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Ayoub et al. Nucleos(t)ide therapy for hepatitis B impacts HCC incidence

tenofovir are first line agents for treating CHB because reported rates of HCC of 3.5% in lamivudine-treated
they have such a high barrier to resistance. Many CHB patients compared to 9.6% in CHB patients who
studies with nucleos(t)ide therapy have confirmed were not treated, over a period of 4 years [18] .
a decrease in the rate of HCC in treated patients,
regardless of the strength of the proposed treatment’s Entecavir and tenofovir
barrier to resistance. The introduction of the third generation NAs, tenofovir
and entecavir, which both have a high genetic barrier
TREATMENT OF HBV AND HCC to resistance, has led to further decreases in HCC
incidence. A retrospective study comparing the
incidence of HCC in entecavir-treated patients to a
Antiviral therapy with NAs and interferon can improve historical cohort of lamivudine-treated patients without
liver fibrosis and suppress HBV viral replication, which rescue therapy in the event of resistance development
leads to decreased HCC incidence in patients with
CHB [14] . Most of the studies describing the impact of was conducted in Japan. Propensity score matching
treating CHB on the incidence of liver cancer evaluated was used to eliminate baseline differences and the
the first generation drugs, specifically lamivudine authors found that entecavir-treated patients had a
and adefovir. There is less available data regarding lower 5-year cumulative incidence of HCC compared
the effect of the 3rd generation drugs, tenofovir and to historical controls (3.7% vs. 13.7%, P < 0.001).
entecavir. One recent meta-analysis of patients The benefit of treatment was seen mainly in cirrhotic
with HBsAg seroclearance (n = 34,952) showed a patients, 7% in the entecavir group vs. 39% in historic
significantly decreased risk for developing HCC in controls (P = 0.049) compared to the non-cirrhotic
comparison to those with who did not seroconvert [risk group, and 3.3% in the entecavir vs. 3% in controls
[19]
. In an observational study conducted by
ratio (RR) 0.34, 95% confidence interval (CI): 0.20- (P > 0.05) [20]
0.56, P < 0.001], but among those who seroconverted, Wong et al. , there was also decreased incidence of
2.29% (95%CI: 1.19-4.37) still developed HCC [15] . HCC with entecavir treatment compared to historical
controls, also significant only in cirrhotic patients
Adefovir and lamivudine (13.8% vs. 26.4%, P = 0.049). A similar observational
[21]
[3]
Liaw et al. published the only randomized clinical study by Su et al. of patients with cirrhosis
trial that addresses the benefits of using lamivudine demonstrated 5 year cumulative HCC incidence of
in CHB patients with cirrhosis or advanced fibrosis 26.4% in the untreated historical cohort and 11.3% in
proven by biopsy. Compared to the placebo group, the treated cohort with entecavir resulting in reduction
the lamivudine group had a significant reduction in of HCC risk by approximately 60% (HR 0.40, 95%CI
HCC, 7.4% vs. 3.9% respectively (HR 0.49, P = 0.047). 0.28-0.57). In another propensity score-matched
Additionally, the group treated with lamivudine had a study of Japanese patients (n = 234), Kumada et al. [22]
nearly 50% reduction in progression of disease (7.8% determined that entecavir therapy significantly reduced
vs. 17.7%, HR 0.45, P = 0.001). As a result of the HCC incidence; the 5- and 10-year cumulative
significant difference found between the 2 arms, the incidence of HCC were 11.3% and 40% in untreated
study was stopped prematurely after a mean duration controls, respectively, compared to 2.7% and 3.3% in
of 32.4 months. patients treated with entecavir. Long-term entecavir
treatment has been shown to reduce fibrosis by
The advantages of using the first-generation NAs to more than 1 point by the Ishak fibrosis score in 88%
reduce HCC risk has since been supported in meta- of patients who were treated for 6 years [23] . A large
analyses and systematic reviews. In a meta-analysis retrospective study of Taiwanese patients (n = 21,595),
evaluating 5 studies that compared oral treatment assessed a cohort of NA-treated patients and a cohort
to placebo, treatment with NAs was associated with of patients receiving hepatoprotective agents, but no
78% reduced incidence of HCC (RR 0.22, P < 0.001) NA treatment matched by propensity score. The 7-year
irrespective of cirrhosis. Treatment with NAs has incidence of HCC was significantly lower in the cohort
also been shown to benefit patients who developed treated with NA (7.3%), compared to the non-NA
treatment resistance (NA 3.3% vs. control 6.4%, RR treated cohort (22.7%) (adjusted HR 0.37; P < 0.001).
0.52, P = 0.04) [16] . Similar results were reported in a In this study, the benefits of NA therapy were noted
systematic review that assesses adefovir, lamivudine, among patients without (HR 0.27) cirrhosis in addition
and the combination of both vs. placebo in 3,881 CHB to patients with cirrhosis (HR 0.72) [24] .
patients naive to treatment with NAs. Over a period
of 42 months, HCC incidence was lower in treated A recent retrospective study conducted in Canada
patients (2.8%) compared to patients who were not utilized the REACH-B scoring system to evaluate
treated (6.4%; P = 0.003) [17] . Another meta-analysis the risk of developing HCC among patients treated

304 Hepatoma Research ¦ Volume 3 ¦ December 20, 2017