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Selection has advanced from strict Milan morphometric limits toward biomarker- and biology-informed candidacy using AFP measures and kinetics, DCP/PIVKA-II, AFP-L3, metabolic imaging, inflammatory indices, response to locoregional therapy, and emerging radiomic and liquid-biopsy surrogates. Downstaging now functions as a structured biologic stress test, distinguishing stable tumors from rapid re-progression. Current evidence supports personalized transplant oncology models incorporating recurrence risk, survival benefit, and donor/graft ethics, and highlights a future of continuous risk modeling with 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is liver transplantation considered uniquely curative for HCC in selected patients with cirrhosis?","Question",{"text":63,"@type":64},"It simultaneously treats the tumor and resets the carcinogenic cirrhotic field, reducing both macroscopic disease and the underlying drivers of multifocal recurrence and liver failure.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How have selection criteria for LT in HCC evolved beyond Milan criteria?",{"text":68,"@type":64},"Modern selection increasingly integrates biomarkers (e.g., AFP levels and kinetics, DCP/PIVKA-II, AFP-L3), metabolic imaging (e.g., FDG-PET), inflammatory indices, and response to locoregional therapy, along with emerging radiomic and liquid-biopsy indicators.",{"name":70,"@type":61,"acceptedAnswer":71},"What role does downstaging play in contemporary transplant selection?",{"text":72,"@type":64},"Downstaging has shifted from being only a way to improve list access into a structured biologic stress test, helping distinguish tumors that stabilize biologically from those that re-progress rapidly despite technical response.","https://schema.org",{"og:url":32,"og:type":75,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":77,"canonical":32},"index,follow",{"doc_id":79,"site_id":7},508526,1791397784,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,110,115,119,122,126],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":85,"show_sort_weight":86,"slug":87},"Story & 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Liver Transplant in Treatment of HCC  \nPiyush Gupta 1,\\#  \n1 Department of Transplant Surgery, MedStar Georgetown Hospital, Washington DC 20007, USA  \nAbstract: Liver transplantation (LT) remains the most definitive curative treatment for carefully selected patients with hepatocellular carcinoma (HCC) because it simultaneously removes macroscopic tumor and the cirrhotic field in which de novo carcinogenesis, portal hypertension, and hepatic failure are embedded. The discipline has, however, moved decisively beyond a purely morphometric paradigm. Milan criteria remain the benchmark for transplant legitimacy, but modern selection increasingly integrates alpha-fetoprotein (AFP), AFP kinetics, des-gamma-carboxy prothrombin (DCP/PIVKA-II), AFP-L3, fluorodeoxyglucose positron-emission tomography (FDG-PET), inflammatory indices, response to locoregional therapy (LRT), and emerging radiomic and liquid-biopsy surrogates of occult biologic aggressiveness. Downstaging has similarly evolved from a strategy for list access into a structured biologic stress test. Tumors that can be reduced, stabilized, and biochemically quieted over time are biologically distinct from those that re-progress rapidly despite technical response. This distinction is especially relevant in living donor liver transplantation (LDLT), where reduced waitlist attrition must be balanced against healthy-donor risk and the loss of a prolonged 'test of time'. Contemporary evidence therefore supports a personalized transplant oncology model in which candidacy is judged not by lesion size and number alone but by integrated estimates of recurrence risk, survival benefit, and donor or graft ethics. In parallel, selected patients with portal vein tumor thrombus (PVTT) may now be considered after successful downstaging in expert programs, whereas hepatic vein tumor thrombus (HVTT) remains investigational. The future of LT for HCC will likely be defined by continuous risk modeling that combines morphology, biomarkers, metabolic imaging, molecular residual disease assays, and artificial intelligence within a maturing specialty of transplant oncology.  \nKeywords: Hepatocellular carcinoma; Liver transplantation; Transplant oncology; Downstaging; Living donor liver transplantation; Alpha-fetoprotein.  \nIntroduction  \nHCC accounts for the great majority of primary liver cancers and remains a leading cause of cancer-related mortality worldwide. For the patient with cirrhosis and otherwise transplantable disease, LT is uniquely attractive because it treats both the tumor and the carcinogenic liver in which multifocal recurrence and hepatic decompensation are rooted. No other local therapy offers that dual oncologic and physiologic reset[1−4] .  \nThe original success of LT for HCC was not simply technical; it was ethical. Before the mid-1990s, transplantation for HCC produced heterogeneous and often disappointing outcomes, making the use of scarce grafts difficult to justify. The Milan study changed that landscape by showing that patients with a single lesion up to 5 cm or up to three lesions each up to 3 cm, without macrovascular invasion or extrahepatic spread, could achieve recurrence-free survival similar to accepted nonmalignant indications[5] . Milan therefore did more than define a threshold—it established that HCC could be a legitimate transplant indication  \n\\# Correspondence: Piyush Gupta. E-mail: [piyushesama@gmail.com](piyushesama@gmail.com. Address: Department)[. Address: Department](piyushesama@gmail.com. Address: Department)  \n[of Transplant Surgery](of Transplant Surgery), [MedStar Georgetown Hospital](MedStar Georgetown Hospital), [Washington DC 20007](Washington DC 20007), USA.  \nReceived 20 April 2026; Revised 21 May 2026; Accepted 1 July 2026; Available Online 12 August 2026  \nDOI: 10.54457/DR.202603001  \n© The Author(s) 2026. This is an open access article under the CC BY ","cbCaipHGVpLe9haL","https://ap.wps.com/l/cbCaipHGVpLe9haL","pdf",6606914,11,"English","# Introduction\n# Milan criteria and their ethical foundation\n# From morphometric eligibility to biologic transplantability\n# Current guidance and biomarker-based prognostication\n# Contemporary pivots in patient selection\n## Downstaging and the test of time\n## LDLT versus DDLT\n## PVTT and HVTT after downstaging\n## Molecular diagnostics, AI, and benefit-based allocation","[{\"question\":\"Why is liver transplantation considered uniquely curative for HCC in selected patients with cirrhosis?\",\"answer\":\"It simultaneously treats the tumor and resets the carcinogenic cirrhotic field, reducing both macroscopic disease and the underlying drivers of multifocal recurrence and liver failure.\"},{\"question\":\"How have selection criteria for LT in HCC evolved beyond Milan criteria?\",\"answer\":\"Modern selection increasingly integrates biomarkers (e.g., AFP levels and kinetics, DCP/PIVKA-II, AFP-L3), metabolic imaging (e.g., FDG-PET), inflammatory indices, and response to locoregional therapy, along with emerging radiomic and liquid-biopsy indicators.\"},{\"question\":\"What role does downstaging play in contemporary transplant selection?\",\"answer\":\"Downstaging has shifted from being only a way to improve list access into a structured biologic stress test, helping distinguish tumors that stabilize biologically from those that re-progress rapidly despite technical response.\"}]","Current Status and Evolving Selection Criteria for Liver Transplant in Treatment of HCC - Review | PDF",1791226085,28]