Clinical, Translational and Basic Research on Liver Diseases

Dear Colleagues,

Personalized medicine is one of the new approaches to liver disease management. Liver research over the last decade has shown that response to therapy is variable, hence personalization and identifying factors that will enhance the predictive utility of targeted therapy are critical. There are assays such as the lymphocyte toxicity assay which can identify the hypersensitivity of each individual to a drug of use or misuse. The knowledge of the drug adverse events can save lives and can reduce health care costs dramatically. Biomarkers can help identify diseases of the liver. Cancer immunotherapy, which aims to control the immune system to eradicate cancer, needs to be personalized, because anticancer immune responses can be inhibited in various ways from patient to patient. Cancer immunotherapy includes immune checkpoint inhibitors and monoclonal antibodies, as well as cell therapy, immunogene therapy, and vaccines. Combinations of programmed apoptosis protein 1 (PD-1)/ligand 1 (PD-L1) chemotherapy and radiation therapy, are being explored. Biomarkers are important for predicting the response to immunotherapy in hepatocellular and cholangio- carcinomas. Molecular diagnostics and immunohistochemistry are important technologies for guiding treatment in diseases of the liver.

The scope of the present Topic is to present the need for

• The identification of molecular targets as predictive biomarkers is important for matched targeted therapy in alcoholic and non-alcoholic steatohepatitis.

• Constant evaluation of assays to predict and diagnose drug-induced liver injury (DILI).

• Integration of viral-induced liver diseases as a possible co-morbidity in alcohol and drugs of misuse liver disease laboratory diagnosis.

• Validation of biomarkers to predict response to combination therapies, including those that characterize the tumor microenvironment and targeted signaling pathways in carcinoma of the liver.

Prof. Dr. Neuman Manuela
Prof. Dr. Stephen Malnick
Topic Editors

Deadline for abstract submissions: 30 June 2022.
Deadline for manuscript submissions: 31 August 2022.

Topic Board

Prof. Dr. Neuman Manuela
E-Mail Website
Topic Editor-in-Chief
In Vitro Drug Safety and Biotechnology, Département of Pharmacology and Toxicology, Faculty of Medicine, University of Toronto, Toronto, Ontario, M2R 1W6, Canada
Interests: inflammation and repair in liver disease; clinical, translational and molecular events in liver disease; gastroenterology; autoimmune hepatitis; alcoholic and non-alcoholic steato hepatitis; metabolic diseases; drug-induced organ injury; drug-induced liver injury; personalized therapies in the diseases of the liver; personalized immuno-oncology in hepatocellular carcinoma
Prof. Dr. Stephen Malnick
E-Mail Website
Topic Editor
Internal Medicine C, Kaplan Medical Center, Rehovot, Israel
Interests: clinical liver disease; gastroenterology; autoimmune hepatitis; alcoholic and non-alcoholic steatohepatitis; metabolic liver disease

Keywords

  • apoptosome
  • inflammasome
  • personalized medicine
  • pharmacovigilance
  • alcoholic and non-alcoholic fatty liver
  • drug interactions and the liver
  • molecular triggers for viral disease

Relevant Journals List

Journal Name Impact Factor CiteScore Launched Year First Decision (median) APC
Biomedicines
biomedicines
6.081 3.6 2013 16.34 Days 2000 CHF Submit
Current Issues in Molecular Biology
cimb
2.081 4.3 1999 16.15 Days 1600 CHF Submit
Diagnostics
diagnostics
3.706 1.4 2011 15.87 Days 1600 CHF Submit
International Journal of Molecular Sciences
ijms
5.923 6.0 2000 14.32 Days 2000 CHF Submit
Reports
reports
- - 2018 21.45 Days 1200 CHF Submit

Published Papers (5 papers)

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Article
Weight Gain after Interferon-Free Treatment of Chronic Hepatitis C—Results from the German Hepatitis C-Registry (DHC-R)
by , , , , , , , , , , and
Biomedicines 2021, 9(10), 1495; https://doi.org/10.3390/biomedicines9101495 (registering DOI) - 19 Oct 2021
Abstract
Chronic hepatitis C can be treated very effectively with direct-acting antivirals (DAA) with only minor side effects compared to an interferon-containing treatment regimen. The significance of metabolic comorbidities after HCV cure is not well defined. This study aims to investigate short- and long-term [...] Read more.
Chronic hepatitis C can be treated very effectively with direct-acting antivirals (DAA) with only minor side effects compared to an interferon-containing treatment regimen. The significance of metabolic comorbidities after HCV cure is not well defined. This study aims to investigate short- and long-term weight change of patients receiving interferon-free antiviral treatment for chronic hepatitis C. The German Hepatitis C-registry (DHC-R) is a national multicenter real-world cohort. A total of 5111 patients were followed prospectively after DAA treatment for up to 3 years. Weight change compared to baseline was analyzed at end of treatment and at years 1, 2, and 3 after completion of antiviral therapy. Regression analysis was performed to identify baseline predictors for weight change. While there was no relevant mean weight change (−0.2 kg, SD 4.3 kg) at the end of antiviral treatment, weight started to increase during long-term follow-up reaching +1.7 kg (SD 8.0 kg, p < 0.001) compared to baseline at 3 years (follow-up year 3, FU3) after completion of antiviral therapy. 48%, 31%, and 22% of patients had a weight gain greater than 1, 3, and 5 kg at FU3, respectively. During follow-up, a body mass index (BMI) <30 proved to be the only consistent predictor for weight gain. DAA treatment is followed by a substantial weight gain (+3 kg or more) in one-third of the patients during long-term follow-up. Non-obese patients seemed to be most vulnerable to weight gain. The body compartment involved in weight gain as well as the mechanism of weight gain remain to be elucidated. Full article
Article
Progranulin A Promotes Compensatory Hepatocyte Proliferation via HGF/c-Met Signaling after Partial Hepatectomy in Zebrafish
by , , , , , and
Int. J. Mol. Sci. 2021, 22(20), 11217; https://doi.org/10.3390/ijms222011217 (registering DOI) - 18 Oct 2021
Abstract
Compensatory hepatocyte proliferation and other liver regenerative processes are activated to sustain normal physiological function after liver injury. A major mitogen for liver regeneration is hepatocyte growth factor (HGF), and a previous study indicated that progranulin could modulate c-met, the receptor for HGF, [...] Read more.
Compensatory hepatocyte proliferation and other liver regenerative processes are activated to sustain normal physiological function after liver injury. A major mitogen for liver regeneration is hepatocyte growth factor (HGF), and a previous study indicated that progranulin could modulate c-met, the receptor for HGF, to initiate hepatic outgrowth from hepatoblasts during embryonic development. However, a role for progranulin in compensatory hepatocyte proliferation has not been shown previously. Therefore, this study was undertaken to clarify whether progranulin plays a regulatory role during liver regeneration. To this end, we established a partial hepatectomy regeneration model in adult zebrafish that express a liver-specific fluorescent reporter. Using this model, we found that loss of progranulin A (GrnA) function by intraperitoneal-injection of a Vivo-Morpholino impaired and delayed liver regeneration after partial hepatectomy. Furthermore, transcriptome analysis and confirmatory quantitative real-time PCR suggested that cell cycle progression and cell proliferation was not as active in the morphants as controls, which may have been the result of comparative downregulation of the HGF/c-met axis by 36 h after partial hepatectomy. Finally, liver-specific overexpression of GrnA in transgenic zebrafish caused more abundant cell proliferation after partial hepatectomy compared to wild types. Thus, we conclude that GrnA positively regulates HGF/c-met signaling to promote hepatocyte proliferation during liver regeneration. Full article
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Article
Assessment of Bioavailability after In Vitro Digestion and First Pass Metabolism of Bioactive Peptides from Collagen Hydrolysates
Curr. Issues Mol. Biol. 2021, 43(3), 1592-1605; https://doi.org/10.3390/cimb43030113 - 13 Oct 2021
Abstract
Collagen hydrolysates (CHs) are composed of bioactive peptides (BAPs), which possess health enhancing properties. There is a knowledge gap regarding the bioavailability of these BAPs that involves intestinal transport and hepatic first pass effects. A simulated gastrointestinal model was used to generate digesta [...] Read more.
Collagen hydrolysates (CHs) are composed of bioactive peptides (BAPs), which possess health enhancing properties. There is a knowledge gap regarding the bioavailability of these BAPs that involves intestinal transport and hepatic first pass effects. A simulated gastrointestinal model was used to generate digesta from two CHs (CH-GL and CH-OPT), which were applied to a novel transwell co-culture of human intestinal epithelium cell line-6 (HIEC-6) and hepatic (HepG2) cells to simulate in vivo conditions of absorption and first pass metabolism. Peptide transport, hepatic first pass effects, and bioavailability were determined by measuring BAPs (Gly-Pro, Hyp-Gly, Ala-Hyp, Pro-Hyp, Gly-Pro-Hyp) using an innovative capillary electrophoresis method. All peptides were transported across the intestinal cell layer to varying degrees with both CHs; however, Gly-Pro-Hyp was transported only with CH-GL, but not CH-OPT. Notable hepatic production was observed for Ala-Hyp with both CH treatments, and for Pro-Hyp and Gly-Pro with CH-GL only. All peptides were bioavailable (>10%), except for Gly-Pro-Hyp after CH-OPT. Overall, a high degree of transport and hepatic first pass effects on CH-derived BAPs were observed. Further research is needed to explore the hepatic mechanisms related to the production of BAPs and the bifunctional effects of the bioavailable BAPs noted in this study. Full article
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Article
The Persistence of Hepatitis C Virus Infection in Hepatocytes Promotes Hepatocellular Carcinoma Progression by Pro-Inflammatory Interluekin-8 Expression
Biomedicines 2021, 9(10), 1446; https://doi.org/10.3390/biomedicines9101446 (registering DOI) - 11 Oct 2021
Abstract
Background: A large amount of epidemiological evidence indicates that persistent HCV infection is the main risk factor for HCC. We aimed to study the effects of persistent HCV infection on the interaction of the virus and host cell to identify cancer gene profiles. [...] Read more.
Background: A large amount of epidemiological evidence indicates that persistent HCV infection is the main risk factor for HCC. We aimed to study the effects of persistent HCV infection on the interaction of the virus and host cell to identify cancer gene profiles. Methods: Next-generation sequencing (NGS) was used to identify differentially expressed genes between uninfected Huh7.5.1 control cells, short-term HCV (S-HCV), early long-term HCV (eL-HCV), and long-term HCV (L-HCV) infections, which were analyzed using different dynamic bioinformatics and analytic tools. mRNA expression was validated and quantified using q-PCR. One hundred ninety-six serum samples of HCV patients with IFN/RBV treatment were used to study chemokine levels. Results: S-HCV activates an inflammatory response and drives cell death and apoptosis through cell cycle arrest via MAPK signaling. L-HCV promotes cell growth and alters cell adhesion and chemokine signaling via CXCL8-mediated-SRC regulation. A total of 196 serum samples from the HCV and HCV-HCC cohorts demonstrated significantly upregulated pro-inflammatory CXCL8 in non-SVR (persistent HCV infection) patients in the HCV-HCC group. Conclusions: Persistent infection with HCV induced pro-inflammatory CXCL8 and the oncogene SRC, thereby triggering and promoting hepatocarcinogenesis. CXCL8 may be a potential biomarker for monitoring HCV-related HCC progression. Full article
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Article
Gravity-Based Flow Efficient Perfusion Culture System for Spheroids Mimicking Liver Inflammation
Biomedicines 2021, 9(10), 1369; https://doi.org/10.3390/biomedicines9101369 - 01 Oct 2021
Abstract
The spheroid culture system provides an efficient method to emulate organ-specific pathophysiology, overcoming the traditional two-dimensional (2D) cell culture limitations. The intervention of microfluidics in the spheroid culture platform has the potential to enhance the capacity of in vitro microphysiological tissues for disease [...] Read more.
The spheroid culture system provides an efficient method to emulate organ-specific pathophysiology, overcoming the traditional two-dimensional (2D) cell culture limitations. The intervention of microfluidics in the spheroid culture platform has the potential to enhance the capacity of in vitro microphysiological tissues for disease modeling. Conventionally, spheroid culture is carried out in static conditions, making the media nutrient-deficient around the spheroid periphery. The current approach tries to enhance the capacity of the spheroid culture platform by integrating the perfusion channel for dynamic culture conditions. A pro-inflammatory hepatic model was emulated using a coculture of HepG2 cell line, fibroblasts, and endothelial cells for validating the spheroid culture plate with a perfusable channel across the spheroid well. Enhanced proliferation and metabolic capacity of the microphysiological model were observed and further validated by metabolic assays. A comparative analysis of static and dynamic conditions validated the advantage of spheroid culture with dynamic media flow. Hepatic spheroids were found to have improved proliferation in dynamic flow conditions as compared to the static culture platform. The perfusable culture system for spheroids is more physiologically relevant as compared to the static spheroid culture system for disease and drug analysis. Full article
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