Hepatocellular carcinoma
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.
Overview
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.
State of the art
- IO doublets first line.
- GPC3 CAR-T and bispecifics emerging.
- 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.
- 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.
Show survival figures (2)
Averages across everyone diagnosed, often years ago. Your stage, subtype, age, fitness and the treatment you receive matter more than the average, and the numbers are improving quickly.
- 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.
- 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).
Anatomy and lymph node drainage
- Right lobe (segments V-VIII)
- Left lobe (segments II-IV)
- Portal vein (macrovascular invasion)
- Capsule and diaphragm surface
- Nodes: hepatic hilar
- Nodes: coeliac
- Nodes: paracaval
Hepatocellular carcinoma grows in a cirrhotic liver and spreads first inside it and into the portal vein, so staging depends on liver function and vascular invasion as much as on size.
- Right lobe (segments V-VIII)Viral (HBV, HCV) HCC · Alcohol-related HCC · MASLD/MASH-related HCC (often non-cirrhotic) · Fibrolamellar carcinoma (young adults, DNAJB1-PRKACA fusion)
- Left lobe (segments II-IV)
- Portal vein (macrovascular invasion)
- Capsule and diaphragm surface
- hepatic hilar
- coeliac
- paracaval
Same organ: Intermediate hepatocellular carcinoma (BCLC B)
Preclinical models
6 cell lines, 1 mouse models and 6 repositories are listed for this cancer.
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.
Show survival figures (1)
Averages across everyone diagnosed, often years ago. Your stage, subtype, age, fitness and the treatment you receive matter more than the average, and the numbers are improving quickly.
- 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.
Advanced diseaseShow Hide where advanced disease can reach, and what treats itThe sites decide which scans are done at staging and follow-up, and every site listed has a treatment approach.
Most people reading this do not have advanced disease. The map describes what can happen over the whole course of the illness, across autopsy and registry series; today's staging scans find spread earlier, and each site has treatments, from focused radiotherapy for a few spots to drugs that reach the brain.
What helpsAtezolizumab-bevacizumab, durvalumab-tremelimumab or nivolumab-ipilimumab; radioembolisation and TACE for liver-confined disease; transplant after downstaging in selected patients.
Nothing recorded yet.
Nothing recorded yet.
Also on Nuclide: Indications.
- Elsewhere in the liver and portal veinmost common
Intrahepatic spread and portal vein invasion dominate and drive staging.
- Lungscommon
- Regional lymph nodescommon
- Bonecommon
- Adrenal glandsless common
- Peritoneumless common
TACE/TARE ± systemic therapy.
Atezolizumab-bevacizumab, durvalumab-tremelimumab, or nivolumab-ipilimumab.
Universal HBV vaccination; antiviral suppression of HBV; direct-acting antiviral cure of HCV; alcohol and metabolic risk reduction.
Six-monthly ultrasound ± AFP in cirrhosis and high-risk HBV carriers; abbreviated MRI where ultrasound is inadequate.
Ablation (RFA/microwave) for ≤3 cm; resection for preserved liver function; transplantation within Milan or downstaged criteria; radiation segmentectomy as an alternative.
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).
Atezolizumab + bevacizumab (IMbrave150), STRIDE tremelimumab + durvalumab (HIMALAYA), or nivolumab + ipilimumab (CheckMate 9DW); lenvatinib or sorafenib if immunotherapy is contraindicated (transplant, active autoimmune disease).
After immunotherapy: lenvatinib, sorafenib, cabozantinib or regorafenib by extrapolation (no dedicated phase 3); ramucirumab if AFP ≥400 ng/mL; clinical trials.
No approved adjuvant therapy; IMbrave050 benefit not sustained. Surveillance imaging every 3-6 months.
Systemic immunotherapy; Y-90 radioembolisation where TACE is contraindicated; radiotherapy to the thrombus in selected patients.
Subtypes & biomarkers
top- 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
- 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)
How often this target appears
| Target / alteration | Prevalence | Measure | Source |
|---|---|---|---|
| Glypican-3 | 70-80% | IHC, any expression | Wikipedia |
How common each drug target or alteration is in this cancer. Population-level and approximate; see the target page for detail.
- 1941Hepatocellular carcinoma linked to cirrhosis in large autopsy series
Establishes the disease-in-a-diseased-organ paradigm.
- 1964Hepatitis B surface antigen discovered (Blumberg)
Nobel Prize 1976; leads to the vaccine.
- 1984Taiwan begins universal HBV vaccination
Childhood HCC incidence later falls ~70%.
- 1996Milan criteria for liver transplantation
Mazzaferro: ~70% five-year survival for small tumours.
- 1999BCLC staging system published
- 2002TACE proven to prolong survival (Llovet, Lo)
- 2007Sorafenib: first systemic therapy
- 2007SHARP: sorafenib, the first systemic therapy
- 2014Direct-acting antivirals cure hepatitis C
HCC risk falls ~70% after cure.
- 2017RESORCE: regorafenib, first second-line benefit; SARAH/SIRveNIB negative for Y-90 vs sorafenib
- 2018REFLECT: lenvatinib non-inferior first line; CELESTIAL: cabozantinib second line
- 2020IMbrave150: atezolizumab-bevacizumab
- 2020IMbrave150: atezolizumab + bevacizumab beats sorafenib
First regimen to improve OS over sorafenib; new standard.
- 2022HIMALAYA: STRIDE approved; BCLC update adds systemic therapy for some BCLC-B
- 2024EMERALD-1 and LEAP-012: TACE + systemic therapy improves PFS; HIMALAYA 5-year OS 19.6%
- 2025CheckMate 9DW approval (nivolumab + ipilimumab); second FDA CRL for camrelizumab-rivoceranib
- 2026EMERALD-3 positive for PFS; LEAP-012 final OS HR 0.98; IMbrave050 update negative; third camrelizumab-rivoceranib CRL (23 July)
Dated changes read from the records linked to this indication: approvals, regulatory steps, reported trials, guideline versions and milestones. Newest first; no date is inferred.
All 30 changes by month →- 2026-09-04This recordHepatocellular carcinomaFacts on this page last checked
When this page itself was last checked or edited.
- 2026MilestoneHepatocellular carcinomaEMERALD-3 positive for PFS; LEAP-012 final OS HR 0.98; IMbrave050 update negative; third camrelizumab-rivoceranib CRL (23 July)
A milestone in how this cancer is treated.
- 2025ApprovalYttrium-90 resin microspheresYttrium-90 resin microspheres approved in US
Local tumour control of unresectable hepatocellular carcinoma (no macrovascular invasion, Child-Pugh A, well-compensated liver function, good performance status)
- 2025MilestoneHepatocellular carcinomaCheckMate 9DW approval (nivolumab + ipilimumab); second FDA CRL for camrelizumab-rivoceranib
A milestone in how this cancer is treated.
- 2024MilestoneHepatocellular carcinomaEMERALD-1 and LEAP-012: TACE + systemic therapy improves PFS; HIMALAYA 5-year OS 19.6%
A milestone in how this cancer is treated.
- 2023GuidelineHepatocellular carcinomaGuideline AASLD 2023 / EASL 2025: Prevention
Universal HBV vaccination; antiviral suppression of HBV; direct-acting antiviral cure of HCV; alcohol and metabolic risk reduction. (NCCN Hepatobiliary Cancers)
What is in development for Hepatocellular carcinoma, drawn from the whole corpus: 8 items. Drugs are grouped by the most advanced trial phase they have reached anywhere; approved treatments sit under standard of care. Technologies are the methods being tested for this cancer, trials are the studies recorded here, and ideas are proposals not yet in a trial.
Technologies being tested · 1
Trials under way · 3
- A US Study to Evaluate Transarterial Radioembolization (TARE) in Combination With Durvalumab and Bevacizumab Therapy in People With Unresectable Hepat · phase 2 · AstraZeneca
- Study of the Theranostic Pair RYZ811 (Diagnostic) and RYZ801 (Therapeutic) to Identify and Treat Subjects With GPC3+ (Glypican-3) Unresectable HCC · phase 1/2 · RayzeBio, Inc.
- TheraSphere With Durvalumab and Tremelimumab for HCC · phase 2 · Boston Scientific Corporation
Trials reported · 1
- SARAH and SIRveNIB · phase 3 · 2017 · negative
Targets under investigation · 1
Combinations being explored · 2
Open problems and what is being done
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.
Trials
topTrials recruiting now
Country and place are remembered in this browser only. A postcode is sent to OpenStreetMap's Nominatim service to find coordinates when you press the button; nothing else leaves your device.
Landmark trials
Direct links plus the targets, companies, and technologies of this cancer's products.
isotopes
3fronts
2technologies
4targets
2drugs
8companies
8institutions
5terms
2trials
4pairings
2opportunities
1Latest papers
topQuery for this indication: (TITLE:"Hepatocellular carcinoma" OR ABSTRACT:"Hepatocellular carcinoma" OR TITLE:"Liver Cancer" OR ABSTRACT:"Liver Cancer") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Hepatocellular carcinoma, not a curated reading list.
Similar pages
not linked directly; found by shared links- IndicationThyroid cancer
Shares Donafenib, Eli Lilly (incl. Loxo), Sorafenib, Memorial Sloan Kettering Cancer Center.
- IndicationDiffuse large B-cell lymphoma
Shares Chinese PLA General Hospital, Mayo Clinic, Merck & Co. (MSD), Bristol Myers Squibb.
- IndicationRenal cell carcinoma
Shares Sorafenib, Merck & Co. (MSD), Bristol Myers Squibb, Memorial Sloan Kettering Cancer Center.
- AgentTechnetium Tc-99m albumin aggregated (MAA)
Shares Yttrium-90 glass microspheres, Yttrium-90 resin microspheres, Radioembolisation (TARE / SIRT, yttrium-90), Yttrium-90.
- AgentLead-212 PSV359
Shares Merck & Co. (MSD), Pembrolizumab, FAP, FAPI PET.
- IndicationSmall-cell lung cancer
Shares Durvalumab, Merck & Co. (MSD), Bristol Myers Squibb, Memorial Sloan Kettering Cancer Center.
- IndicationNeuroendocrine tumours
Shares TARE / SIRT (radioembolisation with yttrium-90), Bristol Myers Squibb, University Hospital Düsseldorf / CIO Düsseldorf, Memorial Sloan Kettering Cancer Center.
- CompanyBWXT Medical
Shares Boston Scientific, Radioembolisation (TARE / SIRT, yttrium-90), Yttrium-90.