Although nucleos(t)ide analogue (NA) therapy can effectively suppress HBV replication,
the ideal therapeutic endpoints, including hepatitis B surface antigen(HBsAg)
seroclearance, is difficult to achieve.(1) Therefore, chronic hepatitis B (CHB) patients
often require long-term HBV suppression to achieve the therapeutic goals, with the
adherence to long-term NA therapy being an important clinical issue.(2, 3) ETV is one of
the standard treatments for CHB,(4, 5) but its absorption can be significantly reduced by
food.(6) ETV users must take the pills two hours before or after meals, and the blood
level of ETV may thus be affected if this recommendation is not fully followed.In
addition, the metabolism of ETV is involved by renal excretion, therefore the dosage of
ETV should be adjusted according to renal function.(7) For example, among patients in
chronic kidney disease (CKD) stage 4, i.e.,eGRF15-29 ml/min/1.73m, the frequency of ETV
taking should be reduced from once daily to every 72-96 hours, which may be forgettable
and inconvenient to ETV users.However, the adherence of NA therapy is an essential part
for long-term HBV suppression, and the efficacy of ETV therapy may be affected by the
reduced adherence during long-term therapy.
Except ETV, TAF is also a HBV antiviral recommended by the current practice guidelines in
the treatment of CHB, with a high potency in antiviral efficacy and low rate in
virological resistance.(4, 5) In addition, TAF can be a 2nd-line rescue antiviral
recommendation for HBV with resistance to ETV therapy.(4, 5) Moreover, because TAF is
formulated to deliver the active metabolite to target cells more efficiently than
tenofovir disoproxil fumarate (TDF) at a much lower dose, thereby reducing systemic
exposure to tenofovir. In the randomized controlled trials,(8, 9) patients in the TAF arm
had improved renal function and bone marrow density (BMD),as compared to patients in the
TDF arm. Furthermore, in some retrospective studies, switching from ETV to TAF may
present a superior efficacy in HBV DNA suppression and HBsAg level reduction,(10-13) and
renal safety was comparable between the TAF switch group and the ETV continuation
group.(10, 11) Interestingly, switching from ETV to TAF is associated with improvement of
the medication adherence,(6) which may be particularly important to patients under
long-term NA therapy.
In a small retrospective study conducted in Japan,(14) medication adherence and
satisfaction were compared between before and after switch antiviral therapy in patients
who switched to TAF from ETV (n = 15), and medication adherence was found to be
significantly improved (P = 0.04). In a prospective study aimed to evaluate the changes
of serum HBsAg levels during a 48-week period after switching ETV to TAF,(6) the degree
of HBsAg reduction was higher during the TAF administration period than during the ETV
administration period in patients without cirrhosis, with genotype B HBV, or with
undetectable serum hepatitis B core-related antigen (HBcrAg).The HBV cccDNA-related
biomarkers, such as quantitative HBsAg (qHBsAg) or HBcrAg, have been considered important
outcome predictors.(15, 16) With expected adherence improvement in TAF switch therapy,
the changes of above-mentioned biomarkers may be improved. The investigators therefore
aim to conduct a prospective cohort study of TAF switch therapy for CHB patients who are
unsatisfied to ETV therapy.