Acute-on-Chronic Liver Failure: Pathophysiological Mechanisms and Management

Acute-on-chronic liver failure (ACLF) is a multifaceted condition with poor treatment options and high short-term mortality. ACLF can develop in patients with or without liver cirrhosis, where patients with decompensated cirrhosis display a higher risk of short-term mortality. Pathophysiological mechanisms include systemic inflammation due to bacterial and fungal infections and acute hepatic insult with drug, alcohol, and viral hepatitis. Cryptogenic factors also contribute to the development of ACLF. The clinical outcome of patients with ACLF gets further complicated by the occurrence of variceal hemorrhage, hepatorenal syndrome, hepatic encephalopathy, and systemic immune dysfunction. Regardless of the better understanding of pathophysiological mechanisms, no specific and definitive treatment is available except for liver transplantation. The recent approach of regenerative medicine using mesenchymal stem cells (MSCs) could be advantageous for the treatment of ACLF as these cells can downregulate inflammatory response by inducing antiinflammatory events and prevent hepatic damage and fibrosis by inhibiting hepatic stellate cell activation and collagen synthesis. Moreover, MSCs are involved in tissue repair by the process of liver regeneration. Considering the broad therapeutic potential of MSCs, it can serve as an alternative treatment to liver transplant in the near future, if promising results are achieved.

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Increased IL-17-producing CD8+ T cell frequency predicts short-term mortality in patients with hepatitis B virus-related acute-on-chronic liver failure

Therapeutics and Clinical Risk Management ◽

10.2147/tcrm.s184809 ◽

2018 ◽

Vol Volume 14 ◽

pp. 2127-2136 ◽

Cited By ~ 5

Author(s):

Geng-lin Zhang ◽

Ting Zhang ◽

Qi-yi Zhao ◽

Chan Xie ◽

Chao-shuang Lin ◽

...

Keyword(s):

Hepatitis B Virus ◽

Hepatitis B ◽

Liver Failure ◽

Chronic Liver ◽

Chronic Liver Failure ◽

Short Term ◽

Cell Frequency ◽

B Virus ◽

Short Term Mortality

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Clinical Features of Hepatitis C Virus-Related Acute-On-Chronic Liver Failure in a Korean Population

10.21203/rs.3.rs-181706/v1 ◽

2021 ◽

Author(s):

Jung Woo Choi ◽

Jin-Kyu Cho ◽

Sang Soo Lee ◽

Jae Heon Kim ◽

Hankyu Jeon ◽

...

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Hepatitis B Virus ◽

Liver Failure ◽

Chronic Liver ◽

Chronic Liver Failure ◽

Short Term ◽

B Virus ◽

Short Term Mortality ◽

Very High

Abstract Background Acute-on-chronic liver failure (ACLF) is a widely recognized concept in which acute decompensation (AD) in patients with cirrhosis results in organ failures and high short-term mortality. However, few studies reflecting the various etiologies of cirrhosis are available. We aimed to investigate the clinical features of patients with hepatitis C virus (HCV)-related ACLF. Methods Between January 2005 and December 2018, 109 HCV-related cirrhosis patients who were hospitalized for AD (ascites, hepatic encephalopathy, gastrointestinal hemorrhage, and/or bacterial infection) were enrolled for ACLF defined by European Association for the Study of the Liver (EASL). Results ACLF developed in 35 patients (32.1%) on admission. Eight patients had ACLF grade 1, eight had ACLF grade 2, and 19 had ACLF grade 3. The 28-day and 90-day mortality rates were very low (2.7% and 5.4%, respectively) in patients without ACLF and very high (60.0% and 74.3%, respectively) in those with ACLF. In patients with HCV-related ACLF, the prevalence of liver failure was very low (17.1%), whereas that of kidney failure was very high (71.4%) compared to previous studies on hepatitis B virus-related ACLF and alcohol-related ACLF. Compared with all other prognostic scores, Chronic liver failure Consortium Organ Failure score most accurately predicted 90-day mortality, with an area under the receiver operator characteristic of 0.921. Conclusions HCV-related ACLF has unique clinical characteristics that are distinct from hepatitis B virus-related and alcohol-related ACLF. ACLF defined by EASL can be useful in predicting short-term mortality in HCV-related cirrhosis.

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APACHE II score is superior to SOFA, CTP and MELD in predicting the short-term mortality in patients with acute-on-chronic liver failure (ACLF)

Journal of Digestive Diseases ◽

10.1111/1751-2980.12074 ◽

2013 ◽

Vol 14 (9) ◽

pp. 484-490 ◽

Cited By ~ 47

Author(s):

Ajay Duseja ◽

Narendra S Choudhary ◽

Sachin Gupta ◽

Radha Krishan Dhiman ◽

Yogesh Chawla

Keyword(s):

Liver Failure ◽

Chronic Liver ◽

Apache Ii ◽

Apache Ii Score ◽

Chronic Liver Failure ◽

Short Term ◽

Short Term Mortality

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Acute-On-Chronic Liver Failure Defined by Asian Pacific Association for the Study of the Liver Should Include Decompensated Cirrhosis

Frontiers in Medicine ◽

10.3389/fmed.2021.750061 ◽

2021 ◽

Vol 8 ◽

Author(s):

Manman Xu ◽

Ming Kong ◽

Pengfei Yu ◽

Yingying Cao ◽

Fang Liu ◽

...

Keyword(s):

Liver Disease ◽

Liver Failure ◽

Chronic Liver Disease ◽

Chronic Liver ◽

Decompensated Cirrhosis ◽

Chronic Liver Failure ◽

Short Term ◽

Asian Pacific ◽

Long Term Mortality

Background and Aims: Acute-on-chronic liver failure (ACLF) is an acute deterioration of chronic liver disease with high short-term mortality. The inclusion or exclusion of previously decompensated cirrhosis (DC) in the diagnostic criteria of ACLF defined by the Asian Pacific Association for the Study of the Liver (APASL-ACLF) has not been conclusive. We aimed to evaluate the prognostic impact of decompensated cirrhosis in ACLF.Methods: We retrospectively collected a cohort of patients with a diagnosis of APASL-ACLF (with or without DC) hospitalized from 2012 to 2020 at three liver units in tertiary hospitals. Baseline characteristics and survival data at 28, 90, 180, 360, 540, and 720 days were collected.Results: Of the patients assessed using APASL-ACLF criteria without the diagnostic indicator of chronic liver disease, 689 patients were diagnosed with ACLF, of whom 435 had no decompensated cirrhosis (non-DC-ACLF) and 254 had previously decompensated cirrhosis (DC-ACLF). The 28-, 90-, 180-, 360-, 540-, and 720-day mortality were 24.8, 42.9, 48.7, 57.3, 63.4, and 68.1%, respectively, in DC-ACLF patients, which were significantly higher than in non-DC-ACLF patients (p < 0.05). DC was independently associated with long-term (180/360/540/720 days) but not short-term (28/90 days) mortality in patients with ACLF. Age, total bilirubin, international normalized ratio, and hepatic encephalopathy were independent risk factors for short- and long-term mortality risk in ACLF patients (p < 0.05).Conclusions: Patients with DC-ACLF have a higher mortality rate, especially long-term mortality, compared to non-DC-ACLF patients. Therefore, DC should be included in the diagnostic criteria of APASL-ACLF and treated according to the ACLF management process.

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