Aetiological factors in immune-mediated liver disease

Efficacy of a Peruvian Botanical Remedy (Sabell A4+) for Treating Liver Disease and Protecting Gastric Mucosal Integrity

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2019/5486728 ◽

2019 ◽

Vol 2019 ◽

pp. 1-11

Author(s):

Mark G. Swain ◽

John L. Wallace ◽

D. Lorne Tyrrell ◽

José Cabanillas ◽

Steven K. H. Aung ◽

...

Keyword(s):

Hepatitis C Virus ◽

Liver Disease ◽

Hepatitis C ◽

Gastric Mucosa ◽

Virus Replication ◽

Positive Interactions ◽

Mucosal Integrity ◽

Immune Mediated ◽

Anti Inflammatory

The purpose of this study was to determine the efficacy of a Peruvian botanical formulation for treating disorders of hepatic function and gastric mucosal integrity. The formulation A4+ (Sabell Corporation) contains extracts of Curcuma longa rhizome, Cordia lutea flower, and Annona muricata leaf. Individually these plants have been used as traditional remedies for liver disease. We report the efficacy of A4+ and its components using a variety of in vitro and in vivo disease models. The methods used included tests for antioxidant, anti-inflammatory, and antiviral activity as well as mouse models of liver disease, including Concanavalin A-induced immune-mediated hepatitis and a bile duct ligation model for evaluating sickness behaviour associated with liver disease. Rat models were used to evaluate the gastric mucosal protective property of A4+ following indomethacin challenge and to evaluate its anti-inflammatory action in an “air pouch” model. In all tests, A4+ proved to be more effective than placebo. A4+ was antioxidant and anti-inflammatory and diminished Hepatitis C virus replication in vitro. In animal models, A4+ was shown to protect the liver from immune-mediated hepatitis, improve behavioural function in animals with late stage liver disease, and protect the rat gastric mucosa from ulceration following NSAID exposure. We conclude that A4+ ameliorated many aspects of liver injury, inhibited hepatitis C virus replication, and protected the gastric mucosa from NSAIDs. These varied beneficial properties appear to result from positive interactions between the three constituent herbs.

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The clinical usage and definition of autoantibodies in immune-mediated liver disease: A comprehensive overview

Journal of Autoimmunity ◽

10.1016/j.jaut.2018.10.004 ◽

2018 ◽

Vol 95 ◽

pp. 144-158 ◽

Cited By ~ 15

Author(s):

Benedetta Terziroli Beretta-Piccoli ◽

Giorgina Mieli-Vergani ◽

Diego Vergani

Keyword(s):

Liver Disease ◽

Comprehensive Overview ◽

Immune Mediated ◽

Definition Of

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Incidence of chronic immune-mediated inflammatory diseases after diagnosis with Kawasaki disease: a population-based cohort study

Rheumatology ◽

10.1093/rheumatology/keab680 ◽

2021 ◽

Author(s):

Stephen G Fung ◽

Richard Webster ◽

M Ellen Kuenzig ◽

Braden D Knight ◽

Michelle Batthish ◽

...

Keyword(s):

Multiple Sclerosis ◽

Cohort Study ◽

Liver Disease ◽

Kawasaki Disease ◽

Sclerosing Cholangitis ◽

Rate Ratio ◽

Incidence Rate Ratio ◽

Population Based ◽

Immune Mediated ◽

Increased Risk

Abstract Objectives Kawasaki disease (KD) is an immune-mediated vasculitis of childhood with multi-organ inflammation. We determined the risk of subsequent immune-mediated inflammatory disease (IMID), including arthritis, type 1 diabetes, IBD, autoimmune liver disease, primary sclerosing cholangitis and multiple sclerosis. Methods We conducted a matched population-based cohort study using health administrative data from Ontario, Canada. Children aged <18 years born between 1991 and 2016 diagnosed with KD (n = 3753) were matched to 5 non-KD controls from the general population (n = 18 749). We determined the incidence of IMIDs after resolution of KD. Three- and 12-month washout periods were used to exclude KD-related symptoms. Results There was an elevated risk of arthritis in KD patients compared with non-KD controls, starting 3 months after index date [103.0 vs 12.7 per 100 000 person-years (PYs); incidence rate ratio 8.07 (95% CI 4.95, 13.2); hazard ratio 8.08 (95% CI 4.95, 13.2), resulting in the overall incidence of IMIDs being elevated in KD patients (175.1 vs 68.0 per 100 000 PYs; incidence rate ratio 2.58 (95% CI 1.93, 3.43); hazard ratio 2.58, 95% CI 1.94, 3.43]. However, there was no increased risk for diabetes, IBD, autoimmune liver disease, primary sclerosing cholangitis or multiple sclerosis in KD patients. Similar results were observed using a 12-month washout period. Conclusion Children diagnosed with KD were at increased risk of arthritis following the acute KD event, but not other IMIDs. Health-care providers should monitor for arthritis in children following a diagnosis of KD.

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CXCR3 Deficiency Exacerbates Liver Disease and Abrogates Tolerance in a Mouse Model of Immune-Mediated Hepatitis

The Journal of Immunology ◽

10.4049/jimmunol.1003750 ◽

2011 ◽

Vol 186 (9) ◽

pp. 5284-5293 ◽

Cited By ~ 61

Author(s):

Annette Erhardt ◽

Claudia Wegscheid ◽

Benjamin Claass ◽

Antonella Carambia ◽

Johannes Herkel ◽

...

Keyword(s):

Liver Disease ◽

Mouse Model ◽

Immune Mediated

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Pediatric autoimmune liver disease and extra-hepatic immune-mediated comorbidities

Digestive and Liver Disease ◽

10.1016/j.dld.2018.07.033 ◽

2019 ◽

Vol 51 (2) ◽

pp. 281-285

Author(s):

Giulia Paolella ◽

Marcello Farallo ◽

Irene Degrassi ◽

Carlo Agostoni ◽

Chiara Amoruso ◽

...

Keyword(s):

Liver Disease ◽

Autoimmune Liver Disease ◽

Immune Mediated

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Extracellular Vesicles as Inflammatory Drivers in NAFLD

Frontiers in Immunology ◽

10.3389/fimmu.2020.627424 ◽

2021 ◽

Vol 11 ◽

Author(s):

Akshatha N. Srinivas ◽

Diwakar Suresh ◽

Prasanna K. Santhekadur ◽

Deepak Suvarna ◽

Divya P. Kumar

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Extracellular Vesicles ◽

Mammalian Cells ◽

Cell Communication ◽

Alcoholic Fatty Liver ◽

Whole Process ◽

Obesity And Diabetes ◽

Immune Mediated ◽

End Stage

Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent chronic liver disease in most parts of the world affecting one-third of the western population and a growing cause for end-stage liver diseases such as hepatocellular carcinoma (HCC). Majorly driven by obesity and diabetes mellitus, NAFLD is more of a multifactorial disease affected by extra-hepatic organ crosstalk. Non-alcoholic fatty liver (NAFL) progressed to non-alcoholic steatohepatitis (NASH) predisposes multiple complications such as fibrosis, cirrhosis, and HCC. Although the complete pathogenic mechanisms of this disease are not understood, inflammation is considered as a key driver to the onset of NASH. Lipotoxicity, inflammatory cytokines, chemokines, and intestinal dysbiosis trigger both hepatic and systemic inflammatory cascades simultaneously activating immune responses. Over a few years, extracellular vesicles studied extensively concerning the pathobiology of NAFLD indicated it as a key modulator in the setting of immune-mediated inflammation. Exosomes and microvesicles, the two main types of extracellular vesicles are secreted by an array of most mammalian cells, which are involved mainly in cell-cell communication that are unique to cell type. Various bioactive cargoes containing extracellular vesicles derived from both hepatic and extrahepatic milieu showed critical implications in driving steatosis to NASH reaffirming inflammation as the primary contributor to the whole process. In this mini-review, we provide brief insights into the inflammatory mediators of NASH with special emphasis on extracellular vesicles that acts as drivers of inflammation in NAFLD.

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Regulatory T-Cell Therapy in Liver Transplantation and Chronic Liver Disease

Frontiers in Immunology ◽

10.3389/fimmu.2021.719954 ◽

2021 ◽

Vol 12 ◽

Author(s):

Angus Hann ◽

Ye H. Oo ◽

M. Thamara P. R. Perera

Keyword(s):

T Cells ◽

Liver Disease ◽

T Cell ◽

Cell Lineage ◽

Solid Organ ◽

T Helper 1 ◽

T Cell Therapy ◽

Immune Mediated ◽

And Function ◽

Type Of Injury

The constant exposure of the liver to gut derived foreign antigens has resulted in this organ attaining unique immunological characteristics, however it remains susceptible to immune mediated injury. Our understanding of this type of injury, in both the native and transplanted liver, has improved significantly in recent decades. This includes a greater awareness of the tolerance inducing CD4+ CD25+ CD127low T-cell lineage with the transcription factor FoxP3, known as regulatory T-Cells (Tregs). These cells comprise 5-10% of CD4+ T cells and are known to function as an immunological “braking” mechanism, thereby preventing immune mediated tissue damage. Therapies that aim to increase Treg frequency and function have proved beneficial in the setting of both autoimmune diseases and solid organ transplantations. The safety and efficacy of Treg therapy in liver disease is an area of intense research at present and has huge potential. Due to these cells possessing significant plasticity, and the potential for conversion towards a T-helper 1 (Th1) and 17 (Th17) subsets in the hepatic microenvironment, it is pre-requisite to modify the microenvironment to a Treg favourable atmosphere to maintain these cells’ function. In addition, implementation of therapies that effectively increase Treg functional activity in the liver may result in the suppression of immune responses and will hinder those that destroy tumour cells. Thus, fine adjustment is crucial to achieve this immunological balance. This review will describe the hepatic microenvironment with relevance to Treg function, and the role these cells have in both native diseased and transplanted livers.

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Potential Effects of Coronaviruses on the Liver: An Update

Frontiers in Medicine ◽

10.3389/fmed.2021.651658 ◽

2021 ◽

Vol 8 ◽

Author(s):

Xinyi Wang ◽

Jianyong Lei ◽

Zhihui Li ◽

Lunan Yan

Keyword(s):

Clinical Trials ◽

Liver Disease ◽

Liver Injury ◽

Severe Acute Respiratory Syndrome ◽

Respiratory Tract ◽

Liver Diseases ◽

Direct Damage ◽

Animal Trials ◽

Immune Mediated ◽

Coronavirus Infection

The coronaviruses that cause notable diseases, namely, severe acute respiratory syndrome (SARS), middle east respiratory syndrome (MERS) and coronavirus disease 2019 (COVID-19), exhibit remarkable similarities in genomic components and pathogenetic mechanisms. Although coronaviruses have widely been studied as respiratory tract pathogens, their effects on the hepatobiliary system have seldom been reported. Overall, the manifestations of liver injury caused by coronaviruses typically involve decreased albumin and elevated aminotransferase and bilirubin levels. Several pathophysiological hypotheses have been proposed, including direct damage, immune-mediated injury, ischemia and hypoxia, thrombosis and drug hepatotoxicity. The interaction between pre-existing liver disease and coronavirus infection has been illustrated, whereby coronaviruses influence the occurrence, severity, prognosis and treatment of liver diseases. Drugs and vaccines used for treating and preventing coronavirus infection also have hepatotoxicity. Currently, the establishment of optimized therapy for coronavirus infection and liver disease comorbidity is of significance, warranting further safety tests, animal trials and clinical trials.

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