• antivirals
• hepatitis B virus
• mother-to-child transmission
• pregnancy
• safety
• tenofovir

• 2020 Bumsuk Academic Research Fund

Among nucleos(t)ide analogue therapies for hepatitis B virus (HBV) treatment, entecavir (ETV) and tenofovir disoproxil fumarate (TDF)/tenofovir alafenamide are associated with the lowest rate of drug resistance. ETV is a drug requiring at least three substitutions in the reverse transcriptase (RT) domain to develop resistance, which is a rare occasion in treatment-naïve patients. However, pre-existing or acquired single mutations in the RT domain could lead to a virological breakthrough, after viral suppression. The present case report describes a 58-year-old female patient with hepatitis B virus (HBV) and high viral load who started HBV treatment with ETV. After 85 weeks of treatment, HBV-DNA declined to 0 IU/ml and remained undetectable for 3 years. However, after that period of time, the HBV-DNA rebounded, followed by the rise of liver enzymes (aspartate aminotransferase and alanine transaminase). Only the substitution M204I was detected in the HBV polymerase region. The patient was then switched to TDF treatment, achieving normalization of the liver enzymes and a decline in HBV-DNA levels. The present case report suggests that nucleoside-naïve patients should be cautiously monitored for resistance, even more than biochemically (transaminases, bilirubin) and virologically (HBV-DNA), even if complete HBV suppression is achieved.

• HBV
• HBV resistance
• entecavir therapy

Immunization programmes against hepatitis-B are being carried out since more than three decades but still HBV is a major public health problem. Hepatitis B virus (HBV) genome consists of circular and partial double stranded DNA. Due to partial double stranded DNA, it uses an RNA intermediate during replication. This replicative strategy of HBV and lack of polymerase proofreading activity give rise to error occurrences comparable to retroviruses. The low fidelity of polymerase, overlapping reading frames and high replication rate produces many non-identical variants at every cycle of replication. Therefore, HBV spreads with mutations and variations. The mutations have been reported both in non-structural as well as structural genes of HBV genome. Recent advances in molecular biology have made easier to analyse these mutations. Hepatitis B antiviral therapy and immunization are all influenced by genetic variability. The analysis and understanding of these mutations are important for therapy against hepatitis B and updating of diagnostic tools. The present review discusses about mutations occurring in whole HBV genome. The mutation occurring both in structural and non-structural genes and non-coding regions have been described in details. It is much more informative because most of literature available, covers only individual gene or DNA regions of HBV.

• HBV variants
• Hepatitis B virus
• liver disease
• mutation

• DAAs
• HBV
• HCV
• PCR

Hepatitis B virus (HBV) DNA polymerase mutations usually occur to long term use of nucleos(t)ide analogues (NAs), but they can occur spontaneously in treatment-naïve chronic hepatitis B (CHB) patients. The naturally occurring HBV DNA polymerase mutations might complicate antiviral therapy with NAs, leading to the generation of drug-resistant viral mutants and disease progression. The most common substitutions are known to be YMDD-motif mutations, but their prevalence and the influence on antiviral therapy is unclear.

To investigate prevalence of the naturally occurring rtM204I mutations in treatment-naïve CHB genotype C2 patients and their influence on antiviral therapy.

A total of 410 treatment-naïve CHB patients infected with HBV genotype C2 strains were enrolled in this retrospective study. Among the 410 patients, 232 were treated with NAs for at least 12 mo. Significant fibrosis was defined as fibrosis-4 index > 3.25 or aspartate aminotransferase to platelet ratio index > 1.5. Complete viral response (CVR) during NAs was defined as undetectable serum HBV DNA (< 24 IU/mL). The rtM204I variants were analyzed by a newly developed locked nucleotide probe (LNA probe) based real-time PCR (LNA-RT-PCR) method.

The LNA-RT-PCR could discriminate rtM204I mutant-type (17 patients, 4.2%) from rtM204 wild-type (386 patients, 95.8%) in 403 of 410 patients (98.3% sensitivity). Multivariate analysis showed that naturally occurring rtM204I variants were more frequently detected in patients with significant fibrosis [odd-ratio (OR) 3.397, 95% confidence-interval (CI) 1.119-10.319, P = 0.031]. Of 232 patients receiving NAs, multivariate analysis revealed that achievement of CVR was reversely associated with naturally occurring rtM204I variants prior to NAs treatment (OR 0.014, 95%CI 0.002-0.096, P < 0.001). Almost patients receiving tenofovir achieved CVR at 12 mo of tenofovir, irrespective of pre-existence of naturally occurring rtM204I mutations (CVR rates: patients with rtM204I, 100%; patients without rtM204I, 96.6%), whereas, pre-existence of naturally-occurring rtM204I-mutations prior to NAs significantly affects CVR rates in patients receiving entecavir (at 12 mo: Patients with rtM204I, 16.7%; patients without rtM204I, 95.6%, P < 0.001).

The newly developed LNA-RT-PCR method could detect naturally occurring rtM204I mutations with high-sensitivity. Theses mutations were more frequent in patients with liver fibrosis. Tenofovir is a more suitable treatment than entecavir for CHB patients carrying the naturally occurring rtM204I mutations.

• Chronic hepatitis B
• Entecavir
• Hepatitis B virus
• Liver fibrosis
• Mutation
• Tenofovir

• Adult
• DNA Mutational Analysis/methods
• DNA Probes/genetics
• DNA, Viral/isolation & purification
• Drug Resistance, Viral/genetics
• Feasibility Studies
• Female
• Gene Products, pol/genetics
• Guanine/analogs & derivatives
• Guanine/pharmacology
• Guanine/therapeutic use
• Hepatitis B virus/drug effects
• Hepatitis B virus/genetics
• Hepatitis B, Chronic/drug therapy
• Hepatitis B, Chronic/virology
• Humans
• Male
• Middle Aged
• Mutation
• Oligonucleotides/genetics
• Real-Time Polymerase Chain Reaction
• Retrospective Studies
• Tenofovir/pharmacology
• Tenofovir/therapeutic use

• Chronic hepatitis B
• KASL guidelines
• Treatment

• Epidemiology
• HBV
• Hepatitis B
• Mutation
• Phylogeny

• Argentina
• genomic characterization
• genotypes
• hepatitis B virus
• molecular epidemiology

• HBV DNA
• genotype
• nucleoside analog-resistant (NAr) mutants
• occult HBV infection
• surface antigen mutants
• vaccination

• Adefovir
• Entecavir
• Lamivudine
• Monotherapy
• Tenofovir

• Adenine/analogs & derivatives
• Adenine/therapeutic use
• Antiviral Agents/therapeutic use
• Drug Resistance, Multiple, Viral/physiology
• Drug Therapy, Combination
• Guanine/analogs & derivatives
• Guanine/therapeutic use
• Hepatitis B Surface Antigens/blood
• Hepatitis B virus/drug effects
• Hepatitis B virus/genetics
• Hepatitis B, Chronic/blood
• Hepatitis B, Chronic/drug therapy
• Humans
• Lamivudine/therapeutic use
• Organophosphonates/therapeutic use
• Tenofovir/therapeutic use

• 9G DNA technology
• Drug-resistant HBV
• Genotyping
• HBV
• INNO-LiPA HBV Multi-DR test

• Chronic hepatitis B
• KASL guidelines
• Mangement

• Antiviral Agents/therapeutic use
• Carcinoma, Hepatocellular/diagnosis
• Carcinoma, Hepatocellular/etiology
• DNA, Viral/blood
• Drug Resistance, Viral
• Elasticity Imaging Techniques
• Hepatitis B virus/genetics
• Hepatitis B, Chronic/diagnosis
• Hepatitis B, Chronic/drug therapy
• Hepatitis B, Chronic/pathology
• Humans
• Liver Cirrhosis/diagnostic imaging
• Liver Cirrhosis/etiology
• Liver Neoplasms/diagnosis
• Liver Neoplasms/etiology
• Risk Factors

Liver transplantation (LT) is a life-saving treatment for patients with end-stage liver disease and for patients with liver cell cancer related to liver disease. Acute and chronic liver diseases related to hepatitis viruses are between the main indications for liver transplantation. The risk of viral reinfection after transplantation is the main limiting factor in these indications. Before the availability of antiviral prophylaxis, hepatitis B virus (HBV) recurrence was universal in patients who were HBV DNA-positive before transplantation. The natural history of recurrent HBV was accelerated by immunosuppression, and it progressed rapidly to graft failure and death. Introduction of post-transplant prophylaxis with immunoglobulin alone first, and associated to antiviral drugs later, drastically reduced HBV recurrence, resulting in excellent long-term outcomes. On the contrary, recurrence of hepatitis C is the main cause of graft loss in most transplant programs. Overall, patient and graft survival after LT for hepatitis C virus (HCV)-associated cirrhosis is inferior compared with other indications. However, successful pretransplant or post transplant antiviral therapy has been associated with increased graft and overall survival. Until recently, the combination of pegylated interferon and ribavirin was the standard of care for the treatment of patients with chronic hepatitis C. Highly active antiviral compounds have been developed over the past decade, thanks to new in vitro systems to study HCV entry, replication, assembly, and release.

• Liver transplantation
• Hepatitis B virus
• Hepatitis C virus
• Recurrence post-transplantation
• Antiviral therapy
• Prophylactic therapy

• Antiviral Agents/therapeutic use
• Disease Progression
• End Stage Liver Disease/diagnosis
• End Stage Liver Disease/surgery
• End Stage Liver Disease/virology
• Graft Rejection/immunology
• Graft Rejection/prevention & control
• Graft Rejection/virology
• Graft Survival
• Hepatitis B/complications
• Hepatitis B/diagnosis
• Hepatitis B/surgery
• Hepatitis B/virology
• Hepatitis C/complications
• Hepatitis C/diagnosis
• Hepatitis C/surgery
• Hepatitis C/virology
• Humans
• Immunosuppressive Agents/therapeutic use
• Liver Transplantation/adverse effects
• Recurrence
• Risk Factors
• Treatment Outcome

Hepatitis B virus (HBV) affects approximately two billion people worldwide and more than 240 million people in the world are currently chronic carrier that could develop serious complications in the future, like liver cirrhosis and hepatocellular carcinoma. Although an extended HBV immunization program is being carried out since the early ‘80s, representing effective preventive measure, leading to a dramatic reduction of HBV hepatitis incidence, globally HBV infection still represents a major public health problem. The HBV virus is a DNA virus belongs to the Hepadnaviridae family. The HBV-DNA is a circular, partial double strand genome. All coding information is on the minus DNA strand and it is organized into four open reading frames. Despite hepatitis B virus is a DNA virus, it has a high mutation rate due to its replicative strategy, that leads to the production of many non-identical variants at each cycle of replication. In fact, it contains a polymerase without the proofreading activity, and uses an RNA intermediate (pgRNA) during its replication, so error frequencies are comparable to those seen in retroviruses and other RNA viruses rather than in more stable DNA viruses. Due to the low fidelity of the polymerase, the high replication rate and the overlapping reading frames, mutations occur throughout the genome and they have been identified both in the structural and not structural gene. The arise of mutations being to develop of a whole of viral variants called “quasi-species” and the prevalent population, which favors virus replication, was selected by viral fitness, host’s immune pressure and external pressure, i.e., vaccination or antiviral therapy. Naturally occurring mutations were found both in acute and chronic subjects. In the present review we examine and discuss the most recent available data about HBV genetic variability and its significance.

• Hepatitis B virus
• Mutations
• Open reading frames
• Molecular biology tools
• Liver disease

• Drug Resistance, Viral/genetics
• Genome, Viral
• Hepatitis B/drug therapy
• Hepatitis B/epidemiology
• Hepatitis B/virology
• Hepatitis B virus/drug effects
• Hepatitis B virus/genetics
• Humans
• Mutation
• Viral Proteins/genetics

AIM: To evaluate the long-term efficacy adefovir (ADV)-based combination therapies in entecavir (ETV)-resistant chronic hepatitis B (CHB) patients.

METHODS: Fifty CHB patients with genotypic resistance to ETV at 13 medical centers in South Korea were included for the analysis. All the patients received rescue therapy with the combination of ADV plus ETV (ADV/ETV, n = 23) or ADV plus lamivudine (LMV) (ADV/LMV, n = 27) for more than 12 mo. Patients were monitored at least every 3-4 mo during ADV-based combination therapy by clinical examination as well as biochemical and virological assessments. Hepatitis B virus (HBV) DNA levels were measured by real-time PCR and logarithmically transformed for analysis. Cumulative rates of virologic response (VR; HBV DNA < 20 IU/mL) were calculated using the Kaplan-Meier method, and the difference was determined by a log-rank test. Multivariate logistic regression and Cox proportional hazards models were used to identify independent risk factors significantly associated with short-term and long-term VR, respectively.

RESULTS: Baseline median HBV DNA levels were 5.53 (2.81-7.63) log₁₀ IU/mL. The most commonly observed ETV genotypic mutation sites were rt184 and rt202. Patients were treated for a median of 27 (12-45) mo. Overall, cumulative VR rates at 6, 12, 24, and 36 mo were 26%, 36%, 45%, and 68%, respectively. Patients treated with the ADV/ETV combination showed higher cumulative VR rates (35%, 43%, 65%, and 76%, respectively) than those with the ADV/LAM combination (18%, 30%, 30%, and 62%, respectively; P = 0.048). In the multivariate analysis, low baseline HBV DNA levels (< 5.2 log₁₀ IU/mL) and initial virologic response at 3 mo (IVR-3; HBV DNA < 3.3 log₁₀ IU/mL after 3 mo) were independent predictive factors for VR. Patients with favorable predictors achieved cumulative VR rates up to 90% at 36 mo. During the same period, the cumulative incidence of virologic breakthrough was as low as 6% in patients with the both favorable predictors.

CONCLUSION: If tenofovir is not available, ADV/ETV combination could be considered in ETV-resistant patients with low HBV DNA titers, and may be continued if IVR-3 is achieved.

• Adefovir
• Chronic hepatitis B
• Entecavir
• Lamivudine
• Resistance

• Adenine/analogs & derivatives
• Adenine/therapeutic use
• Adult
• Aged
• Antiviral Agents/therapeutic use
• DNA, Viral/blood
• Drug Resistance, Viral
• Drug Therapy, Combination
• Female
• Guanine/analogs & derivatives
• Guanine/therapeutic use
• Hepatitis B, Chronic/blood
• Hepatitis B, Chronic/drug therapy
• Humans
• Lamivudine/therapeutic use
• Male
• Middle Aged
• Organophosphonates/therapeutic use
• Viral Load
• Young Adult

• chronic hepatitis B
• entecavir
• partial virological response
• switch
• tenofovir

• antiviral drug resistance
• genotypic resistance testing
• hepatitis B virus
• nucleos(t)ide analogs

The hepatitis B virus (HBV) is a global public health problem with more than 240 million people chronically infected worldwide, who are at risk for end-stage liver disease and hepatocellular carcinoma. There are an estimated 600000 deaths annually from complications of HBV-related liver disease. Antiviral therapy with nucleos/tide analogs (NA) targeting the HBV polymerase (P) can inhibit disease progression by long-term suppression of HBV replication. However, treatment may fail with first generation NA therapy due to the emergence of drug-resistant mutants, as well as incomplete medication adherence. The HBV replicates via an error-prone reverse transcriptase leading to quasispecies. Due to overlapping open reading frames mutations within the HBV P can cause concomitant changes in the HBV surface gene (S) and vice versa. HBV quasispecies diversity is associated with response to antiviral therapy, disease severity and long-term clinical outcomes. Specific mutants have been associated with antiviral drug resistance, immune escape, liver fibrosis development and tumorgenesis. An understanding of HBV variants and their clinical relevance may be important for monitoring chronic hepatitis B disease progression and treatment response. In this review, we will discuss HBV molecular virology, mechanism of variant development, and their potential clinical impact.

• Molecular virology
• Genetic heterogeneity
• Quasispecies
• Drug resistance
• Immune escape
• Viral lymphotropism
• Hepatitis B virus

• Acute hepatitis B
• Hepatitis B virus
• Immune-escape mutations
• preC/C mutations
• preS/S mutations

• Hepatitis B virus
• Mutation
• Quasispecies

Studies are limited regarding the association between the quantity of hepatitis virus B (HBV) DNA loads in serum and peripheral blood mononuclear cells (PBMCs) in patients with drug resistance and few studies focus on the mutational pattern of the polymerase gene of HBV in PBMCs of patients with drug resistance. The aim of the present study was to investigate the association between the quantity of HBV DNA loads in serum and PBMCs in patients with lamivudine (LAM) or telbivudine (LdT) resistance and to explore the mutational pattern of the polymerase gene of HBV in PBMCs of these patients. A total of 51 patients underwent antiviral therapy with LAM or LdT for at least half a year. The present study applied quantitative polymerase chain reaction for the quantification of total HBV DNA, and direct sequencing was used to detect the mutation. In total, 31 patients (60.78%) were detected to have drug resistance. The mean serum HBV DNA levels were significantly higher than the HBV DNA levels of PBMCs, whether in patients with LAM or LdT resistance. The PBMCs HBV DNA loads were correlated with the serum HBV DNA loads in the two groups. Three and two mutational patterns were found in the serum of patients with LAM and LdT resistant, respectively. In total, 85.71% of patients with LAM resistance and 75.00% of patients with LdT resistance presented the same mutational pattern in paired PBMCs and serum. The HBV DNA levels in the PBMCs of patients with LAM or LdT resistance were significantly lower than those in serum and there were positive correlations between them. The majority of the mutational patterns of the polymerase gene of HBV DNA in PBMCs were the same as those in the paired serum. These findings may help to increase knowledge regarding HBV drug resistance.

• hepatitis B virus
• hepatitis B virus DNA
• lamivudine
• mutation pattern
• peripheral blood mononuclear cells
• resistance
• telbivudine

• Hepatitis B virus
• Liver transplantation
• Prophylaxis
• Recurrence

Assessment of therapeutic response is important for monitoring the prognosis and to take decision for cessation of nucleoside analogues therapy in chronic hepatitis B patients. In addition to serum alanine aminotransferase (ALT), hepatitis B virus (HBV) deoxyribonucleic acid (DNA) load and HBeAg status, identification of molecular markers associated with host immune response would be essential to assess therapeutic response. In this regard the current study was performed with the aim to detect expression of platelet endothelial cell adhesion molecule (PECAM)-I gene in peripheral blood monocytes (PBMCs) of treated chronic hepatitis B patients and also to correlate expression of this gene with serum HBV DNA load and serum ALT levels.

The study analyzed 60 chronic hepatitis B (CHB) patients, including 30 untreated and 30 nucleoside analogs treated and 10 healthy controls. PECAM-1 gene expression/ transcripts were detected by conventional RT-PCR.

The expression PECAM-1 mRNA in the PBMCs of CHB patients was significantly higher in untreated (3.17 ± 0.75) than the treated patients (1.64 ± 0.29) (p < 0.01). Expression of PECAM-1 was positively correlated with serum ALT levels of both untreated (r = 0.580) and treated (r = 0.566) CHB patients. Moreover, in both untreated and treated groups, these gene expressions were positively correlated to serum HBV DNA load with the correlation coefficient r = 0.545 and r = 0.591 respectively.

PECAM-1 may be used as a biomarker for assessment of inflammatory activity as well as therapeutic response in CHB patients.

How to cite this article: Sultana N, Tabassum S, Munshi SU, Hossain M, Imam A. Nucleoside Analog-treated Chronic Hepatitis B Patients showed Reduced Expression of PECAM-1 Gene in Peripheral Blood Mononuclear Cells in Bangladesh. Euroasian J Hepato-Gastroenterol 2014;4(2):87-91.

• CD31
• Conventional RT-PCR
• NA therapy.
• PBMC
• PECAM-1

Hepatitis B virus (HBV) infection is a major cause of acute and chronic hepatitis, and of its long-term complications. It is the most variable among DNA viruses, mostly because of its unique life cycle which includes the activity of error-prone enzyme, reverse transcriptase, and the very high virion production per day. In last two decades, numerous research studies have shown that the speed of disease progression, reliability of diagnostic methods and the success of antiviral therapy and immunization are all influenced by genetic variability of this virus. It was shown that mutations in specific regions of HBV genome could be responsible for unwanted clinical outcomes or evasion of detection by diagnostic tools, thus making the monitoring for these mutations a necessity in proper evaluation of patients. The success of the vaccination programs has now been challenged by the discovery of mutant viruses showing amino acid substitutions in hepatitis B surface antigen (HBsAg), which may lead to evasion of vaccine-induced immunity. However, the emergence of these mutations has not yet raised concern since it was shown that they develop slowly. Investigations of HBV genetic variability and clinical implications of specific mutations have resulted in significant advances over the past decade, particularly in regard to management of resistance to antiviral drugs. In the era of drugs with high genetic barrier for resistance, on-going monitoring for possible resistance is still essential since prolonged therapy is often necessary. Understanding the frequencies and clinical implications of viral mutations may contribute to improvement of diagnostic procedures, more proper planning of immunization programs and creating the most efficient therapeutic protocols.

• Hepatitis B virus
• Hepatitis B virus variability
• Mutation
• Drug resistance
• Vaccine escape

• Acute Disease
• Antiviral Agents/therapeutic use
• Drug Resistance, Viral/genetics
• Genotype
• Hepatitis B/diagnosis
• Hepatitis B/drug therapy
• Hepatitis B/virology
• Hepatitis B Antigens/genetics
• Hepatitis B virus/drug effects
• Hepatitis B virus/genetics
• Hepatitis B virus/immunology
• Hepatitis B virus/pathogenicity
• Hepatitis B, Chronic/virology
• Humans
• Mutation
• Phenotype
• Trans-Activators/genetics
• Treatment Outcome
• Viral Core Proteins/genetics
• Viral Regulatory and Accessory Proteins

• chronic hepatitis B
• genotype
• hepatitis B virus
• nucleos(t)ide analogs
• reverse transcriptase
• semi-nested PCR

The progress in treatment against hepatitis B virus (HBV) with the development of effective and well tolerated nucleotide analogues (NAs) has improved the outcome of patients with HBV decompensated cirrhosis and has prevented post-transplant HBV recurrence. This review summarizes updated issues related to the management of patients with HBV infection before and after liver transplantation (LT). A literature search using the PubMed/Medline databases and consensus documents was performed. Pre-transplant therapy has been initially based on lamivudine, but entecavir and tenofovir represent the currently recommended first-line NAs for the treatment of patients with HBV decompensated cirrhosis. After LT, the combination of HBV immunoglobulin (HBIG) and NA is considered as the standard of care for prophylaxis against HBV recurrence. The combination of HBIG and lamivudine is related to higher rates of HBV recurrence, compared to the HBIG and entecavir or tenofovir combination. In HBIG-free prophylactic regimens, entecavir and tenofovir should be the first-line options. The choice of treatment for HBV recurrence depends on prior prophylactic therapy, but entecavir and tenofovir seem to be the most attractive options. Finally, liver grafts from hepatitis B core antibody (anti-HBc) positive donors can be safely used in hepatitis B surface antigen negative, preferentially anti-HBc/anti-hepatitis B surface antibody positive recipients.

• Hepatitis B virus
• Liver transplantation
• Hepatitis B virus immunoglobulin
• Antivirals
• Lamivudine
• Adefovir
• Entecavir
• Tenofovir
• Telbivudine
• Resistance

• Antiviral Agents/adverse effects
• Antiviral Agents/therapeutic use
• Carcinoma, Hepatocellular/diagnosis
• Carcinoma, Hepatocellular/surgery
• Carcinoma, Hepatocellular/virology
• Hepatitis B/complications
• Hepatitis B/diagnosis
• Hepatitis B/drug therapy
• Humans
• Liver Cirrhosis/diagnosis
• Liver Cirrhosis/surgery
• Liver Cirrhosis/virology
• Liver Neoplasms/diagnosis
• Liver Neoplasms/surgery
• Liver Neoplasms/virology
• Liver Transplantation/adverse effects
• Risk Factors
• Secondary Prevention
• Treatment Outcome
• Virus Activation/drug effects

Post-transplant malignancy is the major cause of later death of recipients after liver transplantation. Tumor recurrence after liver transplantation for patients with hepatocellular carcinoma in the end stage of cirrhosis has been frequently encountered. However, de novo hepatocellular carcinoma originating from the liver allograft has only rarely been reported. Here we reported a case of de novo hepatocellular carcinoma developed 2 years after living donor liver transplantation for hepatitis B-related liver cirrhosis with viral YMDD mutation. To the best of our knowledge, this is the first report of de novo hepatocellular carcinoma in a liver graft with recurrent hepatitis B virus infection after liver transplantation for hepatitis B-related liver cirrhosis with YMDD mutation. Moreover, the de novo cancer first presented as a lung mass with minimal liver involvement and was obscured by a pulmonary fungal infection.

To investigate pre-existing hepatitis B virus (HBV) quasispecies and the genotypic evolution of several variants.

From six patients with lamivudine (LAM) failure, serum samples at pretreatment, 6 months of LAM therapy, and virologic breakthrough were obtained. One hundred clones with HBV inserts in each patient were sequenced at each time point. Pretreatment serum samples were also analyzed from six patients who achieved good responses to LAM therapy.

Among the six patients with LAM failure, the analysis of 100 clones from patient 1 revealed the substitutions L180M in 1% of clones and V173L in 2% of clones. Patient 2 had substitutions of L80V, W153Q, and L180M. In patient 3, mutations conferring resistance to adefovir at V84I (5%), I169L (1%), and N236H (7%) and entecavir at S202G (2%) were detected. Patient 4 had mutations at T128N (1%), I169L (1%), V173L (2%), A181V (1%), and Q215H (1%). In patient 5, M204V/I was detected in 1% and 2% of clones, respectively. L80I and V173L were also identified in patient 6. In the six patients who responded to LAM, the degree of overall quasispecies was less than those with LAM failure.

Various HBV quasispecies associated with drug resistance existed before treatment, and the quasispecies dynamically changed through LAM therapy.

• Adefovir
• Entecavir
• Hepatitis B virus
• Lamivudine
• Quasispecies

• Alanine Transaminase/blood
• Disease Management
• Hepatitis B e Antigens/blood
• Hepatitis B e Antigens/immunology
• Hepatitis B virus/immunology
• Hepatitis B, Chronic/blood
• Hepatitis B, Chronic/diagnosis
• Hepatitis B, Chronic/therapy
• Humans
• Severity of Illness Index

Antiviral therapy using nucleos(t)ide analogues (NAs) is an effective control measure of chronic hepatitis B virus (HBV) infection; however they need long term treatment. Presence of drug-resistance mutations may get in the way of the efficacy of antiviral therapy. Our study was aimed at defining the prevalence of HBV drug-resistance in HBVrt region in a population of 147 HBsAg positive patients.

HBV/D has shown multiple types of HBVrt mutations both among treatment naïve (65.0%, 13 of 20 HBV/D) and treated patients (56.2%, 9 of 16 HBV/D). In additional, several mutations, with a suggested role in drug resistance, were detected among the treatment naïve as well as the treated patients. The mutations reported to be involved in reduction of drug effectiveness, was common among non-responders to therapy as well as among the naïve patients. Notably, classical antiviral resistance mutations (rtL80I/V-rtI169T-rtV173L-rtL180M-rtA181T/V/S-rtT184A/S/G/C-rtA194T-rtS202C /G/I -rtM204V/I-rtN236T-rtM250V) were not detected.

The prevalence of putative NAr mutations among non responders to therapy suggests that they might have role in reduced efficacy of currently available antivirals and requires further investigations.

• Drug-Resistance
• Hepatitis B Virus
• Iran
• Therapy

• Chronic hepatitis B
• KASL guidelines
• Management

• Acute Disease
• Adolescent
• Adult
• Aged
• Alanine Transaminase/blood
• Antiviral Agents/therapeutic use
• Asian People
• Aspartate Aminotransferases/blood
• Carcinoma, Hepatocellular/diagnosis
• Carcinoma, Hepatocellular/etiology
• Child
• Child, Preschool
• Coinfection/drug therapy
• DNA, Viral/blood
• Drug Resistance, Viral
• Drug Therapy, Combination
• Female
• Hepatitis B Surface Antigens/blood
• Hepatitis B e Antigens/blood
• Hepatitis B virus/genetics
• Hepatitis B, Chronic/complications
• Hepatitis B, Chronic/diagnosis
• Hepatitis B, Chronic/drug therapy
• Humans
• Immunosuppression Therapy
• Infectious Disease Transmission, Vertical/prevention & control
• Liver/pathology
• Liver/physiology
• Liver Cirrhosis/physiopathology
• Liver Neoplasms/diagnosis
• Liver Neoplasms/etiology
• Liver Transplantation
• Male
• Middle Aged
• Pregnancy
• Renal Dialysis
• Republic of Korea

• Adefovir
• Hepatitis B
• Lamivudine-resistant
• Telbivudine