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1055
HEPATOCELLULAR CARCINOMA INCIDENCE WITH TENOFOVIR
VS ENTECAVIR IN CHRONIC HEPATITIS B: A SYSTEMATIC
REVIEW AND META-ANALYSIS
Cheng-Hao Tseng1,2, Yao-Chun Hsu3, Tzu-Haw Chen4, Fanpu
Ji Jr.5, I-Sung Chen4, Ying-Nan Tsai6, Hoang Hai7, Thuy
Thi Thanh Le8, Tetsuya Hosaka9, Hitomi Sezaki9, John A.
Borghi10, Ramsey Cheung11, Masaru Enomoto7,8 and Mindie
H. Nguyen11,12, (1)E-DA Cancer Hospital, (2)Gastroenterology
and Hepatology, E-DA Cancer Hospital, Kaohsiung, Taiwan, (3)
Center of Liver Diseases, E-Da Hospital, (4)Gastroenterology
and Hepatology, E-DA Hospital, (5)Infectious Diseases, The
Second Affiliated Hospital of Xi’an Jiaotong University, (6)
Gastroenterology and Hepatology, E-DA Cancer Hospital,
(7)Hepatology, Osaka City University Graduate School
of Medicine, (8)Department of Hepatology, Osaka City
University Graduate School of Medicine, (9)Hepatology,
Toranomon Hospital, (10)Lane Medical Library & Knowledge
Management Center, Stanford University, (11)Division of
Gastroenterology and Hepatology, Department of Medicine,
Stanford University Medical Center, (12)Gastroenterology
and Hepatology, Stanford University Medical Center
Background: Whether TDF and ETV differ in their association
with HCC risk in CHB patients remains controversial We
identified eight existing meta-analyses with inconsistent
conclusions, which was likely due to heterogeneity that
were not fully addressed and study limitations that were
overlooked This meta-analysis aims to analyze the updated
data and elucidate where the heterogeneity originate from
Methods: We searched PubMed, Embase, Web of Science,
and the Cochrane library for relevant studies published
between January 1, 2006 and April 17, 2020 and abstracts
from major international conferences in 2018 and 2019
The hazard ratio (HR) for incident HCC was pooled using a
random-effects model Results: A total of 31 studies involving
119,053 patients were analyzed: The 5-year cumulative HCC
incidence with ETV and TDF were respectively 5 97% (95%
CI, 5 81-6 13%) versus 3 06% (95% CI, 2 86-3 26%) from
28 unmatched studies, and 3 44% (95% CI, 3 08-3 80%)
versus 3 39% (95% CI, 2 94-3 83%) from 8 matched studies,
indicating preexisting confounders between the ETV and TDF
groups in unmatched studies Analysis of 14 comparative
studies with covariate adjustment found that TDF and ETV
were not significantly associated with different HCC risks
(adjusted HR, 0 88; 95% CI, 0 73-1 07; P=0 20), though
heterogeneity was significant (I2=56 4%, P=0 004) (Figure
1). Subgroup analysis identified the source of heterogeneity
among the different study settings and confirmed that there
was no difference between TDF and ETV among hospitalbased
clinical cohort studies (adjusted HR of 1 03, 95% CI,
0 88-1 21; I2=0%), while TDF was found to be superior in
administrative database research (adjusted HR, 0 67, 95%
CI, 0 59-0 76; I2=0%).There was also no significant difference
ETV and TDF from studies with no or minimal disparity in
follow-up duration (adjusted HR, 0·88; 95% CI, 0·70-1·11;
I2=51·1%), while TDF was associated with lower HCC risk as
compared to ETV (adjusted HR, 0·69; 95% CI, 0·61-0·79; I2=0
%) among studies where the follow-up duration for ETV was
one year or longer Conclusion: Comprehensive analysis
found no significant difference between TDF and ETV with
incident HCC The superiority of TDF in administrative
database research is likely due to incomplete adjustment
for confounders as relevant clinical and laboratory data are
generally not available in these databases Thus, the choice
of which agent should depend on patient factors such as cost
and tolerability. |
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