Comparison of Criteria for Liver Transplantation in Hepatocellular Carcinoma

Hepatocellular cancer is the 6th most common seen disease in the world and the 3rd in cancer-related deaths. Liver transplantation is the primary curative treatment of HCC, as it eliminates liver cancer and underlying cirrhosis. However, liver transplantation is not offered to every HCC patient, since advanced stage HCC patients are lost with tumor recurrence early after liver transplantation. The Milan criteria, which are accepted worldwide, are the patient selection criteria that we have to follow in cadaver-to-liver transplantation for HCC in our country. However, as the Milan criteria are very strict criteria, it pushes patients out of liver transplantation who exceed the Milan criteria but who can benefit from liver transplantation. Liver transplantation centers all over the world have declared their own criteria under the expanded Milan criteria. In our country, Malatya Criteria have been defined by İnönü University on this subject, and our studies on this subject still continue. When we scan the original articles of all these defined criteria, incomplete data are formed and therefore the strength of the criteria cannot be clearly revealed. For this reason, we aimed to analyze the results of our center and present information about the power of the criteria to the literature.

Study Overview

• Status: Completed
• Conditions: Hepatocellular Carcinoma; Cirrhosis, Liver; Liver Cancer; Liver Transplant Disorder; Advanced Adult Hepatocellular Carcinoma; Unresectable Liver Cancer

Detailed Description

Aim: To investigate the criteria with the longest overall and disease-free survival and lowest recurrence rates in liver transplantation for hepatocellular cancer (HCC).

Introduction: When the liver transplant criteria for HCC were examined, we saw that many criteria defined in their original articles did not include the rates of extending the Milan criteria, survival and recurrence rates of non-milan patients who were within the newly defined criteria. Therefore, information on which of the criteria defined for liver transplantation in HCC extends the Milan criteria more, which has a longer survival rate and which has a lower recurrence rate is lacking. In order to eliminate this deficiency or at least to have a rough idea, we aimed to compare the results of liver transplantation, performed for HCC in our institute which is a high-volume liver transplant center, by analyzing it according to the existing defined criteria. Thus, we were able to compare the criteria in a homogeneous patient group that was formed as a result of the same inclusion and exclusion criteria in the same period of time. The highest overall and disease-free survival, the lowest recurrence rate, and the criterion that extends the Milan criteria will be introduced. In addition, this study is the first comprehensive comparison of liver transplant criteria for HCC.

Methods: Between March 2002 and July 2020, the data of 424 patients who underwent liver transplantation due to HCC at the Liver Transplantation Institute of İnönü University will be retrospectively analyzed from the prospectively recorded data bank and automation system. Tumor size, tumor number, differentiation and microscopic venous invasion data will all be recorded from the data in the explant pathology report. Since the primary aim of our study is cancer-related survival in patients who can be transplanted, 31 patients with tumor invasion outside the liver (extrahepatic portal vein tumor thrombosis, perihilar lymph node metastasis, diaphragmatic invasion etx) and 70 patients with follow-up period after liver transplantation below 90 days will be excluded from the study. The remaining 323 patients will be included in the study and their data will be analyzed. First, demographic data, tumor characteristics, overall and disease-free survival and recurrence rate of 323 HCC patients who were the study group, will be calculated, and then these patients will be divide groups according to be within or beyond the criteria, than survival and recurrence rates will be calculated. It was then examined whether these expanded criteria actually extended the Milan criteria. It was checked whether a defined Expanded criterion allowed liver transplantation for patients outside of Milan while excluding patients within Milan from liver transplantation. How far the expanded criteria expand the Milan and survival of the patients who beyond Milan but within the criteria were analyzed separately. Thus, the most useful criterion for liver transplantation in HCC treatment will be revealed.

• Study Type: Observational
• Enrollment (Actual): 424

Contacts and Locations

Study Locations

• Turkey
  • Battalgazi
    • Malatya, Battalgazi, Turkey, 44280
      • Liver Transplantation Institute, Inonu University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Between 2002 - 2020 August, patients undergone Liver Transplantation at Liver Transplant Institute of Inonu University.

Description

Inclusion Criteria:

• Patients undergone liver transplantation due to hepatocellular carcinoma
• Incidentally detected hepatocellular carcinoma at the explant pathology report

Exclusion Criteria:

• Patients with follow up period below 90 days
• Advanced Tumors which have lymph node positivity, main PV tumor thrombosis, adjacent tissue invasion defined by explant pathology etc.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease Free Survival	Tumor free survival after liver transplantation	five years
Overall Survival	Overall survival after liver transplantation	five years
Tumor recurrence	Tumor recurrence following liver transplantation	5 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Best Criteria	Liver Transplant criteria which has the best survivals	5 years

Collaborators and Investigators

• Sponsor: Inonu University
• Investigators: Principal Investigator: Volkan Ince, MD, Inonu University, Liver Transplant Institute

Study record dates

Study Major Dates

• Study Start (Actual): June 15, 2020
• Primary Completion (Actual): July 30, 2020
• Study Completion (Actual): September 30, 2020

Study Registration Dates

• First Submitted: September 30, 2020
• First Submitted That Met QC Criteria: September 30, 2020
• First Posted (Actual): October 6, 2020

Study Record Updates

• Last Update Posted (Actual): October 6, 2020
• Last Update Submitted That Met QC Criteria: September 30, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: liver transplantation; malignancy; liver cancer; living donor; Hepatic malignancy; expanded criteria; extended
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Fibrosis; Carcinoma; Carcinoma, Hepatocellular; Liver Cirrhosis; Liver Neoplasms
• Other Study ID Numbers: LT-Criteria-HCC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: all IPD that underlie results in publication
• IPD Sharing Time Frame: 01.01.2022
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No