What is the management for itching due to liver cirrhosis?

Management of Pruritus in Liver Cirrhosis

Cholestyramine should be used as first-line therapy for pruritus in liver cirrhosis, followed by rifampicin as second-line treatment if cholestyramine fails or is not tolerated. 1

First-Line Treatment: Cholestyramine

• Start with cholestyramine 4 g/day, titrating up to a maximum of 16 g/day as tolerated 2
• Administer at breakfast time (one hour before or after eating) if the gallbladder is in situ; rarely is there incremental benefit beyond 8-12 g/day 2
• Must be given 2-4 hours before or after UDCA (typically give UDCA at night) to prevent binding and loss of efficacy 2, 3
• Mixing with orange squash and refrigerating overnight improves palatability 2
• Common side effect is constipation 2
• The evidence basis for cholestyramine is limited as it entered widespread use before the era of evidence-based medicine, but it remains guideline-recommended first-line therapy 2

Important Caveat About UDCA

• UDCA does not reduce cholestatic itch in cirrhosis (except in intrahepatic cholestasis of pregnancy), and paradoxical worsening of itch has been reported anecdotally 2
• UDCA may worsen pruritus in late-stage disease 4

Second-Line Treatment: Rifampicin

• Rifampicin has strong evidence as second-line therapy and should now be considered first-line based on recent meta-analyses 2, 1
• Start at 150 mg once to twice daily, then titrate upwards to 300-600 mg/day based on symptoms and liver function test monitoring 2
• Monitor liver function tests every 2-4 weeks initially due to risk of drug-induced hepatotoxicity (reported in up to 12% of cholestatic patients after 2-3 months) 2
• Use caution in advanced liver disease 2
• Patients should be informed that urine, tears, and other body secretions will be discolored 2
• Ongoing efficacy is reported over up to 2 years of treatment 2

Third-Line Treatment: Sertraline

• Sertraline 75-100 mg daily should be used as third-line therapy before opiate antagonists 2, 1
• Titrate dose to symptoms and as tolerated 2
• One small randomized controlled trial supports its use and it was well tolerated 2
• The mechanism of action remains unclear 2

Fourth-Line Treatment: Opiate Antagonists

• Naltrexone 50 mg/day can be used as fourth-line therapy 2, 1
• Start at 12.5 mg/day and titrate slowly to avoid opiate withdrawal-like reactions 2
• Some patients require an intravenous naloxone induction phase where the dose is rapidly escalated before conversion to oral therapy 2
• Significant side effects include ongoing opiate withdrawal-like reactions, reduced pain threshold, and confusion 2
• Opioid antagonists have significantly more side-effects than cholestyramine and rifampicin, which may limit their use 2

Fifth-Line and Experimental Therapies

For patients resistant to standard therapies:

• Gabapentin should NOT be used - it failed to show benefit over placebo in trials 2, 1
• Physical approaches in specialized centers include UV light therapy, plasmapheresis, albumin exchange, nasobiliary drainage, and MARS (molecular absorbance recirculating system) 2, 1
• UV light therapy is relatively easy to access compared to other experimental treatments 2
• Plasmapheresis or albumin exchange may provide temporary relief in extreme situations 2, 1

Emerging Therapies

• Novel agents under investigation include bile acid reuptake inhibitors and drugs targeting the autotaxin/lysophosphatidic acid pathway 2

Treatments to Avoid

• Antihistamines are not recommended as specific therapy but may provide non-specific relief through sedative properties 2, 1
• Ondansetron has shown inconsistent results and is not routinely recommended 1

Liver Transplantation

• Liver transplantation is highly effective for cholestatic pruritus, with rapid reduction in severity (frequently within the first 24 hours) 2, 1
• Should only be considered when pruritus is "persistent and intractable" after all therapeutic options have been exhausted 2, 1

Monitoring Recommendations

• Use visual analogue scales to assess response to interventions 1
• Monitor liver function tests regularly when using rifampicin due to hepatotoxicity risk 1
• Evaluate for dominant biliary strictures in patients with worsening pruritus, increasing bilirubin, or progressive bile duct dilation 1