Acute-on-chronic liver failure (ACLF) in 2022: have novel treatment paradigms already arrived?

Abbas, Nadir; Rajoriya, Neil; Elsharkawy, Ahmed M.; Chauhan, Abhishek

doi:10.1080/17474124.2022.2097070

Cited by 24 publications

(26 citation statements)

References 136 publications

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“…Some studies have claimed that patients with ACLF of alcoholic etiology have significantly prolonged hospital stay, severe COVID-19, admission to the intensive care unit and higher mortality[ 37 , 38 ], while others have shown that ACLF is often triggered not only by ongoing alcohol consumption, but also gastrointestinal bleeding and/or infections, and from a pathophysiological point of view it is characterized by uncontrolled systemic inflammation coupled with paradoxical immunoparesis. ACLF has a clear pathogenesis and epidemiological burden and is different from decompensated cirrhosis; it represents a challenging condition with a rapid clinical course, high short-term mortality and varying clinical phenotypes[ 39 , 40 ].…”

Section: Sars-cov-2 Effects On the Livermentioning

confidence: 99%

Alcohol use disorder and liver injury related to the COVID-19 pandemic

Marano¹,

Traversi²,

Gaetani³

et al. 2022

World J Hepatol

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Alcohol use disorder is a complex and heterogeneous phenomenon that can be studied from several points of view by focusing on its different components. Alcohol is a hepatotoxin whose metabolism creates profound alterations within the hepatocyte. The liver is the central organ in the metabolism of alcohol, a process that also involves other organs and tissues such as the brain, heart and muscles, but the most relevant organ is the liver. The anatomopathological alterations in the liver associated with the prolonged use of alcohol range from the simple accumulation of neutral fats in the hepatocytes, to cirrhosis and hepatocellular carcinoma. Alcohol abuse frequently leads to liver disease such as steatosis, steatohepatitis, fibrosis, cirrhosis, and tumors. Following the spread of coronavirus disease 2019 (COVID-19), there was an increase in alcohol consumption, probably linked to the months of lockdown and smart working. It is known that social isolation leads to a considerable increase in stress, and it is also recognized that high levels of stress can result in an increase in alcohol intake. Cirrhotic patients or subjects with liver cancer are immunocompromised, so they may be more exposed to COVID-19 infection with a worse prognosis. This review focuses on the fact that the COVID-19 pandemic has made the emergence of alcohol-induced liver damage a major medical and social problem.

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Section: Sars-cov-2 Effects On the Livermentioning

confidence: 99%

Alcohol use disorder and liver injury related to the COVID-19 pandemic

Marano¹,

Traversi²,

Gaetani³

et al. 2022

World J Hepatol

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“…Recent evidence suggests systemic inflammation is the key to AD and ACLF disease progression[ 3 , 10 , 26 ]. Briefly, in patients with sepsis as the precipitant event, the inflammatory response is triggered by the recognition of pathogen-associated molecular patterns by pattern recognition receptors.…”

Section: Precipitants Factors For Aclf and Prognosismentioning

confidence: 99%

Current and future perspectives on acute-on-chronic liver failure: Challenges of transplantation, machine perfusion, and beyond

Guardia¹,

Boteon²,

Matielo³

et al. 2022

World J Gastroenterol

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Acute-on-chronic liver failure (ACLF) is a syndrome that occurs in patients with chronic liver disease and is characterized by acute decompensation, organ failure and high short-term mortality. Partially due to the lack of universal diagnostic criteria, the actual ACLF prevalence remains unclear; nevertheless, it is expected to be a highly prevalent condition worldwide. Earlier transplantation is an effective protective measure for selected ACLF patients. Besides liver trans-plantation, diagnosing and treating precipitant events and providing supportive treatment for organ failures are currently the cornerstone of ACLF therapy. Although new clinical specific therapies have been researched, more studies are necessary to assess safety and efficacy. Therefore, future ACLF management strategies must consider measures to improve access to liver transplantation because the time window for this life-saving therapy is frequently narrow. Thus, an urgent and global discussion about allocation and prioritization for transplantation in critically ill ACLF patients is needed because there is evidence suggesting that the current model may not portray their waitlist mortality. In addition, while donor organ quality is meant to be a prognostic factor in the ACLF setting, recent evidence suggests that machine perfusion of the liver may be a safe tool to improve the donor organ pool and expedite liver transplantation in this scenario.

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“…Multiple stages of cirrhosis are recognized; in the compensated cirrhosis phase symptoms are modest and mortality low. Acute liver injuries result in hepatic and systemic inflammation in cirrhotic patients which then drive hepatic decompensation as manifest by the development of one or a combination of ascites, portal hypertensive gastrointestinal bleeding and or encephalopathy ( 4 ). The one year mortality increases from 3% in patients with compensated cirrhosis to 57% with acute decompensation; median patient survival falls from 12 years to only 2 years ( 4 ).…”

Section: Introductionmentioning

confidence: 99%

“…Acute liver injuries result in hepatic and systemic inflammation in cirrhotic patients which then drive hepatic decompensation as manifest by the development of one or a combination of ascites, portal hypertensive gastrointestinal bleeding and or encephalopathy ( 4 ). The one year mortality increases from 3% in patients with compensated cirrhosis to 57% with acute decompensation; median patient survival falls from 12 years to only 2 years ( 4 ). There is a subgroup of patients that after acutely decompensating develop progressive extrahepatic organ failures on a background of severe systemic inflammation ( 5 ), this syndrome is referred to as ACLF ( 6 ) and has a short term mortality as high as 80% at 28 days ( 7 ); ACLF in fact represents the leading cause of mortality amongst patients with decompensated cirrhosis ( 7 ).…”

Section: Introductionmentioning

confidence: 99%

“…There is a subgroup of patients that after acutely decompensating develop progressive extrahepatic organ failures on a background of severe systemic inflammation ( 5 ), this syndrome is referred to as ACLF ( 6 ) and has a short term mortality as high as 80% at 28 days ( 7 ); ACLF in fact represents the leading cause of mortality amongst patients with decompensated cirrhosis ( 7 ). Precipitating events for decompensation and eventually ACLF in patients with established cirrhosis include drugs, infections, bleeds and flares of the underlying disease ( 4 ).…”

Section: Introductionmentioning

confidence: 99%

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The role of platelet mediated thromboinflammation in acute liver injury

Morris

Chauhan

2022

Front. Immunol.

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Acute liver injuries have wide and varied etiologies and they occur both in patients with and without pre-existent chronic liver disease. Whilst the pathophysiological mechanisms remain distinct, both acute and acute-on-chronic liver injury is typified by deranged serum transaminase levels and if severe or persistent can result in liver failure manifest by a combination of jaundice, coagulopathy and encephalopathy. It is well established that platelets exhibit diverse functions as immune cells and are active participants in inflammation through processes including immunothrombosis or thromboinflammation. Growing evidence suggests platelets play a dualistic role in liver inflammation, shaping the immune response through direct interactions and release of soluble mediators modulating function of liver sinusoidal endothelial cells, stromal cells as well as migrating and tissue-resident leucocytes. Elucidating the pathways involved in initiation, propagation and resolution of the immune response are of interest to identify therapeutic targets. In this review the provocative role of platelets is outlined, highlighting beneficial and detrimental effects in a spatial, temporal and disease-specific manner.

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Acute-on-chronic liver failure (ACLF) in 2022: have novel treatment paradigms already arrived?

Cited by 24 publications

References 136 publications

Alcohol use disorder and liver injury related to the COVID-19 pandemic

Alcohol use disorder and liver injury related to the COVID-19 pandemic

Current and future perspectives on acute-on-chronic liver failure: Challenges of transplantation, machine perfusion, and beyond

The role of platelet mediated thromboinflammation in acute liver injury

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