Small‐for‐size grafts increase recurrence of hepatocellular carcinoma in liver transplantation beyond milan criteria

Abstract

Living donor liver transplantation (LDLT) has been reported to have high rates of hepatocellular carcinoma (HCC) recurrence compared with deceased donor liver transplantation (DDLT). This has been assumed to be due to the frequent use of small-for-size grafts (SFSGs) in LDLT rather than DDLT, but the relationship between graft size and prognosis remains controversial. This study aimed to clarify the effect of SFSGs on the oncologic outcomes of patients with HCC who underwent LDLT. Between January 2005 and December 2015, 597 consecutive patients underwent LDLT. Among these patients, those with HCC who underwent LDLT were randomly matched at a 1:3 ratio (graft-to-recipient body weight ratio [GRWR] < 0.8%:GRWR > 0.8%) according to propensity score. HCC recurrence and patient survival were analyzed using the Kaplan-Meier method and log-rank test. In addition, stratified subgroup analysis based on the Milan criteria was performed. SFSG was defined as a GRWR < 0.8%. Using propensity score matching, 82 patients with GRWR < 0.8% and 246 patients with GRWR 0.8% were selected. For patients with HCC within the Milan criteria, no significant difference of HCC recurrence (P 5 0.82) and patient survival (P 5 0.95) was found based on GRWR. However, for patients with HCC beyond the Milan criteria, 1-, 3-, and 5-year recurrence-free survival rates were 52.4%, 49.3%, and 49.3%, respectively, for patients with GRWR < 0.8%, and 76.5%, 68.3%, and 64.3%, respectively, for patients with GRWR 0.8% (P 5 0.049). The former group exhibited poor patient survival rates (P 5 0.047). In conclusion, for patients with HCC within the Milan criteria, no significant difference in oncologic outcomes was found based on liver graft size. However, among the patients with HCC beyond the Milan criteria, SFSG recipients showed poor oncologic outcomes. Because extended criteria are frequently used in LDLT for HCC, a recipient's prognosis can be improved if a liver graft of appropriate size is carefully selected during donor selection. Liver Transplantation 24 35-43 2018 AASLD.Received May 24, 2017; accepted August 27, 2017. Although living donor liver transplantation (LDLT) was initiated because of the shortage of deceased donor livers, it was accepted as an established method of treatment for end-stage liver diseases in the 1990s. The first LDLT was performed to transplant the left lateral section of the liver from a mother to a child with biliary atresia in 1989. (1)(2)(3) After the mid-1990s, right lobe LDLT started to be performed on adult recipients with high metabolic demands, and significant improvements in the outcomes were observed.A major limitation of LDLT is the size of the liver graft that can be obtained safely from living donors. Small-for-size grafts (SFSGs) cannot appropriately deal with the portal flow in the recipient due to decreased liver volume. Shear stress caused by transient portal hypertension can cause acute mechanical injury, which then induces severe inflammatory responses to negatively affect the outcomes of liver transpla...

Controlling Nutritional Status score does not predict patients' overall survival or hepatocellular carcinoma recurrence after deceased donor liver transplantation

“…Such results are in line with previous reports and meta‐analysis . Persistent chronic inflammation induced by postoperative surgical complications, infections, renal failure, and relapse of previous underlying liver disease, combined with the effect of immunosuppression therapies, may induce immune dysfunctions that may create a favorable microenvironment for migration, adhesion, invasion, and growth of circulating tumor cells resulting in post‐LT HCC recurrence . Clinically, PLR and NLR seemed to correlate well with these post‐LT pathogenic mechanisms, although further studies investigating their efficacy as postoperative markers are needed.…”

Essential updates 2018/2019: Liver transplantation

“…Small‐for‐size grafts defined as GRWR <0.8% showed poor oncologic outcomes, including recurrence‐free survival and overall survival, among the patients with HCC, beyond the Milan criteria . It has been speculated that one of the possible mechanisms can be that high portal pressure and liver congestion affects inflammation of endothelial cells and tumor immunity in the liver.…”

Liver transplantation for hepatocellular carcinoma - non-cancer factors and implications for improving outcome beyond standard tumor criteria

“…Li et al . [106] reported on significantly better 1-and 3-year OS rates in graft-to-recipient body weight ratio (GRWR) ≤ 0.8% vs. > 0.8% (P = 0.009), whereas the corresponding RFS rates tended to be different (P = 0.133). Besides vascular invasion, GRWR was identified as the only independent and significant prognostic factor for OS.…”

“…Besides vascular invasion, GRWR was identified as the only independent and significant prognostic factor for OS. Analyzing 597 consecutive LDLT patients, Lee et al [106] were able to demonstrate that RFS in Milan Out patients was significantly better in GRWR < 0.8% (P = 0.049) [ Table 5].…”