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Journal of Perinatology : Official... Dec 2014Our objective was to provide a comprehensive review of the current knowledge regarding pregnancy and hepatitis B virus (HBV) or hepatitis C virus (HCV) infection as well... (Review)
Review
Our objective was to provide a comprehensive review of the current knowledge regarding pregnancy and hepatitis B virus (HBV) or hepatitis C virus (HCV) infection as well as recent efforts to reduce the rate of mother-to-child transmission (MTCT). Maternal infection with either HBV or HCV has been linked to adverse pregnancy and birth outcomes, including MTCT. MTCT for HBV has been reduced to approximately 5% overall in countries including the US that have instituted postpartum neonatal HBV vaccination and immunoprophylaxis with hepatitis B immune globulin. However, the rate of transmission of HBV to newborns is nearly 30% when maternal HBV levels are greater than 200 000 IU ml(-1) (>6 log10 copies ml(-1)). For these patients, new guidelines from the European Association for the Study of the Liver (EASL) and the Asian Pacific Association for the Study of the Liver (APASL) indicate that, in addition to neonatal vaccination and immunoprophylaxis, treating with antiviral agents such as tenofovir disoproxil fumarate or telbivudine during pregnancy beginning at 32 weeks of gestation is safe and effective in preventing MTCT. In contrast to HBV, no therapeutic agents are yet available or recommended to further decrease the risk of MTCT of HCV, which remains 3 to 10%. HCV MTCT can be minimized by avoiding fetal scalp electrodes and birth trauma whenever possible. Young women with HCV should be referred for treatment post delivery, and neonates should be closely followed to rule out infection. New, better-tolerated treatment regimens for HCV are now available, which should improve outcomes for all infected individuals.
Topics: Antiviral Agents; Breast Feeding; Cesarean Section; Contraindications; DNA, Viral; Female; Hepatitis B virus; Hepatitis B, Chronic; Hepatitis C, Chronic; Humans; Infectious Disease Transmission, Vertical; Lamivudine; Mass Screening; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Outcome; Telbivudine; Thymidine; Viremia
PubMed: 25233195
DOI: 10.1038/jp.2014.167 -
Alimentary Pharmacology & Therapeutics Jul 2008The long-term goals of therapy for chronic hepatitis B are to reduce serum HBV DNA to low or undetectable levels and ultimately reduce or prevent the development of... (Review)
Review
BACKGROUND
The long-term goals of therapy for chronic hepatitis B are to reduce serum HBV DNA to low or undetectable levels and ultimately reduce or prevent the development of cirrhosis and hepatocellular carcinoma.
AIM
To review the current treatment of chronic hepatitis B, with a focus on diagnosis and management of resistance and active management of suboptimal responses.
METHODS
A systematic review of the literature, with a focus on recent guidelines, was undertaken.
RESULTS
Among the six drugs licensed for the treatment of chronic hepatitis B in the US, the preferred agents in 2008 will include entecavir, peginterferon alfa-2a, possibly telbivudine, and tenofovir following licensure. When using an oral agent, a major focus of management is on the selection of a drug with high potency and low rate of resistance, and active on-treatment management to optimize therapy. Preventing the sequelae of antiviral drug resistance and appropriate management when resistance is initially detected are also the major focus of current management. The addition of an antiviral agent that is not cross-resistant is critical to restore suppression of viral replication.
CONCLUSIONS
Newer agents and modified treatment strategies, especially using combination therapy, hold promise to optimize the management of patients with chronic hepatitis B by achieving the high potency and the lowest rate of resistance.
Topics: Adenine; Antiviral Agents; Carcinoma, Hepatocellular; Deoxycytidine; Drug Resistance, Viral; Emtricitabine; Guanine; Hepatitis B virus; Hepatitis B, Chronic; Humans; Interferon alpha-2; Interferon-alpha; Lamivudine; Liver Cirrhosis; Nucleosides; Organophosphonates; Polyethylene Glycols; Pyrimidinones; Recombinant Proteins; Reverse Transcriptase Inhibitors; Telbivudine; Tenofovir; Thymidine; Virus Replication
PubMed: 18466358
DOI: 10.1111/j.1365-2036.2008.03731.x -
World Journal of Virology Dec 2012Antiviral treatment is the only option to prevent or defer the occurrence of hepatocellular carcinoma (HCC) in patients chronically infected with hepatitis B virus (HBV)... (Review)
Review
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.
PubMed: 24175223
DOI: 10.5501/wjv.v1.i6.174 -
Clinical Microbiology and Infection :... Feb 2014There are limited data comparing the clinical outcomes between telbivudine and entecavir. We consecutively enrolled 115 telbivudine-naive and 115 entecavir-naive chronic... (Comparative Study)
Comparative Study
There are limited data comparing the clinical outcomes between telbivudine and entecavir. We consecutively enrolled 115 telbivudine-naive and 115 entecavir-naive chronic hepatitis B patients, who were matched for age, sex, hepatitis B e antigen (HBeAg) status and cirrhosis, and treated for at least 2 years or less than 2 years but had developed resistance. Except for the rate of HBeAg seroconversion, which was similar, patients in the entecavir group had better clinical outcomes than those in the telbivudine group for alanine aminotransferase normalization (85.2% vs 78.4%, p <0.048), undetectable HBV DNA (96.5% vs 74.8%, p <0.001), and viral resistance (0.9% vs 21.7%, p <0.001) after 2 years of treatment, After applying roadmap or super-responders concepts, entecavir still had better outcomes than telbivudine in undetectable HBV DNA and viral resistance. The cumulative incidence of hepatocellular carcinoma development was similar between telbivudine-naive and entecavir-naive patients (p 0.565). In renal function analysis, there were significantly more patients with estimated glomerular filtration rate (eGFR) category improvement in both the telbivudine and entecavir groups at year 1 (p 0.006 and p 0.047, respectively). The rate of virological improvement was significantly higher with entecavir than with telbivudine after 2 years of treatment, whether applying the concepts of roadmap or super-responders. The incidence of hepatocellular carcinoma was similar between telbivudine and entecavir. Both telbivudine and entecavir were associated with eGFR improvement, especially in patients with renal insufficiency.
Topics: Adult; Aged; Alanine Transaminase; Antiviral Agents; Carcinoma, Hepatocellular; DNA, Viral; Drug Resistance, Viral; Drug-Related Side Effects and Adverse Reactions; Female; Glomerular Filtration Rate; Guanine; Hepatitis B, Chronic; Humans; Incidence; Liver Neoplasms; Male; Middle Aged; Retrospective Studies; Telbivudine; Thymidine; Treatment Outcome
PubMed: 23659493
DOI: 10.1111/1469-0691.12220 -
Health Technology Assessment... Oct 2009This paper presents a summary of the evidence review group (ERG) report into the clinical effectiveness and cost-effectiveness of telbivudine for the treatment of... (Review)
Review
This paper presents a summary of the evidence review group (ERG) report into the clinical effectiveness and cost-effectiveness of telbivudine for the treatment of chronic hepatitis B (CHB) in adults based upon a review of the manufacturer's submission to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal (STA) process. The submission's evidence came from one randomised controlled trial (RCT) (GLOBE) of reasonable methodological quality comparing telbivudine with lamivudine. One other RCT that appeared to meet the inclusion criteria was excluded from the submission. For the primary outcome of therapeutic response telbivudine was statistically superior to lamivudine at weeks 52 and 104 for hepatitis B e antigen (HBeAg)-positive patients, and at week 104 for HBeAg-negative patients. There were statistically significant differences in favour of telbivudine for some secondary outcomes at 2 years including hepatitis B virus (HBV) DNA reduction, HBV DNA non-detectability and alanine aminotransferase normalisation though not for HBeAg-positive patients. In HBeAg-positive patients there was no significant difference between treatment groups for HBeAg loss or seroconversion at any time point. The incidence of adverse events was similar between treatments. Two RCTs comparing entecavir with lamivudine were included in the indirect comparison; however, this was poorly conducted and the results should be treated with caution. The manufacturer developed two economic models to determine the cost-effectiveness of telbivudine. Evidence on the efficacy of telbivudine and lamivudine was taken from the GLOBE trial; efficacy of adefovir was based on assumption. There was a lack of critical assessment and assurance of the quality of the data used to populate the models. The manufacturer concluded that telbivudine is a cost-effective option compared with lamivudine using evidence from the viral load model [HBeAg-positive patients/HBeAg-negative patients: mean incremental cost 19,087 pounds/49,003 pounds, mean quality-adjusted life-year (QALY) gain 1.30/4.67, incremental cost-effectiveness ratio (ICER) 14,665 pounds/10,497 pounds per QALY]. Resubmitted results after a request for clarification by the ERG gave less favourable ICERs (HBeAg-positive patients/HBeAg-negative patients: mean incremental cost 23,983 pounds/41,910 pounds, mean QALY gain 1.56/2.07, ICER 15,377 pounds/20,256 pounds per QALY). The manufacturer concluded that telbivudine is a cost-effective option (on its own or followed by adefovir) for patients who have developed resistance to first-line telbivudine treatment; however, the presentation of the results was not ideal. In conclusion, although telbivudine was statistically superior to lamivudine for most antiviral outcomes, the difference was not clinically significant; in addition, the cost-effectiveness evidence for telbivudine presented in the manufacturer's submission was limited. The NICE guidance issued as a result of the STA states that telbivudine is not recommended for the treatment of chronic hepatitis B and that people currently receiving telbivudine should have the option to continue therapy until they and their clinicians consider it appropriate to stop.
Topics: Adult; Antiviral Agents; Cost-Benefit Analysis; Hepatitis B, Chronic; Humans; Nucleosides; Pyrimidinones; Telbivudine; Thymidine
PubMed: 19846025
DOI: 10.3310/hta13suppl3/04 -
The Journal of International Medical... Dec 2023Herein, we describe a case of acute rhabdomyolysis in a man in his early 50s undergoing haemodialysis and receiving the antiviral drug, telbivudine, for chronic... (Review)
Review
Herein, we describe a case of acute rhabdomyolysis in a man in his early 50s undergoing haemodialysis and receiving the antiviral drug, telbivudine, for chronic hepatitis B virus (HBV) infection. Following diagnosis by electromyography (EMG), magnetic resonance image (MRI) scans and laboratory data (i.e., elevated serum creatinine kinase (CK) and myoglobin) telbivudine was discontinued and the patient was treated with methylprednisolone. While his CK and myoglobin levels decreased rapidly, his muscle weakness and pain improved slowly. Learning points include: patients undergoing haemodialysis and concomitantly receiving antiviral treatment for HBV, should have their serum levels of CK and myoglobin monitored regularly; treatment with corticosteroids maybe required; relief from rhabdomyolysis-induced muscle weakness and pain may be slow due to nerve fibre damage.
Topics: Male; Humans; Telbivudine; Hepatitis B, Chronic; Antiviral Agents; Myoglobin; Thymidine; Rhabdomyolysis; Renal Dialysis; Pain; Muscle Weakness
PubMed: 38140948
DOI: 10.1177/03000605231222244 -
Clinical Microbiology and Infection :... Mar 2016There are few studies directly comparing the efficacy and safety of telbivudine and entecavir. The present prospective cohort study aimed to evaluate the long-term...
There are few studies directly comparing the efficacy and safety of telbivudine and entecavir. The present prospective cohort study aimed to evaluate the long-term efficacy and safety of these compounds in 196 hepatitis B e antigen (HBeAg)-positive patients with chronic hepatitis B for a median follow-up period of 172 weeks; 97 were treated with telbivudine and 99 were treated with entecavir. Patients showing suboptimal responses could also take adefovir at 24-48 weeks and all patients with viral breakthrough were started on adefovir. The 240-week cumulative proportions of patients showing undetectable hepatitis B DNA levels and serum alanine transaminase (ALT) normalization were similar in the two study groups. Viral breakthrough developed in 14% of the telbivudine group and in 2% of the entecavir group (p 0.002). Interestingly, the cumulative proportions of patients treated with entecavir and telbivudine showing HBeAg seroconversion were 12% versus 21% at 48 weeks (p 0.041), 15% versus 38% at 96 weeks (p 0.001), 24% versus 50% at 144 weeks (p 0.001), 33% versus 53% at 192 weeks (p 0.004) and 36% versus 53% at 240 weeks (p 0.005), respectively. Patients treated with telbivudine were therefore significantly more likely to show HBeAg seroconversion than those receiving entecavir and similar results were observed in study sub-groups matched for age, serum ALT, and HBV DNA levels. A safety analysis identified no differences between grade 3/4 creatine kinase elevations in the study groups and only telbivudine was associated with improved kidney function.
Topics: Adult; Aged; Antiviral Agents; Biomarkers; China; Female; Follow-Up Studies; Guanine; Hepatitis B; Hepatitis B e Antigens; Hepatitis B virus; Hepatitis B, Chronic; Humans; Male; Middle Aged; Telbivudine; Thymidine; Treatment Outcome; Viral Load; Young Adult
PubMed: 26548508
DOI: 10.1016/j.cmi.2015.10.024 -
Health Technology Assessment... Oct 2009This paper presents a summary of the evidence review group (ERG) report into the clinical and cost-effectiveness of entecavir for the treatment of chronic hepatitis B... (Review)
Review
This paper presents a summary of the evidence review group (ERG) report into the clinical and cost-effectiveness of entecavir for the treatment of chronic hepatitis B (CHB) in adults based upon a review of the manufacturer's submission to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal (STA) process. The submission's evidence came from five randomised controlled trials (RCTs), of good methodological quality and measuring a range of clinically relevant outcomes, comparing entecavir with lamivudine. After 1 year of treatment entecavir was statistically superior to lamivudine in terms of the proportion of patients achieving hepatitis B virus (HBV) DNA suppression, alanine aminotransferase (ALT) normalisation and histological improvement, but not in terms of the proportion of patients achieving hepatitis B e antigen (HBeAg) seroconversion. The incidence of adverse or serious adverse events was similar for both treatments. The results of the manufacturer's mixed treatment comparison (MTC) model to compare entecavir with the comparator drugs in nucleoside-naive patients were considered to be uncertain because of concerns over its conduct and reporting. For the economic evaluation the manufacturer constructed two Markov state transition models, one in HBeAg-positive and one in HBeAg-negative patients. The modelling approach was considered reasonable subject to some uncertainties and concerns over some of the structural assumptions. In HBeAg-positive patients the base-case incremental cost-effectiveness ratios (ICER) for entecavir compared with lamivudine and pegylated interferon alpha-2a were 14,329 pounds and 8403 pounds per quality-adjusted life-year (QALY) respectively. Entecavir was dominated by telbivudine. In HBeAg-negative patients the base-case ICERs for entecavir compared with lamivudine, pegylated interferon alpha-2a and telbivudine were 13,208 pounds, 7511 pounds and 6907 pounds per QALY respectively. In HBeAg-positive lamivudine-refractory patients entecavir dominated adefovir added to lamivudine. In one-way deterministic sensitivity analysis on all key input parameters for entecavir compared with lamivudine in nucleoside-naive patients, ICERs generally remained under 30,000 pounds per QALY. In probabilistic sensitivity analysis in nucleoside-naive HBeAg-positive patients the probability of the ICER for entecavir being below 20,000 pounds per QALY was 57%, 82% and 45% compared with lamivudine, pegylated interferon alpha-2a and telbivudine respectively. In nucleoside-naive HBeAg-negative patients the probabilities were 90%, 100% and 96% respectively. The manufacturer's lifetime treatment scenario for HBeAg-negative patients and the ERG's 20-year treatment scenario for HBeAg-positive patients increased the ICERs, particularly in the latter case. Amending the HBeAg-negative model so that patients with compensated cirrhosis would also receive lifetime treatment gave probabilities of entecavir being cost-effective at a willingness to pay of 20,000 pounds and 30,000 pounds of 4% and 40% respectively. The NICE guidance issued in August 2008 as a result of the STA states that entecavir is recommended as an option for the treatment of people with chronic HBeAg-positive or HBeAg-negative hepatitis B in whom antiviral treatment is indicated.
Topics: Adult; Antiviral Agents; Cost-Benefit Analysis; Guanine; Hepatitis B, Chronic; Humans; Randomized Controlled Trials as Topic
PubMed: 19846026
DOI: 10.3310/hta13suppl3/05 -
BMC Gastroenterology Apr 2017To evaluate the efficacy and safety of treating HBV-positive mothers with telbivudine in early and middle pregnancy to prevent mother-to-infant HBV transmission.
BACKGROUND
To evaluate the efficacy and safety of treating HBV-positive mothers with telbivudine in early and middle pregnancy to prevent mother-to-infant HBV transmission.
METHODS
The subject population comprised pregnant women with chronic hepatitis B (CHB; n = 188) from January 2013 to June 2015, with HBV DNA ≥1.0 × 10copies/mL and increased alanine aminotransferase levels. Groups A (n = 62) and B (n = 61) were treated with telbivudine starting at 12 weeks or 20-28 weeks after gestation, respectively. Telbivudine was discontinued at postpartum 12 weeks. Group C (n = 65) received no antiviral. All infants were vaccinated with hepatitis B immunoglobulin (200 IU) and HBV vaccine (20 with hepatitis B The maternal HBV DNA levels of the groups were compared. Mother-to-infant transmission of HBV was indicated by the presence of HBsAg in infants 7 months after birth.
RESULTS
Before treatment, the HBV DNA levels of the 3 groups were similar. Before delivery and 12 weeks after delivery, the HBV DNA levels of groups A and B were similar, but both were significantly lower than that of group C (P < 0.01, all). No infants in groups A and B were HBsAg-positive, but the infection rate of group C was 18.4% (P < 0.01). The HBV infection rate of infants was positively associated with the HBV DNA levels of the pregnant mothers.
CONCLUSION
Administration of telbivudine to HBV-infected mothers, started during early and middle pregnancy, completely blocked mother-to-infant HBV transmission.
TRIAL REGISTRATION
The study was registered retrospectively on Janurary 25 in 2016 at Chinese Clinical Trial Registry ( ChiCTR-OPC-16007899 ).
Topics: Adult; Alanine Transaminase; Antiviral Agents; DNA, Viral; Female; Hepatitis B Surface Antigens; Hepatitis B, Chronic; Humans; Infant, Newborn; Infectious Disease Transmission, Vertical; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Trimester, First; Pregnancy Trimester, Second; Telbivudine; Thymidine; Viral Load; Young Adult
PubMed: 28407735
DOI: 10.1186/s12876-017-0608-7 -
Journal of Viral Hepatitis Jul 2005In the last years, marked progress has been made in the treatment of chronic hepatitis B. The efficacy of lamivudine, the first nucleoside analogue available, is limited... (Review)
Review
In the last years, marked progress has been made in the treatment of chronic hepatitis B. The efficacy of lamivudine, the first nucleoside analogue available, is limited by the high incidence of resistance. Adefovir, which was recently approved has a comparable efficacy with a very low frequency of resistance. However, adefovir needs to be indefinitely administered as withdrawal of therapy is generally associated with reactivation and sustained response is uncommon. Recent large randomized controlled trials showed that PEG IFNs induce relatively high sustained response rates both in HBeAg positive and HBeAg negative chronic hepatitis B. So far, the combination of PEG IFN with lamivudine, used simultaneously, is disappointing in terms of short-term efficacy. However, long-term efficacy needs to be assessed and different schedules of combination (for example sequential) need to be evaluated. A number of nucleoside analogues, with favourable toxicity profiles and a promise of increased effectiveness against HBV, are at various stages of clinical development. Results of phase III trials of entecavir and emtricitabine confirmed their efficacy. However, while entecavir is associated with a low incidences of resistance, emtricitabine is associated with a relatively high incidence of resistance which limits its use as a monotherapy. The efficacy and safety of new and more potent drugs like telbivudine and clevudine need to be confirmed. The future of chronic hepatitis B therapy seems to be in the combination of different drugs. Ideally, the optimal drugs to combine would meet the following criteria: they should have different sites of action on HBV DNA replication, a potent antiviral effect, an excellent safety profile and they should induce a sustained response with a limited duration of therapy. Indeed, the concept of combination therapy has been recently developed in order to increase efficacy and to decrease the occurrence of viral resistance. However, so far few combinations have been evaluated. No combination therapy demonstrated a benefit as compared with monotherapy. More potent drugs and new combinations together with the understanding of the mechanisms of resistance to therapy are important challenges to improve the efficacy of treatment and decrease in the future the global burden related to chronic hepatitis B.
Topics: Animals; Antiviral Agents; Hepatitis B, Chronic; Humans
PubMed: 15985003
DOI: 10.1111/j.1365-2893.2005.00599.x