Evolving thresholds for liver transplantation in hepatocellular carcinoma: A Western experience

Ju, Michelle R.; Yopp, Adam C.

doi:10.1002/ags3.12316

Cited by 14 publications

(8 citation statements)

References 49 publications

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“…However, the global trend of HCC recurrence seemed to be decreasing with time when a meta-regression was conducted on the year of study completion (β = −0.0015, SE: 0.002, p = 0.434, Figure 3 ). Recent improvements in the prevalence of HCC recurrence may be attributed to novel immunosuppressant strategies, including the use of mTOR inhibitors such as sirolimus and everolimus [ 28 , 29 ], and improved patient selection with stringent criteria [ 30 ]. Adherence to MC was a significant factor, with patients beyond MC experiencing HCC recurrence more frequently when compared to those within MC, which corroborated with previously existing meta-analyses [ 31 ].…”

Section: Discussionmentioning

confidence: 99%

A Meta-Analysis on the Rate of Hepatocellular Carcinoma Recurrence after Liver Transplant and Associations to Etiology, Alpha-Fetoprotein, Income and Ethnicity

Tan

Wong

et al. 2021

JCM

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Hepatocellular carcinoma (HCC) recurrence after liver transplant is associated with a poor prognosis and significantly increases morbidity and mortality among liver transplant patients. Therefore, this meta-analysis aims to evaluate the overall prevalence of HCC recurrence following liver transplant. Medline and Embase databases were searched, and a meta-analysis of proportions was conducted. Observational studies reporting the prevalence of recurrent hepatocellular carcinoma (HCC) after liver transplant were included, with the analysis being stratified by adherence to Milan criteria, ethnicity, socio-economic status, alpha fetoprotein (AFP) levels, living donor vs. deceased donor, and the underlying aetiology of the liver disease. A meta-regression on the date of the study completion was also performed. Of a total 40,495 patients, 3888 developed an HCC recurrence. The overall prevalence of recurrent HCC was 13% (CI: 0.12–0.15). Patients beyond the Milan criteria (MC) were more likely to recur than patients within MC. Asian populations had the greatest prevalence of HCC recurrence (19%; CI: 0.15–0.24) when compared to Western (12%; CI: 0.11–0.13) and Latin American populations (11%; CI: 0.09–0.14). The prevalence of recurrent HCC was the highest in patients infected with hepatitis B virus (HBV) (18%; CI: 0.11–0.27) compared to other aetiologies. A higher AFP also resulted in an increased recurrence. This highlights interesting differences based on ethnicity, income, and aetiology, and further studies are needed to determine the reasons for the disparity.

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Section: Discussionmentioning

confidence: 99%

A Meta-Analysis on the Rate of Hepatocellular Carcinoma Recurrence after Liver Transplant and Associations to Etiology, Alpha-Fetoprotein, Income and Ethnicity

Tan

Wong

et al. 2021

JCM

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“…As there has been a trend in performing curative resections for the larger HCC lesions to render patients disease-free, likewise the selection criteria for LT are mounting the extent to include more HCC patients for curative intent. 174 , 175 One of the studies (Bruix and colleagues) proposed that LT for HCC be performed when 5 years expected patient’s survival is more than 50%. 176 When LT is being considered for patients outside the Milan Criteria it should be considered only when 5 years expected survival is no less than 61% (Volk et al).…”

Section: Transplantationmentioning

confidence: 99%

Portal Vein Tumor Thrombosis and Hepatocellular Carcinoma – The Changing Tides

Khan¹,

Wei²,

Xu³

2021

JHC

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Portal vein involvement is considered one of the most fearful complications of hepatocellular carcinoma (HCC). Portal vein tumor thrombosis (PVTT) is associated with aggressive tumor biology (high grade), high tumor burden (number and size of lesions), high levels of serum markers (AFP), poor liver function (deranged LFT), and poor performance status of patients. The Barcelona Clinic Liver Cancer staging system places HCC patients with PVTT in advanced stage (BCLC Stage-C). This group contains a fairly heterogeneous patient population, previously considered candidates for palliative systemic therapy with sorafenib. However, this provided modest overall survival (OS) benefit. The results of a recent Phase III (IMbrave150) trial favor the combination of atezolizumab and bevacizumab over sorafenib as a standard of care in advanced unresectable HCC. While only lenvatinib proved to be non-inferior against sorafenib in a phase III (REFLECT trial), regorafenib (RESORCE trial), ramucirumab (REACH-2), and cabozantinib (CELESTIAL) have been approved second-line therapy in phase III clinical trials. Recently, the data on the prospect of other modalities in the management of HCC with PVTT is mounting with favorable results. Targeting multiple pathways in the HCC cascade using a combination of drugs and other modalities such as RT, TACE, TARE, and HAIC appear effective for systemic and loco-regional control. The quest for the ideal combination therapy and the sequence set is still widely unanswered and prospective trials are lacking. With the armament of available therapeutic options and the advances and refinements in the delivery system, down-staging patients to make them eligible for curative resection has been reported. In a rapidly evolving treatment landscape, performing surgery when appropriate, in the form of LR and even LT to achieve cure does not seem farfetched. Likewise, adjuvant therapy and prompt management of the recurrences holds the key to prolong OS and DFS. This review discusses the management options of HCC patients with PVTT.

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“…However, tumor recurrence after transplant could still happen, especially in patients who have tumors beyond the Shanghai Fudan criteria. In China, more HCCs are diagnosed at advanced stage and some patients receive salvage LT; even in western world, the post-Milan-criteria era has witnessed the growing experience with downstage of tumor via locoregional therapies to become a candidate for transplantation 12 , 13 . These patients are generally at relatively high risk of tumor recurrence after LT.…”

Section: Discussionmentioning

confidence: 99%

Plasma MicroRNA Panel Predicts Early Tumor Recurrence in Patients with Hepatocellular Carcinoma after Liver Transplantation

Huang¹,

Guo²,

Wang³

et al. 2021

J. Cancer

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Background: This study aimed to evaluate the role of plasma microRNA panel (miR-122, miR-192, miR-21, miR-223, miR-26a, miR-27a and miR-801) for prediction and surveillance of early tumor recurrence in hepatocellular carcinoma (HCC) patients who had undergone liver transplantation (LT). Methods: The expression of plasma microRNA panel was assayed in 193 HCC patients (training cohort, n =151; validation cohort, n = 42). Sensitivity and specificity for detecting post-transplant HCC recurrence, and the relationship of microRNA panel expression with clinical characteristics were analyzed accordingly. The prognostic value of microRNA panel was compared with that of AFP (alpha-fetoprotein) and DCP (Des-gamma-carboxyprothrombin). Cox regression analyses were used to evaluate independent prognostic factors. Results: In the training cohort, the rate of positive plasma microRNA panel status at 7-14 days after LT (late phase; 44.2%) decreased than that before (76.2%, P < 0.001) and 1-6 days after LT (early phase; 78.5%, P < 0.001). At late phase, positive microRNA panel status correlated with higher early tumor recurrence rate (one year after LT) than negative status (45.9% vs 10.7%; P < 0.001). Patients with persistent positive microRNA panel status both before and after LT had the highest early tumor recurrence rate in this cohort (54.9%, P < 0.001). The results were consistent in the validation cohort. Cox regression analysis found that positive plasma microRNA panel status at late phase was the only independent risk factor for early recurrence (HR: 4.903, 95% CI = 2.195 - 10.951; P < 0.001). Dynamic monitoring demonstrated plasma microRNA panel status changed from negative to positive earlier than AFP and DCP upon recurrence, and the median time between positivity of plasma microRNA and imaging evidence of recurrence was 2.4 (0.5-10.0) months. Conclusions: Plasma microRNA panel could be a noninvasive biomarker for prediction and surveillance of early tumor recurrence in HCC patients who have undergone LT.

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Evolving thresholds for liver transplantation in hepatocellular carcinoma: A Western experience

Cited by 14 publications

References 49 publications

A Meta-Analysis on the Rate of Hepatocellular Carcinoma Recurrence after Liver Transplant and Associations to Etiology, Alpha-Fetoprotein, Income and Ethnicity

A Meta-Analysis on the Rate of Hepatocellular Carcinoma Recurrence after Liver Transplant and Associations to Etiology, Alpha-Fetoprotein, Income and Ethnicity

Portal Vein Tumor Thrombosis and Hepatocellular Carcinoma – The Changing Tides

Plasma MicroRNA Panel Predicts Early Tumor Recurrence in Patients with Hepatocellular Carcinoma after Liver Transplantation

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