12 Alcoholic HepatitisJaundice, fever, ascites, HE, AST/ALT > 2 with AST/ALT < 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 HRS
13 DILI Acetaminophen Antibiotics: Bactrim, Augmentin, E-cin Phenytoin Valproic acidImmunomodulatorsINH
14 Viral Hepatitis: Transmission Fecal-Oral: Hepatitis A and ESexual: Hepatitis B and D; also C (to a lesser extent)Note: Hepatitis D requires coexisting Hep. B infection
15 Viral Hepatitis: Clinical Symptoms include fatigue, anorexia nausea and vomitingLab shows elevated AST/ALT and biliMay resolve, turn fulminant, or become chronic
16 Hepatitis A Fecal-oral transmission Symptoms: Adult > children Transplacental transmission occursNo carrier states, rarely fulminantCan have cholestasis for up to 6 mosVaccine: Patients with liver dz/risks/ travelersAcute infection: + IgM anti-HAV, Vaccination: + IgG anti-HAVIG prophylactic for Hep AHAV Vaccination 2 doses 6-12 months apart.
17 Hepatitis B Incubation 1-6 months Transmitted sexually, parenterally, mucous membrane exposureCan present with serum sickness (fever, arthritis, urticaria, angioedema)Associated with polyarteritis nodosa (PAN)
18 Extra intestinal Manifestations of Hep B Polyarteritis NodosaArthritisGlomerulonephritisUrticariaMixed CryoglobulinemiaPolyneuropathy
19 Celiac arteriogram in PAN Radiology. 1999;212: , 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
22 HepB vaccine/prophylaxis 95% 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 mothersHBIG reduces chance of developing chronic infection
24 Interferon: less resistance, more potent, shorter duration 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.
25 Treatment of CHB HBeAg + HBV DNA > 20000, ALT > 2 x ULN Observe for 6 months and treat if no spontaneous conversion.Consider Liver BxRx: Peg IFN oEntecavir, tenofovir, telbivudineContinue Rx for 6 months after seroconversion
26 Treatment of CHB HbeAG – HBV DNA > 20000 , ALT > 2 x ULN RX Continue till HBsAG loss
28 Hepatitis C Most common liver disease in the US IVDU, cocaine use, prisons, blood products prior to 1990, tattooGenotype 1 most common in the US85 % of Hep C infected become chronic25% cirrhosis post years of infection5 %/yr risk to develop HCC in those with cirrhosis5% sexual transmission over yrs<5% trans placental transmission. HIV co-infection increases transmission rate.
29 Serological Tests Third generation anti-HCV+ >95% sensitive If 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 only
33 Recommended regimen for treatment-naive patients with HCV genotype 1 who are eligible to receive IFN.Daily sofosbuvirRBVplus 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 sofosbuvirRBV for 12 weeks is recommended for IFN-ineligible patients with HCV genotype 1 infection, regardless of subtype.
34 Recommended regimen for treatment-naive patients with HCV genotype 2, regardless of eligibility for IFN therapy:Daily sofosbuvirRBV for 12 weeks is recommended for treatment-naive patients with HCV genotype 2 infection.Recommended regimen for treatment-naive patients with HCV genotype 3, regardless of eligibility for IFN therapy:Daily sofosbuvirRBV for 24 weeks is recommended for treatment-naive patients with HCV genotype 3 infection.
35 Hepatitis D Requires coexistent B Usually found in IVDA Coinfection: does not worsen acute Hep B or risk for chronic stateSuperinfection: frequently severe/fulminantDx: Anti-HDV IgM
36 Hepatitis E Monsoon flooding Fecal-oral route No chronic forms Fulminant hepatitis in 3rd trimester of pregnancy
37 A 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.
38 Autoimmune Hepatitis AIH: Asymptomatic mild disease to Fulminant Liver failure.Fatigue, Jaundice, MaliaseType I:ANA +, ASMA +, Increased IG,SLA/LP AbCommon in USAType II: LKM1Common in Europe, poor prognosis, Rx failuresRX:SteroidsImmunomodulators.
40 Primary Biliary Cirrhosis Usually middle aged womenPruritis, fatigueIncreased alk phosThe clue:elevated Antimitochondrial Antibodies (AMA)Anticentromere antibodiesAssociated with sicca syndrome and sclerodermaTreat with ursodiol
41 Primary Sclerosing Cholangitis An 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
44 Other liver testsABNORMAL 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
45 Hemochromatosis Most common genetic disease in Caucasians Iron deposits in liver, heart, pancreas, pituitary, JointsBronze pigmentation, new onset DM,arthritis,hypogonadism.Can lead to cirrhosis and HCCIron Sat > 45%Increased FerritinAbnormal Lft’sHFE gene mutation C282Y and H63DRX: PhlebotomyGoal ferritin < 50
46 Wilson’s Disease Rare Autosomal Recessive d/o 1:30000 Increased cooper uptake and decreased biliary excretion.May present as fulminant liver failureNeuropsychiatry symptomsIncreased AST/ALTLow ALPLow CerruloplasminIncreased urinary copper excretionKF rings on slit lamp
53 WorkupASCITESNeed 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<1.1 = ascites is NOT from portal hypertension“Higher SAAG = higher pressure”
54 Workup Tap all new ascites Tap all ascites in cirrhotics with clinical changeLabs< 250 cells/μl1 neutrophil/250 RBC2 lymphocyte/750 RBCInnoculate cultures at the bedsideGram stainIf TB is suspected, you need a peritonal bx
55 Treatment 2g Na restriction/day No benefit in restricting fluids ASCITES2g Na restriction/dayNo benefit in restricting fluidsSpironolactone 100mg/day + Lasix 40mg/dayLarge volume paracentesisTIPS for paracentesis-resistant ascites
56 SBPTranslocation of bacteria across they bowel wall into susceptible ascites.SubclinicalFever, Abd pain,encepahlopathyDX:PMN > 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.
59 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.
60 HRS Rx: Avoiding and holding all nephrotoxics. Hold diuretics IV AlbuminMidodrine and octreotideOLT is the definitive treatment
61 Fulminant Hepatic Failure Jaundice 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
62 Fulminant Hepatic Failure Complications: 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 B
63 Liver Biochemistry Pattern DiseaseAPTBiliHistorical FeaturesDiagnostic EvaluationPrimary biliary cirrhosis↑↑↑More 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 feverDrug-induced cholestasisHistory of drug/medication use within 3 months, often of a drug previously associated with liver injuryImprovement with cessationInfiltrative liver diseaseCT, MRI, liver biopsy
64 Ischemic hepatitis Disease ALT AST History DX Viral hepatitis A ↑↑↑ ↑↑ Liver Enzyme PatternDiseaseALTASTHistoryDXViral hepatitis A↑↑↑↑↑Fecal oral exposure(IgM anti-HAV)Viral hepatitis BBlood/body fluid exposure(IgM anti-HBc) and + (HBsAg)Viral hepatitis C↑Recent intravenous drug use(HCV RNA); variable presence of (anti-HCV)Alcoholic hepatitisHeavy alcohol use, either binge or chrAST:ALT >2, AST usually <500Drug-induced hepatitis↑↑↑↑H/of drug/med use within 3 moAbsence of other liver diseaseFatty liver, nonalcoholLate pregnancy, amiodaroneHistory of medication use, absence of other liver diseaseIschemic hepatitisSevere hypotensionrapid improvement with resolution of hypotensionAcute liver failureIngestion of an associated agent; rapid progressionSigns of impaired hepatic synthetic functionAlcoholic hepatitis: Absence of other diagnostic markers of liver disease; improvement with cessation of alcohol useHep C variable presence of (anti-HCV) within the first 3 months after exposure
65 Liver Enzyme PatternDiseaseALTASTHistorical FeaturesDiagnostic FindingsViral hepatitis B↑↑↑Fecal oral exposure, endemic areaHBsAg; may have hepatitis B DNA (HBV DNA)Viral hepatitis CIVDA, blood tx prior to 1992, Vert Tx , parenteral exposAnti-HCV, HCV RNAFatty liver, nonalcoholPresence of metabolic syndrome (obesity, insulin resistance, hypertriglycer)Absence of other liver dz imaging shows fatAlcoholic liver diseaseRemote history of heavy alcohol useAbsence of other liver diseaseAutoimmune hepatitisMore common in womenPositive , ANA and anti–SMAHemochromatosisArthritis, diabetes, family historyFerritin (>1000) and iron sat (>55%), HFE gene mutationsWilson diseaseYoung, movement disorders, psychiatric disease, KF ringsHemolysis, low ALP, low ceruloplasminα1-Antitrypsin deficiencyLung diseaseLow serum A1AT, liver biopsy
78 Pearls Acute Pancreatitis is a clinical and lab Dx and not imaging Alcohol and Gall Stones most important causesProphylactic Abx (Imipenum) in necrotising pancreatitisEarly enteral Feeding is preferred.
79 Pancreatic Adenocarcinoma Risk 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, ERCPNon-tender palpabale GB (Courvoisier sign)Trousseau syndrome of migrating thrombophelibitis.