377 adult participants (23.8-49.0 age years; 45.5-88.6% males) were eligible and finally included. The estimated prevalence of non-fibrosis, significant fibrosis, advanced fibrosis, and cirrhosis was, for HBeAg-positive immune-tolerant phase: 31.2% (95%CI 15.6-46.7), 16.9% (95%CI 7.8-26.1), 5.4% (95%CI 0.0-11.2), and 0.0% (95%CI 0.0-1.5); HBeAg-positive immune-active phase: 6.9% (95%CI 3.6-10.2), 50.6% (95%CI 39.2-61.9), 32.1% (95%CI 24.2-40.0), and 12.8% (95%CI 8.6-17.0); HBeAg-negative immune-inactive phase: 32.4% (95%CI 0.0-100.0), 24.8% (95%CI 4.5-45.1), 3.0% (95%CI 0.0-8.3), and 0.0% (95%CI 0.0-1.0); and HBeAg-negative immune-reactive phase: 6.3% (95%CI 3.5-9.2), 50.3% (95%CI 38.9-61.7), 30.3% (95%CI 20.9-39.6), and 10.0% (95%CI 6.6-13.5), respectively. There was only one study for HBsAg-negative phase, thus not allowing further meta-analyses. Fibrosis risk persists through CHB natural course. These data can support risk estimation in clinical practice and provide reference for noninvasive investigation.

Liver Cirrhosis in Chronic Hepatitis B Patients Is Associated with Genetic Variations in DNA Repair Pathway Genes.

Simple SummaryAs DNA repair enzymes affect dynamics of liver damage and are involved in HBV viral replication, this study focused on the role of genetic variations within genes representing key DNA-repair pathways in HBV-induced liver cirrhosis. The obtained results have demonstrated that SNPs within XRCC1, ERCC2 genes may confer susceptibility to liver cirrhosis in chronic hepatitis B patients. Liver cirrhosis (LC), contributing to more than 1 million of deaths annually, is a major healthcare concern worldwide. Hepatitis B virus (HBV) is a major LC etiological factor, and 15% of patients with chronic HBV infection (CHB) develop LC within 5 years. Recently, novel host genetic determinants were shown to influence HBV lifecycle and CHB course. DNA repair enzymes can affect dynamics of liver damage and are involved in HBV covalently closed circular DNA (cccDNA) formation, an essential step for viral replication. This study aimed to evaluate the possible role of genes representing key DNA-repair pathways in HBV-induced liver damage. MALDI-TOF MS genotyping platform was applied to evaluate variations within XRCC1, XRCC4, ERCC2, ERCC5, RAD52, Mre11, and NBN genes. Apart from older age (p < 0.001), female sex (p = 0.021), portal hypertension (p < 0.001), thrombocytopenia (p < 0.001), high HBV DNA (p = 0.001), and high aspartate aminotransferase (AST) (p < 0.001), we found that G allele at rs238406 (ERCC2, p = 0.025), T allele at rs25487 (XRCC1, p = 0.012), rs13181 GG genotype (ERCC2, p = 0.034), and C allele at rs2735383 (NBN, p = 0.042) were also LC risk factors. The multivariate logistic regression model showed that rs25487 CC (p = 0.005) and rs238406 TT (p = 0.027) were independently associated with lower risk of LC. This study provides evidence for the impact of functional and potentially functional variations in key DNA-repair genes XRCC1 and ERCC2 in HBV-induced liver damage in a Caucasian population.

Body sensitization to various antigens in children with chronic hepatitis B and concomitant giardiasis

The aim of the study was to evaluate body sensitization by measuring antigen-binding lymphocytes specific to various antigens in children with chronic hepatitis B and intestinal giardiasis. The study of ASL was carried out in 126 children with CHB and 30 apparently healthy children aged 4 to 14 years. Among children with CHB, 93 had confirmed intestinal giardiasis (group I), and the remaining 33 were patients without lambliasis (group II). Sensitization and an autoimmune process were detected by assessing activity of specific immunity parameters such as ASL amount by indirect rosette formation against HBsAg, G. lamblia and intestinal tissue. We found that intensity of disease activity and ASL level against the examined antigens were paralleled evidencing about sensitization and autoimmune reactions related to giardiasis invasion in children with CHB. Depending on the duration of CHB with lamblial invasion ASL study data showed that prolonging disease duration resulted in lowered ASL to HBsAg peaking upon disease lasting up to 3 years. Apparently, it might be accounted for by body mobilization fighting against infection in general biological sense, and their further decline may occur due to host adaptation to increased antigenic load. The amount of ASL to the intestinal tissue was also somehow related with duration of the disease. The data obtained indicate increased self-sensitization along with increased duration of the disease. Similar data were obtained while studying amount of ASL to G. lamblia, thereby confirming a role of sensitization and self-sensitization in pathogenetic mechanisms of the developing CHB with giardial invasion especially during long-term course. Thus, the course of CHB with lambliasis invasion is accompanied by reaction of specific immune arm. Rise in amount of ASL to HBsAg, intestinal tissue and G. lamblia occurs along with deteriorating degree of disease activity and duration of hepatic disease suggesting about importance of sensitization and self-sensitization in pathogenesis of CHB development with giardiasis invasion, aggravating the course and outcome of the disease. The data reliability allows to conclude that giardiasis infection and prolongation of both hepatic pathological process and entire infectious process in children with CVH are directly interconnected. These data clearly underscore importance of timely eradication of G. lamblia upon liver damage. At the same time, administration of specific drugs (scheme) should be performed by taking into account its hepatotoxicity, bioavailability and effectiveness.

Serum GSDMD as a New Biomarker for Assessing Clinical Progression&amp;nbsp;Of &amp;nbsp;Chronic HBV Infection

Background: Distinguishing the natural course of chronic HBV infection (CHB) development is extremely desired. The pore-forming protein Gasdermin D (GSDMD) contributes to the development of HBV infection and might be used to distinguish different phases of CHB. We aim to investigate the serum expression of GSDMD in the natural course of CHB development and to evaluate its diagnostic efficacy. Methods: Levels of GSDMD were measured with ELISA kits that we developed. We evaluated the ability of serum GSDMD to differentiate clinical stages in 73 CHB patients. Besides, The HepG2-NTCP cells infected by virus from HepAD38-cell and CHB patients’ serum were applied to evaluate the GSDMD expression in vitro. Findings: The GSDMD elevated gradually with the development of HBV infection (P 178 ng/mL, the sensitivity was 52·174 %. Interpretation: Serum GSDMD, varied along with the development of HBV-related diseases, making it an early and efficacious serum biomarker for auxiliary definitions of the natural course of CHB. Funding Statement: This work was supported by the Outstanding Young Talents Plan of the Second Hospital of Chongqing Medical University (Pu Li). Declaration of Interests: There are no conflicts of interest. Ethics Approval Statement: The study was carried out based on the principles of the Declaration of Helsinki and was approved by the medical ethics committee of the Second Affiliated Hospital of Chongqing Medical University.

Role of Biomarkers in Guiding Cure of Viral Hepatitis B.

Chronic hepatitis B (CHB) virus infection is a global public health threat affecting approximately 257 million individuals worldwide. Hepatitis B surface antigen (HBsAg) loss has been the classic endpoint to define functional cure and decrease the large pool of individuals with CHB. Current treatments with nucleos(t)ide analogues persistently suppress hepatitis B virus (HBV) deoxyribonucleic acid in most CHB patients, but rarely achieve functional cure. New viral biomarkers, such as quantitative HBsAg, hepatitis B core-related antigen, and HBV ribonucleic acid, and combinations of these markers have the potential role of guiding HBV cure by enabling selection of the best candidates for therapy, identifying individuals with a higher likelihood of achieving HBsAg loss, and helping in the design of studies with new drugs. However, some of the assays used to analyze these markers require standardization and improvements in the level of detection. Analysis of host biomarkers to assess the host immune response to HBV is also important, as the natural course of CHB is determined by the interplay between viral replication and the immune response. These biomarkers are, however, in an early phase of development.

TNF-α polymorphisms affect persistence and progression of HBV infection.

BackgroundHepatitis B virus (HBV) infections are a major threat worldwide. Disease progression and outcome is diverse and depends on host genetic background. Recently, a high rate of HBV reactivation in individuals receiving tumor necrosis factor‐α (TNF‐α) antagonists showed the importance of this cytokine in HBV infection control. Here, we investigated the influence of TNF‐α promoter polymorphisms on susceptibility to chronic HBV infection (CHB), liver injury progression and outcomes.MethodsA total of 231 patients with CHB constituted the study group and 100 healthy volunteers—the local control group. TNF‐α −1031T/C, −863C/A, −857C/T, −308G/A, and −238G/A were genotyped using MALDI‐TOF mass spectrometry.Results TNF‐α −1031C and −863A alleles were observed more frequently in CHB group than in healthy controls. Carriers of TNF‐α −1031C and −863A variant alleles had lower baseline levels of serum HBV DNA and lower liver necroinflammatory activity than dominant homozygotes. A −857CT genotype predisposed to higher necroinflammatory activity. No associations between TNF‐α variants and liver fibrosis were found.ConclusionThis study indicates that TNF‐α −863A and −1031C alleles are associated with increased susceptibility to CHB in individuals from northern Poland. The same variants determine the course of CHB, lowering viremia and reducing necroinflammatory activity of the liver.

Serum HBV RNA quantification: useful for monitoring natural history of chronic hepatitis B infection

BackgroundAs an alternative biomarker of intrahepatic covalently closed circular DNA (cccDNA) transcriptional activity, hepatitis B virus (HBV) RNA may evolve during long-lasting virus-host interactions during chronic hepatitis B viral infection. The distribution pattern of serum HBV RNA levels in the natural course of chronic HBV infection remains unclear. The aim of this study was to evaluate the levels of HBV RNA during the natural course of CHB and the role in distinguishing the natural history of HBV infection.MethodsA total of 291 treatment-naïve chronic HBV carriers were enrolled. Based on the clinical, biochemical, serological, and histological data as well as HBV DNA levels, patients were classified into the following four categories: the immune-tolerant phase (IT,n = 35), HBeAg-positive immune-active phase (EPIA,n = 121), inactive chronic hepatitis B(ICH,n = 77) and HBeAg-negative immune reactive hepatitis (ENH,n = 58). The parameters and distribution patterns of serum HBV RNA were evaluated in relation to viral replication status, immune phase, disease category and Child-Pugh class. The relationships between serum HBV RNA and other serum hepatitis B viral markers were also analyzed.ResultsSerum HBV RNA levels were significantly lower in the HBeAg-negative patients compared to those in the HBeAg-positive patients, with the lowest levels seen in inactive carriers. In HBeAg-negative patients, serum HBV RNA levels increased if there is reactivation to active hepatitis and showed obvious superiority for the combination of serum HBV DNA (cutoff>3.39 Log copies/mL) and HBsAg (cutoff>2.74 Log IU/mL) in discriminating between ‘HBeAg-negative immune reactive’ phase and inactive chronic hepatitis B phases of HBeAg-negative chronic HBV infection. Serum HBV RNA levels were positively correlated with serum HBV DNA and HBsAg levels in all chronic HBV-infected patients. A stratified analysis revealed that a correlation between serum HBV RNA and HBV DNA or HBsAg was present in HBeAg-positive patients; however, in HBeAg-negative patients, serum HBV RNA was positively correlated with HBV DNA only.ConclusionDuring the natural course of chronic HBV infection, serum HBV RNA levels vary. Serum HBV RNA can act as a biomarker to predict the natural history of disease in chronic hepatitis B patients. In treatment-naïve HBeAg-negative chronic HBV-infected individuals, serum HBV RNA shows superiority in differentiating the ‘HBeAg-negative reactive’ phase.

Hair cortisol and chronic stress exposure in chronic Hepatitis B patients

Background: The purpose of this study is to address the prolonged exposure to stress associated with chronic HBV infection. We, therefore, explored the measure of stress cortisol hormone (CORT) in the hair as a biomarker of chronic stress in CHB patients. Materials and Methods: Eligible CHB patients identified from an existing patient cohort were enrolled in this prospective study. Data collection was done using medical chart reviews, face-to-face interview in Korean or English, and hair and blood samples. Results: We collected hair samples of 50 CHB patients (age 34-74 years) with the duration of CHB diagnosis (1-51 years, 23.8 ± 10). About three-fourths were male. More than 40% had family history of HBV infection. Hair samples weighing 19.6-29.9 mg were processed and analyzed for cortisol. Mean cortisol levels were 16.42 pg/ mg (27.59 SD) ranging from 2.7 to 168.1 pg/mg. About 16% (n=8) had below normal hair cortisol level ( =4) was 48%. Distress was positively correlated with hair cortisol level (r=.395, p<.05) among those with below-normal hair cortisol levels. Conclusion: The mean of hair CORT in our CHB patients (16.4, 95% CI: 8.5-24.4) was lower than other studies of adults, suggesting long-term suppression of hair cortisol production in the course of CHB and antiviral therapy. This study indicates a possible hypothesis that the cortisol levels of CHB patients might have been suppressed and their HPA-axis down-regulated after having been stressed for years related to the disease. This study suggests a need for further research to determine the longitudinal effects of chronic stress on hair cortisol levels and liver disease progression in CHB patients.

Monitoring of patients with chronic hepatitis B without liver cirrhosis while determining the tactics of treatment

Aim. The purpose of the work is to reveal the features of CHB without liver cirrhosis when assessing the need for the appointment of antiviral therapy for the implementation of the State Target Program; to compare the criteria for monitoring CHB patients without cirrhosis in existing international recommendations. Material and methods . When assessing the features of the course of CHB in 286 patients without cirrhosis, the recommendations of NICE (2013) and WHO (2015) were taken into account to determine the need for antiviral treatment, which is the basis of the clinical protocol in Ukraine. The work analyzes the international guidelines for monitoring CHB patients without cirrhosis: the American Association for the Study of the Liver Diseases (2016), the European Association for the Study of the Liver (2012), the National institute for Health and Care Excellence (2013), World Health Organization (2015). Results . In the work, we analyzed the features of the course of CHB without cirrhosis using criteria for the distribution of patients depending on the indications for antiviral treatment, which are set out in the clinical protocol in Ukraine and are based on the international recommendations of NICE (2013) and WHO (2015). It is shown that 8.0 % (23 of 286) of patients require priority antiviral treatment according to laboratory criteria. The course of CHB in these patients is characterized by more frequent astheno-vegetative manifestations, more pronounced cytolytic syndrome and more frequent detection of HBeAg. Among 38.1 % (109 of 286) patients with CHB without cirrhosis with a low viral load <2000 IU / ml, which is not recommended for antiviral drugs, one third has cytolytic syndrome (34.3 %), one tenth is HBeAg-positive (10.5 %), and one fourth has liver fibrosis of F 2–3 stages (27.3 %), which requires an improvement in the monitoring of these patients. The analysis of international recommendations showed complex and different approaches to monitoring CHB patients without cirrhosis of the liver when deciding on the appointment of antiviral treatment. The AASLD recommendations (2016) differ from the others in the mandatory determination of the patient's HBeAg status and the clearly established norm of ALT. The EASL (2012) recommendations do not require mandatory determination of HBeAg status, with the main criterion being the amount of HBV-DNA in the blood. NICE recommendations (2013) determine the mandatory identification of a combination of factors in addressing this issue, taking into account the patient's age, viral load, the severity of the cytolytic syndrome. WHO recommendations (2015) are the most adapted for countries with limited resources. Conclusion . When using the recommendations of NICE 2013 and WHO 2015 among 38.1 % of CHB patients without cirrhosis with a low viral load <2000 IU/ml, which is not recommended for antiviral therapy, 34.3 % have cytolytic syndrome, 10.5 % are HBeAg-positive, and 27.3 % have liver fibrosis F 2–3 stages, which makes it necessary to improve monitoring of these patients. Monitoring CHB patients without cirrhosis in determining the need for antiviral treatment in the world remains a complex issue and has no unambiguous approaches to the solution, as evidenced by the existence of several international clinical recommendations: AASLD 2016, EASL 2012, NICE 2013, WHO 2015.

Preliminary study: Predictors for success in an important premedical subject at a South African medical school

Background . Admission to Sefako Makgatho Health Sciences University, Pretoria, South Africa is determined by the student’s Matriculation (Matric) results, while the writing of the National Benchmark Test (NBT) is not compulsory. An average student pass rate of 80.1% in physiology (MB ChB II) in the past 13 years compelled this institution to investigate which criteria in the selection process could be predictors for success in physiology, a fundamental discipline for medical studies. Objectives . To compile a profile of very successful physiology students and those who failed the subject, and to identify predictors for success in physiology. Methods . A quantitative study, using Matric and available NBT results, was conducted among the MB ChB II group (N=228) of 2011. Two target groups were identified: highly successful students in physiology (n=37) and those who failed (n=46). Statistical analysis of the results was performed on SAS 9.2, Microsoft Windows (SAS Institute Inc., USA) (p-values ≤0.05 are significant) using the t-test, Fisher’s exact test and the simple linear regression test. Results . These indicated that a good Matric symbol (≥5) in English and life science and a good performance in the quantitative literacy domain of the NBT were statistically significant predictors for success in physiology. Conclusion . This preliminary study indicates the need for our institution to rethink the effectiveness of the selection criteria, redesign the selection process of students for the MB ChB course, and consider making use of the NBT.

Virus evolution during chronic hepatitis B virus infection as revealed by ultradeep sequencing data.

Despite chronic hepatitis B virus (HBV) infection (CHB) being a leading cause of liver cirrhosis and cancer, HBV evolution during CHB is not fully understood. Recent studies have indicated that virus diversity progressively increases along the course of CHB and that some virus mutations correlate with severe liver conditions such as chronic hepatitis, cirrhosis and hepatocellular carcinoma. Using ultradeep sequencing (UDS) data from an intrafamilial case, we detected such mutations at low frequencies among three immunotolerant patients and at high frequencies in an inactive carrier. Furthermore, our analyses indicated that the HBV population from the seroconverter patient underwent many genetic changes in response to virus clearance. Together, these data indicate a potential use of UDS for developing non-invasive biomarkers for monitoring disease changes over time or in response to specific therapies. In addition, our analyses revealed that virus clearance seemed not to require the virus effective population size to decline. A detailed genetic analysis of the viral lineages arising during and after the clearance suggested that mutations at or close to critical elements of the core promoter (enhancer II, epsilon encapsidation signal, TA2, TA3 and direct repeat 1-hormone response element) might be responsible for a sustained replication. This hypothesis requires the decline in virus load to be explained by constant clearance of virus-producing hepatocytes, consistent with the sustained progress towards serious liver conditions experienced by many CHB patients.

Anne Bryson Sutherland

Anne Bryson Sutherland was the only child of David Murdoch Sutherland and his wife, Margaret Bryson. Her father ran the family drapery business in Bathgate, where he was also a...

Observation of T cell receptor Vbeta gene usage in the peripheral blood of patients with chronic hepatitis B after being treated by Hejie Decoction

AIM: To date, few studies have been conducted to determine whether T cell receptor (TCR) variable regions (V)of βare involved in the clinical course of chronic hepatitis B. This study was performed to assess the TCR Vβusage and clinical course of CHB and clinical parameters. METHODS: Fluorescence Quantitative PCR (FQ-PCR) technique was used to detect the TCRVβ subfamilies gene expression in the peripheral blood of 3 patients with chronic hepatitis B before and after being treated by Hejie Decoction, and clinical parameters (ALT, AST, and viral load) were observed in the same time. RESULTS: The percentage of TCRVb gene usage was determined during acute exacerbation and the remission stages. Figure 1 illustrates the percentage of TCRVb usage in the acute exacerbation and the remission stages. Those whose expressions were increased during remission stages compared with that during acute exacerbation stages were TCRVβ1(t=7.00, P

Computer awareness among medical students: a survey.

The objective of the study was to assess the attitude of Edinburgh University medical students towards computers and to evaluate the effects of changes in the curriculum and intercalated BSc towards computer knowledge. During March to November 1995 a questionnaire was distributed in lectures, seminars and tutorials to all Edinburgh University medical students. Overall, 65% of students returned the questionnaire, divided equally between both genders. Only 2% of students had not used a computer in the previous year. The most frequent application used was E-mail and the most frequent site, the Greenfield suite micro lab, within the medical school. The average score for self-perceived computer knowledge on a scale of 0-10 was 4.19. This score was significantly higher for the students who own a computer and who have an intercalated BSc honours degree as well as the pre-clinical students compared to the clinical students. There is also a strong correlation between computer use and doing a second year special option module. With regards to attitude towards computers, 86% of students agreed that computer skills will be beneficial to them in their future career and 62% of all students wanted a structured course in computer use as part of the MB ChB course. There has been a general increase in computer literacy amongst the medical students in Edinburgh. This is specially so for the pre-clinical students who have had the brunt of the changes in the curriculum. The tendency for both the lower knowledge and use by the clinical students can, in part, be due to the accessibility of computers to these students.