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Journal of Viral Hepatitis Jul 2011Primary or secondary failure of adefovir dipivoxil (ADV) therapy of chronic hepatitis B is not infrequent. The reasons for suboptimal responses are not well defined. In...
Primary or secondary failure of adefovir dipivoxil (ADV) therapy of chronic hepatitis B is not infrequent. The reasons for suboptimal responses are not well defined. In HIV and hepatitis C virus infection, failure of antiviral drug therapy has been linked with low blood drug levels. We have studied 20 well-defined patients with chronic hepatitis B who were treated with ADV for drug and virus kinetics. Importantly, neither Cmax levels (mean 26 ng/mL, range 14-59 ng/mL) nor the time to maximal drug levels (mean 4 h, range 2-8 h) differed between patients showing a complete virological response to adefovir (n = 10), patients with secondary treatment failure (n = 7) and patients with suboptimal primary response (hepatitis B virus-DNA >10,000 IU/mL after 6 months of treatment; n = 3). Thus, adefovir treatment failure is unlikely to be due to an inability to mount sufficient drug levels in the blood.
Topics: Adenine; Adult; Aged; Aged, 80 and over; Antiviral Agents; Chromatography, High Pressure Liquid; Female; Hepatitis B e Antigens; Hepatitis B, Chronic; Humans; Male; Middle Aged; Organophosphonates; Treatment Failure
PubMed: 21692930
DOI: 10.1111/j.1365-2893.2010.01404.x -
Virology Journal Feb 2011Although entacavir and adefovir were widely used in most Asian countries, there were few conclusions drawn from a meta-analysis for comparing the efficacy between... (Comparative Study)
Comparative Study Meta-Analysis Review
BACKGROUND
Although entacavir and adefovir were widely used in most Asian countries, there were few conclusions drawn from a meta-analysis for comparing the efficacy between entecavir and adefovir in nucleos(t)ide-naïve Asian patients with chronic hepatitis B (CHB). The aim of this study was to evaluate the 48-week efficacy between the two drugs in HBeAg-positive nucleos(t)ide-naïve Asian CHB patients with the method of Meta analysis, which was generally accepted by the international as the best evidence for evaluating the efficacy of drugs.
METHODS
We searched all data documented in Pubmed, Embase, Wanfang Database and CNKI (China National Knowledge Infrastructure) before November 30, 2010. Heterogeneity was examined by Chi-square test, the relative risk calculated and forest plot drawn. Rates of undetected serum HBV DNA, serum alanine aminotransferase (ALT) normalization, HBeAg clearance and HBeAg seroconversion were analyzed. A total of 6 articles was included. Meta analysis showed that the rate of undetected serum HBV DNA (relative risk, 1.73; 95% confidence interval, 1.38-2.17; P < 0.00001) and that of serum ALT normalization (relative risk, 1.25; 95% confidence interval, 1.06-1.49; P = 0.009) in the entecavir group were higher than those in the adefovir group. However, no statistic significance existed between the two groups in the rate of HBeAg clearance (relative risk, 0.77; 95% confidence interval, 0.44-1.35; P = 0.36), or the rate of HBeAg seroconversion (relative risk, 0.74; 95% confidence interval, 0.28-1.94; P = 0.53).
CONCLUSIONS
Entecavir is superior to adefovir in decreasing serum HBV DNA and normalizing ALT but similar with adefovir in clearing HBeAg and encouraging HBeAg seroconversion for the HBeAg-positive nucleos(t)ide-naive Asian patients with chronic hepatitis B. Adefovir can be still used for first-line therapy in these patients.
Topics: Adenine; Antiviral Agents; Asia; Guanine; Hepatitis B e Antigens; Hepatitis B, Chronic; Humans; Organophosphonates; Randomized Controlled Trials as Topic
PubMed: 21342505
DOI: 10.1186/1743-422X-8-75 -
Journal of Bone and Mineral Metabolism Mar 2013Osteomalacia is a metabolic bone disease that leads to softening of the bones and can be caused by hypophosphatemia. Large clinical studies of low-dose adefovir... (Review)
Review
Osteomalacia is a metabolic bone disease that leads to softening of the bones and can be caused by hypophosphatemia. Large clinical studies of low-dose adefovir dipivoxil (adefovir) have found no evidence of renal tubular dysfunction leading to hypophosphatemia after 48 weeks of treatment. We report two cases of low-dose adefovir-induced hypophosphatemic osteomalacia that initially presented with diffuse musculoskeletal pain. The first patient was a 62-year-old man with a 2-year history of bone pain involving the dorsal mid-thorax, lower anterior chest wall, right sacroiliac joint area, and both knees. The patient had been receiving adefovir for 5 years before confirmation of hypophosphatemia and urinary phosphate wasting. Bone scintigraphy revealed multifocal lesions including multiple ribs, costochondral junctions, costovertebral junctions, sacrum, both posterior iliac bones, both proximal tibia, right calcaneus, and the left second metatarsophalangeal joint area, which were suggestive of metabolic bone disorder. Bone pain was significantly reduced within 3 months after supplementation with phosphate and calcitriol. The second patient was a 54-year-old male who presented with an 18-month history of severe bone pain of the right medial knee and low back. The patient had been taking adefovir for approximately 40 months before the development of bone pain. Laboratory data revealed hypophosphatemia and vitamin D deficiency. Bone scintigraphy showed increased uptake in bilateral ribs, sternum, both scapulae, both costovertebral junctions, both pelvic bones, medial cortex of the right proximal femur, right proximal tibia, and the left lateral tarsal bone. The symptoms improved by changing the antiviral agent from adefovir to entecavir. Because osteomalacia often presents with diffuse bone pain, non-specific radiologic findings and non-characteristic routine serum biochemical changes, the disease can be confused with various musculoskeletal diseases and a high index of suspicion is necessary for an early diagnosis in patients receiving adefovir therapy.
Topics: Adenine; Bone and Bones; Dose-Response Relationship, Drug; Humans; Hypophosphatemia; Male; Middle Aged; Organophosphonates; Osteomalacia; Radionuclide Imaging; Tomography, X-Ray Computed
PubMed: 22976054
DOI: 10.1007/s00774-012-0384-y -
Clinical Nuclear Medicine Sep 2017Adefovir-induced hypophosphatemic osteomalacia in the context of hepatocarcinoma is rare and needs to be differentiated from metastatic hepatocarcinoma. We here report a...
Adefovir-induced hypophosphatemic osteomalacia in the context of hepatocarcinoma is rare and needs to be differentiated from metastatic hepatocarcinoma. We here report a case of severe osteomalacia whose focal uptakes of radiotracer on the Tc-MDP SPECT/CT images mimicked that of metastatic hepatocarcinoma.
Topics: Adenine; Bone Neoplasms; Humans; Hypophosphatemia; Liver Neoplasms; Male; Middle Aged; Organophosphonates; Osteomalacia; Single Photon Emission Computed Tomography Computed Tomography
PubMed: 28719445
DOI: 10.1097/RLU.0000000000001756 -
Journal of Chromatography. B,... Sep 2019As a tool to be used in transporter-mediated drug-drug interaction studies, a sensitive LC-MS/MS method for the simultaneous quantification of adefovir and pitavastatin...
As a tool to be used in transporter-mediated drug-drug interaction studies, a sensitive LC-MS/MS method for the simultaneous quantification of adefovir and pitavastatin in human plasma and adefovir in urine was developed and successfully validated. Plasma samples were processed by protein precipitation using methanol with a subsequent concentrating step. Urine samples were diluted using 0.1% formic acid. Separation was achieved on a Synergy Polar-RP reversed phase column (50 × 4.6 mm, 2.5 μm) in gradient elution using a mobile phase composed of water and 0.1% formic acid and a mixture of methanol and acetonitrile (50:50, v/v) containing 0.1% formic acid at a flow rate of 1.0 mL/min. The linear range covered concentrations from 0.273 to 52.6 ng/mL for adefovir and from 0.539 to 104.2 ng/mL for pitavastatin in human plasma, respectively. The calibration curve for adefovir in urine ranged from 0.104 to 10.0 μg/mL. The weighted linear regression (1/conc) implied excellent linearity with correlation coefficients ≥0.999.
Topics: Adenine; Chromatography, High Pressure Liquid; Humans; Organophosphonates; Plasma; Quinolines; Tandem Mass Spectrometry
PubMed: 31330406
DOI: 10.1016/j.jchromb.2019.121718 -
Clinical Transplantation 2013Chronic hepatitis B is prevalent in the transplant setting and may cause significant complications. Effective control of viral replication is needed. Besides lamivudine,...
Chronic hepatitis B is prevalent in the transplant setting and may cause significant complications. Effective control of viral replication is needed. Besides lamivudine, very little data are available on safety and efficacy of other drugs. We describe our experience with adefovir dipivoxil (ADV) in eight heart transplant recipients. Studies included a baseline liver biopsy, thrice-monthly clinical, biochemical, and virological evaluations, including genotyping and viral load, polymerase gene sequencing for resistance mutations, liver and kidney function tests, and liver ultrasound. Of eight patients, six had fibrosis score ≤2 and negative HBeAg and seven had hepatitis B virus (HBV) genotype D. Upon ADV start, median HBV-DNA was 5.8 logs IU/mL and alanine aminotransferase (ALT) levels were mostly normal. All patients had prior mild-to-moderate renal functional impairment. Seven of eight patients started ADV after a previous course of lamivudine. Five of these seven patients became HBV-DNA undetectable within eight months. One patient with low baseline viremia started ADV de novo and suppressed HBV-DNA. Median treatment duration was 66 months. ADV daily dose was halved in one patient due to renal function worsening. No ALT flares, hypophosphatemia, liver decompensation, liver cancer, or emergence of resistance was observed. Our data suggest that ADV may be a safe and effective rescue treatment for heart transplant recipients with lamivudine-resistant chronic hepatitis B.
Topics: Adenine; Adult; Antiviral Agents; DNA, Viral; Female; Follow-Up Studies; Heart Diseases; Heart Transplantation; Hepatitis B virus; Hepatitis B, Chronic; Humans; Male; Middle Aged; Organophosphonates; Postoperative Complications; Prognosis; Prospective Studies; Viral Load
PubMed: 23517019
DOI: 10.1111/ctr.12109 -
Journal of Hepatology Dec 2005The susceptibility of adefovir-resistant hepatitis B virus (HBV) mutants is only reduced by 3-10-fold in in vitro studies, suggesting that virologic breakthrough and...
BACKGROUND/AIMS
The susceptibility of adefovir-resistant hepatitis B virus (HBV) mutants is only reduced by 3-10-fold in in vitro studies, suggesting that virologic breakthrough and clinical deterioration are unlikely. The aim of this study was to describe the clinical course of patients with adefovir-resistant HBV infection.
METHODS
Testing for adefovir-resistant mutations was performed on patients who had a suboptimal response or virologic breakthrough on adefovir. Adefovir-resistant mutations were detected using a line probe assay and direct sequencing of the HBV P-gene.
RESULTS
Eight male patients with pre-existing lamivudine resistance or breakthrough (mean age 47+/-13 years) were found to have adefovir-resistant mutations rtA181V/T or rtN236T. Baseline median ALT was 66 IU/L (range, 27-1161) and median HBV DNA 7.9 log10 copies/ml (range, 6-8.3). At the time of adefovir resistance (mean of 20+/-9 months), HBV DNA increased to > or = 5 log10 copies/ml in 7 patients. After detection of adefovir resistance, hepatic decompensation occurred in 2 patients, 1 of whom died. Salvage therapy with lamivudine, entecavir or tenofovir was given to 7 patients and a reduction in HBV DNA by > or = 3 log10 was seen in 3 patients.
CONCLUSIONS
In conclusion, adefovir resistance can be associated with significant viral rebound and hepatic decompensation which may be fatal.
Topics: Adenine; Adult; Aged; Antiviral Agents; Disease Progression; Drug Resistance, Viral; Hepatitis B; Hepatitis B virus; Humans; Liver Failure; Male; Middle Aged; Mutation; Organophosphonates; Viral Load
PubMed: 16168522
DOI: 10.1016/j.jhep.2005.05.037 -
Alimentary Pharmacology & Therapeutics Apr 2013Chronic hepatitis B patients (CHB) treated with adefovir were followed up to evaluate nephrotoxicity and its outcome.
BACKGROUND
Chronic hepatitis B patients (CHB) treated with adefovir were followed up to evaluate nephrotoxicity and its outcome.
AIM
To assess the incidence of renal dysfunction during adefovir therapy in Asian patients and factors associated with it, and evaluate strategies to improve adefovir-related renal dysfunction and their impact on viral suppression.
METHODS
Chronic hepatitis B clinic patients from a tertiary hospital on adefovir treatment, with their clinical and laboratory parameters were extracted from the hospital electronic clinical database in an observational study design. Patients were excluded if they had liver/renal transplant, baseline renal impairment or were on dialysis. Adefovir-related renal dysfunction was defined as adefovir-related abnormal serum creatinine (ARASC) > 125 μmol/L (males), >90 μmol/L (females); adefovir-related abnormal GFR <60 mL/min; and adefovir-related increased serum creatinine >0.5 mg/dL, without other known causes of nephrotoxicity.
RESULTS
A total of 271/383 adefovir-treated patients were suitable for analysis and 33(12%) patients developed abnormal serum creatinine. Cumulative increase in proportion of patients with ARASC was 33.8% and GFR ≤60 mL/min was 38.3% by 6 years, while serum creatinine increase ≥0.5 mg/dL was 21.48% by 5 years. Using multivariate analysis, the only independent baseline predictor of ARASC was GFR ≤76.1 mL/min. Patients who had ARASC had similar levels of viral suppression to those who did not have ARASC. Those who had ARASC either continued adefovir (24%), switched therapy (24%) or had adefovir dose reduction (52%). ARASC resolved and GFR normalised in almost all patients after either switching therapy or reducing adefovir dose, with no difference between the two strategies (P = 0.737). Those with adefovir dose reduction had no significant increase in HBV DNA (P = 0.170).
CONCLUSIONS
Adefovir-related renal dysfunction occurred in a significant number of adefovir-treated patients, but reduction of the dose led to renal improvement without compromising treatment efficacy.
Topics: Adenine; Adult; Antiviral Agents; Asian People; Creatinine; Dose-Response Relationship, Drug; Female; Glomerular Filtration Rate; Hepatitis B, Chronic; Humans; Kidney Diseases; Male; Middle Aged; Organophosphonates
PubMed: 23432107
DOI: 10.1111/apt.12251 -
La Clinica Terapeutica 2014Chronic hepatitis B is an important health problem worldwide. Lamivudine, adefovir, entecavir and telbivudine are the oral drugs licensed for the treatment of patients...
BACKGROUND AND AIMS
Chronic hepatitis B is an important health problem worldwide. Lamivudine, adefovir, entecavir and telbivudine are the oral drugs licensed for the treatment of patients with chronic hepatitis B. Implementation of antiviral therapy leads to the emergence of mutant strains during the treatment in chronic hepatitis B. Primary antiviral resistance may be rarely encountered. The aims of this study were to detect the resistance patterns of Hepatit B Virus strains in treatment-naive chronic hepatitis B patients.
MATERIALS AND METHODS
A total of 147 CHB patients were included to this study which was carried on between January 2007- December 2010. HBV DNA levels were detected by using the Real time PCR (COBAS Ampli- Prep/COBAS TaqMan HBV Test). HBV-DNA was extracted from the sera of the patients by using extraction kit (Invisorb, Instant Spin DNA/RNA Virus Mini Kit, Germany). A line prob assay (Inno-Lipa HBV DR v2, Innogenetics N.V, Ghent, Belgium) was used to determine motif variants at viral polymerase gene fragment in HBV-DNA samples of these patients and evaluated colorimetrically.
RESULTS
In 147 patients antiviral resistance rate was found 17% (25/147) for lamivudin, 5.44% (8/147) adefovir, 0.68%(1/147) lamivudin and adefovir. Various mutations were detected. This mutations; responsible for lamivudine resistance YMDD+YVDD (n=10), YMDD+YIDD (n=12), YIDD (n=2), YVDD (=1); responsible for adefovir resistance N236T (n=3), A181T (n=5); responsible for lamivudine and adefovir resistance YMDD+YIDD+N236T (n=1).
CONCLUSIONS
As a conclusion, it is thought that drug resistance should be followed up regularly, the determination of HBV drug resistance as immediate as possible period may be instructive for the treatment and follow-up in CHB patients. Although determination of known mutations with Inno Lipa DR v2 method is disadvantage, because of ease of application and the determination of both lamivudin-adefovir resistance in a short time, it can be used for the treatment and follow-up in CHB patients.
Topics: Adenine; Antiviral Agents; DNA, Viral; Drug Resistance, Viral; Hepatitis B virus; Hepatitis B, Chronic; Humans; Lamivudine; Mutation; Organophosphonates; Protein Domains
PubMed: 24589944
DOI: 10.7471/CT.2014.1654 -
Digestive and Liver Disease : Official... Dec 2014
Topics: Adenine; Adult; Antiviral Agents; Female; Heart Defects, Congenital; Humans; Male; Organophosphonates; Paternal Exposure; Pregnancy; Teratogens; Ultrasonography, Prenatal
PubMed: 25174874
DOI: 10.1016/j.dld.2014.08.035