Liver and Pancreas

Liver and Pancreas

AST/ALT> 300Viral, toxin-induced, ischemia, meds< 300EtOH Hepatitis, cholestasisAST/ALT ratio> 2 = EtOH< 1 = Viral or obstructiveABNORMAL LIVER TESTS

Alcoholic HepatitisJaundice, fever, ascites, HE, AST/ALT > 2 with AST/ALT < 300-400.Increased WBCPATH: Steatosis, Fibrosis,Mallory bodiesTreatment: If MDF > 32 start prednisone 40 mg X 4 wksAfter 7 days on steroids if no improvement and Lillie score >.45 Stop Steroids. If steroids are C/I add pentoxifiline to prevent HRSDILIAcetaminophenAntibiotics: Bactrim, Augmentin, E-cinPhenytoinValproic acidImmunomodulatorsINHViral Hepatitis: TransmissionFecal-Oral: Hepatitis A and ESexual: Hepatitis B and D; also C (to a lesser extent)Note: Hepatitis D requires coexisting Hep. B infectionViral Hepatitis: ClinicalSymptoms include fatigue, anorexia nausea and vomitingLab shows elevated AST/ALT and biliMay resolve, turn fulminant, or become chronicHepatitis AFecal-oral transmissionSymptoms: Adult > childrenTransplacental transmission occursNo carrier states, rarely fulminantCan have cholestasis for up to 6 mosVaccine: Patients with liver dz/risks/ travelers Acute infection: + IgM anti-HAV, Vaccination: + IgG anti-HAVIG prophylactic for Hep AHAV Vaccination 2 doses 6-12 months apart.

16Hepatitis BIncubation 1-6 monthsTransmitted sexually, parenterally, mucous membrane exposureCan present with serum sickness (fever, arthritis, urticaria, angioedema)Associated with polyarteritis nodosa (PAN)

17Extra intestinal Manifestations of Hep BPolyarteritis NodosaArthritisGlomerulonephritisUrticariaMixed CryoglobulinemiaPolyneuropathy

19Celiac arteriogram in PANRadiology. 1999;212:359-364, Case 13: Polyarteritis Nodosa-Systemic Necrotizing Vasculitis with Involvement of Hepatic and Superior Mesenteric Arteries1 , Klaus D. Hagspiel, MD, J. Fritz Angle, MD, David J. Spinosa, MD and Alan H. Matsumoto, MD Hepatitis B Serology

HBV ScenariosHBsAganti-HBsanti-HBcIgManti-HBcIgGHBeAgDX+-+-++--++-+----+-+---+-----+-Acute infectionCarrierVaccinatedExposedImmuneAcuteWindowExposedAb lost21HepB vaccine/prophylaxis95% of immunocompetent pts develop antibody (anti-HBs)Only 50% of HD pts develop antibodyMay be given to pregnant pts3 doses at 1, 2 and 6 monthsHBIG Alone:sexual contacts of carriers and household members of acute Hep BHBIG + vaccine (exposed is HBsAg negative)blood exposure to pt w/acute Hep Bnewborns of Hep B mothers22HBIG reduces chance of developing chronic infection

Interferon: less resistance, more potent, shorter duration. Not indicated in decompensated Hep BHbe Ag + Antiviral to be continued 6 months after the seroconversionHbe Ag - Antiviral to be continued > 1 year or until HBS Ag seroconverts.

24Treatment of CHBHBeAg + HBV DNA > 20000, ALT > 2 x ULN Observe for 6 months and treat if no spontaneous conversion.Consider Liver Bx Rx: Peg IFN oEntecavir, tenofovir, telbivudineContinue Rx for 6 months after seroconversionTreatment of CHBHbeAG HBV DNA > 20000 , ALT > 2 x ULNRXContinue till HBsAG loss

Hepatitis CMost common liver disease in the US IVDU, cocaine use, prisons, blood products prior to 1990, tattooGenotype 1 most common in the US 85 % of Hep C infected become chronic25% cirrhosis post 20-25 years of infection5 %/yr risk to develop HCC in those with cirrhosis5% sexual transmission over 10-20 yrs95% sensitiveIf high pre-test probability and anti-HCV negative can do PCR testing (more often in renal failure or transplant)Genotype testing required for treatment candidates only29Extrahepatic ManifestationsGlomerulonephritis/MPGNCryoglobulinsPorphyria cutanea tarda (PCT)ThrombocytopeniaAutoantibodyITPNeuropathyThyroiditisSjogrens SyndromeInflammatory arthritis

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Recommended regimen for treatment-naive patients with HCV genotype 1 who are eligible to receive IFN.Daily sofosbuvir RBV plus weekly PEG for 12 weeks is recommended for IFN-eligible persons with HCV genotype 1 infection, regardless of subtype.Recommended regimen for treatment-naive patients with HCV genotype 1 who are not eligible to receive IFN.Daily sofosbuvir RBV for 12 weeks is recommended forIFN-ineligiblepatients with HCV genotype 1 infection, regardless of subtype.Recommended regimen for treatment-naive patients with HCV genotype 3, regardless of eligibility for IFN therapy:Daily sofosbuvir RBV for 24 weeks is recommended for treatment-naive patients with HCV genotype 3 infection.Recommended regimen for treatment-naive patients with HCV genotype 2, regardless of eligibility for IFN therapy:Daily sofosbuvir RBV for 12 weeks is recommended for treatment-naive patients with HCV genotype 2 infection.Hepatitis DRequires coexistent BUsually found in IVDACoinfection: does not worsen acute Hep B or risk for chronic stateSuperinfection: frequently severe/fulminant Dx: Anti-HDV IgM

35Hepatitis EMonsoon floodingFecal-oral routeNo chronic formsFulminant hepatitis in 3rd trimester of pregnancy

36A 30 y/o female presents with c/o fatigue,arthralgias,weight loss, amenorrhea. PE reveals Icterus and HSM. No h/o alcohol or drug abuse. No FH of Liver disease.Labs: T.Bili 6mg/dl, AST 300 U/L,ALT350 U/L, ALP 100 U/ml, Albumin 2.9 g/dl. Iron studies are normal. Hepatitis profile and HIV is negative. Which of the following are correct:

1. ANA and ASMA are likely to be positive2. Liver Biopsy should be done to confirm Dx3. She will likely respond to steroid therapy4. All of the above are correct.Autoimmune HepatitisAIH: Asymptomatic mild disease to Fulminant Liver failure.Fatigue, Jaundice, MaliaseType I:ANA +, ASMA +, Increased IG,SLA/LP Ab Common in USAType II: LKM1 Common in Europe, poor prognosis, Rx failuresRX:SteroidsImmunomodulators.

Primary Biliary CirrhosisUsually middle aged womenPruritis, fatigueIncreased alk phosThe clue: elevated Antimitochondrial Antibodies (AMA)Anticentromere antibodiesAssociated with sicca syndrome and sclerodermaTreat with ursodiol

Primary Sclerosing CholangitisAn autoimmune fibrosis of large bile ductsClinical: RUQ pain, fatigue, weight loss70% of cases associated with ulcerative colitisIncreased risk of cholangiocarcinomaDiagnose with ERCPBeading of the bile ducts on ERCP/MRCP10-15% get bile duct carcinoma

NAFLDNAFLD: SteatosisNASH: SteatohepatitisCharacteristics: Metabolic SyndromeElevated AST/ALTLiver BiopsyDx of exclusion:RX:RF ModificationAntioxidantsOral hypoglycemics

Other liver testsAutoimmune hepatitis (ANA, ASMA, Anti-liver/kidney microsomal, anti-SLA) PBC (AMA)PSC (p-ANCA 70%)Hemochromatosis Iron Saturation >45% Wilsons Disease (low ceruloplasmin, incresed serum and urine Cu)Alfa 1 antitrypsin def

ABNORMAL LIVER TESTSHemochromatosisMost common genetic disease in CaucasiansIron deposits in liver, heart, pancreas, pituitary, JointsBronze pigmentation, new onset DM,arthritis,hypogonadism.Can lead to cirrhosis and HCCIron Sat > 45%Increased FerritinAbnormal LftsHFE gene mutation C282Y and H63DRX: PhlebotomyGoal ferritin < 50Wilsons DiseaseRare Autosomal Recessive d/o 1:30000Increased cooper uptake and decreased biliary excretion.May present as fulminant liver failureNeuropsychiatry symptomsIncreased AST/ALTLow ALPLow CerruloplasminIncreased urinary copper excretionKF rings on slit lamp

1st Trimester2nd Trimester3rd TrimesterAcute viral hepatitisA-EAcute viral hepatitisA-EAcute viral hepatitisA-EHyperemesis GVGallstonesGallstonesGallstonesHerpes HepatitisHerpes HepatitisICPICPAFLPPre-eclampsiaHELLPLiver Diseases in Pregnancy

Portal HTNIncreased portal blood flow: Increased cardiac index Splanchnic vasodilation HypervolemiaIncreased resistance to portal blood flow: Fixed resistance from fibrosis Dynamic resistanceRX:NSBBOctreotideDiureticsTIPS

Portal HTNMost common cause is cirrhosisManifestations:Hepatic EncephalopathyGastro-esophageal VaricesAscitesApproach to the Patient with AscitesWorkupNeed to know if ascites is CHF, cirrhosis or malignancy (exudate)Serum-ascites albumin gradient > 1.1 = transudate (Portal HTN)If ascites protein > 2.5, then CHFIf ascites protein < 2.5, then cirrhosis 250GN organisms E.coli most commonTreat SBP with 3rd generation cephalosporin IV for 5 day and then PO AbxPplx with oral quinolones after SBPIV Albumin to prevent HRS.

Hepatic EncephalopathyPpting Factors:GI bleed, SBP, Sepsis, sedatives, constipation, electrolyte abnormalities, acute liver injury, HCC, surgery.RX:Recognize and Correcting ppting factorsCorrect electrolytes.LactuloseRifaximin.Hepatorenal syndrome (HRS)HRS Type I: Rapid decline in renal functionHRS Type II: Chronic usually due to refractory ascites.DDX: ATN, Pre-renalDX: Sr Creatinine > 1.5No improvement after holding diuretics and volume expansion with IV AlbuminAbsence of shock, hypotension,proteinuria,nephrotoxicsLow urine sodium.HRSRx:Avoiding and holding all nephrotoxics.Hold diureticsIV AlbuminMidodrine and octreotideOLT is the definitive treatmentFulminant Hepatic FailureJaundice and hepatic encephalopathy in the absence of chronic liver disease.Acetaminophen is the most common cause in US ( worsened by alcohol, malnutrition and fasting state)Acute viral hepatitis is the most common cause world wide.Other meds: INH, NSAIDS, herbal medsOther causes: AIH, BCS, AFLP, HELLP, Amanita Phalloids

Fulminant Hepatic FailureComplications: Hypoglycemia, Cerebral edema,coagulopathy,infectionRX;Supportive care in ICUEarly recognition and transfer to the transplant center.NAC for acetaminophen toxicityAcyclovir for HSV hepatitis.Pen G for mushroom toxicityAntiviral for acute hepatitis BLiver Biochemistry PatternDiseaseAPTBiliHistorical FeaturesDiagnostic EvaluationPrimary biliary cirrhosisMore common in women, fatigue, pruritusAntimitochondrial antibodies present in 95%, liver biopsyPrimary sclerosing cholangitisMore common in men, history of inflammatory bowel diseaseCholangiographyLarge bile duct obstructionPain and feverCholangiographyDrug-induced cholestasisHistory of drug/medication use within 3 months, often of a drug previously associated with liver injuryImprovement with cessationInfiltrative liver diseaseCT, MRI, liver biopsyLiver Enzyme PatternDiseaseALTASTHistoryDXViral hepatitis AFecal oral exposure(IgM anti-HAV)Viral hepatitis BBlood/body fluid exposure(IgM anti-HBc) and + (HBsAg)Viral hepatitis CRecent intravenous drug use (HCV RNA); variable presence of (anti-HCV) Alcoholic hepatitisHeavy alcohol use, either binge or chrAST:ALT >2, AST usually 1000) and iron sat (>55%), HFE gene mutations Wilson diseaseYoung, movement disorders, psychiatric disease, KF ringsHemolysis, low ALP, low ceruloplasmin1-Antitrypsin deficiencyLung diseaseLow serum A1AT, liver biopsy

ABNORMAL LIVER TESTSHistory PearlsPruritus/CholestasisPBC, PSCUndercooked food, oysters, daycareHep AICU, hypotension, Rt. Sided heart failureHepatic congestionChronic pancreatitisStenosis of CBDHistory PearlsNeurological/Psych findingsWilsons diseaseMetabolic syndromeFatty liverHyperpigmentationHemochromatosis or PBCKayser-Fleischer rings and sunflower cataractsWilsons disease

ABNORMAL LIVER TESTSHistory PearlsSplenomegalyPortal HTN or infiltrative processPulsatile liverTricuspid insufficienyHepatic bruitsHCCABNORMAL LIVER TESTSAcute PancreatitisAlcoholBiliary Tract DiseaseTraumaPost ERCPHyperlipidemiaPancreatic MalignancyObstructiveGallstones (45%)Pancreas divisumMalignancyCholedochoceleParasites (Ascaris lumbricoides) Toxins/DrugsAlcohol (35%)AzathioprineSulfa drugsAminosalicylatesMetronidazolePentamidineDidanosine MetabolicHyperlipidemiaHypercalcemia InfectiousViral (Cytomegalovirus, Epstein-Barr virus)Parasites (Toxoplasma, Cryptosporidium) VascularIschemiaVasculitis Causes of Acute Pancreatitis

Poor Prognostic Indicators In PancreatitisSBP < 90 , HR > 130PO2 < 60 mmHgUrine out put < 50ml/hr or BUN/Cr ElevationGI BleedingPancreatic necrosisHCT > 44CRP > 150Apache score > 8Ranson score > 3Complications of PancreatitisSepsis; Necrosis, infected pseudocyst,AbscessEarly: Shock, ARDS, GIB, DIC, Uremia,hypocalcemia Splenic infarction & rupture, Pl Effusion. Late: Phlegmon, Pseudocyst, abscess Ascites, Pleural Effusion Splenic Vein thrombosis GV--GIB Ranson CriteriaAdmissionAge > 55WBC > 15KGlucose > 200AST > 250LDH > 350 During 48 hrsPO2 < 60 mmHgDrop in HCT > 10 %BUN increases > 5mg/dlCalcium < 8 mg/dlFluid sequestration77PearlsAcute Pancreatitis is a clinical and lab Dx and not imagingAlcohol and Gall Stones most important causesProphylactic Abx (Imipenum) in necrotising pancreatitisEarly enteral Feeding is preferred.Pancreatic AdenocarcinomaRisk Factors: Age, Smoking, Chronic pancreatitis,Hereditary pancreatitis, Obesity, Fatty dietManifestation: Pain radiating to back, Wt Loss, jaundice, Painless jaundice due obstruction of CBD by pancreatic head massDiagnosis: CT-Scan pancreas protocol, EUS, MRI, ERCP

Non-tender palpabale GB (Courvoisier sign)Trousseau syndrome of migrating thrombophelibitis.79GOOD LUCK !