NutritionNutrition andand PrimaryPrimary SclerosingSclerosing CholangitisCholangitis (PSC)(PSC) JaimeJaime ArandaAranda--Michel,Michel, M.D.M.D. AssociateAssociate ProfessorProfessor ofof MedicineMedicine DivisionDivision ofof Gastroenterology,Gastroenterology, hepatologyhepatology andand transplantationtransplantation MayoMayo ClinicClinic JacksonvilleJacksonville PrimaryPrimary SclerosingSclerosing CholangitisCholangitis ChronicChronic LiverLiver DiseaseDisease ComplicationsComplications FluidFluid retentionretention –– ascitesascites andand peripheralperipheral edemaedema EncephalopathyEncephalopathy -- confusionconfusion GastrointestinalGastrointestinal bleedingbleeding –– varicesvarices CholangiocarcinomaCholangiocarcinoma andand HepatocellularHepatocellular carcinomacarcinoma MalnutritionMalnutrition MalnutritionMalnutrition isis commoncommon inin cirrhosiscirrhosis DeficienciesDeficiencies ofof vitaminsvitamins andand mineralsminerals maymay developdevelop inin chronicchronic liverliver diseasedisease withoutwithout cirrhosiscirrhosis –– PrimaryPrimary BiliaryBiliary CirrhosisCirrhosis andand PrimaryPrimary SclerosingSclerosing CholangitisCholangitis OtherOther deficienciesdeficiencies cancan bebe presentpresent ifif InflammatoryInflammatory BowelBowel DiseaseDisease isis presentpresent –– CrohnCrohn’’ss DiseaseDisease MalnutritionMalnutrition 99GeneralGeneral risksrisks forfor malnutritionmalnutrition inin chronicchronic liverliver diseasedisease 99SpecificSpecific risksrisks forfor malnutritionmalnutrition inin primaryprimary sclerosingsclerosing cholangitischolangitis LipidsLipids –– fatfat metabolismmetabolism VitaminsVitamins --A,D,E,KA,D,E,K BoneBone diseasedisease inin chronicchronic liverliver diseasedisease NutritionNutrition inin LiverLiver DiseaseDisease ““FactsFacts”” ●● MalnutritionMalnutrition isis commoncommon butbut frequentlyfrequently ““underdiagnosedunderdiagnosed”” ●● MalnutritionMalnutrition isis multifactorialmultifactorial ●● DegreeDegree ofof malnutritionmalnutrition correlatescorrelates toto thethe severityseverity ofof liverliver diseasedisease ●● MalnutritionMalnutrition isis universaluniversal inin patientspatients withwith endend--stagestage liverliver diseasedisease waitingwaiting forfor liverliver transplantationtransplantation regardlessregardless ofof thethe etiologyetiology ●● MalnutritionMalnutrition cancan bebe diagnoseddiagnosed inin 25%25% inin patientspatients withwith cirrhosis.cirrhosis. ●● MalnutritionMalnutrition isis presentpresent inin >> 6060 %% inin patientspatients withwith complicationscomplications ofof cirrhosis.cirrhosis. ●● ModerateModerate toto severesevere malnutritionmalnutrition isis foundfound inin >> 80%80% ofof liverliver transplanttransplant patients.patients. Campillo B Nutrition 2003 *Alvares-da-Silva MR Nutrition 2005 ““MultifactorialMultifactorial”” PoorPoor dietarydietary intakeintake ● Anorexia, hospitalization ● Dietary restrictions (Na and protein) ● Ascites / encephalopathy ● Increased in inflammation ““MultifactorialMultifactorial”” continue..continue.. Nutrient malabsorption ● Cholestatic liver disease ● Excessive protein losses Medications ● Neomycin, lactulose, cholestyramine, prednisone Iatrogenic ● Large volume paracentesis ● Sodium and protein restriction PSCPSC -- CholestasisCholestasis ““lacklack ofof bilebile flowflow”” ●● FatigueFatigue ●● PruritusPruritus –– itchingitching ●● DiarrheaDiarrhea -- looseloose fattyfatty stoolsstools (Steatorrhea)(Steatorrhea) 99FoulFoul smelling,smelling, flatulenceflatulence ●● FatFat--solublesoluble vitaminvitamin deficienciesdeficiencies (A,D,E,K)(A,D,E,K) ●● HyperlipidemiaHyperlipidemia ●● MetabolicMetabolic bonebone diseasedisease 99BoneBone painpain 99BoneBone fracturesfractures HyperlipidemiaHyperlipidemia inin PSCPSC ●● TriglycerideTriglyceride levelslevels ●● CholesterolCholesterol levelslevels ●● MayMay developdevelop xanthomasxanthomas andand xanthelasmaxanthelasma ●● NotNot associatedassociated withwith CardiovascularCardiovascular mortalitymortality VitaminsVitamins VitaminVitamin AA VitaminVitamin AA ●●AbsorptionAbsorption requiresrequires fatfat andand bilebile acidsacids ●●SerumSerum levelslevels areare frequentlyfrequently lowlow -- 82% ●Antioxidant ●●OccasionallyOccasionally symptomaticsymptomatic 9 Eye 9 Skin 9 Bone 9 Immune system VitaminVitamin AA ●●EyeEye –– xerophthalmiaxerophthalmia ●●SkinSkin -- hyperkeratosishyperkeratosis VitaminVitamin EE ●Absorption requires fat and bile acids ●Prevalence is 17% ●Antioxidant ●Significance in PSC is unknown ●Symptoms are rare 9 Neurological 9 Eye muscles 9 Muscle VitaminVitamin KK ●Absorption requires fat and bile acids ●Required for clotting factors 9 Prothrombin time (INR) ●Bone metabolism - osteocalcin VitaminVitamin KK ●Easy bruising ●Mucosal bleeding VitaminVitamin DD Vitamin D Metabolism DietDiet Skin/UVBSkin/UVB Ca,Ca, PO4PO4 VitaminVitamin D3D3 Resorption & Mineralization 2525--OHOH--VitVit--DD 1,25(OH)2Vit1,25(OH)2Vit--D3D3 MoreMore ThanThan 1.51.5 MillionMillion FracturesFractures YearlyYearly Vertebral 46% (700,000) Wrist Hip 16% 19% (250,000) (300,000) Other 19% NIH/ORBD National Resource Center, October 2000 (300,000) CommonCommon CausesCauses ofof Vit.DVit.D DeficiencyDeficiency ●●DecreasedDecreased intakeintake ●●DefectDefect inin liverliver 99PoorPoor oraloral intakeintake 9 Liver disease 99↓↓ uVuV lightlight ●●DefectiveDefective activationactivation inin KidneyKidney ●●Impaired gut absorption Impaired gut absorption 9 Aging 99MalabsorptionMalabsorption (short(short 9 Renal failure (GFR < 60 bowel,bowel, pancreatitis,pancreatitis, IBD,IBD, ml/min) celiacceliac spruesprue,, cholestaischolestais)) DHC: dihydro-cholesterol. VDB: vitamin D binding. GFR: glomerular filtration rate. BONE QUANTITY BONE QUALITY BONE STRENGHT Trauma OsteoporosisOsteoporosis TrabecularTrabecular MicroMicro--architecturalarchitectural ChangeChange Normal Osteoporosis Dempster, 2000 Horizontal Perforations Micro-callous DiagnosticDiagnostic toolstools OsteoporosisOsteoporosis CentralCentral DualDual--EnergyEnergy--XrayXray-- AbsorptiometryAbsorptiometry (DXA)(DXA) MeasurementMeasurement ● Measures multiple skeletal sites 9 Spine 9 Hip 9 Forearm 9 Total body ● Office based ● DXA bone density measurement considered the clinical standard WorldWorld HealthHealth OrganizationOrganization (WHO)(WHO) DiagnosticDiagnostic CriteriaCriteria forfor OsteoporosisOsteoporosis T-Score The WHO criteria were established for use in a postmenopausal female population HepaticHepatic OsteodystrophyOsteodystrophy (Metabolic(Metabolic BoneBone Disease)Disease) ●● MostMost ofof thethe patientspatients havehave osteopeniaosteopenia // osteoporosisosteoporosis regardlessregardless ofof thethe causecause ofof liverliver diseasedisease ●● FrequentlyFrequently foundfound inin patientspatients withwith PSCPSC andand PBCPBC ●● FracturesFractures priorprior toto transplantationtransplantation --35%35% ●● EndEnd--StageStage LiverLiver DiseaseDisease isis consideredconsidered anan independentindependent factorfactor forfor bonebone diseasedisease RisksRisks factorsfactors ●● AgeAge ●● BMDBMD -- DEXADEXA ●● AlcoholismAlcoholism ●● SmokingSmoking ●● HypogonadismHypogonadism-- postpost--menopausalmenopausal ●● AbnormalAbnormal VitaminVitamin DD metabolismmetabolism ●● MalabsorptionMalabsorption -- malnutritionmalnutrition ●● Medication:Medication: steroids,steroids, looploop diureticsdiuretics ((lasixlasix)) TreatmentTreatment ●● BeginBegin calciumcalcium supplementationsupplementation ●● MultivitaminsMultivitamins ●● VitaminVitamin DD supplementationsupplementation ●● WeightWeight bearingbearing andand exerciseexercise ●● SmokeSmoke cessationcessation ●● ConsiderConsider antianti--resorptiveresorptive agentsagents GeneralGeneral GuidelinesGuidelines Patients with cirrhosis have malnutrition until proven otherwise Anorexia is a major problem – calorie counts, frequent meals – snack at bedtime – early feeding tube placement Do not restrict protein even in the presence of encephalopathy Look for malabsorption– fat soluble vitamins (ADEK) and replace if deficient Physical activity very important and more aggressive in patients awaiting liver transplantation All patients with cirrhosis should receive multivitamins DEXA scan to assess bone density DiscussionDiscussion Kanis JA, et al. Osteoporosis Int 2008;19:385-397. FRAXFRAXTMTM CalculatorCalculator ●● WHOWHO 1010--yearyear fracturefracture riskrisk assessmentassessment tooltool 99RiskRisk factors:factors: age,age, BMD,BMD, priorprior fracture,fracture, steroids,steroids, etc.etc. ●● TreatmentTreatment guidelinesguidelines:: 99HipHip fracturefracture riskrisk >> 3%3% 99MajorMajor osteoporoticosteoporotic fracturefracture >> 20%20% Kanis JA, et al. Osteoporosis Int 2008;19:385-397. http://www.shef.ac.uk/FRAX/ OsteoporosisOsteoporosis TherapyTherapy ●● BoneBone AntiAnti--resorptiveresorptive AgentsAgents 99CalciumCalcium andand VitaminVitamin--DD 99BisphosphonatesBisphosphonates (several(several oraloral andand intravenousintravenous drugs)drugs) 99EstrogenEstrogen (oral(oral oror skinskin patch)patch) 99SERMsSERMs (Evista® - raloxifene) 99CalcitoninCalcitonin (Miacalcin®) ●● BoneBone FormativeFormative (Anabolic)(Anabolic) AgentsAgents 99ParathyroidParathyroid hormonehormone (Forteo®, teriparatide - rhPTH) 99SodiumSodium FluorideFluoride (controversial,(controversial, notnot FDAFDA approved)approved) 99TiboloneTibolone andand StrontiumStrontium (not(not FDAFDA approved)approved) 99TestosteroneTestosterone (hypogonadal(hypogonadal men)men) Vit.DVit.D