Itching for Answers: A Comprehensive Review of Cholestatic Pruritus Treatments

Abstract

Cholestasis is a clinical and laboratory syndrome indicating impaired bile production or excretion. One of the hallmark symptoms of cholestasis is pruritus. Itch can be severe and debilitating for patients, impacting their quality of life similarly to pain, and, in some cases, it can be refractory. Current therapies like anion exchange resins and rifampicin, offer partial relief but with side effects. Effective, well-tolerated treatments are urgently needed. This literature review examines existing options (bile acid sequestrants, antihistamines, opioid antagonists, sertraline, and rifampicin) and explores novel therapies (monoclonal antibodies, PPAR agonists, and bile-acid-based therapies). We analyze mechanisms, limitations, and adverse effects to aid clinicians and researchers. Novel approaches include monoclonal antibodies to inhibit bile recirculation and PPAR agonists targeting pruritus signaling. Despite the limited current options, ongoing research promises better treatments for cholestatic pruritus, addressing its distressing impact. In summary, cholestasis-associated pruritus poses a significant challenge with limited treatments. Advancements in understanding its pathophysiology offer hope for more effective therapies in the future.

Keywords: IBAT; K opioid receptor agonist; PPAR agonist; cannabinoid; cholestasis; drug pipeline; elafibranor; fibrates; pruritus.

Figure 1

PRISMA flow diagram for studies selection.

Figure 2

Most common causes of cholestatic pruritus. BRIC = benign recurrent intrahepatic cholestasis, PFIC = progressive familial intrahepatic cholestasis, DILI = drug-induced liver injury, HILI = herb-induced liver injury. Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) can present without abnormalities on cholangiography.

Figure 3

Multistep approach for cholestatic itch treatment and adverse events.