What is the best treatment for pruritis (itching) in patients with cirrhosis (liver scarring)?

Treatment of Pruritus in Cirrhosis

Rifampicin should be your first-line treatment for pruritus in cirrhosis, starting at 150 mg twice daily and titrating up to 600 mg daily as needed, with regular liver function monitoring. 1

Treatment Algorithm

First-Line: Rifampicin

• Start rifampicin at 150 mg twice daily, increasing to a maximum of 600 mg daily based on symptom response and liver function tests. 1
• Meta-analyses of randomized controlled trials demonstrate that rifampicin effectively reduces hepatic pruritus with a strength of recommendation A (Level 1+ evidence). 1
• Monitor liver function tests every 2-4 weeks due to hepatotoxicity risk—approximately 7.3% of patients develop significant hepatitis with rifampicin therapy. 1, 2
• Warn patients that rifampicin changes the color of bodily secretions (urine, tears, sweat) to orange-red. 1
• In one randomized crossover study, pruritus completely disappeared in 11 of 14 patients and partially improved in 3 patients, compared to only 2 partial responders with placebo (P < 0.001). 3

Second-Line: Cholestyramine

• If rifampicin fails, is not tolerated, or causes hepatotoxicity, switch to cholestyramine 4 g daily, titrating up to a maximum of 16 g daily. 1
• The British Association of Dermatologists recommends cholestyramine as second-line treatment (Strength D, Level 4 evidence), though it is FDA-approved for pruritus associated with partial biliary obstruction. 1, 4
• Critical timing requirement: Administer cholestyramine 2-4 hours before or after all other medications to prevent binding interactions and loss of efficacy. 1, 5, 6
• Most patients derive no additional benefit beyond 8-12 g/day, and constipation is the primary limiting side effect. 1, 5
• Mixing with orange juice and refrigerating overnight improves palatability. 1, 5
• Consider vitamin K supplementation in icteric patients taking cholestyramine, as it may worsen vitamin K deficiency in cholestatic patients. 1, 6

Third-Line: Sertraline

• For patients who fail both rifampicin and cholestyramine, initiate sertraline 75-100 mg daily. 1
• One small randomized controlled trial supports sertraline's efficacy in hepatic pruritus with good tolerability. 1
• Sertraline should be chosen before opioid antagonists due to a more favorable side effect profile. 1

Fourth-Line: Naltrexone

• Naltrexone 50 mg daily is reserved for refractory cases after sertraline failure. 1
• Start at 12.5 mg daily and titrate slowly to avoid opiate withdrawal-like reactions (dysphoria, anxiety, reduced pain threshold). 1
• Some patients require intravenous induction in specialized settings. 1
• Meta-analyses show opioid antagonists reduce pruritus but have significantly more side effects than rifampicin or cholestyramine. 1

Treatments to Avoid

Do Not Use Gabapentin

• Gabapentin has no proven efficacy for hepatic pruritus in controlled trials and should not be used. 1, 5
• A small randomized trial failed to show benefit over placebo despite theoretical benefits. 1

Limited Role for Antihistamines

• Antihistamines provide only non-specific relief through sedative properties, not through antihistamine action. 1
• They are useful adjuncts for some patients but not recommended as specific therapy. 1

Ondansetron Not Recommended

• Two early trials showed benefit, but two more recent randomized controlled trials failed to demonstrate efficacy. 1

Advanced/Experimental Options for Refractory Cases

When all standard therapies fail, consider referral to specialized centers for:

• Ultraviolet (UV) light therapy (relatively accessible compared to other experimental approaches). 1
• Plasmapheresis or albumin exchange for temporary relief in extreme situations. 1
• Nasobiliary drainage (provides transient relief but requires repeated treatments, is technically complicated, and carries pancreatitis risk). 1
• Molecular absorbance recirculating system (MARS) dialysis. 1
• Liver transplantation is highly effective, with pruritus frequently resolving within 24 hours, but should only be considered when all available interventions have failed. 1, 5

Emerging Therapies

• Novel agents targeting bile acid reuptake inhibitors and the autotaxin/lysophosphatidic acid pathway are under investigation in clinical trials. 1

Common Pitfalls

• Do not use cholestyramine as first-line therapy despite its historical use—the evidence now clearly supports rifampicin as superior. 1
• Do not forget the 2-4 hour separation rule when prescribing cholestyramine with other medications. 1, 5, 6
• Do not continue rifampicin without regular liver function monitoring—hepatotoxicity can be severe enough to necessitate liver transplantation. 2
• Do not use gabapentin based on theoretical benefits—clinical trials have disproven its efficacy. 1, 5