In this real-life retrospective cohort study of CHB patients switching from TDF to TAF antiviral therapy, we compared fasting serum lipid profiles at the onset of therapy switch (at enrollment) and 48 weeks after either TAF treatment or continuation of TDF. The TCHO and HDL profiles of the TAF group increased compared with patients continuing TDF therapy after 48 weeks. Meanwhile, we found a significant increase in TCHO in patients who received TAF therapy after 48 weeks (versus baseline). These findings suggested that TAF therapy may be associated with some degree of dyslipidemia.
Previous studies have reported that the profiles of TCHO, HDL, and LDL are increased in HIV patients switching from TDF to TAF therapy 14,15. We found similar results based on elevated TCHO levels observed herein for TAF-treated CHB patients, however no significant differences in HDL or LDL were observed. As previous studies reported at 48 week follow-up, a higher proportion of TAF-treated CHB patients experienced grade 3 or higher levels of fasting LDL compared with the TDF group [14, 15], however, the increased rate of LDL with TAF treatment represented a small change, and the use of lipid-lowering agents was not described in this RCT trial. In the present study, no significant changes in LDL profile were observed compared with baseline levels in the patients who received TAF. To further confirm the severity of dyslipidemia in the TAF group, we used the NCEP ATP III classification for the categorization of dyslipidemia, finding no significant difference in the proportions of post-treatment serum lipid profiles compared with baseline levels. Therefore, whether the effect of TAF on elevated serum TCHO is a true indicator of an increased risk of metabolism-related diseases requires additional follow up.
Several studies have reported the direct lipid-lowering effect of TDF monotreatment in HBV patients as well as in other TDF-containing antiretroviral therapy regimens in HIV patients4,16,17. The current study similarly demonstrated serum lipoprotein lipid levels were significantly lower after 48 weeks of therapy compared to baseline levels in the continuing on TDF therapy group(Table 3). After 48 weeks of TAF treatment, the TCHO was elevated compared to the continuing TDF group༈Table 1). This result seems to reflect a combination of two aspects, the lipid-raising effect of TAF and the lipid-lowering effect of TDF. Therefore, further study is required to demonstrate that TAF has a "lipid increasing effect” compared with entecavir, which is known to have a ‘‘lipid neutral” effect. A recent study demonstrated that TDF modulated lipid metabolism by upregulating hepatic CD36 via PPAR-a activation in HBV infection18. In hepatocytes, CD36 was reported to be involved in the uptake of free fatty acids and oxidation of LDL19,20, while PPAR-a was associated with lipoprotein metabolism21. However, a precise mechanism for the TAF relevance of serum lipid elevation has not been ascertained. Further research is needed to clarify the potential mechanism of TAF on lipid lipoproteins in CHB patients.
With regard to clinical factors significantly associated with the elevated TCHO levels, multivariate logistic regression analysis indicated CREA, baseline TCHO, NAFLD and FBG. Consistent with our finding, one study similarly showed that the level of CREA was correlated with altered lipid profiles, and that TCHO was inversely associated with CREA level. 22 Meanwhile, the present study found that NAFLD was not a high risk factor of elevated TCHO according to multivariate analysis. In addition, the increased risk of elevated TCHO could not be explained by the patients’ age, BMI, or selected comorbidities such as hypertension and DM. Overall, the results appear to have little metabolic factor impact on the elevation of serum lipids caused by TAF. These metabolic syndrome factors may not be confounding factors of TAF treatment for CHB patients.
Apart from the potential serum lipid effect, the levels of HBeAg and HBV-DNA in patients switching to TAF therapy were not significantly different compared to those continuing on TDF therapy. Similarly, CREA and GFR values showed no significant differences (Table 1). However, the level of HBsAg 48 weeks after TAF therapy was significantly lower than in patients continuing on TDF therapy at the same time point. Thus, this research demonstrates the efficacy and safety of TAF for the treatment of CHB patients, with no significant changes in renal function (CREA and GFR) following switch to TAF from TDF, consistent with previous studies23–25.
Some of the limitations of the present study include that the individuals in our cohort were already on anti-virus therapy prior to switching to TAF, enabling the possibility that the previous anti-viral regimens may have influenced lipid levels in some way. Secondly, due to the retrospective design of the study, not all relevant clinical data were obtained continuously. Important data elements such as lifestyle risk factors (i.e., exercise, diet) and family history were in some cases incompletely documented in the patient file. Thus, these data were not taken into account in the statistical analysis. Finally, this study was not a multicenter study and the number of patients was relatively small. Therefore, a large-scale, multicenter prospective study should be conducted in order to further assess the impact of switching to TAF on lipid metabolism and renal function in CHB patients. Despite these limitations, this study provides real-world clinical data for the association of anti-HBV therapy with serum lipid profile changes in CHB patients, and indicates that switching from TDF to TAF does not result in a better renal function if the switch is not reason for renal dysfunction.
In conclusion, this real-life retrospective cohort study of Chinese patients found a significant association of TAF on increasing serum lipid TCHO in CHB patients after 48 weeks of therapy. The relationship between antiviral drugs and dyslipidemia has not been widely recognized, especially in CHB patients with NAFLD. Long-term dyslipidemia may increase the risk of NAFLD and liver-related adverse events. Our study findings indicated the need for future assessment of the direct impacts of TAF on cholesterol metabolism in CHB patients. It is worth further exploring whether it is necessary to indiscriminately switch to TAF due to fear of the risk of kidney impairment.