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HCC - Liver Transplant For Hepatocellular Carcinoma
Organ Transplant

HCC - Liver Transplant For Hepatocellular Carcinoma

About This Department

 
Organ Transplantation

A liver transplant removes the cancer and the cirrhosis that caused it in one operation. For carefully selected patients, three out of four are alive five years later.

Hepatocellular carcinoma grows, in most patients, in a liver already scarred by hepatitis or alcohol, and treating the tumor alone leaves a damaged liver that can grow new ones. Transplantation treats both. The results depend on selection, the size and number of tumors, the tumor marker alpha-fetoprotein, and the absence of spread into the major veins. For international patients in Turkey the new liver comes from a living donor, in most cases a relative, who gives part of their own liver after a full evaluation and approval by an ethics committee. Send us your scans, blood tests and treatment history, and a transplant hepatologist and surgeon will tell you whether a transplant is possible, what it would take and how long to plan.

75%
Four-year survival in the first Milan criteria series
77.5% vs 31.2%
Five-year survival, transplant against no transplant after downstaging
2 to 3 months
In Istanbul for the recipient
Free
Transplant team's review of your file
Free consultation

When is a transplant the answer?

Why a new liver treats two diseases

Most liver cancer arises in cirrhosis. The scarring comes from years of hepatitis B or C, alcohol or fatty liver disease. Removing the tumor or destroying it with heat or chemoembolization treats the visible cancer and leaves a liver in which new tumors keep forming and which may itself be failing.

A transplant removes the whole diseased organ, the visible tumors, any too small to see, and the cirrhosis. No other treatment addresses both. For a patient whose cancer is still confined to the liver and not too large, it offers the best chance of cure. The difficulty lies in choosing the patients whose cancer will not return in the new liver.

The Milan criteria

The study that set the rule

In 1996 a group in Milan reported 48 patients with cirrhosis and small tumors that could not be removed, selected by strict rules, a single tumor of 5 centimeters or less, or up to three tumors each of 3 centimeters or less. Four years after transplantation, 75 percent were alive and the cancer had returned in 8 percent. Among the patients whose removed livers confirmed that the tumors met the rules, survival reached 85 percent. Where the tumors turned out larger, it was 50 percent.

These limits, now called the Milan criteria, remain the reference worldwide. A patient within them can expect results close to those of a transplant for cirrhosis without cancer.

  1. Milan criteria. One tumor up to 5 cm, or up to three tumors each up to 3 cm, with no invasion of major vessels.
  2. UCSF criteria. One tumor up to 6.5 cm, or up to three tumors with the largest up to 4.5 cm and a combined diameter up to 8 cm.
  3. Up-to-seven. The size of the largest tumor in centimeters plus the number of tumors adds up to seven or less, with no microscopic vessel invasion.
  4. AFP model. A score combining tumor size, number and the alpha-fetoprotein level, used in France and increasingly elsewhere.
  • Tumor in the main veins.
  • Spread outside the liver, to the lungs, the bones or the lymph nodes around the liver and in the chest, found on the staging scans before listing.
  • Alpha-fetoprotein above 1,000 that stays high despite treatment.
  • Ongoing alcohol use, or severe heart or lung disease that makes a long operation unsafe.
Liver transplantation is an effective treatment for small, unresectable hepatocellular carcinomas in patients with cirrhosis.
Mazzaferro and colleagues, New England Journal of Medicine, 1996
Beyond the Milan criteria

In San Francisco, patients meeting the wider UCSF limits had 75.2 percent survival at five years, against 50 percent at one year for those beyond them. An international study of 1,556 patients found 73.3 percent five-year survival within Milan and 53.6 percent beyond it, and 71.2 percent for patients beyond Milan who met the up-to-seven rule without microscopic vessel invasion.

Numbers of tumors and centimeters describe only part of the cancer's behavior. The French AFP model showed that a high alpha-fetoprotein predicted recurrence better than size. Patients beyond Milan with a low score had a 14.4 percent recurrence risk at five years, and patients within Milan with an alpha-fetoprotein above 1,000 had 37.1 percent.

Downstaging

Some tumors shrink.

When the tumors are too large, treatment can sometimes shrink them first. The Italian XXL trial treated patients beyond Milan with chemoembolization, ablation, surgery or drugs for a median of six months. Those whose tumors came back within the limits and stayed there were randomized. Five years later 77.5 percent of the transplanted patients were alive, against 31.2 percent of those who continued other treatments. The trial was small, 45 patients, and closed early. Its result supports transplantation after successful downstaging.

After effective and sustained downstaging of eligible hepatocellular carcinomas beyond the Milan criteria, liver transplantation improved tumor event-free survival and overall survival compared with non-transplantation therapies.
XXL trial, Lancet Oncology, 2020

How are patients and donors selected?

Two people are evaluated.

Both must be safe.

The living donor

Who can donate

Turkey performs more living donor liver transplants than almost any country, and for international patients the donor is a living person. Relatives may donate. Anyone else needs the hospital ethics committee's approval. Buying or selling an organ is a crime in Turkey and in the patient's home country, and no legitimate program will consider it. The donor and recipient travel together with documents proving their relationship.

A donor must be a healthy adult between 18 and 55 in most programs, with a compatible blood group, a liver large enough to leave both donor and recipient with enough tissue, and no fatty liver or other disease. Evaluation takes one to two weeks. It covers blood tests, CT and MRI of the liver, heart tests, and interviews with a psychologist and an independent physician. Refusal remains possible at any point, and the team will say only that the donor is unsuitable.

Risks for the donor

Donors give the right or left part of the liver in an operation of six to eight hours. Both halves regrow. Within two to three months each is close to full size. Complications such as bile leaks or infection occur in a minority, and the risk of death is small and real, estimated at well under one percent in experienced centers. Every donor must hear that figure before agreeing, from a doctor who is not part of the recipient's team, with time to think and the freedom to withdraw without explaining why to anyone in the family.

Prediction of tumor recurrence is improved significantly by a model that incorporates AFP.
French liver transplant study, Gastroenterology, 2012
What the recipient's evaluation covers

Imaging comes first. A CT or MRI of the liver within the last month, a CT of the chest and a bone scan rule out spread, and alpha-fetoprotein and a full check of heart, lungs, kidneys and infections complete the picture. The tumor board of hepatologists, transplant surgeons, radiologists and oncologists decides whether the cancer meets the program's criteria, and whether treatment to control or shrink it is needed first.

More patients with hepatocellular carcinoma could be candidates for transplantation if the current dual approach to candidacy, based on the strict Milan criteria, were replaced with a more precise estimation of survival.
Up-to-seven study, Lancet Oncology, 2009

What does the operation involve, and what are the results?

The operation and the risks for the recipient

Donor and recipient operations run side by side. The recipient's liver comes out, and the donor graft is joined to the recipient's blood vessels and bile duct over eight to twelve hours of painstaking microsurgery on arteries only a few millimeters wide, which is where the experience of the team shows most. The recipient spends several days in intensive care and three to four weeks in hospital.

Early problems include bleeding, bile leaks, narrowing of the blood vessels and infection. Rejection is treated with a short course of stronger immunosuppression. Anti-rejection medicines are lifelong. They raise the risk of infections, kidney problems and skin cancers. The cancer itself can return, most frequently within the first two years, and the risk rises with tumor size, alpha-fetoprotein and vessel invasion found in the removed liver.

The current criteria for liver transplantation based on tumor size may be modestly expanded while still preserving excellent survival.
University of California San Francisco series, Hepatology, 2001

This table scrolls sideways on a narrow screen. Swipe or drag to see every column.

Survival after transplantation by selection rule
Group Study Survival
Within Milan criteria Milan 1996, 48 patients 75 percent at four years
Within UCSF criteria San Francisco 2001, 70 patients 75.2 percent at five years
Within Milan International study 2009, 1,556 patients 73.3 percent at five years
Beyond Milan, within up-to-seven, no vessel invasion International study 2009 71.2 percent at five years
Beyond Milan, downstaged, transplanted XXL trial 2020, 45 patients 77.5 percent at five years, against 31.2 without transplant
Evaluation, two to three weeks
Recipient and donor are assessed in parallel. The tumor board and ethics committee meet, the donor gives written consent twice, and the date is set.
Surgery and hospital, three to four weeks
The donor leaves hospital in about a week and the recipient in three to four, after intensive care and the first adjustments of the anti-rejection medicines.
Nearby follow-up, one to two months
Blood tests twice a week, then weekly, and imaging of the vessels and bile ducts. Donors fly home after four to six weeks in most cases, the recipient after two to three months, once medicines are stable and a hepatologist at home has agreed to take over.

One coordinator stays with you from the first message. The team works in seven languages. Interpreters cover the rest. An invitation letter naming the hospital, the surgeon, the recipient and the donor goes out ten days before travel. The international patients office arranges transfers and an apartment near the hospital for the months of the stay, for the recipient, the donor and a companion. Halal, vegetarian and diabetic meals are available, there is a prayer room, and a request for a female doctor is passed to the department and met wherever the rota allows. Back home, the coordinator stays reachable on the same WhatsApp number, and the transplant team reviews blood results sent from home for life. Before you leave, the team writes to your hepatologist with the operation notes, the pathology of the removed liver, the anti-rejection doses and the target blood levels, the schedule of scans for recurrence, and the signs that should bring you back or to the nearest transplant center, and it agrees who answers a call on a weekend, since the first year after a liver transplant is the time when quick decisions matter most.

Cost follows the same logic.

It depends on the work-up of both people, the two operations, the intensive care and hospital days, the medicines of the first months and the follow-up. A quote should name each part and state the daily rate for any extra days. Your own figure follows the free review of your file.

Liver transplant for HCC FAQ

Who qualifies for a liver transplant for liver cancer?
Patients whose cancer is confined to the liver, within the Milan criteria or wider accepted limits, without invasion of major veins or spread, and fit enough for the operation. Some patients beyond the limits qualify after downstaging.
What is the survival after transplant for HCC?
Within the Milan criteria, around three in four patients are alive at five years. After successful downstaging, the XXL trial reported 77.5 percent five-year survival.
Can a foreigner receive a deceased donor liver in Turkey?
No. International patients receive part of a liver from a living donor, in most cases a relative, with approval from the hospital ethics committee.
Is it safe to donate part of my liver?
The remaining liver regrows within months and most donors return to normal life. The risk of death is small but real, estimated at well under one percent in experienced centers.
Can the cancer come back after transplant?
Yes. Recurrence is most likely within two years and depends on tumor size, number, alpha-fetoprotein and vessel invasion. Regular scans and blood tests catch it early.
How long do we stay in Istanbul?
Plan two to three months for the recipient and four to six weeks for the donor, including the evaluation before surgery.

References

  1. Mazzaferro V, Regalia E, Doci R, et al. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. New England Journal of Medicine. 1996;334(11):693-699.
  2. Yao FY, Ferrell L, Bass NM, et al. Liver transplantation for hepatocellular carcinoma: expansion of the tumor size limits does not adversely impact survival. Hepatology. 2001;33(6):1394-1403.
  3. Mazzaferro V, Llovet JM, Miceli R, et al. Predicting survival after liver transplantation in patients with hepatocellular carcinoma beyond the Milan criteria: a retrospective, exploratory analysis. Lancet Oncology. 2009;10(1):35-43.
  4. Duvoux C, Roudot-Thoraval F, Decaens T, et al. Liver transplantation for hepatocellular carcinoma: a model including alpha-fetoprotein improves the performance of Milan criteria. Gastroenterology. 2012;143(4):986-994.
  5. Mazzaferro V, Citterio D, Bhoori S, et al. Liver transplantation in hepatocellular carcinoma after tumour downstaging (XXL): a randomised, controlled, phase 2b/3 trial. Lancet Oncology. 2020;21(7):947-956.

Editor's note

Written by the Biruni Hospital medical editorial team. Reviewed by Hilal Yıldırım Deryol, Endocrinology and Metabolic Diseases.

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