Significance of switching of the nucleos(t)ide analog used to treat Japanese patients with chronic hepatitis B virus infection from entecavir to tenofovir alafenamide fumarate

Abstract

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.

Superiority of tenofovir alafenamide fumarate over entecavir for serum HBsAg level reduction in patients with chronic HBV infection: A 144-week outcome study after switching of the nucleos(t)ide analog

“…Controversy exists, however, as to whether TAF exerts superior efficacy to ETV in reducing the serum HBsAg level [16][17][18][19][20][21]. Kumada T, et al reported results similar to ours [11] in patients in whom the nucleos(t)ide analog used for treatment was switched from ETV to TAF [16]; on the other hand, Ogawa E, et al [17] did not find any superiority of TAF over ETV, in terms of the efficacy of the drugs in reducing the serum HBsAg levels. Moreover, Hagiwara et al reported similar degrees of reduction of the serum HBsAg level between patients in whom the nucleos(t)de analog was switched from ETV to TAF and those who had received ETV monotherapy [18,19].…”

“…In our previous study, in which the extent of reduction of the serum HBsAg level between the 48-week periods before and after switching of the nucleos(t)ide analog used for treatment from ETV to TAF were compared in 92 patients with chronic HBV infection, the extent of reduction, overall, was greater during the 48-week TAF treatment period after the drug switching than during the 48-week ETV treatment period prior to the drug switching (Log IU/mL; 0.068 vs. 0.041), although the difference was not significant (P = 0.069); the extent of reduction during the TAF treatment period was, however, significantly greater in patients without underlying cirrhosis, patients with genotype B HBV infection, and patients with serum HBcrAg levels of <3.0 Log U/mL [11]. Moreover, the McNemar test revealed that the antiviral efficacy of TAF was superior to that of ETV when increase and decrease of the serum HBsAg level by 0.08 Log IU/mL/48 weeks or more were defined as "increase" and "decrease," respectively (P = 0.022) [11]. Controversy exists, however, as to whether TAF exerts superior efficacy to ETV in reducing the serum HBsAg level [16][17][18][19][20][21].…”

“…Thus, we previously conducted a prospective clinical study to compare the antiviral effect, in terms of decreasing the serum HBsAg level, between ETV and TAF in patients with chronic HBV infection, after switching the nucleos(t)ide analog used for treatment from ETV to TAF, and revealed the superiority of TAF over ETV in the short term, over an observation period of 48 weeks after the drug switching [11]. In that study, the extent of reduction of the HBsAg level during the 48-week TAF treatment period was higher than that during a 48-week ETV treatment period, especially in patients without underlying cirrhosis, patients with genotype B HBV infection, and patients with serum HBcrAg levels of <3.0 Log U/mL [11].…”

“…Thus, we previously conducted a prospective clinical study to compare the antiviral effect, in terms of decreasing the serum HBsAg level, between ETV and TAF in patients with chronic HBV infection, after switching the nucleos(t)ide analog used for treatment from ETV to TAF, and revealed the superiority of TAF over ETV in the short term, over an observation period of 48 weeks after the drug switching [11]. In that study, the extent of reduction of the HBsAg level during the 48-week TAF treatment period was higher than that during a 48-week ETV treatment period, especially in patients without underlying cirrhosis, patients with genotype B HBV infection, and patients with serum HBcrAg levels of <3.0 Log U/mL [11]. In the present study, the same cohort was followed up further for 144 weeks, and antiviral efficacy and safety of TAF over the long term, that is, 144 weeks after the switching of the nucleos(t)ide analog from ETV to TAF were evaluated, by comparing the relevant parameters between a 144-week treatment period with ETV prior to the drug switching and 144-week treatment period with TAF after the drug switching, in patients who had received ETV at least for 192 weeks before the drug switching.…”

Tenofovir Alafenamide Rescues Renal Tubules in Patients with Chronic Hepatitis B

“…Hagiwara, et al reported that it was particularly prominent in patients with serum HBs antigen levels < 800 IU/mL after switching from ETV to TAF [36]. Uchida et al found that the degree of reduction in serum HBs antigen levels after switching from ETV to TAF was significantly higher, particularly in patients with cirrhosis, genotype B HBV infection, and serum hepatitis B core related antigen levels <3.0 log U/mL [37].…”