Liver Failure — Symptoms, Causes & Treatment | MyMedicPlus

Liver failure is the inability of the liver to perform its vital functions including detoxification, protein synthesis, and coagulation factor production. Acute liver failure (ALF) develops within 26 weeks in a person without pre-existing liver disease. Acute-on-chronic liver failure (ACLF) is a distinct syndrome with high short-term mortality. Liver failure occurs when the liver loses sufficient functional capacity to maintain normal physiological processes, including detoxification of metabolic byproducts, synthesis of clotting factors and albumin, metabolism of drugs and bilirubin, and gluconeogenesis. Acute liver failure (ALF) develops rapidly in a previously normal liver — most commonly from paracetamol (acetaminophen) overdose (accounting for 50% of ALF in the UK), viral hepatitis B, drug-induced liver injury, or Wilson's disease; it carries 50-80% mortality without emergency liver transplantation. Acute-on-chronic liver failure (ACLF) occurs when an acute insult (infection, bleeding, alcohol) precipitates decompensation in chronic liver disease — carrying 30-day mortality of 30-50% depending on organ failure count. Chronic liver failure represents the end-stage of progressive cirrhosis from any cause.

Acetaminophen (paracetamol) overdose is the leading cause of ALF in Western countries, accounting for over 50% of cases. Other causes include viral hepatitis A and B, idiosyncratic drug reactions, autoimmune hepatitis, Wilson's disease, and Budd-Chiari syndrome. ACLF is precipitated by infection, GI bleeding, or alcohol in pre-existing cirrhosis. The most common causes of acute liver failure include: paracetamol hepatotoxicity (dose-dependent direct hepatocyte necrosis above 10-15 g; predictable and preventable), idiosyncratic drug reactions (anti-TB drugs isoniazid and rifampicin, NSAIDs, antibiotics, halothane), acute hepatitis B (including reactivation in immunosuppressed patients), hepatitis E (particularly in pregnant women — 20% maternal mortality), Budd-Chiari syndrome (hepatic vein thrombosis causing acute hepatic congestion), and Wilson's disease crisis. Causes of chronic liver failure/cirrhosis include: alcohol-related liver disease, NAFLD/NASH (the fastest growing cause), chronic hepatitis B and C, primary biliary cholangitis, primary sclerosing cholangitis, autoimmune hepatitis, haemochromatosis, and alpha-1-antitrypsin deficiency.

Jaundice, coagulopathy (bruising, bleeding), hepatic encephalopathy (altered consciousness, asterixis, coma), ascites, acute kidney injury, and hypoglycemia are hallmarks. Cerebral edema is the most feared complication of ALF and a leading cause of death. Multi-organ failure is common in severe cases. Jaundice is universal in significant liver failure — bilirubin accumulates as hepatic conjugation and excretion fail. Coagulopathy manifests as easy bruising, petechiae, prolonged bleeding from minor cuts, and gum bleeding. Hepatic encephalopathy presents as personality change, confusion, asterixis (flapping tremor when arms are outstretched), drowsiness, and in severe cases, coma. Ascites causes progressive abdominal distension, early satiety, and dyspnoea from diaphragmatic elevation. Muscle wasting and nutritional deficiency from impaired protein synthesis and anorexia are hallmarks. Splenomegaly from portal hypertension causes hypersplenism — low platelets, white cells, and red blood cells. Fetor hepaticus — a characteristic sweet musty breath from mercaptans — is pathognomonic of severe hepatic failure.

Serum bilirubin, ALT, AST, INR, albumin, creatinine, blood glucose, and ammonia levels are measured urgently. Acetaminophen levels are checked in all ALF patients. Liver ultrasound with Doppler rules out vascular causes. Brain CT or MRI evaluates for cerebral edema. Liver biopsy guides etiology when safe. Liver function tests assess severity: bilirubin (elevated — jaundice), ALT and AST (elevated — hepatocellular damage), ALP and GGT (elevated — cholestasis), and albumin (reduced — impaired synthetic function). Prothrombin time (PT/INR) is the most reliable indicator of synthetic function — elevated INR above 1.5 in acute liver failure defines the condition. Arterial blood gas and lactate. Factor V (or ATIII) level — critical in deciding liver transplantation eligibility (Clichy criteria for paracetamol-induced ALF: factor V below 20% in patients under 30 or below 30% in patients over 30, combined with grade III-IV encephalopathy). Kings College Criteria define transplant criteria for non-paracetamol ALF. Paracetamol levels and toxicology screen. Abdominal ultrasound with Doppler (hepatic vasculature, portal vein flow, splenomegaly).

ICU admission with close monitoring is mandatory. N-acetylcysteine (NAC) is the antidote for acetaminophen-induced ALF and beneficial in non-acetaminophen ALF. Hepatic encephalopathy: lactulose, rifaximin, avoid sedation. Cerebral edema: osmotic therapy, head elevation. Coagulopathy: vitamin K and blood products. Emergency liver transplantation is lifesaving in eligible patients meeting King's College criteria. Acute liver failure management is in an ICU setting with liver transplantation centre involvement. N-acetylcysteine (NAC) is the antidote for paracetamol hepatotoxicity — effective within 8-10 hours; in non-paracetamol ALF, NAC also shows benefit in improving transplant-free survival. Hepatic encephalopathy management: lactulose (targets colonic ammonia production by acidifying colonic contents — dose 30-50 mL three times daily titrated to 2-3 soft stools/day); rifaximin (non-absorbable antibiotic reducing colonic bacterial ammonia production — 550 mg twice daily); low-protein diet is no longer recommended. Ascites management: sodium restriction (88 mmol/day); aldosterone antagonists (spironolactone 100-400 mg/day); loop diuretics (furosemide); large-volume paracentesis with 8 g albumin per litre removed for refractory ascites. Variceal bleeding: IV terlipressin (splanchnic vasoconstrictor — 2 mg every 4-6 hours), endoscopic band ligation (EBL), and prophylactic ceftriaxone 1 g IV daily for 7 days (reduces infection-related mortality). Liver transplantation for acute liver failure meeting King's College or Clichy criteria achieves 1-year survival of approximately 80%.

Cerebral edema and intracranial hypertension, acute kidney injury (hepatorenal syndrome), severe coagulopathy with GI or intracranial bleeding, sepsis, hypoglycemia, and multi-organ failure are the principal life-threatening complications. Without transplantation, mortality of ALF with grade 3-4 encephalopathy exceeds 80%. Hepatorenal syndrome (HRS) — functional acute kidney injury with serum creatinine above 133 mcmol/L in the absence of intrinsic renal disease or hypovolaemia — occurs in 50% of decompensated cirrhosis patients within 5 years of diagnosis. Type 1 HRS (rapidly progressive, creatinine doubling to above 221 mcmol/L within 2 weeks) has 90% in-hospital mortality without liver transplantation. Type 2 HRS (slower, associated with refractory ascites) has 50% 6-month mortality. Sepsis from spontaneous bacterial peritonitis, urinary infection, pneumonia, and line infection is the leading precipitant of acute-on-chronic liver failure — mortality doubles with each additional organ failure.

Avoid acetaminophen overdose and do not exceed 4g per day (2g in those with alcohol use). Vaccinate against hepatitis A and B. Avoid hepatotoxic drugs in patients with liver disease. Manage chronic liver disease proactively to prevent ACLF precipitants: treat infections promptly, control alcohol use, and perform prophylaxis for bacterial infections. Prevention of liver failure centres on eliminating causative exposures. Avoid paracetamol overdose — the maximum safe dose is 4 g/day in healthy adults; 2 g/day in alcohol users and liver disease — never exceed this dose, and be aware of paracetamol in combination products. Alcohol abstinence is essential in alcoholic liver disease — even moderate drinking accelerates cirrhosis progression. Hepatitis B vaccination prevents HBV-related liver failure — universal infant vaccination and vaccination of high-risk adults (healthcare workers, sexual contacts of HBV-infected persons) is recommended. Hepatitis C treatment with direct-acting antivirals (DAAs) achieves cure in 95-99%, preventing progression to cirrhosis and liver failure. Treat NASH risk factors (obesity, diabetes, metabolic syndrome) through lifestyle modification, GLP-1 receptor agonists (semaglutide, liraglutide), and emerging antifibrotic agents.

Call emergency services (999/911) or attend Emergency Department immediately for: confusion, drowsiness, or altered consciousness in someone with known liver disease or recent paracetamol (acetaminophen) overdose — acute hepatic encephalopathy is an emergency; paracetamol overdose of any amount — attend Emergency immediately regardless of symptoms; the antidote (N-acetylcysteine) must be given within 8-10 hours of overdose for maximum benefit; severe jaundice (deep yellow skin and whites of eyes) with nausea and confusion developing over days; haematemesis (vomiting blood) or melaena (black tarry stools) in anyone with liver disease — variceal bleeding emergency; sudden severe abdominal pain in someone with ascites — possible spontaneous bacterial peritonitis (SBP) requiring emergency antibiotics; significant bruising, unexplained bleeding (nosebleeds, gum bleeding, blood in urine), or very prolonged clotting — coagulopathy of liver failure. If someone has taken a paracetamol overdose: do not wait for symptoms — liver failure may be prevented entirely by attending Emergency within 8-10 hours and receiving NAC treatment.