Tenofovir Disoproxil Fumarate Associated With Higher Rates of Elastographic Reversion in Patients With Hepatitis B

Hepatitis B
Hepatitis B
TDF therapy resulted in greater rates of elastographic reversion of cirrhosis in patients with chronic hepatitis B at year 5 compared with entecavir.

Tenofovir disoproxil fumarate (TDF) therapy resulted in greater rates of elastographic reversion of cirrhosis in patients with chronic hepatitis B (CHB) at year 5 compared with entecavir (ETV). The results from the multicenter study were published in the Journal of Hepatology.

Researchers included white patients (N=1935) with CHB, who were treated with ETV and/or TDF for at least 12 months through December of 2012, from the PAGE-B ongoing cohort. CHB was defined as HBsAg seropositivity for a minimum of 6 months, elevated alanine aminotransferase ≥40 IU/L, and serum HBV DNA >2000 IU/mL. Patients were treated with ETV (n=772) or TDF (n=1163) monotherapies. The patients were followed for a mean of 7.1±3.0 years.

Hepatocellular carcinoma (HCC) rates after 8 years did not differ based on treatment (ETV 7.7% vs TDF 8.6%; P =.282). Significantly more patients with cirrhosis developed HCC (19.3% vs 3.0%; P <.001) than those without cirrhosis. However, the treatments did not affect rates of HCC (non-cirrhotic cases: 3.7% ETV vs 2.5% TDF; P =.171; cirrhotic cases: 16.9% vs 20.4%; P =.341).

The researchers did not observe significant differences in virological remission (92.7% vs 92.2%; P =.567), HBsAg loss (7.1% vs 7.4%; P =.906), liver transplant (1.0% vs 1.1%; P =1.000), or liver-related mortality (2.6% vs 2.6%; P =1.000) in patients treated with ETV or TDF, respectively.

After 5 years, liver stiffness measurements below 12 kPa were observed among 70.6% of patients with pretreatment cirrhosis. The patients treated with TDF had significantly higher rates of elastographic reversion than those treated with ETV (73.8% vs 61.5%; P =.038). Patients who achieved elastographic reversion had lower body mass indices (OR, 3.18; 95% CI, 1.37-7.36; P =.007), lower diabetes mellitus rates (OR, 2.94; 95% CI, 1.14-7.58; P =.026), and more normal alanine aminotransferase levels (OR, 2.57; 95% CI, 1.06-6.23; P =.036).

One limitation of this study was that the treatment groups were not well balanced. The patients treated with ETV were younger (P =.043), had higher rates of smoking (P =.001), had lower rates of diabetes mellitus (P =.029), had lower HBsAg (P =.001), and lower alanine aminotransferase levels (P <.001). Furthermore, as only white patients were included in the study, it is unclear how these results relate to previously published studies of HCC in Asian patients.

The researchers concluded that among white patients, risk for HCC, rates of biochemical and virological remission, HBsAg loss, and liver transplantation or death was independent of ETV or TDF treatments, but also that ETV often resulted in increased elastographic reversion after 5 years.

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.


Papatheodoridis G V, Dalekos G N, Idilman R, et al. Similar risk of hepatocellular carcinoma during long-term entecavir or tenofovir therapy in Caucasian patients with chronic hepatitis B. J Hepatol. 2020;S0168-8278(20)30382-2. doi:10.1016/j.jhep.2020.06.011