fumarates and Hepatitis-B--Chronic

Nucleoside analogues are currently applied as a first-line treatment for chronic hepatitis B (CHB) patients. However, the long-term effects of this type of treatment on kidney and bone tissue need to be further investigated.. We conducted a search of entecavir (ETV), tenofovir disoproxil fumarate (TDF), and tenofovir alafenamide fumarate (TAF) for treatment of CHB patients through October 29, 2023. Side effects of the three drugs were compared. Standardized mean difference (SMD), 95% confidence interval (95%CI), and surface under the cumulative ranking curve (SUCRA) were reported for each outcome. Further subgroup analysis was conducted according to duration of administration.. ETV and TAF exhibited less effect on estimated glomerular filtration rate (eGFR) than TDF (SMD = -3.60 (95%CI: -1.94 ~ -5.26) and SMD = -4.27 (95%CI: -2.62 ~ -5.93)). ETV also exhibited less effect on creatinine rise than TAF and TDF (SMD = -0.55 (95%CI: -0.09 ~ -1.01) and SMD = -0.61 (95%CI: -0.15 ~ -1.06)). Moreover, the effect of TAF on bone mineral density (BMD) was less than that of TDF (SMD = -0.02 (95%CI: -0.01 ~ -0.02)). The probabilities of the three drugs changing relevant indicators exhibited similar patterns: eGFR (TDF (100.0%) > ETV (41.2%) > TAF (8.8%)), creatinine (TDF (94.7%) > TAF (54.7%) > ETV (0.6%)), BMD (TDF (79.7%) > ETV (50.6%) > TAF (19.6%)), and blood phosphorus (TDF (90.6%) > TAF (49.8%) > ETV (9.7%)). After 6 and 24 months of treatment, no statistically significant difference in renal function or bone tissue was observed between ETV and TDF. However, greater adverse effects on renal function were observed for TDF than ETV at 60 months compared to 12 months. TDF also exhibited greater adverse effects on bone tissue than ETV at 36 months than at 12 months.. Long-term administration of TDF has resulted in stronger adverse effects than TAF and ETV in regard to both renal function and bone tissue in CHB patients. The effect of TAF on creatinine increase was greater than ETV. The difference in side effects between ETV and TDF was independent of treatment duration.

Topics: Adenine; Alanine; Antiviral Agents; Bone and Bones; Creatinine; Fumarates; Hepatitis B; Hepatitis B, Chronic; Humans; Kidney; Network Meta-Analysis; Tenofovir; Treatment Outcome

Tenofovir disoproxil (TD), modified from tenofovir disoproxil fumarate (TDF), was developed as a salt-free formulation, removing fumarate to improve the ease of oral intake by reducing the tablet's size. We evaluated the maintenance of antiviral effects and overall safety profile of TD 245 mg after switching from TDF 300 mg in patients with chronic hepatitis B (CHB).. CHB patients with HBV-DNA <69 IU/mL after ≥24 weeks of TDF therapy were enrolled. The primary efficacy endpoint was the HBV-DNA suppression rate (HBV-DNA <69 IU/mL) at week 48; We evaluated the non-inferiority (10% margin) of TD to TDF in terms of efficacy. Safety was assessed based on adverse events (AEs), laboratory tests, bone mineral density, and renal function abnormalities.. TD was non-inferior to TDF for maintaining viral suppression in CHB patients, showing the less decline of renal function.

Topics: Adenine; Antiviral Agents; Creatinine; DNA, Viral; Fumarates; Hepatitis B e Antigens; Hepatitis B virus; Hepatitis B, Chronic; Humans; Tablets; Tenofovir; Treatment Outcome; Viral Load

Entecavir (ETV) and tenofovir alafenamide fumarate (TAF) have been used widely to treat patients with chronic hepatitis B virus (HBV) infection, but it is still unclear how best to use these drugs. Although some studies compared the efficacies of treatment switch from ETV to TAF, there has been no randomized study.. We performed a prospective multicenter randomized controlled study in which subjects were enrolled from April 2018 to June 2019 and observed for 2 years until March 2021 to clarify the efficacy and safety of switching from ETV to TAF.. Thirty-three patients were enrolled and randomized into 2 groups, and a total of 30 patients were evaluated; a TAF-switching group (n = 16) and an ETV-continuing group (n = 14). The mean age of the 30 patients was 61 years old and 18 patients (60%) were male. The serum HBV DNA in all patients were below detection limit. The mean change in hepatitis B surface antigen (HBsAg) levels after 2 years was not significantly different between the TAF and ETV groups (-0.08 vs -0.20 log IU/mL, P = .07). Comparing the group with a HBsAg decline (≤ -0.1 log IU/mL) and a group without a HBsAg decline in an overall analysis, the prior ETV duration was significantly shorter in the HBsAg-declined group (49 vs 92 months, P = .03). Although the eGFR levels tended to decrease in the TAF group compared to ETV (-6.15 vs -2.26 mL/min/1.73 m2, P = .09), no significant differences were observed in patients with baseline eGFR < 60 (-2.49 vs 0.40 mL/min/1.73 m2, P = .25).. The efficacy and safety were comparable in the TAF-switching group and the ETV-continuing group. Because the present study was conducted in limited patients, a larger study will be required.

Topics: Adenine; Alanine; Antiviral Agents; DNA, Viral; Female; Fumarates; Guanine; Hepatitis B Surface Antigens; Hepatitis B, Chronic; Humans; Male; Middle Aged; Prospective Studies; Tenofovir; Treatment Outcome

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 (300 mg/day, n = 36) and TAF (25 mg/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 ± 15.26 ng/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.

Topics: Alanine; Antiviral Agents; Female; Fumarates; Hepatitis B virus; Hepatitis B, Chronic; Humans; Infant; Infectious Disease Transmission, Vertical; Pregnancy; Tenofovir; Treatment Outcome; Viral Load

To evaluate the long-term efficacy of switching of the nucleos(t)ide analog used for treatment from entecavir (ETV) to tenofovir alafenamide fumarate (TAF) in patients with chronic HBV infection.. A total of 103 patients with serum HBsAg levels of ≥100 IU/mL who had received ETV were enrolled. The nucleos(t)ide analog used for the treatment was switched from ETV to TAF, and the changes in serum HBsAg levels during the 144-week period before and after the drug switching were compared in 74 patients who had received ETV at least for 192 weeks.. Significant decreases of serum HBsAg levels were observed during both the ETV and the TAF administration period, although the degree of reduction was greater during the latter period than during the former period (P<0.001). Significant decreases of serum HBsAg levels were seen in both patients with genotype B HBV infection and genotype C HBV infection, irrespective of the serum HBsAg and HBcrAg levels at the time of the drug switching.. Switching of the nucleos(t)ide analog used for treatment from ETV to TAF merits consideration in patients with chronic HBV infection, since the extent of reduction of the serum HBsAg level was greater during the TAF treatment period than during the ETV treatment period.

Topics: Aged; Alanine; Antiviral Agents; Drug Substitution; Female; Follow-Up Studies; Fumarates; Genotype; Guanine; Hepatitis B Surface Antigens; Hepatitis B virus; Hepatitis B, Chronic; Humans; Male; Middle Aged; Nucleosides; Prospective Studies; Tenofovir; Treatment Outcome

Topics: Adenine; Alanine; Bone Density; Fumarates; Hepatitis B, Chronic; Humans; Kidney; Tenofovir

Topics: Adenine; Alanine; Bone Density; Fumarates; Hepatitis B, Chronic; Humans; Kidney; Tenofovir

Nucleos(t)ide analogues (NAs) suppress hepatitis B virus (HBV) replication, but the risk of hepatocellular carcinoma still remains. The presence of detectable HBV DNA in the serum during NA therapies for chronic hepatitis B patients has been reported to be associated with the risk of hepatocellular carcinoma. In this study, we investigated the antiviral effect of switching from entecavir (ETV) to tenofovir alafenamide fumarate (TAF) in chronic hepatitis B patients who had detectable HBV DNA in the serum at least once within a year. Among a total of 77 cases in 7 hospitals that switched NAs from ETV to TAF, 23 patients with detectable HBV DNA in a year before switching were analyzed. When the detection frequencies of HBV DNA in the 1st and 2nd years after switching to TAF were analyzed, they were significantly lower than those in the year before switching (68.8% vs. 34.1% for the 1st year and 21.3% for the 2nd year, P < 0.001 for both). The HBsAg decline tended to be larger after switching than before (-2.5% vs. -3.0% for 1st year and -3.1% for 2nd year), but the difference was not significant. One patient died of a cardiovascular event 11 months after the treatment switch, but no adverse effects due to TAF including renal function were observed. In conclusion, it was suggested that switching from ETV to TAF might be effective to suppress the HBV DNA level further in patients whose HBV DNA is detectable, even if at a very low level.

Topics: Adenine; Antiviral Agents; Carcinoma, Hepatocellular; DNA, Viral; Fumarates; Hepatitis B, Chronic; Humans; Liver Neoplasms; Tenofovir; Treatment Outcome

Tenofovir alafenamide (TAF), a new tenofovir prodrug, has been developed to circumvent the less favorable safety profile of tenofovir disoproxil fumarate (TDF). We investigated reductions in hepatitis B surface antigen (HBsAg) levels in patients with HBV infection who received continuous entecavir (ETV) monotherapy or sequential therapy with ETV and TAF.. This retrospective cohort study included 286 patients who were divided into two groups: continuous ETV monotherapy (ETV group, n = 168) and sequential therapy with ETV and TAF (ETV-TAF group, n = 108). Factors associated with a 90% reduction in HBsAg levels were analyzed by a Cox proportional hazards model using a time-dependent covariate in both groups.. In the multivariate Cox proportional hazards model, the ETV-TAF group [adjusted hazard ratio (aHR) 2.750; 95% confidence interval (CI), 1.265-3.405; P = 0.0038] and BMI ≤ 25.0 kg/m2 (aHR 0.520, 95% CI, 0.308-0.875; P = 0.0139) demonstrated a 90% reduction in HBsAg levels. HBsAg levels of patients in the TAF phase in the ETV-TAF group showed greater yearly percent reductions than those in the ETV group and those in the ETV phase in the ETV-TAF group (P = 0.0361 and P = 0.0022, respectively, Steel-Dwass test).. HBsAg levels decreased more rapidly after patients switched from ETV to TAF. Switching to TAF may be an effective treatment option to reduce HBsAg levels.

Topics: Adenine; Alanine; Antiviral Agents; Fumarates; Guanine; Hepatitis B Surface Antigens; Hepatitis B, Chronic; Humans; Retrospective Studies; Tenofovir; Treatment Outcome

Topics: Alanine; Canada; Fumarates; Hepatitis B, Chronic; Humans; Kidney; Tenofovir

The significance of switching of the nucleos(t)ide analog used to treat patients with hepatitis B virus (HBV) from entecavir (ETV) to tenofovir alafenamide fumarate (TAF) is uncertain. The subjects of this study were 159 patients with HBV who received treatment with ETV followed by TAF. Among these patients, serial changes in the HBV marker levels were monitored in 92 patients in whom the serum HBsAg levels were ≥100 IU/mL during the 48-week period immediately before and after the switching. A questionnaire survey for medication compliance was performed in 127 patients. The serum HBsAg levels (log IU/mL) decreased by 0.041 during the ETV treatment period and by 0.068 during the TAF administration period. The degree of reduction was higher during the TAF administration period than during the ETV administration period in patients without cirrhosis (P = .030), patients with genotype B HBV (P = .014), and patients with undetectable serum HBcrAg (P = .038). Multivariate analysis revealed the HBV genotype (B vs C; odds ratio, 3.400; P = .025) and serum aspartate aminotransferase level (every 1+; 1.111; P = .015) at the time of switching as factors influencing the treatment efficacy. Thirty-six patients (28%) responded that the number of days that they forgot to take the drug decreased after the drug switching, and 77 patients (61%) reported feeling satisfied with the drug switching. Switching of the nucleos(t)ide analog used from ETV to TAF may be useful in the treatment of patients with HBV infection, as it is associated with both a decrease in the serum HBsAg level and improvement of the medication compliance.

Topics: Adenine; Aged; Alanine; Antibodies, Viral; Antiviral Agents; Female; Fumarates; Genotype; Guanine; Hepatitis B Surface Antigens; Hepatitis B, Chronic; Humans; Japan; Male; Medication Adherence; Middle Aged; Multivariate Analysis; Surveys and Questionnaires; Tenofovir; Transaminases; Treatment Outcome

We describe a case of a 61-year-old man with chronic hepatitis B, hepatitis B e antibody (HBeAb) positive, treated with tenofovir disoproxil fumarate (TDF), who developed virological and biochemical viremic reactivation with an increase in transaminase plasma levels. The patient's history revealed that he had discontinued TDF about 5 days before admission and, from December 2013, had been taking venlafaxine, paroxetine and zolpidem for some episodes of depression. Clinical evaluation and laboratory findings excluded the presence of systemic diseases that might have been able to explain the drug inefficacy, while pharmacological evaluation suggested a possible drug-drug interaction. In order to assess the possible occurrence of resistance, mutational analysis of hepatitis B virus (HBV) was performed and excluded the presence of resistance for TDF. TDF was prescribed, and venlafaxine, paroxetine and zolpidem were discontinued. The follow-up at 3, 6 and 12 months documented a good response to TDF with a time-related decrease of HBV-DNA and alanine aminotransferase.

Topics: Alanine Transaminase; Antiviral Agents; Central Nervous System Agents; Depression; Drug Interactions; Drug Resistance, Viral; Drug Therapy, Combination; Fumarates; Hepatitis B virus; Hepatitis B, Chronic; Humans; Male; Medication Adherence; Middle Aged; Tenofovir; Transaminases; Viral Load; Virus Activation