Liver Transplantation for the Treatment of Small Hepatocellular Carcinomas in Patients with Cirrhosis
- Study type
- Observational study
- Study name
- Milan criteria
- Design
- Prospective single-arm study (no control group) in patients with cirrhosis who underwent liver transplantation
- Sample size
- 48 patients
- Source
- N Engl J Med · 1996
In plain words
In some people with cirrhosis, the liver cancer is small, but because of the underlying liver disease the tumour cannot be removed by surgery. In this study, 48 patients in this situation had a liver transplant. Four years after the transplant, about three quarters of the patients were alive and the cancer came back in only 4 people. Results were better in patients whose tumours were within set limits (one tumour up to 5 cm, or at most three tumours each up to 3 cm).
Key results
Treatment arms and regimens
Orthotopic liver transplantation (pre-transplant entry criterion: single tumour ≤5 cm or at most 3 nodules each ≤3 cm, not amenable to resection). 33 patients with adequate liver function received tumour treatment before transplantation, mainly chemoembolisation (chemoembolisation drugs and doses are not stated in the abstract; details in the full text of the paper). No anticancer treatment was given after transplantation.
Source of the regimen details: Abstract of the paper
Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.
Study population
Patients with cirrhosis and small, unresectable hepatocellular carcinoma who underwent liver transplantation. In 94% of patients the cirrhosis was associated with hepatitis B virus infection, hepatitis C virus infection or both. The tumour was confirmed by biopsy or serum alpha-fetoprotein measurement. Eligibility criteria for transplantation: for a single tumour, diameter 5 cm or less; for multiple tumours, no more than three nodules, each 3 cm or less in diameter.
Endpoints
Overall and recurrence-free survival after liver transplantation (actuarial survival at 4 years). Patients were followed prospectively with a median follow-up of 26 months (range 9 to 54 months). Survival was compared according to whether the predefined criteria were met at pathological examination of the explanted liver.
Safety and side effects
The abstract gives no detailed information on adverse events. Overall mortality was reported as 17%.
Clinical significance and place in guidelines
This study showed that liver transplantation can be an effective treatment for small, unresectable hepatocellular carcinoma in patients with cirrhosis, and that the patient selection criteria it used (one tumour ≤5 cm or at most three tumours ≤3 cm) were associated with better outcomes. The abstract gives no information on impact on guidelines or drug approvals; the current status of these criteria in clinical guidelines should be checked separately.
Limitations
The small sample size (48 patients), the absence of a control group and randomisation, and the relatively short median follow-up (26 months) are limitations of the study. The comparison was based on pathological findings after transplantation, and 33 patients had received tumour treatment before transplantation. Most patients had cirrhosis related to hepatitis B or C.
This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.