Review article: the endocannabinoid system in liver disease, a potential therapeutic target

Basu, Patrick; Aloysius, Mark M.; Shah, Niraj James; Brown, RE

doi:10.1111/apt.12673

Cited by 40 publications

(47 citation statements)

References 94 publications

(181 reference statements)

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“…Cannabinoid receptor type 1 (CB1) is a promoter of fibrosis, while Cannabinoid receptor type 2 (CB2) is an inhibitor 59 . In response to alcohol feeding, steatosis and fibrogenesis are increased in CB2 receptor-deficient mice and decreased in CB1 receptor knockouts 60 .…”

Section: Current Therapies and Future Approachesmentioning

confidence: 99%

Pathogenesis of Alcoholic Liver Disease

Dunn

Shah

2016

Clinics in Liver Disease

147

119

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Alcoholic Liver Disease includes a broad clinical-histological spectrum from simple steatosis, cirrhosis, acute alcoholic hepatitis with or without cirrhosis to hepatocellular carcinoma as a complication of cirrhosis. The pathogenesis of ALD can be conceptually divided into 1) Ethanol mediated liver injury, 2) Inflammatory Immune response to injury, 3) Intestinal permeability and microbiome changes. Corticosteroids may improve outcomes, but this is controversial and probably only impacts short-term survival. New pathophysiology-based therapies are under study, including IL22, anakinra, and others. These studies provide hope for better future outcomes for this difficult disease.

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Section: Current Therapies and Future Approachesmentioning

confidence: 99%

Pathogenesis of Alcoholic Liver Disease

Dunn

Shah

2016

Clinics in Liver Disease

147

119

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“…Cannabinoid receptors CB1 and CB2 are upregulated in chronic liver diseases and several studies have convincingly demonstrated antagonism between CB1 and CB2; that is, CB1 promotes while CB2 suppresses liver damage [77, 78]; therefore CB1 antagonists and CB2 agonists were investigated as potential therapeutic approaches for liver diseases. Clinically, daily cannabis (CB1 and CB2 agonist) promoted fibrosis progression in chronic hepatitis C [79].…”

Section: Developments In Targeted Therapy Related To Liver Fibrosismentioning

confidence: 99%

Clinical Advancements in the Targeted Therapies against Liver Fibrosis

Bansal

Nagórniewicz

Prakash

2016

Mediators of Inflammation

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Hepatic fibrosis, characterized by excessive accumulation of extracellular matrix (ECM) proteins leading to liver dysfunction, is a growing cause of mortality worldwide. Hepatocellular damage owing to liver injury leads to the release of profibrotic factors from infiltrating inflammatory cells that results in the activation of hepatic stellate cells (HSCs). Upon activation, HSCs undergo characteristic morphological and functional changes and are transformed into proliferative and contractile ECM-producing myofibroblasts. Over recent years, a number of therapeutic strategies have been developed to inhibit hepatocyte apoptosis, inflammatory responses, and HSCs proliferation and activation. Preclinical studies have yielded numerous targets for the development of antifibrotic therapies, some of which have entered clinical trials and showed improved therapeutic efficacy and desirable safety profiles. Furthermore, advancements have been made in the development of noninvasive markers and techniques for the accurate disease assessment and therapy responses. Here, we focus on the clinical developments attained in the field of targeted antifibrotics for the treatment of liver fibrosis, for example, small molecule drugs, antibodies, and targeted drug conjugate. We further briefly highlight different noninvasive diagnostic technologies and will provide an overview about different therapeutic targets, clinical trials, endpoints, and translational efforts that have been made to halt or reverse the progression of liver fibrosis.

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“…ECs are involved in numerous physiological and pathophysiological processes in chronic liver diseases (CLDs). The upregulation of cannabinoid receptors CB1 and CB2 in NAFLD, alcoholic liver disease, autoimmune and viral hepatitis, I/R, cirrhosis, and related disturbances (intrahepatic vascular resistance, hyperdynamic circulatory syndrome, hepatic encephalopathy) were convincingly demonstrated, leading to the intriguing hypothesis of functional antagonism of these receptors in liver pathophysiology, suggesting CB1 to promote and CB2 to protect from liver damage …”

Section: Ecsmentioning

confidence: 99%