Prophylactic liver transplantation for high-risk recurrent hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) is the second most common cause of cancer-related death in the world. Radical treatment of HCC in early stages results in a long disease-free period and improved overall survival. The choice of optimal management strategy for HCC mainly depends on the severity of the underlying liver disease. For patients with decompensated liver cirrhosis and HCC within Milan criteria (MC), liver transplant (LT) is the choice of treatment. However, for patients with good residual liver reserve and HCC within MC, selection of other curative treatments such as liver resection (LR) or radiofrequency ablation may be a reasonable alternative. For patients without cirrhosis, LR can result in an overall survival similar to that provided by LT. Therefore, it is an accepted alternative to LT especially in areas with organ shortage. However, the cumulative 5-year recurrence rate of HCC post LR might be as high as 70%. For initial transplant-eligible (within MC) patients with recurrent HCC post LR, salvage liver transplant (SLT) was first proposed in 2000. However, most patients with recurrent HCC considered for SLT are untransplantable cases due to HCC recurrence beyond MC or comorbidity. Thus, the strategy of opting for SLT results in the loss of the opportunity of LT for these patients. Some authors proposed the concept of “de principe liver transplant” (i.e., prophylactic LT before HCC recurrence) to prevent losing the chance of LT for these potential candidates. Factors associated with the failure of SLT will be dissected and discussed in three parts: Patient, tumor, and underlying liver disease. Regarding patient-related factors, the rate of transplantability depends on patient compliance. Patients without regular follow-up tend to develop HCC recurrence beyond MC at the time of tumor detection. Advancing age is another factor related to severe comorbidities when LT is considered for HCC recurrence, and these elderly candidates become ineligible as time goes by. Regarding tumor-related factors, histopathological features of the resected specimen are used mostly for determining the prognosis of early HCC recurrences. Such prognostic factors include the presence of microvascular invasion, poor tumor differentiation, the presence of microsatellites, the presence of multiple tumors, and the presence of the gene-expressing signature associated with aggressive HCC. These prognostic factors might be used as a selection tool for SLT or prophylactic LT, while remaining mindful of the fact that most of them are also prognostic factors for post-transplant HCC recurrence. Regarding underlying liver disease-related factors, progression of chronic viral hepatitis and high viral load may contribute to the development of late (de novo) HCC recurrence as a consequence of sustained inflammatory reaction. However, correlation between the severity of liver fibrosis and tumor recurrence is still controversial. Some prognostic scoring systems that integrate these three factors have been proposed to predict recurrence pattern...

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“… 1 Despite a variety of therapeutic approaches have been improving in recent years, the survival of HCC patients is still poor due to recurrence and metastasis. 2 Thus, the identification of new therapeutic strategies and molecular targets for the treatment of HCC is critical.…”

A SOX9‐AS1/miR‐5590‐3p/SOX9 positive feedback loop drives tumor growth and metastasis in hepatocellular carcinoma through the Wnt/β‐catenin pathway

“…Hepatocellular carcinoma (HCC) is a solid tumor prevalent around the globe and is recognized as the second leading cause of tumor-associated mortality in China (Thomas et al, 2010). Although the therapeutic strategies for HCC have been upgraded, the 5-year survival rate in HCC patients is still dismal, owing to a major extent to the high recurrence rate and easy metastasis following surgical dissection (Aldrighetti et al, 2009;Yang et al, 2016). Therefore, a better understanding of the molecular mechanism related to HCC progression and metastasis is needed.…”

Interaction between the tumor microenvironment and resection margin in different gross types of hepatocellular carcinoma

“…12,13 Recently, tumor biology has emerged as an important factor for prognosis, especially in liver transplantation. 14 Numerous factors that could represent tumor biology were investigated including tumor markers, stemness markers, and positron emission tomography results. [12][13][14] HCC that showed positivity for these factors tended to have aggressive pathologic characteristics and showed poor surgical outcomes.…”

“…14 Numerous factors that could represent tumor biology were investigated including tumor markers, stemness markers, and positron emission tomography results. [12][13][14] HCC that showed positivity for these factors tended to have aggressive pathologic characteristics and showed poor surgical outcomes. Many investigators tried to determine the reason for this difference by examining the tumor microenvironment (TME).…”