Liver Transplant for HCC: UCSF Criteria and Downstaging

Liver transplant can cure hepatocellular carcinoma (HCC), the most common primary liver cancer, when the tumour is confined to the liver and falls within accepted size limits. Dr. Ashish George, Principal Consultant & Unit Head Liver Transplant, Fortis Hospital, Shalimar Bagh, New Delhi, India, uses the UCSF criteria to decide which patients benefit, and downstaging treatments to bring larger tumours within them.

This article covers that selection logic: why HCC is the cancer most often treated by transplant, what the UCSF and Milan criteria measure, how downstaging and bridging work, which other cancers confined to the liver can be transplanted, and why cancer outside the liver closes the door. The wider indications for transplant are set out in the complete guide to liver transplant.

Why HCC is the cancer most often treated by liver transplant

HCC is the cancer for which liver transplant is most often performed, and, as Dr. George noted, it most commonly arises in patients who already have chronic liver disease, that is, cirrhosis. The tumour and the failing liver are two expressions of the same disease.

That pairing shapes the treatment choice. In a cirrhotic liver, removing the tumour by resection leaves behind the diseased liver in which it arose, and that liver may have little functional reserve and remains at risk of new tumours. A transplant removes both the tumour and the cirrhotic liver in a single operation. This is the reason transplant, where the tumour is within criteria, can offer a cure that a partial operation cannot.

The UCSF criteria for liver transplant in HCC

The selection criteria Dr. George follows are those developed at the University of California, San Francisco (UCSF). A patient with HCC is within the UCSF criteria if imaging shows either:

• a single tumour no larger than 6.5 cm, or
• up to three tumours, none larger than 4.5 cm, with a total tumour diameter no greater than 8 cm.

In both cases the tumour must be confined to the liver, with no major blood vessel invasion and no spread outside the organ. In the original UCSF series, patients transplanted within these limits had five-year survival of about 75 percent, comparable to patients transplanted within the older and stricter Milan criteria.

UCSF vs Milan criteria for HCC

The Milan criteria, published in 1996, were the first widely adopted standard: a single tumour no larger than 5 cm, or two or three tumours each no larger than 3 cm, without vascular invasion or spread outside the liver. The UCSF criteria extended these limits modestly without a loss of survival, which allowed more patients with HCC to be offered transplant. Dr. George described UCSF as the criteria usually followed today.

Criteria that continue to expand

The limits are not fixed. With progress in immunotherapy and other fields of medicine, Dr. George noted, the criteria are expanding, and tumours even larger than the UCSF limits are now being considered for transplant in selected patients.

Downstaging HCC to qualify for liver transplant

Downstaging is treatment that shrinks an HCC confined to the liver until it falls within the transplant criteria. Dr. George described it as the route back to transplant for patients whose tumour is outside the criteria but still confined to the liver.

The process has three steps:

1. Treat the tumour. The patient receives treatment that reduces the size and the activity of the tumour.
2. Wait and re-image. After a period of time, the team reassesses the patient on imaging.
3. Offer transplant if the tumour now qualifies. If there is still no disease outside the liver and the tumour has come within the transplant criteria, the patient can be offered a transplant.

The treatments used for downstaging are locoregional therapies delivered directly to the tumour: transarterial chemoembolisation (TACE), which delivers chemotherapy into the artery feeding the tumour and then blocks it; transarterial radioembolisation, which delivers radioactive microspheres by the same route; and thermal ablation, which destroys the tumour with heat. Transplant programmes generally require a period of observation after successful downstaging, to confirm that the response is durable before the transplant goes ahead.

Dr. George's point on the potential was clear: advanced HCC that remains confined to the liver can be successfully downstaged in a significant number of patients, and those patients can then be offered a liver transplant. For a referring doctor, the practical message is that a large tumour confined to the liver is a reason to seek a transplant opinion, not a reason to rule transplant out.

Bridging therapy while the patient waits

Bridging therapy is related but different. It is given to a patient whose tumour is already within criteria, to stop it growing beyond the limits while the patient waits for a liver. The same locoregional treatments are used. Where a suitable living donor is available, the transplant can be scheduled rather than awaiting a deceased-donor organ, which shortens the period in which the tumour can progress. How a living donor is assessed is explained in who can donate a liver: eligibility, safety and regrowth.

Liver transplant for other cancers: cholangiocarcinoma and metastases

HCC is not the only cancer treated by transplant. Dr. George listed several other malignancies that may be offered liver transplantation when they are confined to the liver:

• Cholangiocarcinoma, cancer of the bile ducts, in its hilar (at the point where the main bile ducts leave the liver) or intrahepatic (within the liver) form.
• Colorectal cancer that has spread only to the liver, where the liver metastases cannot be removed by resection and no disease exists elsewhere.
• Neuroendocrine tumours, sometimes called carcinoids, that have spread to the liver.
• Haemangioendothelioma, a rare tumour of the blood vessel lining that often affects the liver at several sites at once.

These indications are far less common than HCC, and they are offered to carefully selected patients under strict protocols at specialised centres. For hilar cholangiocarcinoma, for example, transplant is generally preceded by chemotherapy and radiotherapy. For colorectal liver metastases, it is reserved for patients whose primary tumour has been removed and whose cancer has remained confined to the liver.

For most patients with cholangiocarcinoma the first curative option is resection. Dr. George sets out how surgeons classify perihilar tumours and plan that operation in his 2026 masterclass, in cholangiocarcinoma surgery: Bismuth-Corlette and resection.

Why cancer outside the liver rules transplant out

Cancer that has spread beyond the liver is one of Dr. George's three absolute contraindications to transplant. The reasoning is direct: a transplant replaces the liver, but it cannot remove disease elsewhere in the body. Lifelong immunosuppression after transplant also weakens the body's own defences against cancer cells that remain, so a patient with spread outside the liver would carry the full risk of the operation without the prospect of a cure.

This is why staging is the first question in every transplant assessment for cancer. Before a patient with HCC is listed, the team confirms on imaging that the tumour is confined to the liver and that it meets the criteria. The same check is repeated after downstaging, because a tumour that shrinks in the liver while spreading elsewhere is no longer a transplant candidate.

Where transplant sits among the curative options for HCC

Transplant is one of three curative treatments for HCC, alongside resection and ablation. The choice depends on the number and size of the tumours, on how well the rest of the liver works, and on whether the patient has cirrhosis. A patient with a small tumour and a well-preserved liver may be best served by resection or ablation. A patient with cirrhosis and a tumour within criteria is usually best served by transplant, because it treats the cancer and the liver disease at once.

Dr. George sets out this decision in detail in his separate 2026 masterclass on primary liver cancers, in HCC treatment: resection, ablation or liver transplant, which also describes the downstaging protocol he follows. The diagnosis of HCC, including screening, tumour markers and imaging, is covered in the complete guide to the management of primary liver cancers.

When to refer a patient with HCC for liver transplant

The criteria translate into a short checklist for any doctor managing a patient with cirrhosis and a liver tumour:

1. Count and measure the tumours on cross-sectional imaging (CT or MRI), and compare them with the UCSF limits.
2. Look for disease outside the liver. Spread beyond the liver is an absolute contraindication.
3. Assess liver function, including the MELD-sodium score, which also governs the timing of transplant for the underlying cirrhosis.
4. Do not rule out a larger tumour that is confined to the liver. Refer for a downstaging opinion.

Transplant results for HCC depend on selection as much as on surgery. As Dr. George put it in his summary, offering the treatment to the right patient at the right time is the key to excellent results. Survival after transplant overall, and the long-term effects of immunosuppression, are covered in liver transplant survival rates and life after surgery. Indicative figures for liver transplant costs, hepatectomy for liver cancer and TACE are published separately.