Liver transplantation outcomes, systemic immune–inflammatory phenotype, and predictors of hepatocellular carcinoma recurrence in an HBV/HDV-endemic region: a retrospective cohort study
Abstract
Chronic hepatitis B and D virus (HBV/HDV) coinfection sustains a hepatic inflammatory microenvironment from which hepatocellular carcinoma (HCC) arises. Although advances in liver transplantation have improved survival, HCC recurrence remains a major challenge affecting long-term outcomes. This study aimed to evaluate post-transplant outcomes and identify risk factors associated with HCC recurrence among liver transplant recipients in Mongolia, and to characterize their pre-transplant systemic immune–inflammatory phenotype. This single-center retrospective cohort study included 146 patients with HCC who underwent liver transplantation at the National Cancer Center of Mongolia from 2018 through February 2026. Survival was estimated using Kaplan–Meier analysis with the log-rank test, and factors associated with HCC recurrence were assessed using univariable Cox regression. Pre-transplant neutrophil (ANC) and lymphocyte (ALC) counts and their ratio (NLR) were available for 139 recipients; lymphopenia was an ALC below 1.0 ×109/L. The 1-, 3-, and 5-year overall survival rates were 88.7%, 82.1%, and 80.5%, respectively, with no significant difference between patients within versus beyond the Milan criteria (p = 0.097). HCC recurrence occurred in 3.4% of recipients and was significantly more common among patients beyond the Milan criteria (p = 0.001). Macrovascular invasion (HR, 12.76; p = 0.005), beyond-Milan status (HR, 10.04; p = 0.039), higher Edmondson–Steiner grade (HR, 9.25; p = 0.047), and elevated AFP (HR, 15.95; p = 0.003) were associated with recurrence in univariate analysis. HCV/HBV/HDV coinfection was significantly associated with higher post-transplant mortality. Median NLR was 1.84 and 39.6% of recipients were lymphopenic; NLR varied inversely with the ALC (ρ = −0.61) and positively with the ANC (ρ = +0.67, both p < 0.001). Lymphopenia increased with tumor burden (34.4% within Milan, 51.2% beyond, 3 of 5 recurrences), NLR was higher when HCC was histologically confirmed on the explant (2.10 vs 1.44, p = 0.015), and recurrence deaths showed the highest NLR with the lowest ALC, rejection deaths the reverse. Liver transplantation achieved favorable survival outcomes in patients with HCC in Mongolia. In exploratory univariate analysis, incorporating pre-transplant tumor characteristics, biomarkers, and viral etiology, together with the pre-transplant lymphocyte compartment, may improve prediction of recurrence and post-transplant mortality, particularly among patients beyond the Milan criteria.
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BibTeX
@article{radnaabazar2026liver,
title = {{Liver transplantation outcomes, systemic immune–inflammatory phenotype, and predictors of hepatocellular carcinoma recurrence in an HBV/HDV-endemic region: a retrospective cohort study}},
author = {Munkhbat Radnaabazar and Allabyergyen Myeryemkhaan and Munkhtsetseg Munkhbold and Injinaash Ogoosambuu and Munkhdelger Byambaragchaa and Annie Enerelt Bat-Erdene and Yerbolat Amankyeldi and Amgalantuul Batdelger and Nomin Dashdondov and Munkhzaya Chogsom and Jongman Kim and Mendjargal Adilsaikhan and Chinburen Jigjidsuren and Odgerel Tsogbadrakh},
journal = {Frontiers in Immunology},
year = {2026},
month = nov,
doi = {10.3389/fimmu.2026.1992407},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1992407},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Liver transplantation outcomes, systemic immune–inflammatory phenotype, and predictors of hepatocellular carcinoma recurrence in an HBV/HDV-endemic region: a retrospective cohort study
AU - Munkhbat Radnaabazar
AU - Allabyergyen Myeryemkhaan
AU - Munkhtsetseg Munkhbold
AU - Injinaash Ogoosambuu
AU - Munkhdelger Byambaragchaa
AU - Annie Enerelt Bat-Erdene
AU - Yerbolat Amankyeldi
AU - Amgalantuul Batdelger
AU - Nomin Dashdondov
AU - Munkhzaya Chogsom
AU - Jongman Kim
AU - Mendjargal Adilsaikhan
AU - Chinburen Jigjidsuren
AU - Odgerel Tsogbadrakh
PY - 2026
DA - 2026/11/02
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1992407
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1992407
AB - Chronic hepatitis B and D virus (HBV/HDV) coinfection sustains a hepatic inflammatory microenvironment from which hepatocellular carcinoma (HCC) arises. Although advances in liver transplantation have improved survival, HCC recurrence remains a major challenge affecting long-term outcomes. This study aimed to evaluate post-transplant outcomes and identify risk factors associated with HCC recurrence among liver transplant recipients in Mongolia, and to characterize their pre-transplant systemic immune–inflammatory phenotype. This single-center retrospective cohort study included 146 patients with HCC who underwent liver transplantation at the National Cancer Center of Mongolia from 2018 through February 2026. Survival was estimated using Kaplan–Meier analysis with the log-rank test, and factors associated with HCC recurrence were assessed using univariable Cox regression. Pre-transplant neutrophil (ANC) and lymphocyte (ALC) counts and their ratio (NLR) were available for 139 recipients; lymphopenia was an ALC below 1.0 ×109/L. The 1-, 3-, and 5-year overall survival rates were 88.7%, 82.1%, and 80.5%, respectively, with no significant difference between patients within versus beyond the Milan criteria (p = 0.097). HCC recurrence occurred in 3.4% of recipients and was significantly more common among patients beyond the Milan criteria (p = 0.001). Macrovascular invasion (HR, 12.76; p = 0.005), beyond-Milan status (HR, 10.04; p = 0.039), higher Edmondson–Steiner grade (HR, 9.25; p = 0.047), and elevated AFP (HR, 15.95; p = 0.003) were associated with recurrence in univariate analysis. HCV/HBV/HDV coinfection was significantly associated with higher post-transplant mortality. Median NLR was 1.84 and 39.6% of recipients were lymphopenic; NLR varied inversely with the ALC (ρ = −0.61) and positively with the ANC (ρ = +0.67, both p < 0.001). Lymphopenia increased with tumor burden (34.4% within Milan, 51.2% beyond, 3 of 5 recurrences), NLR was higher when HCC was histologically confirmed on the explant (2.10 vs 1.44, p = 0.015), and recurrence deaths showed the highest NLR with the lowest ALC, rejection deaths the reverse. Liver transplantation achieved favorable survival outcomes in patients with HCC in Mongolia. In exploratory univariate analysis, incorporating pre-transplant tumor characteristics, biomarkers, and viral etiology, together with the pre-transplant lymphocyte compartment, may improve prediction of recurrence and post-transplant mortality, particularly among patients beyond the Milan criteria.
SN - 1664-3224
ER -