Table 2. Summary of management recommendations for two cholestatic liver disease.

	Primary biliary cirrhosis (PBC)	Primary sclerosing cholangitis (PSC)
Disease-Specific Medical Therapy	UDCA 13–15 mg/kg/day orally for patients with abnormal liver enzymes (even if asymptomatic) Medication should be continued indefinitely throughout disease course.3,11 Initiate gradually over 2–3 weeks to full dose to avoid triggering pruritus. US FDA Pregnancy Category B drug Not US FDA-approved for use in breastfeeding	UDCA not recommended in adult PSC patients38 Corticosteroids and other immunosuppressants as indicated for PSC-overlap syndromes38
Fatigue	Investigate alternate causes; discontinue potentially inciting medications if possible11 Consider referral to psychological counseling services for management of concomitant disorders and development of coping strategies11
Pruritus	Stepwise therapy, starting from first- to fourth-line (1–4, below). Advancement to next step for treatment failure, intolerance, or significant side effects to aforementioned option:11,16 1)Bile acid sequestrants such as cholestyramine dosed 4 g orally up to 4 times/day. Increase gradually to maximum dose of 600 mg/day. 2)Rifampicin 150–300 mg orally twice daily. Start at 150 mg daily and increase to maximum dose of 600 mg/day. Close monitoring of liver biochemistries and blood counts. 3)Opioid antagonists such as naltrexone starting at 25 mg orally/day; can be increased to 50 mg/day. 4) Sertraline starting at low doses and increasing to maximum of 100 mg/day. Consider experimental treatment or referral to specialized center for resistant cases LT effective but should only be considered in severe, refractory cases after failure of all alternatives
Fat-Soluble Vitamin Deficiency	Serologic laboratory monitoring of vitamins A, D, & E (particularly in advanced disease) Yearly testing recommended if bilirubin >2.0 mg/dL3 Enteral vitamin A, D, & E supplementation in cases of overt cholestasis, steatorrhea and malabsorption, or when diagnosed with deficiency38 Parenteral vitamin K administered empirically before invasive procedures in overt cholestasis or in the setting of bleeding11
Metabolic Bone Disease	DEXA scan at PBC diagnosis with follow-up assessment at 1–3 year intervals based on individual risks and lifestyle factors11,16,38,115 Cholestasis with normal BMD: T-score (>−1.0) Follow basic measures for MBD prevention or delayed progression: Supplemental calcium + vitamin D3 Regular weight-bearing exercise Abstinence from smoking Avoidance of excess alcohol intake Assessment and modification of individual risk factors Hepatic Osteopenia: T-score (−1.0 to −2.5) DEXA scan every 2 years Follow basic preventive measures Bisphosphonate therapy may be appropriate at T-score <−1.5 in the presence of other risk factors such as prolonged glucocorticoid use Hepatic Osteoporosis: T-score (<−2.5) or history of fragility fracture Consider other causes of low BMD+ Follow basic preventive measures Bisphosphonate therapy Consider HRT in postmenopausal females, patients with early (age <45) menopause or female hypogonadism. Consider testosterone in male patients with hypogonadism. Risks and benefits of such therapies must be weighed, especially with regard to malignancy risks, and treatment individualized. Refer to bone specialist for management of severe or complex cases requiring consideration of alternative therapy. Interval DEXA monitoring (every 1–3 years) based on degree of cholestasis and presence of other individual risk factors.
	LT Patients 115,191 Follow basic preventive measures Pre-LT: Screen with DEXA, thoracolumbar spine X-rays, free testosterone (males), 25-OH vitamin D, serum calcium MBD therapy for LT candidates ideally started prior to surgery and continued post-transplant given rapid bone loss surrounding LT Post-LT: Yearly DEXA for initial 5 years in osteopenic patients and every 2–3 years in patients with normal BMD DEXA screening there after is determined by the presence of risk factors
Hyperlipidemia	UDCA may provide initial step in lowering low-density lipoprotein and total cholesterol levels in PBC
	Further lipid-lowering medical therapy based on individual risks with close monitoring of liver biochemical profile Large-volume plasmapheresis for management of xanthomas (particularly planar) is rarely employed but may be considered in cases causing pain or limitations of manual dexterity/mobility166
Other Disease-Related Considerations	Sicca Syndrome 3 Dry eyes Artificial tears as initial management Pilocarpine or cevimeline if symptoms persist Cyclosporine ophthalmic emulsion for refractory cases under direction of ophthalmologist Xerostomia & Dysphagia Saliva substitutes Pilocarpine or cevimeline if symptoms persist Encourage oral hygiene regimen (mouth-rinsing, use of fluoride-containing toothpaste, dental flossing) and regular dental care Suggest salivary gland stimulation with sugar-free gum or hard candy; lip care with oil or petroleum-based balm/lipstick Careful swallowing (especially of pills) with copious water and maintenance of upright position after swallowing Vaginal dryness Topical moisturizers	Inflammatory Bowel Disease 38 IBD treatment per standard practice guidelines Complete colonoscopy with biopsies at initial PSC diagnosis Surveillance colonoscopy with biopsies performed yearly given high risk of colorectal cancer UDCA not recommended for PSC treatment or for colorectal cancer chemoprevention Dominant Bile Duct Strictures 38 Should be considered in the setting of clinical changes, including increases in serum bilirubin or ALP, cholangitis, or progressive biliary dilation on imaging ERCP should be performed for diagnostic and therapeutic purposes Treatment is individualized and options (conservative v. endoscopic v. surgical including LT) require careful consideration Recurrent Cholangitis 38 Empiric, long-term antibiotic regimen may be indicated Refractory cholangitis is rarely an indication for LT
Follow-up Care and Medical Maintenance	Liver function tests every 3–6 months16 Yearly thyroid stimulating hormone level Familial screening, particularly among first-degree female relatives	Liver function test monitoring Malignancy screening as outlined in Table 1
	Screening Recommendations in Cirrhosis: Variceal Screening: Upper endoscopy for initial assessment of variceal status Repeat endoscopy as determined by previous findings and standard practice guidelines194 Management of portal hypertensive complications based on standard practice guidelines194 Hepatocellular Carcinoma Screening: Abdominal ultrasound every 6 months193 Serum alpha-fetoprotein measurement every 6–12 months can be considered11,16,38,193
Liver Transplantation	Consideration in setting of end-stage liver disease with decompensation/symptomatic portal hypertension/hepatic failure16	Consideration in setting of end-stage liver disease with decompensation/symptomatic portal hypertension/hepatic failure; recurrent or recalcitrant cholangitis38

Abbreviations: UDCA (ursodeoxycholic acid); US FDA (United States Food and Drug Administration); LT (liver transplantation); DEXA (dual-energy X-ray absorptiometry); BMD (bone mineral density); MBD (metabolic bone disease); HRT (Hormone Replacement Therapy); IBD (inflammatory bowel disease).

⁺including: serum alkaline phosphatase, calcium, phosphate, 25-hydroxyvitamin D, creatinine, protein electrophoresis, testosterone (males), and complete blood count; medication assessment; thoracolumbar radiography.