Liver Cirrhosis

Overview

Cirrhosis is the advanced stage of chronic liver injury characterised by widespread fibrosis, regenerative nodules and distortion of normal hepatic architecture. This causes two major consequences:

• Portal hypertension
• Reduced hepatic function

Cirrhosis may remain asymptomatic for years before progressing from a compensated to a decompensated stage.

Anatomy and Physiology

Aetiology and Risk Factors

• Alcohol-associated liver disease
• Metabolic dysfunction-associated steatotic liver disease—MASLD/MASH
• Chronic hepatitis B or C
• Autoimmune hepatitis
• Primary biliary cholangitis
• Primary sclerosing cholangitis
• Haemochromatosis
• Wilson disease
• Alpha-1 antitrypsin deficiency
• Chronic biliary obstruction
• Congestive cardiac disease
• Drugs and toxins
• Cryptogenic cirrhosis—cause not identified

Several causes may coexist, particularly metabolic liver disease and alcohol exposure.

Pathophysiology

• Chronic hepatocyte injury causes inflammation and activation of hepatic stellate cells.
• Stellate cells produce excess collagen and extracellular matrix.
• Progressive fibrosis forms fibrous septa and regenerative nodules.
• Distortion of the hepatic vasculature increases intrahepatic resistance, causing portal hypertension.
• Splanchnic vasodilatation reduces effective circulating arterial volume.
• This activates the renin–angiotensin–aldosterone system, sympathetic nervous system and antidiuretic hormone.
• Sodium and water retention subsequently contribute to ascites and oedema.
• Loss of functioning hepatocytes causes impaired:
  • Albumin production
  • Coagulation-factor production
  • Bilirubin metabolism
  • Drug and toxin clearance
  • Immune and metabolic function.

Clinical Manifestations

Compensated cirrhosis

Patients may be asymptomatic or have:

• Fatigue and weakness
• Reduced appetite
• Unintentional weight loss
• Nausea or abdominal discomfort
• Pruritus
• Reduced libido
• Muscle loss

Clinical examination

• Jaundice
• Spider naevi
• Palmar erythema
• Easy bruising
• Muscle wasting
• Gynaecomastia
• Testicular atrophy
• Loss of body hair
• Hepatomegaly or a small nodular liver
• Splenomegaly
• Dupuytren contracture
• Clubbing

Decompensated cirrhosis

• Ascites and abdominal distension
• Peripheral oedema
• Variceal gastrointestinal bleeding:
  • Haematemesis
  • Melaena
  • Haematochezia with severe bleeding
• Hepatic encephalopathy:
  • Sleep-pattern reversal
  • Confusion
  • Personality change
  • Asterixis
  • Reduced consciousness
• Jaundice
• Infection or sepsis
• Reduced urine output from acute kidney injury or hepatorenal syndrome.

Investigations

Blood tests

• FBC:
  • Thrombocytopenia from portal hypertension and hypersplenism
  • Anaemia from bleeding, nutritional deficiency or hypersplenism
  • Leukopenia
• Liver enzymes:
  • ALT and AST may be raised but can be normal in advanced cirrhosis
  • ALP and GGT may suggest cholestatic disease
• Synthetic liver function:
  • Low albumin
  • Prolonged INR
  • Raised bilirubin
• UEC and creatinine:
  • Hyponatraemia
  • Acute kidney injury
  • Hepatorenal syndrome
• Glucose, calcium and phosphate
• CRP and cultures if infection is suspected

Determine the underlying cause

• Hepatitis B and C serology
• Ferritin and transferrin saturation
• ANA, ASMA and serum immunoglobulins
• Antimitochondrial antibodies
• Alpha-1 antitrypsin level
• Ceruloplasmin and urinary copper in appropriate younger patients
• Alcohol and medication history
• Metabolic assessment: BMI, lipids and HbA1c

Fibrosis assessment

• FIB-4 or other serum fibrosis score
• Transient elastography—FibroScan
• Magnetic resonance elastography in selected cases
• Liver biopsy if the diagnosis or underlying cause remains uncertain

Non-invasive blood and elastography-based assessments are increasingly used to identify advanced fibrosis and cirrhosis and reduce the need for liver biopsy.

Imaging

• Abdominal ultrasound with Doppler:
  • Nodular liver
  • Splenomegaly
  • Ascites
  • Portal-vein flow
  • Focal liver lesions
• CT or MRI if complications, vascular thrombosis or hepatocellular carcinoma are suspected.

Ascitic-fluid analysis

Perform diagnostic paracentesis for:

• New-onset ascites
• Hospital admission with cirrhosis and ascites
• Abdominal pain, fever, encephalopathy, hypotension or renal deterioration

Tests include cell count, neutrophils, culture, albumin and total protein.

• SAAG ≥1.1 g/dL: suggests portal-hypertensive ascites.
• Neutrophils ≥250 cells/mm³: diagnostic of spontaneous bacterial peritonitis and requires treatment.

Classification

Child–Pugh score

Assesses the severity and prognosis of cirrhosis using five clinical and laboratory variables.

Child–Pugh score
Parameter	1 point	2 points	3 points
Bilirubin	<34 µmol/L	34–51 µmol/L	>51 µmol/L
Albumin	>35 g/L	28–35 g/L	<28 g/L
INR	<1.7	1.7–2.3	>2.3
Ascites	None	Mild/diuretic-responsive	Moderate–severe/refractory
Encephalopathy	None	Grade I–II	Grade III–IV
A total Child–Pugh score of 5–6 corresponds to Class A, indicating well-compensated liver disease. A score of 7–9 corresponds to Class B, indicating significant functional impairment. A score of 10–15 corresponds to Class C, indicating decompensated liver disease and the poorest prognosis.

Ascites and encephalopathy assessment can be subjective and may change with treatment.

MELD-based score

The Model for End-stage Liver Disease estimates short-term mortality and helps determine liver-transplant urgency.

Component	Significance
Bilirubin	Reflects hepatic excretory dysfunction
INR	Reflects impaired hepatic synthesis of clotting factors
Creatinine	Reflects renal dysfunction, an important predictor of mortality
Serum sodium	Hyponatraemia indicates advanced circulatory dysfunction
Albumin and sex	Included in MELD 3.0 to improve mortality prediction

• Calculated using a validated electronic calculator rather than manually.
• A higher score indicates greater predicted 90-day mortality and greater transplant urgency.
• MELD is more objective than Child–Pugh because it mainly uses laboratory values.
• It does not directly include ascites, encephalopathy, frailty or quality of life.

MELD score	Severity	Interpretation
6–9	Lower severity	Relatively low short-term mortality
10–19	Moderate	Increasing liver-disease severity
20–29	Severe	Significant 90-day mortality risk; transplant assessment is often appropriate
30–39	Very severe	High short-term mortality and high transplant urgency
≥40	Critical	Extremely high short-term mortality and greatest transplant urgency

Treatment

General

• Hepatology follow-up.
• Avoid alcohol.
• Review all prescribed, over-the-counter and complementary medications.
• Avoid NSAIDs, particularly with ascites or kidney dysfunction.
• Vaccinate against hepatitis A and B, influenza, pneumococcus and other infections as appropriate.
• Adequate nutrition with approximately 1.2–1.5 g/kg/day of protein.
• Do not routinely restrict protein in hepatic encephalopathy.
• Avoid prolonged fasting; consider a late-night protein-containing snack.
• Assess and treat malnutrition, sarcopenia, frailty and osteoporosis.

Treatment of complications will be discussed separately

Complications and Prognosis

Complications of liver cirrhosis

• Portal hypertension
• Oesophageal or gastric varices
• Variceal haemorrhage
• Ascites
• Spontaneous bacterial peritonitis
• Hepatic encephalopathy
• Hepatorenal syndrome
• Hepatopulmonary syndrome
• Portopulmonary hypertension
• Hepatic hydrothorax
• Portal-vein thrombosis
• Coagulopathy and bleeding
• Hypersplenism and cytopenias
• Malnutrition, sarcopenia and frailty
• Osteoporosis
• Recurrent infections and sepsis
• Hepatocellular carcinoma
• Acute-on-chronic liver failure
• Multiorgan failure and death.

For more information on the complications of liver cirrhosis click here

Prognosis

• Prognosis depends on the underlying cause, whether disease remains compensated, development of complications, renal function and response to treatment.
• Compensated cirrhosis may remain stable for several years.
• Development of ascites, variceal bleeding or encephalopathy marks decompensation and substantially worsens survival.
• The development of ascites is associated with a reduction in five-year survival from approximately 80% to 30%.
• Refractory ascites, hepatorenal syndrome, recurrent infection, severe encephalopathy and hepatocellular carcinoma indicate a poor prognosis.
• Child–Pugh and MELD-based scores assist with risk assessment.
• Liver transplantation can provide long-term survival for appropriately selected patients with decompensated disease.

Liver transplantation

• Definitive treatment for selected patients with end-stage liver disease, acute liver failure or certain hepatocellular carcinomas.
• Refer early after decompensation, including ascites, variceal bleeding, encephalopathy, progressive jaundice or hepatorenal syndrome.
• Transplant priority is largely based on the MELD score, which estimates short-term mortality using bilirubin, INR, creatinine and sodium.
• Assessment considers disease severity, cardiac and respiratory fitness, renal function, infection, malignancy, frailty, substance use, adherence and social support.

References

1. European Association for the Study of the Liver. EASL clinical practice guidelines for the management of patients with decompensated cirrhosis. J Hepatol. 2018;69(2):406–460. doi:10.1016/j.jhep.2018.03.024.
2. Biggins SW, Angeli P, Garcia-Tsao G, Ginès P, Ling SC, Nadim MK, et al. Diagnosis, evaluation, and management of ascites, spontaneous bacterial peritonitis and hepatorenal syndrome. Hepatology. 2021;74(2):1014–1048. doi:10.1002/hep.31884.
3. Kaplan DE, Ripoll C, Thiele M, Fortune BE, Simonetto DA, Garcia-Tsao G, et al. AASLD practice guidance on risk stratification and management of portal hypertension and varices in cirrhosis. Hepatology. 2024;79(5):1180–1211. doi:10.1097/HEP.0000000000000647.
4. European Association for the Study of the Liver. EASL clinical practice guidelines on non-invasive tests for evaluation of liver disease severity and prognosis—2021 update. J Hepatol. 2021;75(3):659–689. doi:10.1016/j.jhep.2021.05.025.
5. Karvellas CJ, Bajaj JS, Kamath PS, McPhail MJW, Piano S, Sanyal AJ, et al. AASLD practice guidance on acute-on-chronic liver failure and the management of critically ill patients with cirrhosis. Hepatology. 2024;79(6):1463–1502. doi:10.1097/HEP.0000000000000671.