Predictors of survival after liver transplantation for hepatocellular carcinoma associated with Hepatitis C

Shimoda, Mitsugi; Ghobrial, Rafik M.; Carmody, Ian C.; Anselmo, Dean M.; Farmer, Douglas G.; Yersiz, Hasan; Chen, Pauline; Dawson, Sherfield; Durazo, Francisco; Han, Steve; Goldstein, Leonard I.; Saab, Sammy; Hiatt, Jonathan R.; Busuttil, Ronald W.

doi:10.1002/lt.20303

Cited by 88 publications

(85 citation statements)

References 43 publications

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“…8,21,22 The risk of developing tumor recurrence is the main argument against expanding eligibility criteria. 13,23,24 In a recent metaanalysis of 74 studies by Germani and associates, the authors found that patients receiving LT beyond the Milan criteria have increased risk of recurrence and worse overall survival, which includes an increased risk of death if transplanted outside the Milan criteria, but within the more inclusive UCSF criteria. 25 Therefore, relaxing the tight parameters defined in the Milan criteria on pre-LT tumor size adversely affects post-LT outcomes.…”

Section: Pretransplant-prevention Of Hepatocellular Carcinoma Recurrementioning

confidence: 99%

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Management of Recurrent Hepatocellular Carcinoma in Liver Transplant Recipients: A Systematic Review

Rubin

Ayoub²,

Kaldas³

et al. 2012

Exp Clin Transplant

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Hepatocellular carcinoma is the most common form of liver cancer, representing 70% to 85% of primary hepatic malignancies in adults. Liver transplant is an optimal treatment for patients with hepatocellular carcinoma because it eliminates the malignancy as well as the oftenunderlying liver cirrhosis and restores normal liver function. Since the development of strict selection criteria in hepatocellular carcinoma patients undergoing liver transplant with the implementation of the Milan criteria, patient survival and recurrence rates after liver transplant have dramatically improved. However, several research groups are now seeking to expand this criteria to include more patients with larger tumors who may achieve similar postliver transplant survival rates as those patients meeting current eligibility requirements. Currently, in approximately 20% of patients, hepatocellular carcinoma recurrence is still the rate-limiting event that clearly affects patient survival.Given the limited number of grafts available for transplant, the poor prognosis of untreated hepatocellular carcinoma, and the recent notion of expanding selection criteria, strategies for reducing the rate of, monitoring and treating hepatocellular carcinoma recurrence, in both pretransplants and posttransplants, are explored in this review. We review the available literature to better understand current strategies available to optimize long-term clinical outcomes.

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Section: Pretransplant-prevention Of Hepatocellular Carcinoma Recurrementioning

confidence: 99%

“…Factors associated with tumor recurrence include tumor burden and vascular invasion. 4,5,7,9,[11][12][13][14][15][16][17] Recurrence tends to occur in 6.4% to 21.2% of patients 8,9,11,12 ( Table 1). The 5-year patient survival rate after HCC recurrence is only 22%.…”

Section: Introductionmentioning

confidence: 99%

Management of Recurrent Hepatocellular Carcinoma in Liver Transplant Recipients: A Systematic Review

Rubin

Ayoub²,

Kaldas³

et al. 2012

Exp Clin Transplant

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“…13,14 The persistence of HCV and the recurrence of hepatitis C are constant after LT, 15 resulting in accelerated progression toward fibrosis and impaired patient and allograft survival. 16,17 The mechanisms underlying accelerated liver fibrosis after LT are poorly understood.…”

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confidence: 99%

Interleukin-4 induces the activation and collagen production of cultured human intrahepatic fibroblasts via the STAT-6 pathway

Aoudjehane

Pissaia

Scatton

et al. 2008

Laboratory Investigation

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Interleukin-4 (IL-4) is overexpressed in liver grafts in a context of severe recurrent hepatitis C, during which the development of fibrosis is dramatically accelerated. In this study, we examined the effects of IL-4 on the activation and collagen production of cultured human intrahepatic (myo)fibroblasts (hIHFs), and investigated the underlying mechanisms. The myofibroblastic nature of cells was evaluated morphologically using activation markers (smooth muscle a-actin, vimentin and prolyl 4-hydroxylase). Quiescent hIHFs were obtained by cell incubation in serum-free medium or cell culture on Matrigel. We first analyzed IL-4 receptor expression, STAT-6 activation by IL-4, and STAT-6 inhibition by an anti-IL-4 antibody or by STAT-6 small-interfering RNA (siRNA) transfection. We then focused on collagen production, using quantitative real-time PCR to analyze the effect of IL-4 on the mRNA expression of collagens I, III and IV, and on collagen levels in supernatants of hIHFs, using the Sircol collagen assay. hIHFs cultured in plastic wells appeared to be morphologically activated. The expression of activation markers was reduced by serum deprivation or culture on Matrigel, and restored by IL-4 incubation. The IL-4 receptor was expressed by hIHFs, and STAT-6 was activated following incubation with IL-4. Both anti-IL-4 antibody and STAT-6 siRNA transfection inhibited this activation. The treatment of hIHFs with IL-4 increased the mRNA expression of collagens I, III and IV (Po0.05) and elevated collagen levels in supernatants (P ¼ 0.01 vs untreated cells). Therefore, IL-4 exerts profibrotic effects by activating hIHFs and inducing collagen production and secretion. This effect requires IL4-R binding and STAT-6 activation. IL-4 may thus be involved in accelerated course of fibrogenesis during recurrent hepatitis C.

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“…Chronic HCV hepatitis, chronic HBV infection, exposure to aflatoxins, tyrosinemia, exogenous hormone intake, and heavy alcohol use are important risk factors associated with the development of HCC. 3,4 Orthotopic liver transplant (OLT) remains the preferred curative modality for patients with cirrhosis and HCC because it removes the tumor and premalignant cirrhotic liver, which is the main risk factor for recurrence. Nonetheless, recurrence after OLT is occurring with growing evidence, and many reports suggest that the tumor biology of HCC (perhaps the most important predictor of HCC recurrence) can be highly variable.…”

Section: Introductionmentioning

confidence: 99%

Untitled

2015

Exp Clin Transplant

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Objectives: To identify the predictors of overall survival and tumor-free survival of 88 hepatocellular carcinoma patients who were treated with orthotopic liver transplant at Shiraz Organ Transplant Center. Metarials and Methods: We performed this retrospective study after reviewing the transplant database of all patients who underwent orthotopic liver transplant secondary to hepatocellular carcinoma and liver cirrhosis. Hepatocellular carcinoma was diagnosed in 70 patients before liver transplant and 18 patients on histologic examination of the explanted livers. Cox regression identified independent factors that affected posttransplant survival. Results: The overall survival rate was 83% and the tumor-free survival rate was 79.5%. Independent factors for tumor recurrence were Milan criteria, alpha-fetoprotein level before operation ≥ 400 ng/mL, tumor grade, vascular invasion, and age. Vascular invasion (odds ratio, 5; 95% confidence interval, 1.1 to 25.496; P = .049) and tumor grade (odds ratio, 14.42; 95% confidence interval, 3.652 to 56.95; P < .001 were statistically significant. Conclusions: Vascular invasion and tumor grade were predictive factors for tumor-free survival.

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Predictors of survival after liver transplantation for hepatocellular carcinoma associated with Hepatitis C

Cited by 88 publications

References 43 publications

Management of Recurrent Hepatocellular Carcinoma in Liver Transplant Recipients: A Systematic Review

Management of Recurrent Hepatocellular Carcinoma in Liver Transplant Recipients: A Systematic Review

Interleukin-4 induces the activation and collagen production of cultured human intrahepatic fibroblasts via the STAT-6 pathway

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