Search

Purpose: Adefovir (as dipivoxil) was selected as a probe drug in a previous transporter cocktail phenotyping study to assess renal organic anion transporter 1 (OAT1), with renal clearance (CLR) as the primary parameter describing renal elimination. An approximately 20% higher systemic exposure of adefovir was observed when combined with other cocktail components (metformin, sitagliptin, pitavastatin, and digoxin) compared to sole administration. The present evaluation applied a population pharmacokinetic (popPK) modeling approach to describe adefovir pharmacokinetics as a cocktail component in more detail. Methods: Data from 24 healthy subjects were reanalyzed. After establishing a base model, covariate effects, including the impact of co-administered drugs, were assessed using forward inclusion then backward elimination. Results: A one-compartment model with first-order absorption (including lag time) and a combination of nonlinear renal and linear nonrenal elimination best described the data. A significantly higher apparent bioavailability (73.6% vs. 59.0%) and a lower apparent absorption rate constant (2.29 h−1 vs. 5.18 h−1) were identified in the combined period compared to the sole administration period, while no difference was seen in renal elimination. The population estimate for the Michaelis-Menten constant (Km) of the nonlinear renal elimination was 170 nmol/L, exceeding the observed range of adefovir plasma maximum concentration, while the maximum rate (Vmax) of nonlinear renal elimination was 2.40 µmol/h at the median absolute estimated glomerular filtration rate of 105 mL/min. Conclusion: The popPK modeling approach indicated that the co-administration primarily affected the apparent absorption and/or prodrug conversion of adefovir dipivoxil, resulting in the minor drug-drug interaction observed for adefovir as a victim. However, renal elimination remained unaffected. The high Km value suggests that assessing renal OAT1 activity by CLR has no relevant misspecification error with the cocktail doses used. [ABSTRACT FROM AUTHOR]

Human adenovirus type 55 (HAdV-55) can usually cause acute respiratory diseases. Unfortunately, there is no available specific antiviral drug. In the present study, 14 nucleotide analogs were screened for their anti -HAdV-55 activities in vitro. The results suggested that cidofovir could inhibit HAdV-55 infection in HEp-2 cells, providing strong evidence for further research on treating HAdV-55 infection. [ABSTRACT FROM AUTHOR]

Background: It is a challenging issue regarding the optimal antiviral treatment of children with chronic hepatitis B (CHB). The efficacy comparison of interferon (IFN) or nucleos(t)ide analogs (NAs) monotherapy with their combination could better understand this issue. Methods: PubMed, EMBASE, Cochrane Library, Wanfang, CNKI, and abstracts of major international hepatology meetings were searched from inception to Feb 8, 2022. Randomized control trials and observational studies reporting the efficacy of combination therapy with IFN and NAs in children with CHB were eligible. Results: A total of 17 studies were included. Compared with IFN monotherapy, combination therapy with IFN and NAs was significantly associated with increased rates of HBV DNA undetectable, HBeAg clearance, HBeAg seroconversion, alanine transaminase (ALT) normalization as well as the composite treatment response both at the end of treatment and during the follow-up period (RRs ranged from 1.23 to 1.75). A favorable trend for HBsAg seroconversion was found in IFN plus NAs-treated children, but not for the HBsAg clearance at the end of treatment. Although a similar trend towards the superiority of the combination therapy versus NAs monotherapy was observed (RRs ranged from 1.24 to 2.33) except for the HBV DNA undetectable rate at the end of treatment, the number of reported studies was limited. Conclusions: Combination therapy with IFN and NAs is more effective than IFN monotherapy in viral suppression and serological response for children with CHB. More studies were still needed to reveal the efficacy of this combination therapy compared with NAs monotherapy. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 (ZrMo2O8) was synthesized by a wet chemical method, and a composite with multi-walled carbon nanotubes (MWCNTs) was made. ZrMo2O8-MWCNTs composite was dropped onto the surface of a glassy carbon electrode (GCE) to prepare ZrMo2O8-MWCNTs/GCE, and ZrMo2O8-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, ZrMo2O8-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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

7-Hydroxycoumarin (7-HC) is a natural coumarin compound rich in Chinese herbal medicines and has various pharmacological activities. After oral administration of 7-HC in rodents, its conjugated metabolites 7-hydroxycoumarin-β-D-glucuronide (7-HCG) and 7-hydroxycoumarin sulfate (7-HCS), exhibit high systemic exposure and urinary excretion. Organic anion transporters 1 and 3 (OAT1 and OAT3), mainly expressed in the proximal renal tubules, play an important role in drug-drug interactions and drug-induced kidney injury. We aimed to explore the mechanisms of OAT-mediated drug interactions and renal protective mechanisms of 7-HC and its conjugates. OAT-overexpressing cell models revealed that 7-HC was not a substrate for OAT1 and OAT3, while 7-HCG was specifically transported by OAT3. In contrast, 7-HCS can be transported by both OATs. Besides, 7-HC significantly inhibited the activity of OAT1 and OAT3, while 7-HCS had a strong inhibitory effect on OAT1 (IC 50  < 10 μM). After co-administration of 100 mg/kg of 7-HC to mice, systemic exposure and clearance of furosemide (a clinical substrate of OATs) were significantly increased and decreased, respectively. In addition, 7-HC decreased OAT-mediated cytotoxicity and reduced the renal distribution of adefovir in mice. Together, these findings will provide support for OAT-mediated drug interactions and the renal protection of 7-HC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Abstract Background Entecavir (ETV) is recommended as a first-line anti-HBV treatment. However, many chronic hepatitis B patients initiate anti-HBV treatment such as lamivudine and telbivudine with low genetic barriers in China, which leads to compensatory mutations and increases the rate of ETV resistance. The management of ETV resistance in China is an essential clinical issue. Methods Patients from 2011 to 2017 with nucleos(t)ide analog resistance were screened and 72 patients with ETV resistance were included. These patients received different rescue therapies including an ETV and adefovir (ADV) combination therapy group (n = 25), a tenofovir (TDF) monotherapy group (n = 27), and an ETV and TDF combination therapy group (n = 20). Virologic, biochemical, and serologic responses were compared among the three groups. Results The rate of ETV resistance among all HBV-resistant variants increased from 6.04% in 2011 to 15.02% in 2017. TDF monotherapy and TDF combination groups showed similar rates of negative HBV DNA at 48 weeks (74.07% vs 70.00%, P > 0.05), while the ETV and ADV group showed the worst virologic response (28.00%). Also, TDF monotherapy and TDF combination therapy showed similar decline of HBV DNA at weeks 12, 24, and 48. There was no significant difference in the rates of HBeAg clearance, ALT normalization, and abnormal renal function among the three groups. Conclusions TDF monotherapy showed a comparable virologic response to TDF and ETV combination therapy and a better virologic response than ETV and ADV combination therapy. Thus, TDF monotherapy is the preferred rescue therapy for ETV resistance.

[Display omitted] • Adefovir accumulated in the renal interstitium causes renal interstitial fibrosis when Oat1/3 were inhibited by probenecid for long-term. • Adefovir accumulation in the renal interstitium triggers mast cell degranulation and promotes renal interstitial fibrosis. • Mast cell membrane stabilizer sodium cromoglycate and angiotensin receptor antagonist valsartan ameliorate adefovir-associated fibrosis. Organic anion transporters 1 (OAT1) and OAT3 are responsible for transporting adefovir (ADV) into renal tubular epithelial cells. Our previous research found that ADV accumulated in the renal interstitium and caused renal interstitial fibrosis when Oat1/3 were inhibited by OATs inhibitor probenecid for long-term. Mast cells (MCs) in the interstitial space are considered to be key drivers of renal fibrosis. The current work investigated the effect of ADV on MCs in vitro and during the development of interstitial fibrosis in rats. Results indicate that ADV triggers chymase release from cultured RBL-2H3 mast cells in a time-and concentration-dependent manner. Angiotensin II (Ang II) in renal interstitium is generated mainly by chymase, renin and other products released from MCs, and has a direct effect on fibrosis through the angiotensin receptor. The concentrations of Ang II and fibrosis was significantly increased after administration of ADV alone or with probenecid for 4 weeks. The MCs membrane stabilizer sodium cromoglycate (SCG) and the angiotensin receptor antagonist Valsartan (VAL) could ameliorate ADV-induced nephrotoxicity. Additionally, SCG or VAL could reduce the accumulation of ADV in the renal interstitium by upregulating the expression of Oat1/3 and multidrug resistance-associated protein 4. Therefore, ADV accumulation in the renal interstitium could promote the degranulation of interstitial MCs and drive the development of renal fibrosis. SCG or VAL could ameliorate ADV-associated fibrosis by decreasing degranulation of MCs and accelerating renal clearance of ADV. [ABSTRACT FROM AUTHOR]

Background: Due to the embryotoxicity found in animal studies and scarce clinical data in pregnant women, it is still controversial whether entecavir (ETV) and adefovir dipivoxil (ADV) are safe during human pregnancy. This is of paramount importance when counseling pregnant women with hepatitis B virus (HBV) on risks and benefits to their offspring. Objective: To quantify the association between administration of ETV and ADV in pregnant women and occurrence of adverse events (AEs) during pregnancy (AEDP). Methods: Pregnancy reports from the FDA Adverse Event Reporting System (FAERS) were used to perform a retrospective analysis of AEDP associated with ETV or ADV. Disproportionality analysis estimating the reporting odds ratio (ROR) was conducted to identify the risk signals. A signal was defined as ROR value >2, and lower limit of 95% confidence interval (CI)> 1. Results: A total of 1,286,367 reports involving AEDP were submitted to FAERS by healthcare professionals. Of these, there were 547 cases reporting ETV and 242 cases reporting ADV as primary suspected drugs. We found a moderate or strong signal for increased risk of spontaneous abortion when comparing ETV with tenofovir disoproxil fumarate (TDF) and telbivudine (LdT), with RORs equal to 1.58 (95% CI, 1.09–2.30) and 2.13 (95% CI, 1.04–4.36), respectively. However, when the included reports were limited to indication containing HBV infection, no signals for increased AEDP were detected. Futhermore, a strong signal for increased risk of spontaneous abortion was identified in patients with HBV infection when comparing ETV or ADV with lamivudine (LAM), with RORs of 3.55 (95% CI, 1.54–8.18) and 2.85 (95% CI, 1.15–7.08), respectively. Conclusion: We found a strong signal for increased risk of spontaneous abortion in patients with HBV infection taking ETV or ADV, in comparison with those prescribed with LAM. Moreover, no obvious signal association of human teratogenicity with exposure to ETV or ADV was identified in fetuses during pregnancy. Nevertheless, owing to the limitations of a spontaneous reporting database, which inevitably contains potential biases, there is a pressing need for well-designed comparative safety studies to validate these results in clinical practice. [ABSTRACT FROM AUTHOR]

Introduction and Objectives: Covalently closed circular (ccc)DNA acts as a viral reservoir in the liver of patients with a chronic hepatitis B (CHB) infection and can only be quantified in liver biopsies. Hepatitis B core-related antigen (HBcrAg) levels in plasma/serum have been proposed to reflect intrahepatic cccDNA-levels and may therefore monitor treatment efficacy. This study aimed to validate the relationship between HBcrAg and other intrahepatic and circulating viral markers in CHB patients with high viral load, before and after combination treatment. Materials and methods: Plasma/serum levels of HBcrAg, HBsAg, HBV-DNA, and HBV pregenomic RNA (HBVpgRNA), and intrahepatic cccDNA and HBV-DNA levels and fibrosis scores were measured in 89 CHB patients with HBV-DNA levels of >100,000 copies/mL (17,182 IU/mL). Measurements were done before and after a 48-week treatment with pegylated interferon alfa-2a and adefovir in a prospective study (ISRCTN77073364). Results: Baseline HBcrAg-values correlated strongly with intrahepatic cccDNA (r 0.77, p < 0.001), intrahepatic HBV-DNA (r 0.73, p < 0.001) and plasma/serum HBV-DNA (r 0.80, p < 0.001), HBV-pgRNA (r 0.80, p < 0.001), and to lesser extend HBsAg (r 0.56, p < 0.001). Baseline HBcrAg-levels could not predict functional cure (FC) but HBcrAg-levels declined more strongly in patients who developed FC or HBeAg-loss. Furthermore, most correlations persisted at the end of treatment and follow-up. Conclusions: HBcrAg reflects cccDNA transcription activity more accurately than HBsAg and may replace HBV-DNA as a marker during future treatment regimens, especially when cccDNA transcription is targeted or nucleot(s)ide analogues are included in the treatment regime. [ABSTRACT FROM AUTHOR]

Background/Aims Suboptimal responses to lamivudine or telbivudine plus adefovir (LAM/LdT+ADV) rescue therapy are common in patients with LAM-resistant hepatitis B virus (HBV) infections. We compared patients switched to entecavir plus tenofovir (ETV+TDF) to those maintained on LAM/LdT+ADV. Methods This prospective randomized controlled trial examined 91 patients whose serum HBV DNA levels were greater than 60 IU/mL after at least 24 weeks of treatment with LAM/LdT+ADV for LAM-resistant HBV. Patients were randomized to receive a new treatment (ETV+TDF, n=45) or maintained on the same treatment (LAM/LdT+ADV, n=46) for 48 weeks. Patients with baseline ADV resistance were excluded. Results Compared to LAM/LdT+ADV group, ETV+TDF group had more patients with a virologic response (42/45 [93.33%] vs. 3/46 [6.52%], P

Background: Due to the embryotoxicity found in animal studies and scarce clinical data in pregnant women, it is still controversial whether entecavir (ETV) and adefovir dipivoxil (ADV) are safe during human pregnancy. This is of paramount importance when counseling pregnant women with hepatitis B virus (HBV) on risks and benefits to their offspring.Objective: To quantify the association between administration of ETV and ADV in pregnant women and occurrence of adverse events (AEs) during pregnancy (AEDP).Methods: Pregnancy reports from the FDA Adverse Event Reporting System (FAERS) were used to perform a retrospective analysis of AEDP associated with ETV or ADV. Disproportionality analysis estimating the reporting odds ratio (ROR) was conducted to identify the risk signals. A signal was defined as ROR value >2, and lower limit of 95% confidence interval (CI)> 1.Results: A total of 1,286,367 reports involving AEDP were submitted to FAERS by healthcare professionals. Of these, there were 547 cases reporting ETV and 242 cases reporting ADV as primary suspected drugs. We found a moderate or strong signal for increased risk of spontaneous abortion when comparing ETV with tenofovir disoproxil fumarate (TDF) and telbivudine (LdT), with RORs equal to 1.58 (95% CI, 1.09–2.30) and 2.13 (95% CI, 1.04–4.36), respectively. However, when the included reports were limited to indication containing HBV infection, no signals for increased AEDP were detected. Futhermore, a strong signal for increased risk of spontaneous abortion was identified in patients with HBV infection when comparing ETV or ADV with lamivudine (LAM), with RORs of 3.55 (95% CI, 1.54–8.18) and 2.85 (95% CI, 1.15–7.08), respectively.Conclusion: We found a strong signal for increased risk of spontaneous abortion in patients with HBV infection taking ETV or ADV, in comparison with those prescribed with LAM. Moreover, no obvious signal association of human teratogenicity with exposure to ETV or ADV was identified in fetuses during pregnancy. Nevertheless, owing to the limitations of a spontaneous reporting database, which inevitably contains potential biases, there is a pressing need for well-designed comparative safety studies to validate these results in clinical practice.

Introduction and Objectives: Covalently closed circular (ccc)DNA acts as a viral reservoir in the liver of patients with a chronic hepatitis B (CHB) infection and can only be quantified in liver biopsies. Hepatitis B core-related antigen (HBcrAg) levels in plasma/serum have been proposed to reflect intrahepatic cccDNA-levels and may therefore monitor treatment efficacy. This study aimed to validate the relationship between HBcrAg and other intrahepatic and circulating viral markers in CHB patients with high viral load, before and after combination treatment. Materials and methods: Plasma/serum levels of HBcrAg, HBsAg, HBV-DNA, and HBV pregenomic RNA (HBV-pgRNA), and intrahepatic cccDNA and HBV-DNA levels and fibrosis scores were measured in 89 CHB patients with HBV-DNA levels of >100,000 copies/mL (17,182 IU/mL). Measurements were done before and after a 48-week treatment with pegylated interferon alfa-2a and adefovir in a prospective study (ISRCTN77073364). Results: Baseline HBcrAg-values correlated strongly with intrahepatic cccDNA (ρ 0.77, p

Background: In countries with unavailable tenofovir, a combination of lamivudine (LMV) and adefovir (ADV) is recommended for the treatment of LMV-resistant chronic hepatitis B (CHB). Considering that telbivudine (L-dT) was demonstrated to be superior to LMV in previous studies, L-dT and ADV combination therapy is expected to show better antiviral efficacy than the combination of LMV and ADV in patients with LMV-resistant CHB. Methods: This was a prospective randomized multicenter study. The primary endpoint was Hepatitis B Virus (HBV) DNA reduction after 52 weeks of treatment. The secondary endpoints were HBV DNA undetectability, hepatitis B e antigen seroconversion, the incidence of virological and biochemical breakthroughs, and safety during the study period. Results: A total of 43 LMV-resistant CHB patients were enrolled. Twenty-one were treated with LMV + ADV and 22 with L-dT + ADV. After 52weeks of antiviral treatment, the HBV DNA reduction showed no significant intergroup difference (-4.54 1.23 log IU/mL in the LMV + ADV group, -4.24 1.46 log IU/mL in the L-dT + ADV group, P = 0.475). There were no significant intergroup differences in HBV DNA undetectability rates, mean HBV DNA level, or hepatitis B e antigen seroconversion rate at 13, 26, 39, and 52 weeks of treatment. In terms of safety, the mean creatine phosphokinase level was significantly higher in the L-dT + ADV group. Conclusions: In the treatment of LMV-resistant CHB, the combination of L-dT and ADV did not show any clinical benefit compared to the combination of LMV and ADV. [ABSTRACT FROM AUTHOR]

Background: Entecavir (ETV) is recommended as a first-line anti-HBV treatment. However, many chronic hepatitis B patients initiate anti-HBV treatment such as lamivudine and telbivudine with low genetic barriers in China, which leads to compensatory mutations and increases the rate of ETV resistance. The management of ETV resistance in China is an essential clinical issue.Methods: Patients from 2011 to 2017 with nucleos(t)ide analog resistance were screened and 72 patients with ETV resistance were included. These patients received different rescue therapies including an ETV and adefovir (ADV) combination therapy group (n = 25), a tenofovir (TDF) monotherapy group (n = 27), and an ETV and TDF combination therapy group (n = 20). Virologic, biochemical, and serologic responses were compared among the three groups.Results: The rate of ETV resistance among all HBV-resistant variants increased from 6.04% in 2011 to 15.02% in 2017. TDF monotherapy and TDF combination groups showed similar rates of negative HBV DNA at 48 weeks (74.07% vs 70.00%, P > 0.05), while the ETV and ADV group showed the worst virologic response (28.00%). Also, TDF monotherapy and TDF combination therapy showed similar decline of HBV DNA at weeks 12, 24, and 48. There was no significant difference in the rates of HBeAg clearance, ALT normalization, and abnormal renal function among the three groups.Conclusions: TDF monotherapy showed a comparable virologic response to TDF and ETV combination therapy and a better virologic response than ETV and ADV combination therapy. Thus, TDF monotherapy is the preferred rescue therapy for ETV resistance. [ABSTRACT FROM AUTHOR]

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 (ZrMo2O8) was synthesized by a wet chemical method, and a composite with multi-walled carbon nanotubes (MWCNTs) was made. ZrMo2O8-MWCNTs composite was dropped onto the surface of a glassy carbon electrode (GCE) to prepare ZrMo2O8-MWCNTs/GCE, and ZrMo2O8-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, ZrMo2O8-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.

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.

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. [ABSTRACT FROM AUTHOR]