Perioperative Immunotherapy Is Redefining Curative-Intent HCC Treatment: JHEP Reports | September 2026

Introduction:

Resection and liver transplantation remain the main curative-intent treatments for hepatocellular carcinoma (HCC), but recurrence after surgery is common and many patients present outside conventional surgical or transplant criteria. The success of immune checkpoint inhibitors (ICIs) in advanced HCC is now moving systemic therapy earlier into the neoadjuvant, perioperative, conversion, and pre-transplant settings.

Why is this topic important?

Recurrence after HCC resection may exceed 50–70% at 5 years.

Neoadjuvant ICI may generate stronger antitumour immunity while the tumour remains in situ.

Modern systemic therapy can potentially convert selected unresectable HCC to resectable disease.

Pre-transplant ICI may improve downstaging but introduces a risk of allograft rejection.

Purely adjuvant ICI after curative treatment has so far shown limited benefit.

Major Clinical Messages:

Neoadjuvant ICI is feasible before HCC resection, although toxicity varies considerably between regimens.

CARES-009 provided the first randomized evidence supporting perioperative therapy: camrelizumab + rivoceranib improved event-free survival versus surgery alone (42.1 vs 19.4 months; HR 0.59).

Major pathological response may be more informative than imaging response; ≥90% tumour regression is emerging as a potential threshold associated with better recurrence-free survival.

ICI + TKI ± locoregional therapy can achieve meaningful conversion to resection in selected patients with initially unresectable HCC.

Complete radiological response does not necessarily mean complete tumour eradication; viable HCC may remain despite apparently complete imaging response.

Purely adjuvant immunotherapy has been disappointing: IMbrave050 and KEYNOTE-937 did not establish a sustained recurrence-free survival benefit.

Pre-transplant ICI may facilitate bridging or downstaging, but reported acute rejection rates remain approximately 15–40% across heterogeneous studies.

A longer ICI-to-transplant washout interval appears safer, with several studies suggesting lower rejection risk when the interval approaches or exceeds 90 days.

Much of the current perioperative evidence comes from Asian, predominantly HBV-related populations, and broader validation is required.

Future Direction:

Perioperative HCC treatment will likely become biomarker- and response-driven, integrating pathological response, ctDNA, AFP dynamics, and tumour biology to guide treatment escalation or de-escalation.

Clinical Impact:

Resectability should no longer be viewed as fixed—patients with borderline or unresectable HCC who achieve a major response to modern systemic therapy should be reassessed for potentially curative resection or transplantation.

Bottom Line:

Perioperative immunotherapy is moving HCC toward response-adapted multimodal treatment. CARES-009 supports perioperative ICI, while conversion therapy may expand curative options. Adjuvant ICI remains unproven, and pre-transplant ICI requires caution because of rejection risk.