Raut S, Naik E P. Letter to the Editor: Toward biology-driven transplant oncology: The role of PIVKA-II in alpha-fetoprotein-normal hepatocellular carcinoma. World J Gastrointest Oncol 2026; 18(8): 118170 [DOI: 10.4251/wjgo.118170]
Corresponding Author of This Article
Sagar Raut, MD, Assistant Professor, Department of Radiotherapy and Oncology, PGIMER Satellite Centre, Patiala Road, Sangrur 148001, India. snraut161@gmail.com
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Gastroenterology & Hepatology
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letter
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Raut S, Naik E P. Letter to the Editor: Toward biology-driven transplant oncology: The role of PIVKA-II in alpha-fetoprotein-normal hepatocellular carcinoma. World J Gastrointest Oncol 2026; 18(8): 118170 [DOI: 10.4251/wjgo.118170]
World J Gastrointest Oncol. Aug 15, 2026; 18(8): 118170 Published online Aug 15, 2026. doi: 10.4251/wjgo.118170
Letter to the Editor: Toward biology-driven transplant oncology: The role of PIVKA-II in alpha-fetoprotein-normal hepatocellular carcinoma
Sagar Raut, Pradeep Naik E
Sagar Raut, Department of Radiotherapy and Oncology, PGIMER Satellite Centre, Sangrur 148001, India
Pradeep Naik E, Department of Radiation Oncology, All India Institute of Medical Sciences, Nagpur 441108, Mahārāshtra, India
Author contributions: Raut S and Naik EP designed the report, conducted the literature review, analyzed the data, and wrote the paper; all authors read and approved the final version of the manuscript.
AI contribution statement: ChatGPT was used for language polishing and writing assistance.
Conflict-of-interest statement: All authors have no conflicts of interest related to the manuscript.
Corresponding author: Sagar Raut, MD, Assistant Professor, Department of Radiotherapy and Oncology, PGIMER Satellite Centre, Patiala Road, Sangrur 148001, India. snraut161@gmail.com
Received: December 26, 2025 Revised: January 28, 2026 Accepted: February 4, 2026 Published online: August 15, 2026 Processing time: 219 Days and 3.6 Hours
Abstract
Liver transplantation is the most effective therapy for selected patients with hepatocellular carcinoma (HCC). However, post-transplant recurrence limits long-term survival. Current transplant selection guidelines predominantly rely on morphological criteria, such as the Milan criteria. These criteria incompletely capture the biological heterogeneity of HCC. This limitation is particularly evident in HCC in which alpha-fetoprotein (AFP) levels are normal, leading to clinically occult aggressive tumor biology. This invited letter to the editor examines the clinical implications of the recent study published in the World Journal of Gastrointestinal Oncology by Abbas et al in which they identified PIVKA-II as a marker of aggressive tumor behavior in AFP-normal HCC. The elevated PIVKA-II levels were strongly associated with adverse biological features, including disease beyond the Milan criteria and portal vein tumor thrombosis despite normal AFP levels. PIVKA-II successfully stratified patients with a high likelihood of aggressive disease even when conventional imaging criteria were met. The framework for transplant oncology is constantly evolving, and we highlight that PIVKA-II may complement existing morphologic and biomarker-based selection models. We particularly emphasize the potential role of PIVKA-II in refining transplant eligibility, guiding downstaging strategies, and improving surveillance and waitlist management in patients with normal AFP levels. While prospective validation is required, incorporation of PIVKA-II for transplant evaluation represents a meaningful step toward biology-driven, precision-based allocation in HCC management.
Core Tip: Hepatocellular carcinoma with normal alpha-fetoprotein (AFP) levels is a frequently missed when transplantation selection relies heavily on morphological criteria and AFP levels. Emerging evidence identified PIVKA-II as a robust marker of aggressive tumor biology in this subgroup. PIVKA-II successfully categorized high-risk disease despite favorable imaging and normal AFP levels. Integration of PIVKA-II with existing selection frameworks will enable a shift toward biology-driven transplant oncology and reduce post-transplant recurrence.
