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Cancers
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Advances in the Prevention and Treatment of Liver Cancer
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Advances in the Prevention and Treatment of Liver Cancer

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

Deadline for manuscript submissions: 30 June 2025 | Viewed by 13450

Special Issue Editor

Dr. Ewa Janczewska

E-Mail Website
Guest Editor
Department of Basic Medical Sciences, Faculty of Health Sciences in Bytom, Medical University of Silesia, 41-902 Bytom, Poland
Interests: liver cancer

Special Issue Information

Dear Colleagues,

Advances in the prevention and treatment of liver cancer have made significant strides in recent years. New screening techniques, such as enhanced imaging and biomarker tests, have improved early detection, allowing for timely intervention. Minimally invasive procedures, like radiofrequency ablation and transarterial chemoembolization, have become more effective alternatives to traditional surgery.

Innovations in targeted therapies and immunotherapies, like sorafenib and checkpoint inhibitors, have expanded treatment options for advanced cases. Personalized medicine approaches, guided by genetic profiling, help tailor treatments to individual patients, optimizing outcomes and reducing side effects.

Prevention efforts have emphasized the importance of reducing risk factors such as hepatitis B and C infections, excessive alcohol consumption, and obesity. Vaccination against hepatitis B has been a crucial tool in decreasing liver cancer incidence. Public health campaigns promoting lifestyle changes and regular screenings have contributed to better liver cancer outcomes globally.

Dr. Ewa Janczewska
Guest Editor

Manuscript Submission Information

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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

  • new screening techniques
  • enhanced imaging
  • biomarker tests
  • radiofrequency ablation
  • transarterial chemoembolization

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Published Papers (8 papers)

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Research

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17 pages, 3856 KiB  
Article
Image-Guided Stereotactic Body Radiotherapy (SBRT) with Enhanced Visualization of Tumor and Hepatic Parenchyma in Patients with Primary and Metastatic Liver Malignancies
by Alexander V. Kirichenko, Danny Lee, Patrick Wagner, Seungjong Oh, Hannah Lee, Daniel Pavord, Parisa Shamsesfandabadi, Allen Chen, Lorenzo Machado, Mark Bunker, Angela Sanguino, Chirag Shah and Tadahiro Uemura
Cancers 2025, 17(7), 1088; https://doi.org/10.3390/cancers17071088 - 25 Mar 2025
Viewed by 383
Abstract
Goal: This study evaluates the feasibility and outcome of a personalized MRI-based liver SBRT treatment planning platform with the SPION contrast agent Ferumoxytol® (Sandoz Inc.; Princeton, NJ, USA) to maintain a superior real-time visualization of liver tumors and volumes of functional hepatic [...] Read more.
Goal: This study evaluates the feasibility and outcome of a personalized MRI-based liver SBRT treatment planning platform with the SPION contrast agent Ferumoxytol® (Sandoz Inc.; Princeton, NJ, USA) to maintain a superior real-time visualization of liver tumors and volumes of functional hepatic parenchyma for radiotherapy planning throughout multi-fractionated liver SBRT with online plan adaptations on an Elekta Unity 1.5 T MR-Linac (Elekta; Stockholm, Sweden). Materials and Methods: Patients underwent SPION-enhanced MRI on the Elekta Unity MR-Linac for improved tumor and functional hepatic parenchyma visualization. An automated contouring algorithm was applied for the delineation and subsequent guided avoidance of functional liver parenchyma volumes (FLVs) on the SPION-enhanced MR-Linac. Radiation dose constraints were adapted exclusively to FLV. Local control, toxicity, and survival were assessed with at least 6-month radiographic follow-up. Pre- and post-transplant outcomes were analyzed in the subset of patients with HCC and hepatic cirrhosis who completed SBRT as a bridge to liver transplant. Model of End-Stage Liver Disease (MELD-Na) was used to score hepatic function before and after SBRT. Results: With a median follow-up of 23 months (range: 3–40 months), 23 HCC patients (26 lesions treated) and 9 patients (14 lesions treated) with hepatic metastases received SBRT (mean dose: 48 Gy, range: 36–54 Gy) in 1–5 fractions. Nearly all patients in this study had pe-existing liver conditions, including hepatic cirrhosis (23), prior TACE (7), prior SBRT (18), or history of hepatic resection (2). Compared to the non-contrast images, SPIONs improved tumor visibility on post-SPION images on the background of negatively enhancing functionally active hepatic parenchyma. Prolonged SPION-contrast retention within hepatic parenchyma enabled per-fraction treatment adaptation throughout the entire multi-fraction treatment course. FLV loss (53%, p < 0.0001) was observed in cirrhotic patients, but functional and anatomic liver volumes remained consistent in non-cirrhotic patients. Mean dose to FLV was maintained within the liver threshold tolerance to radiation in all patients after the optimization of Step-and-Shoot Intensity-Modulated Radiotherapy (SS-IMRT) on the SPION-enhanced MRI-Linac. No radiation-induced liver disease was observed within 6 months post-SBRT, and the MELD-Na score in cirrhotic patients was not significantly elevated at 3-month intervals after SBRT completion. Conclusions: SPION Ferumoxytol® administered intravenously as an alternative MRI contrast agent on the day of SBRT planning produces a long-lasting contrast effect between tumors and functional hepatic parenchyma for precision targeting and guided avoidance during the entire course of liver SBRT, enabling fast and accurate online plan adaptation on the 1.5 T Elekta Unity MR-Linac. This approach demonstrates a safe and effective bridging therapy for patients with hepatic cirrhosis, leading to low toxicity and favorable transplant outcomes. Full article
(This article belongs to the Special Issue Advances in the Prevention and Treatment of Liver Cancer)
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26 pages, 7489 KiB  
Article
Introducing and Validating the Multiphasic Evidential Decision-Making Matrix (MedMax) for Clinical Management in Patients with Intrahepatic Cholangiocarcinoma
by Ali Ramouz, Ali Adeliansedehi, Elias Khajeh, Keno März, Dominik Michael, Martin Wagner, Beat Peter Müller-Stich, Arianeb Mehrabi and Ali Majlesara
Cancers 2025, 17(1), 52; https://doi.org/10.3390/cancers17010052 - 27 Dec 2024
Viewed by 752
Abstract
Background: Despite the significant advancements of liver surgery in the last few decades, the survival rate of patients with liver and pancreatic cancers has improved by only 10% in 30 years. Precision medicine offers a patient-centered approach, which, when combined with machine learning, [...] Read more.
Background: Despite the significant advancements of liver surgery in the last few decades, the survival rate of patients with liver and pancreatic cancers has improved by only 10% in 30 years. Precision medicine offers a patient-centered approach, which, when combined with machine learning, could enhance decision making and treatment outcomes in surgical management of ihCC. This study aims to develop a decision support model to optimize treatment strategies for patients with ihCC, a prevalent primary liver cancer. Methods: The decision support model, named MedMax, was developed using three data sources: studies retrieved through a systematic literature review, expert opinions from HPB surgeons, and data from ihCC patients treated at Heidelberg University Hospital. Expert opinions were collected via surveys, with factors rated on a Likert scale, while patient data were used to validate the model’s accuracy. Results: The model is structured into four decision-making phases, assessing diagnosis, treatment modality, surgical approach, and prognosis. Prospectively, 44 patients with ihCC were included for internal primary validation of the model. MedMax could predict the appropriate treatment considering the resectability of the lesions in 100% of patients. Also, MedMax could predict a decent surgical approach in 77% of the patients. The model proved effective in making decisions regarding surgery and patient management, demonstrating its potential as a clinical decision support tool. Conclusions: MedMax offers a transparent, personalized approach to decision making in HPB surgery, particularly for ihCC patients. Initial results show high accuracy in treatment selection, and the model’s flexibility allows for future expansion to other liver tumors and HPB surgeries. Further validation with larger patient cohorts is required to enhance its clinical utility. Full article
(This article belongs to the Special Issue Advances in the Prevention and Treatment of Liver Cancer)
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11 pages, 980 KiB  
Article
The Real-World Efficacy and Safety of Direct-Acting Antivirals for Chronic Hepatitis C in Patients Active Malignancies
by Maria Dąbrowska, Jerzy Jaroszewicz, Marek Sitko, Justyna Janocha-Litwin, Dorota Zarębska-Michaluk, Ewa Janczewska, Beata Lorenc, Magdalena Tudrujek-Zdunek, Anna Parfieniuk-Kowerda, Jakub Klapaczyński, Hanna Berak, Łukasz Socha, Beata Dobracka, Dorota Dybowska, Włodzimierz Mazur, Łukasz Ważny and Robert Flisiak
Cancers 2024, 16(17), 3114; https://doi.org/10.3390/cancers16173114 - 9 Sep 2024
Viewed by 1071
Abstract
Background: Over the past years, the introduction of direct-acting antivirals (DAAs) revolutionized chronic hepatitis C treatment. We aimed to characterize and assess treatment efficacy in three specific groups of patients treated with DAAs: those with active solid malignant tumors (SMTs), hematological diseases (HDs) [...] Read more.
Background: Over the past years, the introduction of direct-acting antivirals (DAAs) revolutionized chronic hepatitis C treatment. We aimed to characterize and assess treatment efficacy in three specific groups of patients treated with DAAs: those with active solid malignant tumors (SMTs), hematological diseases (HDs) and hepatocellular carcinomas (HCCs). Methods: A total of 203 patients with active oncological disease (SMT n = 61, HD = 67, HCC n = 74) during DAA treatment in 2015–2020 selected from the EpiTer-2 database were analyzed retrospectively and compared to 12,983 patients without any active malignancy. Results: Extrahepatic symptoms were more frequent in HD patients (17.2% vs. SMT = 10.3%, HCC = 8.2%, without = 7.8%, p = 0.004). HCC patients characterized with the highest ALT activity (81 IU/L vs. SMT = 59.5 IU/L, HD = 52 IU/L, without = 58 IU/L, p = 0.001) more often had F4 fibrosis as well (86.11% vs. SMT = 23.3%, HD = 28.8%, controls = 24.4%, p = 0.001). A significant majority of subjects in HCC, HD and SMT populations completed the full treatment plan (HCC = 91%; n = 67, HD = 97%; n = 65, SMT = 100%; n = 62). Concerning the treatment efficacy, the overall sustained virologic response, excluding non-virologic failures, was reported in 93.6% HD, 90.16% SMT and 80.6% in HCC patients. Conclusions: As presented in our study, DAA therapy has proven to be highly effective and safe in patients with active SMTs and HDs. However, therapy discontinuations resulting from liver disease progression remain to be the major concern in HCC patients. Full article
(This article belongs to the Special Issue Advances in the Prevention and Treatment of Liver Cancer)
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20 pages, 1847 KiB  
Article
A Multicenter International Retrospective Investigation Assessing the Prognostic Role of Inflammation-Based Scores (Neutrophil-to-Lymphocyte, Lymphocyte-to-Monocyte, and Platelet-to-Lymphocyte Ratios) in Patients with Intermediate-Stage Hepatocellular Carcinoma (HCC) Undergoing Chemoembolizations of the Liver
by Roberto Minici, Massimo Venturini, Giuseppe Guzzardi, Federico Fontana, Andrea Coppola, Filippo Piacentino, Federico Torre, Marco Spinetta, Pietro Maglio, Pasquale Guerriero, Michele Ammendola, MGJR Research Team, Luca Brunese and Domenico Laganà
Cancers 2024, 16(9), 1618; https://doi.org/10.3390/cancers16091618 - 23 Apr 2024
Cited by 3 | Viewed by 1626
Abstract
Background: The utilization of inflammation-based scores, such as the Neutrophil-to-Lymphocyte Ratio (NLR), Lymphocyte-to-Monocyte Ratio (LMR), and Platelet-to-Lymphocyte Ratio (PLR), has garnered attention for their potential as prognostic indicators in various cancers. However, their predictive role in patients with intermediate-stage HCC undergoing transcatheter arterial [...] Read more.
Background: The utilization of inflammation-based scores, such as the Neutrophil-to-Lymphocyte Ratio (NLR), Lymphocyte-to-Monocyte Ratio (LMR), and Platelet-to-Lymphocyte Ratio (PLR), has garnered attention for their potential as prognostic indicators in various cancers. However, their predictive role in patients with intermediate-stage HCC undergoing transcatheter arterial chemoembolization (TACE) remains an area that requires further investigation, as early recognition of TACE refractoriness holds the potential to guide tailored therapeutic interventions. Methods: This multicenter international retrospective study analyzed data from patients with intermediate-stage HCC undergoing TACE between 2018 and 2024. Inflammation-based scores (NLR, LMR, PLR) were assessed preoperatively to predict treatment outcomes. Results: Two hundred and fourteen patients were enrolled. Preoperative LMR showed the largest area under the curve for the prediction of 6-months PFS, based on the ROC curve analysis. Both high LMR (≥2.24) and low NLR (<4.72) were associated with improved objective response rates and 6-month progression-free survival. Lymphocyte count emerged as a strong predictor of treatment response in both simple (p < 0.001) and multiple (p < 0.001) logistic regression analyses. Conclusions: This study highlights the prognostic value of inflammation-based scores, particularly LMR and NLR, in predicting the treatment response and short-term outcomes of patients with intermediate-stage HCC undergoing TACE. Future investigations should focus on validating these scores’ clinical applicability and assessing their impact on long-term patient survival and therapeutic decision-making. Full article
(This article belongs to the Special Issue Advances in the Prevention and Treatment of Liver Cancer)
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8 pages, 886 KiB  
Article
Long-Term Intake of Proton-Pump Inhibitors Could Be Associated with an Increased Incidence of Liver Cancer in Women
by Sven H. Loosen, Markus S. Jördens, Catherine Leyh, Tom Luedde, Christoph Roderburg and Karel Kostev
Cancers 2024, 16(8), 1517; https://doi.org/10.3390/cancers16081517 - 16 Apr 2024
Cited by 1 | Viewed by 1651
Abstract
Background: Proton pump inhibitors (PPIs) are among the most commonly prescribed drugs in gastroenterology. Although PPIs are mostly well tolerated, long-term PPI intake has been linked with diabetes mellitus, osteoporosis and infectious disease. In the present study, we evaluated a potential association between [...] Read more.
Background: Proton pump inhibitors (PPIs) are among the most commonly prescribed drugs in gastroenterology. Although PPIs are mostly well tolerated, long-term PPI intake has been linked with diabetes mellitus, osteoporosis and infectious disease. In the present study, we evaluated a potential association between PPI intake and a subsequent diagnosis of liver cancer in a large real-world cohort of outpatients in Germany. Methods: A total of 1766 patients with liver cancer, as well as 8830 propensity-score-matched controls, were identified from the Disease Analyzer database (IQVIA). The outcome of the study was the association between PPI use and a subsequent diagnosis of liver cancer, which was evaluated using multivariable logistic regression analyses. Results: Overall, 42.9% of the liver cancer patients and 39.0% of the controls received at least one PPI prescription before the index date. PPI prescriptions at any time before the index date were associated with an increased risk of subsequent liver cancer (OR: 1.18; 95% CI: 1.06–1.31). The positive association was observed in all age groups, as well as in women and men, but only in women (OR: 1.30; 95% 1.09–1.55) did it reach the predefined level of significance (p < 0.01). When considering the duration of PPI therapy, only PPI therapy for at least two years was significantly associated with an increased risk of liver cancer (OR: 1.28; 95% 1.09–1.50). In an analysis stratified by age and sex, this association was strongest in the age group < 60 years (OR: 1.99; 95% 1.21–3.26). Conclusions: Our data suggest that long-term PPI intake in women as well as in patients < 60 years might be associated with an increased risk of liver cancer. These findings support current efforts to reduce the inappropriate use of PPIs in routine clinical practice and to link PPI prescribing to a clear medical indication. Full article
(This article belongs to the Special Issue Advances in the Prevention and Treatment of Liver Cancer)
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18 pages, 1512 KiB  
Article
Outcome of Atezolizumab Plus Bevacizumab Combination Therapy in High-Risk Patients with Advanced Hepatocellular Carcinoma
by Sang Youn Hwang, Hyun Young Woo, Jeong Heo, Hyung Jun Kim, Young Joo Park, Ki Youn Yi, Yu Rim Lee, Soo Young Park, Woo Jin Chung, Byoung Kuk Jang and Won Young Tak
Cancers 2024, 16(4), 838; https://doi.org/10.3390/cancers16040838 - 19 Feb 2024
Cited by 3 | Viewed by 2779
Abstract
Real-world data regarding treatment with atezolizumab plus bevacizumab in high-risk patients with advanced HCC are lacking. In this multicenter retrospective cohort study, a total of 215 patients with advanced HCC received atezolizumab plus bevacizumab treatment at four tertiary hospitals. High-risk patients were those [...] Read more.
Real-world data regarding treatment with atezolizumab plus bevacizumab in high-risk patients with advanced HCC are lacking. In this multicenter retrospective cohort study, a total of 215 patients with advanced HCC received atezolizumab plus bevacizumab treatment at four tertiary hospitals. High-risk patients were those with grade Vp4 portal vein thrombus, bile duct invasion, or more than 50% liver infiltration. In total, 98 (45.6%) were the high-risk population, 186 (86.5%) were considered to be Child–Pugh class A, and 128 (59.5%) had previously received neoadjuvant or concomitant radiation treatment. Median overall survival (OS) was 11.25 months (95% CI, 9.50–13.10), and the median progression-free survival (PFS) was 8.00 months (95% CI, 6.82–9.18). In the high-risk population, the median OS was 10 months (95% CI, 8.19–11.82) and the median PFS was 6.50 months (95% CI, 3.93–9.08). In the high-risk population, multivariate analysis indicated that radiation therapy and lower ALBI grade were associated with better OS and PFS. A total of 177 (82.3%) patients experienced adverse events of any grade, the most common being proteinuria (23.7%). Atezolizumab plus bevacizumab treatment showed consistent efficacy and tolerability in both the total and high-risk population. Radiation therapy combined with atezolizumab plus bevacizumab treatment might be helpful to improve PFS and OS in high-risk populations. Full article
(This article belongs to the Special Issue Advances in the Prevention and Treatment of Liver Cancer)
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Review

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15 pages, 757 KiB  
Review
The Influence of Diet and Its Components on the Development and Prevention of Hepatocellular Carcinoma (HCC)
by Barbara Janota and Barbara Szymanek
Cancers 2024, 16(5), 1030; https://doi.org/10.3390/cancers16051030 - 2 Mar 2024
Cited by 5 | Viewed by 2679
Abstract
Hepatocellular carcinoma (HCC) is diagnosed annually in nearly a million people worldwide, with approximately half of them being diagnosed at an advanced stage of the disease. Non-infectious risk factors for the development of HCC include an unbalanced lifestyle, including poor dietary choices characterized [...] Read more.
Hepatocellular carcinoma (HCC) is diagnosed annually in nearly a million people worldwide, with approximately half of them being diagnosed at an advanced stage of the disease. Non-infectious risk factors for the development of HCC include an unbalanced lifestyle, including poor dietary choices characterized by a low intake of antioxidants, such as vitamins E and C, selenium, and polyphenols, as well as an excessive consumption of energy and harmful substances. Repeated bad dietary choices that contribute to an unbalanced lifestyle lead to the accumulation of fatty substances in the liver and to it entering an inflammatory state, which, without intervention, results in cirrhosis, the main cause of HCC. This review of the English language literature aims to present the food components that, when included in the daily diet, reduce the risk of developing HCC, as well as identifying foods that may have a carcinogenic effect on liver cells. Full article
(This article belongs to the Special Issue Advances in the Prevention and Treatment of Liver Cancer)
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16 pages, 4347 KiB  
Systematic Review
Impact of Thrombocytopenia on Survival in Patients with Hepatocellular Carcinoma: Updated Meta-Analysis and Systematic Review
by Leszek Kraj, Paulina Chmiel, Maciej Gryziak, Laretta Grabowska-Derlatka, Łukasz Szymański and Ewa Wysokińska
Cancers 2024, 16(7), 1293; https://doi.org/10.3390/cancers16071293 - 27 Mar 2024
Cited by 1 | Viewed by 1788
Abstract
Background: Platelets (PLT) have a role in the pathogenesis, progression, and prognosis of hepatocellular carcinoma (HCC) and could represent a readily measurable laboratory parameter to enhance the comprehensive evaluation of HCC patients. Methods: The PubMed, Web of Science, and Scopus databases were searched [...] Read more.
Background: Platelets (PLT) have a role in the pathogenesis, progression, and prognosis of hepatocellular carcinoma (HCC) and could represent a readily measurable laboratory parameter to enhance the comprehensive evaluation of HCC patients. Methods: The PubMed, Web of Science, and Scopus databases were searched with a focus on survival as well as patient and tumor-specific characteristics in correlation to reported PLT counts. Survival outcomes were analyzed with both common-effect and random-effects models. The hazard ratio (HR) and its 95% confidence interval (CI) from analyzed trials were incorporated. Studies that did not provide survival data but focused on platelet count correlation with HCC characteristics were reviewed. Results: In total, 26 studies, including a total of 9403 patients, met our criteria. The results showed that thrombocytopenia in HCC patients was associated with poor overall survival (common-effect HR = 1.15, 95% CI: 1.06–1.25; random-effect HR = 1.30, 95% CI: 1.05–1.63). Moreover, three studies reveal significant correlations between PLT indices and tumor characteristics such as size, foci number, and etiology of HCC development. Conclusion: Our meta-analysis confirmed that PLT count could act as a prognostic marker in HCC, especially with a PLT count cut off <100 × 103/mm3. Further prospective studies focusing on the role of PLT in clearly defined subgroups are necessary. Full article
(This article belongs to the Special Issue Advances in the Prevention and Treatment of Liver Cancer)
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