Table 1.
Summary of recommendations and statements
| Level of evidence |
Strength of recommendation |
|
|---|---|---|
| Assessment of candidates with HCC for liver transplantation | ||
| 1. When considering treatment options for patients with HCC, the BCLC staging system is the preferred staging system to assess the prognosis of patients with HCC | 2b (P) | Strong |
| 2. The TNM system (7th edn) including pathological examination of the explanted liver, should be used for determining prognosis after transplantation with the addition of assessment of microvascular invasion | 2b (P) | Strong |
| 3. Either dynamic CT or dynamic MRI with the presence of arterial enhancement followed by washout on portal venous or delayed imaging is the best non-invasive test to make a diagnosis in cirrhotic patients suspected of having HCC and for preoperative staging | 1b (D) | Strong |
| 4. Extrahepatic staging should include CT of the chest, and CT or MRI of the abdomen and pelvis | 3b (D) | Strong |
| 5. Tumour biopsy is not required in cirrhotic patients considered for liver transplantation who have high-quality dynamic CT or MRI findings typical for HCC and a lesion larger than 1 cm according to current AASLD guidelines | 1b (D) | Weak |
| 6. For patients with lesions smaller or equal to 10 mm, non-invasive imaging does not allow an accurate diagnosis and should not be used to make a decision for or against transplantation | 1b (D) | Strong |
| Criteria for listing candidates with HCC in cirrhotic livers for DDLT | ||
| 7. Liver transplantation should be reserved for HCC patients who have a predicted 5-year survival comparable to non-HCC patients | NA | Weak |
| 8. Preoperative assessment of the size of the largest tumour or total diameter of tumours should be the main consideration in selecting patients with HCC for liver transplantation | 2a (P) | Strong` |
| 9. The Milan criteria are currently the benchmark for the selection of HCC patients for liver transplantation, and the basis for comparison with other suggested criteria | 2a (P) | Strong |
| 10. A modest expansion of the number of potential candidates may be considered on the basis of several studies showing comparable survival for patients outside the Milan criteria | 3b (P) | Weak |
| 11. Patients with worse prognosis may be considered for liver transplantation outside the Milan criteria if the dynamics of the waiting list allow it without undue prejudice to other recipients with a better prognosis | NA | Weak |
| 12. α-fetoprotein concentrations add prognostic information in HCC patients and may be used for making decisions regarding transplantation in combination with imaging criteria | 2b (P) | Weak |
| 13. Biomarkers other than α-fetoprotein cannot yet be used for clinical decision making regarding liver transplantation for HCC | 2b (P) | Strong |
| 14. Indication for liver transplantation in HCC should not rely on microvascular invasion because it cannot be reliably detected prior to transplantation | 2b (P) | Strong |
| Criteria for HCC candidates with non-cirrhotic livers | ||
| 15. The Milan criteria and its modifications are not applicable to patients with HCC developing in a non-cirrhotic liver. Such patients with non-resectable HCC and absence of macrovascular invasion and extrahepatic spread may be considered as appropriate candidates for liver transplantation | 4 (P) | Weak |
| 16. Patients with HCC in non-cirrhotic liver who were treated by resection, and have intrahepatic recurrence of HCC and no evidence of lymph node or macrovascular invasion, may be considered for salvage transplantation | 4 (P) | Weak |
| Role of downstaging | ||
| 17. Transplantation may be considered after successful downstaging | 5 (P) | Weak |
| 18. Liver transplantation after successful downstaging should achieve a 5-year survival comparable to that of HCC patients who meet the criteria for liver transplantation without requiring downstaging | 5 (P) | Strong |
| 19. Criteria for successful downstaging should include tumour size and number of viable tumours | 4 (P) | Strong |
| 20. α-fetoprotein concentrations before and after downstaging may add additional information | 4 (P) | Weak |
| 21. Based on existing evidence, no recommendation can be made for preferring a specific locoregional therapy for downstaging over others | NA | None |
| Managing patients on the waiting list | ||
| 22. Periodic waiting-list monitoring should be performed by imaging (dynamic CT, dynamic MRI, or contrast-enhanced ultrasonography) and α-fetoprotein measurements | 5 (P) | Strong |
| 23. Based on current absence of evidence, no recommendation can be made on bridging therapy in patients with UNOS T1 (≤2 cm) HCC | NA | None |
| 24. In patients with UNOS T2 (one nodule 2–5 cm or three or more nodules each ≤3 cm) HCC (Milan criteria) and a likely waiting time longer than 6 months, locoregional therapy may be appropriate | 4 (P) | Weak |
| 25. No recommendation can be made for preferring any type of locoregional therapy to others | NA | None |
| 26. Patients found to have progressed beyond criteria acceptable for listing for liver transplantation should be placed on hold and considered for downstaging | 5 (P) | Strong |
| 27. Patients with progressive disease in whom locoregional intervention is not considered appropriate, or is ineffective, should be removed from the waiting list | 5 (P) | Strong |
| Role of LDLT | ||
| 28. LDLT is acceptable for HCC patients who have an expected 5-year survival similar to comparably staged patients receiving a deceased donor liver. In LDLT, careful attention should be given to psychosocial considerations regarding both donor and recipient | NA | Weak |
| 29. LDLT must be restricted to centres of excellence in liver surgery and liver transplantation to minimise donor risk and maximise recipient outcome | NA | Strong |
| 30. In patients following LDLT for HCC within the accepted regional criteria for DDLT, retransplantation for graft failure is justified | 5 (P) | Weak |
| 31. In patients following LDLT for HCC outside the accepted regional criteria for DDLT, retransplantation for graft failure using a deceased donor organ is not recommended | 5 (P) | Strong |
| Post-transplant management | ||
| 32. Post-transplant monitoring may include 6–12 monthly contrast-enhanced CT or MRI imaging and α-fetoprotein measurements | 5 (P) | Weak |
| 33. There is currently insufficient evidence from clinical trials to base a recommendation for choosing the type or dose of immunosuppression therapy to influence the incidence of HCC recurrence or its prognosis | NA | None |
| 34. Based on current evidence, no recommendation can be made on the use of mTOR inhibitors solely to reduce the risk of HCC recurrence outside clinical trials | NA | None |
| 35. The current evidence does not justify the routine use of adjuvant antitumour therapy after liver transplantation for HCC outside of a controlled clinical trial | NA | Weak |
| 36. HCC recurrence after liver transplantation may be treated by surgery for resectable lesions or by locoregional therapy or systemic therapy (including sorafenib) for unresectable lesions | 4 (P) | Weak |
| 37. Liver retransplantation is not appropriate treatment for recurrent HCC | NA | Strong |
Level of evidence for each recommendation refers to the Oxford classification.4 HCC=hepatocellular carcinoma. BCLC=Barcelona Clinic Liver Cancer. TNM=tumour, node, metastasis. P=prognosis. D=diagnosis. AASLD=American Association for the Study of Liver Diseases. NA=not applicable. OLT=orthotopic liver transplantation. UNOS=United Network for Organ Sharing. LDLT=living donor liver transplantation. DDLT=deceased donor liver transplantation.