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The Brazilian Journal of Infectious... 2013The aim of this study was to conduct a cost-utility study of adefovir, entecavir, interferon alpha, pegylated interferon alpha, lamivudine and tenofovir for chronic... (Review)
Review
The aim of this study was to conduct a cost-utility study of adefovir, entecavir, interferon alpha, pegylated interferon alpha, lamivudine and tenofovir for chronic hepatitis B in the context of Brazilian Public Health Care System. A systematic review was carried out for efficacy and safety. Another review was performed to collect utility data and transition probabilities between health states. A Markov model was developed in a time horizon of 40 years with annual cycles for three groups of: HBeAg positive, HBeAg negative, and all patients. These strategies were compared to a fourth group that received no treatment. Discount rates of 5% were applied and sensitivity analyses were performed. Tenofovir offered the best cost-utility ratio for the three evaluated models: U$397, U$385 and U$384 (per QALY, respectively, for HBeAg positive, negative, and all patients). All other strategies were completely dominated because they showed higher costs and lower effectiveness than tenofovir. The sequence of cost-utility in the three models was: tenofovir, entecavir, lamivudine, adefovir, telbivudine, pegylated interferon alpha, and interferon alpha. In the sensitivity analysis, adefovir showed lower cost-utility than telbivudine in some situations. The study has some limitations, primarily related to the creation of scenarios and modeling. In this study, tenofovir presented the best cost-utility ratio. The results obtained in this study will be valuable in decision-making and in the review of the clinical protocol, mainly involving the allocation of available resources for health care.
Topics: Adenine; Antiviral Agents; Brazil; Cost-Benefit Analysis; Drug Therapy, Combination; Female; Guanine; Hepatitis B e Antigens; Hepatitis B, Chronic; Humans; Interferon-alpha; Lamivudine; Male; Markov Chains; Organophosphonates; Polyethylene Glycols; Recombinant Proteins; Tenofovir
PubMed: 23849851
DOI: 10.1016/j.bjid.2012.12.005 -
Food Science & Nutrition Jan 2022To investigate whether HBV genotype influences the effect of tenofovir and telbivudine on HBV DNA and RNA levels in HBsAg-positive pregnant women. This was a...
To investigate whether HBV genotype influences the effect of tenofovir and telbivudine on HBV DNA and RNA levels in HBsAg-positive pregnant women. This was a retrospective study of 74 HBsAg-positive pregnant women in Guizhou of China. All patients were treated with telbivudine or tenofovir from 12 weeks of pregnancy and HBV infection to the date of delivery. Blood samples were collected at 12-24, 28-32, and 36-40 weeks of pregnancy for the measurement of genotype, HBsAg, hepatitis B e antigen (HBeAg), HBV DNA, HBV RNA, and liver function, including alanine transaminase, aspartate transaminase, total bilirubin, total bile acids, cholinesterase, alkaline phosphatase (ALP), and gamma-glutamyl transferase. All women with HBsAg were followed up. The HBV genotype was B in 64.9% and C in 35.1%. There were 37 patients of telbivudine and tenofovir group respectively. The telbivudine and tenofovir groups showed no differences in demographic and clinical characteristics, including liver function tests, HBsAg, HBeAg, log(HBV DNA), and log(HBV RNA). Compared with baseline (12-24 weeks), telbivudine group showed a significant increase in ALP and significant reductions in HBsAg, HBeAg, log(HBV DNA), and log(HBV RNA) at 36-40 weeks ( < .05). Tenofovir group exhibited a significant increase in ALP and significant reductions in HBeAg, log(HBV DNA), and log(HBV RNA) at 36-40 weeks, compared with baseline ( < .05). HBV genotype (B vs. C) was independently associated with HBV DNA change after therapy ( = .005). In telbivudine group, log (HBV DNA) increased from 3.38 (2.00-7.30) to 7.43 (4.68-8.70). In tenofovir group, log (HBV DNA) decreased from 7.52 (3.32-8.70) to 2.98 (2.00-5.01). HBV genotype was independently associated with HBV DNA change response to telbivudine or tenofovir in pregnant women with hepatitis B. These findings might be helpful for risk assessment regarding vertical transmission of HBV in HBeAg-positive mothers treated with nucleos(t)ide analogues.
PubMed: 35035905
DOI: 10.1002/fsn3.2619 -
Clinical Microbiology and Infection :... Jan 2016This study aims to assess the nephrotoxicity and efficacy of tenofovir disoproxil fumarate (tenofovir), telbivudine and entecavir. A retrospective study of 587 patients...
This study aims to assess the nephrotoxicity and efficacy of tenofovir disoproxil fumarate (tenofovir), telbivudine and entecavir. A retrospective study of 587 patients with chronic hepatitis B treated with tenofovir (n = 170), telbivudine (n = 184) and entecavir (n = 233) for at least 1 year. Renal function and efficacy were assessed. The estimated glomerular filtration rate (eGFR) decreased significantly in the tenofovir group after a mean of 17 months treatment (from 92.2 to 85.6 mL/min/1.73 m(2), p < 0.001), but increased in the telbivudine group after a mean of 32 months of treatment (from 86.1 to 95 mL/min/1.73 m(2), p < 0.001). There was no significant change in eGFR in the entecavir group after a mean of 44 months. By multivariate analysis, pre-existing renal insufficiency (p = 0.003), tenofovir (p = 0.007) and diuretic treatment (p = 0.001) were independent predictors for renal function deterioration. Cumulative virological breakthrough was 0% in tenofovir after 2 years, 3.4% in entecavir after 7 years and 22.9% in telbivudine after 5 years. Liver cirrhosis (p = 0.008) and virological breakthrough (p = 0.040) were independently associated with increased risk of hepatocellular carcinoma development. Tenofovir may lead to deterioration in renal function as assessed by serial eGFR measurements. Although telbivudine appeared to be associated with an improvement in eGFR, it was associated with high rates of virological breakthrough, which was an independent risk factor for HCC development. With low rates of virological breakthrough and preservation of renal function, entecavir could be the best choice among these three agents.
Topics: Adult; Aged; Aged, 80 and over; Antiviral Agents; Drug-Related Side Effects and Adverse Reactions; Female; Glomerular Filtration Rate; Guanine; Hepatitis B, Chronic; Humans; Kidney Diseases; Kidney Function Tests; Male; Middle Aged; Retrospective Studies; Telbivudine; Tenofovir; Thymidine; Treatment Outcome
PubMed: 26055419
DOI: 10.1016/j.cmi.2015.05.035 -
Drug Design, Development and Therapy Dec 2013The People's Republic of China has one of the highest rates of hepatitis B virus (HBV) infection. This review summarizes recent data from studies of entecavir, one of... (Review)
Review
The People's Republic of China has one of the highest rates of hepatitis B virus (HBV) infection. This review summarizes recent data from studies of entecavir, one of the recommended first-line oral therapies for treating chronic hepatitis B, in Chinese HBV-infected patients. Long-term treatment with entecavir is efficacious and well tolerated, and studies comparing entecavir with other nucleos(t)ide therapies, such as lamivudine, adefovir, and telbivudine, demonstrate superior antiviral effects for entecavir therapy and comparable safety profiles. Entecavir monotherapy and combination treatment with other nucleos(t) ide analogs has been shown to be efficacious in the treatment of lamivudine-resistant and adefovir-resistant patients with HBV infection, as well as in patients with multidrug-resistant disease. Entecavir has also been shown to be effective in patients with HBV-associated clinical morbidity, including cirrhosis and liver failure, as well as in preventing recurrence of HBV following liver transplantation and in preventing reactivation of HBV after immunosuppres-sive therapy. Although the cost of anti-HBV therapy is a particular concern in the People's Republic of China, a number of studies have recently demonstrated that entecavir (particularly long-term therapy) represents a more cost-effective treatment strategy compared with other nucleos(t)ide therapies. Further research is required to assess the effects of entecavir combination therapy on hepatitis B surface antigen clearance, and in drug-resistant patients in the People's Republic of China.
Topics: Adenine; Antiviral Agents; China; Cost-Benefit Analysis; Drug Resistance, Viral; Hepatitis B, Chronic; Humans; Liver Transplantation; Organophosphonates
PubMed: 24376343
DOI: 10.2147/DDDT.S41423 -
PloS One 2019As debate rumbles on about whether anti-hepatitis B virus (HBV) nucleos(t)ide analogue treatments modulate host immune system during end-stage liver diseases, we studied...
As debate rumbles on about whether anti-hepatitis B virus (HBV) nucleos(t)ide analogue treatments modulate host immune system during end-stage liver diseases, we studied effects of two potent anti-HBV agents, telbivudine or entecavir, on humoral immune activities including cytokine secretion, immunoglobulin production, and IgG-Fc agalactosylation, which is known to induce proinflammatory responses, in liver cirrhosis. Serum IgG-Fc N-glycan structures in patients with HBV-related liver cirrhosis, who had received either telbivudine treatment or entecavir treatment for at least 48 weeks were analyzed using liquid chromatography tandem-mass spectrometry. Levels of cytokines and each immunoglobulin isotype were measured using enzyme-linked immunosorbent assays. Results showed that 48 weeks of entecavir treatment caused HBV DNA loss, alanine aminotransferase normalization, and an amelioration of hypergammaglobulinemia in cirrhotic patients; however, telbivudine treatment, though possessing similar efficacies on HBV suppression and an improvement in liver inflammation to entecavir treatment, did not mitigate IgG-related hypergammaglobulinemia. Levels of IgG and transforming growth factor (TGF)-β1 in sera of the cirrhotic patients before and during treatment were positively correlated. In vitro assays revealed that telbivudine treatment induced TGF-β1 expression in human macrophagic cells. Moreover, recombinant TGF-β1 treatment stimulated cell proliferation and IgG overproduction in human IgG-producing B cell lines. Finally, we found that telbivudine treatment enhanced the proportion of serum IgG-Fc agalactosylation in cirrhotic patients, which was associated with enhanced levels of TGF-β1 and IgG. In conclusion, telbivudine therapy was associated with TGF-β1 hyperactivity, IgG-related hypergammaglobulinemia, and IgG-Fc agalactosylation in HBV-related liver cirrhosis.
Topics: Adult; Aged; Antiviral Agents; B-Lymphocytes; Cell Proliferation; Cytokines; Female; Hepatitis B virus; Hepatitis B, Chronic; Humans; Hypergammaglobulinemia; Immunoglobulin G; Liver Cirrhosis; Macrophages; Male; Middle Aged; Recombinant Proteins; Retrospective Studies; Telbivudine; Transforming Growth Factor beta1
PubMed: 31770396
DOI: 10.1371/journal.pone.0225482 -
BMC Gastroenterology Apr 2018Current treatment options for chronic hepatitis B (CHB) are pegylated interferon alpha and nucleoside analogues (NAs). NAs have relatively fewer side effects than...
BACKGROUND
Current treatment options for chronic hepatitis B (CHB) are pegylated interferon alpha and nucleoside analogues (NAs). NAs have relatively fewer side effects than interferon alpha, and generally well tolerated. Previously 12.9% of patients on telbivudine treatment were reported to develop severe elevation of serum creatine phosphokinase (CPK) levels, but related clinical disease, like lactic acidosis (LA) and rhabdomyolysis (RM) were rare. The pathophysiology may be mitochondrial toxicity, for the NAs inhibit not only hepatitis B virus (HBV) polymerase, but also the host mitochondrial DNA polymerase γ. As mitochondria are the main sites of oxidative phosphorylation, there will be an increase of pyruvate reduction to lactic acid and insufficient adenosine triphosphate. The accumulation of lactic acid causes LA, while lack of energy leads to cell dysfunction and mitochondria-associated disease, including RM. All five NAs, except tenofovir, have been reported causing LA and RM. Here we report the first case of CHB patients developing fatal LA and RM during telbivudine and tenofovir treatment.
CASE PRESENTATION
The patient is a 51-year-old man who was hospitalized in November 2015. He had taken telbivudine regularly because of CHB. Later, tenofovir was added to antiviral treatment because of HBV resistance. Then he had myalgia, chest tightness and anorexia. The blood lactate was 12.7 mmol/L. The arterial blood gas analysis showed pH 7.25, base excess 21.1 mmol/L. CPK was 991 U/L, myoglobin was 1745 ng/ml and creatine was 83 μmol/L. Abdomen magnetic resonance revealed cirrhosis. Muscle biopsy revealed myogenic lesion with abnormality of mitochondria and fat metabolism. The patient was diagnosed with Hepatitis B envelope Antigen positive CHB, cirrhosis, LA and RM characterized by myalgia and elevated myoglobin. He was given tenofovir alone as antiviral treatment instead. After hemodialysis and 4 weeks` treatment of corticosteroids, his symptoms recovered, and blood lactate gradually returned to a normal range.
CONCLUSIONS
This case shows that tenofovir may trigger muscle damage and fatal RM in combination with telbivudine treatment in CHB patients. Thus, patients receiving tenofovir and telbivudine should be closely monitored for muscular abnormalities, blood lactate level and other mitochondrial toxicity associated side effects.
Topics: Acidosis, Lactic; Antiviral Agents; DNA Polymerase gamma; Drug Therapy, Combination; Hepatitis B, Chronic; Humans; Male; Middle Aged; Rhabdomyolysis; Telbivudine; Tenofovir; Thymidine
PubMed: 29625557
DOI: 10.1186/s12876-018-0773-3 -
Journal of Receptor and Signal... Dec 2020Recently, a pathogen has been identified as a novel coronavirus (SARS-CoV-2) and found to trigger novel pneumonia (COVID-19) in human beings and some other mammals. The...
Virtual screening, ADME/T, and binding free energy analysis of anti-viral, anti-protease, and anti-infectious compounds against NSP10/NSP16 methyltransferase and main protease of SARS CoV-2.
Recently, a pathogen has been identified as a novel coronavirus (SARS-CoV-2) and found to trigger novel pneumonia (COVID-19) in human beings and some other mammals. The uncontrolled release of cytokines is seen from the primary stages of symptoms to last acute respiratory distress syndrome (ARDS). Thus, it is necessary to find out safe and effective drugs against this deadly coronavirus as soon as possible. Here, we downloaded the three-dimensional model of NSP10/NSP16 methyltransferase (PDB-ID: 6w6l) and main protease (PDB-ID: 6lu7) of COVID-19. Using these molecular models, we performed virtual screening with our anti-viral, inti-infectious, and anti-protease compounds, which are attractive therapeutics to prevent infection of the COVID-19. We found that top screened compound binds with protein molecules with good dock score with the help of hydrophobic interactions and hydrogen bonding. We observed that protease complexed with Cyclocytidine hydrochloride (anti-viral and anti-cancer), Trifluridine (anti-viral), Adonitol, and Meropenem (anti-bacterial), and Penciclovir (anti-viral) bound with a good docking score ranging from -6.8 to -5.1 (Kcal/mol). Further, NSP10/NSP16 methyltransferase complexed with Telbivudine, Oxytetracycline dihydrate (anti-viral), Methylgallate (anti-malarial), 2-deoxyglucose and Daphnetin (anti-cancer) from the docking score of -7.0 to -5.7 (Kcal/mol). In conclusion, the selected compounds may be used as a novel therapeutic agent to combat this deadly pandemic disease, SARS-CoV-2 infection, but needs further experimental research.HighlightsNSP10/NSP16 methyltransferase and main protease complex of SARS CoV-2 bind with selected drugs.NSP10/NSP16 methyltransferase and protease interacted with drugs by hydrophobic interactions.Compounds show good DG binging free energy with protein complexes.Ligands were found to follow the Lipinski rule of five.
Topics: Acyclovir; Ancitabine; Antiviral Agents; Betacoronavirus; COVID-19; Coronavirus Infections; Drug Evaluation, Preclinical; Guanine; Humans; Meropenem; Methyltransferases; Models, Molecular; Molecular Docking Simulation; Pandemics; Pneumonia, Viral; Protein Conformation; Ribitol; SARS-CoV-2; Trifluridine; User-Computer Interface; Viral Nonstructural Proteins; Viral Regulatory and Accessory Proteins
PubMed: 32476594
DOI: 10.1080/10799893.2020.1772298 -
Evidence Report/technology Assessment Oct 2008Synthesize evidence of the natural history of chronic hepatitis B (CHB) and effects and harms of antiviral drugs on clinical, virological, histological, and biochemical... (Review)
Review
OBJECTIVES
Synthesize evidence of the natural history of chronic hepatitis B (CHB) and effects and harms of antiviral drugs on clinical, virological, histological, and biochemical outcomes.
DATA SOURCES
MEDLINE, electronic databases, and manual searches of systematic reviews.
REVIEW METHODS
We included original observational studies to assess natural history and randomized controlled trials (RCTs) of adults with CHB published in English to assess treatment effects and harms if they reported mortality, incidence of hepato-cellular carcinoma (HCC), cirrhosis or failure, HBeAg or HBsAg, viral load (HBV DNA), alanine aminotransferase (ALT) levels, histological necroinflammatory and fibrosis scores, and adverse events after interferon alfa-2b, pegylated interferon alfa 2-a, lamivudine, adefovir, entecavir, tenovir or telbivudine. We excluded pregnant women, transplant patients, and individuals undergoing cancer chemotherapy. We calculated relative risk or absolute risk differences at end of treatment and post-treatment.
RESULTS
Observational studies (41 publications) suggested that male gender, coinfection with hepatitis C, D, or HIV, increased HBV DNA, and cirrhosis were associated with increased risk of HCC and death. Drugs did not reduce death, liver failure, or HCC in 16 RCTs not designed to test long-term clinical outcomes. Evidence from 93 publications of 60 RCTs suggested drug effects on viral load or replication, liver enzymes, and histology at end of treatment and lasting from 3 to 6 months off treatment. No one treatment improved all outcomes and there was limited evidence on comparative effects. Two RCTs suggested interferon alfa-2b increased CHB solution versus placebo. Interferon alfa-2b or lamivudine improved off treatment HBV DNA and HBeAg clearance and seroconversion and ALT normalization. Adefovir improved off treatment ALT normalization and HBV DNA clearance. Pegylated interferon alfa 2-a versus lamivudine improved off-treatment HBV DNA and HBeAg clearance and seroconversion, ALT normalization and liver histology. Lamivudine combined with interferon alfa-2b versus lamivudine improved off treatment HBV DNA clearance and HBeAg seroconversion and reduced HBV DNA mutations. Pegylated interferon alfa 2-a plus lamivudine improved off treatment HBV DNA and HBeAg clearance and seroconversion and ALT normalization compared to lamivudine but not pegylated interferon alfa 2-a monotherapy. Adverse events were common but generally mild and did not result in increased treatment discontinuation. Longer hepatitis duration, male gender, baseline viral load and genotype, HBeAg, and histological status may modify treatment effect on intermediate outcomes. Adefovir and pegylated interferon alfa 2-a with lamivudine improved off treatment viral clearance in HBeAg negative patients. There was insufficient evidence to determine if biochemical, viral, or histological measures are valid surrogates of treatment effect on mortality, liver failure, or cancer.
CONCLUSION
Adults with CHB have an increased risk of death, hepatic decompensation, and HCC. Mono or combined drug therapy improves selected virological, biochemical, and histological markers with no consistent effects on all examined outcomes. Patient and disease characteristics may modify treatment-induced intermediate outcomes. Evidence was insufficient to assess treatment effect on clinical outcomes, predict individualized patient response, or determine if intermediate measures are reliable surrogates. Future research should assess long-term drug effects on clinical outcomes and among patient subpopulations.
Topics: Antiviral Agents; Carcinoma, Hepatocellular; Chronic Disease; Female; Hepatitis B; Hepatitis B virus; Humans; Interferon alpha-2; Interferon-alpha; Liver Neoplasms; Liver Transplantation; Male; Recombinant Proteins; Treatment Outcome; Viral Load
PubMed: 19408969
DOI: No ID Found -
Kidney International Nov 2013Although the prevalence of chronic hepatitis B virus (HBV) infection in patients with chronic kidney disease remains low in developed countries, clinicians should be... (Review)
Review
Although the prevalence of chronic hepatitis B virus (HBV) infection in patients with chronic kidney disease remains low in developed countries, clinicians should be aware of the rationale for treatment in this setting. This patient population presents particular features and various complicating conditions requiring special treatment strategies. Interferon, the standard treatment for HBV infection, has been poorly tolerated by patients with chronic kidney disease, has presented relatively low efficacy, and has posed renal transplant recipients under the risk of acute rejection. The advent of effective nucleos(t)ide analogs (NAs) has offered the opportunity to minimize the consequences of HBV infection in HBV-positive patients with chronic kidney disease. Combination with immunosuppressive agents might be considered in cases of rapid renal function deterioration and/or severe proteinuria. Among the newer NAs, entecavir may be preferred, because of its high potency, high genetic barrier to resistance, and favorable renal safety profile. However, entecavir presented low efficacy in case of lamivudine or telbivudine resistance, and thus tenofovir may be a better option in that setting. All HBsAg-positive candidates should be treated with NAs before renal transplantation in order to maintain undetectable HBV DNA, reduce liver fibrosis, and prevent hepatic decompensation after renal transplantation. This review summarizes updated issues related to treatment of chronic HBV infection in all categories of population with chronic kidney disease (those exhibiting HBV-associated glomerular disease, those treated with hemodialysis, as well as renal transplant candidates, donors, and recipients).
Topics: Antiviral Agents; Comorbidity; Hepatitis B, Chronic; Humans; Immunosuppressive Agents; Kidney Transplantation; Renal Dialysis; Renal Insufficiency, Chronic; Risk Factors; Time Factors; Treatment Outcome
PubMed: 23783238
DOI: 10.1038/ki.2013.249 -
Clinical and Molecular Hepatology Jun 2019Despite all these exciting developments, there remain some unmet needs in the management for patients with chronic hepatitis B (CHB). As majority of CHB patients are... (Review)
Review
Despite all these exciting developments, there remain some unmet needs in the management for patients with chronic hepatitis B (CHB). As majority of CHB patients are going to use oral nucleos(t)ide analogues (NAs) for decades, Safety profile of NAs is of no doubt an important issue. The newest nucleotide analogue tenofovir alafenamide is potent in terms of viral suppression, together with favourable renal and bone safety profile. Biochemical response as reflected by alanine aminotransferase (ALT) normalization is recently found to be prognostically important. Patients who achieved ALT normalization have reduced the risk of hepatic events by 49%. Functional cure as reflected by hepatitis B surface antigen seroclearance not only implies patients may stop NA treatment, it also confers to a reduced risk of hepatocellular carcinoma and other hepatic events. Hence functional cure should be the ultimate treatment goal in CHB patients. Preemptive antiviral treatment may reduce mother-to-child transmission of hepatitis B virus, especially if birth dose of vaccination cannot be given in the first two hours after delivery. Lastly, despite the currently first-line NAs have high-genetic barrier to drug resistance mutations, there are still are many patients who were previously treated with low barrier of resistance including lamivudine, telbivudine or adefovir dipivoxil which could lead to antiviral resistance and affecting the choice of NAs.
Topics: Alanine Transaminase; Antiviral Agents; Drug Resistance, Viral; Hepatitis B Surface Antigens; Hepatitis B, Chronic; Humans; Infectious Disease Transmission, Vertical; Prognosis; Renal Insufficiency, Chronic; Tenofovir
PubMed: 30754963
DOI: 10.3350/cmh.2018.0106