# Hepatocellular carcinoma

Source: https://nuclide.cc/indications/hcc/  
Nuclide record `hcc` (Indication). Data CC BY-NC 4.0, attribute "Data from Nuclide (nuclide.cc)"; commercial use needs a licence.

## TL;DR

Liver cancer almost always grows in a liver already damaged by hepatitis, alcohol or fatty liver disease. It is one of the most preventable cancers, and since 2020 immunotherapy combinations have roughly doubled how long people with advanced disease live.

## Summary

Hepatocellular carcinoma is the dominant primary liver cancer (~75-85%) and one of the most preventable: HBV vaccination and HCV cure have cut incidence wherever they were deployed. Its defining feature is that it arises in a diseased organ: chronic hepatitis B, hepatitis C, alcohol-related and metabolic (MASLD) cirrhosis account for most cases, so the liver's remaining function (Child-Pugh, ALBI) matters as much as tumour stage. The BCLC system integrates both and maps each stage to a treatment: ablation, resection or transplantation for early disease; TACE or radioembolisation for intermediate disease; systemic therapy for advanced disease. Surveillance of at-risk patients with six-monthly ultrasound is recommended but poorly adopted, and most patients still present beyond curative stages, which is why it remains the third leading cause of cancer death worldwide.

Systemic therapy changed completely between 2018 and 2026. Sorafenib (SHARP, 2007) was the only option for a decade. Lenvatinib matched it (REFLECT), then IMbrave150 made atezolizumab plus bevacizumab the first regimen to beat sorafenib on survival (OS 19.2 vs 13.4 months). HIMALAYA's STRIDE regimen (single-dose tremelimumab plus durvalumab) followed with a doubling of five-year survival (19.6% vs 9.4%), and CheckMate 9DW's nivolumab plus ipilimumab reached a median OS of 23.7 months (approved 2025). Camrelizumab plus rivoceranib (CARES-310, OS 23.8 vs 15.2 months) is approved in China but has received three FDA complete response letters for manufacturing reasons, most recently in July 2026. Second-line options after sorafenib (regorafenib, cabozantinib, ramucirumab for AFP ≥400) lack data after immunotherapy, the setting most patients now reach.

The frontier is combining local and systemic therapy. Three phase 3 trials (EMERALD-1, LEAP-012, EMERALD-3) show that adding immunotherapy and anti-VEGF drugs to TACE prolongs progression-free survival by about 30%, but LEAP-012's final overall-survival hazard ratio of 0.98 shows PFS is a weak surrogate here, and adjuvant atezolizumab-bevacizumab (IMbrave050) lost its early benefit with follow-up. Open questions include the right therapy after first-line immunotherapy, the role of immunotherapy before transplantation, GPC3-directed cell therapy, and above all prevention: HBV vaccination and HCV cure could avert most cases, while MASLD-driven HCC in non-cirrhotic livers is rising and escapes surveillance.

## Fields

- Kind: Indication
- Last checked: 2026-09-04
- Also known as: Liver Cancer
- Tags: gi; spike
- Group: gastrointestinal
- Burden: Roughly 900,000 liver cancer cases a year worldwide (GLOBOCAN), ~80% in Asia and Africa, and largely preventable: HBV vaccination and HCV cure have cut incidence in Taiwan, Japan and Egypt. Deaths are ~800,000 a year, and in the United States the death rate has risen faster than for any other cancer over the past two decades, driven by hepatitis C and fatty liver disease.
- Subtypes: Viral (HBV, HCV) HCC; Alcohol-related HCC; MASLD/MASH-related HCC (often non-cirrhotic); Fibrolamellar carcinoma (young adults, DNAJB1-PRKACA fusion); Combined hepatocellular-cholangiocarcinoma; BCLC stages 0/A, B, C, D
- Biomarkers: AFP; GPC3 (trials); Child-Pugh / ALBI liver function; AFP (prognosis; ≥400 ng/mL for ramucirumab); BCLC stage and performance status; Portal vein tumour thrombus; HBV/HCV status; AFP-L3 and DCP (GALAD score)

## Standard of care

- Early: Resection, ablation, transplant.
- Intermediate: TACE/TARE ± systemic therapy. ([Radioligand therapy (beta emitters)](https://nuclide.cc/technologies/radioligand-therapy/))
- Advanced: Atezolizumab-bevacizumab, durvalumab-tremelimumab, or nivolumab-ipilimumab. ([Durvalumab](https://nuclide.cc/drugs/durvalumab/))
- Prevention: Universal HBV vaccination; antiviral suppression of HBV; direct-acting antiviral cure of HCV; alcohol and metabolic risk reduction.
- Surveillance: Six-monthly ultrasound ± AFP in cirrhosis and high-risk HBV carriers; abbreviated MRI where ultrasound is inadequate.
- Very early / early (BCLC 0-A): Ablation (RFA/microwave) for ≤3 cm; resection for preserved liver function; transplantation within Milan or downstaged criteria; radiation segmentectomy as an alternative. ([Radioembolisation (TARE / SIRT, yttrium-90)](https://nuclide.cc/technologies/radioembolisation-tare/))
- Intermediate (BCLC B): TACE (conventional or DEB-TACE) or TARE; systemic therapy for high tumour burden or TACE-refractory disease; TACE + durvalumab-bevacizumab or STRIDE + lenvatinib prolong PFS (OS unproven). ([Radioembolisation (TARE / SIRT, yttrium-90)](https://nuclide.cc/technologies/radioembolisation-tare/))
- Advanced (BCLC C), first line: Atezolizumab + bevacizumab (IMbrave150), STRIDE tremelimumab + durvalumab (HIMALAYA), or nivolumab + ipilimumab (CheckMate 9DW); lenvatinib or sorafenib if immunotherapy is contraindicated (transplant, active autoimmune disease). ([Durvalumab](https://nuclide.cc/drugs/durvalumab/), [Sorafenib](https://nuclide.cc/drugs/sorafenib/))
- Advanced, second line and beyond: After immunotherapy: lenvatinib, sorafenib, cabozantinib or regorafenib by extrapolation (no dedicated phase 3); ramucirumab if AFP ≥400 ng/mL; clinical trials. ([Cabozantinib](https://nuclide.cc/drugs/cabozantinib/))
- Adjuvant after resection/ablation: No approved adjuvant therapy; IMbrave050 benefit not sustained. Surveillance imaging every 3-6 months.
- Portal vein tumour thrombosis: Systemic immunotherapy; Y-90 radioembolisation where TACE is contraindicated; radiotherapy to the thrombus in selected patients. ([Radioembolisation (TARE / SIRT, yttrium-90)](https://nuclide.cc/technologies/radioembolisation-tare/))

## State of the art

- IO doublets first line.
- GPC3 CAR-T and bispecifics emerging.
- Three first-line immunotherapy regimens with overall-survival benefit over sorafenib; median OS approaching two years and five-year survival of one in five with STRIDE.
- Choice of regimen is driven by bleeding risk (varices), autoimmune disease and transplant candidacy rather than a predictive biomarker.
- Radioembolisation and radiation segmentectomy offer curative-intent options for small tumours and for portal vein thrombosis.
- TACE plus systemic therapy prolongs PFS in intermediate-stage disease in three phase 3 trials, but overall survival is unproven (LEAP-012 OS HR 0.98).
- Prevention works: HBV vaccination and HCV antivirals have cut incidence in Taiwan, Japan and Egypt; MASLD is the rising cause.
- Living-donor transplantation and downstaging widen the pool of curable patients, led by Asian high-volume centres.

## Open problems

- Liver function limits therapy.
- Surveillance uptake in cirrhosis is poor.
- No predictive biomarker chooses among the three first-line immunotherapy regimens; PD-L1, TMB and viral aetiology are weak.
- Second-line therapy after immunotherapy failure is extrapolated from the sorafenib era; no dedicated phase 3 has read out.
- TACE combinations prolong PFS but not (yet) OS; sequencing local and systemic therapy is unresolved.
- Adjuvant therapy after curative resection remains unproven; recurrence is ~70% at five years.
- Surveillance uptake is below 25% and ultrasound misses early tumours in obese, steatotic livers; MASLD-HCC often arises without cirrhosis.
- Immunotherapy in transplant candidates risks rejection; safe washout intervals are undefined.
- Child-Pugh B patients are excluded from almost every trial yet make up a large share of real-world patients.
- Global inequity: most cases occur in Asia and Africa, where HBV vaccination, HCV treatment and systemic therapy access are uneven.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Hepatocellular_carcinoma
- Wikipedia: https://en.wikipedia.org/wiki/Hepatocellular_carcinoma

## Connected records

- technologies: [FAPI PET](https://nuclide.cc/technologies/fapi-pet/), [Quantitative imaging biomarkers (RECIST, PERCIST, SUV, ADC)](https://nuclide.cc/technologies/quantitative-imaging-biomarkers/), [Radioembolisation (TARE / SIRT, yttrium-90)](https://nuclide.cc/technologies/radioembolisation-tare/), [Radioligand therapy (beta emitters)](https://nuclide.cc/technologies/radioligand-therapy/)
- targets: [FAP](https://nuclide.cc/targets/fap/), [Glypican-3](https://nuclide.cc/targets/gpc3/)
- companies: [AstraZeneca](https://nuclide.cc/companies/astrazeneca/), [Bayer](https://nuclide.cc/companies/bayer/), [Boston Scientific](https://nuclide.cc/companies/boston-scientific/), [Bristol Myers Squibb](https://nuclide.cc/companies/bms/), [Eli Lilly (incl. Loxo)](https://nuclide.cc/companies/eli-lilly/), [Merck & Co. (MSD)](https://nuclide.cc/companies/merck/), [Quirem Medical](https://nuclide.cc/companies/quirem-medical/), [Sirtex Medical](https://nuclide.cc/companies/sirtex/)
- institutions: [Chinese PLA General Hospital](https://nuclide.cc/institutions/pla-general-hospital/), [Mayo Clinic](https://nuclide.cc/institutions/mayo-clinic/), [Memorial Sloan Kettering Cancer Center](https://nuclide.cc/institutions/mskcc/), [QST Hospital (National Institutes for Quantum Science and Technology)](https://nuclide.cc/institutions/qst-hospital/), [University Hospital Düsseldorf / CIO Düsseldorf](https://nuclide.cc/institutions/uk-duesseldorf/)
- terms: [Dosimetry](https://nuclide.cc/terms/dosimetry/), [TARE / SIRT (radioembolisation with yttrium-90)](https://nuclide.cc/terms/tare/)
- drugs: [Cabozantinib](https://nuclide.cc/drugs/cabozantinib/), [Donafenib](https://nuclide.cc/drugs/donafenib/), [Durvalumab](https://nuclide.cc/drugs/durvalumab/), [Holmium-166 microspheres](https://nuclide.cc/drugs/ho-166-microspheres/), [Pembrolizumab](https://nuclide.cc/drugs/pembrolizumab/), [Sorafenib](https://nuclide.cc/drugs/sorafenib/), [Yttrium-90 glass microspheres](https://nuclide.cc/drugs/y-90-glass-microspheres/), [Yttrium-90 resin microspheres](https://nuclide.cc/drugs/y-90-resin-microspheres/)
- trials: [A US Study to Evaluate Transarterial Radioembolization (TARE) in Combination With Durvalumab and Bevacizumab Therapy in People With Unresectable Hepat](https://nuclide.cc/trials/nct06040099/), [SARAH and SIRveNIB](https://nuclide.cc/trials/sarah-sirvenib/), [Study of the Theranostic Pair RYZ811 (Diagnostic) and RYZ801 (Therapeutic) to Identify and Treat Subjects With GPC3+ (Glypican-3) Unresectable HCC](https://nuclide.cc/trials/nct06726161/), [TheraSphere With Durvalumab and Tremelimumab for HCC](https://nuclide.cc/trials/nct05063565/)
- indications: [Intermediate hepatocellular carcinoma (BCLC B)](https://nuclide.cc/indications/hcc-intermediate/)
- opportunities: [GPC3 imaging of the indeterminate liver nodule, led from China](https://nuclide.cc/opportunities/opp-gpc3-hcc-china/)
- fronts: [Dosimetry](https://nuclide.cc/fronts/f-dosimetry/), [Radioembolisation](https://nuclide.cc/fronts/f-radioembolisation/)
- isotopes: [Holmium-166](https://nuclide.cc/isotopes/ho-166/), [Rhenium-188](https://nuclide.cc/isotopes/re-188/), [Yttrium-90](https://nuclide.cc/isotopes/y-90/)
- pairings: [Radioembolisation (TARE) compared with sorafenib in hepatocellular carcinoma](https://nuclide.cc/pairings/tare-vs-sorafenib-caution/), [Radioembolisation (TARE) with durvalumab in hepatocellular carcinoma](https://nuclide.cc/pairings/tare-plus-durvalumab-hcc/)

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