Acute Hepatitis Final - Handout.ppt
Acute HepatitisSean G. Kelly, MDAssistant Clinical ProfessorDivision of Gastroenterology, Hepatology & NutritionThe Ohio State University Wexner Medical CenterAcute Hepatitis Overview Viral hepatitis – Hepatitis A-E and EBV DILI – Acetaminophen, Augmentin andmore! Alcohol and Biliary stones Ischemia Autoimmune hepatitis Remaining causes1
Acute hepatitis vs. ALF Management is very differentAcutehepatitisYes 1.5NoPossiblyAST and/or ALT 400INRAny EncephalopathyPre-existing liverdiseaseALFYes 1.5YesNoHAV Most common form of acute viral hepatitisworldwide Fecal-oral transmission, contaminated food/water Typically self-limited,no chronic form May have prolonged orrelapsing course Incubation 2-4 wks,rarely up to 6 wkswww.cdc.gov2
HBV 350-400 million people worldwide have chronicHBV; 75% in Asia and western Pacific 1.25 million Hep B carriers in US – HBsAg positive 6 months 15-40% will develop serious sequelae Increased risk of cirrhosis and hepatocellularcarcinoma (HCC) Chronic HBV causes 1 million deaths worldwide –chief cause of cirrhosis and HCCWells, J and Perrillo R. Hepatitis B. Gastrointestinal and LiverDisease. 2016 Vol 2, 10th Edition. 1309-1321HBV 100 x more virulent that HIV, 10 x more virulentthan HCV Most infections worldwide – transmission frommother to neonate 60-90% of HBsAg and HBeAg positive motherstransmit infection to offspring 15-20% transmission among mothers with antiHbe (envelope protein) CDC reported cases – 40% intimate contactamong heterosexuals, 15-20% IV drug use, 12%MSMWells, J and Perrillo R. Hepatitis B. Gastrointestinal and LiverDisease. 2016 Vol 2, 10th Edition. 1309-13213
HBV Horizontal spread among children in highprevalence areas Risk of chronic HBV 90% in newborns of HBeAg positive mothers 25-30% in infants and children under 5 Less than 5% in adult Age at time of infection is main determinant ofclinical outcome Progressive liver disease seen in 1/4-1/3 of ptswith chronic HBVWells, J and Perrillo R. Hepatitis B. Gastrointestinal and LiverDisease. 2016 Vol 2, 10th Edition. 1309-1321HBV labs: Antigen DiseaseSurfaceAntigenAcutePos or negChronicPosExposed onlyNegExposed re AbDNAPos or NegPosPosPosPosPosNegNegPosNegNegWells, J and Perrillo R. Hepatitis B. Gastrointestinal and LiverDisease. 2016 Vol 2, 10th Edition. 1309-13214
HCV United States Estimated at 5million peopleSources of Infection for Persons withHepatitis C (CDC) US.pngHCV Slow progression 30 years with female gender,early age of developsin 80%ChronichepatitisCirrhosisdevelopsin 20%HCC risk3-5%yearly Fast progression 20 years with alcohol use,coinfectionWedemeyer, H. Hepatitis C. Gastrointestinal and LiverDisease. 2016 Vol 2, 10th Edition. 1309-13215
HCV testing One-time HCV testing is recommended forpersons born between 1945 and 1965 Positive HCV Ab should be confirmed byHCV quant RNA test Those with anti-HCV test and negativeresults for HCV RNA PCR do not havecurrent HCV infection. Class I, Level AAASLD-IDSA. Recommendations for testing, managing, and treatingHCV. http://www.hcvguidelines.org. Accessed 9/6/2016.HCV Treat all patients with chronic HCV exceptthose with short life expectancies thatcannot be remediated by treating HCV,transplantation or other directed therapy.Class I, Level A Acute HCV – may clear spontaneously Chronic hepatitis develops in 50-90% ofpatients with acute HCV infection6
HDV and HEV HDV – coinfection with hepatitis B HEV – Acute HEV: similar to acute HAV or HBV, mostasymptomatic Pregnancy (2nd/3rd trimester) ALFwith mortality 5-25% Increased rates of infection inpregnancy 9-19% Week 1: malaise, fever, chills, abdominalpain, anorexia, aversion to smoking,vomiting, diarrhea, arthralgias, transientmacular rash Weeks 2-4: jaundice, pruritus, darkurine/clay colored stools Weeks 4-8: spontaneous resolutionBehrendt et al, 2014 J of HepatologyEBV Infants / Children typically asymptomatic or mild disease Adolescents / Adults: Pharyngitis, fever, lymphadenopathy EBV hepatitis more severe in adults 30 years Splenomegaly is common Liver involvement is nearly universal: 90% have AST/ ALT / LDH elevations 2-3x ULN. Rise over 1-2 wks, peak 5x ULN (lower than acuteHAV, HBV or HEV) 45% with high alk phos and mildly elevated bilirubin,LFTs typically normal in 1 month7
EBV Diagnosis Monospot positive after 10 daysafter infection Anti-EBV IgM peaks early, persistsfor months EBV serum PCR Treatment is supportive: No benefitfrom Acyclovir; Ganciclovir not wellstudiedDILI Most common reason for post-marketingdrug withdrawals 10% overall mortality for patientshospitalized with DILI, varies greatly Accounts for 50% of ALF cases in U.S. Only serious events require report to FDA,but less than 10% of adverse reactionsreported by physicians and pharmacists toMedWatchhttp://www.livertox.nih.gov/8
DILI Necrosis – Acetaminophen, isoniazid Cholestasis - Augmentin (clavulanic acid),anabolic steroids, sulfonamides, antifungals, warfarin, ibuprofen, rarely OCPs Steatosis – Methotrexate, amiodarone Mixed – Tamoxifen, nitrofurantoin,tetracycline, phenytoinBiliary stones(Choledocholithiasis) Risk assessment per 2010 ASGE Guideline —Very strong predictors Common bile duct (CBD) stone on abdominalultrasound Clinical acute cholangitis Serum bilirubin 4Strong predictors – CBD 6 mm on US inpatient with a gallbladder in situ Serum bilirubin 1.8 - 49
Alcoholic hepatitis Occurs after decades of alcohol abuse, typical age40-60, female gender is independent risk factor Cardinal sign – rapid onset of jaundice Other common signs - fever, ascites and proximalmuscle loss, hepatomegaly, RUQ pain,encephalopathy AST twice ULN, but rarely over 300,AST / ALT 2; elevated WBC and INR, total bili 5Lucey MR. NEJM 2009; 360: 2758‐2769.Ischemia Labs similar to acetaminophen overdosewith towering AST and ALT, high INR, mildelevation of bilirubin; LDH especially high Seen in patients with risk factors, includingCAD, PAD, Afib who experience sepsis,arrhythmia or other hemodynamic event Supportive care, circumstances calling fortransplant are rare10
Autoimmune hepatitis Markedly elevated aminotransferases Most patients have positive ANA and antismooth muscle antibody with high titers,elevated IgG level; liver biopsy to confirm Typically have other autoimmune conditionsand family history of autoimmune disease Prednisone and azathioprine arecornerstones of treatmentManns MP, et al. Diagnosis and management of autoimmune hepatitis. Hepatology 2010; 51; 2193.Remaining causes Wilson’s disease: copper metabolismdisorder, hemolytic anemia, Kayser-Fleischerrings, may present with ALF Budd-Chiari: thrombosis of the hepatic veins(outflow of liver) Disorders specific to pregnancy: Hyperemesisgravidarum - 1st trimesterHELLP (Hemolysis, Elevated Liver enzymes, LowPlatelets) andAcute fatty liver of pregnancy – 3rd TrimesterHay JE. Liver Disease in Pregnancy.Hepatology. 2008; 47 (3): 1067-1076.11
References AASLD-IDSA. Recommendations for testing, managing and treating HCV.http://www.hcvguidelines.org. Accessed 9/6/2016.Behrendt P, Steinmann E, Manns MP and Wedemeyer H. The impact of hepatitis E in theliver transplant setting. Journal of Hepatology. 2014; 61: 1418-1429.Bernal W and Wendon J. Acute Liver Failure. NEJM. 2013; 369(26): 2525-2534.Birrer R, Takuda Y, Takara T. Hypoxic hepatopathy: pathophysiology and prognosis.Intern Med. 2007: 46; 1063.Dooley JS, et al. Sherlock’s Diseases of the Liver and Biliary System, 12th edition.Chapter 21 – Hepatitis due to Non-A-E viruses by Antonio Craxi and Rosa Di Stefano, pp.427-436.Dooley JS, et al. Sherlock’s Diseases of the Liver and Biliary System, 12th edition.Chapter 24 – Drug-induced liver injury by Leonard B. Seeff and Robert B Fontana, pp.478-499.Hay JE. Liver Disease in Pregnancy. Hepatology. 2008; 47 (3): 1067-1076.Lok ASF and McMahon BJ. Chronic hepatitis B. AASLD practice guidelines. Hepatology2007; 45: 507-539.Lucey MR. NEJM 2009; 360: 2758-2769Manns MP, Czaja AJ, Gorham JD, et al. Diagnosis and management of autoimmunehepatitis Hepatology 2010; 51; 2193.Sleisinger and Fordtran. Gastrointestinal and Liver Disease, 8th edition. Chapter 75 –Hepatitis B and D by Robert Perrillo and Satheesh Nair, pp. 1647-1679.Sources of Infection for Persons with Hepatitis C (CDC) US.pngWedemeyer, H. Hepatitis C. Gastrointestinal and Liver Disease. 2016 Vol 2, 10th edition,1309-1321.Wells J and Perillo R. Hepatitis B. Gastrointestinal and Liver Disease. 2016 Vol 2, 10thedition, 1309-1321.Approach to AcuteLiver FailureJames Hanje, MDDirector of HepatologyAssociate Professor-ClinicalDivision of Gastronenterology, Hepatologyand NutritionThe Ohio State University Wexner Medical Center12
Educational ObjectivesUnderstand common etiologies and prognosisExecute early management stepsDiscuss management of late complicationsDisclosureSalix pharmaceuticals13
King’s College CriteriaALFSG14
DefinitionDefinition “ACUTE LIVER FAILURE” (no longerreferred to as Fulminant) Rare disease Life threatening Rapidly progressive Requires sub-specialized, multidisciplinarycare Requires prompt recognition and earlyreferral to tertiary care center with livertransplant program15
Definition Biochemical evidence of moderate to severeacute hepatitis (AST/ALT 5x ULN) Evidence of coagulopathy (INR 1.5) ANDencephalopathy No pre-existing cirrhosis Duration of illness 26 weeks Wilson’s disease, HBV, and AIH may beincluded if disease recognized for 26weeksEtiology and prognosis16
Etiology of Acute Liver Failure in the USAAdult Registry (n 1,696)46%n12%13%Acetaminophen cases as %of all cases17
‘Suicidal’ vs. ‘Accidental’ APAP casesN 606(56 unk)Intentional Unintentional p-value(n 251)(n 296)AgeACM dose(g)Coma (% 3)ALT (IU/L)Alcohol use/abuse (%)Antidepress’tHistory of depressionNarcotic cpd (%)Multiple prepsSpont surv 424633865 0.001NS 0.026 0.0001NSNS 0.001 0.001 0.001NSComparison of Different ALF Etiology GroupsAPAPn 787Drugn 202Indeterminate HepA/HepB All Othersn 219n 37/123N 328Age (median)37473848/4345Sex (% F)76666046/4573Jaundice(Days)(median)0883/54Coma 3 (%)53375051/5543ALT (median)38466858492124/1702677Bili (median)4.419.822.012.5/19.114.6Tx (%)9404532/4130SpontaneousSurvival (%)OverallSurvival (%)67312754/243875686984/616518
“Hyperacute Phenomenon”in APAP CasesAPAP Drugn 787 n 202Indeterminaten 219HepA/HepBn 37/123Age (median)37473848/43AllOthersN 32845Sex (% F)76666046/4573Jaundice(Days)(median)0883/54Coma 3 (%)53375051/5543ALT (median)38466858492124/1702677Bili (median)4.419.822.012.5/19.114.6Tx (%)9404532/4130SpontaneousSurvival (%)OverallSurvival (%)67312754/243875686984/6165“Subacute Phenomenon” in DILI CasesAPAPn 787Drugn 202Indeterminaten 219All OthersN 32838HepA/HepBn 37/12348/43Age (median)3747Sex (% F)76666046/4573Jaundice(Days)(median)0883/54Coma 3 (%)53375051/5543ALT (median)38466858492124/1702677Bili (median)4.419.822.012.5/19.114.6Tx (%)9404532/4130SpontaneousSurvival (%)OverallSurvival (%)67312754/243875686984/61654519
Prognosis in ALF: Etiology is a MainDeterminantTransplant free survival rates differ greatlyGood prognosis: APAP66% Ischemia66% Pregnancy55% Hepatitis A56%Bad prognosis: Drugs Indeterminate Autoimmune Hepatitis B Wilson Disease27%25%26%26%0%*Schiødt FV, et al., Liver Transplant 2009Prognosis models King’s College Criteria for predicting poorprognosis‒ High positive predictive value (70-100%)‒ Low sensitivity ALFSG for predicting good prognosis‒ Based on bilirubin, INR, etiology, pressoruse, coma grade All prognostic scoring systems inaccurate Predicting prognosis requires a case-bycase, multidisciplinary approach20
Initial ManagementInitial Management Must have high index of suspicion at timeof admission Condition progresses rapidly Changes in consciousness occur hour-byhour Admission or early transfer to ICUwarranted21
History Often provided by family or friends due toaltered level of consciousness Focus should be on possible exposures todrugs (prescription medications, OTCanalgesics, herbal supplements or CAM) orviral infectionExam Careful documentation of neurologic status(hyperreflexia, mental status) Can change rapidly, need frequent neurochecks Jaundice often (but not always) present Need careful evaluation of stigmata ofchronic liver disease Spider nevi, palmar erythema22
Principals of Care Intensive care management of severe,rapidly progressive multi-organ systemfailure Only effective treatment: emergent livertransplant Rapid psycho-social evaluation critical Clinical course requires managing bothaspects simultaneouslyTreatment23
Treatment Plasmapheresis/ N-acetylcysteine (NAC)exchange transfusion Acetaminophen and Wilson’sNon-acetaminophen ALF Penicillin G and silymarin Nucleos(t)ide analogues(milk thistle) Acute hepatitis B Mushroom poisoning Acyclovir(Amanita phalloides) Acute HSV Outcome benefit not Steroidsestablished, data scarce AIH24
Primary/secondary outcomes in the NAC trialp 0.28*p 0.04*p 0.01p 0.09*p 0.035p 0.09The most impressive difference was in transplant free survival in comagrades I-II. * statistically significantCentral Nervous System Cerebral edema and intracranialhypertension (ICH) leading cause of death1 Herniation, ischemic, and hypoxic injury allpotential contributors to CNS injury Pathophysiology poorly understood, likelyinvolving multiple factors, includingammonia1. Stravitz RT, et al. Crit Care Med 2009;37:S258.25
Incidence Incidence of cerebral edema increases withworsening grade of encephalopathy1 Grade I – II: rare Grade III: 25 – 35% Grade IV: 65 – 75% Close monitoring warranted with emphasison early identification, prevention andtreatment1. Munoz SJ, et al. Semin Liver Disease 1993;13:395.Grading of EncephalopathyGrade IGrade IIGrade IIIGrade IVCognitivesymptomsMuscularsymptomsAwake, with slightdisorientation,forgetfulness, slow inanswering questionsDecreased level ofconsciousness, openseyes spontaneously,confusionSomnolent, arousable toverbal and painfulstimuli, does not openeyes spontaneouslyComatose, no responseMuscularincoordination,tremors, insomniaHyporeflexia, ataxiaasterixis, slurredspeechUnable to cooperatewith exam,nystagmusSeizures, rigidity,dilated pupils26
Prevention and Treatment ofEncephalopathy Grade I – II Avoid all sedating, centrally actingmedications Benzodiazepines, narcotics, antihistamines Avoid overstimulation Lactulose, Rifaxamin Head CT to rule out alternate explanations Not sensitive in detection of cerebraledemaPrevention and Treatment ofEncephalopathy Grade III – IV Transfer to ICU, intubation for airwayprotection Propofol recommended as sedation agent May reduce cerebral blood flow1 Elevate HOB to 30, avoid suctioning Prophylactic use of phenytoin notrecommended2,31.2.3.Wijkicks EFM, et al. Transplant Proc 2002; 34:1220Ellis AJ, et al. Hepatology 2000;32:536Bhatia V, et al. J Hepatol2004;41:8927
Management of IntracranialHypertension Avoid over-resuscitation with fluids Minimize any fluids given, especially bloodproducts Goal: Intracranial pressure (ICP) 20 mmHg Cerebral perfusion pressure (CPP) 60 – 80mmHg CPP MAP - ICPArterial ammonia and encephalopathy andintracranial hypertension in ALF Elevated arterialammonia thought tocause astrocyteswelling Increased arterialammonia levels 100associated withworsening grade ofencephalopathy andICHBernal W, et al. Hepatology 1002/hep.21838/full#fig428
Increased arterial ammoniaclosely associated with ALFManagement of IntracranialHypertension Low systemic vascular resistance common Systemic vasopressors frequently requiredto maintain Mean Arterial Pressure (MAP) 75 mmHg and CPP to 60 - 80 mmHg Norepinephrine used as first line agent‒ Vasopressin often added if secondagent required1. Clemmesen JO, et al. Scand J Gastroenterol 199;34:9229
Management of IntracranialHypertension Hypertonic saline1 Goal is induction and maintenance of serumsodium between 145 – 155 mmol/L Decreased ICP and intracranial hypertension intreatment group Mannitol2, 3 Short term benefit for acute increase in ICP 0.5 – 1 g/kg; dose repeated 1-2 times as needed Risks: volume overload, hyperosmolality (keepserum osmolality 320 mosm/L),hypernatremia1.2.3.Murphy N, et al. Hepatology 2004;39:464Nath F, et al. J Neurosurg 1986;65:41Canalese J, et al. Gut 1982;23:625New updates on olderrecommendations NO LONGER RECOMMENDED: Placement of intracranial pressure monitor(ICP) Mild hypothermia Prophylactic hyperventilation Prophylactic antibiotics Barbiturate coma30
Current Acute Liver FailureTrials at OSU ALFSG Registry (OPEN) STOP-ALF: OPA infusion forencephalopathy and hyperammonemia(CLOSED) Methacetin Breath Test (OPEN) ROTEM (OPEN)Summary Definition of ALF requires COAGULOPATHYand/or encephalopathy in the patient withacute hepatitis Acetaminophen still the most commoncause (intentional and unintentional use) Successful management of ALF requiresearly recognition and rapid transfer to aTransplant Center NAC indicated for ALL causes of ALF31
Hepatitis B and D by Robert Perrillo and Satheesh Nair, pp. 1647-1679. Sources of Infection for Persons with Hepatitis C (CDC) US.png Wedemeyer, H. Hepatitis C. Gastrointestinal and Liver Disease. 2016 Vol 2, 10th edition, 1309-1321. Wells J and Perillo R. Hepatitis B. Gastroi
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Hepatitis C 2 What is hepatitis C? Hepatitis C is a disease caused by a virus that infects the liver. This virus, called the hepatitis C virus or HCV for short, is just one of the hepatitis viruses. The other common hepatitis viruses are A and B, which differ somewhat from hepatitis C in the way they are spread and treated.
ICD-10-CM Version - Red Fu Associates, Ltd. 1 January 2021 190.33 - Hepatitis Panel/Acute Hepatitis Panel HCPCS Codes (Alphanumeric, CPT AMA) Code Description 80074 Acute Hepatitis Panel ICD-10-CM Codes Covered by Medicare Program The ICD-10-CM codes in the table below can be viewed on CMS' website as part of
Mar 22, 2010 · with hepatitis B and hepatitis C can vary considerably between, and within, countries and therefore, even in areas of low overall prevalence, rates in certain sub-populations can be very high.3 Both hepatitis B and hepatitis C are efficiently transmitted through contact with infected bloo
Hepatitis B virus (HBV) and hepatitis C virus (HCV) can cause acute and chronic hepatitis and potentially lead to the development of cirrhosis, liver cancer and death. In the EU/EFTA, an estimated 4.7 million people have a chronic hepatitis B virus infection, and 3.9 million people have chronic
atitis B, the hepatitis B surface antigen (HBsAg).1 According to a recent report from the Institute of Medicine (IOM), most obstetrical care providers do screen pregnant women for hepatitis B and ad-vise that newborns of HBsAg-positive mothers receive both hepatitis B im-mune globulin and hepatitis
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Archaeological illustration (DRAWING OFFICE) – DM‐W This week the class will be divided into two groups, one on the 25. th, the other on the 26. th, as the drawing office is too small for the entire group. Week 10 01.12.09 Introduction to the archaeology of standing remains (OUT) – DO’S Week 11 8.12.09 Interpreting environmental data (LAB) ‐ RT. 3 AR1009 28 September 2009 Reading The .
