Future surgical strategies for hepatocellular carcinoma in Italy: a strategic framework and scenario-based projection of liver transplantation and hepatic resection from 2027 onwards

Abstract Hepatocellular carcinoma (HCC) in Italy is undergoing a dual transition: a decline in viral (HCV/HBV) etiology following direct-acting antivirals (DAAs) and a rise in metabolic (MASLD/MASH)-related disease. Concurrently, the deceased-donor pool is being reshaped by donation after circulatory death (DCD) and machine perfusion, and neoadjuvant immune checkpoint inhibition is emerging as a possible route to transplant eligibility. This work explores, through scenario-based quantitative projections, how these forces may reshape the balance between hepatic resection and liver transplantation (LT) for HCC in Italy through 2035. This is a strategic framework supported by quantitative scenario projections, not a fully executed patient-level modelling study. Aggregate published data and registry annual reports (Piano Nazionale Esiti [PNE]; Centro Nazionale Trapianti [CNT]; European Liver Transplant Registry [ELTR]; ITA.LI.CA) and peer-reviewed literature were used; direct patient-level access to PNE and CNT datasets was not obtained. A deterministic scenario framework (conservative, baseline, expanded) was applied over 2027–2035. DCD growth was modelled with a saturating (logistic) function with an explicit carrying capacity. An explicit allocation layer bounds the HCC share of grafts by historical Italian values and does not permit it to rise as competing non-HCC demand grows. Immunotherapy-driven downstaging was parameterized from published neoadjuvant response data and treated as a promising but still-evolving input. Each headline output is reported with a scenario-based plausible range. Under the baseline scenario, total liver graft availability is projected to increase by ≈16–17% by 2035 (scenario range +11% to +23%), driven principally by a logistic rise in DCD activity toward ≈450 liver transplants/year (expanded corner ≈600/year) and by improved marginal-graft utilization via machine perfusion. Projected HCC incidence is broadly stable-to-declining overall, with a rising MASLD/MASH -related fraction offsetting the viral-related decline. Because HCC has historically represented ~44–49% of Italian LT waitlistings, while non-HCC demand (alcohol-related disease, MASLD/MASH, acute-on-chronic liver failure [ACLF]) is rising, the HCC share of grafts is constrained to ~45–50% in the scenario framework rather than assumed to expand; this yields ≈1,020–1,135 LT for HCC/year even in the expanded scenario. Immunotherapy-driven conversion from unresectable to transplantable disease is modelled conservatively (15% conservative, ~18–24% baseline, 30% only as an optimistic sensitivity extreme). Net reallocation of highly selected early-stage cirrhotic patients from resection to transplantation is estimated at ≈11–15% of the reallocatable resection pool. Within the constraints of a finite, allocation-governed graft supply and rising competing demand, a modest, highly selective shift from resection toward transplantation in early-stage cirrhotic HCC is plausible but not automatic. Realizing it would require integrated national planning across transplant oncology, hepatobiliary surgery, donor-pool optimization, and centralization of complex care, together with prospective validation of immunotherapy-facilitated downstaging. Graphical abstract The visual abstract details a predicted system-level shift in hepatocellular carcinoma (HCC) surgical management between 2027 and 2035. Causal factors include the etiological substitution from declining HCV-related HCC (via DAA therapies) to rising MASLD/MASH-related HCC [Panel (1)], the method-driven expansion of the organ donor pool through DCD donation and machine perfusion [Panel (2)], and the therapy-driven expansion of patient candidacy via immunotherapy-driven downstaging to convert unresectable patients [Panel (3)]. These converging forces may produce a selective redistribution of curative-intent treatment pathways, characterized by increased LT volumes for HCC and a selective reallocation of some early-stage cirrhotic patients from HR to transplantation, while highlighting the potential need for greater centralization of complex care within high-volume centers [Panel (4)].