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- 1. Acute on Chronic Liver Failure Ulva Yogia Guslaf 1 SMF/Bagian Ilmu Penyakit Dalam Fakultas Kedokteran Universitas Syiah Kuala Rumah Sakit Zainoel Abidin Banda Aceh 2021/2022
- 2. 2 Introduction Liver Failure presented as Acute Liver Failure Acute-on chronic liver failure End-stage liver disease Sarin et al. Hepatology International. 2019 4 weeks 4-12 weeks
- 4. 4 Introduction Sarin et al. Hepatology International. 2019
- 5. 5 Pathophysiology Acute on Chronic Liver Failure Alam A et al. J Biomed Res, 2017
- 6. 6 The clinical course of cirrhosis Arroyo et al. Acute‐on‐chronic liver failure in cirrhosis. 2016
- 7. 7 Common multiple organ dysfunctions in acute-on- chronic liver failure Alam A et al. J Biomed Res, 2017
- 8. 8 Role of liver histology in ACLF Alam A et al. J Biomed Res, 2017 Liver biopsy is helpful in patients where the presence and stage of underlying chronic liver disease and/or the cause of chronic liver disease are not clear Liver biopsy can identify stage of fibrosis, measure in prognostic and outcome, and distinguish ACLF from Decompensated Cirrhosis
- 9. 9 Scoring System in Determining the Grading of Liver Failure Sarin et al. Hepatology International. 2019
- 10. 10 Scoring System in Determining the Grading of Liver Failure Sarin et al. Hepatology International. 2019
- 11. • Jaundice (serum bilirubin > 5 mg/dL [> 85 lmol/L]) and coagulopathy (INR > 1.5 or prothrombin activity < 40%) are mandatory parameters to assess liver failure • Ascites and/or encephalopathy as determined by physical examination also reliably reflect significant hepatic functional impairment • Liver failure score (AARC score) which includes total bilirubin, INR, grade of HE, plasma lactate and serum creatinine reliably predicts the disease severity and outcome • Grading of liver failure as per AARC score I (5–7), II (8–10), III (11–15) effectively prognosticates and guides the therapy • Coagulation anomalies 11 Defining the liver failure in ACLF Sarin et al. Hepatology International. 2019
- 12. 12 Golden Window Period of ACLF Sarin et al. Hepatology International. 2019 SIRS needs consideration for organ support, antibiotics for occult sepsis and prioritization for definitive therapy, i.e., liver transplan C-reactive protein and procalcitonin, The most frequent infections are SBP, pneumonia, UTI, and bacteremia Routine examination of blood and body fluids is recommended
- 13. • The diagnosis of invasive fungal infection can be proven, probable or possible, depends on mycological evidence, and clinical evidence • Invasive pulmonary aspergillosis (IPA) is increasingly recognized as a cause of morbidity and mortality in patients with ACL • Prophylaxis with fluconazole followed by echinocandins needs to be evaluated in ACLF patients • Biomarkers such as galactomanan or B–D Glucan can be used for supporting diagnosis if there is invasive fungal infection in ACLF. 13 Invasive fungal infection in ACLF Sarin et al. Hepatology International. 2019
- 14. • AKI criteria (defined as an absolute increase in serum creatinine of 0.3 mg/dl within 48 h or by percentage increase in serum creatinine of more than 50% from baseline, which is known, or presumed, to have occurred within the previous 7 days • A cutoff value of 1.1 mg/dl is a reliable marker of significant renal dysfunction and 1.5 mg/dl of kidney failure in patients with ACLF • Initiate RRT emergently when life-threatening changes in volume overload, hyperkalemia, hypernatremia and worsening metabolic acidosis not responding to conservative management. The threshold for initiating RRT should be lowered when AKI occurs as part of multi-organ failure, or in non-oliguric patients if the daily fluid balance cannot be maintained. • Biomarkers of tubular damage, urine NGAL and IL-18 need to be evaluated for a role in patients with ACLF to determine the need for early RRT or artificial liver support 14 Defining the Renal failure in ACLF Sarin et al. Hepatology International. 2019
- 15. • HE, including grade 1-2 HE (organ dysfunction) and grade 3-4 HE (organ failure), is present in about a third of the ACLF patients • Ammonia is a simple surrogate marker for HE in ACLF and correlates with severity of HE/cerebral failure • Lactulose, rifaximin, NH3-lowering strategies remain the main therapy for HE in patients with cirrhosis • Patients need to be characterized as bleeding or thrombosis phenotype by clinical assessment of major bleeding and d-dimer assay, respectively 15 Defining the HE in ACLF Sarin et al. Hepatology International. 2019
- 16. • ACLF is a hypocoagulable state and this can get escalated with the development of SIRS and sepsis • Traditional coagulation measures, including prothrombin time (PT), activated partial thromboplastin time (aPTT), international normalized ratio (INR), fibrinogen levels and bleeding time (BT) do not measure bleeding risk in ACLF • Patients need to be characterized as bleeding or thrombosis phenotype by clinical assessment of major bleeding and d-dimer assay, respectively 16 Coagulation in ACLF Sarin et al. Hepatology International. 2019
- 17. 17 Summary Definition Acute decompensation of cirrhosis previous decompensation AND Multi organ failure AND High short-term mortality Acute decompensation of cirrhosis ± previous decompensation (due to infection) AND Extrahepatic organ failure (2 or more of respiration, brain, coagulation, and circulation) AND High short-term mortility (30 day) Acute hepatic injury in chronic liver disease ± compensated cirrhosis (development of jaundice and coagulopathy) AND Ascites ± HE within 4 weeks from onset Acute hepatic injury in chronic liver disease ± compensated cirrhosis (development of jaundice and prolonged INR) AND Extrahepatic organ failure (1 or more) AND High short-term mortility Criteria for Organ Failure Liver : sBr > 205 𝜂mol/L Coagulation : INR >2.5 Renal : sCr 177 𝜂mol/L or RRT Brain : HE grade 3 or 4 CVDs : Vasopressors Respiratory Pa02/Fi02 < 200 or Sa02/Fi02 <214 Renal : RRT Brain : HE grade 3 or 4 CVDs : MAP < 60 or fall in SBP of 40 from baseline Respiratory : MV Liver : sBr > 205 𝜂mol/L Coagulation : INR > 1,5 Renal : AKI Brain : HE grade 3 or 4 Grading Grade 1 : Single renal failure, Single liver, coagulation, Circulatory or respiratory failure + sCr 133-168 205 𝜂mol/L +/- HE 1-2. Single brain failure + sCr 133-168 𝜂mol/L Grade 2 : 2 or more organ failures Grade 3 : 3 or more organ failures
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