Therapy Of Chronic Hepatitis B Virus Infection Research Articles

CD8 cis-targeted IL-2 drives potent antiviral activity against hepatitis B virus.

CD8+ T cells are key antiviral effectors against hepatitis B virus (HBV), yet their number and function can be compromised in chronic infections. Preclinical HBV models displaying CD8+ T cell dysfunction showed that interleukin-2 (IL-2)-based treatment, unlike programmed cell death ligand 1 (PD-L1) checkpoint blockade, could reverse this defect, suggesting its therapeutic potential against HBV. However, IL-2's effectiveness is hindered by its pleiotropic nature, because its receptor is found on various immune cells, including regulatory T (Treg) cells and natural killer (NK) cells, which can counteract antiviral responses or contribute to toxicity, respectively. To address this, we developed a cis-targeted CD8-IL2 fusion protein, aiming to selectively stimulate dysfunctional CD8+ T cells in chronic HBV. In a mouse model, CD8-IL2 boosted the number of HBV-reactive CD8+ T cells in the liver without substantially altering Treg or NK cell counts. These expanded CD8+ T cells exhibited increased interferon-γ and granzyme B production, demonstrating enhanced functionality. CD8-IL2 treatment resulted in substantial antiviral effects, evidenced by marked reductions in viremia and antigenemia and HBV core antigen-positive hepatocytes. In contrast, an untargeted CTRL-IL2 led to predominant NK cell expansion, minimal CD8+ T cell expansion, negligible changes in effector molecules, and minimal antiviral activity. Human CD8-IL2 trials in cynomolgus monkeys mirrored these results, achieving a roughly 20-fold increase in peripheral blood CD8+ T cells without affecting NK or Treg cell numbers. These data support the development of CD8-IL2 as a therapy for chronic HBV infection.

Antiviral Therapy for Chronic HBV Infection With Persistently Normal Alanine Aminotransferase: Controversy and Consensus.

ALT is one of the most sensitive biochemical indexes to reflect liver injury. It is generally believed that hepatitis B virus (HBV) infected patients with normal ALT levels are in either immune tolerance or low replication stage of the natural history of hepatitis B, and there is no or only mild inflammation in liver tissue, so antiviral therapy is not recommended. However, chronic HBV-infected patients with normal ALT levels are not always in a stable state. A considerable number of patients will develop active hepatitis or occult progress to liver fibrosis, cirrhosis, and hepatocellular carcinoma. Therefore, whether antiviral therapy should be recommended for chronic HBV infection with normal ALT level has been a hot topic in clinical practice. In this paper, the definition of immune tolerance, the relationship between ALT and liver inflammation, and the benefits of antiviral therapy were reviewed, and we hope it will be helpful for clinicians to have a deeper understanding of whether antiviral therapy should be considered for chronic HBV infection with normal ALT.

Current status of the treatment of chronic hepatitis B

Chronic hepatitis B caused by hepatitis B virus (HBV) infection is a global public health issue. Antiviral therapy for chronic HBV infection plays a critical role, and the goal of antiviral therapy is mainly defined by virological, serological, and biochemical parameters. As the two types of antiviral drugs approved for marketing, both interferon and nucleos(t)ide analogues can alleviate liver inflammation and liver fibrosis and reduce the incidence rates of liver cirrhosis and hepatocellular carcinoma. However, the ideal goal of antiviral therapy is functional cure, which significantly improves the long-term outcome of chronic hepatitis B. The limitation of current treatment is that it can inhibit HBV replication, but cannot clear the virus, with low serological clearance rates of HBeAg and HBsAg. Development of new drugs with the goal of functional cure and evaluation of the synergistic and combined effects of existing drugs are important directions for HBV treatment and development.

Recent developments with advancing gene therapy to treat chronic infection with hepatitis B virus.

The available vaccine and therapies against hepatitis B virus (HBV) rarely eliminate chronic infection with the virus. High mortality resulting from complicating cirrhosis and hepatocellular carcinoma makes improving anti-HBV therapy an important priority. Recent advances with using gene therapy to counter HBV have potential and are the focus of this review. The stable replication-competent HBV intermediate comprising covalently closed circular DNA (cccDNA) is the template for expression of all viral genes. Inactivating cccDNA has thus been a focus of research aimed at achieving cure for HBV infection. Many studies have reported profound inhibition of replication of the virus using silencing and editing techniques. Therapeutic gene silencing with synthetic short interfering RNA is now in clinical trials. Ability to mutate and permanently inactivate cccDNA with engineered gene editors, such as those derived from CRISPR/Cas or TALENs, is particularly appealing but has not yet reached clinical evaluation. Gene silencing and gene editing potentially provide the means to cure HBV infection. However, achieving efficient delivery of therapeutic sequences, ensuring their specificity of action and progress with other antiviral strategies are likely to determine utility of gene therapy for chronic HBV infection.

High Incidence of Hepatitis B Viral Reactivation in Chronic Myeloid Leukemia Patients Treated with Tyrosine Kinase Inhibitors

Background: Reactivation of hepatitis B virus (HBV) is a well-recognized complication in patients with chronic HBV infection undergoing cytotoxic or immunosuppressive therapy. Currently, BCR-ABL1 tyrosine kinase inhibitors (TKIs) have been a standard of first-line treatment for chronic myeloid leukemia (CML) about last two decades. As there have been several case reports of HBV reactivation in CML patients treated with TKIs, the test for hepatitis B infection before initiating TKIs is recommended. Therefore, this study aimed to evaluate the risk of HBV reactivation in a large cohort of CML patients on TKIs treatment.Methods: We retrospectively reviewed the medical records of 1817 patients, who were diagnosed with CML and had available HBV serology between 2001 and 2017 from St. Mary's Hospital, Seoul, Korea.Results: Among 1817 patients, 76 patients (4.2%) were HBs-antigen (HBs-Ag) positive and 1741 (95.2%) were HBs-Ag negative. 302 patients (17.3%) of 1741 HBs-Ag negative patients were HBc-antibody positive indicating past infection of HBV. After exclusion of 7 patients who did not receive TKIs treatment, 69 patients were analyzed for HBV reactivation. The median age at diagnosis of CML was 42 (range 21-73) years and 44 (64%) were males. Median duration of follow-up from the recognition of HBs-Ag was 66.7 months (range, 2.4 - 192.7 months). Of 69 patients, a patient had been on antiviral therapy for chronic HBV infection before the diagnosis of CML. Eighteen patients (26% of 68) received antiviral prophylaxis prior to or concomitantly with the initiation of TKIs. Additional 4 patients were simultaneously initiated antiviral treatment with TKIs due to the evidence of active HBV infection such as the high titer of HBV DNA or elevated level of Alanine aminotransferase. Among 46 patients who did not receive antiviral prophylaxis, 12 patients (26%; 95% CI, 12-36%) eventually required antiviral treatment due to the development of active HBV hepatitis while on TKI therapy. HBV reactivation according to each TKI treatment was developed in 7 patients with imatinib, 2 patients in dasatinib, 1 patient in nilotinib, and 1 patient in radotinib therapy. One patient developed HBV reactivation permanently discontinued TKI therapy. Median time to HBV reactivation from CML diagnosis was 22.1 (range, 6.3-124.6 months) months. Median duration of antiviral therapy of 35 patients who received antiviral therapy was 38.2 months (95% CI, 25.7 ~ 50.7 months). 9 patients were off antiviral therapy at the last follow-up, 5 patients from prophylaxis group and 4 patients from treatment group. There was no difference in the duration of antiviral treatment between prophylactic and treatment groups. The initial choice of antiviral therapy as prophylaxis or treatment were entecavir for 14 (41% of 34), lamivudine for 8 (24%), tenofovir for 8 (24%), telbivudine for 3 (9%), and adefovir for 1 (3%).Conclusion: We evaluated HBV reactivation in a large cohort of HBs-Ag positive patients with CML from a single center, who received TKIs treatment. The reactivation rate of HBV was high at 26% without antiviral prophylaxis, which strongly support the routine screening of HBV serology prior to initiation of TKI therapy to identify HBs-Ag positive patients and the close monitoring of hepatic functions and HBV serology during TKI therapy. Given the high incidence of HBV reactivation with TKI treatment, concomitant antiviral prophylaxis with TKIs should be considered in HBs-Ag positive patients receiving TKI treatment. [Display omitted] DisclosuresKim:Ilyang: Research Funding; Novartis: Research Funding; BMS: Research Funding; Pfizer: Research Funding.

The Effectiveness and Cost-Effectiveness of Screening for and Vaccination Against Hepatitis B Virus among Migrants in the EU/EEA: A Systematic Review

Migrants from hepatitis B virus (HBV) endemic countries to the European Union/European Economic Area (EU/EEA) comprise 5.1% of the total EU/EEA population but account for 25% of total chronic Hepatitis B (CHB) infection. Migrants from high HBV prevalence regions are at the highest risk for CHB morbidity. These migrants are at risk of late detection of CHB complications; mortality and onwards transmission. The aim of this systematic review is to evaluate the effectiveness and cost-effectiveness of CHB screening and vaccination programs among migrants to the EU/EEA. We found no RCTs or direct evidence evaluating the effectiveness of CHB screening on morbidity and mortality of migrants. We therefore used a systematic evidence chain approach to identify studies relevant to screening and prevention programs; testing, treatment, and vaccination. We identified four systematic reviews and five additional studies and guidelines that reported on screening and vaccination effectiveness. Studies reported that vaccination programs were highly effective at reducing the prevalence of CHB in children (RR 0.07 95% CI 0.04 to 0.13) following vaccination. Two meta-analyses of therapy for chronic HBV infection found improvement in clinical outcomes and intermediate markers of disease. We identified nine studies examining the cost-effectiveness of screening for CHB: a strategy of screening and treating CHB compared to no screening. The median acceptance of HB screening was 87.4% (range 32.3–100%). Multiple studies highlighted barriers to and the absence of effective strategies to ensure linkage of treatment and care for migrants with CHB. In conclusion, screening of high-risk children and adults and vaccination of susceptible children, combined with treatment of CHB infection in migrants, are promising and cost-effective interventions, but linkage to treatment requires more attention.

Diagnosis and treatment of chronic hepatitis B and D. National consensus guideline in Hungary from 22 September 2017

Diagnosis and treatment of hepatitis B virus (HBV) and hepatitis D virus infection mean for the patient to be able to maintain working capacity, to increase quality of life, to prevent cancer, and to prolong life expectancy, while the society benefits from eliminating the chances of further transmission of the viruses, and decreasing the overall costs of serious complications. The guideline delineates the treatment algorithms from 22 September 2017 set by a consensus meeting of physicians involved in the treatment of these diseases. The prevalence of HBV infection in the Hungarian general population is 0,5-0,7%. The indications of treatment are based upon viral examinations (including viral nucleic acid determination), determinations of disease activity and stage (including biochemical, pathologic, and/or non-invasive methods), and excluding contraindications. To avoid unnecessary side effects and for a cost-effective approach, the guideline stresses the importance of quick and detailed virologic evaluations, the applicability of transient elastography as an acceptable alternative of liver biopsy in this regard as well as the relevance of appropriate consistent follow-up schedule for viral response during therapy. The first choice of therapy in chronic HBV infection can be pegylated interferon for 48 weeks or continuous entecavir or tenofovir therapy. The latter two must be continued for at least 12 months after hepatitis B surface antigen seroconversion. Lamivudine is no longer the first choice; patients currently taking lamivudine must switch if the response is inadequate. Appropriate treatment of patients taking immunosuppressive medications is highly recommended. Pegylated interferon based therapy is recommended for the treatment of concomitant hepatitis D infection. Orv Hetil. 2018; 159(Suppl 1): 24-37.

Effect of Nucleos(t)ide Analogue Therapy on Risk of Intrahepatic Cholangiocarcinoma in Patients With Chronic Hepatitis B

Chronic infection with hepatitis B virus (HBV) increases risk of intrahepatic cholangiocarcinoma (ICC), but it is not clear whether antiviral therapy reduces risk. We investigated the association between nucleos(t)ide analogue therapy and ICC risk. We performed a nationwide long-term cohort study using Taiwan's National Health Insurance Research Database to obtain data on 185,843 patients with chronic HBV infection from October 1, 2003 through December 31, 2012. We excluded patients with confounding disorders such as infection with hepatitis C virus, HIV, or other hepatitis-associated viruses; liver flukes; biliary stone diseases; cholangitis; congenital biliary anomalies; biliary tract surgeries; or cancer. We identified 10,062 patients who received nucleos(t)ide analogue therapy (the treated group), and used propensity scores to match them (1:1) with patients who received hepatoprotectants (the untreated group). Cumulative incidences of and hazard ratios (HRs) for ICC development were analyzed. The cumulative incidence of ICC was significantly lower in the treated group after 3 years of therapy (1.28%; 95% CI, 0.56-2.01) than in the untreated group (3.14%; 95% CI, 2.02-4.27) and after 5 years of therapy (1.53%; 95% CI, 0.73-2.33 vs 4.32% in untreated group; 95% CI, 2.96-5.6869). In multivariable regression analysis, nucleos(t)ide analogue therapy was independently associated with a reduced risk of ICC (HR, 0.44; 95% CI, 0.25-0.78; P= .005). Older age (HR 1.05 per year; 95% CI, 1.03-1.07) and cirrhosis (HR, 2.80; 95% CI, 1.52-5.1415) were independently associated with an increased risk of ICC. Sensitivity analyses verified the association between nucleos(t)ide analogue therapy and a reduced ICC risk. A nationwide long-term cohort study in Taiwan showed that nucleos(t)ide analogue therapy for chronic HBV infection is significantly associated with a reduced ICC risk.

Tenofovir in treatment of Iranian patients with chronic hepatitis B virus infection: An open-label case series.

Objective:Tenofovir is among the first-line treatments for chronic hepatitis B (CHB) virus infection. We evaluated the efficacy and safety of Tenofovir in treatment of Iranian patients with CHB.Methods:Forty treatment-native patients with CHB but without concurrent hepatitis C or human immunodeficiency virus infections were treated with Tenobiovir(™) 300 mg/day. The hepatitis B virus (HBV) DNA load, hepatitis B e antigen (HBe Ag), anti-hepatitis B e antibody (HBe Ab), liver enzymes, and creatinine were measured before and at least 3 months after the treatment.Findings:The mean age of patients was 38.1 ± 12.4 years and 65% of them were male. Seventeen (42.5%) patients were HBe Ag-positive and 15 (37.5%) patients had alanine aminotransferase (ALT) of two times above the normal. The HBV DNA load was significantly decreased after the treatment (P < 0.001). Twenty-seven (67.5%) patients had viral load of ≤2000 IU/ml and 22 (55%) patients had undetectable HBV DNA level after the treatment. Among positive HBe Ag patients, the HBe Ag became negative in 15 (88.2%) patients after the treatment and HBe Ab became positive in 3 (17.6%) patients. Liver enzymes’ levels were significantly decreased after the treatment (P <0.05) and ALT transaminase level became normalized in 86.7% (13 out of 15) of cases with baseline levels twice the normal.Conclusion:Treatment response rate to Tenofovir in Iranian patients with CHB was high. The virological and serological response rate and safety of Tenofovir in our population was comparable to other populations. Considering availability and costs, Tenobiovir(™) could be recommended as the first-line therapy of chronic HBV infection in Iran.

Mapping of histone modifications in episomal HBV cccDNA uncovers an unusual chromatin organization amenable to epigenetic manipulation

Chronic hepatitis B virus (HBV) infection affects 240 million people worldwide and is a major risk factor for liver failure and hepatocellular carcinoma. Current antiviral therapy inhibits cytoplasmic HBV genomic replication, but is not curative because it does not directly affect nuclear HBV closed circular DNA (cccDNA), the genomic form that templates viral transcription and sustains viral persistence. Novel approaches that directly target cccDNA regulation would therefore be highly desirable. cccDNA is assembled with cellular histone proteins into chromatin, but little is known about the regulation of HBV chromatin by histone posttranslational modifications (PTMs). Here, using a new cccDNA ChIP-Seq approach, we report, to our knowledge, the first genome-wide maps of PTMs in cccDNA-containing chromatin from de novo infected HepG2 cells, primary human hepatocytes, and from HBV-infected liver tissue. We find high levels of PTMs associated with active transcription enriched at specific sites within the HBV genome and, surprisingly, very low levels of PTMs linked to transcriptional repression even at silent HBV promoters. We show that transcription and active PTMs in HBV chromatin are reduced by the activation of an innate immunity pathway, and that this effect can be recapitulated with a small molecule epigenetic modifying agent, opening the possibility that chromatin-based regulation of cccDNA transcription could be a new therapeutic approach to chronic HBV infection.

Antiviral Therapy for Chronic Hepatitis B Virus Infection and Development of Hepatocellular Carcinoma in a US Population

Antiviral therapy could reduce the risk of hepatocellular carcinoma (HCC) among persons with chronic hepatitis B virus (HBV) infection. We evaluated the relationship between therapy for chronic HBV infection and HCC incidence using data from a longitudinal study of patients at 4 US healthcare centers. We analyzed electronic health records of 2671 adult participants in the Chronic Hepatitis Cohort Study who were diagnosed with chronic HBV infection from 1992 through 2011 (49% Asian). Data analyzed were collected for a median of 5.2 years. Propensity-score adjustment was used to reduce bias, and Cox regression was used to estimate the relationship between antiviral treatment and HCC. The primary outcome was time to event of HCC incidence. Of study subjects, 3% developed HCC during follow-up period: 20 cases among the 820 patients with a history of antiviral HBV therapy and 47 cases among the 1851 untreated patients. In propensity-adjusted Cox regression, patients who received antiviral therapy had a lower risk of HCC than those who did not receive antiviral therapy (adjusted hazard ratio, 0.39; 95% confidence interval, 0.27-0.56; P < .001), after adjusting for abnormal level of alanine aminotransferase. In a subgroup analysis, antiviral treatment was associated with a lower risk of HCC after adjusting for serum markers of cirrhosis (adjusted hazard ratio, 0.24; 95% confidence interval, 0.15-0.39; P < .001). In a separate subgroup analysis of patients with available data on HBV DNA viral load, treated patients with viral loads >20,000 IU/mL had a significantly lower risk of HCC than untreated patients with viral loads >20,000 IU/mL. In a large geographically, clinically, and racially diverse US cohort, antiviral therapy for chronic HBV infection was associated with a reduced risk for HCC.

Therapy for HBV Infection in Hemodialysis Patients: Is it Possible?

Despite the use of preventive measures, particularly hepatitis B virus (HBV) vaccine, and recent advances in antiviral therapy, chronic HBV infection has still remained a public health concern among infected dialysis patients because it results in an increased risk of morbidity and mortality [1]. However, Alavian et al. have shown that the prevalence of HBV infection among hemodialysis (HD) patients in Iran declined to 2.4 - 2.6% in 2005 [2][3]. Furthermore, the clinical course and natural history of HBV infection are different in dialysis and nondialysis patients, and it may lead to a unique clinical problem in dialysis subjects. In addition, limited data are available on the optimal therapy of chronic HBV infection in dialysis patients. Therefore, in this article we discuss whether antiviral therapy is possible in infected dialysis patients with HBV.

Immunosuppressive functions of hepatic myeloid-derived suppressor cells of normal mice and in a murine model of chronic hepatitis B virus

The immunosuppressive state of tumour-bearing hosts is attributable, at least in part, to myeloid-derived suppressor cells (MDSC). However, the role of MDSC in physiological conditions and diseases other than cancer has not been addressed. As the liver is a tolerogenic organ, the present study attempted to localize and assess functions of hepatic MDSC in a normal liver and in a murine model of chronic hepatitis B virus (HBV) infection. MDSC was identified in the liver of normal mice and HBV transgenic mice (TM) as CD11b(+) Gr1(+) cells by dual-colour flow cytometry. Highly purified populations of MDSC and their subtypes were isolated by fluorescence-activated cell sorting. The functions of MDSC and their subtypes were evaluated in allogenic mixed lymphocyte reaction (MLR) and hepatitis B surface antigen (HBsAg)-specific T cell proliferation assays. Normal mice-derived liver MDSC, but not other myeloid cells (CD11b(+) Gr1(-) ), suppressed T cell proliferation in allogenic MLR in a dose-dependent manner. Alteration of T cell antigens and impaired interferon-γ production seems to be related to MDSC-induced immunosuppression. In HBV TM, the frequencies of liver MDSC were about twice those of normal mice liver (13·6±3·2% versus 6·05±1·21%, n=5, P<0·05). Liver-derived MDSC from HBV TM also suppressed proliferative capacities of allogenic T cells and HBsAg-specific lymphocytes. Liver MDSC may have a critical role in maintaining homeostasis during physiological conditions. As liver MDSC had immunosuppressive functions in HBV TM, they may be a target of immune therapy in chronic HBV infection.

Clinical profile, genotype and management updates of hepatitis B virus.

Hepatitis B virus (HBV) is a well known agent of acute and chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. Around 400 million people worldwide carrier of HBV of which more than 250 million reside in Asia, and 1-2million people have died from it. It has a partially double-stranded DNA, having 3.2-kb genome size and replicate via reverse transcription of RNA intermediate. In the natural history or during the antiviral therapy of chronic HBV infection, seroconversion from HBeAg to anti-HBeAg is usually accompanied by a decrease in viral replication and remission of liver disease. Based on genomic sequence data HBV is classified into eight genotypes A-H and four major serotypes ayw, ayr, adw and adr on the basis of complete genome and S gene sequence analysis. Genotypes and serotypes are useful tools in understanding the epidemiology of HBV infection. HBV genotypes have distinct geographical distributions. The HBV variants appear during HBeAg seroconversion and they bring mutations in the precore region (PC) that prevent HBeAg synthesis. Another common HBeAg variant is the basal core promoter mutant (BCP) characterized by point mutation in the promoter of both HBeAg mRNA and core protein mRNA. The most frequent core promoter mutation is the double A1762T and G1764A nucleotide exchange, which results in a substantial decrease in HBeAg expression but enhanced viral genome replication. The approved antiviral drugs such as Interferon, lamivudine, adefovir dipivoxil, entecavir and telbivudine for purpose of treating chronic HBV infection is to prevent or stop the progression of liver injury by suppressing viral replication or eliminating infection. Sustained losses of viral markers of active viral replication (HBeAg and HBV DNA) are the standard end point of the therapies.

New globally faces of hepatitis B and C in the world.

Worldwide, infections with hepatitis B virus (HBV) and hepatitis C virus (HCV) have become a major cause of chronic hepatitis, cirrhosis and hepatocellular carcinoma (HCC) and the major global problems for public health in the world and Iran (1–3). HBV infection is the main cause of chronic liver disease in Iran (4) and the seroprevalence of HBV infection in Iran has been decreased during the last two decades (5). The main risk factor for HBV transmission was related to maternal-to-infantile transmission and the infantile vaccination with high coverage is the main cause for changes in epidemiology of HBV infection. But today, we have more risk factors for transmission in adulthood. The community contacts more in adolescence and the health policy makers should attend more for control of HBV infection. People awareness, risk factors modifications, harm reduction programmes in young addicted persons, vaccination against HBV in adults should be consider for control of HBV infection in future. We have less new cases, but we will have more cirrhotic cases and we need to consider the best therapy for prevention of HBV infection to end-stage phases. Therapy of HBV infection in which phase and which drugs are the debate. The goal of therapy in chronic hepatitis B (CHB) patients is sustained suppression of HBV viremia and decrease progression of liver disease to cirrhosis and HCC with the ultimate goal of improving survival. This can be pursued by maintaining constant inhibition of viral replication through a long term treatment with nucleos(t)ide analogs or by inducing, through the combined antiviral and immunomodulatory effects of interferon, a sustained immune response (6). Standard interferon is the oldest approved drug in therapy of HBV infection, but it has a limited response rate. Recently new published data have shown the better response with pegylated interferon in therapy of chronic HBV infection (7, 8). PEG-IFNα-2a has been licensed for the treatment of both HBeAg-positive and HBeAg-negative chronic HBV as a 48-week course, given by subcutaneous injection once weekly in a dosage of 180 mg. The main side effects of therapy with nucleos(t)ide analogs such as lamivudine, adefovir and entecavir, is emergence of resistance (9, 10). These events will decrease benefit of therapy with anti-viral agents. HBs Ag level in prediction of therapy response The main question was and is regarding how and when we can conclude the therapy in HBV infection is effective and we should continue or it is ineffective and we should discontinue it. During recent years serum HBsAg is hypothesized to be a marker for immunological response to therapy, independent of virological response as measured using HBV DNA levels, because of its correlation with intrahepatic HBV covalently closed circular (ccc) DNA, the main replicative template of HBV (11). HBsAg levels appear to differentiate patients in the inactive carrier state from those with active disease or from inactive carriers with a high probability of subsequent relapse. Furthermore, recent studies have shown that on- treatment HBsAg levels are predictive of a durable off-treatment response to peginterferon (PEG-IFN), and can accurately identify non-responders early during therapy, both in HBeAg-positive, and HBeAg-negative patients. Among those who underwent HBsAg loss within 6 years of follow-up, serum HBsAg levels were a better predictor than HBV DNA levels. Low serum levels of HBsAg, alone or in combination with HBV DNA levels, 1 year after HBeAg seroconversion can predict HBsAg loss in patients with HBV infection (12). Currently, multiple diagnostic assays are available for quantification of HBsAg. That we should use the validate method for diagnosis.

Review article: Hepatitis B and dialysis

The incidence of hepatitis B virus (HBV) infection in dialysis populations has declined over recent decades, largely because of improvements in infection control and widespread implementation of HBV vaccination. Regardless, outbreaks of infection continue to occur in dialysis units, and prevalence rates remain unacceptably high. For a variety of reasons, dialysis patients are at increased risk of acquiring HBV. They also demonstrate different disease manifestations compared with healthy individuals and are more likely to progress to chronic carriage. This paper will review the epidemiology, modes of transmission and diagnosis of HBV in this population. Prevention and treatment will be discussed, with a specific focus on strategies to improve vaccination response, new therapeutic options and selection of patients for therapy.

Management of Chronic Hepatitis B in Children

Hepatitis B virus (HBV) infection is a worldwide problem and can cause acute liver failure, acute hepatitis, chronic hepatitis, liver cirrhosis, and liver cancer. In areas of high prevalence such as in Asia, Africa, southern Europe, and Latin America, the hepatitis B surface antigen positive rate ranges from 2% to 20%.In endemic areas, HBV infection occurs mainly during infancy and early childhood. Mother-to-infant transmission accounts for approximately half of the chronic HBV infections. In contrast to infection in adults, HBV infection during early childhood results in a much higher rate of persistent infection and long-term serious complications such as liver cirrhosis and HCC.Three phases of chronic hepatitis B have been identified: the immune-tolerant phase, the immune-active phase, and the inactive hepatitis B phase. These phases of infection are characterized by variations in viral replication, hepatic inflammation, spontaneous clearance, and response to antiviral therapy.The optimal goal of antiviral therapy for chronic HBV infection is to eradicate HBV and to prevent its related liver complications. However, due to the limited effect of available therapies in viral eradication, the goal of treatment is to reduce viral replication, to minimize liver injury, and to reduce infectivity. In this review the current recommendations for monitoring and treating chronic HBV infection in children are reviewed.

Novel Lamivudine Resistance

With great interest I have read and appreciate the recent publication by Warner and coworkers (6). Those authors described the effects of a novel mutation in the hepatitis B virus (HBV) polymerase reverse transcriptase domain, namely, the rtL80I substitution that confers resistance to lamivudine. This mutation was initially described to occur in Japanese patients with lamivudine treatment failure, but its impact remained to be investigated (3). Not surprisingly, based on molecular modeling of the reverse transcriptase domain of the HBV polymerase, Warner et al. (6) concluded that this novel mutation is not located in the supposed drug binding domain. Nevertheless, the fact that rtL80I is able to mediate lamivudine resistance also in vitro, as shown by phenotyping, is of high general interest and deserves foremost attention for two reasons. First, the fact that mutations in the periphery of the nucleos(t)ide binding site may lead to resistance has to be taken into account in all future resistance testing approaches. Second, the observation by Warner and colleagues (6) may be true not only for lamivudine but also for other drugs and may thus have an impact also on further therapy and monitoring regimens, mainly as the therapy for chronic HBV infection is becoming more and more complex (1). Especially for adefovir, it is believed that besides mutations, host factors such as failures in liver uptake, defective or nonappropriate esterases, and phosphorylation failures may also confer resistance to the drug (5). Yet, although extensively discussed, novel mutations (e.g., see references 2 and 4) or mutations in the periphery of the nucleos(t)ide binding site have been taken into account only marginally or even disbelieved (5). Based on the observations of Warner et al., investigators should systematically check as to whether new or unexpected mutation patterns in the nucleos(t)ide binding site in concert with or even without mutations in the periphery lead to resistance or predispose to resistance to antivirals.

Hepatitis B Virus: Something Old, Something New

Hepatitis B Virus: Something Old, Something New

Management of chronic hepatitis B virus infection: Current perspectives for the nurse practitioner

To address the clinical management of chronic hepatitis B virus (HBV) infection. Studies from the National Library of Medicine that examine the natural history, prevention, and antiviral therapy of chronic HBV infection, with emphasis on recent studies. Chronic infection with HBV is a frequent cause of cirrhosis, liver cancer, and liver-related mortality worldwide. Strategies to prevent infection, screen for liver cancer in HBV carriers, and treat chronic hepatitis B are all important in managing this disorder. Much can be done to prevent and treat infection. Both classes of drugs to treat hepatitis B, nucleoside analogues and interferons, have advantages and disadvantages. Selection of therapy should be based on biochemical, histological, and virological parameters as well as consideration of several practical issues.