Acute Liver Failure (ALF) PDF

## Acute Liver Failure ### Definition Highly specific, rare and devastating syndrome caused by a variety of hepatic insults characterised by acute deterioration of liver function without underlying chronic liver disease, severe metabolic derangements, neurologic complications and ultimately, mult...

## Acute Liver Failure ### Definition Highly specific, rare and devastating syndrome caused by a variety of hepatic insults characterised by acute deterioration of liver function without underlying chronic liver disease, severe metabolic derangements, neurologic complications and ultimately, multiorgan failure. ### It is characterized by: 1. Acute liver injury 2. Hepatic encephalopathy 3. An elevated prothrombin time/international normalized ratio (INR) ### It has also been referred to as a. Fulminant hepatic failure b. Acute hepatic necrosis c. Fulminant hepatic necrosis d. Acute fulminant hepatitis (FH) The gold standard therapy for patients with irreversible FH or Acute liver failure is Liver transplantation ### Pathogenesis The pathogenesis of acute liver failure (ALF) includes: 1. Direct liver injury 2. Immune-mediated liver injury: Innate immune-mediated injury is initiated early and may then be followed by injury resulting from adaptive immune responses. The most common causes of death in patients with ALF: - Cerebral oedema, multi-organ system failure and septicemia. These events are precipitated by the systemic inflammatory response syndrome (SIRS), which is mediated by release of pro-inflammatory cytokines such as: tumour necrosis factor-a, interleukin (IL)-1ẞ, and IL-6. ### Principal Etiologies of ALF 1. **Drugs**: - The most frequent cause of severe ALI and ALF: - Paracetamol, anti-tuberculous, chemotherapy, statins, NSAIDs, phenytoin, carbamazepine, ecstasy flucloxacillin and Amoxicillin-clavulanic acid. 2. **Viral**: - Hepatitis B, A, E (less frequent CMV, HSV, VZV, Dengue). 3. **Toxins**: - Amanita phalloides, phosphorus. 4. **Vascular**: - Budd-Chiari syndrome, Hypoxic hepatitis. 5. **Pregnancy**: - Pre-eclamptic liver rupture, HELLP, fatty liver of pregnancy 6. **Other**: - Wilson disease, autoimmune, lymphoma, malignancy. ### Clinical Course and Classification of ALF #### Clinical Course: **Severe Acute Liver Injury (ALI) y (ALI)** - No underlying chronic liver disease - Liver damage (serum aminotransferases 2-3x ULN) - Impaired liver function (jaundice and coagulopathy*) **Hepatic Encephalopathy (HE)** - Crucial for the diagnosis of ALF - Mental alterations may initially be subtle - Intensive screening at the first sign of HE is mandatory Up to 12 weeks post-jaundice, depending on sub-classification. **Acute Liver Failure (ALF)** **Classification of ALF according to weeks from development of jaundice to development of hepatic encephalopathy** | Time frame (in weeks) | Hyperacute | Acute | Subacute | Severity of coagulopathy | Severity of jaundice | Degree of intracranial hypertension | Chance of spontaneous recovery | Typical cause | |---|---|---|---|---|---|---|---|---| | 0 | +++ | ++ | + | + | ++ | +++ | ++ | Paracetamol | | 4 | + | ++ | +++ | ++ | ++ | +/- | + | HBV | | 12 | | | | | | | | Non-paracetamol drug-induced | | >28 weeks | | | | | | | | Chronic liver disease | Key: - +++ High severity - ++ Medium severity - + Low severity - +/- Present or absent ### Agenda: 1. Assessment and management at presentation 2. Organ-specific management - Cardiovascular - Respiratory - Gastrointestinal - Metabolic - Acute kidney injury and renal replacement therapy - Coagulation - Sepsis, inflammation and anti-inflammatory 3. The brain in ALF 4. Artificial and bioartificial liver devices 5. Liver transplantation ### Assessment and Management At Presentation **Immediate Measures:** 1. **Exclude cirrhosis, alcohol-induced liver injury or malignant infiltration** - The clinical picture and the radiology of subacute liver failure can mimic cirrhosis. - The indications for liver biopsy in ALF are limited. - Incidence of underlying chronic liver disease, malignancies or alcohol-induced liver disease should be excluded. 2. **Initiate early discussions with tertiary liver/transplant centre even if not immediately relevant** - Early referral of patients to a specialist centre will allow appropriate delineation of those likely to benefit from transplantation and offers an environment where focused expertise provides immediate relevantnts. 3. **Screen intensively for hepatic encephalopathy** - The greatest chance of spontaneous survival without LTx. 4. **Determine aetiology to guide treatment, especially LTx** **Primary or secondary causes of ALF and need for transplantation** | Disease Group | Hepatic/primary ALF (LT) | Extrahepatic/secondary liver failure and ACLF | |---|---|---| | Acute liver failure | Drug related. <br> Acute viral hepatitis <br> Toxin-induced ALF <br> Budd-Chiari syndrome <br> Autoimmune <br> Pregnancy related | Hypoxic hepatitis (aka ischaemic) <br> Systemic diseases: <br> Haemophagocytic syndromes <br> Metabolic disease <br> Infiltrative disease <br> Lymphoma <br> Infections (e.g. malaria) <br> Liver resection for either secondary deposits or primary liver cancer <br> Alcoholic hepatitis | | CLD presenting with a phenotype of ALF | Fulminant presentation of Wilson disease. <br> Autoimmune liver disease. <br> Budd-Chiari <br> HBV reactivation | | **Possible indication for emergency LTx** **No indication for emergency LTx** ### General Support Outside ICU: **Questions for patients and relatives at admission:** **Search for an aetiology** - Has the patient used any medication, in particular paracetamol, over the last 6 months? - Has the patient any history of substance abuse? - Has the patient ever experienced depression or made a suicide attempt? - Has the patient complained of gastrointestinal affects after eating mushrooms? **Identify conditions that could cause ALF** - Is the patient pregnant? - Has the patient travelled in HBV or HEV endemic areas? - Has the patient received immunosuppressive therapy or chemotherapy? - Does the patient have a history of autoimmune disease? **Decide whether emergency LTx is feasible** - Does the patient currently using and dependent on alcohol or other drugs?* - Do they have a recent history of cancer?# - Do they have severe congestive heart disease or a respiratory co-morbidity? - What was the interval between onset of jaundice and first signs of HE? ### Laboratory analyses at admission: **Assess disease severity** - PT, INR or factor Vand full coagulation screen - Liver blood tests* - Renal function - Urine output: hourly - Urea - Creatinine may be difficult to assay in the context of elevated bilirubin. - Arterial blood gas and lactate - Arterial ammonia **Check aetiology** - Toxicology screen in urine and paracetamol serum level - Viral serological screen - HBsAg, anti-HBc IgM (HBV DNA), HDV if positive for HBV - anti HAV IgM - anti-HEV IgM - anti-HSV IgM, anti-VZV IgM, CMV, HSV, EBV, parvovirus and VZV PCR - Autoimmune markers+ **Test for complications** - Lipase or amylase *Including LDH, conjugated and unconjugated bilirubin and creatinine kinase; +Low urea is a marker of severe liver dysfunction; ANAS, ASMA, anti-soluble liver antigen, globulin profile, ANCAS, HLA typing. ### Diagnosis, monitoring and care at admission **Diagnostic tests** - Cultures (respiratory, blood, urine) - Chest X-ray/ECG/liver echography: axial imaging of the abdomen and chest may also be required - ECG **Routine monitoring** - Oxygen saturation, blood pressure, heart rate, respiratory rate, hourly urine output - Clinical neurological status **Standard care** - Glucose infusions ((10-20%)* - Stress ulcer prophylaxis - Restrict clotting factors unless active bleeding - NAC in early stage, even in non-paracetamol cases. **Preventative measures** - Avoid sedatives - Avoid hepatotoxic and nephrotoxic drugs **In case of HE** - Transfer to an appropriate level of care (ideally critical care) at the first symptoms of mental alterations. - Quiet surrounding, head of bed >30°C, head in neutral position and intubate, ventilate, and sedate if progression to >3 coma. - Low threshold for empirical start of antibiotics if haemodynamic deterioration and/or increasing encephalopathy with inflammatory phenotype. - In case of evolving HE, intubation and sedation prior to the transfer. - Ensure volume replete and normalize biochemical variables (Na, Mg, PO4, K). **Assess suitability for liver transplant** - Assess suitability for liver transplant and initiate early discussions with transplant unit even if not immediately relevant. - Contraindications should not preclude transfer to tertiary liver/transplant centre. *Glycaemic target ± 140 mg/dl, Na 135-145 mmol/l;