A recent study published in Scientific Reports investigates the efficacy and safety of switching from entecavir (ETV) to tenofovir alafenamide (TAF) in patients with chronic hepatitis B. The observational pilot study provides insights into long-term outcomes, particularly concerning HBsAg levels, renal function, and the development of hepatocellular carcinoma (HCC).
Key Findings on Viral Suppression
The study, which followed patients for 240 weeks, found that the mean changes in hepatitis B surface antigen (HBsAg) levels were similar between the group that continued ETV and the group that switched to TAF. This suggests that switching to TAF does not compromise viral suppression in patients already responding to ETV. Previous studies have shown that TDF demonstrates a greater reduction, but this study focused on patients already on ETV.
Renal Function and Safety Profile
An important aspect of the study was the evaluation of renal function. The results indicated no significant difference in the mean change in estimated glomerular filtration rate (eGFR) between the two groups. Furthermore, levels of NAG/Cr and β2MG/Cr, markers of renal tubular disorder, were comparable. Serum phosphorus levels also remained similar, suggesting that both ETV and TAF have similar effects on renal function, ensuring long-term safety.
Impact on Bone Density
The study also assessed the impact on bone density. While no significant decrease was observed in the lumbar spine, both groups showed decreased bone density in the femoral region. The researchers suggest that this decrease may be related to long-term aging rather than the effects of the antiviral medications themselves. They noted that neither ETV nor TAF exacerbated renal tubular disorders or decreased serum phosphorus values, factors known to contribute to bone mineral density reduction.
Hepatitis B Core-Related Antigen (HBcrAg) and HCC Risk
The study also monitored hepatitis B core-related antigen (HBcrAg), a marker increasingly recognized as a risk factor for HCC development, even when HBsAg levels are low. The average change in HBcrAg levels was similar in both groups. Notably, two cases of HCC developed in the ETV continuation group. In these cases, HBsAg levels had decreased compared to baseline, but HBcrAg levels had not decreased sufficiently. This finding underscores the importance of monitoring HBcrAg levels in patients treated with nucleos(t)ide analogues.
Comparison with Tenofovir Disoproxil Fumarate (TDF)
While the study did not directly compare TAF to tenofovir disoproxil fumarate (TDF), it referenced previous research indicating that TDF may lead to a greater reduction in HBsAg levels in treatment-naive patients. However, TAF is known to have a better safety profile than TDF, with fewer side effects related to renal dysfunction and decreased bone density.
Real-World Effectiveness of Tenofovir Amibufenamide (TMF)
Another recent study evaluated the real-world effectiveness and safety of tenofovir amibufenamide (TMF) in chronic hepatitis B patients. The study, which included both treatment-naive and treatment-experienced patients, found that TMF was comparable to TDF in terms of treatment effectiveness, with better renal safety and no impact on lipid levels. In treatment-experienced patients, switching to TMF did not affect antiviral treatment outcomes.
Limitations and Future Directions
The original study has several limitations, including its single-center design, small sample size, and relatively short observation period of five years. The researchers emphasize the need for future research with larger patient populations and longer follow-up periods to confirm these findings and further elucidate the long-term effects of switching from ETV to TAF.
Clinical Implications
The findings suggest that switching from ETV to TAF is a safe and effective strategy for managing chronic hepatitis B, particularly in patients who may benefit from the improved renal and bone safety profile of TAF. However, careful monitoring of HBcrAg levels is crucial for assessing the risk of HCC development, even in patients with reduced HBsAg levels.
