Scratching the surface: A systematic review of modern approaches to diagnosing and treating cholestatic pruritus

Table 1 Causes of cholestatic pruritus

Etiology	Examples	Typical features
Autoimmune	PBC, PSC	Chronic, nocturnal pruritus
Genetic	PFIC, ALGS	Severe, early onset
Hormonal	ICP	Third trimester
Drug-induced	Antibiotics, anabolic steroids	Temporal association
Obstructive	Malignancy, stones	Jaundice-predominant

PBC: Primary biliary cholangitis; PSC: Primary sclerosing cholangitis; PFIC: Progressive familial intrahepatic cholestasis; ALGS: Alagille syndrome; ICP: Intrahepatic cholestasis of pregnancy.

Table 2 Diagnostic tools and biomarkers

Tool	Utility	Limitations
Serum bile acids	Reflect cholestasis	Poor correlation with symptom severity
Autotaxin	Emerging biomarker for cholestatic pruritus	Limited availability; not standardized
5-D Itch Scale	Assesses multidimensional symptom severity	Subjective patient-reported measure
Imaging	Exclude biliary obstruction or malignancy	Does not quantify itch severity

Table 3 Pharmacologic therapies for cholestatic pruritus

Therapy	Mechanism	Evidence	Key adverse effects
Cholestyramine	Bile acid binding	Low	GI intolerance
Rifampin	PXR induction	Strong	Hepatotoxicity
Naltrexone	Opioid blockade	Moderate	Withdrawal symptoms
Sertraline	Central modulation	Low-moderate	Sexual dysfunction, weight gain
Fibrates	PPAR activator	Strong (recent)	Myalgia, transaminitis
IBAT inhibitors	BA circulation blockade	Strong (recent)	Diarrhea

IBAT: Ileal bile acid transporter; PXR: Pregnane X receptor; PPAR: Peroxisome proliferator-activated receptor; BA: Bile acid; GI: Gastrointestinal.

Table 4 Emerging and advanced therapies

Therapy	Population studied	Clinical role
Odevixibat	PFIC, ALGS	Refractory pruritus
Maralixibat	ALGS	Pediatric cholestasis
Linerixibat	PBC	Adult cholestasis
Fibrates	PBC, PSC, SSC	Cholestatic pruritus
UVB phototherapy	Mixed etiologies	Adjunctive

UVB: Ultraviolet B; PFIC: Progressive familial intrahepatic cholestasis; ALGS: Alagille syndrome; PBC: Primary biliary cholangitis; PSC: Primary sclerosing cholangitis; SSC: Secondary sclerosing cholangitis.