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Advances in Pathogenesis and Therapeutics of Hepatobiliary Diseases Volume II
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Advances in Pathogenesis and Therapeutics of Hepatobiliary Diseases Volume II

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Molecular and Translational Medicine".

Deadline for manuscript submissions: closed (31 July 2024) | Viewed by 13777

Special Issue Editor

Dr. Jinghua Wang

E-Mail Website
Guest Editor
Institute of Oriental Medicine, Dongguk University, 32, Dongguk-ro, Goyang 10326, Gyeonggi-do, Republic of Korea
Interests: functional dyspepsia; gut microbiota; herbal medicine; gastrointestinal diseases
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

In mammals, the hepatic and biliary system comprises serval essential organs, including the liver, bile duct, and gallbladder, for participating in the metabolism of both diets and drugs. In recent decades, the burden of hepatobiliary disease has been heavy, and the overall trend is gradually upwards worldwide. Specifically, around two million patients die annually in the world due to liver cirrhosis, viral hepatitis, and hepatic carcinoma. Nevertheless, a feasible therapeutic strategy is still not available because of the heterogeneity of pathophysiologic mechanisms. Recently, with the rapid improvement of cutting-edge technology, e.g., OMICs, more and more evidence has demonstrated that symbiotic bacteria, as a hidden “organ” in the holobiont, can disrupt the normal function of the hepatic and biliary system. For instance, gut-microbiota-derived PAMPs (pathogen-associated molecular patterns) and bile acid metabolites affect liver cancer progression and metastasis through immune-regulation, such as NKT cells and cytotoxic T cells. Further, many studies have shown that commensal microbes play a crucial role in non-alcoholic fatty liver disease. However, the causality and corresponding mechanisms are still indistinct. Beyond that, many explicit molecular mechanisms and pathological factors regarding other hepatobiliary diseases are still to be discovered. Therefore, this Special Issue, titled “Advances in Pathogenesis and Therapeutics of Hepatobiliary Diseases”, welcomes the submission of original research and review articles to address hepatobiliary disorders concerning novel insights into pathogenesis and therapeutic strategies. We look forward to your contributions.

Dr. Jinghua Wang
Guest Editor

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Keywords

  • acute/chronic liver diseases
  • NAFLD/MAFLD
  • viral hepatitis
  • cholestatic liver diseases
  • cholangitis
  • gallbladder diseases
  • metabolic disorders
  • bile acid metabolite
  • gut microbiota
  • precision medicine

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Published Papers (7 papers)

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Research

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19 pages, 19102 KiB  
Article
Single and Mixed Strains of Probiotics Reduced Hepatic Fat Accumulation and Inflammation and Altered Gut Microbiome in a Nonalcoholic Steatohepatitis Rat Model
by Maneerat Chayanupatkul, Panrawee Machchimapiro, Natthaya Chuaypen, Natcha Wanpiyarat, Somying Tumwasorn, Prasong Siriviriyakul and Duangporn Werawatganon
Biomedicines 2024, 12(8), 1847; https://doi.org/10.3390/biomedicines12081847 - 14 Aug 2024
Viewed by 924
Abstract
As gut dysbiosis has been implicated in the pathogenesis of nonalcoholic steatohepatitis (NASH), probiotic supplementation might be a potential treatment for this condition. The aim of this study was to evaluate the effects of single- and mixed-strain probiotics on the severity of NASH [...] Read more.
As gut dysbiosis has been implicated in the pathogenesis of nonalcoholic steatohepatitis (NASH), probiotic supplementation might be a potential treatment for this condition. The aim of this study was to evaluate the effects of single- and mixed-strain probiotics on the severity of NASH induced by a high-fat, high-fructose (HFHF) diet and their mechanisms of action. Male Sprague–Dawley rats were divided into four groups (n = 7 per group): control group, NASH group, NASH + single-strain group, and NASH + mixed-strain group. In the single-strain and mixed-strain groups, rats received Lactobacillus plantarum B7 and Lactobacillus rhamnosus L34 + Lactobacillus paracasei B13 by oral gavage once daily, respectively. The duration of the study was 6 weeks. Liver tissue was used for histopathology, hepatic fat content was assessed by Oil Red O staining and hepatic free fatty acid (FFA), and hepatic TLR4 and CD14 expression were assessed by immunohistochemistry. Fresh feces was collected for gut microbiota analysis. Liver histology revealed a higher degree of fat accumulation, hepatocyte ballooning, and lobular inflammation in the NASH group, which improved in probiotics-treated groups. The amounts of hepatic fat droplets and hepatic FFA levels were more pronounced in the NASH group than in the control and treatment groups. Serum TNF- α levels were significantly higher in the NASH group than in control and probiotic groups. The expression of CD14 and TLR4 increased in the NASH group as compared with the control and probiotics-treated groups. Alpha diversity was reduced in the NASH group, but increased in both treatment groups. The relative abundance of Lactobacillus significantly decreased in the NASH group, but increased in both treatment groups. The relative abundance of Akkermansia significantly increased in the NASH group, but decreased in both treatment groups. In conclusion, both single-strain and mixed-strain probiotics could improve NASH histology by suppressing inflammatory responses in the liver, with this improvement potentially being associated with changes in the gut microbiota. Full article
(This article belongs to the Special Issue Advances in Pathogenesis and Therapeutics of Hepatobiliary Diseases Volume II)
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12 pages, 1198 KiB  
Article
Angiographic Aspects of Transarterial Radioembolization: A Comparison of Technical Options to Avoid Extrahepatic Microsphere Depositions
by Peter Etzel, Robert Drescher, Florian Bürckenmeyer, Martin Freesmeyer and Anke Werner
Biomedicines 2024, 12(8), 1794; https://doi.org/10.3390/biomedicines12081794 - 7 Aug 2024
Viewed by 598
Abstract
The influence of the interventional treatment approach for transarterial radioembolization (TARE) on the incidence of extrahepatic microsphere depositions and to angiographic complications was evaluated. In total, 398 TARE cycles were analyzed. Interventional treatment approaches were classified as single treatment position (TP) with interventional [...] Read more.
The influence of the interventional treatment approach for transarterial radioembolization (TARE) on the incidence of extrahepatic microsphere depositions and to angiographic complications was evaluated. In total, 398 TARE cycles were analyzed. Interventional treatment approaches were classified as single treatment position (TP) with interventional occlusion (IO), multiple TPs without IO, and multiple TPs with IO. Correlations with extrahepatic microsphere depositions, angiographic complications, and periprocedural clinical events were performed. Alternative treatment strategies were evaluated. Applications from multiple TPs could have ensured the safe application of microspheres in 48.2% of cases that were originally performed from a single TP after IO. Extrahepatic microsphere accumulations were detected after 5.2%, 5.3%, and 1.5% of TARE procedures from a single TP without IO, a single TP with IO, and multiple TPs without IO, respectively. Applications from multiple TPs did not increase angiographic complications. During the 30-day follow-up, nausea/vomiting and upper abdominal discomfort were observed more frequently in the group with IO than in the group without IO (7.9%/4.6% and 9.2%/5.9%, respectively). In many TARE procedures, the same target liver can be treated from multiple TPs instead of a single TP, reducing the need for the interventional occlusion of aberrant arteries and potential extrahepatic microsphere depositions. Full article
(This article belongs to the Special Issue Advances in Pathogenesis and Therapeutics of Hepatobiliary Diseases Volume II)
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15 pages, 2689 KiB  
Article
Bile Acid Sequestration via Colesevelam Reduces Bile Acid Hydrophobicity and Improves Liver Pathology in Cyp2c70−/− Mice with a Human-like Bile Acid Composition
by Anna Palmiotti, Hilde D. de Vries, Milaine V. Hovingh, Martijn Koehorst, Niels L. Mulder, Esther Verkade, Melany K. Veentjer, Theo H. van Dijk, Vincent W. Bloks, Rick Havinga, Henkjan J. Verkade, Jan Freark de Boer and Folkert Kuipers
Biomedicines 2023, 11(9), 2495; https://doi.org/10.3390/biomedicines11092495 - 8 Sep 2023
Cited by 1 | Viewed by 3527
Abstract
Bile acids (BAs) and their signaling pathways have been identified as therapeutic targets for liver and metabolic diseases. We generated Cyp2c70−/− (KO) mice that were not able to convert chenodeoxycholic acid into rodent-specific muricholic acids (MCAs) and, hence, possessed a more hydrophobic, [...] Read more.
Bile acids (BAs) and their signaling pathways have been identified as therapeutic targets for liver and metabolic diseases. We generated Cyp2c70−/− (KO) mice that were not able to convert chenodeoxycholic acid into rodent-specific muricholic acids (MCAs) and, hence, possessed a more hydrophobic, human-like BA pool. Recently, we have shown that KO mice display cholangiopathic features with the development of liver fibrosis. The aim of this study was to determine whether BA sequestration modulates liver pathology in Western type-diet (WTD)-fed KO mice. The BA sequestrant colesevelam was mixed into the WTD (2% w/w) of male Cyp2c70+/+ (WT) and KO mice and the effects were evaluated after 3 weeks of treatment. Colesevelam increased fecal BA excretion in WT and KO mice and reduced the hydrophobicity of biliary BAs in KO mice. Colesevelam ameliorated diet-induced hepatic steatosis in WT mice, whereas KO mice were resistant to diet-induced steatosis and BA sequestration had no additional effects on liver fat content. Total cholesterol concentrations in livers of colesevelam-treated WT and KO mice were significantly lower than those of untreated controls. Of particular note, colesevelam treatment normalized plasma levels of liver damage markers in KO mice and markedly decreased hepatic mRNA levels of fibrogenesis-related genes in KO mice. Lastly, colesevelam did not affect glucose excursions and insulin sensitivity in WT or KO mice. Our data show that BA sequestration ameliorates liver pathology in Cyp2c70−/− mice with a human-like bile acid composition without affecting insulin sensitivity. Full article
(This article belongs to the Special Issue Advances in Pathogenesis and Therapeutics of Hepatobiliary Diseases Volume II)
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18 pages, 488 KiB  
Article
Is the Development of Ascites in Alcoholic Liver Patients Influenced by Specific KIR/HLA Gene Profiles?
by Isabel Legaz, Raquel Morales, José Miguel Bolarín, Aurelia Collados-Ros, José Antonio Pons and Manuel Muro
Biomedicines 2023, 11(9), 2405; https://doi.org/10.3390/biomedicines11092405 - 28 Aug 2023
Viewed by 1653
Abstract
Decompensated cirrhosis is the most common cause of ascites due to hemodynamic and renal alteration by continuous fluid leakage from the hepatic sinusoids and splanchnic capillaries into the interstitial space. Then, fluid leakage exceeds lymphatic return, leading to progressive fluid accumulation directly into [...] Read more.
Decompensated cirrhosis is the most common cause of ascites due to hemodynamic and renal alteration by continuous fluid leakage from the hepatic sinusoids and splanchnic capillaries into the interstitial space. Then, fluid leakage exceeds lymphatic return, leading to progressive fluid accumulation directly into the peritoneal cavity. Alcohol consumption is one of the main risks of developing alcoholic cirrhosis (AC), but not all AC patients develop ascites. Avoiding the development of ascites is crucial, given that it deteriorates prognosis and increases the patient mortality patient. The innate immune system plays a crucial role in cirrhosis through natural killer cells, which are abundant in the liver. The aim of this study was to analyze the KIR/HLA-C genetic profile in AC patients with and without ascites to understand this pathology and find predictive clinical susceptibility biomarkers that can help to establish risks and prevent the development of ascites in AC patients. A total of 281 AC patients with and without ascites were analyzed and compared with 319 healthy controls. Genomic DNA was extracted from peripheral blood in all groups. A PCR-SSO assay was performed for KIR/HLA genotyping analysis. A total of 16 activating and inhibitor KIR genes and their corresponding known ligands, epitopes of HLA-C, and their genotypes were analyzed. According to our analysis, C1 epitopes were statistically significantly decreased in AC patients with and without ascites. When comparing AC patients with ascites and healthy controls, a significant decrease in C1 epitope frequency was also observed. A statistically significant decrease was also found when comparing the C1C2 genotype in AC patients without ascites with controls. In conclusion, the absence of KIR2DL2 and KIR3DL1 genes may be a predisposing factor for the development of ascites in AC patients. The KIR2DS2/KIR2DL2 may could be involved in grade I ascites development, and the presence of the C1+ epitope and the homozygous C2C2 genotype may be protective genetic factors against ascites development in AC patients. Full article
(This article belongs to the Special Issue Advances in Pathogenesis and Therapeutics of Hepatobiliary Diseases Volume II)
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16 pages, 9711 KiB  
Article
Clinical Results of Transarterial Radioembolization (TARE) with Holmium-166 Microspheres in the Multidisciplinary Oncologic Treatment of Patients with Primary and Secondary Liver Cancer
by Robert Drescher, Alexander Köhler, Philipp Seifert, René Aschenbach, Thomas Ernst, Falk Rauchfuß and Martin Freesmeyer
Biomedicines 2023, 11(7), 1831; https://doi.org/10.3390/biomedicines11071831 - 26 Jun 2023
Cited by 7 | Viewed by 3204
Abstract
Holmium-166 microspheres are used for the transarterial radioembolization (TARE) treatment of primary and secondary liver cancers. In this study, its efficacy regarding local tumor control and integration into the oncological treatment sequence of the first 20 patients treated in our institution were examined. [...] Read more.
Holmium-166 microspheres are used for the transarterial radioembolization (TARE) treatment of primary and secondary liver cancers. In this study, its efficacy regarding local tumor control and integration into the oncological treatment sequence of the first 20 patients treated in our institution were examined. A total of twenty-nine 166Ho-TARE procedures were performed to treat hepatocellular carcinoma (HCC, fourteen patients), metastatic colorectal cancer (mCRC, four patients), intrahepatic cholangiocarcinoma (ICC, one patient), and hemangioendothelioma of the liver (HE, one patient). In eight patients, 166Ho-TARE was the initial oncologic treatment. In patients with HCC, the median treated-liver progression-free survival (PFS), overall PFS, and overall survival after 166Ho-TARE were 10.3, 7.3, and 22.1 months; in patients with mCRC, these were 2.6, 2.9, and 20.6 months, respectively. Survival after 166Ho-TARE in the patients with ICC and HE were 5.2 and 0.8 months, respectively. Two patients with HCC were bridged to liver transplantation, and one patient with mCRC was downstaged to curative surgery. In patients with HCC, a median treatment-free interval of 7.3 months was achieved. In line with previous publications, 166Ho-TARE was a feasible treatment option in patients with liver tumors, with favorable clinical outcomes in the majority of cases. It was able to achieve treatment-free intervals, served as bridging-to-transplant, and did not prevent subsequent therapies. Full article
(This article belongs to the Special Issue Advances in Pathogenesis and Therapeutics of Hepatobiliary Diseases Volume II)
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Review

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15 pages, 1175 KiB  
Review
Gut Microbiota, Deranged Immunity, and Hepatocellular Carcinoma
by Emidio Scarpellini, Giuseppe Guido Maria Scarlata, Valeria Santori, Marialaura Scarcella, Nazarii Kobyliak and Ludovico Abenavoli
Biomedicines 2024, 12(8), 1797; https://doi.org/10.3390/biomedicines12081797 - 7 Aug 2024
Cited by 1 | Viewed by 1072
Abstract
Background: Liver cancer, particularly hepatocellular carcinoma (HCC), is a significant gastrointestinal disease with a mortality rate as high as nearly 80% within five years. The disease’s pathophysiology involves deranged immune responses and bile acid metabolism, with the gut microbiota (GM) playing a crucial [...] Read more.
Background: Liver cancer, particularly hepatocellular carcinoma (HCC), is a significant gastrointestinal disease with a mortality rate as high as nearly 80% within five years. The disease’s pathophysiology involves deranged immune responses and bile acid metabolism, with the gut microbiota (GM) playing a crucial role. Recent research highlights the potential of GM in influencing HCC treatment outcomes, especially regarding immune checkpoint inhibitors (ICIs). However, few patients currently benefit from ICIs due to a lack of effective response biomarkers. Aims and methods: This review aimed to explore the literature on HCC treatment issues, focusing on immune response, bile acid metabolism, and GM dysbiosis. This review included studies from PubMed, Medline, and major gastroenterology and hepatology meetings, using keywords like gut microbiota, immune system, liver cancer, and checkpoint inhibitors. Results: GM dysbiosis significantly impacts immune response and bile acid metabolism, making it a promising biomarker for ICI response. Modulating GM can enhance ICI treatment efficacy, although more research is needed to confirm its direct therapeutic benefits for HCC. Conclusions: GM dysbiosis is integral to liver cancer pathogenesis and treatment response. Its modulation offers promising therapeutic avenues for improving HCC prognosis and response to immunotherapy. Full article
(This article belongs to the Special Issue Advances in Pathogenesis and Therapeutics of Hepatobiliary Diseases Volume II)
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17 pages, 315 KiB  
Review
Updated Insights into Probiotics and Hepatobiliary Diseases
by Xiaoyu Xu, Cheng Zhang, Guoyi Tang, Ning Wang and Yibin Feng
Biomedicines 2024, 12(3), 515; https://doi.org/10.3390/biomedicines12030515 - 25 Feb 2024
Cited by 3 | Viewed by 2066
Abstract
Hepatobiliary diseases have a high prevalence worldwide, with a wide range of diseases involved in the liver and biliary system. Modifications in gut microbiota have been proven to have an association with unbalanced intestinal homeostasis and the dysfunction of host metabolism and the [...] Read more.
Hepatobiliary diseases have a high prevalence worldwide, with a wide range of diseases involved in the liver and biliary system. Modifications in gut microbiota have been proven to have an association with unbalanced intestinal homeostasis and the dysfunction of host metabolism and the immune system, which can be the risk factors for many hepatobiliary diseases, such as nonalcoholic fatty liver disease (NAFLD), alcoholic liver disease (ALD), nonalcoholic fatty steatohepatitis (NASH), hepatitis, cirrhosis, hepatocellular carcinoma (HCC) and cholestasis, as well as infection due to liver transplantation. Probiotics are commonly used gut microbiota-targeted strategies to treat dysbiosis and intestinal dysfunction, as well as the gut–liver axis, which can enhance the effectiveness of probiotics in the management of liver diseases. Recent studies have explored more potential single or mixed strains of probiotics, and bioinformatics methods can be used to investigate the potential mechanisms of probiotics on liver diseases. In this review, we summarize the preclinical and clinical studies on the role of probiotics in hepatobiliary diseases from 2018 to 2023, revealing the possible mechanism of probiotics in the treatment of hepatobiliary diseases and discussing the limitations of probiotics in treating hepatobiliary diseases. This review provides updated evidence for the development of probiotic products, exploration of new probiotic strains, and support for clinical studies. Further studies should focus on the safety, viability, and stability of probiotics, as well as medication dosage and duration in clinical practice. Full article
(This article belongs to the Special Issue Advances in Pathogenesis and Therapeutics of Hepatobiliary Diseases Volume II)
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