Increasing antiviral treatment uptake improves survival in patients with HBV-related HCC
Vicki Wing-Ki Hui 1 2 3 , Stephen Lam Chan 4 , Vincent Wai-Sun Wong 1 2 3 , Lilian Yan Liang 1 , Terry Cheuk-Fung Yip 1 2 3 , Jimmy Che-To Lai 1 , Becky Wing-Yan Yuen 1 , Hester Wing-Sum Luk 1 , Yee-Kit Tse 1 2 3 , Hye-Won Lee 5 , Henry Lik-Yuen Chan 1 2 3 , Grace Lai-Hung Wong 1 2 3
Affiliations
Affiliations
1
Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China.
2
Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China.
3
Medical Data Analytic Centre, The Chinese University of Hong Kong, Hong Kong SAR, China.
4
Department of Clinical Oncology, The Chinese University of Hong Kong, Hong Kong SAR, China.
5
Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea.
Background & aims: Antiviral treatment is known to improve survival in patients with chronic hepatitis B (CHB)-related hepatocellular carcinoma (HCC). Yet, the treatment uptake in CHB patients remains low. We aimed to report the secular trend in antiviral treatment uptake from 2007-2017, and to compare the effect of different nucleos(t)ide analogue (NA) initiation times (before vs. after HCC diagnosis) on survival.
Methods: A 3-month landmark analysis was used to compare overall survival in patients not receiving NA treatment (i.e. no NA), patients receiving NAs after their first HCC treatment (i.e. post-HCC NA), and patients receiving NAs ≤3 months before their first HCC treatment (i.e. pre-HCC NA). A propensity score-weighted Cox proportional hazards model was used to balance clinical characteristics between the 3 groups and to estimate hazard ratios (HRs).
Results: The uptake of antiviral treatment in HCC patients increased from 47.3% in 2007 to 98.3% in 2017. The pre-HCC NA group contributed mostly to the uptake rate, which increased from 72.7% to 96.0% in the past decade. In addition, 3,843 CHB patients (407 no NA; 2,932 pre-HCC NA; 504 post-HCC NA) with HCC, receiving at least 1 type of HCC treatment, were included in the analysis. Lack of NA treatment at the time of HCC diagnosis increased the risk of death (weighted HR 3.05; 95% CI 2.70-3.44; p <0.001). The impact of the timing of NA treatment was insignificant (weighted HR 0.90; 95% CI 0.78-1.04; p = 0.161).
Conclusions: The uptake of antiviral treatment in HCC patients increased over the past decade. NA treatment, regardless of whether it was initiated before or after HCC diagnosis, improved survival. It is never too late to initiate NA treatment, even after HCC diagnosis.
Lay summary: More and more patients who have hepatitis B-related liver cancer received antiviral treatment over the past decade. The timing of starting antiviral treatment, regardless of whether it was before or after liver cancer happens, does not really matter in terms of survival benefits.
Keywords: AFP, alpha-fetoprotein; ALT, alanine aminotransferase; ASMD, absolute standardised mean difference; CDARS, Clinical Data Analysis and Reporting System; CHB, chronic hepatitis B; Entecavir; GGT, gamma-glutamyl transpeptidase; HCC, hepatocellular carcinoma; HR, hazard ratio; Hazard ratio; ICD-9-CM, International Classification of Diseases, Ninth Revision, Clinical Modification; IPTW, inverse probability of treatment weighting; IQR, inter-quartile range; KS, Kolmogorov-Smirnov; Lamivudine; Local ablative therapy; MICE, multivariate imputation by chained equations; NA, nucleos(t)ide analogue; PS, propensity score; Propensity scores; Surgical resection; TACE, transarterial chemoembolisation; TDF, tenofovir disoproxil fumarate; Transarterial chemoembolisation; aHR, adjusted hazard ratio.