Therapeutic advances in alcohol-associated hepatitis

Szabó, Gyöngyi; Thursz, Mark; Shah, Vijay H.

doi:10.1016/j.jhep.2022.03.025

Cited by 12 publications

(26 citation statements)

References 73 publications

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“…When testing new therapeutic approaches, it is equally important to use modern and comparable study concepts. A central problem with pharmacological studies in the field of AH is the selection of the primary endpoint 36,99 . Several previous studies used 28‐day mortality as the primary endpoint.…”

Section: Current Management Approaches Of Ahmentioning

confidence: 99%

Management of alcoholic hepatitis: A clinical perspective

Kasper,

Lang,

Steffen

et al. 2023

Liver International

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Alcohol‐associated liver disease is the primary cause of liver‐related mortality worldwide and one of the most common indications for liver transplantation. Alcoholic hepatitis represents the most acute and severe manifestation of alcohol‐associated liver disease and is characterized by a rapid onset of jaundice with progressive inflammatory liver injury, worsening of portal hypertension, and an increased risk for multiorgan failure in patients with excessive alcohol consumption. Severe alcoholic hepatitis is associated with a poor prognosis and high short‐term mortality. During the COVID‐19 pandemic, rates of alcohol‐associated hepatitis have increased significantly, underscoring that it is a serious and growing health problem. However, adequate management of alcohol‐associated hepatitis and its complications in everyday clinical practice remains a major challenge. Currently, pharmacotherapy is limited to corticosteroids, although these have only a moderate effect on reducing short‐term mortality. In recent years, translational studies deciphering key mechanisms of disease development and progression have led to important advances in the understanding of the pathogenesis of alcoholic hepatitis. Emerging pathophysiology‐based therapeutic approaches include anti‐inflammatory agents, modifications of the gut‐liver axis and intestinal dysbiosis, epigenetic modulation, antioxidants, and drugs targeting liver regeneration. Concurrently, evidence is increasing that early liver transplantation is a safe treatment option with important survival benefits in selected patients with severe alcoholic hepatitis not responding to medical treatment. This narrative review describes current pathophysiology and management concepts of alcoholic hepatitis, provides an update on emerging treatment options, and focuses on the need for holistic and patient‐centred treatment approaches to improve prognosis.

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Section: Current Management Approaches Of Ahmentioning

confidence: 99%

Management of alcoholic hepatitis: A clinical perspective

Kasper,

Lang,

Steffen

et al. 2023

Liver International

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“…established a machine learning model based on proteomics, constructed a diagnostic model superior to the existing clinical analysis, and discovered novel circulating protein markers on the basis of confirming the previous diagnostic markers, which provided potential protein targets with diagnostic, prognostic, and therapeutic value for ALD ( 21 ). Currently, the treatment of ALD still mainly relies on abstinence and nutritional support but also affected by the lack of advanced and effective therapeutic breakthroughs ( 22 ). Divertingly, based on the inherent ability of KCs to absorb most nanomaterials efficiently and non-specifically and the importance of KCs in the process of ALD, it may be possible to target myeloid cells, especially KCs, in the treatment of ALD by nano-drugs.…”

Section: Alcoholic Liver Diseasesmentioning

confidence: 99%

Myeloid cells in alcoholic liver diseases: Mechanism and prospect

Chen

et al. 2022

Front. Immunol.

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Alcoholic liver disease (ALD) is a leading chronic liver disease in which immune cells play a vital role. Myeloid cells have been extensively studied in ALD, including granulocytes, macrophages, monocytes, and dendritic cells, which are involved in the occurrence and progression of steatosis, inflammation, fibrosis, and eventual cirrhosis. These cells can be popularly targeted and regulated by factors from different sources, including cytokines secreted by other cells, extracellular vesicles, and substances in serum—for example, infiltration of monocytes or neutrophils, activation of Kupffer cells, and polarization of macrophages. These processes can affect and change the function and phenotype of myeloid cells. Here we mainly review the key mediators that affect the infiltration and function of mainly myeloid cells in ALD as well as their regulatory mechanisms on target cells, which may provide novel immunotherapeutic approaches. The single-cell multimodal omics of myeloid cells is also discussed to help transform them into basic research or therapeutic strategy of ALD clinically.

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“…Reactive oxygen species (ROS) as pleiotropic physiological signaling agents can regulate Nrf2 signal pathway, and the activation of Nrf2 will lead to the activation of downstream HO-1, NQO1, and so on ( Sies and Jones, 2020 ). Furthermore, it has long been established that the gut-liver axis and alcohol-induced increased alcohol-induced gut permeability are important in the pathogenesis of ALD ( Szabo et al, 2022 ). The induction of alcohol metabolites leads to the destruction of the intestinal barrier.…”

Section: Introductionmentioning

confidence: 99%

Jia-ga-song-tang protection against alcoholic liver and intestinal damage

Fang

Gan

et al. 2022

Front. Pharmacol.

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Gut-liver axis and cellular homeostasis play key roles in alcohol liver disease (ALD). Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a stress-sensitive guarantor of cellular homeostasis. We investigated whether the beneficial effects and underlying mechanisms of Jia-ga-song Tang (JGST) against ALD were associated with gut-liver axis and cellular homeostasis. A predictive network depicting the relationship between Jia-Ga-Song-Tang (JGST) and alcoholic liver disease (ALD) was designed by Network pharmacology. Next, 5% v/v Lieber-DeCarli alcohol liquid diet was used to establish the ALD. JGST protected the liver damage, repaired the intestines to alleviate the Two-hit on the liver, and balanced the cellular homeostasis. It was manifested in repairing the liver and intestinal pathological structure, reducing serum ALT, AST, and liver TG, TC, MDA, CAT, and increasing liver GSH, and intestine GSH-Px. JGST mainly inhibited the liver mRNA levels of HO-1, NQO1, GCLC, FASN, and PPARα and activated the intestinal mRNA levels of HO-1 and NQO1, while inhibiting the liver protein levels of HO-1, NQO1. Furthermore, LPS and LBP in the plasma and the expression of inflammatory factors such as IL-1β, TNF-α, IL-6, TGFβ1, CD14, and Myd88 were reduced after treatment to prove that JGST protects the liver from Two-hit. Ethanol was used to intervene in HepG2 and IEC-6 to establish an ALD cell model and treated by Germacrone, ML385, and TBHQ. repaired the intestinal barrier, and inhibited Nrf2 in IEC-6, but protect the HepG2 by activating Nrf2 to balance cellular homeostasis. Our results reinforce that JGST provides an effective protective method for alcoholic liver disease (ALD) by regulating Gut-liver axis and cellular homeostasis.

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Therapeutic advances in alcohol-associated hepatitis

Cited by 12 publications

References 73 publications

Management of alcoholic hepatitis: A clinical perspective

Management of alcoholic hepatitis: A clinical perspective

Myeloid cells in alcoholic liver diseases: Mechanism and prospect

Jia-ga-song-tang protection against alcoholic liver and intestinal damage

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