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Liver Transplantation and Hepatocellular Carcinoma

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A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: closed (30 November 2021) | Viewed by 11450

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Special Issue Editor

Prof. Dr. Yasutsugu Takada

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Guest Editor

Ehime University Hospital, Toon, Japan
Interests: Liver transplantation; Hepatocellular carcinoma

Special Issue Information

Dear colleagues,

Liver transplantation (LT) has become widely accepted as the treatment of choice for early hepatocellular carcinoma (HCC). Among appropriately selected candidates, both deceased donor LT (DDLT) and living donor LT (LDLT) provide excellent results, with overall survival rates exceeding 70%. The Milan criterion (MC), that is, “a single tumor no larger than 5 cm in diameter, or with no more than 3 tumors all no larger than 3 cm in diameter” , has been accepted as an effective way of selecting patients with early-stage HCC for curative LT.

Recently, attempting to afford the chance of cure to patients outside MC, many centers have performed LT using extended criteria beyond MC. However, the expansion of criteria naturally contains a risk of increased post-transplant recurrence. The issue of concern is thus how to preoperatively identify categories beyond MC that still offer predictably good outcomes. At present, it is considered that additional parameters for tumor biological features related to risk of recurrence are necessary. However, optimal selection criteria still remain to be determined.

Another issue is the effect of pre-transplant treatment on transplant outcomes. In DDLT, locoregional therapies such as hepatic resection, RFA, and TACE are usually indicated as a bridging procedure to prevent dropout from the waiting list due to tumor progression. Such therapies are also indicated as downstaging procedures to treat patients with advanced HCC who initially exceed the criteria for LT. In some countries where donor organ shortage is critical, patients with HCC and preserved liver function are initially treated by locoregional therapies, with LDLT held in reserve as a second-line option.

This Special Issue will highlight the present state of LT for HCC, including optimal selection criteria and the significance of pre-transplant treatment.

Prof. Dr. Yasutsugu Takada
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

Liver transplantation
Hepatocellular carcinoma
Locoregional therapies
Hepatic resection
RFA
TACE
Optimal Selection Criteria
Pre-transplant treatment

Published Papers (5 papers)

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Research

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10 pages, 1335 KiB

Open AccessArticle

Patients Benefit from Liver Transplantation for Hepatocellular Carcinoma beyond Milan Criteria without Harming the Health Care System

by Jan-Paul Gundlach, Michael Linecker, Henrike Dobbermann, Felix Wadle, Thomas Becker and Felix Braun

Cancers 2022, 14(5), 1136; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14051136 - 23 Feb 2022

Cited by 1 | Viewed by 1142

Abstract

Liver transplantation (LT) is the only definitive treatment to cure hepatocellular carcinoma (HCC) in cirrhosis. Waiting-list candidates are selected by the model for end-stage liver disease (MELD). However, many indications are not sufficiently represented by labMELD. For HCC, patients are selected by Milan-criteria: Milan-in qualifies for standard exception (SE) and better organ access on the waiting list; while Milan-out patients are restricted to labMELD and might benefit from extended criteria donor (ECD)-grafts. We analyzed a cohort of 102 patients (2011–2020). Patients with labMELD (no SE, Milan-out, n = 56) and matchMELD (SE-HCC, Milan-in, n = 46) were compared. The median overall survival was not significantly different (p = 0.759). No difference was found in time on the waiting list (p = 0.881), donor risk index (p = 0.697) or median costs (p = 0.204, EUR 43,500 (EUR 17,800–185,000) for labMELD and EUR 30,300 (EUR 17,200–395,900) for matchMELD). Costs were triggered by a cut-off labMELD of 12 points. Overall, the deficit increased by EUR 580 per labMELD point. Cost drivers were re-operation (p < 0.001), infection with multiresistant germs (p = 0.020), dialysis (p = 0.017), operation time (p = 0.012) and transfusions (p < 0.001). In conclusion, this study demonstrates that LT for HCC is successful and cost-effective in low labMELD patients independent of Milan-criteria. Therefore, ECD-grafts are favorized in Milan-out HCC patients with low labMELD. Full article

(This article belongs to the Special Issue Liver Transplantation and Hepatocellular Carcinoma)

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14 pages, 838 KiB

Open AccessArticle

Postoperative Trends and Prognostic Values of Inflammatory and Nutritional Biomarkers after Liver Transplantation for Hepatocellular Carcinoma

by Riccardo Pravisani, Federico Mocchegiani, Miriam Isola, Dario Lorenzin, Gian Luigi Adani, Vittorio Cherchi, Maria De Martino, Andrea Risaliti, Quirino Lai, Marco Vivarelli and Umberto Baccarani

Cancers 2021, 13(3), 513; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13030513 - 29 Jan 2021

Cited by 16 | Viewed by 1883

Abstract

Preoperative inflammatory biomarkers such as the Platelet-to-Lymphocyte Ratio (PLR) and the Neutrophil-to-Lymphocyte Ratio (NLR) strongly predict the outcome in surgically treated patients with hepatocellular carcinoma (HCC), while nutritional biomarkers such as the Controlling Nutritional Status (CONUT) and the Prognostic Nutritional Index (PNI) show an analogue prognostic value in hepatic resection (HR) but not in liver transplant (LT) cases. Data on the impact of LT on the inflammatory and nutritional/metabolic function are heterogeneous. Therefore, we investigated the post-LT trend of these biomarkers up to postoperative month (POM) 12 in 324 HCC patients treated with LT. Inflammatory biomarkers peaked in the early post-LT period but at POM 3 leveled off at values similar (NLR) or higher (PLR) than pre-LT ones. CONUT and PNI worsened in the early post-LT period, but at POM 3 they stabilized at significantly better values than pre-LT. In LT recipients with an overall survival >1 year and no evidence of early HCC recurrence, 1 year post-LT NLR and PNI independently predicted patient overall survival, while 1 year post-LT PLR independently predicted late tumor recurrence. In conclusion, at 1 year post-LT, the nutritional status of liver-transplanted HCC patients significantly improved while their inflammatory state tended to persist. Consequently, post-LT PLR and NLR maintained a prognostic value for LT outcome while post-LT CONUT and PNI acquired it. Full article

(This article belongs to the Special Issue Liver Transplantation and Hepatocellular Carcinoma)

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Review

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23 pages, 374 KiB

Open AccessReview

Liver Transplantation for Hepatocellular Carcinoma: How Should We Improve the Thresholds?

by Tsuyoshi Shimamura, Ryoichi Goto, Masaaki Watanabe, Norio Kawamura and Yasutsugu Takada

Cancers 2022, 14(2), 419; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14020419 - 14 Jan 2022

Cited by 11 | Viewed by 2833

Abstract

Hepatocellular carcinoma (HCC) is the third highest cause of cancer-related mortality, and liver transplantation is the ideal treatment for this disease. The Milan criteria provided the opportunity for HCC patients to undergo LT with favorable outcomes and have been the international gold standard and benchmark. With the accumulation of data, however, the Milan criteria are not regarded as too restrictive. After the implementation of the Milan criteria, many extended criteria have been proposed, which increases the limitations regarding the morphological tumor burden, and incorporates the tumor’s biological behavior using surrogate markers. The paradigm for the patient selection for LT appears to be shifting from morphologic criteria to a combination of biologic, histologic, and morphologic criteria, and to the establishment of a model for predicting post-transplant recurrence and outcomes. This review article aims to characterize the various patient selection criteria for LT, with reference to several surrogate markers for the biological behavior of HCC (e.g., AFP, PIVKA-II, NLR, 18F-FDG PET/CT, liquid biopsy), and the response to locoregional therapy. Furthermore, the allocation rules in each country and the present evidence on the role of down-staging large tumors are addressed. Full article

(This article belongs to the Special Issue Liver Transplantation and Hepatocellular Carcinoma)

17 pages, 336 KiB

Open AccessReview

Role of Pretransplant Treatments for Patients with Hepatocellular Carcinoma Waiting for Liver Transplantation

by Kohei Ogawa and Yasutsugu Takada

Cancers 2022, 14(2), 396; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14020396 - 13 Jan 2022

Cited by 4 | Viewed by 1802

Abstract

Recently, there have been many reports of the usefulness of locoregional therapy such as transarterial chemoembolization and radiofrequency ablation for hepatocellular carcinoma (HCC) as pretreatment before liver transplantation (LT). Locoregional therapy is performed with curative intent in Japan, where living donor LT constitutes the majority of LT due to the critical shortage of deceased donors. However, in Western countries, where deceased donor LT is the main procedure, LT is indicated for early-stage HCC regardless of liver functional reserve, and locoregional therapy is used for bridging until transplantation to prevent drop-outs from the waiting list or for downstaging to treat patients with advanced HCC who initially exceed the criteria for LT. There are many reports of the effect of bridging and downstaging locoregional therapy before LT, and its indications and efficacy are becoming clear. Responses to locoregional therapy, such as changes in tumor markers, the avidity of FDG-PET, etc., are considered useful for successful bridging and downstaging. In this review, the effects of bridging and downstaging locoregional therapy as a pretransplant treatment on the results of transplantation are clarified, focusing on recent reports. Full article

(This article belongs to the Special Issue Liver Transplantation and Hepatocellular Carcinoma)

13 pages, 1881 KiB

Open AccessReview

An Update on Hepatocellular Carcinoma in Chronic Kidney Disease

by Fabrizio Fabrizi, Roberta Cerutti, Carlo M. Alfieri and Ezequiel Ridruejo

Cancers 2021, 13(14), 3617; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13143617 - 20 Jul 2021

Cited by 8 | Viewed by 2874

Abstract

Chronic kidney disease is a major public health issue globally and the risk of cancer (including HCC) is greater in patients on long-term dialysis and kidney transplant compared with the general population. According to an international study on 831,804 patients on long-term dialysis, the standardized incidence ratio for liver cancer was 1.2 (95% CI, 1.0–1.4) and 1.5 (95% CI, 1.3–1.7) in European and USA cohorts, respectively. It appears that important predictors of HCC in dialysis population are hepatotropic viruses (HBV and HCV) and cirrhosis. 1-, 3-, and 5-year survival rates are lower in HCC patients on long-term dialysis than those with HCC and intact kidneys. NAFLD is a metabolic disease with increasing prevalence worldwide and recent evidence shows that it is an important cause of liver-related and extra liver-related diseases (including HCC and CKD, respectively). Some longitudinal studies have shown that patients with chronic hepatitis B are aging and the frequency of comorbidities (such as HCC and CKD) is increasing over time in these patients; it has been suggested to connect these patients to an appropriate care earlier. Antiviral therapy of HBV and HCV plays a pivotal role in the management of HCC in CKD and some combinations of DAAs (elbasvir/grazoprevir, glecaprevir/pibrentasvir, sofosbuvir-based regimens) are now available for HCV positive patients and advanced chronic kidney disease. The interventional management of HCC includes liver resection. Some ablative techniques have been suggested for HCC in CKD patients who are not appropriate candidates to surgery. Transcatheter arterial chemoembolization has been proposed for HCC in patients who are not candidates to liver surgery due to comorbidities. The gold standard for early-stage HCC in patients with chronic liver disease and/or cirrhosis is still liver transplant. Full article

(This article belongs to the Special Issue Liver Transplantation and Hepatocellular Carcinoma)

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