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Current Oncology
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Novel Approaches in the Management of Hepatocellular Carcinoma: From Surveillance...
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Novel Approaches in the Management of Hepatocellular Carcinoma: From Surveillance to Treatment

A special issue of Current Oncology (ISSN 1718-7729).

Deadline for manuscript submissions: closed (31 May 2022) | Viewed by 11493

Special Issue Editors

Dr. Gian Paolo Caviglia

E-Mail Website
Guest Editor
Department of Medical Sciences, University of Turin, I-10126 Turin, Italy
Interests: biomarkers; cirrhosis; hepatitis B virus; hepatocellular carcinoma; hepatitis D virus; inflammatory bowel disease; liver fibrosis; non-alcoholic fatty liver disease
Special Issues, Collections and Topics in MDPI journals
Dr. Silvia Gaia

E-Mail Website
Guest Editor
Unit of Gastroenterology, AOU Città della Salute e della Scienza – Molinette Hospital, 10126 Turin, Italy
Interests: biomarkers; cirrhosis; endoscopic ultrasound; hepatitis B virus; hepatocellular carcinoma; interventional ultrasound; liver fibrosis; non-alcoholic fatty liver disease

Special Issue Information

Dear Colleagues,

Liver cancer is the sixth most common cancer in terms of incidence and the third in terms of mortality worldwide, with approximately 841,000 new cases and 782,000 deaths per year; hepatocellular carcinoma (HCC) represents more than 90% of primary liver cancers. Chronic inflammation that characterizes the natural history of chronic hepatitis leads to fibrosis progression, and, overtime, to cirrhosis, a pre-neoplastic condition at high risk for HCC development. Additionally, the molecular alterations that underlie cirrhosis and dysplastic lesions provide dysplastic cells with proliferative, invasive, and survival advantages moving toward the onset of HCC. It is estimated that one-third of patients with cirrhosis will develop HCC during their lifetime.

Major efforts are underway to improve surveillance strategies for the early detection and even the prediction of HCC development. Novel technologies are available, and omics approaches will allow for the identification of new biomarkers that might improve the surveillance of patients at risk of HCC development. On the other hand, biomarkers will help clinicians to tailor the therapeutic approach beyond current guidelines recommendation, as well as to predict patient outcome. Finally, with the recent approval of new different drugs, including tyrosine kinase inhibitors, monoclonal antibodies and immune checkpoint inhibitors as first- and second-line treatments, the current scenario of HCC therapy is rapidly evolving.

For this Special Issue, we encourage the submission of manuscripts on any aspects of HCC management, from surveillance to diagnosis, and from therapy to prognosis.

Dr. Gian Paolo Caviglia
Dr. Silvia Gaia
Guest Editors

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. Current Oncology is an international peer-reviewed open access monthly 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 2200 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

  • biomarkers
  • cirrhosis
  • diagnosis
  • HBV
  • HCC
  • HCV
  • immune checkpoint inhibitors
  • liver transplant
  • liquid biopsy
  • loco-regional therapy
  • microbiota
  • NAFLD/NASH
  • next-generation sequencing
  • omics
  • precision medicine
  • prognosis
  • surgery
  • surveillance
  • systemic therapy

Published Papers (5 papers)

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Research

9 pages, 1247 KiB  
Communication
Liver Cancer-Specific Isoform of Serine Protease Inhibitor Kazal for the Detection of Hepatocellular Carcinoma: Results from a Pilot Study in Patients with Dysmetabolic Liver Disease
by Gian Paolo Caviglia, Aurora Nicolosi, Maria Lorena Abate, Patrizia Carucci, Chiara Rosso, Emanuela Rolle, Angelo Armandi, Serena Aneli, Antonella Olivero, Alessandra Risso, Davide Giuseppe Ribaldone, Christian Fermer, Giorgio Maria Saracco, Silvia Gaia and Elisabetta Bugianesi
Curr. Oncol. 2022, 29(8), 5457-5465; https://doi.org/10.3390/curroncol29080431 - 31 Jul 2022
Cited by 4 | Viewed by 1959
Abstract
Reliable non-invasive biomarkers for the surveillance of patients at risk of hepatocellular carcinoma (HCC) development represent an unmet medical need. Recently, the liver-cancer-specific isoform of serine protease inhibitor Kazal (LC-SPIK) has been proposed as a valuable biomarker for the detection of HCC in [...] Read more.
Reliable non-invasive biomarkers for the surveillance of patients at risk of hepatocellular carcinoma (HCC) development represent an unmet medical need. Recently, the liver-cancer-specific isoform of serine protease inhibitor Kazal (LC-SPIK) has been proposed as a valuable biomarker for the detection of HCC in patients with chronic liver disease of viral etiology. In the present study, we assessed the diagnostic accuracy of LC-SPIK, alone or in combination with standard serologic biomarkers (i.e., alpha-fetoprotein and protein induced by vitamin K absence or antagonist-II, PIVKA-II), for the detection of HCC among patients with dysmetabolic liver disease. A total of 120 patients with non-alcoholic fatty liver disease (NAFLD), including 62 patients with a diagnosis of HCC and 58 with cirrhosis but without tumor, were retrospectively analyzed. The serum levels of LC-SPIK were measured by enzyme-linked immunosorbent assay (ImCare Biotech, Doylestown, PA). The serum LC-SPIK values were significantly different between patients with HCC (24.3, 17.6–39.8 ng/mL) and those with cirrhosis but without tumor (11.7, 8.7–18.2 ng/mL) (p < 0.001). By receiver operating characteristic curve analysis, we observed an area under the curve (AUC) of 0.841 for the detection of HCC; the combination with PIVKA-II further increased the accuracy to AUC = 0.926 (cross-validation). The promising results observed in the present pilot study foster additional research to investigate the usefulness of LC-SPIK for the stratification of the risk of HCC development in patients with NAFLD and advanced liver disease. Full article
(This article belongs to the Special Issue Novel Approaches in the Management of Hepatocellular Carcinoma: From Surveillance to Treatment)
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10 pages, 841 KiB  
Article
Outcomes of Geriatric Patients with Hepatocellular Carcinoma
by Chern-Horng Lee, Tzung-Hai Yen and Sen-Yung Hsieh
Curr. Oncol. 2022, 29(6), 4332-4341; https://doi.org/10.3390/curroncol29060346 - 16 Jun 2022
Cited by 3 | Viewed by 1783
Abstract
Background: The treatment modalities and outcomes of geriatric patients with hepatocellular carcinoma (HCC) remain controversial. This retrospective observational cohort study compared the outcomes of HCC between geriatric and younger patients. Methods: The medical records of patients with HCC managed between January 2001 and [...] Read more.
Background: The treatment modalities and outcomes of geriatric patients with hepatocellular carcinoma (HCC) remain controversial. This retrospective observational cohort study compared the outcomes of HCC between geriatric and younger patients. Methods: The medical records of patients with HCC managed between January 2001 and December 2017 were retrieved from the Chang Gung Memorial Hospital Research Database. Patients were stratified by age into two groups: a geriatric group (65–75 years) and a younger group (<65 years). The two groups were matched through 1:2 propensity score matching (PSM) according to sex, cardiovascular disease, cerebrovascular attack, diabetes mellitus, cirrhosis, hepatitis, and hypertension. Results: Of the 11,033 patients with HCC, 2147 patients aged 65–75 years and 4294 patients aged <65 years were identified after 1:2 PSM. The Kaplan–Meier model revealed that the HCC outcomes in patients older than 65 years were not significantly different after 3 years (p = 0.060). Consistent results were also obtained when the laboratory data associated with HCC incidence were included in the Fine–Gray competing risk model after 1:2 PSM (p = 0.1695). The major risk factors for HCC survival were systemic immune-inflammation index (SII) ≥ 610 × 109 cells/L, advanced tumor stage, and model for end-stage liver disease (MELD) score, etc. Conclusion: Age was not an independent factor for mortality in patients with HCC in the first 3 years. Geriatric patients with HCC should be as aggressively managed as younger patients. Full article
(This article belongs to the Special Issue Novel Approaches in the Management of Hepatocellular Carcinoma: From Surveillance to Treatment)
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13 pages, 1502 KiB  
Article
Living-Donor Liver Transplantation for Hepatocellular Carcinoma: Impact of the MELD Score and Predictive Value of NLR on Survival
by Hao-Chien Hung, Jin-Chiao Lee, Yu-Chao Wang, Chih-Hsien Cheng, Tsung-Han Wu, Ting-Jung Wu, Hong-Shiue Chou, Kun-Ming Chan, Wei-Chen Lee and Chen-Fang Lee
Curr. Oncol. 2022, 29(6), 3881-3893; https://doi.org/10.3390/curroncol29060310 - 29 May 2022
Cited by 3 | Viewed by 2120
Abstract
Background: Patients with hepatocellular carcinoma (HCC) tend to be referred for liver transplantation (LT) at an early stage of cirrhosis, with lower pre-LT Model of End-Stage Liver Disease (MELD) scores. We investigated the impact of high MELD scores on post-LT outcomes in patients [...] Read more.
Background: Patients with hepatocellular carcinoma (HCC) tend to be referred for liver transplantation (LT) at an early stage of cirrhosis, with lower pre-LT Model of End-Stage Liver Disease (MELD) scores. We investigated the impact of high MELD scores on post-LT outcomes in patients with HCC and validated the prognostic significance of the neutrophil-to-lymphocyte ratio (NLR). Patients and Method: This retrospective single-center cohort study enrolled 230 patients with HCC who underwent LDLT from 2004–2019 in our institute. We defined a high MELD score as ≥20. Results: The MELD < 20 and MELD ≥ 20 groups comprised 205 and 25 cases, respectively. Although there was no significant difference in disease-free survival between the two groups (p = 0.629), the incidence of septic shock (p = 0.019) was significantly higher in the high MELD group. The one-, three-, and five-year overall survival rates were not significantly different between the two groups (p = 0.056). In univariate analysis, a high pre-LT NLR was associated with poorer survival in the high MELD group (p = 0.029, hazard ratio [HR]: 1.07, 90% confidence interval [CI]: 1.02–1.13). NLR cut-off values of ≥10.7 and <10.7 were predictive of mortality, with an AUC of 0.705 (90% CI: 0.532–0.879). The one-, three-, and five-year post-LT survival rates were significantly higher among the recipients with an NLR < 10.7 than those with an NLR ≥ 10.7 (p = 0.005). Conclusions: Pre-LT MELD score ≥ 20 was associated with a higher risk of developing post-LT septic shock and mortality. The pre-LT serum NLR is a useful predictive factor for clinical outcomes in patients with HCC with high MELD scores. Full article
(This article belongs to the Special Issue Novel Approaches in the Management of Hepatocellular Carcinoma: From Surveillance to Treatment)
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8 pages, 469 KiB  
Article
Effect of COVID-19 Pandemic on Hepatocellular Carcinoma Diagnosis: Results from a Tertiary Care Center in North-West Italy
by Davide Giuseppe Ribaldone, Gian Paolo Caviglia, Silvia Gaia, Emanuela Rolle, Alessandra Risso, Daniela Campion, Paola Rita Brunocilla, Giorgio Maria Saracco and Patrizia Carucci
Curr. Oncol. 2022, 29(3), 1422-1429; https://doi.org/10.3390/curroncol29030119 - 24 Feb 2022
Cited by 10 | Viewed by 2445
Abstract
The COVID-19 pandemic has forced us to direct most of the available resources towards its management. This has led to the neglect of all other pathologies, including cancer. The aim of this study was to verify whether the difficulty in accessing the health [...] Read more.
The COVID-19 pandemic has forced us to direct most of the available resources towards its management. This has led to the neglect of all other pathologies, including cancer. The aim of this study was to verify whether the difficulty in accessing the health system has led to a reduction in new diagnoses of hepatocellular carcinoma (HCC) and whether this has already been reflected in a more advanced stage of the cancer. A single-center, retrospective study including adult patients with a new diagnosis of HCC was performed. Patients were divided into three groups: the prelockdown phase (May 2019–February 2020), the lockdown phase (March 2020–December 2020), and the postlockdown phase (January 2021–October 2021); 247 patients were included. The number of patients diagnosed with HCC distinctly diminished in the periods March 2020–December 2020 (n = 69; −35%) and January 2021–October 2021 (n = 72; −32%) as compared to the period May 2019–February 2020 (n = 106). Noteworthy was the reduced surveillance in the period January 2021–October 2021 as compared to May 2019–February 2020 (22.9% vs. 36.6%, p = 0.056). No significant changes have yet been observed in tumor characteristics (BCLC staging distribution remained unvaried, p = 0.665). In conclusion, the number of new HCC diagnoses decreased sharply in the first 2 years of the pandemic, with no worsening of the stage. A more advanced stage of the disease could be expected in the next few years in patients who have escaped diagnosis. Full article
(This article belongs to the Special Issue Novel Approaches in the Management of Hepatocellular Carcinoma: From Surveillance to Treatment)
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10 pages, 1211 KiB  
Article
Prognostic Significance of Tumor Growth Rate (TGR) in Patients with Huge Hepatocellular Carcinoma Undergoing Transcatheter Arterial Chemoembolization
by Guobin Chen, Xiaoying Xie, Meixia Wang, Xinkun Guo, Zhenzhen Zhang, Lan Zhang and Boheng Zhang
Curr. Oncol. 2022, 29(2), 423-432; https://doi.org/10.3390/curroncol29020038 - 18 Jan 2022
Cited by 1 | Viewed by 2272
Abstract
The prognostic value of the tumor growth rate (TGR) in huge hepatocellular carcinoma (HHCC) patients treated with transcatheter arterial chemoembolization (TACE) as an initial treatment remains unclear. This two-center retrospective study was conducted in 97 patients suffering from HHCC. Demographic characteristics, oncology characteristics, [...] Read more.
The prognostic value of the tumor growth rate (TGR) in huge hepatocellular carcinoma (HHCC) patients treated with transcatheter arterial chemoembolization (TACE) as an initial treatment remains unclear. This two-center retrospective study was conducted in 97 patients suffering from HHCC. Demographic characteristics, oncology characteristics, and some serological markers were collected for analysis. The TGR was significantly linear and associated with the risk of death when applied to restricted cubic splines. The optimal cut-off value of TGR was −8.6%/month, and patients were divided into two groups according to TGR. Kaplan–Meier analysis showed that the high-TGR group had a poorer prognosis. TGR (hazard ratio (HR), 2.06; 95% confidence interval (CI), 1.23–3.43; p = 0.006), presence of portal vein tumor thrombus (PVTT) (HR, 1.93; 95% CI, 1.13–3.27; p = 0.016), and subsequent combination therapy (HR, 0.59; 95% CI, 0.35–0.99; p = 0.047) were independent predictors of OS in the multivariate analysis. The model with TGR was superior to the model without TGR in the DCA analysis. Patients who underwent subsequent combination therapy showed a longer survival in the high-TGR group. This study demonstrated that higher TGR was associated with a worse prognosis in patients with HHCC. These findings will distinguish patients who demand more personalized combination therapy and rigorous surveillance. Full article
(This article belongs to the Special Issue Novel Approaches in the Management of Hepatocellular Carcinoma: From Surveillance to Treatment)
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