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Cancers
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Assessing and Influencing Prognosis in Hepatocellular Carcinoma
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Assessing and Influencing Prognosis in Hepatocellular Carcinoma

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

Deadline for manuscript submissions: closed (31 May 2022) | Viewed by 8773

Special Issue Editor

Prof. Dr. Xavier Verhelst

E-Mail Website
Guest Editor
Ghent University Hospital, Department of Gastroenterology and Hepatology, Corneel Heymanslaan 10 – route 1241, B9000 Ghent, Belgium
Interests: hepatology; liver transplantation; hepatocellular carcinoma; precision medicine; glycomics; glycobiology; glycan; biomarker

Special Issue Information

Dear Colleagues,

Hepatocellular carcinoma (HCC) is a challenging disease to deal with. Patients are often diagnosed in advanced stages and, in these patients, therapeutic options are often limited to disease control rather than curative treatment. However, this group of patients is heterogeneous; hence, there is a need for better prognostication. First of all, this could allow medical professionals to provide better information to patients and this could support a better selection of the appropriate treatment for every single patient.

This evolution towards precision medicine is developing rapidly in all fields of medicine, as it is in HCC. This Special Issue will be entitled “Assessing and Influencing Prognosis in Hepatocellular Carcinoma” and will cover clinical and translational aspects. Indeed, this issue should provide a comprehensive overview of established or potential prognostic biomarkers in HCC. Review manuscripts of original scientific content will be included. This will be combined with manuscripts dealing with more fundamental aspects that can shed light on the heterogeneity of disease progression and could provide mechanistic clues as regards disease progression.

Prof. Dr. Xavier Verhelst
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

  • HCC
  • biomarker
  • prognosis
  • precision medicine
  • omics
  • mechanisms of tumor development

Published Papers (4 papers)

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Research

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12 pages, 1078 KiB  
Article
Statins Reduce Hepatocellular Carcinoma Risk in Patients with Chronic Kidney Disease and End-Stage Renal Disease: A 17-Year Longitudinal Study
by Fung-Chang Sung, Yi-Ting Yeh, Chih-Hsin Muo, Chih-Cheng Hsu, Wen-Chen Tsai and Yueh-Han Hsu
Cancers 2022, 14(3), 825; https://doi.org/10.3390/cancers14030825 - 06 Feb 2022
Cited by 7 | Viewed by 2018
Abstract
Hepatocellular carcinoma (HCC) is the most common cancer in end-stage renal disease (ESRD) patients in Taiwan. Whether statin therapy associated with the HCC risk in hyperlipidemic patients with chronic kidney disease (CKD) and ESRD is unclear. Using population-based insurance claim data from Taiwan, [...] Read more.
Hepatocellular carcinoma (HCC) is the most common cancer in end-stage renal disease (ESRD) patients in Taiwan. Whether statin therapy associated with the HCC risk in hyperlipidemic patients with chronic kidney disease (CKD) and ESRD is unclear. Using population-based insurance claim data from Taiwan, we identified from hyperlipidemic patients taking statins or not (677,364 versus 867,707) in 1999–2015. Among them, three pairs of propensity score matched statin and non-statin cohorts were established by renal function: 413,867 pairs with normal renal function (NRF), 46,851 pairs with CKD and 6372 pairs with ESRD. Incidence rates of HCC were compared, by the end of 2016, between statin and non-statin cohorts, between hydrophilic statins (HS) and lipophilic statins (LS) users, and between statin-ezetimibe combination therapy (SECT) and statin monotherapy (SM) users. The HCC incidence increased progressively from NRF to CKD and ESRD groups, was lower in the statin cohort than in the non-statin cohort, with the differences of incidence per 10,000 person-years increased from (7.77 vs. 21.4) in NRF group to (15.8 vs. 37.1) in CKD group to (19.1 vs. 47.8) in ESRD group. The incidence increased with age, but the Cox method estimated hazard ratios showed a greater statin effectiveness in older patients. Among statin users, the HCC incidence was lower in HS users than in LS users, and lower in SECT users than in SM users, but the difference was significant only in the NRF group. Hyperlipidemic patients with CKD and ESRD receiving statins are at reduced HCC risks; the treatment effectiveness is superior for HS users than for LS users, and for SECT users than for SM users, but not significant. Full article
(This article belongs to the Special Issue Assessing and Influencing Prognosis in Hepatocellular Carcinoma)
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14 pages, 3926 KiB  
Article
Immunonutritive Scoring for Patients with Hepatocellular Carcinoma Undergoing Transarterial Chemoembolization: Evaluation of the CALLY Index
by Lukas Müller, Felix Hahn, Aline Mähringer-Kunz, Fabian Stoehr, Simon Johannes Gairing, Maurice Michel, Friedrich Foerster, Arndt Weinmann, Peter Robert Galle, Jens Mittler, Daniel Pinto dos Santos, Michael Bernhard Pitton, Christoph Düber and Roman Kloeckner
Cancers 2021, 13(19), 5018; https://doi.org/10.3390/cancers13195018 - 07 Oct 2021
Cited by 16 | Viewed by 2084
Abstract
The novel CRP–albumin–lymphocyte (CALLY) index is an improved immunonutritive scoring system, based on serum C-reactive protein (CRP), serum albumin, and the lymphocyte count. It has shown promise as a prognostic index for patients with hepatocellular carcinoma (HCC) undergoing resections. This study evaluated the [...] Read more.
The novel CRP–albumin–lymphocyte (CALLY) index is an improved immunonutritive scoring system, based on serum C-reactive protein (CRP), serum albumin, and the lymphocyte count. It has shown promise as a prognostic index for patients with hepatocellular carcinoma (HCC) undergoing resections. This study evaluated the prognostic ability of the CALLY index for patients with HCC undergoing transarterial chemoembolization (TACE). We retrospectively identified 280 treatment-naïve patients with HCC that underwent an initial TACE at our institution, between 2010 and 2020. We compared the CALLY index to established risk factors in univariate and multivariate regression analyses for associations with median overall survival (OS). A low CALLY score was associated with low median OS (low vs. high CALLY: 9.0 vs. 24.0 months, p < 0.001). In the multivariate analysis, the CALLY index remained an independent prognostic predictor (p = 0.008). Furthermore, all factors of the CALLY index reached significance in univariate and in-depth multivariate analyses. However, the concordance index (C-index) of the CALLY index (0.60) was similar to the C-indices of established immunonutritive and inflammation scoring systems (range: 0.54 to 0.63). In conclusion, the CALLY index showed promise as a stratification tool for patients with HCC undergoing TACE. Notably, the CALLY index was not superior to other immunonutritive and inflammation scoring systems in predicting the median OS. Thus, future studies should re-evaluate the mathematical calculation of the index, particularly the contributions of individual parameters. Full article
(This article belongs to the Special Issue Assessing and Influencing Prognosis in Hepatocellular Carcinoma)
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16 pages, 4464 KiB  
Article
Expression of Cancer Testis Antigens in Tumor-Adjacent Normal Liver Is Associated with Post-Resection Recurrence of Hepatocellular Carcinoma
by Lisanne Noordam, Zhouhong Ge, Hadiye Özturk, Michail Doukas, Shanta Mancham, Patrick P. C. Boor, Lucia Campos Carrascosa, Guoying Zhou, Thierry P. P. van den Bosch, Qiuwei Pan, Jan N. M. IJzermans, Marco J. Bruno, Dave Sprengers and Jaap Kwekkeboom
Cancers 2021, 13(10), 2499; https://doi.org/10.3390/cancers13102499 - 20 May 2021
Cited by 5 | Viewed by 2399
Abstract
High recurrence rates after resection of hepatocellular carcinoma (HCC) with curative intent impair clinical outcomes of HCC. Cancer/testis antigens (CTAs) are suitable targets for cancer immunotherapy if selectively expressed in tumor cells. The aims were to identify CTAs that are frequently and selectively [...] Read more.
High recurrence rates after resection of hepatocellular carcinoma (HCC) with curative intent impair clinical outcomes of HCC. Cancer/testis antigens (CTAs) are suitable targets for cancer immunotherapy if selectively expressed in tumor cells. The aims were to identify CTAs that are frequently and selectively expressed in HCC-tumors, and to investigate whether CTAs could serve as biomarkers for occult metastasis. Tumor and paired tumor-free liver (TFL) tissues of HCC-patients and healthy tissues were assessed for mRNA expression of 49 CTAs by RT-qPCR and protein expression of five CTAs by immunohistochemistry. Twelve CTA-mRNAs were expressed in ≥10% of HCC-tumors and not in healthy tissues except testis. In tumors, mRNA and protein of ≥ 1 CTA was expressed in 78% and 71% of HCC-patients, respectively. In TFL, CTA mRNA and protein was found in 45% and 30% of HCC-patients, respectively. Interestingly, CTA-expression in TFL was an independent negative prognostic factor for post-resection HCC-recurrence and survival. We established a panel of 12 testis-restricted CTAs expressed in tumors of most HCC-patients. The increased risk of HCC-recurrence in patients with CTA expression in TFL, suggests that CTA-expressing (pre-)malignant cells may be a source of HCC-recurrence, reflecting the relevance of targeting these to prevent HCC-recurrence. Full article
(This article belongs to the Special Issue Assessing and Influencing Prognosis in Hepatocellular Carcinoma)
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Review

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12 pages, 265 KiB  
Review
Different Models to Predict the Risk of Recurrent Hepatocellular Carcinoma in the Setting of Liver Transplantation
by Helena Degroote, Anja Geerts, Xavier Verhelst and Hans Van Vlierberghe
Cancers 2022, 14(12), 2973; https://doi.org/10.3390/cancers14122973 - 16 Jun 2022
Cited by 3 | Viewed by 1618
Abstract
Liver transplantation is the preferred therapeutic option for non-resectable hepatocellular carcinoma in early-stage disease. Taking into account the limited number of donor organs, liver transplantation is restricted to candidates with long-term outcomes comparable to benign indications on the waiting list. Introducing the morphometric [...] Read more.
Liver transplantation is the preferred therapeutic option for non-resectable hepatocellular carcinoma in early-stage disease. Taking into account the limited number of donor organs, liver transplantation is restricted to candidates with long-term outcomes comparable to benign indications on the waiting list. Introducing the morphometric Milan criteria as the gold standard for transplant eligibility reduced the recurrence rate. Even with strict patient selection, there is a risk of recurrence of between 8 and 20% in the transplanted liver, and this is of even greater importance when using more expanded criteria and downstaging protocols. Currently, it remains challenging to predict the risk of recurrence and the related prognosis for individual patients. In this review, the recurrence-risk-assessment scores proposed in the literature are discussed. Currently there is no consensus on the optimal model or the implications of risk stratification in clinical practice. The most recent scorings include additional biological markers for tumour behavior, such as alfa-foetoprotein, and the response to locoregional therapies, in addition to the number and diameter of tumoral nodules. The refinement of the prediction of recurrence is important to better inform patients, guide decisions about prioritization and listing and implement individualized surveillance strategies. In the future, this might also provide indications for tailored immunosuppressive therapy or inclusion in trials for adjuvant treatment. Full article
(This article belongs to the Special Issue Assessing and Influencing Prognosis in Hepatocellular Carcinoma)
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