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Asian Journal of Surgery Apr 2023
Topics: Humans; Fanconi Syndrome; Spinal Fractures; Osteomalacia; Hypophosphatemia; Phosphorus Metabolism Disorders
PubMed: 36274000
DOI: 10.1016/j.asjsur.2022.09.140 -
Annals of Translational Medicine Sep 2022Chronic hepatitis B (CHB) affects a vast population globally. A variety of drugs are available for the treatment of CHB, including tenofovir (TDF) and adefovir (ADV)....
Comparing the efficacy and safety of tenofovir and adefovir or combined drug treatment for the treatment of chronic hepatitis B infection: a systematic review and meta-analysis.
BACKGROUND
Chronic hepatitis B (CHB) affects a vast population globally. A variety of drugs are available for the treatment of CHB, including tenofovir (TDF) and adefovir (ADV). However, the efficacy of monotherapy drug treatment is inconclusive, the safety and efficacy of TDF remain unclear, more data are needed to be included and combined drug treatment is considered to exhibit higher efficacy. To explore this issue, we performed a current literature review and meta-analysis to compare the efficacy and safety of ADV TDF, TDF ADV + lamivudine (LAM); TDF ADV + entecavir (ETV).
METHODS
We systematically searched China National Knowledge Infrastructure, the Cochrane Library, Embase, PubMed, Chinese VIP, and Wanfang Data, for relevant clinical trials since July 2015, all included studies were based on PICOS principles and evaluated independently by the reviewers in accordance with the Cochrane Handbook (Rob2.0). A meta-analysis was performed by using Review Manager 5.4.
RESULTS
We included a total of 32 studies, including 31 randomized controlled trials and one retrospective study involving 2,473 patients. The results revealed a low risk of bias in included studies, that the virologic response of TDF was superior to ADV (P<0.05). And TDF was also superior to ADV in Serum creatinine levels, Immunologic function, and safety profile. However, when ADV was combined with other medications, it was superior to TDF in alanine aminotransferase (ALT) level and Tbil level and adverse reactions, but on other indicators, TDF was superior to drug combination therapy.
CONCLUSIONS
Results showed that TDF was superior to ADV in the parameters of ALT, hepatitis B virus (HBV)-DNA reduction, HBeAg-negative conversion rate, safety, and total bilirubin levels in patients with CHB. However, when ADV was combined with LAM or ETV, they often showed the same therapeutic effect as TDF in parameters such as ALT level and Tbil level and combined therapy can effectively reduce the occurrence of adverse reactions. In this study, because the sample source countries were limited, a greater number of global studies are needed in the future to verify the current findings.
PubMed: 36267714
DOI: 10.21037/atm-22-3747 -
Viruses Sep 2022My collaboration with Prof. Antonín Holý, that spans a period of 3-4 decades (1976-2012), led to the discovery of several acyclic nucleoside phosphonates (ANPs) which...
My collaboration with Prof. Antonín Holý, that spans a period of 3-4 decades (1976-2012), led to the discovery of several acyclic nucleoside phosphonates (ANPs) which were clinically developed by Gilead Sciences: cidofovir, adefovir, and tenofovir. The latter was further converted to two orally bioavailable prodrug forms, TDF and TAF, and both TDF and TAF were further combined with other antiviral drugs, thus giving rise to a broad array of antiviral drug combinations for the treatment of HIV infections. TDF and TAF are both available for the treatment of hepatitis B virus (HBV) infections, and, in combination with emtricitabine, also applicable as Truvada and Descovy, respectively, for the prophylaxis of HIV infections.
Topics: Anniversaries and Special Events; Anti-HIV Agents; Antiviral Agents; Cidofovir; Emtricitabine; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; Hepatitis B; Hepatitis B virus; Humans; Nucleosides; Organophosphonates; Prodrugs; Tenofovir
PubMed: 36146783
DOI: 10.3390/v14091978 -
Molecules (Basel, Switzerland) Sep 2022Adefovir (ADV) is an anti-retroviral drug, which can be used to treat acquired immune deficiency syndrome (AIDS) and chronic hepatitis B (CHB), so its quantitative...
Adefovir (ADV) is an anti-retroviral drug, which can be used to treat acquired immune deficiency syndrome (AIDS) and chronic hepatitis B (CHB), so its quantitative analysis is of great significance. In this work, zirconium molybdate (ZrMoO) was synthesized by a wet chemical method, and a composite with multi-walled carbon nanotubes (MWCNTs) was made. ZrMoO-MWCNTs composite was dropped onto the surface of a glassy carbon electrode (GCE) to prepare ZrMoO-MWCNTs/GCE, and ZrMoO-MWCNTs/GCE was used in the electrochemical detection of ADV for the first time. The preparation method is fast and simple. The materials were characterized by X-ray powder diffraction (XRD), scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS) and cyclic voltammetry (CV). It was electrochemically analysed by differential pulse voltammetry (DPV). Compared with single-material modified electrodes, ZrMoO-MWCNTs/GCE showed a vastly improved electrochemical response to ADV. Moreover, the sensor complements the study of the electrochemical detection of ADV. Under optimal conditions, the proposed electrochemical method showed a wide linear range (from 1 to 100 μM) and a low detection limit (0.253 μM). It was successfully tested in serum and urine. In addition, the sensor has the advantages of a simple preparation, fast response, good reproducibility and repeatability. It may be helpful in the potential applications of other substances with similar structures.
Topics: Adenine; Electrochemical Techniques; Electrodes; Limit of Detection; Molybdenum; Nanocomposites; Nanotubes, Carbon; Organophosphonates; Reproducibility of Results; Zirconium
PubMed: 36144756
DOI: 10.3390/molecules27186022 -
Frontiers in Immunology 2022Patients after kidney transplantation need to take long-term immunosuppressive and other drugs. Some of these drug side effects are easily confused with the symptoms of...
BACKGROUND
Patients after kidney transplantation need to take long-term immunosuppressive and other drugs. Some of these drug side effects are easily confused with the symptoms of Fanconi syndrome, resulting in misdiagnosis and missed diagnosis, and causing serious consequences to patients. Therefore, improving awareness, early diagnosis and treatment of Fanconi syndrome after kidney transplantation is critical.
METHODS
This retrospective study analyzed 1728 cases of allogeneic kidney transplant patients admitted to the Second Xiangya Hospital of Central South University from July 2016 to January 2021. Two patients with Fanconi syndrome secondary to drugs, adefovir dipivoxil (ADV) and tacrolimus, were screened. We summarized the diagnostic process, clinical data, and prognosis.
RESULTS
The onset of Fanconi syndrome secondary to ADV after renal transplantation was insidious, and the condition developed after long-term medication (>10 years). It mainly manifested as bone pain, osteomalacia, and scoliosis in the late stage and was accompanied by obvious proximal renal tubular damage (severe hypophosphatemia, hypokalemia, hypocalcemia, hypouricemia, glycosuria, protein urine, acidosis, etc.) and renal function damage (increased creatinine and azotemia). The pathological findings included mitochondrial swelling and deformity in renal tubular epithelial cells. The above symptoms and signs were relieved after drug withdrawal, but the scoliosis was difficult to rectify. Fanconi syndrome secondary to tacrolimus has a single manifestation, increased creatinine, which can be easily confused with tacrolimus nephrotoxicity. However, it is often ineffective to reduce the dose of tacrolomus, and proximal renal failure can be found in the later stage of disease development. There was no abnormality in the bone metabolism index and imageological examination findings. The creatinine level decreased rapidly, the proximal renal tubule function returned to normal, and no severe electrolyte imbalance or urinary component loss occurred when the immunosuppression was changed from tacrolimus to cyclosporine A.
CONCLUSIONS
For the first time, drug-induced Fanconi syndrome after kidney transplantation was reported. These results confirmed that the long-term use of ADV or tacrolimus after kidney transplantation may have serious consequences, some of which are irreversible. Greater understanding of Fanconi syndrome after kidney transplantation is necessary in order to avoid incorrect and missed diagnosis.
Topics: Allografts; Antiviral Agents; Creatinine; Fanconi Anemia; Fanconi Syndrome; Humans; Kidney Transplantation; Kidney Tubules, Proximal; Renal Insufficiency; Retrospective Studies; Scoliosis; Tacrolimus
PubMed: 36059468
DOI: 10.3389/fimmu.2022.979983 -
Infection and Drug Resistance 2022To investigate the efficacy and safety of antiviral drugs in the treatment of coronavirus disease 2019 (COVID-19). (Review)
Review
OBJECTIVE
To investigate the efficacy and safety of antiviral drugs in the treatment of coronavirus disease 2019 (COVID-19).
METHODS
All clinical trials of antiviral drug treatment for COVID-19 from December 2019 to December 2021 in CNKI, PubMed, Embase, Wanfang and VIP databases were searched by computer, and the results were systematically reviewed.
RESULTS
A total of 21 studies were included, including 5 randomized controlled studies, 5 non-randomized controlled studies, 3 retrospective cohort studies, 6 retrospective case series studies, and 2 observational studies, with a total of 2118 patients. The evaluated drugs included Ridzevir, Lopinavir/Ritonavir, Jingluwa, Fapiravi, Abidor, Danorivir, and interferon α. The evaluated antiviral drugs did not show superior efficacy for COVID-19 in clinical trials. In terms of safety, particular attention needs to be paid to the gastrointestinal side effects of lopinavir/ritonavir and the serious side effects of redsivir.
CONCLUSION
There is no specific drug. Antiviral drugs have a greater therapeutic benefit for mild and usual patients, and in severe patients, lopinavir/ritonavir may not be effective. For critically ill patients, adefovir or more than two antiviral drugs can be used early. Antiviral drugs combined with traditional Chinese medicine treatment is effective. In view of the safety of the drug, it is necessary to consider the increase of serum uric acid caused by fapravi, the increase of bilirubin caused by abidol, and the gastrointestinal reactions of pitavir. In addition, other adverse reactions should also be noted.
PubMed: 35983302
DOI: 10.2147/IDR.S362946 -
Biomedicines Jul 2022Currently, interferon alpha and nucleos(t)ide analogues (NAs) are clinically available to treat hepatitis B virus (HBV) infection. Several NAs, including lamivudine...
Currently, interferon alpha and nucleos(t)ide analogues (NAs) are clinically available to treat hepatitis B virus (HBV) infection. Several NAs, including lamivudine (LMV), adefovir (ADV), entecavir (ETV) and tenofovir (TDF or TAF) have been approved and administered to chronic hepatitis B (CHB) patients. NAs inhibit HBV DNA synthesis by targeting the reverse transcriptase (RT) domain of HBV polymerase. Several mutations in the RT domain which lead to drug resistance against NAs have been reported, even for TDF and TAF which are highly potent with very low resistance rate. Besifovir (BFV) is a new antiviral dGMP analogue able to be used as a new NA drug for the control of CHB infection. Drug resistance to BFV is not well known due to its shorter duration of clinical use. Recently, we reported that rtL180M (M) and rtM204V (V) mutations, already resistant to LMV, are associated with BFV resistance. However, the susceptibility to BFV of previously known HBV mutants resistant to various drugs has not been studied. To investigate this, we performed in vitro drug susceptibility assays using natural and artificial mutants that are associated with resistance to LMV, ADV, ETV or TDF. As a result, LMV-resistant mutants were not susceptible to BFV and ETV-resistant clones showed partial resistance against BFV as well. However, ADV-resistant mutants were highly sensitive to BFV. In case of tenofovir-resistant mutations, the HBV mutants harboring primary mutations to tenofovir resistance were susceptible to BFV. Therefore, our study revealed that BSV may serve as an alternative drug for patients with ADV-, ETV-, TDF- or TAF-resistance.
PubMed: 35884942
DOI: 10.3390/biomedicines10071637 -
Journal of Gastroenterology and... Nov 2022In HBeAg negative chronic hepatitis B (CHB) patients, clinical relapse (CR) occurs more frequently, much earlier and often more severely after stopping tenofovir (TDF)... (Observational Study)
Observational Study
BACKGROUND AND AIM
In HBeAg negative chronic hepatitis B (CHB) patients, clinical relapse (CR) occurs more frequently, much earlier and often more severely after stopping tenofovir (TDF) and other nucleos(t)ide analogues (Nucs) than after stopping entecavir (ETV). It is unknown whether off-Nuc hepatitis flare can be alleviated by switching from one Nuc to another.
METHODS
HBeAg-negative CHB patients who had stopped Nuc according to the APASL stopping rule and had been followed-up for > 48 weeks after Nuc cessation were recruited. Patients were classified as four groups: ETV monotherapy (mono-ETV), TDF monotherapy (mono-TDF), switched to ETV (switch-ETV), and switched to TDF (switch-TDF). Both switch groups had switched to the replacement Nuc > 12 weeks prior to end of therapy. Propensity score matching (PSM) was performed to minimize confounders among groups. Cox regression analysis was used to identify risks factors for off-Nuc CR and flares.
RESULTS
A total of 1309 patients (1022 mono-ETV, 219 mono-TDF, 40 switch-ETV and 28 switch-TDF) were enrolled. The median time to CR was 39, 13, 38 and 14 weeks in mono-ETV, mono-TDF, switch-ETV and switch-TDF respectively (P < 0.001). After PSM, the mono-ETV (adjusted HR: 0.39, P < 0.001) and switch-ETV patients (adjusted HR: 0.41, P = 0.003) had both significantly later occurrence and lower rates of CR and flare.
CONCLUSION
In summary, the incidence and timing of CR was determined by ETV or TDF in the last 3 months prior to end of treatment. Patients treated with non-ETV-Nuc switched to ETV > 12 weeks before end of the original Nuc therapy may reduce/defer CR.
Topics: Humans; Tenofovir; Hepatitis B, Chronic; Hepatitis B e Antigens; Hepatitis B virus; Antiviral Agents; DNA, Viral; Treatment Outcome; Symptom Flare Up; Recurrence; Withholding Treatment
PubMed: 35869752
DOI: 10.1111/jgh.15966 -
Frontiers in Aging 2021Aging and obesity are common risk factors for numerous chronic pathologies, and the compounding effects of old age and increased adiposity pose a serious threat to...
Aging and obesity are common risk factors for numerous chronic pathologies, and the compounding effects of old age and increased adiposity pose a serious threat to public health. Starting from the assumption that aging and obesity may have shared underpinnings, we investigated the antiobesogenic potential of a successful longevity intervention, the mTORC1 inhibitor rapamycin. We find that rapamycin prevents diet-induced obesity in mice and increases the activity of C/EBP-β LAP, a transcription factor that regulates the metabolic shift to lipid catabolism observed in response to calorie restriction. Independent activation of C/EBP-β LAP with the antiretroviral drug adefovir dipivoxil recapitulates the anti-obesogenic effects of rapamycin without reducing signaling through mTORC1 and increases markers of fat catabolism in the liver. Our findings support a model that C/EBP-β LAP acts downstream of mTORC1 signaling to regulate fat metabolism and identifies a novel drug that may be exploited to treat obesity and decrease the incidence of age-related disease.
PubMed: 35822052
DOI: 10.3389/fragi.2021.738512 -
Frontiers in Pharmacology 2022Although persistent inhibition of HBV replication by antiviral therapy has shown to slow disease progression, cost-related access barriers to these essential medicines...
Although persistent inhibition of HBV replication by antiviral therapy has shown to slow disease progression, cost-related access barriers to these essential medicines are becoming salient. The national volume-based procurement (NVBP) was piloted in China and led to substantial reduction in the list price of prescription drugs. To examine the impact of NVBP on selected antiviral medication costs per defined daily dose (DDD), procurement volumes, and spending. We employed an interrupted time series design to examine changes in cost per defined daily dose (DDD), procurement volumes, and spending for NVBP bid-winning antiviral medications (tenofovir disoproxil fumarate and entecavir) in 11 pilot cities from 2017 to 2020. Procurement transaction data were obtained from 9,454 hospitals in the Chinese Hospital Pharmaceutical Audit (CHPA) database. In the secondary analysis, the control group comprised two non-NVBP drugs (adefovir and lamivudine) procured in 11 cities not exposed to the NVBP. Cost per DDD of the two hepatitis B virus (HBV) antiviral medications reduced by CNY1.598 ( = 0.002) immediately following the implementation of NVBP, dropping from an average cost of CNY16.483 per DDD at baseline to CNY6.420 at the end of the observation period. NVBP implementation resulted in a substantial reduction in daily costs of antivirals and an increase in monthly procurement volumes by 6.674 million DDDs ( = 0.017), while monthly spending was reduced by CNY138.26 million ( = 0.002). In the secondary ITS analysis with a control group, the average cost per DDD of the NVBP bid-winning antivirals declined by CNY4.537 ( < 0.001), monthly procurement volumes increased by 7.209 million DDDs ( = 0.002), and monthly spending dropped by CNY138.83 million ( < 0.001). Volume-based procurement piloted in China may be effective for reducing price and total expenditures and improving drug utilization, which is especially important for HBV patients who need constant access to antiviral therapies.
PubMed: 35734415
DOI: 10.3389/fphar.2022.842944