Liver Failure and Cirrhosis

Overview – Liver Failure and Cirrhosis

Liver failure and cirrhosis represent end-stage hepatic conditions with diverse aetiologies, including viral hepatitis, alcohol misuse, toxins, autoimmune disease, and genetic disorders. Cirrhosis develops as a chronic, fibrosing process in response to sustained liver injury, whereas fulminant hepatic failure is an acute and potentially reversible entity marked by rapid hepatocyte necrosis. Recognising and managing these conditions promptly is critical, as both are major causes of morbidity and mortality worldwide, often requiring liver transplantation as definitive therapy.

Fulminant Hepatic Failure

Definition

Acute and severe liver failure characterised by the sudden onset of hepatic encephalopathy and coagulopathy, typically within 2 weeks of the initial liver insult.

Aetiology

Common causes include:

• Viral hepatitis – Hep A, B, D, E
• Drugs – Paracetamol, halothane, antiepileptics, MDMA (ecstasy)
• Toxins – Amanita mushrooms
• Metabolic – Wilson’s disease
• Autoimmune – Autoimmune hepatitis

Morphology

• Massive, diffuse hepatocellular necrosis throughout the liver parenchyma

Clinical Features

• Symptoms:
  • Jaundice
  • Vomiting
  • Fever
  • Rapid development of encephalopathy (within 2 weeks)
• Signs:
  • Small, soft liver
  • Fetor hepaticus
  • Cerebral oedema

Investigations

• FBC – To explore aetiology
• LFTs – ↑ALT/AST, ↑Bilirubin
• Coagulation screen – ↓Prothrombin time, ↓Factor V
• Ultrasound – Liver size, vascular patency

Management

• Treat underlying cause
• Supportive care (e.g. fluids, ICU monitoring)
• Vitamin K, fresh frozen plasma, platelets for coagulopathy
• Liver transplant – Only definitive treatment

Hepatic Cirrhosis

Aetiology

• Toxins – Alcohol, drugs (60–70%)
• Chronic viral hepatitis – HBV, HCV (10%)
• Biliary disease – PBC, obstructive cholangiopathies (10%)
• Genetic/metabolic – Haemochromatosis, Wilson’s disease, α1-antitrypsin deficiency
• Cryptogenic – 5%
• Other rare causes

Pathogenesis

Chronic hepatocyte injury → inflammation and necrosis → nodular fibrosis → architectural distortion and functional failure.

Morphology

• Macro: Shrunken liver, fibrous septa, nodular surface
• Micro: Regenerating nodules surrounded by fibrotic bands

Clinical Features

• Encephalopathy – Confusion, asterixis, coma (↑Ammonia)
• Portal hypertension – Caput medusae, varices, ascites, splenomegaly
• Hormonal dysregulation:
  • Spider naevi, palmar erythema
  • Gynaecomastia
  • Testicular atrophy

Investigations

• ↓Serum albumin
• ↑Prothrombin time
• ↑ALT/AST (esp. if decompensated)
• ↓Na⁺ (hyponatraemia)
• Screen for Wilson’s (serum copper) and α1-antitrypsin deficiency in young patients

Treatment

• Eliminate or treat underlying cause
• Definitive: Liver transplantation

Prognosis

• Irreversible once established
• High mortality without transplant

Signs & Symptoms of Liver Disease

Acute Liver Disease

• Symptoms: Malaise, fever, anorexia (if viral); may be asymptomatic
• Signs: Jaundice or anicteric, hepatomegaly, pale stools, dark urine

Chronic Liver Disease

• Symptoms:
  • RUQ pain, pruritus, abdominal distension
  • Endocrine symptoms: ↓libido, gynaecomastia, amenorrhoea
  • Encephalopathy: confusion, drowsiness
• Signs:
  • Jaundice, fever, spider naevi, hepatosplenomegaly
  • Ascites, caput medusae, peripheral oedema
  • Dupuytren’s contracture, xanthelasmas, testicular atrophy

Hepatic Encephalopathy

• Cause: ↑Ammonia due to impaired hepatic detoxification
• Symptoms: Confusion, irritability, tremor, seizures, coma
• Signs: Asterixis (flapping tremor)

Ascites

• Mechanisms:
  1. Portal hypertension → ↑hydrostatic pressure
  2. Hypoalbuminaemia → ↓oncotic pressure
• Hepatorenal syndrome exacerbates volume retention → worsens ascites

Portal Hypertension

Causes by Level:

• Pre-hepatic: Portal vein thrombosis
• Intra-hepatic: Cirrhosis, schistosomiasis
• Post-hepatic: Hepatic vein thrombosis, Budd-Chiari Syndrome

Summary – Liver Failure and Cirrhosis

Liver failure and cirrhosis are critical hepatic conditions with wide-ranging causes and clinical impacts, from encephalopathy and ascites to portal hypertension and eventual liver transplant. Early recognition of symptoms, investigation into the underlying cause, and timely management are essential. For further hepatology topics, see our Gastrointestinal Overview page.