How to decide about liver transplantation in patients with hepatocellular carcinoma: Size and number of lesions or response to TACE?
Authors: Andreas Paul, Georgios Sotiropoulos, Guido Gerken, Fuat Hakan Saner
Journal: Journal of Hepatology (2013)

How to decide about liver transplantation in patients with hepatocellular carcinoma: Size and number of lesions or response to TACE?Journal of HepatologyVol. 59Issue 2PreviewLiver transplantation is a curative treatment option for patients with hepatocellular carcinoma (HCC) and liver cirrhosis. To date, patient selection for transplantation is based on size and number of nodules as assessed by imaging before listing. We hypothesized that changes in tumour features resulting from pre-transplant transarterial chemoembolisation (TACE) is a superior criterion to predict tumour recurrence. Full-Text PDF Reply to: “How to decide about liver transplantation in patients with hepatocellular carcinoma: Size and number of lesions or response to TACE?”Journal of HepatologyVol. 60Issue 2PreviewWe appreciate the interest of A. Paul et al. in our recent publication “How to decide about liver transplantation in patients with hepatocellular carcinoma: Size and number of lesions or response to TACE?” [1]. The point in this publication was to demonstrate the vagueness of size and number of HCC nodules in initial imaging to predict tumour recurrence when compared to the results of pretransplant transarterial chemoembolization (TACE). Based on a cohort of 136 patients uniformly treated by repeated TACE, the results of the radiological routine assessment before the first TACE and after the last TACE before liver transplantation (LT) were compared. Full-Text PDF Open Access To the Editor: With great interest we read the paper by Otto et al. [[1]Otto G. Schuchmann M. Hoppe-Lotichius M. Heise M. Weinmann A. Hansen T. et al.How to decide about liver transplantation in patients with hepatocellular carcinoma: size and number of lesions or response to TACE?.J Hepatol. 2013; 59: 279-284Abstract Full Text Full Text PDF PubMed Scopus (93) Google Scholar] retrospectively reviewing 136 patients with hepatocellular carcinoma (HCC) treated with 2 or more cycles of transarterial chemoembolisation (TACE) prior to liver transplantation over a period of 13 years. The authors of this single center study suggested that not preoperative staging (in or out of Milan criteria) but characterisation of tumour response to TACE allows for identification of patients most suitable for liver transplantation by identification of HCC patients with the most favourable tumour biology. The currently accepted concept of “downstaging” is defined by the reduction of intrahepatic HCC burden in order to achieve 5-year survival rates comparable to that of HCC patients to meet transplant criteria without downstaging [2Yao F.Y. Breitenstein S. Broelsch C.E. Dufour J.F. Sherman M. Does a patient qualify for liver transplantation after the down-staging of hepatocellular carcinoma?.Liver Transpl. 2011; 17: 109-116Crossref Scopus (48) Google Scholar, 3Clavien P.A. Lesurtel M. Bossuyt P.M.M. Gores G.J. Langer B. Perrier A. on behalf of the OLT for HCC Consensus GroupRecommendations for liver transplantation for hepatocellular carcinoma: an international consensus conference report.Lancet Oncol. 2012; 13: e11-e22https://doi.org/10.1016/S1470-2045(11)70175-9Abstract Full Text Full Text PDF PubMed Scopus (779) Google Scholar]. Therefore, possible “downstaging” by response to TACE should not be confused with “favourable tumour biology”. We agree with the authors that clinical staging for HCC for “inside” or “outside” Milan criteria (MC) may differ in both directions in up to 25% of cases when compared to histopathology findings [[4]Sotiropoulos G.C. Malago M. Molmenti E. Paul A. Nadalin S. Brokalaki E. et al.Liver transplantation for hepatocellular carcinoma in cirrhosis: is clinical tumour classification before transplantation realistic?.Transplantation. 2005; 79: 483-487Crossref PubMed Scopus (111) Google Scholar]. However, we believe that critical re-evaluation of the data presented is needed before response to repeated TACE can be adopted into clinical decision-making process or for changing allocation rules. It seems, even though not clearly stated, that in this analysis only patients were included who survived the initial in-hospital phase after liver transplantation. Additionally, no data are provided on time from diagnosis to listing or waiting times or drop-outs on the waiting list. No lab-MELD data or match-MELD data at the time of diagnosis or transplant are provided. Specifically, it remains unclear whether patients who experienced downstaging by TACE got the benefit of HCC related match-MELD or were transplanted only after clinical deterioration or with expanded criteria donor organs directly allocated to the transplant center. Seventy-five patients (55%) suffered from Child-Pugh A cirrhosis, 100 patients had only one or two lesions and/ or 120 out of 136 patients had UICC-T1/T2 tumours. Due to the scarcity of available organs, liver resection in Child-Pugh A cirrhotic patients may have been in some of these patients the treatment of choice. In fact, it has to be considered as the gold standard. Additionally, according to a recently published, well conducted systemic review 5-year survival rate (including perioperative mortality of up to 5%) after resection for HCC fulfilling MC was 67% (27–81%) [[5]Lim K.C. Chow P.K.H. Allen J.C. Siddiqui F.J. Chan E.S.Y. Tan S.B. Systematic review of outcomes of liver resection for early hepatocellular carcinoma within the Milan criteria.Br J Surg. 2012; 99: 1622-1629Crossref PubMed Scopus (168) Google Scholar]. Otto et al. [[1]Otto G. Schuchmann M. Hoppe-Lotichius M. Heise M. Weinmann A. Hansen T. et al.How to decide about liver transplantation in patients with hepatocellular carcinoma: size and number of lesions or response to TACE?.J Hepatol. 2013; 59: 279-284Abstract Full Text Full Text PDF PubMed Scopus (93) Google Scholar] report a similar overall 5-year survival rate of 70% following transplantation, but it remains unclear why resection was not attempted at least in selected patients in the presented series. Furthermore, liver transplantation seems to offer a very limited 5-year survival benefit in patients with Child-Pugh A liver cirrhosis when compared with resection (2.8 [4.4–57] months) or radio frequency ablation (RFA) ± TACE (5.7 [0.7–11.4] months) [[6]Berry K. Ioannou G.N. Are patients with child’s A cirrhosis and hepatocellular carcinoma appropriate candidates for liver transplantation?.Am J Transplant. 2012; 12: 706-717Crossref PubMed Scopus (43) Google Scholar]. Moreover, TACE alone is nowadays no longer regarded as the best therapy for inoperable HCC. Combination with radiofrequency ablation, laser induced thermotherapy, selective internal radiotherapy (SIRT) or transarterial radioembolisation (TARE) can be more effective and can control the tumour in up to 70% of cases [[7]Vogl T.J. Naguib N.N.N. Nour-Eldin N.E.A. Rao P. Emami A.H. Zangos S. et al.Review on transarterial chemoembolization in hepatocellular carcinoma: palliative, combined, neoadjuvant, bridging, and symptomatic indications.EJR. 2009; 72: 505-516Abstract Full Text Full Text PDF PubMed Scopus (132) Google Scholar]. We therefore think that the data provided by Otto et al. [[1]Otto G. Schuchmann M. Hoppe-Lotichius M. Heise M. Weinmann A. Hansen T. et al.How to decide about liver transplantation in patients with hepatocellular carcinoma: size and number of lesions or response to TACE?.J Hepatol. 2013; 59: 279-284Abstract Full Text Full Text PDF PubMed Scopus (93) Google Scholar] is less than convincing in that response to repeated TACE should be used to discriminate between patients with good/acceptable vs. impaired/inacceptable prognosis for long-term survival after liver transplantation. In fact, due to multiple biases there is no evidence provided to support this conclusion of the paper. The authors declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.