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World Journal of Clinical Cases Jul 2021Since the initial recognition of coronavirus disease 2019 (COVID-19) in Wuhan, this infectious disease has spread to most areas of the world. The pathogenesis of...
BACKGROUND
Since the initial recognition of coronavirus disease 2019 (COVID-19) in Wuhan, this infectious disease has spread to most areas of the world. The pathogenesis of COVID-19 is yet unclear. Hepatitis B virus (HBV) reactivation occurring in COVID-19 patients has not yet been reported.
CASE SUMMARY
A 45-year-old hepatitis B man with long-term use of adefovir dipivoxil and entecavir for antiviral therapy had HBV reactivation after being treated with methylprednisolone for COVID-19 for 6 d.
CONCLUSION
COVID-19 or treatment associated immunosuppression may trigger HBV reactivation.
PubMed: 34307577
DOI: 10.12998/wjcc.v9.i19.5266 -
Medicina Clinica Mar 2022
Topics: Adenine; Humans; Hypophosphatemia; Organophosphonates; Osteomalacia
PubMed: 34256937
DOI: 10.1016/j.medcli.2021.05.019 -
European Journal of Medicinal Chemistry Oct 2021A series of novel acyclic nucleoside phosphonates (ANPs) was synthesized as potential adenylate cyclase inhibitors, where the adenine nucleobase of adefovir (PMEA) was...
A series of novel acyclic nucleoside phosphonates (ANPs) was synthesized as potential adenylate cyclase inhibitors, where the adenine nucleobase of adefovir (PMEA) was replaced with a 5-substituted 2-aminothiazole moiety. The design was based on the structure of MB05032, a potent and selective inhibitor of fructose 1,6-bisphosphatase and a good mimic of adenosine monophosphate (AMP). From the series of eighteen novel ANPs, which were prepared as phosphoroamidate prodrugs, fourteen compounds were potent (single digit micromolar or submicromolar) inhibitors of Bordetella pertussis adenylate cyclase toxin (ACT), mostly without observed cytotoxicity in J774A.1 macrophage cells. Selected phosphono diphosphates (nucleoside triphosphate analogues) were potent inhibitors of ACT (IC as low as 37 nM) and B. anthracis edema factor (IC as low as 235 nM) in enzymatic assays. Furthermore, several ANPs were found to be selective mammalian AC1 inhibitors in HEK293 cell-based assays (although with some associated cytotoxicity) and one compound exhibited selective inhibition of mammalian AC2 (only 12% of remaining adenylate cyclase activity) but no observed cytotoxicity. The mammalian AC1 inhibitors may represent potential leads in development of agents for treatment of human inflammatory and neuropathic pain.
Topics: Adenylate Cyclase Toxin; Adenylyl Cyclase Inhibitors; Animals; Anti-Bacterial Agents; Bacillus anthracis; Bordetella pertussis; Cell Line; Dose-Response Relationship, Drug; Humans; Mice; Microbial Sensitivity Tests; Molecular Structure; Neuralgia; Organophosphonates; Structure-Activity Relationship; Thiazoles
PubMed: 34102377
DOI: 10.1016/j.ejmech.2021.113581 -
Frontiers in Public Health 2021Germany is a low prevalence country for hepatitis B virus (HBV) infection with higher prevalence in vulnerable groups. The number of treated chronic hepatitis B (CHB)...
Germany is a low prevalence country for hepatitis B virus (HBV) infection with higher prevalence in vulnerable groups. The number of treated chronic hepatitis B (CHB) patients is unknown. We aimed to determine the number of CHB patients treated with nucleos(t)ide analogs (NUCs), the treatment costs within the statutory health insurance (SHI) in Germany and per patient per month. Data on pharmacy bills of NUCs to patients with SHI between 2008 and 2019 were purchased from Insight Health™ and described. Negative binomial regression was used for trend analysis. Number of patients increased between 2008 and 2019 (4.9% per year) with little changes in treatment options. Overall prescription costs were increasing (6.7% per year on average) until the introduction of tenofovir and entecavir generics in 2017 after which costs decreased by 31% in 2019. Average therapy costs peaked at 498 Euro per patient per month in 2016 and decreased to 214 Euro in 2019. Prescriptions changed from 30 to 90 pills per pack over time. HBV therapy was prescribed to 97% by three medical specialist groups, mainly specialists in internal medicine (63%), followed by hospital-based outpatient clinics (20%) and general practitioners (15%). Contrary to guideline recommendation, adefovir was still prescribed after 2011 for 1-5% of patients albeit with decreasing tendency. Prescriptions per 100,000 inhabitants were highest in Berlin and Hamburg. Our data shows, that the number of treated CHB patients increased steadily, while NUC therapy costs decreased. We recommend continued testing and treatment for those eligible to prevent advanced liver disease and possibly decrease further transmission of HBV.
Topics: Antiviral Agents; Berlin; Germany; Hepatitis B; Hepatitis B, Chronic; Humans
PubMed: 34095070
DOI: 10.3389/fpubh.2021.667253 -
Frontiers in Pharmacology 2021Adefovir dipivoxil (ADV) is widely used for chronic hepatitis B therapy in China. To explore the clinical features and prognosis of ADV-induced osteomalacia and to...
Adefovir dipivoxil (ADV) is widely used for chronic hepatitis B therapy in China. To explore the clinical features and prognosis of ADV-induced osteomalacia and to analyze the association between osteomalacia and genetic variants in 51 drug transporters genes. Clinical and follow-up data of the ADV-treated patients were collected. Target capture sequencing was used to identify genetic variations of 51 drug transporter genes. A total of 193 hepatitis B patients treated with ADV were enrolled, of whom 140 had osteomalacia. The other 53 without osteomalacia were included in the control group. The median duration of ADV treatment before the onset of osteomalacia was 6.5 years (range:1.5-7 years). We found that most patients with osteomalacia had hypophosphatemia, high serum alkaline phosphatase levels, hypouricemia, nondiabetic glycosuria, proteinuria. Stopping ADV administration, supplementing calcitriol and calcium were effective treatments. During 3-6 months of follow-up, the clinical symptoms and biochemical indicators of patients with osteomalacia have been significantly improved. There was no significant difference in duration of adefovir treatment in patients with or without osteomalacia ( = 0.791). Through regression analysis, we found that age was a risk factor for osteomalacia [per 1 year, odds ratio (OR), 1.053; 95% confidence interval (95% CI), 1.020-1.087; = 0.015]. 1992 single nucleotide variants were found using target capture sequencing. However, the associations of genetic variants of 51 drug transporter genes and the risk of osteomalacia were negligible. Osteomalacia is prone to occur in patients with chronic hepatitis B treated with long-term ADV at a therapeutic dose. After standard treatment, the prognosis is mostly good. We failed to find genetic variants that can predict the risk of ADV-induced osteomalacia.
PubMed: 33995038
DOI: 10.3389/fphar.2021.636352 -
Clinical Gastroenterology and... Feb 2022It remains unknown whether tenofovir alafenamide (TAF) could replace tenofovir disoproxil fumarate (TDF) in patients with drug-resistant hepatitis B virus (HBV). (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND & AIMS
It remains unknown whether tenofovir alafenamide (TAF) could replace tenofovir disoproxil fumarate (TDF) in patients with drug-resistant hepatitis B virus (HBV).
METHODS
In this multicenter randomized non-inferiority trial, 174 patients with HBV resistant to multiple drugs (lamivudine, entecavir, and/or adefovir) under TDF monotherapy for ≥96 weeks were randomized 1:1 to switch to TAF (n = 87) or continue TDF (n = 87) for 48 weeks. The primary endpoint was proportion of patients with HBV DNA <60 IU/mL at week 48.
RESULTS
At baseline, 84 and 80 patients had HBV DNA <60 IU/mL in the TAF and TDF groups, respectively. At week 48, the proportion of patients with HBV DNA <60 IU/mL was 98.9% (86/87) in TAF group, showing non-inferiority to TDF group (97.7%, 85/87; difference, 1.1%; 95% confidence interval, -2.7% to 5.0%). Changes in median alanine aminotransferase at week 48 from baseline were statistically different between TAF and TDF groups (-3 IU/L vs +2 IU/L; P = .02). TAF group showed a statistically greater increase in bone mineral density at spine (+1.84% vs +0.08%; P = .01) and numerically higher increase in mean estimated glomerular filtration rate (+8.2% vs +4.5%; P = .06) compared with TDF group. Compared with TDF group, TAF group showed significantly greater increases in mean body weight (0.71 vs -0.37 kg; P = .01) and total, low-density lipoprotein, and high-density lipoprotein cholesterol levels (P < .001 for all) at week 48 from baseline.
CONCLUSIONS
TAF could be substituted for TDF in patients with multidrug-resistant HBV for improved bone and renal safety without a loss of efficacy. However, increases in body weight and cholesterol levels with TAF treatment would be a concern. ClinicalTrials.gov no.: NCT03241641.
Topics: Alanine; Antiviral Agents; Hepatitis B; Hepatitis B, Chronic; Humans; Tenofovir; Treatment Outcome
PubMed: 33962041
DOI: 10.1016/j.cgh.2021.04.045 -
European Journal of Clinical... Aug 2021Prophylaxis with hepatitis B immunoglobulin (HBIG) represents an efficient strategy for reducing the risk of hepatitis B virus (HBV) recurrence after liver... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Prophylaxis with hepatitis B immunoglobulin (HBIG) represents an efficient strategy for reducing the risk of hepatitis B virus (HBV) recurrence after liver transplantation (LT). Unfortunately, the long-term use of HBIG presents high costs. Therefore, the use of prophylaxis based only on nucleos(t)ide analogues (NUC) has been recently postulated. The present meta-analysis aimed to evaluate the impact of HBIG ± NUC vs HBIG alone or NUC alone in post-LT HBV recurrence prophylaxis.
MATERIALS AND METHODS
A systematic literature search was performed using PubMed and Cochrane databases. The primary outcome investigated was the HBV recurrence after LT. Three analyses were done comparing the effect of (a) HBIG + NUC vs HBIG alone; (b) HBIG+NUC vs NUC alone; and (c) HBIG alone vs NUC alone. Sub-analyses were also performed investigating the effect of low and high genetic barrierto-recurrence NUC.
RESULTS
Fifty-one studies were included. The summary OR (95%CI) showed a decreased risk with the combination of HBIG + NUC vs HBIG alone for HBV recurrence, being 0.36 (95% CI = 0.22-0.61; P < .001). HBIG + NUC combined treatment reduced HBV reappearance respect to NUC alone (OR = 0.22; 95% CI = 0.16-0.30; P < .0001). Similarly, HBIG alone was significantly better than NUC alone in preventing HBV recurrence (OR = 0.20; 95% CI = 0.09-0.44; P < .0001).
CONCLUSIONS
Prophylaxis with HBIG is relevant in preventing post-LT HBV recurrence. Its combination with NUC gives the best results in terms of protection. The present results should be considered in light of the fact that also old studies based on lamivudine use were included. Studies exploring in detail high genetic barrier-to-recurrence NUC and protocols with definite use of HBIG are needed.
Topics: Antiviral Agents; Drug Therapy, Combination; Hepatitis B; Humans; Immunoglobulins; Liver Transplantation; Nucleosides; Recurrence; Secondary Prevention
PubMed: 33866547
DOI: 10.1111/eci.13575 -
Life (Basel, Switzerland) Mar 2021Nucles(t)ide analogs (NAs) are effective for chronic hepatitis B (CHB). NAs suppress hepatic decompensation and hepatocarcinogenesis, leading to a dramatic improvement...
Nucles(t)ide analogs (NAs) are effective for chronic hepatitis B (CHB). NAs suppress hepatic decompensation and hepatocarcinogenesis, leading to a dramatic improvement of the natural course of patients with CHB. However, renal dysfunction is becoming an important issue for the management of CHB. Renal dysfunction develops in patients with the long-term treatment of NAs including adefovir dipivoxil and tenofovir disoproxil fumarate. Recently, several studies have reported that the newly approved tenofovir alafenamide (TAF) has a safe profile for the kidney due to greater plasma stability. In this mini-review, we discuss the effectiveness of switching to TAF for NAs-related renal tubular dysfunction in patients with CHB.
PubMed: 33806752
DOI: 10.3390/life11030263 -
Antiviral Research May 2021Multidrug-resistance hepatitis B virus (MDR HBV), defined as those with mutations resistant to both nucleoside analogs lamivudine/telbivudine/entecavir (LAM/LdT/ETV) and...
Investigation of multidrug-resistance mutations of hepatitis B virus (HBV) in a large cohort of chronic HBV-infected patients with treatment of nucleoside/nucleotide analogs.
Multidrug-resistance hepatitis B virus (MDR HBV), defined as those with mutations resistant to both nucleoside analogs lamivudine/telbivudine/entecavir (LAM/LdT/ETV) and nucleotide analog adefovir (ADV), has potential to cause treatment difficulty. To clarify clinical prevalence and virological features of MDR HBV, we investigated serum samples from 28,236 chronic HBV-infected patients with treatment of nucleoside/nucleotide analogs. All patients underwent resistance testing in the Fifth Medical Center of Chinese PLA General Hospital between 2007 and 2019. MDR mutations were screened by direct sequencing; MDR strains (with mutations co-located on the same viral genome) were verified by clonal sequencing (≥20 clones/sample) and subjected to phenotypic analysis if necessary. MDR mutations were detected in 0.81% (229/28,236) patients. MDR strains were verified in 83.0% (190/229) of MDR mutation-positive patients. As ETV-resistance mutation (ETVr) had additional mutation(s) on LAMr conferring more resistance, MDR mutations fell into LAMr + ADVr and ETVr + ADVr subsets. Sixteen mutation patterns of MDR strains were verified, including eight with LAMr + ADVr and eight with ETVr + ADVr. Refractory to sequential therapies of LAM/LdT/ETV and ADV were closely linked with MDR HBV development. Ten representative MDR strains (five LAMr + ADVr and five ETVr + ADVr) tested all had decrease in replication capacity compared to wild-type strains and decrease extent was positively related with the number of primary resistance on viral genome. Compared to ADV + ETV, TDF/TDF + ETV showed higher inhibitory rates on MDR HBV, especially for the five ETVr + ADVr strains (74.5%-97.6% vs. 60.2%-79.5%, all P < 0.05). This study significantly extends the knowledge on MDR HBV and has clinical implications for resistance management.
Topics: Adenine; Adult; Antiviral Agents; Cohort Studies; DNA, Viral; Drug Resistance, Multiple, Viral; Female; Guanine; Hepatitis B virus; Hepatitis B, Chronic; Humans; Lamivudine; Longitudinal Studies; Male; Middle Aged; Mutation; Nucleosides; Nucleotides; Organophosphonates; Phylogeny; Telbivudine; Viral Load; Virus Replication
PubMed: 33711338
DOI: 10.1016/j.antiviral.2021.105058 -
Evidence-based Complementary and... 2021Kushenin (KS) has become a traditional Chinese medicine preparation that plays an important role in treating chronic hepatitis B (CHB). Many clinical studies have...
Kushenin (KS) has become a traditional Chinese medicine preparation that plays an important role in treating chronic hepatitis B (CHB). Many clinical studies have discussed its curative effect and safety in combination with adefovir dipivoxil (ADV) or entecavir (ETV) for treating CHB, but there is still a lack of a systematic analysis. Therefore, this study evaluated the efficacy and safety of KS through a meta-analysis to better guide clinical treatment. Seven databases were searched to identify randomized controlled trials (RCTs) concerning KS combined with ADV or ETV for treating CHB. The primary outcomes included serum viral indices and adverse events, and the secondary outcomes were liver function indices. The risk of bias of the included RCTs was appraised by Cochrane software. STATA 15.1 and Review Manager 5.3 software were used for the meta-analysis. Thirty-two RCTs recruiting 3343 patients with CHB were collected for this meta-analysis. KS combined with ETV or ADV led to an amelioration of the CHB index to various degrees. In short, the meta-analysis indicated that the combination group, compared to the single group, showed great improvement in HBeAg seroconversion, frequency of undetectable HBV-DNA levels, loss of serum HBeAg, and loss of serum HBsAg. The combination treatment also decreased serum HBV-DNA levels when compared to the levels after the single treatment. However, KS combined with ADV or ETV displayed no remarkable difference in the incidence of adverse events or in serum ALT levels. Current evidence showed that, compared with the use of either drug alone, KS combined with ADV or ETV can improve the clinical efficacy of CHB treatment.
PubMed: 33708259
DOI: 10.1155/2021/8856319