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Song, Song, Ma, Feng, and Xie: Long-Term Real-World Outcomes of Tenofovir Alafenamide in Chronic Hepatitis B: Detailed Analysis of Treatment-Naive and Experienced Patients
ORIGINAL ARTICLE
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Korean J Gastroenterol 2025;85(1):64-72.

Published online: 25 January 2025

DOI: https://doi.org/10.4166/kjg.2024.140

Long-Term Real-World Outcomes of Tenofovir Alafenamide in Chronic Hepatitis B: Detailed Analysis of Treatment-Naive and Experienced Patients

Yu-Xuan Song, Guang-Jun Song, Hui Ma, Bo Feng, Yan-Di Xie

Peking University People’s Hospital, Peking University Hepatology Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Beijing International Cooperation Base for Science and Technology on NAFLD Diagnosis, Beijing, China

Correspondence to: Yan-Di Xie, Peking University People’s Hospital, Peking University Hepatology Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Beijing International Cooperation Base for Science and Technology on NAFLD Diagnosis, 11 Xizhimen South Street, Beijing 100044, China. Tel： 010-66583771, Fax: 010-66583771, E-mail: xieyandee@163.com, ORCID: https://orcid.org/0000-0001-5002-341X

Received 16 November 2024       Revised 22 December 2024       Accepted 26 December 2024

Copyright © 2025. Korean Society of Gastroenterology.

(open-access):

This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background/Aims

This study assessed the long-term efficacy and safety of tenofovir alafenamide (TAF) in real-world settings. Methods: Patients who were candidates for TAF treatment and were followed up at 12-week intervals over 192 weeks were enrolled in this study.

Results

One hundred and forty-four patients (50 treatment-naive and 94 treatment-experienced) were included in this study. The cumulative incidence rates of cirrhosis and hepatocellular carcinoma at 192 weeks were 3.9% and 0.7%, respectively. In treatment-naive patients, the rates of a virological response, HBeAg conversion, and HBsAg loss at 192 weeks were 100%, 33.3%, and 2%, respectively. The treatment-naive patients exhibited higher baseline HBsAg levels than the treatment-experienced patients (4.31 log10IU/mL vs. 3.97 log10IU/mL). A significant decrease in the HBsAg levels from the baseline was observed at 144 and 192 weeks in the treatment-naive patients (p=0.01). The baseline body mass index (BMI) <25 kg/m2 (p=0.02) and HBsAg <3.3 log10IU/mL (p=0.04) were identified as predictive factors for a decrease in HBsAg ≥0.5 log10IU/mL at 48 weeks. The eGFR levels were consistently lower in the treatment-experienced patients throughout the study. Although the treatment-naive patients showed no abnormal increases in urinary URBP, the treatment-experienced patients showed elevated urinary β2MG and NAG levels at the baseline, which decreased over the treatment course. The total cholesterol, triglyceride, and low-density lipoprotein levels were similar in both groups.

Conclusions

Prolonging the TAF treatment duration enhances the virological response rate. The decline in HBsAg levels was more significant in the treatment-naive patients than in the treatment-experienced patients. The baseline BMI <25 kg/m2 and HBsAg <3.3 log10IU/mL were predictive factors for a significant decline in HBsAg at 48 weeks. TAF has high renal safety and no significant impact on lipid levels.

Keywords: Chronic hepatitis B, Tenofovir, Efficacy, Kidney injury

INTRODUCTION

Infection with the hepatitis B virus (HBV) is a formidable global health challenge, affecting an estimated 296 million people globally and accounting for more than 1.5 million new infections each year and more than 820,000 fatalities annually from cirrhosis and hepatocellular carcinoma (HCC).1 Consequently, it is essential to effectively and safely suppress HBV replication to mitigate the adverse outcomes associated with the virus.2 The frontline nucleoside analogs (NAs) endorsed by international guidelines (entecavir [ETV], tenofovir disoproxil fumarate [TDF], and tenofovir alafenamide [TAF]) are distinguished by their potency and low resistance profiles.3-5
Research has shown that patients showing a suboptimal response to ETV can benefit from a switch to TAF therapy, which prevents the development of further viral resistance and reduces renal and bone toxicity.6-9 TAF, a new prodrug of tenofovir (TFV), efficiently targets hepatocytes with the active metabolite TFV, achieving higher intracellular liver concentrations and lower plasma levels than TDF.10 Evidence from previous studies suggests that chronic hepatitis B (CHB) patients treated with TAF over the long term have higher rates of virological suppression and improved renal and bone safety, albeit with a potential impact on lipid metabolism.11-13 Furthermore, TAF halts the progression of liver fibrosis and even encourages its reversal.14
Considering the scarcity of long-term follow-up data from real-world studies, particularly in China, the long-term safety and efficacy of TAF are unclear in both treatment-naive and treatment-experienced patients. This study addressed this gap by conducting a four-year prospective study to monitor the virological response rates, the reduction in hepatitis B surface antigen (HBsAg) levels, changes in renal function, and fluctuations in lipid levels. Through these observations, the effectiveness and safety of long-term TAF treatment were comprehensively assessed in treatment-naive and treatment-experienced patients.

SUBJECTS AND METHODS

1. Patients

From January to December 2019, CHB patients who met the following criteria were included in this single-center prospective study at Peking University Peoplés Hospital: 1) aged 18 and above, 2) intended to receive TAF monotherapy, and 3) had available clinical data from the 24 weeks preceding the study. The patients were followed up every 12 weeks for 192 weeks.

2. Ethics

This study was approved by the Ethics Committee of Peking University Peoplés Hospital (approval number 2019PHB160-01) and adhered to the ethical principles outlined in the Declaration of Helsinki. Informed consent was obtained using an opt-out approach, and measures were taken to protect the patients' personal information during data collection.

3. Definitions

The virological response (VR) was defined as HBV DNA levels <20 IU/mL or undetectable. The biochemical response (BR) was defined as alanine transaminase (ALT) levels below the upper limit of normal (ULN) (women <40 U/L, men <50 U/L). Low-level viremia (LLV) was defined as detectable but low HBV DNA levels (below 2,000 IU/mL) in CHB patients treated with ETV, TDF, or TAF for at least 48 weeks with good compliance.5

4. Laboratory tests

All laboratory tests were conducted at the Peking University Peoplés Hospital. The biochemical tests were performed using a fully automatic biochemistry analyzer. The HBV DNA levels were measured using the Roche COBAS TaqMan HBV test, with a 20 IU/mL detection limit. The serum HBsAg levels were quantified using the Architect I2000SR (Abbott), with a range of 0.05–250 IU/mL; for levels >250 IU/mL, serial dilutions of 1:100–1:1,000 were performed. The estimated glomerular filtration rate (eGFR) was used to assess the glomerular function, while the urinary tests for retinol-binding protein (URBP), β2-microglobulin (β2MG), and N-acetyl-β-D-glucosaminidase (NAG) were conducted to evaluate the renal tubular function. The normal ranges were defined as eGFR ≥90 mL/min/1.73 m2, urinary URBP ≤0.7 mg/L, β2MG ≤370 μg, and NAG ≤12 U/L.

5. Statistical analysis

The mean±standard deviation was used for continuous quantitative data that were normally distributed, and the groups were compared using t-tests. The non-normally distributed data were described as the median, and the groups were compared using rank-sum tests. The categorical data were expressed as counts (%) and compared using chi-square tests. The HBsAg and HBV DNA levels were log-transformed for statistical analysis, and multivariate logistic regression was applied to identify the predictive factors. Statistical analyses and graphical representations were performed using IBM SPSS 26.0 and GraphPad Prism 8.3.0 software; p-values <0.05 were considered significant.

RESULTS

1. Baseline clinical and serological characteristics

One hundred and forty-four CHB patients were enrolled in this study, comprising 50 treatment-naive patients (34.7%) and 94 treatment-experienced patients (65.3%). After enrollment, all patients initiated TAF monotherapy and were followed up at 12-week intervals for 192 weeks. At study onset, there were five and one case of cirrhosis and HCC among the treatment-naive patients, respectively, and 10 and three cases of cirrhosis and HCC among the treatment-experienced patients, respectively. Throughout the follow-up period, the treatment-naive patients experienced five new cases of cirrhosis and no new cases of HCC. The treatment-experienced patients had no additional cases of cirrhosis, but one new case of HCC was recorded. The cumulative incidence rates of cirrhosis and HCC at 192 weeks were 3.9% (5/129) and 0.7% (1/140), respectively.
At the baseline, 21 (42%) of the treatment-naive patients and 45 (47.9%) of the treatment-experienced patients tested positive for HBeAg. Treatment-naive patients exhibited higher levels of ALT (179.7 U/L vs. 41.6 U/L, p=0.006) and AST (124.0 U/L vs. 34.6 U/L, p=0.009) compared to the treatment-experienced patients. On the other hand, the treatment-experienced patients showed higher albumin levels (45.1 g/L vs. 43.5 g/L, p=0.007), lower HBsAg levels (3.37 log10IU/mL vs. 3.46 log10IU/mL, p=0.029), and lower APRI scores (0.60 vs. 2.53, p=0.033). HBV DNA was undetectable in 72 (76.6%) patients. The treatment-experienced patients, however, presented with higher creatinine levels (82.6 μmol/L vs. 75.7 μmol/L, p=0.020) and lower eGFR (90.74 mL/min/1.73 m2 vs. 98.78 mL/min/1.73 m2, p=0.010) (Table 1).
Among the treatment-experienced patients, the average duration of prior antiviral treatment was 85.3±7.5 months. Tenofovir disoproxil fumarate (62.8%) was the most common antiviral treatment immediately before switching to TAF. The primary reason for switching to the TAF treatment was renal tubular injury (27.7%, 26/94) (Table 2).

2. Virological response, biochemical response, and HBeAg conversion in treatment-naive patients

For the treatment-naive patients, the VR rates at 12, 24, and 48 weeks were 28% (14/50), 42% (21/50), and 76% (38/50), respectively. Those who had not achieved VR by these milestones showed a progressive reduction in HBV DNA from the baseline, with means of −2.9±1.63 log10IU/mL, −3.2±1.89 log10IU/mL, and −3.7±2.15 log10IU/mL at 12, 24, and 48 weeks, respectively. The VR rates were improved further to 90% (45/50), 96% (48/50), and 100% (50/50) at 96, 144, and 192 weeks, respectively. Among the treatment-naive patients who were HBeAg positive at the baseline, the VR rates increased to 61.9% (13/21), 85.7% (18/21), 90.5% (19/21), and 100% (21/21) at 48, 96, 144, and 192 weeks, respectively. For those HBeAg negative at the baseline, the VR rates were 86% (25/29) at 48 weeks, 93.1% (27/29) at 96 weeks, and 100% (29/29) at 144 and 192 weeks. A significant difference between the HBeAg positive and negative groups was observed at 48 weeks (Fig. 1).
At the baseline, 64% (32/50) of treatment-naive patients presented with elevated ALT levels; 93.8% (30/32) of these patients achieved BR by 48 weeks. Patients who achieved VR by 48 weeks also had a higher BR rate than those who did not (97.9% vs. 86.0%). The HBeAg conversion rates for the treatment-naive patients increased to 4.8% (1/21), 14.3% (3/21), 28.6% (6/21), and 33.3% (7/21) at 48, 96, 144, and 192 weeks, respectively.

3. Virological response, biochemical response and HBeAg conversion in treatment-experienced patients

Following the switch to TAF, the treatment-experienced patients showed a VR rate of 89% (83/94) at 48 weeks, which increased to 100% (94/94) at 96, 144, and 192 weeks. For those treatment-experienced patients who were HBeAg positive at the baseline, the VR rate after switching to TAF reached 84.4% (38/45) at 48 weeks. Among those HBeAg negative at the baseline, the VR rate was 91.8% (45/49) at 48 weeks. Of the 11 patients who switched to TAF monotherapy due to LLV, seven achieved VR by 48 weeks, and four achieved VR by 96 weeks.
At the baseline, 14.9% (14/94) of treatment-experienced patients had elevated ALT levels, and 92.9% (13/14) of these patients achieved BR by 48 weeks. The HBeAg conversion rates for the treatment-experienced patients after switching to TAF increased to 6.7% (3/45), 17.8% (8/45), 31.1% (14/45), and 40.0% (18/45) at 48, 96, 144, and 192 weeks, respectively.

4. HBsAg changes

In the treatment-naive patient cohort, no HBsAg loss was observed at 48 and 96 weeks, with cumulative HBsAg loss rates of 2% (1/50) at 144 and 192 weeks. For treatment-experienced patients who switched to TAF, the cumulative HBsAg loss rates were 2.1% (2/94) at 48 weeks, 3.2% (3/94) at 96 weeks, and 4.3% (4/94) at 144 and 192 weeks. The HBsAg levels exhibited a declining trend throughout the antiviral treatment, with a more pronounced decrease in treatment-naive patients. At the outset, the treatment-naive patients had higher average HBsAg levels than the treatment-experienced patients (4.31 log10IU/mL vs. 3.97 log10IU/mL). By 96 weeks, however, the treatment-naive patients showed lower levels (3.37 log10IU/mL vs. 3.67 log10IU/mL), and the reduction in HBsAg levels from the baseline at 144 and 192 weeks was significant (p=0.01) (Fig. 2).
Among all patients, 14 experienced a decrease in HBsAg ≥0.5 log10IU/mL after 48 weeks of TAF treatment. Multivariate logistic regression analysis of the baseline factors showed that a baseline BMI <25 kg/m2 (p=0.02) and HBsAg <3.3 log10IU/mL (p=0.04) were predictive factors for a decrease in HBsAg ≥0.5 log10IU/mL after 48 weeks of TAF treatment (Table 3).

5. Safety evaluation

In this cohort of treatment-experienced patients, 26 individuals transitioned to TAF therapy because of renal tubular injury. Post-switch, six patients exhibited normalized renal tubular function by 48 weeks, while 10 and five recovered at 96 and 144 weeks, respectively. In particular, five patients failed to recover their renal function even after switching. Regarding eGFR, 21 patients switched to TAF because of a decrease; 14 had normalized eGFR by 48 weeks; four recovered by 96 weeks; three did not recover post-switch. All four patients who switched to TAF because of hypophosphatemia showed normal phosphate levels within 48 weeks (Table 2).
The eGFR levels were consistently lower in the treatment-experienced patients at all measured time points compared to their treatment-naive counterparts. The treatment-naive and treatment-experienced patients showed an increase in eGFR at 48 weeks. The eGFR levels decreased in both groups as the treatment progressed. The average eGFR level for the treatment-naive patients remained within the normal range throughout, while the decrease in the treatment-experienced patients was not statistically significant (Fig. 3A).
Neither the treatment-naive nor the treatment-experienced patients showed abnormal increases in URBP, with no statistically significant deviations from the baseline at any measured time point (Fig. 3B). The urinary β2MG levels in the treatment-naive patients were within the normal range throughout the study, with significant decreases from the baseline observed at 96, 144, and 192 weeks (p<0.01). In contrast, the treatment-experienced patients exhibited abnormally elevated baseline β2MG levels, which showed a downward trend after switching to TAF. These levels remained abnormally high at 48 weeks and began to normalize by 96 weeks. Significant reductions from the baseline were observed at 48, 96, 144, and 192 weeks (p<0.01) (Fig. 3C).
The urinary NAG levels of treatment-naive patients were within the normal range at all time points, with a significant increase from the baseline at 48 weeks, but still within the normal limits (p<0.01). No significant differences were observed between 96, 144, and 192 weeks and the baseline. The treatment-experienced patients, who started with abnormally elevated urine NAG levels, showed a downward trend after switching to TAF, remaining elevated at 48 and 96 weeks and beginning to normalize at 144 weeks. Significant decreases from the baseline were recorded at 48, 96, 144, and 192 weeks (p<0.01) (Fig. 3D).
After excluding patients on lipid-lowering medications, the lipid profiles of the remaining 122 individuals were analyzed. The total cholesterol levels were significantly higher at 144 weeks (4.66 mmol/L vs. 4.95 mmol/L, p=0.01) and 192 weeks (4.66 mmol/L vs. 4.91 mmol/L, p=0.03) compared to the baseline but remained within the normal range. Both groups had similar triglyceride and low-density lipoprotein levels (Fig. 4).

DISCUSSION

This real-world, prospective study spanning 192 weeks included treatment-naive and treatment-experienced CHB patients receiving TAF therapy. These findings underscore the efficacy of TAF in achieving virological and biochemical responses, as well as its impact on reducing the HBsAg levels, particularly in treatment-naive patients. In addition, the study evaluated the long-term effects of TAF on the glomerular and tubular renal function and blood lipid profiles.
Considerable evidence suggests that low-level viremia (LLV) after an antiviral treatment is closely linked to the progression of liver fibrosis, the development of decompensated cirrhosis, an elevated risk of HCC, and lower long-term survival rates in CHB patients.15-17 Therefore, the early identification of LLV is critical.5 On the other hand, there is no unified definition and management strategy for LLV within national and international guidelines. Zhang et al.18 reported that there was insufficient evidence to guide decisions as to whether patients with LLV should adhere to their original treatment or opt for a treatment strategy modification. The present study observed a virological response rate of 76% at 48 weeks for treatment-naive patients on TAF, which increased to 100% by 192 weeks. Among the treatment-experienced patients, the virological response rate was 89% at 48 weeks and reached 100% by 96 weeks. These results substantiate the effectiveness of long-term antiviral therapy with TAF, suggesting there is no urgency to assess LLV in patients on TAF because prolonging antiviral treatment may enhance the virological response.
HBsAg loss represents an ideal endpoint for NAs treatment. Despite the NAs efficiently suppressing the HBV DNA levels, the rate of HBsAg loss remains infrequent, with an annual rate of only 0.3–0.8%.19-21 In the present study, the cumulative rates of HBsAg loss at 192 weeks were 2% and 4.3% for the treatment-naive and treatment-experienced patients, respectively. A Korean study22 analyzing 852 patients treated with entecavir or tenofovir reported a HBsAg loss rate of 2.28% over a mean follow-up period of 6.3 years. Consistent with previous studies, this study observed a gradual decline in HBsAg levels with extended antiviral treatment. Lee et al.22 reported a significant decrease in HBsAg levels during the first year of treatment, aligning with these findings. The HBsAg kinetics are significantly influenced by factors such as the baseline DNA levels. In treatment-naive patients, a marked decrease in HBV DNA after the first year of treatment is the primary reason for the significant change in HBsAg levels. Several studies showed that the baseline HBsAg level was the most critical factor for predicting HBsAg loss.22
The safety of oral antiviral therapy for the HBV has been a persistent concern. Previous studies showed that TAF offers greater renal safety compared to TDF and ETV and have investigated indicators for the early detection of renal injury.23-25 In this study, the treatment-naive patients exhibited higher baseline transaminase levels, consistent with their lack of prior antiviral treatment. The treatment-experienced patients with higher albumin, lower HBsAg, and lower APRI levels, and 76.6% having undetectable HBV DNA, showed the benefits of previous antiviral treatments. Nevertheless, the baseline eGFR in the treatment-experienced patients was lower than that in the treatment-naive patients, indicating renal injury associated with prior antiviral therapies. More than 80% of the treatment-experienced patients who switched to TAF because of renal injury showed normal renal injury indicators by 192 weeks, confirming the renal safety of TAF over other antiviral agents. Monitoring the tubular injury indicators may be more effective for the early detection of renal injury than evaluating the glomerular function. Among the tubular injury markers, urinary β2MG and NAG showed higher sensitivity than URBP. Lampertico et al.26 reported that TDF is associated with a higher risk of renal tubular dysfunction than ETV. The statistical results, in conjunction with this finding, suggest that TAF, as a similar drug, may exhibit greater renal toxicity in tubular injury.
Byun et al.13 identified an increased risk of hyperlipidemia in CHB patients treated with TAF. Recent studies confirmed the safety and efficacy of a TAF treatment for up to three years in CHB patients switching from other antiviral agents, noting a significant increase in lipid levels.27,28 In the present study, the total cholesterol levels were significantly elevated at 144 and 192 weeks compared to the baseline but remained within the normal range. The triglyceride and LDL levels showed no significant changes, suggesting that TAF does not significantly affect the blood lipids.
This study boasted several strengths. First, its long-term, real-world follow-up with comprehensive data collection enhances the reference value of these findings. Second, the more frequent data collection every 12 weeks compared to other studies allows for continuous data analysis. Third, the detailed investigation of LLV suggests that the timing of the LLV assessment and potential treatment adjustments can be deferred.
Nevertheless, this study had limitations. The COVID-19 pandemic disrupted the regular follow-up schedules for many patients, resulting in a smaller sample size than anticipated. Moreover, although this study questioned the current definition and management of LLV, a more practical definition or approach could not be proposed. Future large-scale studies are warranted to address these limitations.
In conclusion, this study reported that extending the duration of the TAF treatment enhances virological response rates. The HBsAg levels in treatment-naive patients exhibit a more pronounced decline than in treatment-experienced patients, with baseline BMI <25 kg/m² and HBsAg <3.3 log10IU/mL being favorable factors for a significant HBsAg reduction at 48 weeks. The TAF treatment showed high renal safety and did not significantly affect blood lipids.

ACKNOWLEDGEMENTS

The authors thank the patients for their participation in this study. This research was supported by National Major Project during the 13th Five-Year Plan Period under Grant Number 2017ZX10302201-004-001 and 2017ZX10203202-003, and National Natural Science Foundation of China under Grant Number 82000557.

Notes

Financial support

This research was supported by National Major Project during the 13th Five-Year Plan Period under Grant Number 2017ZX10302201-004-001 and 2017ZX10203202-003, and National Natural Science Foundation of China under Grant Number 82000557.

Conflict of interest

None.

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Fig. 1
Virological response of the treatment-naive patients.
kjg-85-1-64-f1.tif
Fig. 2
Effect of TAF on HBsAg in treatment-naive and treatment-experienced patients. TAF, tenofovir alafenamide; HBsAg, hepatitis B surface antigen.
kjg-85-1-64-f2.tif
Fig. 3
Effect of TAF on renal function. (A) Effect of TAF on eGFR. (B) Effect of TAF on URBP. (C) Effect of TAF on β2MG. (D) Effect of TAF on NAG. TAF, tenofovir alafenamide; eGFR, estimated glomerular filtration rate; URBP, urinary tests for retinol-binding protein; β2MG, β2-microglobulin; NAG, N-acetyl-β-D-glucosaminidase.
kjg-85-1-64-f3.tif
Fig. 4
Effect of TAF on blood lipids. TAF, tenofovir alafenamide; TC, total cholesterol; LDL, low-density lipoprotein; TG, triglyceride.
kjg-85-1-64-f4.tif
Table 1
Baseline Characteristics of the Patients with Treatment-naive or Treatment-experienced
Treatment-naive (n=50) Treatment-experienced (n=94) p-value
Age, yr 47.6±12.2 50.2±16.5 0.278
Male, n (%) 35 (70.0) 75 (79.8)
ALT, U/L 179.7±66.5 41.6±6.1 0.006
AST, U/L 124.0±44.9 34.6±3.7 0.009
TBIL, umol/L 21.6±3.4 15.4±0.7 0.020
Albumin, g/L 43.5±0.5 45.1±0.3 0.007
Creatine, umol/L 75.7±2.3 82.6±1.8 0.020
eGFR, ml/min/1.73m2 98.78±2.19 90.74±2.12 0.010
IP, mmol/L 1.07±0.02 1.03±0.02 0.277
Cholesterol, mmol/L 4.83±0.14 4.56±0.11 0.136
Triglyceride, mmol/L 1.30±0.08 1.30±0.07 0.970
Platelet (×109/L) 190.3±7.6 203.5±7.6 0.222
APRI 2.53±1.16 0.60±0.09 0.033
FIB-4 2.23±0.39 1.69±0.17 0.201
aMAP 52.13±1.06 50.98±0.93 0.417
HBsAg, log10IU/mL 3.46 (3.26–4.58) 3.37 (2.68–3.78) 0.029
HBeAg positive, n (%) 19 (38) 45 (47.87)
HBV DNA, log10IU/mL 4.96 (4.97–8.21) 0 (0–1.86) <0.001

ALT, alanine aminotransferase; AST, aspartate aminotransferase; TBIL, total bilirubin; ALB, eGFR, estimated glomerular filtration rate; IP, inorganic phosphorus; HBsAg, hepatitis B surface antigen; APRI, (AST/upper limit normal×100)/Plateltes (×109/L); FIB-4, age (yrs)×AST (U/L)/(Plateltes [×109/L]×ALT [U/L]); aMAP, age-male-ALBI-Plateltes score.

Table 2
Reasons for Switching to TAF and Previous NAs Immediately before Switching to TAF in Treatment-experienced Patients
Reasons for switching to TAF Number (%) Previous NAs Number (%)
Tubular injury 26 (27.7) Tenofovir disoproxil fumarate 59 (62.8)
Personal preference 24 (25.5) Entecavir 36 (38.2)
Increased creatine 21 (22.3) Adefovir dipivoxil 14 (14.9)
Low-level viremia 11 (11.7) Lamivudine 2 (2.1)
Self-withdrawal followed by treatment 11 (11.7) Telbivudine 2 (2.1)
Decreased blood phosphorus 4 (4.3)
Albuminuria 1 (1.1)
Dizziness 1 (1.1)
Abdominal discomfort 1 (1.1)
Increased creatine kinase 1 (1.1)

TAF, tenofovir alafenamide; NAs, nucleoside analogs.

Table 3
Factors associated with a 0.5 log10 Reduction in the Hepatitis B Surface Antigen Levels in All Patients
Factors Univariate Multivariate
HR (95% CI) p-value HR (95% CI) p-value
Age, yr 1.23 (1.02–2.15) 0.52
Gender
Female 1
Male 0.94 (0.43–1.92) 0.26
BMI, kg/m2
<25 1
≥25 0.63 (0.34–0.92) 0.01 0.65 (0.25–0.83) 0.02
Diabetes mellitus
Absence 1
Presence 1.29 (0.91–2.40) 0.35
HBV DNA, log10IU/mL
<5 1
≥5 0.92 (0.42–1.59) 0.72
HBeAg
Negative 1
Positive 0.84 (0.65–1.95) 0.59
HBsAg, log10IU/mL
<3.3 1
≥3.3 0.79 (0.46–1.84) 0.02 0.53 (0.13–1.39) 0.04
APRI
<2 1
≥2 0.99 (0.34–1.91) 0.74
FIB-4 score
<1.5 1
≥1.5 0.71 (0.23–1.93) 0.83
aMAP
<50 1
≥50 0.63 (0.14–3.92) 0.81

BMI, body mass index; APRI, (AST/upper limit normal×100)/Plateltes (×109/L); FIB-4, age(yrs)×AST(U/L)/(Plateltes [×109/L]×ALT [U/L]); aMAP, age-male-ALBI-Plateltes score.

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