Acute-on-chronic liver failure in patients with alcohol-related liver disease

Gustot, Thierry; Jalan, Rajiv

doi:10.1016/j.jhep.2018.12.008

Cited by 113 publications

(71 citation statements)

References 68 publications

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“…Active alcohol use represents a frequent intrahepatic precipitant of ACLF . The prevalence of alcohol as a precipitating event varies geographically.…”

Section: Alcoholmentioning

confidence: 99%

Precipitants of Acute‐on‐Chronic Liver Failure: An Opportunity for Preventative Measures to Improve Outcomes

et al. 2020

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Acute-on-chronic liver failure (ACLF) is a feared complication that can develop at any stage of chronic liver disease. The incidence of ACLF is increasing, leading to a significant burden to both the affected individual and health care systems. To date, our understanding of ACLF suggests that it may be initiated by precipitants such as systemic infection, alcohol use, or viral hepatitis. The prevalence of these vary significantly by geography and underlying liver disease, and these precipitants have a varying impact on patient prognosis. Herein, we present a review of our current understanding of the precipitants of ACLF, including gaps in current data and opportunities for meaningful intervention and areas of future research. Liver Transplantation 26 283-293 2020 AASLD.liveR tRAnsplAntAtion, vol. 26, no. 2, 2020 cullARo et Al.

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“…Active alcohol use represents a frequent intrahepatic precipitant of ACLF . The prevalence of alcohol as a precipitating event varies geographically.…”

Section: Alcoholmentioning

confidence: 99%

Precipitants of Acute‐on‐Chronic Liver Failure: An Opportunity for Preventative Measures to Improve Outcomes

et al. 2020

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“…Alcoholic liver disease (ALD) originates from excessive alcohol abuse and includes simple liver steatosis, steatohepatitis, fibrosis and/or cirrhosis (Gustot and Jalan, 2019). The etiopathogenesis of ALD is complex.…”

Section: Introductionmentioning

confidence: 99%

Physcion Protects Against Ethanol-Induced Liver Injury by Reprogramming of Circadian Clock

et al. 2020

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The circadian clock plays a key role in our daily physiology and metabolism. Alcohol consumption disrupts the circadian rhythm of metabolic genes in the liver; however, the potential contribution of circadian clock modulation to alcoholic liver disease (ALD) is unknown. We identified a novel liver protective agent, physcion, which can alleviate fat accumulation and inflammation in ALD mice via reprogramming the hepatic circadian clock. The model of alcoholic hepatitis was established by intragastrically administering ethanol. In vitro, physcion was investigated by treating HepG2 cells with ethanol. The role of circadian clock in Physcion caused liver protection was tested by knocking down the core circadian gene Bmal1. Physcion application caused reduced lipogenesis and alleviated inflammation in alcohol-induced mice. In alcoholic hepatosteatosis models, physcion upregulated the core circadian genes. And the circadian misalignment triggered by ethanol was efficiently reversed by physcion. Physcion attenuated lipogenesis via reprogramming the circadian clock in HepG2 cells. Suppression of Bmal1 by RNA interference abolished the protective of physcion. In addition, Physcion binds to the active pocket of BMAL1 and promotes its expression. The study identified the novel liver protective effects of physcion on alcohol-induced liver injury, and modulation of the core circadian clock regulators contributes to ALD alleviation. More importantly, strategies targeting the circadian machinery, for example, Bmal1, may prove to be beneficial treatment options for this condition.

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“…The course of ACLF is highly dynamic and varies in stimulus strength and duration of acute triggers and liver functional reserve [1,2,22]. Therefore, a dynamic model to distinguish between those who will not survive without transplant and those who will recover with their own liver is a challenge [23].…”

Section: Discussionmentioning

confidence: 99%

Dynamic Prognostication in Transplant Candidates with Acute-on-Chronic Liver Failure

Chen

et al. 2020

JPM

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We aimed to extensively investigate clinical markers that are sufficiently dynamic for prognosis of acute-on-chronic liver failure (ACLF). Defined by the Asian Pacific Association for the Study of the Liver (APASL) criteria, patients with ACLF on the liver transplant waitlist in a tertiary center were retrospectively reviewed. Laboratory results and severity scores at three time points (days 1, 7, and 14 after admission) were analyzed. From 2015 to 2019, 64 patients with ACLF were enrolled, of which 24 received a liver transplant from 22 live donors. The hospital mortality rate was 31% (8% for transplant; 45% for nontransplant groups), and the 3-month survival was crucial for determining long-term outcomes. The number of significant variables for mortality, and, specifically, the hazards of international normalized ratio of prothrombin time (INR) and APASL ACLF Research Consortium (AARC) score were increased within two weeks. In multivariable analysis, INR and AARC score (D-14) were associated with poor survival and liver transplant was a protective factor in all patients, while AARC score (D-14) was significant in the nontransplant group. AARC score at day 14 is an independent risk factor for mortality in ACLF. Liver transplant from live donors reversed poor outcomes in patients with ACLF in a timely manner.

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Acute-on-chronic liver failure in patients with alcohol-related liver disease

Cited by 113 publications

References 68 publications

Precipitants of Acute‐on‐Chronic Liver Failure: An Opportunity for Preventative Measures to Improve Outcomes

Precipitants of Acute‐on‐Chronic Liver Failure: An Opportunity for Preventative Measures to Improve Outcomes

Physcion Protects Against Ethanol-Induced Liver Injury by Reprogramming of Circadian Clock

Dynamic Prognostication in Transplant Candidates with Acute-on-Chronic Liver Failure

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