Makindo Medical Notes.com

Related Subjects: |Chronic liver disease |Liver Function Tests |Ascites Assessment and Management |Budd-Chiari syndrome |Alcoholism and Alcoholic Liver Disease |Liver Transplantation

ALF is an acute episode of primary liver dysfunction in someone without chronic liver disease or other systemic illness causing liver disease. Hyperacute causes, the interval from onset to failure is a week or less, and the cause is usually paracetamol toxicity or a viral infection, in the developing world hepatitis A, B, and E. There may be coagulopathy, increased serum transaminases, abnormal bilirubin and altered levels of consciousness which may progress to coma and death

About

• 10 cases per million persons per year in the developed world
• Commonest in previously healthy adults in their 30s
• Fulminant hepatic failure: severe liver injury, potentially reversible in nature and with the onset of hepatic encephalopathy within 8 weeks of the first symptoms in the absence of pre-existing liver disease
• Hepatic injury < 26 weeks in duration, an INR > 1.5 and altered mental status in the absence of chronic liver disease except for Wilson disease, vertically acquired HBV or autoimmune hepatitis
• Possibly reversible if the acute cause can be treated quickly

Classification by time from jaundice to HE

• Onset of jaundice is considered as the first symptom and is time zero
• HE: hepatic encephalopathy
• Acute liver failure: INR>1.5 + HE + no evidence of pre-existing cirrhosis developing over a period of fewer than 6 months.
• Measure time between development of jaundice and encephalopathy

Findings of Acute liver failure

• Hepatocellular jaundice
• High AST/ALT
• Prolongation of the prothrombin time
• Fulminant hepatic failure
• Acute liver failure + encephalopathy
• Jaundice may be missing

Causes

• Viral Hepatitis 40-70%:A/B/B + D/C, E, CMV, EBV, VZV
• Drug Induced/Poisoning 20% : Paracetamol (much higher in UK), Halothane, Isoniazid, Phenytoin, Sulphonamides, Amiodarone, Propylthiouracil, Ecstasy
• Autoimmune disease: Chronic active hepatitis
• Wilsons’s disease can cause fulminant liver failure
• Toxins: Amanita phyllodes, Carbon tetrachloride
• Wilson's disease, Vascular, Budd-Chiari syndrome, Shock, Acute fatty liver of pregnancy
• HELLP syndrome - screen neonate for LCHAD
• Infectious: Leptospirosis, Yellow fever, CMV, Severe Bacterial infections, Amoebic Infection
• Reye's syndrome (Aspirin induced), Unknown 20-30%

Clinical

• History of drug/toxin exposure key,
• Jaundice, Coagulopathy, Bleeding, Hypoglycaemia
• Encephalopathy: Hepatic flap, Fetor hepaticus, Constructional apraxia
• No hepatosplenomegaly or ascites [unless Budd-Chiari syndrome]
• Slit lamp examination for Kayser-Fleischer rings
• Chronic disease
  • Spider naevi, Gynaecomastia
  • Dupuytren’s contracture, Liver palms
• Grading encephalopathy
  • Grade 1 Disorientated
  • Grade 2 Confused
  • Grade 3 Comatose
  • Grade 4 Unconscious

Investigations

• FBC ↑ WCC/ESR/CRP/AST/ALT (they fall eventually) Prothrombin time ?
• VBG: pH - metabolic acidosis and arterial lactate ?
• Viral serology - anti-HAV IgM, HBcAg IgM, anti-HBc IgM, anti-HEV, anti-HCV(very rare cause of ALF)
• Paracetamol levels, Ammonia levels
• USS liver and Doppler of hepatic veins for Budd-Chiari syndrome. Splenomegaly.
• Wilson's disease. Ceruloplasmin and 24-hour urine copper and ophthalmic exam
• Pregnancy test, HIV status
• ANA, Anti-Smooth muscle, Immunoglobulins
• Tap Ascites: microscopy, culture, and sensitivity. Culture/swab blood, urine.

Diagnostic Clues

• Assessment of the clinical context is crucial to identify less common causes of ALF
• If acute gross ascites consider Budd-Chiari syndrome and need Liver USS doppler
• Coombs negative haemolytic anaemia and high bilirubin to alkaline phosphatase ratio are features of ALF due to Wilson disease

General Management

• ABC and Oxygen, HDU or Gastro bed
• Give 4.5% Serum Albumin to keep CVP + 10 cm H₂O
• Consider inotropes to maintain BP
• Prophylactic broad-spectrum antibiotics e.g. Cefotaxime 1 g BD
• Ranitidine 50 mg IV TDS or orally
• Monitor for Metabolic acidosis and Infection (SBP)

Try and talk to liver unit before this

• INR 3.0
• Hepatic encephalopathy
• Hypotension despite fluid resuscitation
• metabolic acidosis
• Prothrombin time in seconds greater than time from OD in paracetamol overdose

Specific Management

• Paracetamol overdose: Give IV NAC. Even if a late presentation and paracetamol level not elevated
• Autoimmune hepatitis causing ALF then Consider Prednisolone 40-60 mg/day once infection excluded
• Mushroom poisoning: Penicillin G and Silymarin (III) and consider for transplantation the only lifesaving option
• Acute fatty liver of pregnancy expeditious delivery
• HELLP syndrome expeditious delivery is recommended especially in case of elevated lactate levels and hepatic encephalopathy. Screening for putative fatty acid defects should be offered
• Autoimmune hepatitis: Prednisolone, 40-60 mg/day
• Ischaemic: optimise cardiac function
• Hepatic vein thrombosis: consider liver transplantation, provided underlying malignancy is excluded
• Wilson disease/ALF: considered for liver transplant
• HSV/VZV: treated with Aciclovir (III).
• Viral hepatitis A/B- (and E-) related ALF must be treated with supportive care. Virus-specific treatment proven

Complications and General Management: Talk to liver unit early

• Hypoglycaemia: Give 10% dextrose if needed
• Coagulopathy: lack of synthesis of clotting factors, defective fibrinogen, poor platelet function. Vitamin K to reverse any deficiency. Haematology advice essential. Treat if bleeding. IV Vitamin K and FFP and platelets if less than 50x 10⁹/L
• Cerebral oedema: positioned with 20-degree head-up tilt mannitol and hyperventilate in some cases
• Hepatorenal/Multiorgan failure: may require haemofiltration or haemodialysis.
• Hepatic encephalopathy: Fluid and electrolyte balance maintain carefully. Avoid sedatives, diuretics, opiates, and N-Saline. Avoid/treat dehydration, hypoglycaemia, hypokalaemia, hypophosphataemia.
• Ensure on Lactulose 30 mls TDS for at least 2-3 bowel motions per day. If not then consider Enemas (MgSO4 or phosphate). Neomycin 1 g QDS PO.
• If Encephalopathy grade 3/4 then consider ITU for ventilation and nutrition.
• Hyponatraemia: usually due to water excess. Fluid restrict.

References

• EASL Clinical Practical Guidelines on the management of acute (fulminant) liver failure 2017
• Acute Liver Failure NEJM 2013