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Gastroenterology Insights
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Feature Papers in Liver Research
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Feature Papers in Liver Research

A special issue of Gastroenterology Insights (ISSN 2036-7422). This special issue belongs to the section "Liver".

Deadline for manuscript submissions: closed (31 December 2023) | Viewed by 45552

Special Issue Editor

Prof. Dr. David A. Gerber

E-Mail Website
Guest Editor
Department of Surgery, University of Cincinnati, Cincinnati, OH, USA
Interests: hepatocellular carcinoma; liver transplantation; liver stem cells

Special Issue Information

Dear Colleagues,

Liver disease encompasses a broad and exciting area of investigation that intersects with multiple areas of ongoing research endeavors. This Special Issue is dedicated to exciting and informative investigations around malignancies of the liver. From the identification of biomarkers, drug discovery and therapeutic interventions to investigations of the molecular phenotypes of various liver pathologies, this field of study is rapidly changing.

This Special Issue aims to collect articles in cutting-edge areas of investigation involving liver cancer research, including those which could contribute towards translational solutions for world-wide health challenges associated with hepatic malignancies using innovative ideas and rigorous scientific methodologies. In the case of review articles, they could provide a synthesis of ideas and have the potential to lead to future innovations, while simultaneously creating novel frameworks capable of advancing our understanding of cancers of the liver. We encourage Editorial Board Members of the liver section to contribute feature papers reflecting the latest progress in their research field, or to invite leading experts to contribute.

Prof. Dr. David A. Gerber
Guest Editor

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. Gastroenterology Insights is an international peer-reviewed open access quarterly 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 1600 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

  • hepatocellular carcinoma
  • cholangiocarcinoma
  • fibrolamellar carcinoma
  • liver cancer
  • diagnosis
  • treatment

Published Papers (7 papers)

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Research

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13 pages, 1089 KiB  
Article
Genetic Variation in Angiotensin II Type 1 Receptor Is Linked to Lipid Levels and Hepatic Steatosis in Alcohol-Associated Liver Disease, but Not to Cirrhosis or Hepatocellular Carcinoma
by Hans Dieter Nischalke, Franziska Schmalz, Janett Fischer, Christine Möller, Madlen Matz-Soja, Benjamin Krämer, Bettina Langhans, Jacob Nattermann, Thomas Berg, Christian P. Strassburg and Philipp Lutz
Gastroenterol. Insights 2024, 15(1), 19-31; https://doi.org/10.3390/gastroent15010002 - 03 Jan 2024
Viewed by 756
Abstract
Background: Development of cirrhosis and hepatocellular carcinoma (HCC) in patients with high alcohol intake is modulated by genetic predispositions. Genetic variation in angiotensin II type 1 receptor (AGTR1) has been described as a risk factor for non-alcoholic fatty liver disease in [...] Read more.
Background: Development of cirrhosis and hepatocellular carcinoma (HCC) in patients with high alcohol intake is modulated by genetic predispositions. Genetic variation in angiotensin II type 1 receptor (AGTR1) has been described as a risk factor for non-alcoholic fatty liver disease in Asian patients. Methods: We analysed Caucasian patients with alcohol–associated cirrhosis without (n = 238) and with (n = 339) HCC, healthy controls (n = 200), and HCV–infected cirrhotic patients with and without HCC (n = 263) for association with the polymorphisms rs3772622 and rs2276736 in AGTR1. Results: Rs2276736 in AGTR1 was associated with both low–density lipoprotein (LDL) cholesterol levels and hepatic steatosis in patients with alcohol–associated liver disease. The distribution of genotypes for both rs3772622 and rs2276736 in AGTR1 were comparable between controls, cirrhosis patients, and those with HCC. Minor allele frequencies were 32% (44%) in healthy controls, 35%/34% (46%/45%) in alcohol–associated liver disease without/with HCC and 31%/38% (43%/39%) in HCV cirrhosis and HCV HCC, respectively. The genotype of the most important genetic risk factor for fatty liver disease, PNPLA3 I148M, did not interact with the AGTR1 polymorphisms. Conclusion: Genetic variation in AGTR1, although associated with blood lipid levels and hepatic steatosis, is not a risk factor for alcohol–associated cirrhosis or HCC in Caucasians. Full article
(This article belongs to the Special Issue Feature Papers in Liver Research)
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11 pages, 1541 KiB  
Article
Lysosomal Acid Lipase Deficiency in the Etiological Investigation of Cryptogenic Liver Disease in Adults: A Multicenter Brazilian Study
by Aline Coelho Rocha Candolo, Guilherme Grossi Lopes Cançado, Patricia Momoyo Zitelli, Daniel Ferraz de Campos Mazo, Claudia Pinto Marques Oliveira, Marlone Cunha-Silva, Raquel Dias Greca, Roberta Chaves Araújo, Amanda Sacha Paulino Tolentino Alustau, Claudia Alves Couto, Mateus Jorge Nardelli, Roque Gabriel Rezende de Lima, Alberto Queiroz Farias, Flair José Carrilho and Mário Guimarães Pessôa
Gastroenterol. Insights 2023, 14(4), 564-574; https://doi.org/10.3390/gastroent14040040 - 09 Nov 2023
Viewed by 1022
Abstract
Background: Lysosomal acid lipase deficiency (LAL-D) is a rare genetic disease associated with the deregulation of lipid metabolism, leading to atherosclerosis, dyslipidemia, and hepatic steatosis, with potential progression to cirrhosis. Our study aims to assess the role of LAL-D in the setting of [...] Read more.
Background: Lysosomal acid lipase deficiency (LAL-D) is a rare genetic disease associated with the deregulation of lipid metabolism, leading to atherosclerosis, dyslipidemia, and hepatic steatosis, with potential progression to cirrhosis. Our study aims to assess the role of LAL-D in the setting of cryptogenic liver disease. Methods: A large multicenter cross-sectional study was conducted, which included 135 patients with cryptogenic liver disease from four liver centers in Brazil. All patients were submitted to the investigation of LAL enzyme activity on dried blood spots. Results: Three patients (two female) presented levels of LAL below the reference limit, compatible with LAL-D (2.2%). They had a mean age of 43.9 ± 10.1 years and a mean body-mass index (BMI) of 23.1 ± 1.7 kg/m2. The mean serum levels of glucose, HDL-cholesterol, and triglycerides were 89.7 ± 3.2, 21.7 ± 3.2, and 206.7 ± 25.5 mg/dL, respectively. All patients had duodenal polyposis with xanthomatous macrophages. LAL-D investigation should be considered for individuals with chronic liver disease of an unknown etiology, especially with a normal BMI, high triglycerides, and low-HDL-cholesterol levels. The identification of LAL-D patients is extremely important since enzyme replacement therapy with Sebelipase Alfa significantly increases their survival. Full article
(This article belongs to the Special Issue Feature Papers in Liver Research)
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10 pages, 1893 KiB  
Article
Blood-Based Non-Invasive Tests of Hepatic Fibrosis in Autoimmune Hepatitis: Application among Selected Patients Leads to Higher Accuracy
by Marco Ferronato, Marco Lenzi, Paolo Muratori and Luigi Muratori
Gastroenterol. Insights 2022, 13(3), 286-295; https://doi.org/10.3390/gastroent13030029 - 09 Sep 2022
Cited by 2 | Viewed by 1689
Abstract
Background. Assessment of liver fibrosis is essential to guide treatment in autoimmune hepatitis (AIH), but non-invasive tests (NITs) showed poor accuracy. Our study aims to evaluate the performance of NITs among different AIH presentations. Methods. Monocentric retrospective study among 122 AIH patients. NITs [...] Read more.
Background. Assessment of liver fibrosis is essential to guide treatment in autoimmune hepatitis (AIH), but non-invasive tests (NITs) showed poor accuracy. Our study aims to evaluate the performance of NITs among different AIH presentations. Methods. Monocentric retrospective study among 122 AIH patients. NITs were compared to histological grading of liver fibrosis. We performed an accuracy analysis among acute (jaundice and/or transaminases > 10 times upper limit of normal) and non-acute patients. Results. A significant difference in the distribution of NIT values for each Ishak stage was found for spleen-diameter-to-platelet-count ratio (SD/PC) (p < 0.001), fibrosis-4-score (FIB-4) (p = 0.002), AST-to-ALT ratio (AAR) (p = 0.002), red-blood-cell-width-distribution-to-platelet-count ratio (RDW/PC) (p = 0.008) and AST-to-platelet-count ratio (APRI) (p = 0.029). The AUC for advanced fibrosis of SD/PC, FIB-4, RDW/PC, APRI and AAR were, respectively, 0.814, 0.770, 0.768, 0.708 and 0.694. The AUC of SD/PC, FIB-4 and APRI in non-acute subgroup were 0.902, 0.834 and 0.758, while in acute patients they were 0.754, 0.724 and 0.716. RDW/PC and AAR weren’t different among the two subgroups. Conclusions. For SD/PC, FIB-4 and APRI, diagnostic accuracy is higher in patients with non-acute presentation. In this context, SD/PC and FIB-4 showed an overall performance that could be of interest in clinical practice alongside other non-invasive techniques. Full article
(This article belongs to the Special Issue Feature Papers in Liver Research)
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Review

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12 pages, 789 KiB  
Review
Benign Recurrent Intrahepatic Cholestasis: Where Are We Now?
by Eleni V. Geladari, Natalia G. Vallianou, Evangelia Margellou, Dimitris Kounatidis, Vassilios Sevastianos and Alexandra Alexopoulou
Gastroenterol. Insights 2024, 15(1), 156-167; https://doi.org/10.3390/gastroent15010011 - 06 Feb 2024
Viewed by 703
Abstract
Benign recurrent intrahepatic cholestasis (BRIC) stands as a rare genetic contributor to cholestasis, aligning itself within the spectrum of inherited intrahepatic cholestasis syndromes, such as progressive familial intrahepatic cholestasis (PFIC) and intrahepatic cholestasis of pregnancy. Manifesting in infancy or early adulthood, BRIC is [...] Read more.
Benign recurrent intrahepatic cholestasis (BRIC) stands as a rare genetic contributor to cholestasis, aligning itself within the spectrum of inherited intrahepatic cholestasis syndromes, such as progressive familial intrahepatic cholestasis (PFIC) and intrahepatic cholestasis of pregnancy. Manifesting in infancy or early adulthood, BRIC is marked by recurrent episodes of jaundice accompanied by intense pruritus, enduring from weeks to years across the lifespan. Normal gamma-glutamyl transferase (GGT) levels are a characteristic laboratory finding. Initially considered unlikely to progress to chronic liver disease or cirrhosis, some reports suggest BRIC may evolve into a continuous and progressive form of cholestasis. Moreover, these recurrent cholestatic episodes significantly impact quality of life, and certain mutations elevate the risk of hepatobiliary malignancy. Between episodes, histological findings of centrilobular cholestasis and abnormal laboratory parameters revert to normal, potentially obviating the need for liver biopsy. This review focuses on the genetic aspects of BRIC, its pathophysiology, clinical presentation, and prognosis. Additionally, it outlines triggering factors and available treatment options. Full article
(This article belongs to the Special Issue Feature Papers in Liver Research)
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22 pages, 1334 KiB  
Review
Hepatitis C and Nonalcoholic Steatohepatitis in the 21st Century: Impact on Liver Disease and Liver Transplantation
by Sonia Samuel, Ahmad Abulawi and Raza Malik
Gastroenterol. Insights 2023, 14(3), 249-270; https://doi.org/10.3390/gastroent14030018 - 29 Jun 2023
Cited by 1 | Viewed by 1822
Abstract
Hepatitis C infection is a leading etiology of hepatic dysfunction and a major indication for liver transplantation due to the development of fibrosis, cirrhosis, and hepatocellular carcinoma. Nonalcoholic fatty liver disease (NAFLD) and, specifically, its subtype nonalcoholic steatohepatitis (NASH) is a rising cause [...] Read more.
Hepatitis C infection is a leading etiology of hepatic dysfunction and a major indication for liver transplantation due to the development of fibrosis, cirrhosis, and hepatocellular carcinoma. Nonalcoholic fatty liver disease (NAFLD) and, specifically, its subtype nonalcoholic steatohepatitis (NASH) is a rising cause of liver disease. It is predicted to surpass hepatitis C as a leading indication for transplant. The introduction of direct-acting antivirals (DAAs) decreased the prevalence of chronic hepatitis C infections, but the obesity epidemic and metabolic syndrome have increased the prevalence of NASH. Weight loss and dietary modifications are recommended NASH therapies, but unlike for hepatitis C, federally approved agents are lacking and currently under investigation. Clinical trials face many barriers in NASH treatment because of the difficulty of diagnosis and a lack of standardized and accurate clinical and histologic responses. Mortality and morbidity in NASH are heightened because of the presence of multiple comorbidities including cardiovascular disease, diabetes, and renal dysfunction. A liver transplant may be indicated, but a thorough screening of candidates, including a comprehensive cardiovascular assessment, is essential to ensuring successful outcomes pre- and post-transplant. Therapeutic agents for NASH are warranted before it becomes a significant and leading cause of morbidity and mortality worldwide. Full article
(This article belongs to the Special Issue Feature Papers in Liver Research)
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10 pages, 667 KiB  
Review
Clinical and Safety Evaluation of Liv.52 in Alcoholic Liver Disease: A Review
by Subramanian Ganesh, Neeraj Joshi, Mukesh Kumar Jain, Lokendra Sharma, Anish Desai, Mohamed Rafiq, Uddagiri Venkanna Babu and Rajesh Kumawat
Gastroenterol. Insights 2022, 13(4), 377-386; https://doi.org/10.3390/gastroent13040037 - 13 Nov 2022
Cited by 2 | Viewed by 36911
Abstract
Alcoholic liver disease (ALD) has been a growing concern in developed and developing nations. Oxidative stress and lipid peroxidation are the most common cause of the development and progression of ALD. Due to paucity in the number and efficacy of hepatoprotective drugs currently [...] Read more.
Alcoholic liver disease (ALD) has been a growing concern in developed and developing nations. Oxidative stress and lipid peroxidation are the most common cause of the development and progression of ALD. Due to paucity in the number and efficacy of hepatoprotective drugs currently available, and with the easy availability of natural therapy and herbal medicines, ALD is managed using a combination of pharmaceutical interventions and herbal medications. However, the effectiveness of these hepatoprotectives is controversial. Preclinical and clinical studies have demonstrated that Liv.52 modulates the lipotropic activity of hepatocytes, reduces inflammation, enhances alcohol and acetaldehyde metabolism, and protects the hepatic parenchyma by restoring the antioxidant levels of hepatocytes. Clinical studies further support that there is improvement in the subjective symptoms of patients as well as improvements in liver function test parameters. Studies suggest that Liv.52 is well tolerated and has no reported side effects. Full article
(This article belongs to the Special Issue Feature Papers in Liver Research)
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Other

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7 pages, 538 KiB  
Case Report
A Case of Advanced Hepatocellular Carcinoma with Bone Metastases Managed with Tyrosine Kinase Inhibitors and Aggressive Palliative Radiation Therapy: Role of Combination Therapy for Extending Survival
by Luca Ielasi, Bernardo Stefanini, Fabio Piscaglia, Alessandro Granito and Francesco Tovoli
Gastroenterol. Insights 2023, 14(1), 38-44; https://doi.org/10.3390/gastroent14010005 - 12 Feb 2023
Cited by 2 | Viewed by 1813
Abstract
We report the case of a 68-year-old man with advanced hepatocellular carcinoma (HCC) with multiple bone metastases (BM) treated with tyrosine kinase inhibitors. Despite an insufficient disease control on BM with a progression free survival (PFS) of 6 months, sorafenib was not discontinued [...] Read more.
We report the case of a 68-year-old man with advanced hepatocellular carcinoma (HCC) with multiple bone metastases (BM) treated with tyrosine kinase inhibitors. Despite an insufficient disease control on BM with a progression free survival (PFS) of 6 months, sorafenib was not discontinued and multiple radiation therapy (RT) sessions with a palliative purpose were performed. Thanks to this aggressive radiotherapy approach in order to control the bone tumor burden, the patient has continued sorafenib for 34.6 months achieving an overall survival (OS) of 41.3 months. This result highlights the importance of a tailored management of patients with advanced HCC and the role of the RT for BM control, even if at lower cumulative radiation dose, for extending patient survival. Full article
(This article belongs to the Special Issue Feature Papers in Liver Research)
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