Seung Up Kim^1,2,3,a, Yeon Seok Seo^4,a, Han Ah Lee⁴, Mi Na Kim⁵, Yu Rim Lee⁶, Hye Won Lee^1,3, Jun Yong Park^1,2,3, Do Young Kim^1,2,3, Sang Hoon Ahn^1,2,3, Kwang-Hyub Han^1,2,3, Seong Gyu Hwang⁵, Kyu Sung Rim⁵, Soon Ho Um⁴, Won Young Tak⁶, Young Oh Kweon⁶, Beom Kyung Kim^1,2,3,b,*, Soo Young Park<sup>6,b,*

1</sup> Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
² Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea
³ Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
⁴ Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea
⁵ Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Republic of Korea
⁶ Department of Internal Medicine, Kyungpook National University Hospital, Daegu, Republic of Korea

^aSeung Up Kim and Yeon Seok Seo have equally contributed to this work as co-first authors.
^bBeom Kyung Kim and Soo Young Park have equally contributed to this work as co-corresponding authors.

^*Corresponding authors : Beom Kyung Kim, Soo Young Park

Background & aims
Which antiviral agent between entecavir (ETV) vs. tenofovir disoproxil fumarate (TDF) is superior in improving prognosis for chronic hepatitis B (CHB) is unclear. Here, we assessed the ability of these two antivirals to prevent liver-disease progression in treatment–naïve CHB patients.

Methods
From 2012 to 2014, treatment-naïve CHB patients who received ETV or TDF as a first–line antiviral agent were recruited from four academic teaching hospitals. Patients with decompensated cirrhosis or hepatocellular carcinoma (HCC) at enrollment were excluded. Cumulative probabilities of HCC and death or orthotopic liver transplant (OLT) were assessed.

Results
In total, 2,897 patients (1,484 and 1,413 in the ETV and TDF groups, respectively) were recruited. The annual HCC incidence was statistically not different between the ETV and TDF groups (1.92 vs. 1.69 per 100 person-years [PY], respectively; adjusted hazard ratio [HR], 0.975 [p=0.852] by multivariate analysis). Propensity score (PS)-matched and inverse probability of treatment weighting (ITPW) analyses yielded similar patterns of results (HR, 1.021 [p=0.884] and 0.998 [p=0.988], respectively). The annual incidence of death or OLT was statistically not different between the ETV and TDF groups (0.52 vs. 0.53 per 100 PY, respectively; adjusted HR, 1.202 [p=0.451]). PS-matched and ITPW analyses yielded similar patterns of results (HR, 1.248 [p=0.385] and 1.239 [p=0.360], respectively). These findings were consistently reproduced in patients with compensated cirrhosis (all p>0.05).

Conclusions
The overall prognosis in terms of HCC and death or OLT were statistically not different between the ETV and TDF groups. Further studies are needed to validate our results.

Keywords : Entecavir; tenofovir; hepatocellular carcinoma; prognosis; comparison