C

Fl

T

abciiiVm5(iswttrrwomtAawftp5Matecw

1d

Digestive and Liver Disease 43 (2011) 754

Contents lists available at ScienceDirect

Digestive and Liver Disease

jou rn al h om epage: www.elsev ier .com/ locate /d ld

[

[

[

[

orrespondence

atal gastric bleeding during sorafenib treatment for hepatocel-ular carcinoma recurrence after liver transplantation

o the Editor,

Sorafenib has recently become the treatment of choice fordvanced hepatocellular carcinoma (HCC). Although the risk ofleeding could be intrinsic to the anti-angiogenetic effect of vas-ular endothelial growth factor receptor (VEGFR) tyrosine-kinasenhibitors, an increased risk of gastrointestinal bleeding was notnitially found [1]. Recently, a meta-analysis of randomized clin-cal trials showed a significant increased risk of bleeding withEGFR tyrosine-kinase inhibitors [2]. However, results of the for-er meta-analysis have been debated. We report the case of a

7-year-old man who underwent orthotopic liver transplantationOLT) for a multi-focal HCC (four lesions of no more than 18 mmn adjoining segments of the liver) on hepatitis C-related cirrho-is in December 2009, after successful radiological down-stagingith trans-arterial chemo-embolization and radiofrequency abla-

ion. An 8 cm G3 HCC with microvascular invasion was found onhe explanted liver. In July 2010, hepatic and peritoneal multipleecurrent HCC nodules were found, in the absence of recurrent cir-hosis. Sorafenib 400 mg twice daily was started and tacrolimusas switched to everolimus. In January 2011, despite the evidence

f a partial HCC response, the patient was admitted because ofelena and sorafenib was stopped. Medical treatment with pro-

on pump inhibitors, somatostatin and terlipressin was started.t endoscopy, oozing bleeding from the entire gastric antrumnd body was evident from an otherwise normal mucosa; thereere no esophago-gastric varices. Endoscopic treatment was inef-

ective in three different sessions, and nine units of blood wereransfused. After fifteen days, the patient died from bleeding com-lications. To our knowledge, this is the first report of a grade

gastrointestinal bleeding due to sorafenib for HCC treatment.oreover, since it happened one year after liver transplantation

nd in the absence of both recurrent cirrhosis and portal hyper-

ension, the cause of bleeding was ascribed to an adverse drugvent. Moreover, the additive effect of everolimus on bleedingannot be excluded. Interestingly, the same drug combinationas effective as treatment of HCC recurrence after OLT in a

590-8658/$36.00 © 2011 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevieroi:10.1016/j.dld.2011.04.022

case report. However, despite a 50% tumour reduction after 3months of therapy, a grade II gastrointestinal bleeding motivatedsorafenib interruption 3 months later [3]. Although promising, cur-rent published data on sorafenib for HCC recurrence after OLTare scanty and uncontrolled [4]. In conclusion, we report a fatalcase of gastric bleeding during sorafenib treatment for HCC recur-rence after liver transplantation. Although more data are needed,the concern of gastrointestinal bleeding should be weighted dur-ing sorafenib therapy for HCC recurrence after OLT. Sorafenibtreatment should be stopped if there is evidence of digestive bleed-ing.

Conflict of interest statementNone declared.

References

1] Llovet JM, Ricci S, Mazzaferro V, et al. Sorafenib in advanced hepatocellularcarcinoma. N Engl J Med 2008;359:378–90.

2] Je Y, Schutz FAB, Choueiri TK. Risk of bleeding with vascular endothelial growthfactor receptor tyrosine-kinase inhibitors aunitinib and sarafenib: a systematicreview and meta-analysis of clinical trials. Lancet Oncol 2009;10:967–74.

3] Bhoori S, Toffanon S, Sposito C, et al. Personalized molecular targeted therapyin advanced, recurrent hepatocellular carcinoma after liver transplantation: aproof of principle. J Hepatol 2010;52:771–5.

4] Kim R, El-Gazzaz G, Tan A, et al. Safety and feasibility of using sorafenib in recur-rent hepatocellular carcinoma after orthotopic liver transplantation. Oncology2010;79:62–6.

Andrea Mancuso ∗

Aldo AiroldiRaffaella Vigano

Giovambattista PinzelloEpatologia e Gastroenterologia, Ospedale Niguarda

Ca’ Granda, Piazza Maggiore 3, CAP 20162,Milan, Italy

∗ Corresponding author. Tel.: +39 0264444435.E-mail addresses: mancandrea@libero.it,

andrea.mancuso@ospedaleniguarda.it(A. Mancuso)

Available online 8 June 2011

Ltd. All rights reserved.