HBV: Protecting the liver… without harming the rest?

#Hepatitis #HBV #Tenofovir #InfectiousDiseases  


Chronic hepatitis B (CHB) affects nearly 300 million people worldwide and remains a leading cause of cirrhosis and hepatocellular carcinoma. While nucleotide analogs like tenofovir disoproxil fumarate (TDF) are effective in suppressing viral replication, long-term use is associated with significant adverse effects, particularly renal, bone, and metabolic complications. A key current challenge in managing CHB is maintaining antiviral efficacy while reducing long-term risks. Tenofovir amibufenamide (TMF) was developed as a next-generation alternative, aiming to offer improved safety without compromising antiviral potency. This study was conducted to evaluate virologic efficacy and metabolic safety, especially regarding lipid metabolism, in patients switching from TDF to TMF.    

TMF: As strong as TDF… but better tolerated?

This was a randomized, controlled, multicenter phase 3 extension study including CHB patients who had previously received TMF or TDF for 96 weeks. All participants were switched to TMF for an additional 48-week extension, resulting in 144 weeks of total follow-up.   

These studies demonstrate that antiviral efficacy is maintained in both groups: prolonged suppression of viral DNA, stable ALT normalization rates, and no emergence of virological resistance.

From a metabolic standpoint, clear differences are observed. TDF induced an early reduction in total cholesterol and LDL, effects that diminished after switching to TMF. TMF, on the other hand, maintained more stable lipid profiles, with no trend toward dyslipidemia. No clinically significant lipid-related adverse events were reported in either group. Bone and renal parameters remained stable, supporting the favorable long-term safety profile of TMF.  

A gentler treatment with consistent efficacy?

Chronic hepatitis B is a persistent viral infection that requires long-term treatment. One of the current major challenges is to maintain sustained viral suppression while minimizing long-term adverse effects, particularly renal, bone, and metabolic. This study aimed to assess whether tenofovir amibufenamide, as an alternative to tenofovir disoproxil fumarate, could combine antiviral efficacy with improved metabolic tolerance over a prolonged period.

The results confirm that TMF maintains a virological response equivalent to that of TDF, while preserving a more stable lipid profile and avoiding notable side effects. These findings strengthen the relevance of TMF as a long-term treatment option for patients with chronic hepatitis B, particularly those at metabolic risk.

Despite a limited extension period of 48 weeks and the absence of a prolonged comparative arm under TDF, the results position TMF as a relevant therapeutic option for patients with chronic hepatitis B, especially those with an increased metabolic risk. Further, longer-term studies targeting populations at high cardiovascular risk will be needed to confirm its long-term benefits.

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