Liver Failure — Acute & Chronic Causes, Symptoms & Transplant Treatment Guide — Symptoms, Causes & Treatment | MyMedicPlus

Liver failure occurs when the liver loses its ability to perform its essential metabolic, synthetic, and detoxification functions — arising when the loss of functional hepatocyte mass is sufficient to impair these processes. Two distinct clinical syndromes exist: Acute liver failure (ALF) — rapid hepatocellular necrosis in a previously healthy liver, causing coagulopathy (INR above 1.5) and encephalopathy within 26 weeks of jaundice onset; fulminant hepatic failure when encephalopathy develops within 8 weeks. Chronic liver failure (decompensated cirrhosis) — the end-stage of chronic progressive liver disease, characterised by loss of hepatic synthetic function (hypoalbuminaemia, coagulopathy) and development of complications: ascites, variceal haemorrhage, hepatic encephalopathy, and hepatorenal syndrome. The distinction between acute and chronic failure has major prognostic and therapeutic implications. Liver transplantation is the only definitive cure for both forms when organ failure is irreversible.

Acute liver failure causes: paracetamol (acetaminophen) overdose — the most common cause in the UK and USA (50% of ALF cases); intentional or unintentional (therapeutic misadventure) overdose. Viral hepatitis: hepatitis B (particularly acute HBV with delta co-infection), hepatitis A and E (especially in pregnancy — HEV can cause fulminant failure). Drug-induced liver injury (DILI): anti-tuberculosis drugs (isoniazid, rifampicin), herbal and dietary supplements (pyrrolizidine alkaloids, kava kava), NSAIDs, amiodarone, ketoconazole, chemotherapy agents. Ischaemic hepatitis ('shock liver') from prolonged hypotension. Wilson's disease (hepatic presentation). Budd-Chiari syndrome (hepatic vein thrombosis). Pregnancy-related: acute fatty liver of pregnancy (AFLP), HELLP syndrome. Chronic liver failure (cirrhosis leading to decompensation): alcohol-related liver disease (most common in Europe — 50% of cirrhosis); chronic viral hepatitis B and C; non-alcoholic fatty liver disease (NAFLD/MASH — the most rapidly growing cause globally); autoimmune hepatitis; primary biliary cholangitis (PBC); primary sclerosing cholangitis (PSC); haemochromatosis; Wilson's disease; alpha-1-antitrypsin deficiency.

Acute liver failure: initial non-specific symptoms — nausea, vomiting, right upper quadrant pain, malaise. Rapid progression (hours to days) to jaundice (rising bilirubin), coagulopathy (bruising, bleeding, elevated INR), and hepatic encephalopathy (stages I: altered affect; II: drowsiness, asterixis; III: stupor, incoherence; IV: coma, cerebral oedema — risk of brainstem herniation). Hypoglycaemia (from impaired gluconeogenesis), metabolic acidosis, and acute kidney injury are common complications. Chronic liver failure (decompensated cirrhosis): jaundice (golden yellow sclera and skin), ascites (abdominal distension, fluid wave, shifting dullness — from portal hypertension and hypoalbuminaemia), peripheral oedema, splenomegaly, spider naevi (above 5 on the upper body), palmar erythema, leukonychia (white nails), Dupuytren's contracture (alcohol), hepatic flap (asterixis), hepatic fetor (sweet-musty smell from mercaptans), caput medusae (dilated periumbilical veins), and muscle wasting.

Acute liver failure: liver function tests (markedly elevated ALT, AST — frequently above 1000 IU/L in ischaemic hepatitis and paracetamol overdose); elevated bilirubin; prolonged prothrombin time (INR) — the most important indicator of synthetic failure; low blood glucose; elevated serum lactate (metabolic acidosis); serum paracetamol level; viral serology (anti-HAV IgM, HBsAg, anti-HCV, anti-HEV); autoimmune markers (ANA, anti-SMA, IgG — autoimmune hepatitis); ceruloplasmin and urinary copper (Wilson's disease); urine and serum toxicology. Brain CT: excludes intracranial haemorrhage before lumbar puncture; cerebral oedema in grade III–IV encephalopathy. Chronic liver failure (cirrhosis): liver function tests (hypoalbuminaemia, elevated bilirubin, coagulopathy — INR above 1.2); FBC (thrombocytopenia from hypersplenism; anaemia — multifactorial); renal function (creatinine — hepatorenal syndrome); serum sodium (dilutional hyponatraemia — poor prognosis); MELD score (model for end-stage liver disease) = 3.78 x loge bilirubin + 11.2 x loge INR + 9.57 x loge creatinine + 6.43 — predicts 90-day transplant-free mortality and guides transplant listing priority; Child-Pugh score. Diagnostic ascitic tap: protein, albumin (SAAG = serum-ascites albumin gradient — above 1.1 g/dL confirms portal hypertension); culture for spontaneous bacterial peritonitis (SBP — neutrophils above 250 cells/mm3). Upper GI endoscopy: grades varices and assesses variceal bleeding risk.

Acute liver failure: Paracetamol-induced ALF: N-acetylcysteine (NAC) IV — the antidote; dramatically reduces mortality if given within 8–10 hours; also benefits non-paracetamol ALF. Viral hepatitis B: entecavir or tenofovir antiviral therapy. Autoimmune hepatitis: IV methylprednisolone. Budd-Chiari: anticoagulation, TIPS (transjugular intrahepatic portosystemic shunt). AFLP: immediate delivery. Management of ALF complications: ICU care; lactulose + rifaximin for encephalopathy; IV dextrose for hypoglycaemia; Fresh frozen plasma for active bleeding (not prophylactically); terlipressin + albumin for hepatorenal syndrome; prophylactic antibiotics; intracranial pressure monitoring for grade III–IV encephalopathy; early listing for liver transplantation (King's College Criteria for paracetamol and non-paracetamol ALF guides listing decisions). Decompensated cirrhosis management: Ascites: sodium restriction (below 2 g/day), spironolactone 100–400 mg + furosemide 40–160 mg; large-volume paracentesis + IV albumin (8 g/L drained) for refractory ascites; TIPS for refractory ascites. Variceal haemorrhage: IV terlipressin + ceftriaxone → urgent upper GI endoscopy with band ligation; secondary prophylaxis with propranolol + band ligation; TIPS for uncontrolled haemorrhage. Hepatic encephalopathy: lactulose TDS–QDS (target 2–3 soft stools/day) + oral rifaximin 550 mg BD. Spontaneous bacterial peritonitis (SBP): IV cefotaxime + IV albumin 1.5 g/kg day 1, 1.0 g/kg day 3 (albumin reduces hepatorenal syndrome risk); prophylactic norfloxacin 400 mg BD in high-risk patients. Hepatorenal syndrome (HRS): terlipressin + IV albumin; renal replacement therapy as bridge to transplant. Liver transplantation: the only definitive cure for irreversible liver failure in selected patients; MELD score above 15 typically qualifies for listing.

Liver failure generates severe systemic complications affecting virtually every organ system. Hepatic encephalopathy — ammonia-driven cerebral dysfunction from impaired urea cycle — progresses from subtle cognitive impairment (Grade I) through confusion and asterixis (Grade II-III) to deep coma (Grade IV); cerebral oedema in acute liver failure causes raised intracranial pressure, Cushing's triad (hypertension, bradycardia, respiratory irregularity), and uncal herniation with fatal outcome. Coagulopathy from reduced hepatic synthesis of coagulation factors (II, V, VII, IX, X) and fibrinogen causes clinical bleeding — gastrointestinal haemorrhage, haematoma, and haemorrhage into the lungs and airways. Hepatorenal syndrome — functional kidney failure from severe splanchnic vasodilatation — occurs in 50% of patients with acute-on-chronic liver failure; Type 1 HRS carries 90% mortality at 2 weeks without liver transplantation. Systemic inflammatory response syndrome (SIRS) and sepsis from bacterial translocation and impaired Kupffer cell function are leading causes of death in both acute and chronic liver failure. Pulmonary complications include hepatopulmonary syndrome (intrapulmonary vascular dilatation causing hypoxaemia — PaO2 below 8 kPa) and portopulmonary hypertension. Hypoglycaemia from impaired glycogen storage and gluconeogenesis. Multi-organ failure — the terminal event in severe liver failure — involves renal, respiratory, circulatory, and haematological system failure; liver transplantation is the only definitive treatment for irreversible liver failure with an overall 5-year survival of approximately 75%.

Prevent alcohol-related liver disease: abstain completely from alcohol if any established liver disease is present (alcohol is the most important modifiable cause of cirrhosis in Western countries). Safe alcohol limits: men below 14 units per week, women below 14 units per week, spread across at least 3 alcohol-free days. Hepatitis B vaccination: universal vaccination in infancy prevents HBV-related cirrhosis — adults at risk should be vaccinated (MSM, healthcare workers, those with multiple sexual partners). Hepatitis C: prevent transmission through safe injecting practices and needle exchanges; treat chronic HCV infection with DAAs before cirrhosis develops — SVR achieved in over 95%. Paracetamol: never exceed 1 g every 4 hours or 4 g per day (3 g per day in those who drink alcohol or have liver disease); avoid paracetamol-containing combination products concurrently. MASH prevention: maintain healthy body weight; exercise 150 minutes per week; Mediterranean diet; control diabetes, hypertension, and dyslipidaemia. Regular monitoring for patients with cirrhosis: 6-monthly liver ultrasound + AFP for hepatocellular carcinoma surveillance; esophagogastroduodenoscopy to screen for varices.

Seek emergency assessment immediately for: confusion or sudden change in behaviour (hepatic encephalopathy), haematemesis or melaena (variceal bleeding), severe abdominal pain or fever with known liver disease (spontaneous bacterial peritonitis), or jaundice with right upper quadrant pain and fever (cholangitis). Any person who has taken a paracetamol overdose — regardless of dose or intention — should attend an emergency department immediately, as liver damage may not be apparent for 24–72 hours and early NAC treatment is life-saving. Seek urgent GP review for: new-onset jaundice (yellowing of skin or eyes), progressive abdominal distension, or leg swelling in someone with known liver disease — these may indicate decompensation. Patients with cirrhosis should attend all surveillance appointments — early detection of hepatocellular carcinoma or varices significantly improves outcomes.