Korean J Transplant.  2023 Nov;37(Suppl 1):S148. 10.4285/ATW2023.F-7348.

Clinical and histopathological findings are more useful in predicting hepatocellular carcinoma recurrence after liver transplantation than genetic markers

• Park J
• Kim DY
• Lee JG
• Yang JD
• Gee HY
• Yu HC

• KMID: 2551768
• DOI: http://doi.org/10.4285/ATW2023.F-7348

Abstract

Background
Liver transplantation (LT) provides the optimal treatment option for patients with unresectable hepatocellular carcinoma (HCC). Despite careful selection of patients, HCC may still recur after LT, which is associated with the dismal prognosis of posttransplant survival. We aimed to discover susceptibility loci by performing the first genome-wide association study (GWAS) of HCC recurrence after LT, along with clinical and histopathological findings.
Methods
All samples of cases and controls were genotyped using Korea Biobank Array with about 830K variants. We used a discovery cohort of 148 patients with HCC recurrence as cases and 1,427 patients without HCC recurrence as controls after LT to perform a GWAS. Additive logistic regression was performed by adjusting age and gender using EPACTS software. We validated our GWAS results using new replication cohort consisting of 53 as cases and 588 as controls. In addition, candidate variants were imputed using IMPUTE v4 with the merged reference panel of 1,000 Genomes project and Korean Reference Genome. On the other hand, the clinical and histopathological findings were estimated for their potential as risk factors for HCC recurrence after LT.
Results
At genome-wide thresholds of significance as P<10^–7, one locus (rs1961614) of the C1orf100 was associated with HCC recurrence after LT. The C1orf100 gene was recently discovered to be associated with white cell telomere length. However, this locus was not reproduced in the replication cohort. On the other hand, among clinical and histopathological findings, a single tumor <5 cm, a maximum of three tumors with <3 cm, no macrovascular invasion, and no metastasis were statistically associated with lower HCC recurrence after LT (P<0.05).
Conclusions
In the limited Korean LT cohort from the Korean Organ Transplantation Registry database, clinical and histopathological findings are more useful in predicting HCC recurrence after LT than genetic markers.