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Multicenter Study
. 2024 Aug 1;80(2):428-439.
doi: 10.1097/HEP.0000000000000752. Epub 2024 Jan 24.

Chronic hepatitis B baseline viral load and on-treatment liver cancer risk: A multinational cohort study of HBeAg-positive patients

Won-Mook Choi  1 , Terry Cheuk-Fung Yip  2 , W Ray Kim  3 , Leland J Yee  4 , Craig Brooks-Rooney  5 , Tristan Curteis  6 , Laura J Clark  6 , Zarena Jafry  5 , Chien-Hung Chen  7 , Chi-Yi Chen  8 , Yi-Hsiang Huang  9   10 , Young-Joo Jin  11 , Dae Won Jun  12 , Jin-Wook Kim  13   14 , Neung Hwa Park  15   16 , Cheng-Yuan Peng  17   18 , Hyun Phil Shin  19 , Jung Woo Shin  15 , Yao-Hsu Yang  20   21 , Grace Lai-Hung Wong  2 , Young-Suk Lim  1
Affiliations
Multicenter Study

Chronic hepatitis B baseline viral load and on-treatment liver cancer risk: A multinational cohort study of HBeAg-positive patients

Won-Mook Choi et al. Hepatology. .

Abstract

Background and aims: A single-nation study reported that pretreatment HBV viral load is associated with on-treatment risk of HCC in patients who are HBeAg-positive without cirrhosis and with chronic hepatitis B initiating antiviral treatment. We aimed to validate the association between baseline HBV viral load and on-treatment HCC risk in a larger, multinational cohort.

Approach and results: Using a multinational cohort from Korea, Hong Kong, and Taiwan involving 7545 adult patients with HBeAg-positive, without cirrhosis and with chronic hepatitis B who started entecavir or tenofovir treatment with baseline HBV viral load ≥5.00 log 10 IU/mL, HCC risk was estimated by baseline viral load. HBV viral load was analyzed as a categorical variable. During continuous antiviral treatment (median, 4.28 y), HCC developed in 200 patients (incidence rate, 0.61 per 100 person-years). Baseline HBV DNA level was independently associated with on-treatment HCC risk in a nonlinear pattern. HCC risk was lowest with the highest baseline viral load (≥8.00 log 10 IU/mL; incidence rate, 0.10 per 100 person-years), but increased sharply as baseline viral load decreased. The adjusted HCC risk was 8.05 times higher (95% CI, 3.34-19.35) with baseline viral load ≥6.00 and <7.00 log 10 IU/mL (incidence rate, 1.38 per 100 person-years) compared with high (≥8.00 log 10 IU/mL) baseline viral load ( p <0.001).

Conclusions: In a multinational cohort of adult patients with HBeAg-positive without cirrhosis and with chronic hepatitis B, baseline HBV viral load was significantly associated with HCC risk despite antiviral treatment. Patients with the highest viral load who initiated treatment had the lowest long-term risk of HCC development.

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Conflict of interest statement

Terry Cheuk-Fung Yip consults, advises, is on the speakers’ bureau, and received grants from Gilead. W. Ray Kim advises Gilead, Inovio, and Roche. Leland J. Yee is employed by and owns stock in Gilead. Craig Brooks-Rooney is employed by Costello Medical. Tristan Curteis has other interests with Gilead. Laura J. Clark has other interests with Gilead. Zarena Jafry is employed by Costello Medical. Yi-Hsiang Huang consults, advises, and received grants from Gilead. He consults, advises, and is on the speakers’ bureau for Eisai and MSD. He advises and received grants from Bristol-Meyers Squibb. He advises AbbVie, AstraZeneca, Eli Lilly, Ipsen, Ono, and Roche. Cheng-Yuan Peng advises Bristol-Myers Squibb and Gilead. Grace Lai-Hung Wong advises, is on the speakers’ bureau for, and received grants from Gilead. She advises and is on the speakers’ bureau for Janssen. She advises AstraZeneca. She is on the speakers’ bureau for Abbott, AbbVie, Ascletis, Bristol-Myers Squibb, Echosens, Furui, and Roche. Young-Suk Lim advises and received grants from Gilead. The remaining authors have no conflicts to report.

Figures

None
Graphical abstract
FIGURE 1
FIGURE 1
Patient flow. Abbreviations: CHB, chronic hepatitis B; ETV, entecavir; TDF, tenofovir disoproxil fumarate.
Figure 2
Figure 2
Cumulative incidence of HCC during treatment by baseline HBV viral load levels. (A) Unweighted analysis. (B) PSW analysis. (C) PSM analysis (high vs. moderate viral load tiers). High and moderate viral loads indicated baseline serum HBV DNA levels ≥8.00 log10 IU/mL and ≥5.00 to <8.00 log10 IU/mL, respectively. Abbreviations: PSM, propensity score matching; PSW, propensity score weighting.
Figure 2
Figure 2
Cumulative incidence of HCC during treatment by baseline HBV viral load levels. (A) Unweighted analysis. (B) PSW analysis. (C) PSM analysis (high vs. moderate viral load tiers). High and moderate viral loads indicated baseline serum HBV DNA levels ≥8.00 log10 IU/mL and ≥5.00 to <8.00 log10 IU/mL, respectively. Abbreviations: PSM, propensity score matching; PSW, propensity score weighting.
Figure 2
Figure 2
Cumulative incidence of HCC during treatment by baseline HBV viral load levels. (A) Unweighted analysis. (B) PSW analysis. (C) PSM analysis (high vs. moderate viral load tiers). High and moderate viral loads indicated baseline serum HBV DNA levels ≥8.00 log10 IU/mL and ≥5.00 to <8.00 log10 IU/mL, respectively. Abbreviations: PSM, propensity score matching; PSW, propensity score weighting.
FIGURE 3
FIGURE 3
Penalized spline regression showing adjusted HR for the risk of HCC by baseline HBV DNA levels. The penalized spline regression model adjusted for HBV viral load.
See this image and copyright information in PMC

Comment in

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