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Advances in Chronic Liver Disease: From Pathophysiology to Clinical Practice
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Advances in Chronic Liver Disease: From Pathophysiology to Clinical Practice

A special issue of Biology (ISSN 2079-7737). This special issue belongs to the section "Physiology".

Deadline for manuscript submissions: closed (15 May 2023) | Viewed by 12115

Special Issue Editors

Dr. Gian Paolo Caviglia

E-Mail Website
Guest Editor
Department of Medical Sciences, University of Turin, 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. Chiara Rosso

E-Mail Website
Guest Editor
Department of Medical Sciences, University of Turin, 10126 Turin, Italy
Interests: non-alcoholic fatty liver disease (NAFLD); non-invasive biomarkers for risk stratification in NAFLD; pathophysiology of insulin resistance; effect of diet and lifestyle intervention on insulin resistance and NAFLD severity
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

In the last years, remarkable advances have been achieved in the management and treatment of chronic liver diseases. The development of novel direct acting antivirals (DAA) represented a milestone in the treatment of chronic HCV infection; other drugs are expected in few years also for the treatment of hepatitis B/delta virus (HBV/HDV) infection. In the setting of non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH), the deeper understanding of the pathophysiological mechanisms involved in the onset and progression of liver damage, unveiled novel potential therapeutic targets.

In addition, novel diagnostic and prognostic biomarkers have been discovered, and are currently under evaluation as potential tools to help clinicians in the management of patients with chronic liver disease. In this regard, the availability of novel high throughput technologies played a pivotal role.

The aim of this Special Issue, entitled “Advances in Chronic Liver Disease: From Pathophysiology to Clinical Practice” is to focus on the novelties in the field of translational research, from basic to clinical studiesin any setting of chronic liver diseases. Authors are kindly invited to submit original papers as well as reviews describing the state of the art and novel perspectives on this topic.

Dr. Gian Paolo Caviglia
Dr. Chiara Rosso
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. Biology 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 2700 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 fibrosis
  • cirrhosis
  • hepatocellular carcinoma
  • biomarkers
  • antiviral therapy
  • extra-hepatic manifestations
  • Omics

Published Papers (5 papers)

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Research

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18 pages, 2756 KiB  
Article
Human Mesenchymal Stem Cells Modified with the NS5A Gene of Hepatitis C Virus Induce a Cellular Immune Response Exceeding the Response to DNA Immunization with This Gene
by Olga V. Masalova, Ekaterina I. Lesnova, Vladimir A. Kalsin, Regina R. Klimova, Natalya E. Fedorova, Vyacheslav V. Kozlov, Natalya A. Demidova, Kirill I. Yurlov, Mikhail A. Konoplyannikov, Tatyana N. Nikolaeva, Alexander V. Pronin, Vladimir P. Baklaushev and Alla A. Kushch
Biology 2023, 12(6), 792; https://doi.org/10.3390/biology12060792 - 30 May 2023
Viewed by 1608
Abstract
Hepatitis C virus (HCV) is one of the basic culprits behind chronic liver disease, which may result in cirrhosis and hepatocarcinoma. In spite of the extensive research conducted, a vaccine against HCV has not been yet created. We have obtained human mesenchymal stem [...] Read more.
Hepatitis C virus (HCV) is one of the basic culprits behind chronic liver disease, which may result in cirrhosis and hepatocarcinoma. In spite of the extensive research conducted, a vaccine against HCV has not been yet created. We have obtained human mesenchymal stem cells (hMSCs) and used them for expressing the HCV NS5A protein as a model vaccination platform. Sixteen hMSC lines of a different origin were transfected with the pcNS5A-GFP plasmid to obtain genetically modified MSCs (mMSCs). The highest efficiency was obtained by the transfection of dental pulp MSCs. C57BL/6 mice were immunized intravenously with mMSCs, and the immune response was compared with the response to the pcNS5A-GFP plasmid, which was injected intramuscularly. It was shown that the antigen-specific lymphocyte proliferation and the number of IFN-γ-synthesizing cells were two to three times higher after the mMSC immunization compared to the DNA immunization. In addition, mMSCs induced more CD4+ memory T cells and an increase in the CD4+/CD8+ ratio. The results suggest that the immunostimulatory effect of mMSCs is associated with the switch of MSCs to the pro-inflammatory phenotype and a decrease in the proportion of myeloid derived suppressor cells. Thus, the possibility of using human mMSCs for the creation of a vaccine against HCV has been shown for the first time. Full article
(This article belongs to the Special Issue Advances in Chronic Liver Disease: From Pathophysiology to Clinical Practice)
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10 pages, 1813 KiB  
Article
Identification of the Best Cut-Off Value of PIVKA-II for the Surveillance of Patients at Risk of Hepatocellular Carcinoma Development
by Gian Paolo Caviglia, Maria Lorena Abate, Giulia Troshina, Patrizia Carucci, Emanuela Rolle, Alessandra Risso, Michela Emma Burlone, Alice Albè, Martina Crevola, Emma Clara Musso, Chiara Rosso, Angelo Armandi, Antonella Olivero, Rosalba Minisini, Giorgio Maria Saracco, Elisabetta Bugianesi, Mario Pirisi, Alessia Ciancio and Silvia Gaia
Biology 2023, 12(1), 94; https://doi.org/10.3390/biology12010094 - 7 Jan 2023
Cited by 2 | Viewed by 2648
Abstract
Patients with cirrhosis are at risk of hepatocellular carcinoma (HCC) development and, according to current guidelines, should undergo surveillance by ultrasound at six month intervals. Due to the known limitations of surveillance strategies based on ultrasonography, the use of tumor biomarkers, although debated, [...] Read more.
Patients with cirrhosis are at risk of hepatocellular carcinoma (HCC) development and, according to current guidelines, should undergo surveillance by ultrasound at six month intervals. Due to the known limitations of surveillance strategies based on ultrasonography, the use of tumor biomarkers, although debated, is common practice in many centers. The aim of the study was to identify the best cut-off value for one of such biomarkers, protein induced by vitamin K absence, or antagonist-II (PIVKA-II). We retrospectively enrolled 1187 patients with liver cirrhosis: 205 with a diagnosis of HCC (median age 67 years, 81.0% males) and 982 without tumor (median age 64 years, 56.2% males). During a median follow-up (FU) of 34.6 (11.4–43.7) months, 118 out of 982 (12.0%) patients developed HCC. Serum PIVKA-II was assessed by chemiluminescence immunoassay on the Lumipulse® G600 II platform (Fujirebio, Tokyo, Japan). In the overall cohort (n = 1187), PIVKA-II showed an area under the curve (AUC) of 0.802 for HCC detection. The best cut-off value that maximized sensitivity was 50 mAU/mL (sensitivity = 80%, specificity = 64%). In the 982 patients without HCC at baseline, PIVKA-II > 50 mAU/mL was associated with an increased risk of HCC development during the FU (HR = 1.74, 95% CI 1.21–2.51; p = 0.003)). In conclusion, the evaluation of serum PIVKA-II showed a good performance for HCC detection; a cut-off value > 50 mAU/mL could be suitable for the surveillance of patients who are at risk of developing HCC. Full article
(This article belongs to the Special Issue Advances in Chronic Liver Disease: From Pathophysiology to Clinical Practice)
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Review

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12 pages, 737 KiB  
Review
Five Decades of HBV Infection in Italy: A Continuous Challenge
by Tommaso Stroffolini and Giacomo Stroffolini
Biology 2023, 12(8), 1075; https://doi.org/10.3390/biology12081075 - 2 Aug 2023
Cited by 1 | Viewed by 1273
Abstract
In Italy, Hepatitis B virus (HBV) infection has been characterized by several changes over the last five decades. In 2019, the incidence of acute HBV among subjects targeted by the vaccination campaign was 0 cases in the age group 0–14 years and 0.1/100,000 [...] Read more.
In Italy, Hepatitis B virus (HBV) infection has been characterized by several changes over the last five decades. In 2019, the incidence of acute HBV among subjects targeted by the vaccination campaign was 0 cases in the age group 0–14 years and 0.1/100,000 in the age group 15–24. Nowadays, the burden of different stages of HBV-related chronic liver diseases is minimal. Intravenous drug use is no longer a risk factor (O.R. 0.7; 95% C.I. 0.5–1.02) for acquiring acute HBV; the proportion of cases reporting this exposure fell from 29.8% to 3.3% over the last two decades. The key public health intervention has been the compulsory vaccination campaign started in 1991 for infants 3 months old and 1–2 years old (the latter group for the first 12 years of the campaign). Moreover, non-immunogenic factors and the availability of effective oral antiviral drugs have played and continue to play a prominent role. The potential availability of new oral antiviral drugs with the inherent ability to eliminate the genomic HBV reservoirs may represent a further crucial step in the elimination of the virus in people that are already infected. Full article
(This article belongs to the Special Issue Advances in Chronic Liver Disease: From Pathophysiology to Clinical Practice)
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23 pages, 1498 KiB  
Review
Burden, Outcome, and Comorbidities of Extrahepatic Manifestations in Hepatitis C Virus Infection
by Busara Songtanin and Kenneth Nugent
Biology 2023, 12(1), 23; https://doi.org/10.3390/biology12010023 - 22 Dec 2022
Cited by 10 | Viewed by 4701
Abstract
Hepatitis C virus (HCV) is a significant cause of chronic liver diseases worldwide and is associated with negative consequences, including cirrhosis, hepatic decompensation, hepatocellular carcinoma, and increased risk of mortality. In addition to liver-related morbidities, HCV is also associated with several extrahepatic manifestations, [...] Read more.
Hepatitis C virus (HCV) is a significant cause of chronic liver diseases worldwide and is associated with negative consequences, including cirrhosis, hepatic decompensation, hepatocellular carcinoma, and increased risk of mortality. In addition to liver-related morbidities, HCV is also associated with several extrahepatic manifestations, including mixed cryoglobulinemia, diabetes mellitus, cardiocerebrovascular disease, lymphoma, and autoimmune diseases. These non-liver-related complications of HCV increase the complexity of this disease and can contribute to the economic burden, morbidity, quality of life, and mortality throughout the world. Therefore, understanding how this virus can contribute to each extrahepatic manifestation is worth investigating. Currently, the advancement of HCV treatment with the advent of direct-acting anti-viral agents (DAAs) has led to a high cure rate as a result of sustained virologic response and tremendously reduced the burden of extrahepatic complications. However, HCV-associated extrahepatic manifestations remain a relevant concern, and this review aims to give an updated highlight of the prevalence, risk factors, associated burdens, and treatment options for these conditions. Full article
(This article belongs to the Special Issue Advances in Chronic Liver Disease: From Pathophysiology to Clinical Practice)
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Other

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9 pages, 702 KiB  
Brief Report
Biomarkers of Type IV Collagen Turnover Reflect Disease Activity in Patients with Early-Stage Non-Alcoholic Fatty Liver (NAFL)
by Ida Lønsmann, Jane I. Grove, Asma Haider, Philip Kaye, Morten A. Karsdal, Diana J. Leeming and Guruprasad P. Aithal
Biology 2023, 12(8), 1087; https://doi.org/10.3390/biology12081087 - 4 Aug 2023
Viewed by 1092
Abstract
Background: Identification of progressive liver disease necessitates the finding of novel non-invasive methods to identify and monitor patients in need of early intervention. Investigating patients with early-liver injury may help identify unique biomarkers. Early-liver injury is characterized by remodeling of the hepatocyte basement [...] Read more.
Background: Identification of progressive liver disease necessitates the finding of novel non-invasive methods to identify and monitor patients in need of early intervention. Investigating patients with early-liver injury may help identify unique biomarkers. Early-liver injury is characterized by remodeling of the hepatocyte basement membrane (BM) of the extracellular matrix. Thus, we quantified biomarkers targeting two distinct neo-epitopes of the major BM collagen, type IV collagen (PRO-C4 and C4M), in patients spanning the non-alcoholic fatty liver disease (NAFLD) spectrum. Methods: We evaluated PRO-C4 and C4M in a cross-sectional study with 97 patients with NAFLD confirmed on histology. Serological levels of PRO-C4 and C4M were quantified using validated competitive enzyme-linked immunosorbent assays (ELISA). Using the fatty liver inhibition of progression (FLIP) algorithm, we stratified patients into two groups: non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH). Biomarker levels were investigated in the two groups in patients stratified by the NAFLD activity score (NAS). In both groups, biomarker measurements were analyzed in relation to histological scorings of steatosis, inflammation, ballooning, and fibrosis. Results: Patients had a body mass index (BMI) of 30.9 ± 5.6 kg/m2, age of 53 ± 13 years and a NAS range of 1–8. Upon stratification by FLIP, the NASH patients had higher platelets, ALT, and AST levels than the NAFL group. Both PRO-C4 (p = 0.0125) and C4M (p = 0.003) increased with increasing NAS solely within the NAFL group; however, a large variability was present in the NASH group. Furthermore, both markers were significantly associated with lobular inflammation (p = 0.020 and p = 0.048) and steatosis (p = 0.004 and p = 0.015) in patients with NAFL. Conclusions: This study found that type IV collagen turnover increased with the increase in NAS in patients with NAFL; however, this was not the case in patients with NASH. These findings support the assessments of the BM turnover using biomarkers in patients with early-disease development. These biomarkers may be used to track specific processes involved in the early pathobiology of NAFL. Full article
(This article belongs to the Special Issue Advances in Chronic Liver Disease: From Pathophysiology to Clinical Practice)
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