Antigen-positive Patients Research Articles

Antiviral treatment to prevent chronic hepatitis B or C-related hepatocellular carcinoma

Antiviral treatment is the only option to prevent or defer the occurrence of hepatocellular carcinoma (HCC) in patients chronically infected with hepatitis B virus (HBV) or hepatitis C virus (HCV). The approved medication for the treatment of chronic HBV infection is interferon-α (IFNα) and nucleos(t)ide analogues (NAs), including lamivudine, adefovir dipivoxil, telbivudine, entecavir and tenofovir disoproxil fumarate. IFNα is the most suitable for young patients with less advanced liver diseases and those infected with HBV genotype A. IFNα treatment significantly decreases the overall incidence of HBV-related HCC in sustained responders. However, side effects may limit its long-term clinical application. Orally administered NAs are typically implemented for patients with more advanced liver diseases. NA treatment significantly reduces disease progression of cirrhosis and therefore HCC incidence, especially in HBV e antigen-positive patients. NA-resistance due to the mutations in HBV polymerase is a major limiting factor. Of the NA resistance-associated mutants, A181T mutant significantly increases the risk of HCC development during the subsequent course of NA therapy. It is important to initiate treatment with NAs that have a high genetic barrier to resistance, to counsel patients on medication adherence and to monitor virological breakthroughs. The recommended treatment for patients with chronic HCV infection is peg-IFN plus ribavirin that can decrease the occurrence of HCC in those who achieve a sustained virological response and have not yet progressed to cirrhosis. IFN-based treatment is reserved for patients with decompensated cirrhosis who are under evaluation of liver transplantation to reduce post-transplant recurrence of HCV. More effective therapeutic options such as direct acting antiviral agents will hopefully increase the response rate in difficult-to-treat patients with HCV genotype 1. However, the risk of HCC remains in cirrhotic patients (both chronic HBV and HCV infection) if treatment is initiated after cirrhosis is established. Future research should focus on investigating new agents, especially for those patients with hepatic decompensation or post-transplantation.

Spectrum of hepatitis B infection in Southern India: A cross-sectional analysis

Background and Aim: Hepatitis B virus (HBV)-related liver disease is not an uncommon problem in India. There are very few reports on pattern of chronic HBV infection from South India. The aim of the present study was to determine the spectrum of chronic HBV infection among patients attending the liver clinic in a tertiary referral center. Materials and Methods: Hepatitis B surface antigen (HBsAg) positive patients registered in the liver clinic between July 2010 and March 2011 were included in the study. All patients had baseline liver function tests, serological markers for HBV infection (hepatitis B e antigen [HBeAg], anti-HBe, anti-HBc total, and anti-HBc IgG, and HBV DNA quantification), serum alpha-fetoprotein, and ultrasound. Based on the viral profile and transaminase levels and ultrasound findings, patients were categorized as immunotolerant, inactive carriers, immune clearance and reactivation phase, and chronic liver disease with or without hepatocellular carcinoma. Results: Majority of the patients were asymptomatic and incidentally detected during blood donation camps, master health checkup (MHC), or during initial screening. Almost 40% of patients were either in immune inactive phase or had features of chronic liver disease. In the immunotolerant phase (24 patients), women were a decade younger than their male counterparts. Alanine aminotransferase (ALT) levels were similar in both HBeAg-positive and negative patients. The mean HBV DNA values were significantly high in HBeAg-positive men and women. In the immune inactive phase (58 patients), there were only three patients who were HBeAg positive. The ALT levels were in the normal range. HBV DNA values were low or not detectable. Among patients with elevated ALT and HBV DNA levels (immune clearance/immune reactive) (fifty patients), the mean ALT levels were higher in HBeAg-negative patients. HBV DNA quantity was significantly high in patients who were HBeAg positive. Conclusion: A significant proportion of HBsAg-positive patients is in inactive or in immunotolerant phase and do not require treatment. Patients with elevated ALT and HBV DNA levels need further evaluation to categorize them into immune clearance or immune reactive phase.

Reassessing the Role for Lamivudine in Chronic Hepatitis B Infection: A Four-Year Cohort Analysis

BACKGROUND⁄ Lamivudine is readily available and inexpensive. Guidelines recommend other antiviral medications because they achieve superior virological suppression with less resistance. These data are based on clinical trial populations and may not be representative of typical hepatitis B virus (HBV) populations. The authors assessed lamivudine in maintaining long-term viral suppression in an adherent, frequently monitored, noninvestigational HBV-infected population. All HBV patients (n=369) between 2000 and 2010 were evaluated in a retrospective, single-centre study. Virological response was defined by complete suppression of HBV DNA (<400 copies⁄mL) and was assessed at six to 12 month intervals over four years. Enzymatic and serological outcomes, as well as treatment failures were assessed. Forty-seven patients (36 men; mean age 44 years, mean alanine aminotransferase level 123 U⁄L; METAVIR stage 3⁄4 [n=21], treatment naive [n=41]) received lamivudine 100 mg to 300 mg daily. The mean pretreatment viremia was 5.19 log10 copies⁄mL, and was above the limit of detection (>6.91 log10 copies⁄mL) in 11 patients (23%). The mean (± SD) dosing duration was 32±22 months. Virological suppression was achieved in 45 (96%) patients. Mean viremia declined to 3.06 log10 copies⁄mL (n=27) and 2.68 log10 copies⁄mL (n=18) at 12 and 48 months, respectively, with 78% and 88% with undetectable viremia at these time points, respectively. The mean alanine aminotransferase level declined to 31 U⁄L and 36 U⁄L at 12 and 48 months, respectively. Seven of 13 (54%) hepatitis B e antigen-positive patients seroconverted. The treatment failure rate was 11%. In a selected group of HBV patients, successful long-term viremia suppression was achieved with low treatment failure rates. With strict dosing adherence and monitoring for virological breakthrough, sustained virological suppression can be reliably achieved with lamivudine in carefully selected patients.

HBeAg and not genotypes predicts viral load in patients with hepatitis B in Denmark: A nationwide cohort study

Objective. To explore the influence of HBV genotype on viral load in patients with HBV infection, and to investigate the relation to gender, age and country of origin or antibodies against hepatitis Be antigen (anti-HBe). Materials. We investigated 1025 patients with hepatitis B virus infection in a nationwide study in Denmark. Results. Prevalence of genotypes were: 10.5% A, 17.3% B, 20.5% C, 45.7% D, 3.2% E, 0.6% F, 1.1% G and 1% had more than one genotype. Nearly 60% of patients with genotype A were from Africa, 82% and 93% with genotypes B or C were from East Asia, 62% with genotype D came from the Middle East and 91% with genotype E came from Africa. More women had genotypes B (p = 0.006) or C (p < 0.001) while more men had genotypes A (p = 0.015) or D (p < 0.001). Women with genotypes B and D were younger than men (p < 0.001, p = 0.026). Viral load differed in genotype A and D compared with B and C (p < 0.001), and between anti-HBe and hepatitis B e antigen (HBeAg) positive patients (median values 5.4 × 103 IU/ml and 7.4 × 107 IU/ml, respectively, p < 0.001). Viral load depended on the presence of HBeAg (p < 0.001; OR, 95% CI: 0.05, 0.03–0.07) in the adjusted analysis and was not affected by origin (p = 0.65), age (p = 0.12), gender (p = 0.06) or genotype (p = 0.10). Conclusion. HBeAg status and not HBV genotype influenced viral load in this nationwide study. HBeAg positive patients had median HBV-DNA levels 10,000 times higher than those anti-HBe positive across genotypes.

Evaluation of current treatment recommendations for chronic hepatitis B: A 2011 update

Guidelines for the treatment of chronic hepatitis B have been recently updated in the 2009 European Association for the Study of the Liver consensus statement, the 2008 US Panel, the 2008 Asian-Pacific consensus statement, and the 2009 American Association for the Study of Liver Disease practice guidelines. We sought to determine whether these guidelines identified patients who developed hepatocellular carcinoma (HCC) or who died of non-HCC liver-related deaths for antiviral therapy. The criteria described in the new treatment guidelines were matched to the database of 369 hepatitis B surface antigen-positive patients, in whom 30 developed HCC and 37 died of non-HCC liver-related deaths during a mean follow up of 84 months. Using criteria for antiviral therapy as stated by the four current guidelines, 19-30% of patients who died of non-HCC liver-related complications, and 23-53% of patients who developed HCC, would have been excluded for antiviral therapy. If baseline serum albumin levels of ≤ 3.5 g/dL or platelet counts of ≤ 130,000 mm(3) were included into the treatment criteria, then 85-94% of patients who developed liver-related complications would have been recommended for antiviral therapy. Also, the addition of precore A1896 mutants and basal core promoter T1762/A1764 mutants would have identified 98.5-100% of these patients. The updated treatment guidelines for hepatitis B still excluded patients who developed serious liver-related complications. The inclusion of baseline serum albumin and platelet counts to current criteria would have identified a majority of these patients for antiviral therapy. These tests should be included into hepatitis B treatment strategies.

Changes in hepatitis B virus DNA levels and liver function after transcatheter arterial chemoembolization of hepatocellular carcinoma

Reports concerning changes in hepatitis B virus (HBV) status and liver function in hepatocellular carcinoma (HCC) during or after transcatheter arterial chemoembolization (TACE) have been rare and the results inconsistent. The objective of this retrospective study was to evaluate these parameters in a large cohort of HBV-related HCC patients. One hundred and seventy-two hepatitis B surface antigen positive HCC patients with Child-Pugh grade A or B liver disease who underwent 228 sessions of TACE were enrolled, and related clinical and laboratory data were analyzed. In total, HBV reactivated in 33 (14.5%), remained stable in 152 (66.7%) and decreased in 43 (18.8%) sessions. Univariate analysis revealed that sex and HBV DNA levels correlated with changes in HBV DNA status after TACE, while hepatitis B e-antigen (HBeAg), prothrombin time and chemotherapeutic agents were marginally significant factors. Multivariate analysis demonstrated that the major factors that influenced the HBV DNA status were baseline HBV DNA levels(P = 0.0002) and HBeAg (P = 0.0387). A comparison of the post-TACE (30-90 days) liver function to the baseline revealed no significant differences. The reactivation group has the highest rate of exacerbation (12.1%) compared with the stable group (5.9%) and downregulation group (4.7%). HBV DNA changes after TACE included reactivated, decreased and stable HBV DNA levels. Although HBV reactivation did not necessarily result in exacerbation of liver damage and most HCC patients with Child-Pugh grade A and B tolerated TACE well, careful post-procedure monitoring and managing is needed.

Antipyretic and Analgesic Effects of Zaltoprofen for the Treatment of Acute Upper Respiratory Tract Infection: Verification of a Noninferiority Hypothesis Using Loxoprofen Sodium

A multicenter, placebo-controlled, double-dummy, randomized, parallel-group, double-blind study was conducted to verify the hypothesis of noninferiority for single-dose administration of zaltoprofen 160 mg, a nonsteroidal anti-inflammatory drug, compared with loxoprofen sodium 60 mg (loxoprofen), in terms of antipyretic and analgesic effects in patients with acute upper respiratory tract infection. The eligible 330 patients were assigned to one of 3 groups: zaltoprofen 160 mg, loxoprofen 60 mg and placebo. The analysis set consisted of 322 patients. Antipyretic effects were assessed by measuring body temperature, and analgesic effects were evaluated using a visual analog scale (VAS) for 4 h under the control of study staff. A detection kit for influenza virus A and B antigens was used to determine the presence of influenza virus infection. Compared with immediately before administration and with the placebo group, significant decreases in body temperature and summary VAS pain scores were noted in both the zaltoprofen and loxoprofen groups at 4 h after drug administration. Based on the degree of decrease in body temperature and the summary VAS pain scores up to 4 h after administration, noninferiority in terms of antipyretic and analgesic effects of zaltoprofen compared with those of loxoprofen was confirmed after single administration. Similar antipyretic and analgesic effects were also confirmed in influenza virus antigen-positive patients (73 patients). No clinical concerns were identified regarding safety. Zaltoprofen and loxoprofen are confirmed to be safe and useful for patients with acute upper respiratory tract infection, including those with influenza infection.

Circulating microRNAs in hepatitis B virus–infected patients

MicroRNAs (miRNAs) are stably present in human serum. The relationship between circulating miRNAs and hepatitis B virus (HBV) infected liver disease has not been previously reported. Applied Biosystems array-based miRNA expression profiling was performed on pooled sera obtained from identified groups of chronic asymptomatic carriers (ASC), patients with chronic hepatitis B (CHB) and HBV-associated acute-on-chronic liver failure (ACLF), as well as healthy controls (HC). Nine miRNAs were verified in more clinical samples by RT-PCR. The correlation between miRNAs expression and the relationship between miRNA levels and clinical characteristics was analysed. Results showed that circulating miRNAs were detected in all disease and control samples, and their numbers increased with symptom severity, from 37 in HC, 77 in ASC, 101 in CHB, to 135 in ACLF. The expression levels of most miRNAs were also up-regulated in HBV-infected patients when compared to HC. Expression of the liver-specific miR-122 was significantly up-regulated in HBV-infected patients. Concomitant regulation of miRNAs not in clusters was disrupted by HBV infection. However, such disruption was not observed for miRNAs in paralogous clusters. Furthermore, the level of miRNAs in the CHB serum was up-regulated most in hepatitis B e antigen-positive patients. The expression levels of miR-122 and miR-194 correlated negatively with the age of patients with CHB or ACLF. Functional analysis showed that miR-122 could inhibit HBV replication in Huh7 and HepG2 cells. In all, our study revealed that a number of miRNAs were differentially expressed during HBV infection and underscored the potential importance of miR-122 in the infection process.

Further Analysis Is Required to Identify an Early Stopping Rule for Peginterferon Therapy That Is Valid for All Hepatitis B e Antigen–Positive Patients. Δ

Further Analysis Is Required to Identify an Early Stopping Rule for Peginterferon Therapy That Is Valid for All Hepatitis B e Antigen–Positive Patients. Δ

Further Analysis Is Required to Identify an Early Stopping Rule for Peginterferon Therapy That Is Valid for All Hepatitis B e Antigen–Positive Patients *†#

Further Analysis Is Required to Identify an Early Stopping Rule for Peginterferon Therapy That Is Valid for All Hepatitis B e Antigen–Positive Patients *†#

Surveillance and Treatment Protocols to Detect and Treat Hepatitis B Virus Reactivation in Hepatitis B Surface Antigen–Negative/Antibody to Hepatitis B Core Antigen–Positive Patients Receiving Chemotherapy for Onco-Hematologic Malignancies

TO THE EDITOR: We read with interest the article by Niitsu et al, and we compliment the authors for having focused their attention on the group of hepatitis B surface antigen–negative/antibody to hepatitis B core antigen–positive patients who are undergoing chemotherapy for onco-hematologic malignancies and who are at high risk for hepatitis B reactivation, especially if receiving rituximab-based protocols. In this setting, the risks of hepatitis B virus (HBV) reactivation and development of difficult-to-treat acute hepatitis characterized by high mortality rates need to be clarified, and appropriate screening and managing protocols should be developed. However, some specific questions regarding the article do arise. What is the cost of monthly dosing of HBV-DNA and the antibody to the hepatitis B surface antigen titer? Has the cost-effectiveness profile of this approach been addressed or compared with alternative strategies? What HBV-DNA levels were detected at reactivation? It would be interesting to provide this information, given that the decision to use a high-potency/high-genetic barrier antiviral such as entecavir to treat low-level HBV-DNA reactivation might be excessive. Actually, in patients with reactivation that is characterized by low levels of HBVDNA, lamivudine still presents an attractive treatment solution, given its relative availability, effectiveness, and low cost. The use of other, more potent antivirals such as entecavir could be considered for the management of patients with higher levels of HBV-DNA or acute hepatitis that develops as a result of HBV reactivation. In addition, the strategy of lamivudine prophylaxis in selected high-risk groups may present an additional option to be considered in the setting of immunosuppression during the treatment of onco-hematologic malignancies. Answers to these questions are crucial to define the applicability of the authors’ findings to everyday practice, especially in countries in which the availability of high-cost medications and surveillance protocols might hamper the feasibility of this approach. Definition of surveillance strategies for isolated patients with an antibody to the hepatitis B core antigen who are undergoing chemotherapy and are at risk for HBV reactivation, and how to manage the manifestations of reactivation, which range from isolated increases of HBV-DNA to severe acute hepatitis and liver failure, still remain debated issues.

The efficacy of lamivudine in the treatment of reactivation of chronic hepatitis B virus infection in patients on immunosuppressive therapy

Reactivation of chronic hepatitis B virus (HBV) infection often occurs in hepatitis B surface antigen (HBsAg) positive patients undergoing immunosuppressive or chemotherapy, but can also occur in HBsAg negative, anti-HB core positive patients. Treatment of HBV reactivation with lamivudin results in favourable outcome in the majority of patients. The aim of the authors was to show the effect of lamivudin therapy to HBV reactivation caused by immunosuppressive therapy. The first patient was a 35-year-old woman with chronic hepatitis B virus infection who underwent prednisolone therapy for pulmonal sarcoidosis. Four months after the beginning of the therapy she presented with jaundice and a significant increase in serum aminotransferase level. Liver biopsy showed chronic viral B hepatitis of strong activity in the stage of rapidly developed cirrhosis. The patient was treated with lamivudine with slow reduction of prednisolone doses, which resulted in full clinical and biochemical recovery. The second patient was a 40-year-old HBsAg negative female with a previous history of resolved acute B hepatitis who received chemotherapy for non-Hodgkin lymphoma. After the third cycle of chemotherapy a significant increase in aminotransferase level occurred, chemotherapy was discontinued, but aminotransferase level still increased. At that moment she was found to be HBsAg positive, and PCR analysis detected a high viral load. Lamivudine treatment resulted in the patient's recovery and allowed further chemotherapy. In case of the reactivation of chronic HBV infection during immunosuppressive therapy, it should be stopped and antiviral therapy should be immediately initiated. The use of lamivudine results in rapid suppression of serum HBV DNA, improves the outcome and enables the continuation of immunosuppressive and chemotherapy.

Intrafamilial occurrence of hepatitis B virus (HBV) infection and the profile of liver disease in close relatives of patients with HBV infection

<b>Aim:</b> To evaluate the occurrence of Hepatitis B surface antigen positivity in family members of HBsAg-positive patients, to assess the profile of HBV infection in them, to identify possible risk factors in a close family environment, and to evaluate the burden of liver disease in these family members.<br> <b>Materials and Methods:</b> All Hepatitis B surface antigen-positive patients who attended the Liver Clinic of the Gastroenterology Department of the Calicut Medical College, from January 2009 to December 2010, were studied. The index case was evaluated with HBeAg, anti HBeAb, HBV DNA, liver function tests (LFTs), ultrasonogram of the abdomen, and alpha fetoprotein, as also liver biopsy in indicated cases. The index patient was interviewed and a detailed history with special emphasis on probable risk factors was taken. All first-degree relatives and relatives staying in the same house of the index case were screened for HBsAg. The relatives who tested negative for the infection were advised HBV vaccination, while the relatives who tested positive were evaluated for disease activity using LFTs, HBeAg, anti-HBeAb, HBV DNA, ultrasonogram of abdomen, alpha fetoprotein, and biopsy as per indication.<br> <b>Results:</b> There were 376 index cases available for the study, 230 males (61.17%) and 146 females (38.83%). Male : Female ratio was 1.57 : 1. Mean age was 32.8 years (range 6-76). Seventy-six persons (20.21%) were detected to be HBsAg-positive during various preprocedural screenings, 42 (11.17%) were detected during medical checkup for jobs in gulf countries, and 30 (7.98%) were detected during screening for blood donation. Among the female patients, 88 (60.27%) were detected during antenatal screening. Ninety-six patients (25.53%) did not turn up after the initial visit.<br>Among the remaining 280 patients, 48 (17.14%) were HBeAg positive. LFT abnormalities were seen in 153 (54.64%) cases. Out of 280 patients, 46 (16.43%) had established cirrhosis and 10 (3.57%) had HCC. Twenty-one cases (7.5%) presented as acute hepatitis. Complete family screening was done for 173 (61.78%) index cases. Out of the 280 index cases, 47 (16.79%) patients were reluctant for family screening. <br>Among the 173 cases whose family members were screened, 95 (54.91%) had at least one family member who was HBsAg positive. Among the 95 index cases with at least one family member affected, 25 (26.31%) were HBeAg positive <b>.</b> On HBsAg screening of the relatives, it was found that brothers were affected in 45 (26.01%), sisters in 33 (19.08%), mothers in 18 (10.40%), fathers in 19 (10.98%), sons in nine (6.08%), and daughters in two (1.35%) cases. Ten (5.78%) index cases had second-degree relatives affected. Among a total of 173 index cases screened, 148 were married and among them 4.72% of the spouses were found to be HBsAg positive on screening.<br>A total of 1115 family members of the 173 index cases were screened, of whom 162 (14.53%) were HBsAg positive. Of the 162 family members who were HBsAg positive, complete evaluation to find the stage of liver disease was performed in 43 family members. Among them 31 (72.09%) had LFT abnormality, four (9.3%) had underlying cirrhosis, and one had HCC. Twelve cases (27.9%) were HBeAg positive. Even though HBV screening was advised for all family contacts of the index cases, there was not much enthusiasm among the patients to get their relatives screened.<br> <b>Conclusion:</b> The occurrence of hepatitis B positivity among family members of HBsAg-positive patients was 14.53% in our study. This prevalence was twenty-eight times more than the community prevalence of HBV infection in our population, which was earlier found to be 0.52% by our group. Brothers and sisters were the most commonly affected group, as against mothers who were positive for HBsAg, only 11.3%. Hence, the infection among siblings and parents may also be due to horizontal transmission. Index cases of 16.79% were totally reluctant for family screening due to various reasons like social stigma, high cost of the investigations, and reluctance to believe that they were having a problem, because they were asymptomatic. In view of the very high occurrence of HBV infection in family members, there is an urgent need for better counseling and vigorous screening of family members, to identify asymptomatic cases in the community and target this pool for curative as well as preventive measures.

Molecular analysis of HBV genotypes and subgenotypes in the Central-East region of Tunisia

BackgroundIn Tunisia, country of intermediate endemicity for Hepatitis B virus (HBV) infection, most molecular studies on the virus have been carried out in the North of the country and little is known about other regions. The aim of this study was to determine HBV genotype and subgenotypes in Central-East Tunisia. A total of 217 HBs antigen positive patients were enrolled and determination of genotype was investigated in 130 patients with detectable HBV DNA. HBV genotyping methods were: PCR-RFLP on the pre-S region, a PCR using type-specific primers in the S region (TSP-PCR) and partial sequencing in the pre-S region.ResultsThree genotypes (D, B and A) were detected by the PCR-RFLP method and two (D and A) with the TSP-PCR method, the concordance between the two methods was 93%. Sequencing and phylogenetic analysis of 32 strains, retrieved the same genotype (D and A) for samples with concordant results and genotype D for samples with discordant results. The sequences of discordant genotypes had a restriction site in the pre-S gene which led to erroneous result by the PCR-RFLP method. Thus, prevalence of genotype D and A was 96% and 4%, respectively. Phylogenetic analysis showed the predominance of two subgenotypes D1 (55%) and D7 (41%). Only one strain clustered with D3 subgenotype (3%).ConclusionsPredominance of subgenotype D7 appears to occur in northern regions of Africa with transition to subgenotype D1 in the East of the continent. HBV genetic variability may lead to wrong results in rapid genotyping methods and sequence analysis is needed to clarify atypical results.

Prevalence of hepatitis delta virus infection among hepatitis B virus surface antigen positive patients circulating in the largest province of Pakistan.

BackgroundHepatitis delta virus (HDV) and Hepatitis B virus (HBV) co-infection is well known to induce a spectrum of acute and chronic liver diseases which further advance to cirrhosis, fulminant hepatitis and hepatocellular carcinoma (HCC).AimThe aim of the present study was to determine the prevalence of hepatitis D virus super-infection among hepatitis B surface antigen (HBsAg) positive individuals in the highly populated province of Pakistan which is not well known.MethodsSera samples were subjected to HBsAg and anti-HDV screening and finally anti-HDV and HBsAg positive coinfected samples were used for HDV active RNA confirmation using nested polymerase chain reaction (PCR).ResultsOut of total 200 HBsAg positive samples by rapid device, 96 (48%) were also found reactive for HBsAg using enzyme linked immunosorbant assay (ELISA). Out of these HBsAg ELISA positive samples, 80 (88.8%) were anti-HDV ELISA positive which were then subjected to PCR. The amplification results further confirmed 24 (30%) samples to be HDV RNA positive. HDV super-infection was more common in male patients than female patients (81% VS 19%).ConclusionThe current study shows a high prevalence rate of HDV-HBV co-infection in Pakistan that tends to increase over time.

Kinetics of Hepatitis B Surface Antigen Decline During 3 Years of Telbivudine Treatment in Hepatitis B e Antigen–Positive Patients

The impact of prolonged direct antiviral therapy on hepatitis B surface antigen (HBsAg) levels in patients with chronic hepatitis B is poorly understood. We quantitatively assessed serum HBsAg levels during 3 years of telbivudine treatment, as well as their relationship with virologic and biochemical characteristics in 162 hepatitis B e antigen-positive patients who maintained undetectable serum hepatitis B virus (HBV) DNA long-term. Telbivudine treatment progressively reduced serum HBsAg levels (mean ± SD) from baseline (3.8 ± 0.6 log₁₀ IU/mL) to treatment week 24 (3.4 ± 0.7 log₁₀ IU/mL), treatment year 1 (3.3 ± 0.8 log₁₀ IU/mL), and treatment year 3 (3.0 ± 1.4 log₁₀ IU/mL) (P <0.0001). In this patient population, HBsAg loss was observed in nine (6%) of 162 patients through year 3. During the first year of treatment, three patterns of HBsAg decline were observed: rapid (≥ 1 log₁₀ IU/mL) in 32 patients, slow (0-1 log₁₀ IU/mL) in 74 patients, and steady levels in 56 patients. These findings were associated with different likelihoods of HBsAg loss during long-term telbivudine therapy. Eight of 32 patients with rapid HBsAg decline versus none of 56 patients with steady HBsAg levels achieved HBsAg loss at year 3 (P = 0.0024). HBV genotype was a significant determinant for HBsAg kinetics, with the fastest decline in genotype A patients. In patients with subsequent HBsAg loss, viral antigens were already undetectable in liver biopsy samples after 1 year of treatment. This was associated with markedly enhanced antiviral T cell reactivity. In patients who have effective suppression of viral replication during telbivudine treatment, a rapid decline in serum HBsAg levels during the first year may identify those with a greater likelihood of achieving HBsAg clearance.

Virologic Relapse following Treatment Induced Hepatitis B e Antigen Seroconversion in Chronic Hepatitis B (CHB) Patients

Purpose: The treatment goal for hepatitis B e antigen (HBeAg) positive patients is HBeAg seroconversion; however, this endpoint may not be durable following discontinuation of antiviral therapy. Our goal was to examine the rate of relapse in these patients. Methods: We retrospectively studied 52 consecutive CHB patients who achieved treatment-induced seroconversion (out of 396 patients treated for a median duration of 18 months). Our cohort consists of patients who maintained on therapy (n=28) and who discontinued therapy (n=24) between January 2001 and November 2009 at 2 community U.S. GI clinics. HBeAg seroconversion is defined as conversion of HBeAg-positive to HBeAg-negative and development of hepatitis B e antibody (anti-HBe). Virologic relapse is defined as reappearance of detectable HBV DNA by PCR testing (>60-100 IU/mL). Results: All patients were Asians and predominantly male (67%). Antiviral medication in which patients achieved seroconversion were lamivudine (17%), adefovir dipivoxil (40%), entecavir (35%), tenofovir (4%), and entecavir+tenofovir (4%). Median treatment duration after seroconversion to treatment discontinuation was 12 (1-41) months, in which all patients had undetectable serum HBV DNA (<60-100 IU/mL) and normal ALT (≤40 U/L). Following seroconversion, 71% of patients received another 12 months or more of therapy prior to discontinuation, 17% with another 6-12 months of therapy, and only 12% having less than 6 months of consolidation therapy. At time of seroconversion, patients who were maintained on therapy had significantly higher HBV DNA (1.36±1.97 vs. 0.33±0.86, p=0.03) and median ALT (33 [11-85] vs. 24 [8-60], p=0.04) compared to patients who discontinued therapy. Median age at seroconversion was similar in both cohorts (39 [19-58] vs. 38 [13-68], p=0.53). Virologic relapse occurred in 23 of 24 patients (96%) who discontinued therapy compared to 0 of 28 patients (0%) who maintained on treatment, p<0.0001. For patients who ceased treatment, the time to relapse was 3 (1-42) months. Conclusion: After achieving HBeAg seroconversion, the majority of patients who discontinued antiviral therapy relapsed with reappearance of viremia. Patients should be monitored closely for relapse when therapy is discontinued, even after HBeAg seroconversion.

Hepatitis B Virus Surface Antigen Variants Clustered Within Immune Epitopes in Chronic Hepatitis B Carriers from Hormozgan Province, South of Iran

Objective(s) The aim of this study was to characterize the hepatitis B virus surface protein genotypes and sequence variations among hepatitis B virus surface antigen (HBsAg) positive chronic patients in Hormozgan province, south of Iran. Materials and Methods A total of 8 patients enrolled in this study. The surface gene was amplified and directly sequenced. Genotypes and nucleotide/amino acid substitutions were identified compared to the sequences obtained from the database. Results All strains belonged to genotype D. Overall 77 “mutations” occurred at 45 nucleotide positions, of them, 44 (57.14%) were silent (no amino acid altering) and 33 (42.86%) were missense (amino acid changing). A number of 24 (80%) out of 30 amino acid changes occurred in different immune epitopes within surface protein, of which, 9 (30%) in B cell epitopes in 7 residues (2 occurred in “a” determinant region); 8 (42.1%) in T helper epitopes in 7 residues and 7 (10%) in 4 residues inside CTL epitopes. Conclusion Hepatitis B virus genome containing mutated immune epitopes no longer could be recognized by specific Tcells of the host immune surveillance and did not enhance anti-HBs production. This could led to the progression of chronicity of hepatitis B virus infection.

Change in Serum Hepatitis B Surface Antigen Level and Its Clinical Significance in Treatment-naïve, Hepatitis B e Antigen-positive Patients Receiving Entecavir

We investigated changes in hepatitis B surface antigen (HBsAg) level and its correlation with clinical outcomes in treatment-naive chronic hepatitis B (CHB) patients undergoing entecavir therapy. Among 51 hepatitis B e antigen (HBeAg)-positive treatment-naive CHB patients receiving entecavir for more than 1 year, 28 were enrolled. HBsAg levels were measured at baseline, 6 months, and 12 months after treatment using the Architect HBsAg QT assay (Abbott, dynamic; range: 0.05 to 125,000 IU/mL). Serum alanine aminotransferase, HBeAg, anti-HBe, and hepatitis B virus (HBV) DNA (Cobas Taqman: low detection limit 1.84 log10 copies/mL) were measured at baseline and every 3 months. The HBsAg response was defined as an HBsAg level that decreased more than 1 log10 IU/mL from baseline level at 12 months after entecavir treatment. Twenty-eight patients were treated for a median period of 21 months (range: 18 to 24 mo). Serum HBsAg level showed a mean of 4.0, 3.7, and 3.6 log10 IU/mL at pretreatment, 6, and 12 months, respectively, and declined significantly (P<0.001). Serum HBV DNA level showed a mean of 8.1, 3.1, and 2.4 log10 copies/mL at pretreatment, 6, and 12 months, respectively, and declined significantly (P<0.001). The decline in HBsAg level was significantly correlated with that of the HBV DNA level at 12 months from baseline (γ=0.391, P=0.044). Five patients showed an HBsAg response, and cumulative incidence of HBeAg loss at 1 year after entecavir treatment was 80% versus 30% in patients with an HBsAg response and those without, respectively (P=0.034). Monitoring changes in quantitative HBsAg level could be a useful parameter for assessing the response to entecavir therapy in HBeAg-positive treatment-naive CHB patients.

Correlation between quantitative serum HBsAg and HBV DNA test in Korean patients who showed high level of HBsAg

AimsThe authors aimed to identify the correlation between quantitative hepatitis B surface antigen (HBsAg) and hepatitis B virus (HBV) DNA in Korean patients with a high level of HBsAg (>250...