Background Information
Definition
Cirrhosis is defined as the end stage of chronic liver disease, characterised by diffuse hepatic fibrosis and the formation of regenerative nodules that disrupt normal liver architecture
The 3 main causes of chronic liver disease (thus cirrhosis) are:
- ARLDAlcohol-related liver disease
- NAFLDNon-alcoholic fatty liver disease
- Chronic viral hepatitis (B and C)
Complications and Manifestations
Complications of decompensated cirrhosis include:
| Pathophysiology mechanism | Manifestations |
|---|---|
| Portal hypertension |
|
| Impaired liver synthetic / detoxification function |
|
| Other |
|
Diagnosis
Cirrhosis Diagnosis
Transient elastographyTransient elastrography measures liver stiffness in kPa. Increased liver stiffness suggests cirrhosis. (e.g. FibroScan) should be offered to the following to diagnose cirrhosis:
- Hepatitis C virus infection
- People who drink excess alcohol (men >50 units and women>35 units per week)
- Alcohol-related liver disease
- NAFLDNon-alcoholic fatty liver disease only if there is advanced liver fibrosis (defined by ELFEnhanced liver fibrosis score ≥10.51) – see this article for more information on NAFLD
For concept-based exam questions:
- Ultrasound is usually the initial imaging modality in those with suspected liver disease, but it has limited sensitivity in diagnosing cirrhosis. So its role is limited to detecting the presence of liver disease, and guiding subsequent testing, but NOT diagnosing cirrhosis.
- 1st line investigation (for cirrhosis): transient elastography (e.g. FibroScan) – increased liver stiffness suggests cirrhosis
- Definitive testing: liver biopsy (not routinely used, only if transient elastography is not feasible and still unclear)
Screening and Monitoring for Complications
Calculate MELD scoreMELD (model for end-stage liver disease) Takes the following into account: - Dialysis or not - Creatinine - Bilirubin - INR every 6 months:
- ≥12 indicates high risk of complications
In patients with cirrhosis, routine monitoring for the following complications is recommended:
| Complication | Test |
|---|---|
| Hepatocellular carcinoma | Ultrasound +/- AFPAlpha-fetoprotein every 6 months |
| Oesophageal varices | Perform upper GI endoscopy after diagnosis (unless planning to take carvedilol or propranolol)
For subsequent actions and monitoring, see below |
Management
Compensated Cirrhosis
No specific management, with the aim of preventing progression of liver disease and complications:
- Complete alcohol abstinence (in patients who drink)
- Weight loss (in overweight / obesity / NAFLD patients)
- Routine vaccinations (for all chronic liver disease patients)
- Annual influenza
- Pneumococcal
- Hepatitis A and B
- SARS-CoV-2
- Ensure adequate nutrition
- Screening and monitoring for complications (see above)
Decompensated Cirrhosis
Portal Hypertension
Primary prevention of decompensation:
- 1st line: carvedilol
- 2nd line: propranolol
Variceal Bleeding
Primary Prevention
Screening upper GI endoscopy should be offered if the patient is NOT taking carvedilol or propranolol:
- No varices → annual surveillance
- Small varices → annual surveillance or primary prophylaxis with carvedilol (if Child Pugh class C)
- Medium / large varices → primary prophylaxis
- 1st line: NSBBNon-selective beta blocker (carvedilol / propranolol)
- 2nd line: endoscopic variceal band ligation
No further surveillance needed if on NSBBNon-selective beta blocker for primary prophylaxis.
Acute Variceal Bleed Management
For management of other causes of acute upper GI bleeds, see the Upper Gastrointestinal (GI) Bleeding article.
Pre-endoscopic management for ALL suspected variceal bleeding:
- Resuscitation (+/- transfusion as needed), and
- Terlipressin (stop after 5 days or after definitive haemostasis), and
- Prophylactic antibiotic
Definitive management: endoscopic interventions once patient is stablised:
- Oesophageal varices → band ligation
- Gastric varices → cyanoacrylate glue injection (chemical ligation)
If endoscopic measures failed → transjugular intrahepatic portosystemic shunt (TIPS) A radiological procedure where a mental stent is placed to create a shunt between the portal vein and hepatic vein (accessed via the jugular vein) Mechanism: blood bypasses the cirrhotic liver → reducing portal pressure
If re-bleeding occurs after successful endoscopic intervention → repeat endoscopic interventions (if the patient is stable).
NICE did not make any recommendations on the use of Sengstaken-Blakemore tube (a type of balloon tamponade), due to the risk of complications like aspiration and oesophageal perforation.
However, it may be used as a temporary measure if:
- The patient cannot be stabilised for endoscopic haemostasis, or
- Endoscopic haemostasis failed to control bleeding and before definitive therapy (e.g. TIPS) can be performed
Post-Acute Variceal Bleed (Secondary Prevention)
Offer all the following:
- Carvedilol
- Variceal band ligation every 4 weeks until eradication
- Surveillance upper GI endoscopy
Hepatic Encephalopathy
Acute Management [Ref]
- Identify & treat precipitantsInfection, GI bleed, constipation, electrolyte disorders, dehydration, TIPS, excess diuretics. Correction alone reverses most cases
- Pharmacological therapy
- Step 1: Oral lactulose (aiming for 2-3 soft stools/day)
- Alternative: if unsafe swallow (impending coma/coma) → phosphate enema
- Step 2: add rifaximin
Poorly-absorbable (acting locally on the gastrointestinal tract), broad-spctrum antibiotic that reduces gut bacteria producing ammonia.
- Step 1: Oral lactulose (aiming for 2-3 soft stools/day)
Secondary prophylaxis (post-encephalopathy episode)
- Step 1: Oral lactulose (continued indefinitely after 1st episode)
- Step 2 (if ≥ 1 recurrence within 6 months): add rifaximin
Note that hepatic encephalopathy can develop after TIPSSTransjugular intrahepatic portosystemic shunt. (35-50%). This can be prevented by using a smaller diameter stent and the use of prophylactic rifaximin before TIPSS.
Embolisation of TIPSS / portosystemic shunts is therefore a management option for refractory encephalopathy (however, not 1st line).
Weight loss and sarcopaenia can worsen hepatic encephalopathy, therefore low-protein nutrition should be avoided, and adequate protein and energy intake maintained.
Ascites
All patients:
- Dietary salt restriction (but no routine fluid restriction)
- Stop exacerbating medications (e.g. NSAIDs, ACE inhibitors)
- Spironolactone
- If inadequate or severe ascites: add furosemide to spironolactone
Other procedures:
- Consider therapeutic large-volume paracentesis for tense
In the grading of ascites, tense ascites is classified as grade 3, which is defined as severe ascites with tense abdominal distension.
Patients often exhibit marked discomfort or compromise of organ function.
or refractory ascites- Followed by IV albumin (20 / 25%) infusion if >5 L is drained to prevent paracentesis-induced circulatory dysfunction
Paracentesis-induced circulatory dysfunction is a complication that occurs after the removal of large volumes of ascitic fluid, typically defined as more than 5 liters, in patients with cirrhosis and tense ascites. It is characterized by a reduction in effective arterial blood volume and activation of vasoconstrictor and antinatriuretic neurohormonal systems, including the renin-angiotensin-aldosterone system and vasopressin, leading to renal impairment, hyponatremia, and increased risk of morbidity and mortality.
- Followed by IV albumin (20 / 25%) infusion if >5 L is drained to prevent paracentesis-induced circulatory dysfunction
- Last resort: TIPSTransjugular intrahepatic portosystemic shunt
Spontaneous Bacterial Peritonitis (SBP)
Management
Empirical antibiotic therapy for SBP:
- IV ceftriaxone, or
- Oral co-amoxiclav (for outpatient management)
IV albumin (20 / 25%) infusion should be given if there are an increased serum creatinine or a rising serum creatinine.
To be given within 6 hours of diagnosis and then 1 g/kg on day 3.
Prophylaxis
Do not routinely offer antibiotics to prevent SBP
Consider prophylactic antibiotic (ciprofloxacin / norfloxacin / co-trimoxazole) if:
- Previous episode of SBP (secondary prevention), or
- Severe liver disease (ascitic protein ≤15 g/litre / Child-Pugh score >9 / MELD score >16), or
- Consequences of SBP could seriously impact the patient’s care (e.g. affect their wait for TIPS)
Duration: antibiotics given to prevent SBP are continued until the ascites resolves
Hepatorenal Syndrome
HRS-AKIHepatorenal syndrome - acute kidney injury (formerly, type 1 HRS)[Ref]
- 1st line: IV vasoconstrictor (terlipressin is preferred, noradrenaline) + IV human albumin solution
HRS-NAKIHepatorenal syndrome - non-acute kidney injury (formerly, type 2 HRS)[Ref]
- The mainstay of treatment is managing the underlying ascites & portal hypertension
- Includes repeated large-volume paracentesis with albumin replacement, sodium restriction, and consideration of TIPSTransjugular intrahepatic portosystemic shunt in selected patients
- Medical therapy with vasoconstrictor / albumin is less effective and not routine in HRS-NAKI
Definitive treatment (both HRS-AKI/HRS-NAKI): liver transplantation
Renal replacement therapy (haemodialysis or continuous venovenous hemofiltration) may be considered as a bridge to transplantation or in cases of severe, refractory renal failure.
Symptoms in Advanced Liver Disease
Selected recommendations from BSG guidelines:
| Symptom | Recommendation |
|---|---|
| Pain |
Avoid the following if possible:
|
| Nausea and vomiting |
|
References
NICE guideline Cirrhosis in over 16s: assessment and management
BSG Guidelines on the Management of Ascites in Cirrhosis
BSG BSG Best Practice Guidance: outpatient management of cirrhosis – part 1: compensated cirrhosis
BSG Best Practice Guidance: outpatient management of cirrhosis – part 2: decompensated cirrhosis