Safety Of Tenofovir Disoproxil Fumarate Research Articles

Evaluation of the Efficacy and Safety of Tenofovir Disoproxil Fumarate in Intercepting Mother-to-Child Transmission of Hepatitis B Virus.

Vertical transmission of hepatitis B virus (HBV), especially in Asia, is a key target in the global elimination of HBV. This study assessed the effects of tenofovir disoproxil fumarate (TDF) in pregnant women for mother-to-infant transmission of HBV. A total of 122 pregnant women at our hospital met the inclusion criteria for high HBV DNA viral loads. They were randomly divided into TDF-treatment (n=70) and placebo (n=52) groups. Maternal liver function and serum HBV DNA load were tested before and after treatment. Clinical and laboratory data of infants were assayed at delivery and 7-months post-partum visit and compared between the two groups. There was no difference in clinical characteristics of participants between the two groups. There were no significant differences in liver function markers, including alanine aminotransferase, total bilirubin, blood creatinine, and blood urea nitrogen levels before and after TDF treatment. The serum HBV DNA viral load of the TDF-treated group became significantly lower than those of the control group and their own pre-medication levels. Infants showed no significant difference in body growth, including weight, height, head size, and five-min Apgar score. At 7 months after birth, 94.29% of infants in the TDF group and 86.54% of control-group infants had protective HBsAb levels ≥ 10 mIU/ml (p>0.05). The HBV infection rate of infants in the TDF-treated group was lower than that in the non-treated group. In high-HBV-DNA-load pregnant women, TDF administered from 28 weeks gestational age to delivery was associated with a lower risk of mother-to-infant transmission of HBV.

Efficacy and safety of Tenofovir Disoproxil Fumarate in Egyptian patients with chronic hepatitis B virus infection

Efficacy and safety of Tenofovir Disoproxil Fumarate in Egyptian patients with chronic hepatitis B virus infection

Efficacy and safety of tenofovir disoproxil fumarate versus entecavir in the treatment of acute-on-chronic liver failure with hepatitis B: a systematic review and meta-analysis.

Oral nucleoside (acid) analogues (NAs) are recommended for patients with acute-on-chronic liver failure (ACLF) associated with hepatitis B virus (HBV-ACLF). The efficacy and safety of tenofovir (TDF) and entecavir (ETV) in these patients remain unclear. A comprehensive literature search in PubMed, Web of Science, The Cochrane Library, and Embase database was conducted to select studies published before December 2022 on TDF or ETV for HBV-ACLF. The primary outcomes were survival rates at 4, 12, and 48 weeks. Secondary outcomes were virologic and biochemical responses, serum antigen conversion, liver function score, and safety. Four prospective and one retrospective cohort studies were selected. The overall analysis showed comparable survival rates at 4, 12, and 48 weeks for all patients receiving TDF or ETV (4-week: RR = 1.17, 95% CI: 0.90-1.51, p = 0.24; 12-week: RR = 1.00, 95% CI: 0.88-1.13, p = 0.94; 48-week: RR = 0.96, 95% CI: 0.58-1.57, p = 0.86). Child-Turcotte-Pugh (CTP) score and model for end-stage liver disease (MELD) score at 12 weeks were comparable in both groups but lower than baseline (CTP: SMD = -0.75, 95% CI:-2.81-1.30, p = 0.47; MELD: SMD = -1.10, 95% CI:-2.29-0.08, p = 0.07). At 48 weeks, estimated glomerular filtration rate (eGFR) levels were found to decrease to different degrees from baseline in both the TDF and ETV groups, and the decrease was greater in the TDF group than in the ETV group. No significant differences were found in biochemical, virologic response, and serum antigen conversion between the two groups during the observation period. TDF treatment of HBV-ACLF is similar to ETV in improving survival, liver function, and virologic response but the effects on renal function in two groups in the long term remain unclear. More and larger long-term clinical trials are required to confirm these findings.

Renal Safety of Long-term Tenofovir Disoproxil Fumarate Treatment in Patients With Chronic Hepatitis B.

Data on renal safety of tenofovir disoproxil fumarate (TDF) treatment among individuals with chronic hepatitis B (CHB) are inconsistent. The current study aimed to assess the effect of long-term TDF treatment on renal outcomes in adult patients with CHB. From a CHB cohort in Ethiopia, we included 233 patients treated with TDF and 126 untreated controls. Levels of creatinine and creatinine clearance over time were described in patients with and without TDF treatment. Linear mixed effects models with a treatment × time interaction were used to investigate the effect of TDF on creatinine and creatinine clearance. In treated patients only, change in creatinine and creatinine clearance was estimated separately in the first year as compared with subsequent years via linear mixed effects models. Median follow-up in the treated group was 51 months (IQR, 27-72), and 75% of patients were male (median age, 33 years; IQR, 26-40). Median follow-up in the untreated group was 69 months (IQR, 66-72), and 48% of participants were male (median age, 33 years; IQR, 27-41). We found no change in creatinine over time in TDF-treated patients as compared with a slight increase in untreated patients (P interaction = .003). There was a decrease in creatinine clearance over time in both groups, which was stronger in patients without TDF treatment (P interaction = .007). In TDF-treated patients, changes in creatinine and creatinine clearance occurred mainly within the first 12 months after treatment initiation. This study showed no evidence of long-term renal toxicity of TDF treatment in patients with CHB.

Pregnancy and neonatal safety outcomes of timing of initiation of daily oral tenofovir disoproxil fumarate and emtricitabine pre-exposure prophylaxis for HIV prevention (CAP016): an open-label, randomised, non-inferiority trial

The safety of tenofovir disoproxil fumarate and emtricitabine as pre-exposure prophylaxis (PrEP) in pregnant women not living with HIV is uncertain. We aimed to compare pregnancy and neonatal outcomes in women exposed and not exposed to PrEP during pregnancy. In this single-site, open-label, randomised, non-inferiority trial in Durban, South Africa, we evaluated pregnancy and neonatal outcomes in pregnant women aged 18 years or older, not living with HIV, and at 14-28 weeks' gestation at the time of enrolment. Eligible participants were randomly assigned (1:1) using a computer-generated permuted block (block size of ten) randomisation list to immediate initiation or deferred initiation of PrEP until breastfeeding cessation. Participants in the immediate PrEP group received a monthly supply of once daily oral tenofovir disoproxil fumarate 300 mg and emtricitabine 200 mg. Participants in the deferred PrEP group received standard of care for HIV prevention. The primary outcomes were the occurrence of preterm live birth (<37 weeks gestational age) and very preterm birth (<34 weeks gestational age) determined by menstrual dating, low birthweight (<2500 g), very low birthweight (<1500 g), stillbirth (≥20 weeks gestational age), and small for gestational age (birthweight less than the tenth percentile). Post-natal safety outcomes will be reported elsewhere. We used binomial regression models to estimate risk differences and two-sided 90% CIs. Immediate PrEP was non-inferior to deferred PrEP if the upper bound of the 90% CI of the risk difference was less than the upper predefined non-inferiority margin for preterm birth (7·5%), very preterm birth (2·6%), low birthweight (5·5%), very low birthweight (1·2%), stillbirth (1·0%), and small for gestational age (3·7%). All outcomes were analysed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT3227731. Between Sept 25, 2017, and Dec 6, 2019, we screened 693 women, of whom 540 were randomly assigned to immediate PrEP (n=271) or deferred PrEP (n=269). The median gestational age was 19 weeks (IQR 15-23 for immediate PrEP and 16-23 for deferred PrEP). The risk difference between the immediate PrEP group and the deferred PrEP group for preterm birth was -4·7% (90% CI -10·7 to 1·2; immediate PrEP was non-inferior), for very preterm birth was 0·6% (-3·4 to 4·6; upper limit exceeded the non-inferiority margin), for low birthweight was 2·5% (-1·6 to 6·6; upper limit exceeded the non-inferiority margin), for very low birthweight was 0% (-1·4 to 1·4; upper limit exceeded the non-inferiority margin), for stillbirth was 1·2% (-1·5 to 3·8; upper limit exceeded the non-inferiority margin), and for small for gestational age was 0·9% (-1·2 to 2·9; immediate PrEP was non-inferior). In our study, PrEP was not associated with preterm birth or small for gestational age infants. Our data support the use of tenofovir disoproxil fumarate and emtricitabine in pregnancy and our reassuring findings can be used to allay safety concerns among pregnant women. South African Medical Research Council and Gilead Sciences.

Efficacy and safety of tenofovir disoproxil fumarate or telbivudine used throughout pregnancy for the prevention of mother-to-child transmission of hepatitis B virus: A cohort study

ObjectiveTenofovir disoproxil fumarate (TDF) use compared with telbivudine (LdT) use throughout pregnancy has not been adequately investigated. To compare the efficacy and safety of TDF and LdT for the prevention of mother-to-child transmission (MTCT) of hepatitis B from highly viremic mothers throughout pregnancy in real-world settings. Study designThis was a single-center, retrospective cohort study. From January 1, 2013, to December 31, 2018, we retrospectively enrolled 602 mothers with chronic hepatitis B (CHB) who received antiviral treatment throughout pregnancy at Beijing Ditan Hospital. A total of 562 mothers met the inclusion criteria, with 167 in the TDF group and 395 in the LdT group. Mothers and infants were followed for 28 weeks postpartum. The primary endpoint was the MTCT rate of HBV. The secondary endpoints were the safety profiles in mothers and infants. ResultsThe MTCT rates were 0 % in both the TDF and LdT groups. The rates of neonatal congenital abnormalities were similar between the TDF and LdT groups (1.2 % vs 1.8 %, P = 0.896). There were no significant differences in perinatal complications between the two groups (all P > 0.05). There were also no significant differences in gestational age or infant height, weight, Apgar score. The level of HBV DNA at 28 weeks postpartum was an independent risk factor for postpartum alanine aminotransferase (ALT) flares (OR = 2.348, 95 % CI: 1.100–5.016, P = 0.027). ConclusionTDF and LdT treatments throughout pregnancy in mothers with CHB were equally effective in preventing MTCT and safe.

Prophylactic effect of tenofovir on viral reactivation in immunocompromised pregnant women living with hepatitis B virus.

The appropriate prophylaxis for hepatitis B virus reactivation (HBVr) during gestation for immunocompromised pregnant women has yet to be determined. The prophylactic efficacy and safety of tenofovir disoproxil fumarate (TDF) in hepatitis B surface antigen (HBsAg)–positive patients and the HBVr risk in hepatitis B core antibody (HBcAb)–positive patients during gestation were investigated. Eligible pregnant women were diagnosed with rheumatic diseases and were administered prednisone (≤10 mg daily) with permitted immunosuppressants at screening. HBsAg‐positive participants were instructed to take TDF; those unwilling to take TDF were followed up as the control group. Propensity score matching was applied to control for differences in confounding factors between the HBcAb‐positive and uninfected groups. Hepatopathy, maternal, pregnancy, and safety outcomes were documented as endpoints. A cohort of 1292 women was recruited from 2017 to 2020, including 58 HBsAg‐positive patients (29 in each group). A total of 120 pairs in the HBcAb‐positive and noninfection groups were analyzed. Among HBsAg‐positive patients, 6 (20.7%) cases of hepatitis flare (hazard ratio [HR]: 7.44; 95% confidence interval [CI]: 1.50–36.89; p = 0.014) and 12 (41.4%) cases of HBVr (HR: 8.71; 95% CI: 2.80–27.17; p < 0.001) occurred in the control group, while 0 occurred in the TDF prophylaxis group. The HBV level at delivery was the lowest (1.6 log10 IU/ml) for those who received TDF during the pregestation period with a good safety profile. More adverse maternal outcomes were observed in the control group (odds ratio: 0.19, 95% CI: 0.05–0.77, p = 0.021), including one death from fulminant hepatitis and two cases of vertical transmission. No HBVr was recorded in HBcAb‐positive participants. Among immunocompromised pregnant women, prophylactic TDF during pregestation was necessary for HBsAg‐positive women, whereas regular monitoring was recommended for HBcAb‐positive women.

Renal safety of tenofovir disoproxil fumarate and entecavir in liver transplant patients: a nationwide Korean registry study.

Tenofovir disoproxil fumarate (TDF) and entecavir (ETV) have been recommended after liver transplantation to prevent recurrence of hepatitis B virus infection. Despite its proven efficacy, the renal safety of TDF has not been established in liver transplant recipients. We aimed to compare the effects of TDF and ETV on renal function in liver transplant recipients and to evaluate risk factors for renal dysfunction after liver transplantation. This is a retrospective, observational multicenter study of data from the Korean Organ Transplantation Registry. We included adults who underwent liver transplantation for hepatitis B virus-related complications from April 2014 to December 2017 and received TDF or ETV post-transplantation. Renal dysfunction was defined as an estimated glomerular filtration rate decline by at least 20% from baseline (1month post-transplantation). Median duration of follow-up was 29months (interquartile range 19-42). A total of 804 liver transplant patients were included. The cumulative probability of renal dysfunction was significantly higher in the TDF group than in the ETV group. Multivariable analysis confirmed that TDF was independently associated with an increased risk of renal dysfunction (hazard ratio = 1.47, 95% confidence interval 1.12-1.92; p = 0.005). Independent risk factors for renal dysfunction included older age, worse baseline renal function, and low body mass index. Overall survival rate was significantly lower in patients with renal dysfunction than in those without. In this nationwide study, the use of TDF was associated with an increased risk of renal dysfunction, when compared with ETV.

The role of tenofovir disoproxil fumarate for preventing vertical transmission of hepatitis B.

Since immunoprophylaxis failure can occur if maternal serum hepatitis B virus (HBV) DNA levels are >200,000IU/ml, tenofovir disoproxil fumarate (TDF) therapy has been investigated for preventing mother to child transmission (PMTCT). A literature search for maternal TDF therapy for PMTCT between 1/1/2015 and 7/1/21 on PUBMED, EMBASE, Cochrane, CNKI, and Wanfang databases was performed. Data from RCTs in English or Chinese were extracted and reviewed. The outcomes of interest included the efficacy and safety of TDF versus placebo for PMTCT. Among 11 RCTs identified from the databases, the risk-of-bias was low. All studies demonstrated that maternal TDF therapy initiated from the second or third trimester for highly viremic chronic hepatitis B mothers is highly effective and safe in the PMTCT of HBV, except one RCT performed in Thailand which showed no therapeutic advantage on TDF treatment versus placebo for PMTCT (0% vs 3% transmission). Recent emerging data suggest that maternal TDF therapy initiated at the 2nd or early 3rd trimester in mothers with HBV DNA >200,000IU/ml achieved viremic control before delivery. In the 4-year long follow-up study for maternal TDF therapy, there were no impacts on infants' physical growth, psychological or mental development, and bone mineral density after fetal exposure to TDF. In the light of updated efficacy and safety data from RCTs, an algorithm was proposed. The approaches in resource-limit areas were discussed. TDF is safe for both mothers and infants as the preferred therapy for PMTCT in highly viremic mothers. TDF should be initiated at the second or early third trimester in the combination of the appropriate infants' immunoprophylaxis.

Tenofovir disoproxil fumarate for multiple nucleos(t)ide analogues treatment failure hepatitis B: Is monotherapy enough?

Background and AimTenofovir disoproxil fumarate (TDF) is a first‐line treatment for chronic hepatitis B virus (HBV) infection for its high potency and a low rate of drug resistance. This study investigated the efficacy and safety of TDF in Chinese patients with chronic hepatitis B (CHB) infection after treatment failure with multiple nucleos(t)ide analogues (NAs).MethodsPatients included were aged 18–65 years, with treatment failure with multiple NAs (serum HBV DNA > 200 IU/mL after more than two different NA treatments). The primary endpoint was proportion of patients with serum HBV DNA < 20 IU/mL at Week 144 of TDF monotherapy. Secondary endpoints and safety were also assessed.ResultsOverall, 213 patients were enrolled. At Week 144, mean HBV DNA decreased significantly from baseline (4.4 vs 1.4 log10 IU/mL), with 77.0% patients (95% confidence interval: 71.1, 82.9) achieving serum HBV DNA < 20 IU/mL. Three (1.4%) patients experienced virological breakthrough during TDF monotherapy, without hepatitis flare. At Week 144, 15.3% and 4.7% patients (hepatitis B e antigen [HBeAg]‐positive at baseline) experienced HBeAg loss and HBeAg seroconversion, respectively; 68.3% patients achieved normalized alanine aminotransferase levels. Overall, 58.7% patients experienced more than one adverse event (AE). Most common AEs were upper respiratory tract infection and blood creatine phosphokinase increase; 8.5% patients experienced study drug‐related AEs; 9.4% patients experienced serious AEs (none were TDF‐related). Among renal safety parameters, overall trend of mean serum phosphorous level remained stable, while mean estimated glomerular filtration rate increased slightly.ConclusionsTenofovir disoproxil fumarate monotherapy is efficacious in CHB patients with multiple NAs treatment failure with no new safety findings.

Evaluation of safety and efficacy of tenofovir disoproxil in hemodialysis and renal transplant patients monoinfected with hepatitis B virus based on real life data.

IntroductionThere are limited data about the safety of tenofovir disoproxil fumarate (TDF) in chronic renal failure (CRF). In this study, we aimed to evaluate the safety and efficacy of TDF in renal transplant recipients and hemodialysis patients with chronic hepatitis B (CHB) during long-term follow-up.Material and methodsCHB patients undergoing hemodialysis (group 1), renal transplant recipients (group 2) and patients with normal renal function were included in the study. All patients were treated with TDF for at least 6 months. The groups were compared with regards to safety and efficacy. HBV-DNA levels were studied using a Cobas-TaqMan 96 system.ResultsA total of 217 patients with CHB (group 1: 8 patients, group 2: 9 patients, group 3: 200 patients) were enrolled in this study. The frequency of clinical adverse effects was significantly higher in groups 1 and 2compared with group 3 (37.5% vs. 11.1% vs. 0.5%, respectively, p < 0.001). However, no patients discontinued the drug due to the adverse effects. Serum creatinine levels were similar at baseline and at the end of follow-up in groups 1 and 2 (6.5 ±1.8 mg/dl and 6.9 ±1.5 mg/dl; 1.3 ±0.2 and 1.4 ±0.4 mg/dl, respectively, p < 0.05). HBV-DNA negativity rates were comparable at the 12th month and at the end of follow-up (50-83% for group 1, 60-67% for group 2 and 70-75% for group 3, respectively, p > 0.05).ConclusionsClinical adverse effects of TDF were more common in patients with CRF in comparison with patients without CRF. However, the occurrence of adverse effects did not necessitate discontinuation of the drug. TDF was safe and effective for this group of patients.

Efficacy and Safety of Tenofovir Disoproxil Fumarate in Senegalese Patients with Chronic Hepatitis B

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Evaluating the renal safety of tenofovir disoproxil fumarate in hepatitis B patients without chronic kidney disease.

The nephrotoxicity of tenofovir disoproxil fumarate (TDF) in chronic hepatitis B (CHB) patients without chronic kidney disease (CKD) remains controversial. We aimed to evaluate nephrotoxicity of TDF in this population. In this hospital-based cohort study, CHB patients who received either TDF or entecavir (ETV) therapy, and did not have underlying CKD, were retrospectively recruited from January, 2008 to January, 2019. After excluding those with confounding conditions, 257TDF-treated patients were matched through propensity scores with 514 ETV-treated patients. Cumulative incidences of, and hazard ratios (HRs) for the CKD guideline-defined renal dysfunction, were analysed. The mean decline in glomerular filtration rate was similar over 60months (TDF vs. ETV: 10.1ml/min/1.73m2 , 95% confidence interval [CI]: 7.4-12.7 vs. 8.0ml/min/1.73m2 , 95% CI: 6.4-9.6; p=.34). The 5-year cumulative incidence of renal dysfunction was not significantly different (TDF vs. ETV: 10.4%, 95% CI: 5.6-18.0 vs. 5.8%, 95% CI: 3.6-9.0; p=.18). However, in multivariable stratified analysis, TDF was associated with an increased risk of renal dysfunction in the elderly (age ≥60years), when compared to ETV (HR 2.86, 95% CI: 1.02-8.01; p<.05). For confirming the effect of TDF amongst the elderly, 61TDF-treated patients were further matched with 183 ETV-treated patients, with 5-year cumulative incidence of renal dysfunction being significantly higher in TDF users (TDF vs. ETV: 34.4%, 95% CI: 17.7-59.8 vs. 15.5%, 95% CI: 9.4-25.1; p<.05). TDF use was independently related to renal dysfunction (HR 2.71, 95% CI: 1.19-6.14; p<.05). Although TDF is generally safe for CHB patients without CKD, it is best to be avoided in the elderly.

Efficacy and safety of tenofovir disoproxil fumarate and tenofovir alafenamide fumarate in preventing HBV vertical transmission of high maternal viral load.

Hepatitis B virus (HBV) infection is a significant global health problem and > 42-52% of patients are infected during perinatal period. Tenofovir alafenamide fumarate (TAF) and tenofovir disoproxil fumarate (TDF) have been widely recognized as the main compounds used for antiviral treatment of hepatitis B. The present study evaluated the efficacy and safety of TAF in reducing HBV vertical transmission. A total of 72 pregnant women, who met the inclusion criteria, were randomly divided into the TDF (300mg/day, n = 36) and TAF (25mg/day, n = 36) groups. Clinical and laboratory data were analyzed and compared between the two groups. No significant differences in alanine aminotransferase, total bilirubin, blood creatinine and blood urea nitrogen levels were noted between the two groups after treatment. The serum HBV DNA viral load and hepatitis B e antigen (HBeAg) levels of the two groups were significantly decreased following treatment, whereas the difference between the two groups was not statistically significant. The levels of urine retinol-binding protein and β2-microglobulin had no significant change after TAF treatment (p > 0.05), but increased significantly after TDF treatment (p < 0.05). All drug concentrations were undetectable in umbilical cord blood (UCB) and breast milk samples of the TAF group, while the drug concentration of UCB and breast milk samples in the TDF group was 2.98 ± 1.44 and 19.16 ± 15.26ng/ml, respectively. All infants were tested negative for serum hepatitis B surface antigen, HBV DNA, and HBeAg. Both TAF and TDF effectively block the mother-to-child transmission of hepatitis B. TAF was superior to TDF with regard to renal safety and breastfeeding.

Safety of Tenofovir Disoproxil Fumarate for Pregnant Women Facing the Coronavirus Disease 2019 Pandemic.

We assessed the teratogenicity of tenofovir, a human immunodeficiency virus (HIV) drug similar to remdesivir currently being evaluated for the treatment of coronavirus disease 2019 (COVID-19). Using US Medicaid Analytic Extract (MAX) claims data (2000-2014), we identified a population-based pregnancy cohort of women with HIV who filled ≥1 prescription for antiretroviral therapies (ART) during the first trimester. Women on tenofovir disoproxil fumarate (TDF) were compared with women receiving ART without TDF. Major malformations were identified by ICD-9 codes using validated algorithms. Relative risks (RR) and 95% confidence intervals (CI) were estimated using propensity score (PS) stratification to control for potential confounders. We incorporated the results into prior knowledge by conducting a systematic literature review and a meta-analysis. Major congenital malformations were diagnosed in 37 out of 866 (4.27%) infants exposed to TDF and 38 out of 1,020 (3.73%) infants exposed to ART other than TDF; the adjusted RR was 1.21 (95% CI 0.77 to 1.90). Estimates for specific malformations were imprecise. The pooled RR from the meta-analysis with six prior studies was 0.88 (0.75 to 1.03). Based on evidence accumulated in patients with HIV, first trimester TDF use does not increase the risk of major congenital malformations overall in the newborn compared to other ART.

Once-daily tenofovir disoproxil fumarate in treatment-naive Taiwanese patients with chronic hepatitis B and minimally raised alanine aminotransferase (TORCH-B): a multicentre, double-blind, placebo-controlled, parallel-group, randomised trial

Antiviral therapy for patients with non-cirrhotic chronic hepatitis B and minimally raised alanine aminotransferase (ALT) is controversial. We aimed to investigate the efficacy and safety of tenofovir disoproxil fumarate in reducing the risk of disease progression in this patient population. TORCH-B is a multicentre, double-blind, placebo-controlled, parallel-group, randomised trial done at six teaching hospitals in Taiwan that enrolled patients with chronic hepatitis B. Eligible patients were aged 25-70 years and had substantial viraemia (viral DNA >2000 IU/mL) and minimally raised serum ALT concentrations more than one-fold but less than two-fold the upper limit of normal (ULN). Exclusion criteria included liver cirrhosis and previous antiviral treatment. Eligible participants were randomly assigned (1:1), stratified by site with a fixed block size of ten, to receive either 300 mg of oral tenofovir disoproxil fumarate or placebo once daily for 3 years. The participants, investigators, research coordinators, pathologists, laboratory personnel, and staff involved in patient care or assessment were masked to treatment assignment. 0·5 mg/day of oral entecavir was added to rescue acute hepatitis flare. The coprimary outcomes were change in necroinflammation severity on the Knodell scale and change in fibrosis stage on the Ishak scale and were evaluated in the modified intention-to-treat population, which comprised all patients with paired liver biopsies. Safety was evaluated in all patients who were randomly assigned. This trial is registered at ClinicalTrials.gov, NCT01522625, and is completed. From Jan 30, 2012, to Nov 10, 2015, 875 patients were screened and 160 were randomly assigned to receive either tenofovir disoproxil fumarate (n=79) or placebo (n=81). The coprimary outcomes were assessed in 146 patients (73 in each group). Liver fibrosis progressed (an increase of ≥1 stage) in 19 (26%, 95% CI 17-38) of 73 patients in the tenofovir disoproxil fumarate group and in 34 (47%, 35-59) of 73 patients in the placebo group (relative risk [RR] 0·56, 95% CI 0·35-0·88; p=0·013), whereas necroinflammation progressed (an increase of ≥2 points) in five (7%, 95% CI 2-15) patients in the tenofovir disoproxil fumarate group and in 12 (16%, 9-27) patients in the placebo group (RR 0·42, 95% CI 0·15-1·12; p=0·084). Two (3%) of 79 patients in the tenofovir disoproxil fumarate group and 13 (16%) of 81 patients in the placebo group had acute hepatitis flare requiring add-on entecavir (RR 0·16, 95% CI 0·04-0·68; p=0·013). The two groups were otherwise similar in occurrences of adverse events. No patients died. Tenofovir disoproxil fumarate reduces the risk of progression in liver fibrosis in patients with chronic hepatitis B and minimally raised ALT, but its effect on necroinflammation is non-significant. The Taiwan Ministry of Science and Technology, E-Da Hospital, the Taipei Institute of Pathology, Gilead Sciences.

Tenofovir disoproxil fumarate for prevention of mother-to-child transmission of hepatitis B virus: A systematic review and meta-analysis of randomised control trials.

Hepatitis B virus (HBV) infection caused by mother-to-child transmission (MTCT) continues to pose challenges to global health. This study aimed to assess the efficacy and safety of tenofovir disoproxil fumarate (TDF) for preventing HBV MTCT. PubMed and the Cochrane Central Register of Controlled Trials were searched through August 2020. Randomised controlled trials (RCTs) were selected that evaluated the efficacy and safety of TDF for preventing MTCT of HBV compared with the standard of care, placebo or other HBV therapies. The primary outcomes were HBV MTCT rate and maternal HBV DNA level. Secondary outcomes were infant and maternal safety outcomes. The review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Guidelines, and prospectively registered on PROSPERO (CRD42020186275). Of 240 citations, three RCTs that involved 651 participants were included. The pooled result showed that TDF can reduce the risk of HBV MTCT after 6 months postpartum by 80% (risk ratio [RR]0.2, 95% confidence interval [CI 0.06-0.7], n=584) with low heterogeneity (I2 =0%). TDF demonstrated HBV DNA suppression at delivery, though there was heterogeneity among individual studies (RR0.13, 95% CI [0.08-0.20] and (RR0.36, 95% CI [0.27-0.49]). Maternal and infant safety outcomes were comparable among treated and untreated mothers and infants born to them. The quality of evidence varied from high to very low. There is evidence that TDF effectively interrupted MTCT of HBV and suppressed HBV DNA level. Available studies on safety are very limited and heterogeneous, emphasising the need for additional RCTs with complete safety indicators.

Renal safety of tenofovir disoproxil fumarate and entecavir in liver transplant patients: a nationwide Korean registry study

Background: Entecavir and tenofovir are currently the first-line drugs in liver transplantation (LT) patients for the prevention of hepatitis B virus recurrence. Despite its proven efficacy, the renal safety of tenofovir in LT patients has not been well defined. We aimed to assess the impact of tenofovir on renal function compared to that of entecavir after LT. Methods: We analyzed 817 LT patients treated with entecavir (n=366) or tenofovir (n=451) between 2014 and 2017. The estimat ed glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation. Renal function deterioration was defined as progression of chronic kidney disease stage and ≥20% eGFR decline from 1 month after LT. Results: Mean eGFR at 1 month after LT was 91.1±22.0 mL/min/1.73 ㎡ for entecavir and 89.1±23.7 mL/min/1.73 ㎡ for tenofo vir group (P=0.312). During a median follow-up of 29 months, the cumulative incidence of renal function deterioration was sig nificantly higher in the tenofovir group than in the entecavir group (355.5% vs. 27.1%, P=0.01). Tenofovir (odd ratio [OR], 1.52; 95% confidence interval [CI], 1.11-2.08; P=0.009), old age (OR, 1.45; 95% CI, 1.01-2.09; P=0.044), low body mass index (OR, 2.02; 95% CI, 1.44-2.84; P<0.001), and diabetes mellitus (OR, 1.68; 95% CI, 1.18-2.08; P=0.009) were independent risk factors for renal func tion deterioration. Conclusions: The use of tenofovir was significantly associated with renal function deterioration in LT patients. In the setting of LT, tenofovir should be used with caution in high-risk patients and renal function should be carefully monitored.

Tenofovir alafenamide vs. tenofovir disoproxil fumarate: an updated meta-analysis of 14 894 patients across 14 trials.

Both tenofovir disoproxil fumarate (TDF)/emtricitabine and tenofovir alafenamide (TAF)/emtricitabine demonstrate excellent efficacy and safety overall, but concerns remain over specific changes in markers of bone and renal function. Lower plasma tenofovir concentrations are seen with TAF and in unboosted regimens. We assess TAF vs. TDF safety with and without booster coformulation. A previous systematic review was updated with recent clinical trials. TAF vs. TDF efficacy and safety were compared in boosted and unboosted subgroups. Efficacy was measured by viral suppression. Key safety endpoints included all adverse events, serious adverse events, Grades 3-4 adverse events and adverse event discontinuation. Further specific renal and bone markers were also assessed. A total of 14 clinical trials comparing TDF and TAF regimens were identified. A significant difference (P = 0.0004) in efficacy was shown in the boosted subgroup in favour of TAF, but no difference was seen in the unboosted subgroup. There were no significant differences between TAF and TDF for any of the key safety endpoints analysed. No differences were seen for the bone markers analysed. No difference was found for renal tubular events. There was a difference in risk for discontinuation due to renal adverse events when boosted (P = 0.03), but none when unboosted. Across all main safety endpoints, no differences between TAF and TDF are seen. Boosted TDF regimens were associated with lesser comparative efficacy than boosted TAF and a higher risk of renal event discontinuation. However, modern antiretroviral regimens are more commonly unboosted. This study finds no difference in efficacy or safety in unboosted TAF vs. TDF.

RENAL SAFETY OF TENOFOVIR DISOPROXIL FUMARATE AND ENTECAVIR WITH HEPATITIS B IMMUNOGLOBULIN IN LIVER TRANSPLANT PATIENTS

Introduction: Potent nucleos(t)ide analogues and hepatitis B immunoglobulin combinations are recommended after liver transplantation to prevent the recurrence of hepatitis B virus (HBV). Despite its proven efficacy, the renal safety of tenofovir disoproxil fumarate (TDF) has not been well established in liver transplant (LT) recipients. We aimed to assess the impacts of TDF and entecavir (ETV) on tubular and glomerular functions. Methods: We analyzed 206 LT patients treated with TDF (n=102) or ETV (n=104) plus hepatitis B immunoglobulin. Serum creatinine, phosphate, and uric acid levels were measured. Proximal tubular dysfunction was defined as the presence of hypophosphatemia (<2mg/dL) and hypouricemia (<2mg/dL). Glomerular dysfunction was defined as an estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73m2 accompanied by a ≥25% eGFR decline from baseline. Results: During a median follow-up of 42.5 months, 48 patients developed proximal tubular dysfunction (30.4% and 16.3% in the TDF and ETV groups; P=0.017). Serum levels of phosphate and uric acid were significantly lower in the TDF group post-LT. TDF (OR, 2.34; 95% CI, 1.16-4.69; P=0.017) and low body mass index (OR, 2.11; 95% CI, 1.06-4.21; P=0.034) were independent risk factors for proximal tubular dysfunction. The prevalence of glomerular dysfunction was not significantly different between the two groups (TDF 51.0% and ETV 54.8%; P=0.582). Conclusion: TDF significantly increased the risk of proximal tubular dysfunction. Although the effect of TDF on glomerular function was comparable to that of ETV, glomerular dysfunction was common after LT.