Very Late Recurrence of Hepatocellular Carcinoma After Liver Transplantation: Case Report and Literature Review

doi:10.1016/j.transproceed.2006.08.095

Transplantation Proceedings

Volume 38, Issue 9, November 2006, Pages 3140-3143

https://doi.org/10.1016/j.transproceed.2006.08.095 Get rights and content

Abstract

Hepatocellular carcinoma (HCC) recurs in 10% to 60% of the patients after liver transplantation (OLT) and is associated with increased mortality. The average time to recurrence ranges from 1 to 2 years following OLT, and the median survival from the time of diagnosis is about 1 year. We report a case of a 69-year-old man who underwent OLT for hepatitis C virus–related cirrhosis with HCC, and was diagnosed with recurrent HCC 6.5 years after OLT. Biopsies from the initial and recurrent tumors showed a well-differentiated HCC with foci of clear cell pattern. The patient was still alive and asymptomatic 32 months after the diagnosis despite extensive tumor burden. He expired 9 years, 9 months after OLT and 3 years, 2 months after the detection of recurrence. In conclusion, HCC may recur more than 6 years after OLT and may exhibit an indolent course. This case illustrates the highly variable rate of tumor growth and progression post-OLT. The impact of this information on the need for long-term surveillance for recurrent HCC post-OLT remains to be determined.

Section snippets

Case report

A 69-year-old Hispanic male was referred to our clinic for evaluation of three suspicious masses on an abdominal magnetic resonance imaging (MRI) study. His past medical history included OLT 6 years and 7 months earlier, at the age of 63, for cirrhosis secondary to chronic hepatitis C virus (HCV) and HCC (Fig 1). Prior to OLT, he was found to have a 4-cm lesion in the right hepatic lobe, which was shown on a computerized tomography (CT) guided biopsy to be a well-differentiated HCC with foci of

Discussion

HCC is a common complication of cirrhosis.1, 2, 3, 4 The only curative options available are surgical resection or OLT.⁵ The risk of HCC recurrence depends on tumor size, differentiation, number of lesions, and the presence of vascular involvement. The Milan criteria are currently employed to determine which patients with HCC are suitable for OLT.⁶ Nevertheless, recurrence is seen even with strict adherence to the Milan criteria. The reported rates of HCC recurrence vary from 10% to 20.6%,6, 7,

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Cited by (15)

Focus on Very Late Hepatocellular Carcinoma Recurring After Liver Transplantation: A Case Report and Literature Review
2019, Transplantation Proceedings
Hepatocellular carcinoma (HCC) recurring after liver transplantation (LT) is a major clinical concern, occurring in up to 20% and being the most frequent cause of death in this setting. Usually recurrence occurs within the first 2 years, whereas late and very late recurrences are rare. We report a 71-year-old woman with HCC recurrence after 25 years from LT, an event never reported before. Diagnosis was achieved with a progressive increase of alpha-fetoprotein (AFP) followed by a computed tomography scan, showing a mediastinal, upper diaphragmatic, right paracaval mass of 5 cm in size. The lesion was treated with a surgical approach involving a multidisciplinary team including hepatobiliary, thoracic, and cardiovascular surgeons. A sternotomy and mass removal was performed without the need of an extracorporeal bypass. A complete resection of the tumor was achieved, with a drop in AFP and without signs of recurrence after 1-year follow up. In conclusion, the possibility of late HCC recurrences after LT, despite being rare, underlines the need of a standardized, cost-benefit, optimal strategy of a long-term surveillance. From a surgical point of view, our case is unusual for the site and the character of the lesion, and for the absence of the need of an extracorporeal bypass during the operation.
Personalized molecular targeted therapy in advanced, recurrent hepatocellular carcinoma after liver transplantation: A proof of principle
2010, Journal of Hepatology
Citation Excerpt :
In the presented case, a mutation in exon 3 of the CTNNB1 gene, and the β-catenin positive nuclear immunostaining indicated aberrant activation of the Wnt pathway: a rather frequent condition indicating the need of DNA microsatellite analysis in both primary and recurrent tumors to confirm the same point mutation and therefore the diagnosis of a true recurrent HCC, also considering that seeding of cancer cells was excluded by the absence of any percutaneous tumor biopsy preceding transplantation. Recurrence of HCC more than 10 years after transplantation is very rare [18] and the pathogenesis of such an event should be investigated in large sample sizes, also in light of the possible role of liver stem cells involvement, due to their capacity of long-lasting latency. Their immunophenotypical characterization as well as their role in HCC development warrant further studies [19].
The advent of molecular medicine that targets specific pathways is changing the therapeutic approach to hepatocellular carcinoma. For several aberrantly activated pathways in hepatocarcinoma, surrogate markers of activation can be assessed by immunohistochemistry, although associations with in vivo response to targeted therapies are still lacking.
A patient, who presented with hepatic and extra-hepatic hepatocarcinoma recurrence 11 years after liver transplantation, was assessed for β-catenin, pERK, and pS6 in primary and secondary tumor specimens, in order to define a possible activation of the Wnt, Ras/MAPK and Akt/mTOR pathways and design a personalized targeted therapy in absence of alternative treatment options. Moreover, mutation analysis of the β-catenin gene (CTNNB1) and DNA microsatellite analyses were performed.
The identification of the same mutation in the β-catenin gene, as well as the same microsatellite pattern in tumor tissues taken 11 years apart, proved that the observed hepatocarcinoma was a true recurrence. Nuclear β-catenin and pS6 in tumor cells were positive, whereas pERK was positive only in the peritumoral endothelium. This pattern of immunohistochemistry, after failure of sorafenib alone, lead to the choice to add the mTOR inhibitor, everolimus, to sorafenib. Three months later a 50% tumor reduction was observed, and after 6 months a further reduction of tumor vital components was confirmed, while a grade II gastrointestinal bleeding episode occurred.
A personalized approach aimed to treat recurrent hepatocarcinoma is possible through analysis of tumoral molecular pathways. Partial success of the selected combination of sorafenib and everolimus supports the pivotal role of mTOR signalling and highlights the importance of reliable biomarkers to route the best molecular-based therapeutic options in HCC.
Natural history and therapeutic management of recurrent hepatocellular carcinoma after liver transplantation
2009, Gastroenterologie Clinique et Biologique
While the natural history and appropriate diagnostic and management practices are relatively well defined for hepatocellular carcinoma (HCC), data are scarce concerning the characteristic features and treatment modalities for recurrent HCC after liver transplantation. The time of recurrence appears to impact survival more significantly than localization, but to date, guidelines for therapeutic management of recurrent HCC have not been established. Data in the literature shows that late and unifocal recurrence has a better prognosis when treated by surgery or radiofrequency. In the event of early recurrence, surgery cannot be recommended due to the lack of evidence and the high risk of advanced disease. Systemic therapy can be discussed in a situation of multifocal recurrence. Proliferative signal inhibitors exhibit both immunosuppressive and antiproliferative properties and liver transplantation teams tend to introduce such treatment despite the lack of extensive data.
Alors que l’histoire naturelle et la prise en charge thérapeutique du carcinome hépatocellulaire (CHC) sont mieux codifiées, il existe peu de données sur les caractéristiques et le traitement de la récidive du CHC après transplantation hépatique. Le délai de récidive semble plus influencer la survie que sa localisation et il n’existe actuellement pas de recommandation précise sur la prise en charge thérapeutique de la récidive du CHC post-transplantation hépatique. La récidive unifocale et tardive apparaît de meilleur prognostic si une résection chirurgicale ou une radiofréquence peuvent être proposées. En cas de récidive tumorale précoce, il ne semble pas licite de proposer la chirurgie d’emblée compte tenu du fort risque de maladie disséminée. La récidive multifocale fait discuter l’opportunité d’un traitement systémique. Actuellement les inhibiteurs du signal de prolifération ont l’avantage d’une activité immunosuppressive et antiproliférative et les équipes de transplantation hépatique introduisent volontiers cette nouvelle classe thérapeutique malgré le peu de données disponibles.
Radiofrequency Ablation of Recurrent Hepatocellular Carcinoma in a Patient after Liver Transplantation: Two-year Follow-up
2007, Journal of Vascular and Interventional Radiology
Citation Excerpt :
The patient presented in this report was diagnosed with recurrent HCC approximately 1 year after he underwent OLT. Fortunately, our patient has survived beyond the median survival time of 12 months from diagnosis (2). At the time of manuscript preparation, the patient had survived for more than 2 years after undergoing successful RF ablation for tumor recurrence.
Orthotopic liver transplantation is frequently performed for patients with end-stage liver disease complicated by the development of small hepatocellular carcinomas (HCCs). Since the adaptation of the Milan criteria, the rate of posttransplantation recurrence has significantly decreased to a rate of 10%–20%. In the setting of recurrence after transplantation, survival rates are poor, with a median of 9 months. Survival can be extended with use of definitive therapies, most often surgical. The present report describes a patient with recurrent intrahepatic HCC after liver transplantation who was treated with radiofrequency ablation and has survived 24 months with normalization of α-fetoprotein levels and no evidence of viable tumor on imaging.
Delayed brain metastasis in recurrent hepatocellular carcinoma following liver transplantation: a case report highlighting the predictive value of microvascular invasion
2023, Clinical Journal of Gastroenterology
Hepatocellular carcinoma with increased afp levels and extrahepatic manifestation after liver transplantation: A case of late-onset recurrence
2019, Duzce Medical Journal

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Case reportLiverVery Late Recurrence of Hepatocellular Carcinoma After Liver Transplantation: Case Report and Literature Review

Abstract

Section snippets

Case report

Discussion

Gastreonterology

Clin Liver Dis

Transplant Proc

Am J Transpl

Liver Transpl

Gastrointest Endosc

Gastroenterology

The prediction of risk of recurrence and time to recurrence of hepatocellular carcinoma after orthotopic liver transplantation: a pilot study

Hepatology

Case report
Liver
Very Late Recurrence of Hepatocellular Carcinoma After Liver Transplantation: Case Report and Literature Review