Hepatitis B Virus DNA-positive Patients Research Articles

Clinical Prevalence of Hepatitis D Virus Among Hepatitis B Patients in Sulaymaniyah Governorate, Northern Iraq.

Hepatitis D virus (HDV), which occurs as a co-infection with the hepatitis B virus (HBV), is a significant public health burden. Currently, there is a scarcity of data regarding this co-infection in the developing countries. This study aims to address the clinical prevalence of HDV among HBV-infected patients in Sulaymaniyah Governorate, Iraq. This prospective cross-sectional study, conducted from May to November 2022, screened HBV DNA-positive patients visiting Sulaimani Teaching Hospital in Sulaymaniyah governorate, Iraq, for anti-HDV antibodies and HDV RNA. The study included 150 confirmed HBV DNA-positive patients. Of these, 54.7% were male. The mean age of the patients was 49.1 ± 10.1 (18-68). Serological assessment found that 23 (15.3%) of the patients had anti-HDV IgG antibodies, suggesting past or chronic HDV infection, while 16 (10.7%) tested positive for anti-HDV IgM, indicating recent/acute infection. Further molecular analysis confirmed HDV RNA in 15 (10%) of HBV patients, indicating real HDV prevalence. The prevalence of anti-HDV and HDV RNA did not significantly differ by age, gender, marital status, residency, medical, family or medical history (p > 0.05). In conclusion, this study demonstrated a relatively high HDV prevalence among HBV patients in Sulaymaniyah Governorate, Iraq, at 10%, which stresses the need for better screening, health strategies and focused research to combat its impact.

Clinical application value of hepatitis B virus basal core promoter 1762/1764 and GGTII and GGT in patients with HBV-DNA-positive primary liver cancer.

Hepatitis B virus (HBV) is closely related to the occurrence and development of primary liver cancer (PLC). The early diagnosis of PLC is difficult. The study explored the clinical application value of the HBV gene basal core promoter (BCP) region 1762/1764 combined with gamma-glutamyl transpeptidase (GGT) and its isozyme II (GGTII) in PLC. From June 2017 to June 2021, 145 hepatitis B surface antigen-positive and HBV DNA-positive patients were enrolled in the Third People Hospital of Zigong. Of them, 67 were chronic hepatitis B (CHB) patients, 30 were liver cirrhosis patients, and 48 were patients with hepatitis B-associated PLC. The HBV BCP 1762/1764 mutation was detected through the amplification refractory mutation system fluorescence PCR method, and GGTII was detected using the double-antibody sandwich method. The results showed that the serum GGT activity, GGTII level, aspartate aminotransferase (AST) activity, AST/alanine aminotransferase (ALT) ratio, GGT/ALT ratio, and GGT/AST ratio were significantly different between the PLC and CHB groups. Statistically significant differences in serum GGT activity, AST activity, and GGT/ALT ratio were observed between the PLC and LC groups. The BCP 1762/1764 mutation rate between the PLC and CHB groups was statistically significant. The GGTII level in the early PLC (stage I + II) group and the advanced PLC (stage III + IV) group was higher than that in the N-PLC group. Serum GGT activity in the early PLC and advanced PLC groups was higher than that in the N-PLC group. The area under the curve of the receiver operator characteristic curve of GGT and GGTII for diagnosing PLC was 0.775 (95% confidence interval [CI] [0.697, 0.854]) and 0.608 (95% CI [0.512, 0.704]), respectively. The area under curve of GGT and GGTII for diagnosing early PLC was 0.732 (95% CI [0.620, 0.845]) and 0.579 (95% CI [0.452, 0.706]), respectively. HBV gene BCP 1762/1764 mutation, GGT, and GGTII may be related to PLC occurrence. The HBV gene BCP region 1762/1764 combined with GGT has certain clinical diagnostic values for PLC and early PLC. However, GGTII is not a good indicator of early PLC and is more relevant to advanced PLC.

Epidemiology, Genotyping, Mutational and Phylogenetic Analysis of Hepatitis B Virus Infection in North-east India

Hepatitis B virus (HBV) infection is a major public health problem globally. Northeast India is home to indigenous tribes with different ethnicity and high rates of drug abuse and HIV infection. The study was designed to estimate the burden of HBV infection across various spectrums of liver diseases from this region. HBV genotypes and subgenotypes play a role in the chronicity of disease, response to treatment and its progression. As very limited data are available from this region, we tried to elucidate the role of HBV genotypes, HBV mutants and their phylogenetic analysis. We designed a prospective multicentric study, and included 7464 liver disease cases, 7432 blood donors and 650 health care workers, who were screened for HBV infection. HBV DNA positive patients were genotyped and subjected to surface protein, precore and core mutation and phylogenetic analysis. The prevalence of HBV infection with respect to different types of liver diseases, blood donors and health care workers was 9.9% (1550/15,546). 49.5% (768/1550) cases were found to be HBV DNA positive. The most common genotype was found to be genotype D 74.2% (570/768), followed by genotype C 6.5% (50/768), A 4.4% (34/768) and I 0.9% (7/768). This study highlights the high hepatitis B burden in Northeast India, reflecting lacunae in health care needs of the region. Also, the different genotype distribution and presence of mutationsmay translate into different rates of liver disease progression, prognosis and ultimately, clinical significance. However, further prospective cohort study from Northeast India is warranted, to elucidate the clinical significance of multiple genotypes and mutation in this unique population.

Prevalence of Anti-HBc Antibodies among HBsAg Negative Individuals and Its Association with Occult Hepatitis B.

Introduction Hepatitis B virus (HBV) infection is an endemic in many Asian countries, and among the major routes of transmission, transfusion is the one that should be prevented. Occult HBV infection (OBI) is defined as the presence of HBV DNA in the absence of detectable HBsAg, with or without anti-HBV antibodies. The aim of this study was to detect the prevalence of anti-HBc total antibodies among the HB surface antigen (HBsAg) negative individuals by way of enzyme-linked immunosorbent assay (ELISA), and detect the presence of HBV DNA among the anti-HBc seropositives by polymerase chain reaction (PCR). Anti-HBs among the HBV DNA positives were also found out by enzyme-linked fluorescent assay (ELFA). Materials and Methods A total of 910 serum samples was subjected to initial screening for HBsAg by MERILISA HBsAg ELISA kits. The anti-HB core (HBc) total antibody titer was evaluated using MONOLISA ELISA (Biorad) kits. If found negative, the samples were discarded. If found positive, the samples underwent HBV DNA testing by nested PCR. Antibody to hepatitis B surface antigen (anti-HBs) was calculated among the DNA positives by ELFA. Results A total of 133 samples were positive for anti-HBC total antibody, resulting in an overall prevalence of 14.6%. Overall prevalence of HBV DNA among the anti-HBc seropositives was 2.2%. Conclusion Among the three HBV DNA positive patients, two belonged to the preoperative screening group, which is an alarming situation. Screening of blood for HBsAg has reduced the incidence of posttransfusion hepatitis, but HBV still remains the major source of transfusion transmitted infection in India.

Study of the inhibitory effect of cell entry inhibitory myrcludex-B synthetic peptide on HepaRG cells infected with hepatitis B virus in an in vitro infection model

Objective: To establish and explore the inhibitory effect of cell entry inhibitor myrcludex-B on human liver cancer cell (HepaRG) infected with hepatitis B virus (HBV) positive serum in an in vitro infection model. Methods: HepaRG induced mature cells were divided into polyethylene glycol (PEG) infection group and non-PEG infection group, and then the two infection groups were divided into treatment group with myrcludex-B peptide fragment and control group without myrcludex-B peptide fragment, and the cells were infected with the serum of HBV DNA-positive patients. The expression of HBV DNA in supernatant was detected by fluorescence quantitative PCR, and the HBsAg and HBeAg content in supernatant were detected by chemical fluorescence. Measurement data of the non-normal distribution between the two groups was determined by rank-sum test, and normal distribution was determined by t-test. P < 0.05 was considered as statistically significant. Results: In the treatment and control group the virus titers of the PEG infection group and the non-PEG infection group were (103 877.00 ± 49 013.24) copies / ml and (5 050.09 ± 631.26) copies/ml, and (116 188.57 ± 50 957.19) copies/ml, (5 119.34 ± 1 102.43) copies/ml, respectively. Virus titers of both groups with PEG infection were significantly higher than non-PEG infection group, and the difference was statistically significant (P < 0.05). In the PEG infection group, the virus titers of the peptide-treated group and the non-peptide control group were (103 877.34 ± 49 013.24) copies /ml and (116 188.57 ± 50 957.19) copies/ml, respectively, and the virus titers of the peptide-treated group was decreased significantly (P < 0.05), and the difference was statistically significant. HBsAg content in the supernatant of this group was positive at 0, 1, 2 and 3 days, while the 0 day HBsAg supernatant treated with peptide fragment was significantly lower than that of the control group without peptide fragment. Conclusion: It is feasible to infect HepaRG cells with HBV positive serum supplemented with PEG in vitro, and the cell entry inhibitor myrcludex-B has a certain inhibitory effect on hepatitis B virus infection in this experimental model.

Peg-interferon and nucleos(t)ide analogue combination at inception of antiviral therapy improves both anti-HBV efficacy and long-term survival among HBV DNA-positive hepatocellular carcinoma patients after hepatectomy/ablation.

Antiviral therapy has been shown to improve the prognosis of hepatitis B virus (HBV) DNA-positive hepatocellular carcinoma (HCC) after radical treatment, but antiviral treatments require further optimization. This study aimed to evaluate the efficacies of different antiviral strategies with HCC patients after hepatectomy/ablation. This prospective, randomized, controlled and multi-centre trial enrolled HBV DNA-positive primary HCC patients after hepatectomy/ablation between January 2007 and January 2009. Patients were divided into four groups: early combination (entecavir plus Peg-interferon [IFN]α-2a co-administration during year 1); late combination (addition of Peg-IFNα-2a for 48weeks after 1year of entecavir); nucleos(t)ide analogue[NA] monotherapy; and non-antiviral treatment. Primary endpoints included recurrence-free survival and overall survival. A total of 447 patients were enrolled. The 2-year and 8-year recurrence-free survival and 8-year overall survival rates were significantly higher in the early combination group than in the other two antiviral groups (P<.05). After 48-week treatment, more patients achieved an HBsAg reduction >1500IU/mL and the mean HBsAg level was significantly lower in the early combination group compared with the late combination and NA monotherapy groups (P<.05). Multivariate analysis showed that early combination therapy and a reduction in HBsAg by >1500IU/mL after 48weeks of therapy correlated with reduced mortality and disease recurrence. Early introduction of combination antiviral treatment may represent a more effective therapeutic strategy for patients with HBV DNA-positive HCC after hepatectomy/ablation. A reduction in HBsAg by >1500IU/mL after 48-week treatment is associated with reduced mortality and disease recurrence of HBV DNA-positive HCC patients after hepatectomy/ablation.

Diagnostic value of gamma-glutamyltransferase/aspartate aminotransferase ratio, protein induced by vitamin K absence or antagonist II, and alpha-fetoprotein in hepatitis B virus-related hepatocellular carcinoma.

BACKGROUNDResearchers have investigated the diagnostic value of protein induced by vitamin K absence or antagonist II (PIVKA-II) and alpha-fetoprotein (AFP) in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), and obtained abundant clinical diagnostic data. However, PIVKA-II and AFP have unsatisfactory specificity and sensitivity in the diagnosis of early-stage HBV-related HCC. Gamma-glutamyltransferase (γ-GT) and aspartate aminotransferase (AST) are common biomarkers for evaluating liver function, and we hypothesized that the γ-GT/AST ratio in combination with PIVKA-II and AFP would improve the diagnosis of early-stage HBV-related HCC.AIMTo evaluate the diagnostic value of γ-GT/AST ratio alone or in combination with PIVKA-II and AFP in HBV-related HCC.METHODSSerum levels of γ-GT, AST, PIVKA-II, and AFP were detected and analysed in 176 patients with HBV-related HCC and in 359 patients with chronic hepatitis B. According to tumour size and serum level of HBV DNA, HBV-related HCC patients were divided into the following categories: Early-stage HCC patients, HCC patients, HBV DNA positive (HBV DNA+) HCC patients, and HBV DNA negative (HBV DNA-) HCC patients. Receiver-operating characteristic (ROC) curves were used to analyse and compare the diagnostic value of the single and combined detection of various biomarkers in different types of HBV-related HCC.RESULTSTumour size was positively correlated with serum levels of PIVKA-II and AFP in HCC patients (r = 0.529, aP < 0.001 and r = 0.270, bP < 0.001, respectively), but there was no correlation between tumour size and the γ-GT/AST ratio (r = 0.073, P = 0.336). The areas under the receiver-operating characteristic curves (AUROCs) of the γ-GT/AST ratio in early-stage HCC patients, HBV DNA+ HCC patients and HBV DNA- HCC patients were not significantly different from that in the total HCC patients (0.754, 0.802, and 0.705 vs 0.779, respectively; P > 0.05). When PIVKA-II was combined with the γ-GT/AST ratio in the diagnosis of early-stage HCC, HCC, and HBV DNA+ HCC, the AUROCs of PIVKA-II increased, with values of 0.857 vs 0.835, 0.925 vs 0.913, and 0.958 vs 0.954, respectively. When AFP was combined with the γ-GT/AST ratio in the diagnosis of early-stage HCC, HCC, HBV DNA+ HCC, and HBV DNA- HCC, the AUROCs of AFP increased, with values of 0.757 vs 0.621, 0.837 vs 0.744, 0.868 vs 0.757, and 0.840 vs 0.828, respectively.CONCLUSIONThe γ-GT/AST ratio may be better than PIVKA-II and AFP in the diagnosis of early-stage HBV-related HCC, and its combination with PIVKA-II and AFP can improve the diagnostic value for HBV-related HCC.

Hepatitis B Virus Subtype Distribution in Bangladeshi Chronic Carriers

Background : Hepatitis B virus (HBV) infection is one of the major global health problems and this virus has many variants that differ from epidemiological distributions, transmission sources, clinical outcomes, diagnostic assays as well as therapeutic responses. HBV was also divided into 9 different subtypes which has distinct geographical distributions and important for the epidemiological studies and vaccine development.Objective : Bangladesh is an intermediate prevalence region for HBV infection, however, very little is known about the incidence of HBV subtypes in circulation. Therefore, we investigated the HBV subtype distribution in Bangladesh.Method : A small cohort was performed on between March 2014 and August 2017 with 172 HBV DNA positive patients from the BSMMU. From them, 29 HBV DNA samples were isolated for sequencing by Sanger method. HBsAg subtypes were determined by identifying of 226 amino acid (aa) positions in the small surface (S) gene.Result : Our study showed that HBV subtype adrq+ was in 17 (58.6%) isolates, ayw3 in 8 (27.5%), ayw2 in 2 (6.9%) and adw2 in 2 (6.9%) isolates.Conclusion : We conclude subtype adrq+ predominant in Bangladesh. This was followed by ayw3, while adw2 and ayw2 were least dominant. Subtype adw2 and adrq+ strains are found to be related with more complication, therefore, patients infected with these HBV strains need to be careful monitoring to assess their clinical outcome in future.Northern International Medical College Journal Vol.9(2) Jan 2018: 286-290

Nail scissors and fingernails as reservoirs of hepatitis B virus DNA: Role of nail scissors in household transmission of hepatitis B virus

No study in the current literature has scientifically clarified the transmission of hepatitis B virus (HBV) via personal hygiene tools. We determined risk of household transmission of HBV via nail scissors. Moreover, we assessed whether nails from HBV-infected people contained HBV, and evaluated correlations of HBV DNA levels of serum, nail specimens, and nail scissors. Seventy patients testing positive for the surface antigen of the hepatitis B virus (63 positive for HBV DNA) treated for HBV infection and 27 healthy individuals were included. Real-time polymerase chain reaction method was used to detect HBV DNA levels in sera, nail, and nail scissors. HBV DNA was detected on 27% of nail scissors and in 50% of nail specimens from 63 serum HBV DNA-positive patients. Serum HBV DNA level >105 IU/mL was associated with 71.8% probability of nail scissors being HBV DNA-positive (P < .05). Serum HBV DNA level >107 IU/mL was associated with 71.5% probability of fingernails being HBV DNA-positive (P > .05). Shared-use of nail scissors was correlated with surface antigen of the hepatitis B virus positivity and total hepatitis B core antibody/immunoglobulin G positivity. A high HBV DNA level was detected in nail scissors and low level HBV DNA in the nails of persons with high serum HBV DNA levels. Nail scissors, shared-use of nail scissors, and duration of shared use play important roles in household transmission of HBV. Level of education within society in this regard should be increased via mass media.

Prevalence and types of drug-resistant variants in Chinese patients with acute hepatitis B.

The presence of therapy-associated hepatitis B virus (HBV) variants is the main drawback of antiviral therapy for HBV infection. Moreover, drug-resistant variants are more insensitive to a second agent and more therapy-associated mutations will be present. To apply better nucleos(t)ide analogues (NA) and reduce the occurrence of resistance, the prevalence and types of drug-resistant mutations in acute hepatitis B patients were investigated in this study. One hundred three HBV DNA-positive patients with symptomatic acute hepatitis B that were observed from 2011 to 2013 were enrolled. Direct polymerase chain reaction sequencing was used firstly to screen HBV reverse-transcriptase domain to detect HBV mutants. Five lamivudine-resistant variants were identified. Clonal sequencing was performed for 5 resistance-positive samples and 10 other random samples. Interestingly, all detected samples harbored drug-resistant mutations, although with different percentage. Thirteen harbored lamivudine-related alone (five) or together with other NA related mutations (five with adefovir, one with entecavir, and one with telbivudine), and two of them harbored adefovir-related mutations. Also, mutations associated with four currently used NA were all detected, and the frequency is in accordance with the popularity of NA used in clinical practice. These data suggest that drug-resistant variants are present in patients with acute hepatitis B and NA should be applied more carefully for chronic hepatitis B patients developed from acute hepatitis B.

Can hepatitis B virus DNA in semen be predicted by serum levels of hepatitis B virus DNA, HBeAg, and HBsAg in chronically infected men from infertile couples?

Hepatitis B virus (HBV) in semen is important for father-to-child transmission of HBV and has adverse effects on sperm quality. However, risk factors associated with HBV in semen remain unclear. Serum HBV DNA and hepatitis B e antigen (HBeAg) levels may pose a risk on HBV in semen. This study aims to examine whether serum HBV DNA, HBeAg, and hepatitis B surface antigen (HBsAg) level were associated with HBV DNA in semen. 151 male patients chronically infected with HBV from infertile couples were included. Serum HBsAg and HBeAg were determined using an electrochemiluminescence immune assay (ECLIA). Serum and seminal plasma HBV DNA were detected by the QIAGEN Real-Time HBV DNA assay. Of 151 patients, 143 (94.7%) were serum HBV DNA-positive and 65 (43.0%) were seminal plasma HBV DNA-positive. Serum HBV DNA and HBeAg level of seminal plasma HBV DNA-positive patients were significantly higher (p < 0.001) as compared with those of seminal plasma HBV DNA-negative patients, HBsAg level of seminal plasma HBV DNA-positive patients was significantly lower (p < 0.001) compared with that of seminal plasma HBV DNA-negative patients. The best serum HBV DNA, HBeAg, and HBsAg value for discriminating between seminal plasma HBV DNA-positive and HBV DNA-negative patients were ≥6.9 log10 IU/mL (sensitivity 100.0%, specificity 90.7%), >14.8 S/CO (sensitivity 96.9%, specificity 81.5%), and <1791.5 S/CO (sensitivity 81.5%, specificity 81.2%), respectively. The combination of serum HBV DNA and HBeAg had high diagnostic sensitivity (100.0%) and specificity (95.4%) for the presence of HBV DNA in semen. As such, these serum markers especially the combination of HBV DNA and HBeAg are useful predictors of the presence of HBV DNA in semen in HBV chronically infected men from infertile couples.

Clinical significance of periodic detection of hepatitis B virus YVDD mutation by ultrasensitive real-time amplification refractory mutation system quantitative PCR during lamivudine treatment in patients with chronic hepatitis B.

Monitoring hepatitis B virus (HBV) mutants periodically during nucleoside analogue treatment is of great clinical significance, particularly in persistently HBV DNA-positive patients. However, few studies have investigated the dynamic changes of HBV YMDD (Tyr-Met-Asp-Asp) and YVDD (Tyr-Val-Asp-Asp) populations in chronic hepatitis B (CHB) patients whilst undergoing lamivudine (LMV) treatment. In this study, we sought to investigate the dynamic changes of HBV YMDD and YVDD variants by ultrasensitive real-time amplification refractory mutation system quantitative PCR (RT-ARMS-qPCR) and evaluate its significance for changes in the treatment of CHB patients. RT-ARMS-qPCR was established and evaluated with standard recombinant plasmids. Fifteen CHB patients receiving LMV (100 mg daily) were consecutively recruited and followed up for 60 weeks. Serum samples were obtained from each patient at baseline and every 12 weeks. The total HBV DNA, HBV YMDD DNA and YVDD DNA levels were measured using RT-ARMS-qPCR at all given time points after treatment. Routine liver biochemistry parameters, including aspartate aminotransferase and alanine aminotransferase, were also measured every 12 weeks. The linear range of the assay was between 1×10(12) and 1×10(5) copies ml(-1). The low detection limit was 1×10(4) copies ml(-1). After 60 weeks of LMV treatment, nine patients experienced virological breakthrough. The YVDD variant could be detected 12-48 weeks before virological breakthrough. The YVDD variant was detected as the predominant population (range 69.4-100 %) in patients by the time virological breakthrough appeared. We concluded that RT-ARMS-qPCR was sensitive for the detection and quantification of low levels of HBV mutation. Periodic detection of HBV YM(V)DD every 12 weeks during LMV treatment is helpful for therapeutic decision making.

Nucleoside analogues for acute-on-chronic liver failure associated with hepatitis B virus infection: a 24-month survival analysis

To investigate the effect of different nucleoside analogues on the long-term survival rate of patients with acute-on-chronic liver failure (ACLF) associated with hepatitis B virus (HBV) infection. One hundred and eighty patients with HBV-related ACLF were enrolled in this prospective cohort study and divided into a basic treatment group (n=30) and an antiviral treatment group, the latter of which was further subdivided into the lamivudine treatment group (n=66), telbivudine treatment group (n=38) and entecavir treatment group (n=46) according to voluntary choice by the patient.All study participants were followed-up for 24 months. The Kaplan-Meier method was applied for survival analysis. The patients in the four antiviral treatment groups had statistically similar baseline clinical characteristics and 1-month survival rates (Breslow =4.475, P=0.215).However, the basic treatment group had a significantly lower survival rate than the antiviral treatment groups that received lamivudine, telbivudine, or entecavir (all P less than 0.05) at the treatment periods of 2, 3, 6, 12 and 18-months; however, these three treatment groups showed no significant differences in survival rates. At the time point of 24 months of treatment, the basic treatment group retained its lower rate of survival than the three antiviral treated groups (lamivudine:Breslow =5.604, P=0.018; telbivudine:Breslow =5.621, P=0.018; entecavir:Breslow =14.701, P less than 0.001); while the survival rates were similar for the lamivudine treatment group and the telbivudine treatment group at this time point, their survival rates were significantly lower than that of the entecavir treatment group (Breslow =4.010, P=0.045; Breslow =4.307, P=0.038).Stratification analysis showed that when the baseline was 30 less than PTA less than or equal to 40 or MELD less than or equal to 29 or HBV DNA more than or equal to 5 log10 IU/mL, the cumulative survival rates of the basic treatment group and antiviral treatment group were statistically similar even though the patients had completed 1 month of treatment After being treated for 2, 3, 6, 12, 18 and 24 months, the cumulative survival rates of the basic treatment group were consistently below those of the overall antiviral treatment group (P less than 0.05). The cumulative survival rate of the basic treatment group followed-up for 1 to 24 months, with PTA values between 20 and 30, was lower than that of the overall antiviral treatment group (P less than 0.05); two groups of patients with PTA less than or equal to 20 or MELD more than or equal to 30 were followed-up for 1 months to 24 months, and their cumulative survival rates showed no significant difference (P more than 0.05). Among the patients whose baseline was HBV DNA less than 5 log10 IU/mL, the comparison of survival rates between the basic treatment group and the overall antiviral treatment group showed no significant differences after treatment for 1, 2, 3, 6, 12 or 18 months, and the survival rate was lower than that of the overall antiviral treatment group (Breslow =4.055, P=0.044) after 24 months. Nucleoside analogues can improve the long-term survival rate of HBV-related ACLF patients.Entecavir is preferred for the long-term treatment of these patients.Patients in the early and middle stages of this disease and HBV DNA-positive patients should adopt antiviral treatment as early as possible.

Evaluation of viral load distribution of HBV DNA positive patients at Suleyman Demirel University Hospital

Hepatitis B virus (HBV) may cause a wide spectrum of liver diseases ranging from an asymptomatic carrier state to severe chronic liver disease, cirrhosis, and hepatocellular carcinoma (HCC). In patients with Chronic hepatitis B (CHB) infection, serum HBV viral load has been shown to be significantly associated with disease activity and disease progression. The aim of this study was to determine the viral load distribution of HBV DNA in patients with HBV infection in Isparta region. Hepatitis B surface antigen (HBs Ag) and HBV DNA levels in serum samples of 1054 patients were analysed retrospectively between January 2013 and December 2013. HBs Ag tests in the serum of patients were measured with chemiluminescence method (Vitros, Johnson&Johnson, USA). The levels of sera HBV DNA were quantified with real-time PCR method by Cobas/AmpliPrep/ Cobas Taqman HBV test v 2.0 (Roche Diagnostics GmbH, Mannheim, Germany) and HBV Quantification Kit v1, Magnesia 16, Montania 483 (Anatolia Geneworks, Turkey). HBV-DNA levels were determined as 1-102 IU/ml (28.6%), 102-3 IU/ml (32.6 %), 103-4 IU/ml (22.7%), 104-5 IU/ml (7.2%), 105-6 IU/ml (2.4%), 106-7 IU/ml (2.4 %), 107-8 IU/ml (1.5%), 108-9 IU/ml (2.4%), ≥109 IU/ml (0.2%). Amounts of the viral load of HBV DNA positive samples were observed to concentrate around the lower levels (1-105 IU/ml) in Isparta region (91%) which predicted lower risk of progression to HCC.

Investigation of Hepatitis B and Hepatitis C Virus Infections by Serological and Molecular Methods in Hemodialysis Patients

Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are significant causes of morbidity and mortality in hemodialysis patients, since those patients are highly susceptible to infections due to immune suppression. The aims of this study were to investigate the presence of HBV and HCV infections in chronic hemodialysis patients by serological and molecular methods, and to determine the rate of occult HBV infection and the viral genotypes. A total of 201 patients who were under hemodialysis due to end-stage renal disease, were retrospectively evaluated. The study involved the patients at three different centers in Antalya, Turkey during 2006. HBV and HCV markers in the patients' sera were screened by ELISA method, viral nucleic acids were investigated by real-time polymerase chain reaction (PCR) in patients' plasma and viral genotypes were determined by DNA sequence analysis. Detection of at least one of the HBV markers HBsAg, anti-HBc total, and HBV DNA, was accepted as HBV infection, and detection of anti-HCV and/or HCV RNA was accepted as HCV infection. HBsAg positive patients with negative HBV DNA were considered as occult HBV infection. Of the patients 80 (40%) were female, 121 (60%) were male and the mean age was 51.16 ± 16.28 (range 17-93) years. In our study, sole anti-HBs positivity due to HBV vaccination, was detected in 89 (44.3%) patients. One hundred (50%) patients were found positive in terms of HBV infection and 40 (20%) were positive for HCV infection, while 24 (12%) patients had HBV and HCV co-infections. Eighty-five (42.3%) patients had no HBV and HCV infection. Among the 5 (2.5%) patients who were HBsAg positive, four were also HBV DNA positive. Occult HBV infection was detected in 1 (0.5%) patient. Anti-HCV and HCV RNA were found positive in 37 (18.4%) and in 24 (12%) patients, respectively. Among the HCV-RNA positive patients, 3 (12.5%) were anti-HCV negative. ALT and AST levels were found normal in all of the HBV DNA positive patients, and 62.5% (15/24) of HCV RNA positive patients. All of the HBV isolates were identified as genotype D and HCV isolates as genotype 1b. No statistically significant correlation was detected between the HBV infection and patients' age, duration of hemodialysis and elevation of serum transaminase levels (p> 0.05). On the other hand, HCV infection was seen to increase with age (p= 0.047). HCV infection showed a statistically significant increase with the duration of hemodialysis. HCV infection risk was increased in patients who were under hemodialysis for ≥ 25 months (p< 0.001, OR: 0224, 95% CI= 0089-0562). There was also a statistically significant correlation between the presence of HCV infection (anti-HCV and/or HCV RNA positive) and high levels of serum transaminases (p< 0.001). However, in two of the three cases who were anti-HCV negative and HCV RNA positive, serum transaminase levels were normal while the viral loads were high. Therefore to follow-up HCV infection in the hemodialysis patients, anti-HCV and serum transaminase levels may not be sufficient alone and these patients should be evaluated periodically for HCV RNA. In addition, the detection of occult HBV infection in one of the study patients, indicated that HBV DNA should also be investigated at regular intervals in the hemodialysis patients.

A proposal for management of rheumatic disease patients with hepatitis B virus infection receiving immunosuppressive therapy

Reactivation of hepatitis B virus (HBV) and de novo HBV hepatitis in patients with rheumatic diseases given intensive and long-term immunosuppressive therapy with or without biological disease-modifying antirheumatic drugs is of great concern, especially in regions where the virus is endemic, including Japan. To ascertain a better benefit–risk balance for immunosuppressive therapy for patients with rheumatic diseases, the Japan College of Rheumatology developed this proposal. All patients with rheumatic diseases commencing immunosuppressive therapy should be screened for hepatitis B surface antigen (HBsAg); those who are negative for HBsAg should be screened for hepatitis B core antibody (HBcAb) and hepatitis B surface antibody (HBsAb) as well. HBV carriers and serum HBV DNA positive patients with resolved infection should receive nucleoside analog as soon as possible, prior to commencing immunosuppressive therapy. For serum HBV DNA negative patients with resolved infection, careful monthly monitoring using serum levels of aspartate and alanine aminotransferases and HBV DNA is recommended during and at least 12 months after withdrawal of immunosuppressive therapy. If serum HBV DNA becomes positive, patients should receive nucleoside analog treatment as soon as possible, while ongoing immunosuppressive therapy should be continued to avoid severe or fulminant hepatitis development. To facilitate proper management of patients with HBV infection, collaboration between rheumatologists and hepatologists is strongly encouraged.

A proposal for management of rheumatic disease patients with hepatitis B virus infection receiving immunosuppressive therapy

Reactivation of hepatitis B virus (HBV) and de novo HBV hepatitis in patients with rheumatic diseases given intensive and long-term immunosuppressive therapy with or without biological disease-modifying antirheumatic drugs is of great concern, especially in regions where the virus is endemic, including Japan. To ascertain a better benefit–risk balance for immunosuppressive therapy for patients with rheumatic diseases, the Japan College of Rheumatology developed this proposal. All patients with rheumatic diseases commencing immunosuppressive therapy should be screened for hepatitis B surface antigen (HBsAg); those who are negative for HBsAg should be screened for hepatitis B core antibody (HBcAb) and hepatitis B surface antibody (HBsAb) as well. HBV carriers and serum HBV DNA positive patients with resolved infection should receive nucleoside analog as soon as possible, prior to commencing immunosuppressive therapy. For serum HBV DNA negative patients with resolved infection, careful monthly monitoring using serum levels of aspartate and alanine aminotransferases and HBV DNA is recommended during and at least 12 months after withdrawal of immunosuppressive therapy. If serum HBV DNA becomes positive, patients should receive nucleoside analog treatment as soon as possible, while ongoing immunosuppressive therapy should be continued to avoid severe or fulminant hepatitis development. To facilitate proper management of patients with HBV infection, collaboration between rheumatologists and hepatologists is strongly encouraged.

Prevalence of hepatitis B virus (HBV) co-infection in HBV serologically-negative South African HIV patients and retrospective evaluation of the clinical course of mono- and co-infection

Hepatitis B virus (HBV) infection with undetectable hepatitis B surface antigen (HBsAg) has been reported in HIV patients, but the clinical significance is unknown. This study presents the prevalence of HBV DNA in HIV-positive patients negative for all HBV serological markers and a retrospective evaluation of the clinical course of mono- and co-infection. Of 502 HIV-positive patients, 222 tested negative for HBsAg, antibody to hepatitis B surface antigen (anti-HBs), and antibody to hepatitis B core antigen (anti-HBc). An in-house real-time PCR targeting the HBV S-region was used to quantify HBV DNA. HBV isolates were genotyped. Baseline demographic and clinical characteristics of HBV DNA-positive and HBV DNA-negative patients were described. Treatment outcomes of patients at 6, 12, and 24 months after initiation of antiretroviral therapy (ART) were summarized. HBV DNA was detected in 5.4% (12/222) of serologically negative patients. Mean HBV viral load was 5359.2 IU/ml (standard deviation (SD) ±12768.27). Eleven HBV isolates belonged to genotype A and one to genotype C. There were no significant differences in baseline characteristics or clinical course between the HBV DNA-positive and HBV DNA-negative groups. We found 5.4% of the HBV serologically-negative HIV-positive patients had low levels of HBV DNA. There were no significant differences in clinical outcome between the mono- and co-infected groups.

Evaluating the risk of hepatitis B reactivation in patients with haematological malignancies: is the serum hepatitis B virus profile reliable?

Patients with an occult hepatitis B virus (HBV) infection undergoing deep immunosuppression are potentially at risk of HBV reactivation. In order to assess whether a polymerase chain reaction (PCR) assay for HBV DNA in serum could be used to predict the reactivation of an occult HBV infection, we performed a retrospective study in a cohort of Sicilian patients with oncohaematological diseases. We studied by a highly sensitive ad hoc nested PCR for serum HBV DNA 75 HBsAg-negative oncohaematological patients requiring chemotherapy. Thirty-three patients (44%) were HBV seronegative (anti-HBc and anti-HBs negative) and 42 patients (56%) were HBV seropositive (anti-HBc and/or anti-HBs positive). Baseline serum HBV DNA was positive in nine out of 33 HBV-seronegative patients and in nine out of 42 HBV-seropositive patients (27.3 vs. 21.4%; P=NS). HBsAg seroconversion was observed in five out of 33 seronegative vs. six out of 42 seropositive patients (15 vs. 14%, P=0.9), and in five out of 18 HBV DNA-positive vs. six out of 57 HBV DNA-negative patients (27.7 vs. 10.6%P=0.11). Hepatitis C virus infection was found in 18 patients (24.3%), although with no correlation to HBV serological status, presence of serum HBV DNA or frequency of HBsAg seroconversion. In oncohaematological patients undergoing chemotherapy, highly sensitive serum HBV DNA testing at baseline has a 28% predictive ability to forecast HBsAg seroconversion in HBV DNA-positive patients, and a 90% ability to forecast persistent HBsAg negativity in HBV DNA-negative patients, a better performance than serological tests.

Relation between hepatitis B virus genotypes and gene mutation of basic core promoter in Li nationality

Objective To investigate the relation between hepatitis B virus(HBV) genotypes and the double mutation of A-to-T nucleotide(nt) 1762 and G-to-A nt 1764 in basic core promoter(BCP T1762/A1764) in patients of the Li nationality. Methods Subjects were 125 HBV DNA positive patients that belong to the Li nationality on Hainan Island. HBV DNA genotype was determined by real time fluorimetry polymerase chain reaction. BCP T1762/A1764 mutation was performed using the direct sequencing method. Results The prevalence rates of genotype B, genotype C, genotype D, genotype C and D mixed infection(genotype C + D) and genotype B and D mixed infection (genotype B + C) were 31.20%, 53.60%, 12.00%, 2.40% and 0.80% respectively. Mutation frequencies in patients infected with HBV genotype C(58.21%) were significantly higher than in those infected with other genotypes ( P < 0.01). The serum viral load of the patients with genotype C(5.74±1.21) was also higher than that of those with genotype B( P < 0.01). Conclusion The major genotypes in the Li nationality were genotype C and genotype B. The infection of genotype D and mixed infection also occurred in the Li nationality. Genotype C HBV has a higher replication rate, and the different degrees of pathogenecity among HBV genotypes may be related to BCP T1762/A1764 mutation frequency.