HCC-Associated Liver Transplantation - Where Are the Limits and What Are the New Regulations?

Abstract

Background: Hepatocellular carcinoma (HCC) represents an increasing health burden worldwide and a challenging disease both in terms of diagnosis and treatment. Methods: The literature available on PubMed for the period of 1990-2016 was reviewed with reference to liver allocation, HCC, liver transplantation (LT), and prediction, and the allocation rules of the German Transplant Act were reviewed. Results: Due to etiological and geographical diversity, HCC is not a homogeneous disease. In the vast majority of patients, HCC develops as a complication of chronic liver disease and cirrhosis. While most patients present with advanced HCC for which palliative strategies are the only available option, LT is the best treatment approach as it not only eliminates the diseased liver and the underlying hepatocarcinogenic mechanisms but also the cancer. The decision for LT is not an easy one to make, because outcome prediction, staging, bridging therapy, and recurrence prevention are difficult and are estimated against the background of the scarce resource of donor organs which are also competitively sought after by patients suffering from non-neoplastic terminal liver diseases, raising the issue of equality of chances in a rationed therapeutic modality. Currently, the Milan criteria are the best evaluated decision tool for LT, but many issues such as down-staging, favorable biological behavior during treatment, expansion of the morphological classification, molecular predictors, and individualized approaches are not yet satisfactorily addressed. Conclusion: In order to provide a fair and effective approach to LT in HCC, the employed allocation rules require continuous development and scientific evaluation. Recently, the allocation rules for standard exception priority according to the German Transplant Act have been revised to improve patient selection for LT in HCC.

Milan criteria in the MELD era—is it justifiable to extend the limits for orthotopic liver transplantation?

“…Patients beyond the MC can be transplanted based on extended allocation policies [9,10]. However, the limit for the exclusion of patients with advanced tumors from liver transplantation should be defined since the increase in tumor burden is related to a poor prognosis following transplantation [11,12].…”

Use of checkpoint inhibitors in liver transplant recipients

“…Owing to long‐term immunosuppression, organ transplant recipients are an at‐risk population for the development of a wide spectrum of malignancies comprising melanoma and haematological cancers 3 . This risk is further increased in patients who underwent transplantation due to hepatocellular carcinoma (HCC) due to a post‐transplant recurrence risk of approximately 10% within five years 4 , 5 . Despite this increased need for effective cancer treatment options, CPIs are considered as contraindicated in organ transplant recipients for fear of organ rejection.…”

Milan criteria in the MELD era – Is it justifiable to extend the limits for orthotopic liver transplantation?

“…Patients beyond the MC can be transplanted based on extended allocation policies 9,10 . However, the limit for the exclusion of patients with advanced tumors from liver transplantation should be de ned since the increase in tumor burden is related to a poor prognosis following transplantation 11,12 .…”