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Acute-on-chronic liver failure: terminology, mechanisms and management

Nature Reviews Gastroenterology & Hepatology volume 13, pages 131–149 (2016)Cite this article

Subjects

Key Points

  • Acute-on-chronic liver failure (ACLF) is a distinct clinical syndrome characterized by liver failure due to an acute hepatic injury on an underlying chronic liver disease with high 28-day mortality

  • Acute insults include alcohol, hepatotropic viruses and drugs whereas the underlying chronic liver disease is generally cirrhosis due to alcohol, hepatitis B or C, or NASH

  • After an acute insult, persistent inflammation, systemic inflammatory response syndrome and the cytokine storm have a central role in the pathogenesis of liver failure and subsequent organ failure

  • A short 'golden window' precedes sepsis development and organ(s) failure, providing opportunity for immunomodulation with granulocyte-colony stimulating factor and other interventions; extrahepatic organ failure indicates severity of illness, prognosis and helps guide management

  • Abstinence, antiviral therapy and withdrawal of harmful drug are specific therapies that could help ameliorate or reverse the liver failure

  • Liver transplantation is the definitive treatment and a good outcome is achieved with early transplantation in carefully selected patients; liver dialysis and plasmapheresis can help as 'bridge therapies'

Abstract

Acute-on-chronic liver failure (ACLF) is a distinct clinical entity and differs from acute liver failure and decompensated cirrhosis in timing, presence of acute precipitant, course of disease and potential for unaided recovery. The definition involves outlining the acute and chronic insults to include a homogenous patient group with liver failure and an expected outcome in a specific timeframe. The pathophysiology of ACLF relates to persistent inflammation, immune dysregulation with initial wide-spread immune activation, a state of systematic inflammatory response syndrome and subsequent sepsis due to immune paresis. The disease severity and outcome can be predicted by both hepatic and extrahepatic organ failure(s). Clinical recovery is expected with the use of nucleoside analogues for hepatitis B, and steroids for severe alcoholic hepatitis and, possibly, severe autoimmune hepatitis. Artificial liver support systems help remove toxins and metabolites and serve as a bridge therapy before liver transplantation. Hepatic regeneration during ongoing liver failure, although challenging, is possible through the use of growth factors. Liver transplantation remains the definitive treatment with a good outcome. Pre-emptive antiviral agents for hepatitis B before chemotherapy to prevent viral reactivation and caution in using potentially hepatotoxic drugs can prevent the development of ACLF.

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Figure 1: Definition and concept of ACLF.
Figure 2: The concept of the hepatic reserve and ACLF.
Figure 3: The mechanism of injury in ACLF.
Figure 4: Histological pattern in ACLF.
Figure 5: Hepatic regeneration in ACLF.
Figure 6: Histological images of liver regeneration in patients with ACLF, ALF and decompensated cirrhosis.
Figure 7: Management algorithm for patients with ACLF.

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Acknowledgements

Authors are grateful to N. Trehanpati, A. Kumar, A. Rastogi, R. K. Gulati, S Baweja and A. Khanam for their intellectual inputs in the preparation of the figures.

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  1. Department of Hepatology, Institute of Liver and Biliary Sciences, D-1, Vasant Kunj, New Delhi, 110070, India

    Shiv K. Sarin & Ashok Choudhury

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A.C. prepared the draft manuscript and designed the sections; S.K.S. conceived, edited, revised and prepared the final draft.

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Sarin, S., Choudhury, A. Acute-on-chronic liver failure: terminology, mechanisms and management. Nat Rev Gastroenterol Hepatol 13, 131–149 (2016). https://doi.org/10.1038/nrgastro.2015.219

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