Switching to tenofovir disoproxil fumarate vs continuing treatment in patients with chronic hepatitis B who maintain long‐term virological response to entecavir therapy: A randomized trial

Abstract

No controlled trial in patients with chronic hepatitis B virus (HBV) infection on long-term entecavir (ETV) treatment, comparing switching to tenofovir disoproxil fumarate (TDF) with continuing the therapy, has been reported. Twenty-seven nucleos(t)ide-naïve patients with chronic HBV who underwent ETV therapy for ≥5 years and maintained virological response were included and randomized into two groups: one group continued ETV, and the other switched to TDF, in a 1:2 ratio. The primary endpoint was changed from baseline in serum hepatitis B surface antigen (HBsAg) level at week 48. The baseline characteristics were not different between nineteen patients in the TDF group and eight patients in the ETV group. Mean decreases in HBsAg level at week 48 were 0.023 and 0.042 log 10 IU/mL in the TDF and ETV groups, respectively (P = 0.94).The mean drops in hepatitis B core-related antigens were also not different between the TDF and ETV groups at week 48 (P = 0.80). HBV DNA was sustainedly <2.1 log 10 copies/ mL in all patients throughout the study period. In contrast, the mean aminotransferase levels were significantly higher in the TDF group than in the ETV group at weeks 12, 24, and 36, although being within the reference range. Estimated glomerular filtration rate was lower in the TDF group than in the ETV group at weeks 24 (P = 0.016) and 48 (P = 0.003). In conclusion, we could not find the effect on reducing HBsAg level by switching to TDF in chronic hepatitis B patients with maintained virological response to ETV for ≥5 years. K E Y W O R D S entecavir, hepatitis B virus, nucleos(t)ide analogs, randomized controlled trial (RCT), tenofovir disoproxil fumarate 1 | INTRODUCTION Hepatitis B virus (HBV) infection affects approximately 250 million people worldwide and is the major cause of cirrhosis and liver cancer, accounting for 780 000 deaths annually. 1 The annual incidence rates of hepatocellular carcinoma were reported to be 0.3% to 0.6% in noncirrhotic patients and 2.2% to 3.7% in cirrhotic patients if left untreated. 2 The ultimate goal of antiviral therapy in patients with persistent HBV infection is to improve survival and quality of life, by inhibiting the activity of hepatitis and progression of fibrosis to reduce the risk of liver cancer. Hepatitis B surface antigen (HBsAg) is considered the most effective surrogate marker for achieving this J Med Virol. 2019;91:1295-1300.wileyonlinelibrary.com/journal/jmv

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

“…Similar results were also obtained in a randomized controlled study conducted to compare patients in whom the nucleos(t)ide analog was switched from ETV to TAF and those in whom the ETV monotherapy was continued . Although both studies were randomized controlled studies, the study sample size was small in both: 27 patients in the former study and 48 patients in the latter study . Thus, we compared the changes in the serum HBsAg level after drug switching, as compared with the value recorded immediately before the switching, in 91 patients, and found that the degree of reduction of the serum HBsAg level was significantly greater during the TAF administration period than during the ETV administration period, especially in patients without underlying cirrhosis, genotype B HBV infection and serum HBcrAg levels of less than 3.0 log U/mL, even though there was no significant difference in the overall degree of reduction between the two treatment periods.…”

“…In the present study, the virologic and clinical features of patients who had received ETV monotherapy for at least 48 weeks were prospectively evaluated after switching of the nucleos(t)ide analog from ETV to TAF. Recently, Iida‐Ueno et al reported, on the basis of a randomized controlled study in patients receiving ETV monotherapy, that the degree of reduction of the serum HBsAg levels was similar between patients in whom the nucleos(t)ide analog was switched from ETV to TDF and those in whom the ETV monotherapy was continued. Similar results were also obtained in a randomized controlled study conducted to compare patients in whom the nucleos(t)ide analog was switched from ETV to TAF and those in whom the ETV monotherapy was continued .…”

Hepatitis B surface antigen reduction as a result of switching from long‐term entecavir administration to tenofovir

“…Since HBsAg loss in ETV therapy is rare, alternative treatments aimed for HBsAg loss are necessary. As an alternative treatment, there have been few reports examining HBsAg reductions following a switch from ETV to TFV . Switching to TFV was not found to enhance HBsAg reduction in these studies; our study also observed similar results.…”

Switching to tenofovir disoproxil fumarate in entecavir‑treated chronic hepatitis B patients: A pilot randomized controlled study

“…The primary aim was to evaluate differences in the decrease in HBsAg signal after the treatment switch, but they were not significant in the overall analysis. A similar result for changes in HBsAg was reported recently in a 48-week randomized trial targeting patients who had been treated with ETV for >5 years (19). However, when analyzed in the TDF-switching group in the present study, a greater decrease in HBsAg signal in HBeAg-positive patients compared with HBeAg-negative patients was observed.…”

“…4) was removed from the analysis, there was still a similar tendency (P=0.068). As most patients (85%) were HBeAg-negative in the previous study (19), it is possible that switching to TDF in ETV-treated patients may have had an additional effect on the HBsAg decrease only in HBeAg-positive patients. Consistent with this, in treatment-naïve patients, TDF was reported to result in a greater decrease in HBsAg signal in HBeAg-positive patients compared with HBeAg-negative patients (-0.37 vs. 0.07 log IU/ml) (13).…”