History, initial treatment and response
A 60-year-old male presented with abnormal liver function test results following a routine health evaluation in 2014. He was asymptomatic, with baseline Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0. Comorbidities included hypertension and dyslipidaemia, managed with amlodipine and a statin, respectively.
Further investigations confirmed chronic hepatitis B virus (HBV) infection. Imaging studies showed coarse liver parenchymal echotexture consistent with chronic liver disease, without focal hepatic lesions or hepatocellular carcinoma. Serology was negative for hepatitis B e-antigen. Baseline serum HBV DNA was at 6.2 log10 IU/mL (approximately 1.5 x 109 IU/mL), with alanine aminotransferase (ALT) of 56 U/L and a mildly reduced platelet count of 130 x 109/L. Liver biopsy revealed advanced hepatic fibrosis (METAVIR stage F3).
In 2014, oral nucleotide analogue monotherapy with tenofovir disoproxil fumarate (TDF) 300 mg QD was initiated. Over 6 years of TDF treatment (2014–2020), virologic and biochemical suppression was achieved without antiviral resistance, with HBV DNA becoming undetectable and ALT normalizing to 20 U/L.
Given the association of long-term TDF exposure with proximal renal tubular dysfunction and bone mineral density (BMD) loss, particularly in older individuals, both were monitored throughout treatment.1,2 Estimated glomerular filtration rate (eGFR) declined from >60 mL/ min/1.73 m² in 2014 to approximately 50 mL/min/1.73 m² in 2020 (stage 3a chronic kidney disease [CKD]). Urinalysis showed no overt proteinuria or haematuria. Bone densitometry in the same year revealed osteopenia, with a lumbar spine BMD T-score of -2.1.3 These findings prompted a switch to another NA.
Treatment with TAF and response
In October 2020, the patient was switched from TDF to tenofovir alafenamide (TAF) monotherapy 25 mg taken daily after breakfast. No adjustments to comedications were required.
TAF was well tolerated, with no reported adverse events (AEs). By January 2021, within 3 months of switching to TAF, the patient’s eGFR improved to 60 mL/min/1.73 m². (Figure 1A) BMD assessment in October 2023 showed that the lumbar spine T-score improved to -1.6. (Figure 1B)
Virologic suppression and normal ALT level were maintained throughout treatment, with stable liver stiffness on transient elastography (8.5–10.0 kPa). LDL-cholesterol (LDL-C) increased from 130 to 150 mg/dL post-switch, but statin therapy remained unchanged as this increase was considered acceptable.1,4
After >5 years of TAF, eGFR remains stable at approximately 58 mL/min/ 1.73 m² without proteinuria or haematuria, with sustained complete virologic suppression and stable liver stiffness (8.5– 10.0 kPa). The patient is clinically well with PS of 0, is followed every 3 months, and will continue TAF monotherapy.
Discussion
TAF as the preferred switch option
Entecavir, TDF and TAF are high-genetic-barrier nucleos(t)ide analogues (NAs) preferred by major guidelines for chronic HBV infection (CHB).1,2,5,6 Choice of NA therapy takes into account patients’ age, renal and bone status, and treatment history. In patients with or at risk of renal dysfunction or bone loss, TAF or entecavir is preferred, while TDF is generally avoided, as long-term TDF is associated with declining renal function and BMD, with bone loss being particularly pronounced in patients aged >60 years and postmenopausal women.1,2,4
In my practice, renal function is monitored every 3 months, while BMD is periodically checked in at-risk patients. A decline in renal function or BMD, rather than a fixed age cut-off, would trigger a therapy switch.
5-year real-world evidence: Renal preservation, deepening virologic control, and fibrosis regression
The multicentre Kyushu University Liver Disease Study (KULDS) included 414 adults with CHB who switched from another NA to TAF.7 Over 5 years, HBV DNA suppression rate increased from 85.0 to 100 percent, and HBV DNA suppression with target not detected rate rose from 74.0 to 91.0 percent. In addition, there were no HBV DNA breakthroughs, including among patients who switched from NA combinations. Renal function remained broadly stable regardless of baseline renal status or prior regimen, demonstrating long-term renal safety.
Within the CKD (defined as eGFR <60 mL/min/1.73m2) subgroup (n=100), renal trajectory differed by prior regimen. The eGFR of patients previously treated with entecavir declined by -1.8 ± 3.4 mL/ min/1.73 m² at year 5. In contrast, patients who switched from TDF or an NA combination showed eGFR improvement of 3.3 ± 2.6 mL/min/1.73 m² by 6 months, followed by a minor decline of -0.6 ± 3.3 mL/ min/1.73 m² by year 5.7 Our patient’s case mirrors the latter pattern, where his eGFR increased from 50 to 60 mL/min/1.73 m² within 3 months of switching to TAF and showed a minor, likely age-related decline to 58 mL/min/1.73 m² 6 years later. ALT normalization rate, as defined by the American Association for the Study of Liver Diseases criteria, significantly improved over 5 years, from 66.0 to 79.0 percent in the CKD group and from 63.4 to 71.0 percent in the non‐CKD group. Among patients with cirrhosis (n=54), the FIB-4 index, a noninvasive fibrosis marker, improved significantly over time in both groups, supporting the long-term hepatic benefits of sustained viral suppression.7
Anticipating a modest lipid trade-off after switching
The post-switch LDL-C increase is a recognized, generally minor trade-off rather than a direct TAF-associated AE. TDF has a mild lipid-lowering effect not shared by TAF. Consequently, lipid levels typically normalize or rise modestly after switching, as observed in TAF registration trials.1,4 Guidance therefore recommends lipid-level monitoring after switching, particularly in patients with pre-existing cardiometabolic risk factors.1
BMD recovery alongside deepened viral suppression
In a prospective, multinational study of 270 patients switching from another NA to TAF (73.3 percent previously on entecavir monotherapy), mean lumbar spine T-score improved significantly from -1.43 to -1.17 within 24 months (p<0.0001), consistent with our patient’s BMD recovery.3 Renal function was also unchanged (eGFR, 88.4 to 89.5 mL/ min/1.73 m²; p=0.13) over the same epriod.3 Over 2 years, virological response increased from 95.2 to 98.8 percent, indicating deeper suppression after switching to TAF in patients with residual low-level viraemia.
These findings reinforce that the rationale for switching to TAF extends beyond treatment failure and includes improved renal and bone safety.3,4
Summary
This case demonstrates how switching from TDF to TAF in an older patient with comorbidities maintained complete viral suppression and stable liver disease while reversing TDF-associated renal function and BMD declines, without new safety concerns. As shown by 5-year real-world and prospective multinational study data, TAF is an effective, well-tolerated long-term option, particularly for older CHB patients who may present with renal and bone safety concerns.3,7
