Practical Approaches to Alleviating Your PSC Symptoms Marion Peters MD University of California San Francisco

Early PSC PSC can be silent 15-40% of patients are asymptomatic at presentation 55% of patients have asymptomatic increase of liver enzymes

Prevalence of symptoms in PSC Frequency, % None 15–55 Fatigue 50–75 Pruritus 40–70 Jaundice 9–69 Abdominal pain 16–60 Weight loss 10–34 Fevers and chills 5–28 Hyperpigmentation 25 Silveira and Lindor 2008

Fatigue Important to exclude other conditions e.g. hypothyroidism, anemia Urso does not seem to help with fatigue Fatigue cannot be explained by depressive symptoms Fatigue may be centrally mediated: e.g. corticotrophin-releasing hormone or serotonergic neurotransmitter systems Van Os et al. J Hepatol. 2007 Jun;46(6):1099-103.

Possible Causes of Pruritus- itching Bile duct obstruction Bile acids Endogenous opioids Histamine Autotaxin-LPA

Management of Pruritus Important to rule out biliary obstruction: increase in serum bilirubin and/or worsening pruritus progressive bile duct dilatation on imaging studies  Start with ultrasound and liver tests Recommend performing an ERC or MRCP if new change in US or LFTs

Cholangitis Symptoms pain in the right upper quarter of the abdomen (pain may also occur in the chest, in the upper back, or the right shoulder)  nausea and vomiting  fever  chills  jaundice -yellowing of the skin and eyes  low blood pressure  lethargy  decreased level of alertness  Worse itching  pale stools  dark urine 

PSC: Treatment for infections Narrowed or blocked bile ducts may cause bacterial infections To prevent and treat these infections, people with PSC may take repeated courses of antibiotics or continue taking rotating antibiotics. With any procedure that could cause an infection, such as an endoscopic procedure or abdominal surgery, antibiotics are needed

Pruritus- itching Pruritus is common symptom in all forms of cholestatic liver diseases The severity does not correlate with levels of serum bile acid Endogenous opioids Histamine Tryptamine Substance P

Pruritus and Autotaxin The severity does correlate with serum Autotaxin levels Autotaxin is an enzyme that produces lysophosphatidic acid Lysophosphatidic acid into skin of mice produces scratching Patients with itching/ cholestasis have high LPA levels

Autotaxin LPA Itching Kremer et al: Gastroenterology. 2010 

Pruritus - Treatment Symptomatic Dermatologic Intestine Liver

Management of Pruritus Skin Therapy Lower bathing water temperature Fewer or lighter clothing and bed coverings Minimize dry skin by using moisturizing soaps (e.g., Dove) Apply topical moisturizers liberally (e.g., Eucerin cream)

Management of Pruritus Stabilize mast cells in skin Doxepin 25–50 mg PO daily taken at night May induce sleepiness so best to take at night

Management of Pruritus INTESTINE Anion-Exchange Resins- binds bile salts Cholestyramine or colestipol: 2-6 packets per day start with 1 three times a day Separated from other medications by 2 hours (especially ursodeoxycholic acid)

Management of Pruritus LIVER Decrease Bile Salts and increases bile flow Ursodeoxycholic acid, 13 mg/kg/day at night Hepatic Microsomal Enzyme Induction Rifampin, 150 mg, PO, two- three times daily Opioid Receptor Antagonists Naltrexone, 12.5 mg PO daily to 50 mg PO daily Naloxone and nalmefene are commonly available only for parenteral use

Monitoring PSC Yearly For Osteoporosis check 25-OH Vitamin D Calcium Calcium  24 hour urine Ca Bone density Vitamin A For Osteoporosis check Calcium 25-OH Vit D HRT Calcitonin Bisphosphonates Water Sol Vit A HRT= hormone replacement therapy

Metabolic bone disease Initial screening for osteopenia is recommended and thereafter at 2-3 year intervals depending upon result Osteopenia is characterized by a T-score between 1 and 2.5 standard deviations below the density Osteoporosis as a T-score beneath 2.5. The incidence of osteoporosis in PSC is between 4 and 10%

Treatment of Osteoporosis Vit D deficiency: bone pain or no symptoms Check 25-OH vitamin D levels If normal give calcium 1.0-1.5 g with vitamin D If low, vitamin D2 should be given to promote calcium absorption If Vitamin D does not rise with D2 then 1,25-OH vitamin D is required (calcitriol) In patients with proven osteoporosis bisphosphonates may be needed

PSC: Self Care Fatigue is common in PSC Some treatment may decrease fatigue but your signs and symptoms may still persist. You might find relief with complementary and alternative treatments that have shown some benefit for fatigue, such as: Exercise, such as walking 30 minutes most days of the week Spending time with friends and family Stress management techniques, such as meditation and relaxation exercises Yoga

Nutrition support Primary sclerosing cholangitis makes it difficult to absorb certain vitamins. Check vitamins Even with a healthy diet, patients may not get all the nutrients need. Night time snacks Your doctor may recommend vitamin supplements If the disease weakens your bones, you may take calcium and vitamin D supplements as well.

Health Maintenance Don't drink alcohol. Get vaccinated against hepatitis A and B. Use care with chemicals at home and at work. Maintain a healthy weight. Follow directions on all medications, both prescription and over-the-counter. Make sure your pharmacist and any doctor prescribing for you know that you have a liver disease. Talk to your doctor about any herbs or supplements you're taking since some can be harmful to your liver.