acute-on-chronic liver failure (ACLF)
Definition of chronic plus acute liver failure
? Acute liver injury in a patient with chronic liver disease (previously diagnosed or undiagnosed) manifested by jaundice and coagulopathy complicated by ascites and/or encephalopathy within 4 weeks (2a, B)
? Level of evidence: 1 (highest) – 5 (lowest)
? Strength of recommendation: A (strongest) – D (weakest)
APASL Consensus. Hepatol Int 2009 ,3:269-282
DDW 2010 ACLF Definition
? ACLF is a clinical syndrome of acute liver injury with loss of hepatic function based on pre-existing chronic liver disease, manifested by jaundice, coagulation disorders, concurrent ascites and hepatic irritability.
ACLF acute events
1 Infectious factors: hepatophilic and non-hepatophilic viral infections (1a, A)
Hepatitis B (dominant or latent) or hepatitis C reactivation (2b, B)
Other infections involving the liver (5, D)
2 Non-infectious factors: frequent heavy alcohol consumption within the last 4 weeks (1a, A)
Use of hepatotoxic drugs or herbal medicines (2b, B)
Autoimmune hepatitis or Wilson’s disease episodes (3b, B)
Surgical procedures (3b, B)
Variceal bleeding (4, C)
3 Unknown factors: (5, D)
APASL Consensus.Hepatol Int 2009 ,3:269-282
chronic liver disease (CLD)
Chronic liver disease definition
? underlying chronic liver disease: compensated cirrhosis of any cause (1a, A)
chronic hepatitis (5, D)
Non-alcoholic steatohepatitis (5, D)
Cholestatic liver disease (2b, B)
Metabolic liver disease (2b, B)
? Excluding: steatosis (5, D)
APASL Consensus.Hepatol Int 2009 ,3:269-282
Chronic liver disease and acute liver injury
? In developing countries, chronic liver disease is mostly cirrhosis and acute liver injury is mostly acute hepatitis virus infection
? In developed countries and regions, chronic liver disease is mostly alcoholic liver disease, and acute liver injury is mostly alcoholic or drug-related liver injury
Li Yu-Yuan. Recent consensus on chronic plus acute liver failure. Chinese Medical Tribune 2010-6-10-D2
ACLF definition of liver failure
ACLF is defined as Required conditions: jaundice (≥5 mg/dl [85 μmol/l]) and coagulopathy (INR ≥1.5 or prothrombin activity of 40%) (2a, B)
? Physical examination reveals ascites and/or encephalopathy (2b, B)
APASL Consensus. Hepatol Int 2009 ,3:269-282
DDW 2010 ACLF diagnostic criteria
? Jaundice rapidly deepening, serum total bilirubin ≥ 5 mg/dl, and prothrombin time significantly prolonged, such as the international normalized ratio (INR) ≥ 1.5, prothrombin activity (PTA) ≤ 40%
The prothrombin activity (PTA) is less than 40%. Most often have ascites and/or hepatic encephalopathy
Li Yu-Yuan. The Latest Consensus on Chronic Plus Acute Liver Failure. Chinese Medical Tribune 2010-6-10-D2
ACLF pathophysiology
ACLF pathophysiology ? Inflammation and neutrophil dysfunction play an important role in organ failure (2a)
? Systemic inflammatory response syndrome needs further validation as a prognostic indicator of ACLF (3a, C)
? Increased dimethylarginine (DMA) concentration (1.23) is a poor prognostic marker in ACLF and the role of ischemia-modified albumin (IMA) in ACLF needs to be evaluated (3b, C)
APASL Consensus.Hepatol Int 2009 ,3:269-282
The role of sepsis and cytokines in ACLF
? It is likely that cytokines influence the development and progression of ACLF (3b)
? Inhibition of inflammatory cytokine response may reduce morbidity and mortality in ACLF (3b, C)
? Circulating toxins during ACLF cause secondary liver injury and impaired liver regeneration (2b)
? TNF-a and IL-6 may have a dual role of inducing hepatocyte necrosis and promoting hepatocyte proliferation (3b)
APASL Consensus.Hepatol Int 2009 ,3:269-282
Hemodynamics of ACLF
? HVPG in ACLF is intermediate between compensated and decompensated chronic liver disease (3b)
? ACLF with severe vascular varices indicates high HVPG and poor prognosis (3b)
? Higher morbidity and mortality in ACLF with higher hepatic blood flow (3b, C)
Histology of ACLF liver
? Liver histology is very helpful in assessing the presence and severity of liver fibrosis and/or cirrhosis (1a, A)
? Two different histological types can be seen (3b, C)
Type I – ballooning degeneration of hepatocytes, roseola node formation, cholestasis, various degrees of interfacial inflammation and fibrosis
Type II-small bile duct hyperplasia, bile emboli, focal necrosis or bridging necrosis of hepatocytes, eosinophilic degeneration, more severe fibrosis and varying degrees of inflammatory activity
? ACLF liver biopsy should be individualized (2a, B )
APASL consensus.Hepatol Int 2009 ,3:269-282
ACLF prognosis
? Using CPT (Child-Turcotte-Pugh), MELD (end-stage liver disease), SOFA (Sequential Organ Failure Assessment), APACHE (Acute Physiology and Chronic Health Evaluation) different scoring systems, there is generally no difference in the prognosis of ACLF for various etiologies (3b, C)
APASL consensus.Hepatol Int 2009 ,3:269-282
Antiviral therapy for ACLF
? Antiviral therapy should be initiated for ACLF caused by hepatitis B (3b, C)
? Lamivudine can be applied short-term, but strong agents such as entecavir or tenofovir may be preferred for long-term viral suppression and less drug resistance (3b, C)
? Prophylactic therapy is recommended for HBsAg-positive patients on chemotherapy (3b, C)
? There is insufficient evidence to recommend antiviral therapy for HBsAg-negative, anti-HBc-positive patients (3b, C)
APASL Consensus.Hepatol Int 2009 ,3:269-282
Artificial liver therapy for ACLF
? Molecular adsorption recirculation system (MARS) does not improve survival in patients with ACLF (1a, A)
? MARS is beneficial as a transitional measure before liver transplantation in patients with ACLF (2b, B)
? MARS improves hepatic encephalopathy in patients with ACLF (1a, A)
? Further studies are needed for plasma exchange in ACLF (3b, C)
APASL Consensus.Hepatol Int 2009 ,3:269-282
ACLF liver transplantation
? Indications for liver transplantation
Prognostic score suggests liver transplantation for death within 3 months (2b, B)
King’s College Hospital criteria for ACLF need to be studied (2b, B)
Early intervention if hepatorenal syndrome occurs (2b, B)
However, liver transplantation should not be performed for HRS without urine (3b, C)
Transplantation is better after partial control of HRS with terlipressin (2b, B)
? Contraindications
Hemodynamic instability requiring massive fluid replacement (sepsis, bleeding) (2a, B)
Severe bacterial infections (2a, B)
Fungal infections (2a, B)
Cerebral edema or intracranial hemorrhage (1a, A)
? Living liver transplantation
Preferred graft weight and venous output tract to match recipient (3b, C)
APASL Consensus. Hepatol Int 2009 ,3:269-282