102 Korea Digestive Disease Week Definition and Treatment of Liver Failure Seung Kak Shin, M.D. Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Korea INTRODUCTION the definition of the European Liver Association (EASL) Chronic Liver Liver failure can be divided into acute liver failure (ALF) due to acute Failure Consortium (CLIF-C) have been most widely used, although liver injury without previous history of liver disease or liver cirrhosis, they have not yet reached a fully uniform definition throughout the and chronic liver failure (also called end stage liver disease) resulting world. In European multicenter study (CANONIC study), bacterial in gradual progression of chronic liver disease. Recently, the new infection and active alcoholism, which are important mechanisms of concept of acute on chronic liver failure (ACLF) has emerged. systemic inflammation, were the most frequent precipitating events. (7) In Korean multicenter study (KACLif study), bacterial infection and gastrointestinal bleeding were more frequent in ACLF patients DEFINITION OF LIVER FAILURE according to the EASL-CLIF definition, while active alcoholism and use 1. Definition of ALF of toxic material were more frequent in ACLF patients according to the The most widely accepted definition of ALF includes evidence of AARC definition.(8) coagulation abnormality, usually an INR ≥ 1.5, and any degree of mental alteration (hepatic encephalopathy, HEP) in a patient without TREATMENT OF LIVER FAILURE preexisting cirrhosis and with an illness of <26 weeks’ duration.(1- 2) In the absence of any alteration of consciousness, the patient who 1. Treatment of ALF develop coagulopathy was defined as acute liver injury (ALI), not liver In patients with severe acute liver injury, screen intensively for failure. If there is no primary liver insult, these patients should be any signs of HEP is required. The presence of cirrhosis, alcohol considered to have a secondary liver injury and not ALF; management induced liver injury or malignant infiltration of the liver should be should focus on the treatment of any underlying disease processes. distinguished. It is important to find the cause of acute liver failure (3) Previously, O’Grady et al. classified ALF according to the period because urgent treatment for causes can determine the prognosis if it from jaundice (or symptom onset) to HEP – hyperacute liver failure is due to acetaminophen poisoning, mushroom poisoning, or hepatitis (< 1 week), acute liver failure (1-4 weeks) and, subacute liver failure B infection. Then, prognostic stratification is needed. Early referral of (4-12 weeks) because the prognosis was considered to be different. patients with a poor prognosis (an INR >1.5 and onset of HEP or other (4) However, it is known that such classification has no prognostic poor prognostic features) to a liver transplant center is essential to significance distinct from the causes of the liver failure. Therefore, in optimize clinical outcomes. Even if the patient does not need transfer 2005, American Association for the Study of Liver Diseases (AASLD) at that time point, early discussion with a transplant unit is needed. guideline suggested that all patients with HEP within 26 weeks of (3) When acute liver failure occurs due to acute liver injury, various symptom onset should be unified to acute liver failure.(5) complications such as cerebral edema, elevated intracranial pressure, hepatic coma, infection, blood clotting disorder, gastrointestinal 2. Definition of ACLF bleeding, hemodynamic instability, renal failure, and metabolic The concept of ACLF was introduced by Jalan and Williams to describe complications may occur. Appropriate prevention and treatment the acute deterioration in liver function over 2 to 4 weeks in a patient is needed. Even if any degree of consciousness alteration occurs, with well-compensated cirrhosis associated with a precipitating event rapid symptom exacerbation may occur, requiring intensive care unit (hepatotoxic: superimposed hepatitis viral infection, drug-induced liver treatment and preparation of liver transplantation. The most commonly injury, hepatotoxins, or excessive alcohol consumption; extrahepatic: used prognostic system is the King’s College Hospital criteria. Recent variceal bleeding or sepsis), leading to severe deterioration in clinical study demonstrated that administration of N-Acetylcysteine could status with jaundice and HEP and/or hepatorenal syndrome (HRS). improve transplant-free survival in early stage non-acetaminophen (6) Since then, the definition of the Asian-Pacific Association for the ALF.(9) The liver assist therapies to either support the patient until the Study of the Liver (APASL)-ACLF Research Consortium (AARC) and native liver has had time to recover, or to bridge the patient to liver PG Course 1. (KASL) Recent Update on Liver Diseases 103 transplantation were studied. In recent RCT study, plasma exchange American Association for the Study of Liver Diseases Position Pa- has been shown to improve transplant-free survival in patients with per on acute liver failure 2011. Hepatology 2012;55:965-967. ALF, and to modulate immune dysfunction.(10) 3. EASL Clinical Practical Guidelines on the management of acute (fulminant) liver failure. J Hepatol. 2017;66:1047–1081. 4. O’Grady JG, Schalm SW, Williams R. Acute liver failure: redefining 2. Treatment of ACLF the syndromes. Lancet 1993;342:273–275. The causes of ACLF such as acute exacerbation of chronic hepatitis B 5. Polson J, Lee WM, AASLD position paper: The management of or infection should be promptly identified and treated. In patients with acute liver failure. Hepatology 2005;41:1179-1197. ACLF and suspected bacterial infection, broad spectrum antibiotics 6. Jalan R, Williams R. Acute-on-chronic liver failure: pathophysi- should be initiated as early as possible. Acute kidney injury is common ological basis of therapeutic options. Blood Purif 2002;20:252– 261. in patients with ACLF. Acute tubular necrosis should be differentiated 7. Moreau R, Jalan R, Gines P et al. Acute-on-chronic liver failure is a from HRS, which justifies vasoconstrictive agents.(11) Liver-specific distinct syndrome that develops in patients with acute decompen- scores such as the CLIF-SOFA(7), CLIF-OF and the CLIF-C ACLF sation of cirrhosis. Gastroenterology. 2013;144:1426-1437. score(12) have been developed to more precisely assess the prognosis 8. Kim TY, Song DS, Kim HY et al. Characteristics and discrepancies in of patients with ACLF. Development or increase in the number of acute-on-chronic liver failure: need for a unified definition. PLoS organ failures needs early or emergency liver transplantation. Recent One. 2016;11:e0146745. trials on extracorporeal liver support failed to demonstrate a survival 9. Lee WM, Hynan LS, Rossaro L et al. Intravenous N-acetylcysteine improves transplant-free survival in early stage non-acetamino- benefit.(13-14) phen acute liver failure. Gastroenterology. 2009;137:856–864. 10. Larsen FS, Schmidt LE, Bernsmeier C et al. High-volume plasma CONCLUSIONS exchange in patients with acute liver failure: An open randomised controlled trial. J Hepatol. 2016;64:69-78. ALF and ACLF are serious diseases with a high risk of mortality. To 11. Durand F, Nadim MK. Management of acute-on-chronic liver fail- improve prognosis, the causes of liver failures should be promptly ure. Semin Liver Dis 2016;36:141–152. identified, and the development of complications or multiple 12. Jalan R, Saliba F, Pavesi M, et al. Development and validation of organ failures should be prevented and intensively managed. Liver a prognostic score to predict mortality in patients with acute on- transplantation is the most definitive step for patients who fail to chronic liver failure. J Hepatol 2014;61:1038–1047. demonstrate recovery. 13. Bañares R, Nevens F, Larsen FS, et al. Extracorporeal albumin dialysis with the molecular adsorbent recirculating system in acute-on-chronic liver failure: the RELIEF trial. 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