Hepatocellular carcinoma recurrence after acute liver allograft rejection treatment: A multicenter European experience

Lai, Quirino; Iesari, Samuele; Finkenstedt, Armin; Hoppe‐Lotichius, Maria; Foguenne, Maxime; Lehner, Konrad; Otto, Gerd; Lerut, Jan

doi:10.1016/j.hbpd.2019.05.006

Cited by 18 publications

(12 citation statements)

References 45 publications

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“…This is important to Lai et al recently reported for the first time on the association between higher overall incidence of HCC recurrence and treatment of AR with steroid boluses. 38 They hypothesized that the usage of steroid boluses to manage AR and exposure to longstanding immunosuppression after AR treatment promotes HCC recurrence. 38 Based on our descriptive data, we cannot confirm or exclude causal links of steroid pulse therapy in episodes of AR and the risk of tumor recurrence.…”

Section: Discussionmentioning

confidence: 99%

“…38 They hypothesized that the usage of steroid boluses to manage AR and exposure to longstanding immunosuppression after AR treatment promotes HCC recurrence. 38 Based on our descriptive data, we cannot confirm or exclude causal links of steroid pulse therapy in episodes of AR and the risk of tumor recurrence. Interestingly, 65% of their matched control group consisted of patients without occurrence of AR.…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, 65% of their matched control group consisted of patients without occurrence of AR. 38 Therefore, their hypothesis is not controversial to our assumption that AR itself as inflammatory immune response could be triggering oncogenesis. Nonetheless, our findings seem to elucidate possible links between modulating immune responses and HCC recurrence after LT.…”

Section: Discussionmentioning

confidence: 99%

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Recurrence of Hepatocellular Carcinoma After Liver Transplantation is Associated with Episodes of Acute Rejections

Gül‐Klein

Kästner

Haber

et al. 2021

JHC

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The impact of acute rejection (AR) after liver transplantation (LT) for hepatocellular carcinoma (HCC) on patient outcome is uncertain. This aim of this study is to investigate whether AR is associated with HCC relapse and overall survival. Patients and Methods: Patients undergoing LT for HCC between 2001 and 2015 were retrospectively analyzed with regard to histopathological proven AR within the median time until recurrence. Cox's regression analysis was conducted revealing risk factors for HCC recurrence. Results: HCC recurred in 47 of 252 analyzed patients with a median time to recurrence of 20 months. Patients with AR (28.6%) had a significantly higher frequency of recurrence compared to patients without AR (13.0%, p=0.002). Multiple Cox regression analyses identified AR within 20 months to be an independent risk factor for HCC recurrence both as dichotomized (HR=2.91, 95%CI: 1.30-6.53; p=0.009) and as a continuous variable (HR=1.81, 95%CI: 1.28-2.54; p=0.001). HCC recurrence and AR were associated with higher grades of liver fibrosis one year after LT, when compared to patients without AR (p=0.019). Conclusion: Our results demonstrate an association of AR with HCC recurrence after LT with implications for intervals of monitoring in tumor surveillance. Graft fibrosis and immune mechanisms are potentially related and causal interactions are worth further investigation.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Recurrence of Hepatocellular Carcinoma After Liver Transplantation is Associated with Episodes of Acute Rejections

Gül‐Klein

Kästner

Haber

et al. 2021

JHC

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“…Gul-Klein et al found that recurrence was over twice as frequent in patients with a history of acute rejection incidents in comparison to patients without such incidents. Lai et al reported that the recurrence risk is 18 times higher in patients treated with steroid bolus in comparison to patients without rejection or without clinical manifestation of rejection who were not treated with steroids [ 112 , 113 ].…”

Section: Post-transplantation Risk Factorsmentioning

confidence: 99%

Recurrence of Hepatocellular Carcinoma After Liver Transplantation: Risk Factors and Predictive Models

et al. 2022

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Liver transplantation (LTx) is the best treatment for patients with early-stage hepatocellular carcinoma (HCC). The Milan criteria positively influenced results of liver transplantation and were adopted by the majority of cancer centers, becoming the criterion standard treatment for early-stage HCC. Despite the use of restrictive criteria, recurrence is still high, affecting between 8% and 20% of cases, and is a significant predictor of survival after LTx. The diagnosis of both micro-and macro-invasion of vessels, which are significant factors in determining the frequency of recurrence and overall survival, significantly decreases the success of transplantation, causing an increase in mortality of 50% in comparison to recipients with no vascular invasion. The risk of recurrence depends on several factors, which are discussed in this review. The authors also discuss the clinical presentation and treatment methods of recurrence and its prognosis. In addition, the role of different models developed to identify groups of patients with high versus low risk of recurrence is discussed, enabling the planning of recommendations and screening protocols after transplantation to help early diagnosis and guide effective treatment. In the era of an increasing numbers of liver transplants due to HCC, the need to create robust screening tools is urgent.

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“…Although LT is valid for treating end-stage liver disease, ACR remains a significant post-transplant complication [ 3 ]. ACR causes infection and cancer recurrence in recipients due to the increased use of immunosuppressants [ 4 ]. To avoid the increased use of immunosuppressive agents, accurate biomarkers are necessary to predict and identify the risk of ACR early [ 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

Identification of High-Mobility Group Box 1 (HMGB1) Expression as a Potential Predictor of Rejection and Poor Prognosis After Liver Transplantation

Zhou

Jia

et al. 2021

Ann Transplant

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Background Acute cellular rejection (ACR) frequently occurs after liver transplantation (LT) and can result in permanent damage of the liver allograft. Specific and sensitive biomarkers for predicting and monitoring ACR are vital for guiding post-transplantation care. In the present study, we aimed to investigate the function of high-mobility group box 1 (HMGB1) in predicting ACR and prognosis after LT. Material/Methods A total of 113 LT recipients were enrolled in the study, including 62 patients in an ACR group and 51 patients in a non-rejection group. Using tissues from the 113 patients, HMGB1 expression was examined by immunohistochemistry, and the total score for HMGB1 expression was calculated by multiplying the percentage of immunoreactive cells score and the staining intensity score. We then analyzed the association between HMGB1 expression and clinical features. Finally, the function of HMGB1 in predicting the prognosis of LT was determined using Kaplan-Meier (K-M) survival and Cox multivariate analyses. Results Immunohistochemical staining results demonstrated that the expression of HMGB1 was significantly increased in the ACR group, compared with that in the non-rejection group ( P <0.05). Clinical characteristic analysis revealed that high HMGB1 levels were related to ACR ( P <0.05). Moreover, K-M survival analysis showed that patients with high HMGB1 expression displayed poorer prognosis ( P <0.05). Cox multivariate analysis demonstrated that HMGB1 was an independent prognostic predictor for post-LT survival (odds ratio, 3.283; P =0.008). Conclusions LT recipients’ HMGB1 levels may be a useful and noninvasive biomarker for the prediction of ACR and prognosis after LT.

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Hepatocellular carcinoma recurrence after acute liver allograft rejection treatment: A multicenter European experience

Cited by 18 publications

References 45 publications

Recurrence of Hepatocellular Carcinoma After Liver Transplantation is Associated with Episodes of Acute Rejections

Recurrence of Hepatocellular Carcinoma After Liver Transplantation is Associated with Episodes of Acute Rejections

Recurrence of Hepatocellular Carcinoma After Liver Transplantation: Risk Factors and Predictive Models

Identification of High-Mobility Group Box 1 (HMGB1) Expression as a Potential Predictor of Rejection and Poor Prognosis After Liver Transplantation

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