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JCM
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From Liver Fibrosis to Carcinoma: Physiopathological Mechanisms, Diagnosis and Treatment
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From Liver Fibrosis to Carcinoma: Physiopathological Mechanisms, Diagnosis and Treatment

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Gastroenterology & Hepatopancreatobiliary Medicine".

Deadline for manuscript submissions: closed (31 July 2023) | Viewed by 17606

Special Issue Editors

Dr. Sharmila Fagoonee

E-Mail Website
Guest Editor
Institute of Biostructure and Bioimaging (CNR), Molecular Biotechnology Center, Via Nizza 52, 10126 Turin, Italy
Interests: correction of metabolic diseases of liver with stem cells as platform for gene therapy; liver diseases and extracellular vesicles: search for new therapies and biomarkers
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Pietro Invernizzi

E-Mail Website
Guest Editor
Division of Gastroenterology, San Gerardo Hospital, University of Milano-Bicocca School of Medicine, 20900 Monza, Italy
Interests: gastroenterology; inflammatory bowel diseases; hepatology; neuroendocrine tumors
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Liver fibrosis, which develops as a response to long-lasting injury or inflammation, is a common final pathway at the cross-section of all chronic liver diseases before the surge of cirrhosis and carcinoma and is responsible for significant levels of morbidity and mortality. Viral infection, dysmetabolism, cholestasis-inducers, and excessive alcohol consumption are common causes of this condition. Liver fibrosis is a multi-staged and tightly regulated process. Accumulating evidence suggests that the fibrotic liver can re-acquire a normal architecture, even in advanced fibrosis and cirrhosis, if an effective treatment for the underlying insult is applied. 

We are becoming more and more aware of the fact that liver fibrosis has etiology-dependent patterns of evolution and numerous underlying mechanisms. This points out the necessity of fully dissecting these physiopathological pathways in order to develop distinct diagnostic and therapeutic modalities for the improved clinical management of chronic liver diseases.

This Special Issue of the Journal of Clinical Medicine is intended to solicit cutting-edge original research and topical reviews on the pathological mechanisms, including on the transcriptional, post-transcriptional, and epigenetic control of liver fibrosis stage-wise advancement to cirrhosis and carcinoma. Papers on new strategies and emerging advanced translational and clinical approaches for the prevention and therapy of chronic liver diseases, clinical studies on current management strategies, and translational research studies that further our knowledge on the molecular pathogenesis underlying the progress of fibrosis to carcinoma and therapeutic approaches are welcome.

With sadness, we regret to inform you about the passing of Dr. Rinaldo Pellicano, Guest Editor of JCM. We are grateful for his many contributions to the journal and the legacy his research has left.

Dr. Sharmila Fagoonee
Prof. Dr. Pietro Invernizzi
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. Journal of Clinical Medicine 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 2600 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

  • transcriptional, post-transcriptional, and epigenetic controls
  • nanotechnology- and bio-engineering-based approaches
  • biomarkers for early diagnosis
  • etiology-based mechanism
  • iron-induced liver injury
  • sarcopenia-associated liver fibrosis
  • autoimmunity
  • microbiota–liver axis
  • anti-fibrotic drugs and therapeutic options
  • novel diagnostic, imaging and treatment modalities
  • organoid technology and “omics”-based approaches

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Published Papers (6 papers)

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Editorial

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2 pages, 152 KiB  
Editorial
Chronic Liver Diseases: What is Up?
by Sharmila Fagoonee and Pietro Invernizzi
J. Clin. Med. 2024, 13(2), 613; https://doi.org/10.3390/jcm13020613 - 22 Jan 2024
Viewed by 837
Abstract
During the preparation of this Special Issue, Dr [...] Full article
(This article belongs to the Special Issue From Liver Fibrosis to Carcinoma: Physiopathological Mechanisms, Diagnosis and Treatment)

Research

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10 pages, 667 KiB  
Article
Cross-Sectional and Longitudinal Performance of Non-Invasive Tests of Liver Fibrosis in Patients with Non-Alcoholic Fatty Liver Disease
by Angelo Armandi, Chiara Rosso, Ramy Younes, Diana Julie Leeming, Morten A. Karsdal, Gian Paolo Caviglia, Nuria Pérez-Diaz-del-Campo, Daphne D’Amato, Amina Abdulle, Aurora Nicolosi, Gabriele Castelnuovo, Giorgio Maria Saracco, Davide Giuseppe Ribaldone and Elisabetta Bugianesi
J. Clin. Med. 2023, 12(2), 650; https://doi.org/10.3390/jcm12020650 - 13 Jan 2023
Cited by 2 | Viewed by 1848
Abstract
Background and aims: Non-invasive tests (NITs) are needed in clinical practice to replace histology for the identification of liver fibrosis and prognostication in Non-Alcoholic Fatty Liver Disease (NAFLD). Novel collagen-derived fibrogenesis markers including N-terminal type III collagen pro-peptide (PRO-C3) are among the most [...] Read more.
Background and aims: Non-invasive tests (NITs) are needed in clinical practice to replace histology for the identification of liver fibrosis and prognostication in Non-Alcoholic Fatty Liver Disease (NAFLD). Novel collagen-derived fibrogenesis markers including N-terminal type III collagen pro-peptide (PRO-C3) are among the most promising tools in this field. The aim of this study was to assess the diagnostic accuracy of PRO-C3, the derivative ADAPT score, and other NITs for the identification of advanced fibrosis (stages 3–4) and changes over 12 months of follow-up. Methods: In this longitudinal study, 96 patients with biopsy-proven NAFLD were evaluated at baseline, of which 50 underwent a follow-up visit after 12 months. Clinical-biochemical parameters, liver stiffness (LS) by transient elastography, PRO-C3, and other NITs (ADAPT, FIB-4, NFS, APRI) were collected at baseline and follow-up. Results: LS showed the best accuracy for the identification of advanced fibrosis, with Area under the Receiving Operator Curve (AUROC) 0.82 (0.73–0.89) for a cut-off value of 9.4 kPa. Among the other NITs, the ADAPT score showed the best accuracy, with AUROC 0.80 (0.71–0.88) for a cut-off of 5.02 (Se 62%, Sp 89%, PPV 74%, NPV 83%). The comparison between the AUROC of LS with that of ADAPT was not statistically different (DeLong test p value 0.348). At follow-up, LS was slightly reduced, whilst PRO-C3 displayed a significant increase from baseline median 11.2 ng/mL to 13.9 ng/mL at follow-up (p = 0.017). Accordingly, ADAPT score increased from median 5.3 to 6.1 (p = 0.019). The other NITs did not significantly change over 12 months. Conclusions: The ADAPT score shows the best performance among non-invasive scores for the identification of advanced fibrosis, not different from LS. Collagen-derived biomarker PRO-C3 and the derivative score ADAPT display significant changes over time, and may be useful tools for monitoring the progression of liver disease or assessing responses to treatments. Full article
(This article belongs to the Special Issue From Liver Fibrosis to Carcinoma: Physiopathological Mechanisms, Diagnosis and Treatment)
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11 pages, 1297 KiB  
Article
Genomic Relevance of FGFR2 on the Prognosis of HCV-Induced Hepatocellular Carcinoma Patients
by Walizeb Khan, Washaakh Ahmad, Anwar M. Hashem, Shadi Zakai, Shafiul Haque, Muhammad Faraz Arshad Malik, Steve Harakeh and Farhan Haq
J. Clin. Med. 2022, 11(11), 3093; https://doi.org/10.3390/jcm11113093 - 30 May 2022
Viewed by 2361
Abstract
The Fibroblast Growth Factor Receptors (FGFRs) are known to regulate cancer metabolism in different tumor types, including hepatocellular carcinoma (HCC). Several risk factors are associated with HCC, of which viral infections (Hepatitis B and C) and cirrhosis are prominent. In Pakistan as well [...] Read more.
The Fibroblast Growth Factor Receptors (FGFRs) are known to regulate cancer metabolism in different tumor types, including hepatocellular carcinoma (HCC). Several risk factors are associated with HCC, of which viral infections (Hepatitis B and C) and cirrhosis are prominent. In Pakistan as well as in highly developed countries like the United States, hepatitis C virus HCV infections are most commonly reported in HCC. Here, we aimed to investigate the clinical relevance of FGFR receptors in HCC and their role in HCV-positive HCC cases. 264 HCC samples along with their clinical information and 96 normal liver samples were collected. qPCR was done to estimate the expression of FGFR1, FGFR2, FGFR3 and FGFR4. Three independent HCV-induced HCC cohorts (containing 293 HCC samples) were used for validation. According to in vitro results, FGFR1 was upregulated in HCV+ HCC patients. However, in all three independent cohorts of HCC, significant a down-regulation of FGFR1 was observed. FGFR2 overexpression was observed in the in vitro cohort as well as in three independent HCC cohorts. Interestingly, a strong correlation of FGFR2 expression was observed between cirrhosis and HCV in all four HCC cohorts. Our study suggested that FGFR2 expression can be used to classify HCC patients based on HCV infection. This FGFR2-based classification may lead to new therapeutic strategies against HCV-positive HCC subtypes. Full article
(This article belongs to the Special Issue From Liver Fibrosis to Carcinoma: Physiopathological Mechanisms, Diagnosis and Treatment)
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Review

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18 pages, 848 KiB  
Review
Autoimmune Hepatitis and Fibrosis
by Rinaldo Pellicano, Arianna Ferro, Francesca Cicerchia, Simone Mattivi, Sharmila Fagoonee and Marilena Durazzo
J. Clin. Med. 2023, 12(5), 1979; https://doi.org/10.3390/jcm12051979 - 2 Mar 2023
Cited by 12 | Viewed by 5170
Abstract
Autoimmune hepatitis (AIH) is a chronic immune-inflammatory disease of the liver, generally considered a rare condition. The clinical manifestation is extremely varied and can range from paucisymptomatic forms to severe hepatitis. Chronic liver damage causes activation of hepatic and inflammatory cells leading to [...] Read more.
Autoimmune hepatitis (AIH) is a chronic immune-inflammatory disease of the liver, generally considered a rare condition. The clinical manifestation is extremely varied and can range from paucisymptomatic forms to severe hepatitis. Chronic liver damage causes activation of hepatic and inflammatory cells leading to inflammation and oxidative stress through the production of mediators. This results in increased collagen production and extracellular matrix deposition leading to fibrosis and even cirrhosis. The gold standard for the diagnosis of fibrosis is liver biopsy; however, there are serum biomarkers, scoring systems, and radiological methods useful for diagnosis and staging. The goal of AIH treatment is to suppress fibrotic and inflammatory activities in the liver to prevent disease progression and achieve complete remission. Therapy involves the use of classic steroidal anti-inflammatory drugs and immunosuppressants, but in recent years scientific research has focused on several new alternative drugs for AIH that will be discussed in the review. Full article
(This article belongs to the Special Issue From Liver Fibrosis to Carcinoma: Physiopathological Mechanisms, Diagnosis and Treatment)
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10 pages, 264 KiB  
Review
Cancer-Associated Fibroblasts in Cholangiocarcinoma: Current Knowledge and Possible Implications for Therapy
by Michele Montori, Chiara Scorzoni, Maria Eva Argenziano, Daniele Balducci, Federico De Blasio, Francesco Martini, Tiziana Buono, Antonio Benedetti, Marco Marzioni and Luca Maroni
J. Clin. Med. 2022, 11(21), 6498; https://doi.org/10.3390/jcm11216498 - 2 Nov 2022
Cited by 12 | Viewed by 2916
Abstract
Cholangiocarcinoma (CCA) is an aggressive neoplasia with an increasing incidence and mortality. It is characterized by a strong desmoplastic stroma surrounding cancer cells. Cancer-associated fibroblasts (CAFs) are the main cell type of CCA stroma and they have an important role in modulating cancer [...] Read more.
Cholangiocarcinoma (CCA) is an aggressive neoplasia with an increasing incidence and mortality. It is characterized by a strong desmoplastic stroma surrounding cancer cells. Cancer-associated fibroblasts (CAFs) are the main cell type of CCA stroma and they have an important role in modulating cancer microenvironments. CAFs originate from multiple lines of cells and mainly consist of fibroblasts and alpha-smooth muscle actin (α-SMA) positive myofibroblast-like cells. The continuous cross-talking between CCA cells and desmoplastic stroma is permitted by CAF biochemical signals, which modulate a number of pathways. Stromal cell-derived factor-1 expression increases CAF recruitment to the tumor reactive stroma and influences apoptotic pathways. The Bcl-2 family protein enhances susceptibility to CAF apoptosis and PDGFRβ induces fibroblast migration and stimulates tumor lymphangiogenesis. Many factors related to CAFs may influence CCA prognosis. For instance, a better prognosis is associated with IL-33 expression and low stromal IL-6 (whose secretion is stimulated by microRNA). In contrast, a worst prognosis is given by the expression of PDGF-D, podoplanin, SDF-1, α-SMA high expression, and periostin. The maturity phenotype has a prognostic relevance too. New therapeutic strategies involving CAFs are currently under study. Promising results are obtained with anti-PlGF therapy, nintedanib (BIBF1120), navitoclax, IPI-926, resveratrol, and controlled hyperthermia. Full article
(This article belongs to the Special Issue From Liver Fibrosis to Carcinoma: Physiopathological Mechanisms, Diagnosis and Treatment)
12 pages, 789 KiB  
Review
Mediterranean Diet: The Beneficial Effects of Lycopene in Non-Alcoholic Fatty Liver Disease
by Ludovico Abenavoli, Anna Caterina Procopio, Maria Rosaria Paravati, Giosuè Costa, Nataša Milić, Stefano Alcaro and Francesco Luzza
J. Clin. Med. 2022, 11(12), 3477; https://doi.org/10.3390/jcm11123477 - 16 Jun 2022
Cited by 17 | Viewed by 3213
Abstract
Non-alcoholic fatty liver disease (NAFLD) presents the most common chronic liver disease globally; it is estimated that 25.24% of the world’s population has NAFLD. NAFLD is a multi-factorial disease whose development involves various processes, such as insulin resistance, lipotoxicity, inflammation, cytokine imbalance, the [...] Read more.
Non-alcoholic fatty liver disease (NAFLD) presents the most common chronic liver disease globally; it is estimated that 25.24% of the world’s population has NAFLD. NAFLD is a multi-factorial disease whose development involves various processes, such as insulin resistance, lipotoxicity, inflammation, cytokine imbalance, the activation of innate immunity, microbiota and environmental and genetic factors. Numerous clinical studies have shown that the Mediterranean diet produces beneficial effects in NAFLD patients. The aim of this review is to summarize the beneficial effects of lycopene, a soluble pigment found in fruit and vegetables, in NAFLD. Full article
(This article belongs to the Special Issue From Liver Fibrosis to Carcinoma: Physiopathological Mechanisms, Diagnosis and Treatment)
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