Abstract

Key words : Long-term survival

Introduction

Liver transplant (LT) evolved from an experimental procedure to a standard therapeutic modality for liver failure. The aim of LT is to increase the length and the quality of the lives of patients with acute and chronic liver failure as well as those with hepatocellular carcinoma (HCC). The number of surviving LT recipients is increasing. After learning curves on surgery were overcome and with better immunosuppression regimens, current databases have shown that the number of survivors with functioning grafts has risen exponentially, which, in turn has increased the demand for adequate care and the need for support by experienced clinicians. In previous studies, 1-year and 10-year survival rates were 90% and 60%, respectively.^1,2 Although several studies have reported short-term and midterm follow-ups of LT recipients, there have been few reports on long-term survivors (LTS) of more than 10 or 20 years. In this present study, we analyzed the data for our LT recipients who survived more than 10 years.

Materials and Methods

Our team performed the first successful deceased donor LT of Turkey on December 8, 1988. On March 15, 1990, the first pediatric segmental living related LT of Turkey, the Middle and Near East, and Europe was performed by our team. One month later, on April 24, 1990, our team performed the first adult segmental living related LT in the world. On May 16, 1992, the first combined liver-kidney transplant from a living related donor, the first of its kind in the world, was performed by our team. Since 1988, we have performed 694 LT (366 adult, 328 pediatric) procedures at our centers. Here, we retrospectively evaluated the data of LT recipients who survived for more than 10 years after transplant with normal graft function. For this analyses, we collected the demographic data, evaluated the cause of the disease, and identified the graft type, donor type, duration of anhepatic phase, de novo malignancy, and acute rejection.

Results

The data of 215 LTS were retrospectively evaluated. We observed that 13 survived for ≥20 years, 86 survived for 15 to 19 years, and 116 survived for 10 to 14 years. The data of 13 LTS who survived ≥20 years after LT are summarized in Table 1. Of these 13 LTS, 7 of the transplants were from deceased donors and 6 were from living donors. Two of the 13 LTS underwent a retransplant to treat chronic rejection, and both of these patients remain alive with normal graft function. Two of these 13 patients died from chronic rejection at 22 and 20 years after LT. There were 17 drug-induced complications (12 with diabetes mellitus, 4 neurological disorder, and 1 nephrotoxicity).

Table 2 shows data from the 86 LTS who survived for 15 to 19 years after LT (16 from deceased donors, 70 from living donors) and for the 116 LTS who survived for 10 to 14 years (24 from deceased donors, 92 from living donors). Three patients received a retransplant to treat chronic graft rejection, 2 of whom remain alive with normal graft functions after the second LT. One patient died during the early period after the second LT; which was year 15 after his first LT. Acute rejection episodes were seen in 72 patients (34%), 7 of whom were steroid resistant. We observed 31 (15%) drug-induced complications: 11 with diabetes mellitus, 4 neurological disorder, 3 nephrotoxicity, and 13 epilepsy. We also observed 10 de novo malignancies: 5 with lymphoma, 2 squamous cell carcinoma, 1 gastrointestinal stromal tumor, 1 thyroid papillary carcinoma, and 1 multiple myeloma. There were also 31 patients with HCC before LT in our LTS series: 13 were beyond Milan criteria, 6 were incidental HCC, and 12 were within Milan criteria.

Discussion

Liver transplant, originally considered an experimental procedure, has become a standard therapeutic modality of liver failure. The number of surviving LT recipients is increasing. With learning curves on surgery and immunosuppression regimens now overcome, the number of survivors with functioning grafts has exponentially increased, which, in turn has increased the demand for adequate care and the need for support from experienced clinicians. In previous studies, 1-year and 10-year survival rates were 90% and 60%, respectively.^1,2 Most of the previously published studies have reviewed the short-term and midterm follow-ups of LTS. There are few reports in the literature of long-term LTS.

We had a total of 215 LTS: 13 survived for ≥20 years, 86 survived for 15 to 19 years, and 116 survived for 10 to 14 years. Compared with previous studies, our data showed a high percentage of LTS (30.9%) who survived for more than 10 years.^1,3-5 When we analyzed the etiology of liver disease for LTS who survived for ≥20 years, for 15 to 19 years, and for 10 to 14 years, the leading causes of death were Wilson disease, hepatitis B and hepatitis C viral cirrhosis, and hepatitis C virus, respectively. In all 3 LTS groups, most were pediatric transplant recipients. Similar to previous conclusions, younger recipient age was an advantage for LTS.^6,7 The overall number of acute rejection episodes was greater in LTS who survived 15 to 19 years versus 10 to 14 years in our study, in agreement with the other reports from the literature.^8,9 Reported rates of incidence of de novo tumors in LT recipients have ranged from 3% to 16%; in our series, the incidence rate was 4.5%. The most common tumor was lymphoma. We treated 10 de novo malignancies in our patients: 5 lymphoma, 2 squamous cell carcinoma, 1 gastrointestinal stromal tumor, 1 thyroid papillary carcinoma, and 1 multiple myeloma.^10,11

In the early period after LT, the main goal was prevention of rejection by treatment with high-dose continuous immunosuppression. As knowledge has grown regarding the toxic effects of these drugs, there has been an ongoing trend toward reduction of immunosuppression.¹⁰ In our study group, we observed 48 (22.7%) drug-induced complications, and 1 patient underwent a renal transplant to treat nephrotoxicity. There were also 31 patients with HCC before LT in our LTS series, 13 of whom had HCC scores beyond the Milan criteria, 6 had incidental HCC, and 12 had HCC scores within the Milan criteria.

Decades of treatment with immunosuppression can affect long-term outcomes of LT patients in terms of morbidity, but long-term survival can be achieved with expert care. The 1-year and 10-year survival rates of LT patients have been shown to exceed 90% and 60%, respectively, which are higher than the expected survival rates if disease was allowed to progress without treatment. There have been many reports on survival outcomes after LT with short-term and midterm follow-up. However, few long-term surveys have been published. Our LTS survey is among the largest series published to date and adds substantial information about cumulative experience to the literature.

References:

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