fulminant hepatitis a - cdn.doctorsonly.co.il hepatitis a.pdf · case cont • pe –apathy, deep...
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Case
• 48 y o female born in Israel s + 048 y o female, born in Israel, s + 0 • Admitted because of the liver enzymes elevation and jaundice
• 1 week before the admission – fever and1 week before the admission fever and malaise, treated with Paracetamol ,1 d b f h d i i j di d k• 1 day before the admission – jaundice, dark urine, pale stool
• Referred to the ER
Case cont
• Past medical history – long history ofPast medical history long history of schizophrenia treated with Risperdal, Tegretol, Paxet socially adopted worked at protectedPaxet, socially adopted , worked at protected facility, compliant with her medications
• NIDDM on Metformin, Januvia, Novonorm• Dyslipidemia on SimovilDyslipidemia on Simovil, • Aspirin• Lives with her brother, no travels
Case cont• PE – apathy, deep jaundice , no signs of chronic liver disease otherwise unremarkabledisease, otherwise unremarkable
• Lab results WBC – 21.K/microL, 75% Neutro• Hb – 11.5 g/dlHb 11.5 g/dl• PLT 466 K/microL, MCV ‐82fL• ALT 4848 IU/l, AST‐ 4758 IU/l, Alk Phos‐306 IU/l/ , / , /• GGT ‐368 IU/l, Bil Tot 12.3 mg/dl, Dir 6.9 mg/dl• LDH – 937 IU/l, creat – 1.3 mg/dlg• INR ‐5.45, Factor V ‐22%• Ammonia 676 microgr/dl, Paracetamol ‐ neg• US , CT, consultation of surgeon • Psychiatric evaluation – found eligible to sign informed consent
Case contCase cont
• Diagnosis of Acute hepatitis with acute liverDiagnosis of Acute hepatitis with acute liver failure was made, admitted to ICU
• At ICU treated with the best supportive care• At ICU treated with the best supportive care• Parvulex according to Acetominophen
lprotocol• FFP and Vit K before puncturesp• CVVH• Broad spectrum antibiotics• Broad spectrum antibiotics• Extensive evaluation of possible liver disease
Case cont• HBsAg negative • Anti HBc IgM negativeg g• Anti HCV negative• Anti HAV IgM positiveAnti HAV IgM positive• EBV negative , CMV IgM borderline, IgG positive• Ceruloplasmin 42 mg/dl• Ceruloplasmin 42 mg/dl• ANA 1:160, AMA neg , AntiSLA neg, p‐ANCA, c‐ANCA neg Anti LKM negativeneg, Anti LKM negative
• ASMA positive , Atypical ANCA +1, • Globulins 3 8 g/dl• Globulins 3.8 g/dl• US , CT – fatty liver, normal spleen , periportaledema small amount of ascitic fluid around the liveredema, small amount of ascitic fluid around the liver
CaseCase • Acute hepatitis A • Continued supportive care • Improvement clinical ( in term ofImprovement clinical ( in term of encephalopathy) and laboratory (transaminases decreased)(transaminases decreased)
• But ….ili bi i d i• Bilirubin continued to increase
• Coaguloathy did not improve g y p• TJLB was performed • Transferred to the internal medicine ward• Transferred to the internal medicine ward
Anti HAV IgMAnti HAV IgM
I M ti HAV ft b d t t d l d b f• IgM anti‐HAV can often be detected several days before symptom onset and is usually detectable for 3–6 months after illness onset
• IgM anti‐HAV can persist for at least 30 months after infection and persons with persistently positive IgM anti‐HAV test results for at least 5 years have been reportedHAV test results for at least 5 years have been reported
• False‐positive test results ‐ in the past due to presence of cross‐reactive antibodies from other viral infection or
d l i ill ( Rh t id f t !)underlying illnesses ( Rheumatoid factor!) • Recent Assay! No false reactivity with samples containing:
rheumatoid factor, ANA, CMV, IgM antibody to HBV, or IgGrheumatoid factor, ANA, CMV, IgM antibody to HBV, or IgGanti‐HAV
• Positive results should be correlated with the patient’s clinical history and epidemiologic exposureclinical history and epidemiologic exposure
Why Biopsy?y p y
• Identification of hepatitis A virus as a trigger for autoimmune chronic hepatitis type 1 in p ypsusceptible individuals
S. Vento,, T. Garofano et al
• To identify factors contributing to the pathogenesis of autoimmune chronic active hepatitishepatitis
The Lancet May 1991, Pages 1183–1187
TJLB H&ETJLB H&E
TSLB H&ETSLB H&E
Biopsy H&EBiopsy H&E
Biopsy H&E CVBiopsy H&E CV
Biopsy MTBiopsy MT
Case cont• At the ward• Encepalopathy deteriorated – Grade 2 through 4Encepalopathy deteriorated Grade 2 through 4, coma
• Bilirubin continued to riseBilirubin continued to rise• Coagulopathy• Put on steroids and UrsolitPut on steroids and Ursolit• EEG – epileptiform abnormality was registered• Trachea was intubated• Trachea was intubated• Transferred to the transplant center P t MARS X 3• Put on MARS X 3
• Listed d th h l d• Died on 26th hospital day
AST
ALTALT
Alk Phos
GGTGGT
Bilirubin Total
AlbuminAlbumin
Factor V
PTPT
Ammonia
CreatinineCreatinine
Lactate
WBC
Acute Liver Failure in HAVAcute Liver Failure in HAV
• Less than 1% of acute hepatitis A cases result in acute liver failure
HAV i f i l f l 3%• HAV infection currently accounts for only 3% of adult acute liver failure (ALF) cases in the United States
King's College CriteriaKing s College CriteriaAcetaminophen‐induced disease
• Arterial pH <7.3 (independent of the grade of encephalopathy) OR• Grade III or IV encephalopathy and• Prothrombin time >100 s and (INR >6.5) • Serum creatinine >3.4 mg/dL (301 μmol/l)All other causes of fulminant hepatic failureProthrombin time >100 s , INR >6.5 (independent of the grade of Prothrombin time 00 s , INR 6.5 (independent of the grade ofencephalopathy)
ORAny three of the following variables (independent of the grade of encephalopathy)
1. Age <10 years or >40 years2. Etiology: non‐A, non‐B hepatitis, halothane hepatitis, idiosyncratic drug
reactions3. Duration of jaundice before onset of encephalopathy >7 days4. Prothrombin time >50 s (INR >3.5) 5. Serum bilirubin >18 mg/dl (308 μmol/l)g/ ( μ / )
Clichy CriteriaClichy Criteria
• Presence of hepatic encephalopathy andPresence of hepatic encephalopathy and factor V level:20% f l i i 30 f• <20% of normal in patients <30 years of age, or
• <30% of normal in patients >30 years of age.
HEPATOLOGY, September 2003
Patients with HAV ALF
Fulminant vs.Non fulminant courseFulminant vs.Non fulminant course
Fulminant HAVFulminant HAV
HAV RNA
Conclusion of this Studyy• Low viremia is the most important factor passociated with liver failure in this setting, presumably owing to a strong immunepresumably owing to a strong immune response.
f d ld h h l bl h h• Our findings could thus help to establish the prognosis of such patients.
• Indeed, a low viral load in an encephalophaticpatient could help for the very difficultpatient could help for the very difficult decision of transplantation
HEPATOLOGY Vol 44 No 6 2006HEPATOLOGY, Vol. 44, No. 6, 2006
Patients
ALT
Creatinine
Predictors of Transplant/Deathp
Conclusions of this Studyy• The incidence of fulminant HAV has significantly decreased over the past 7 yearssignificantly decreased over the past 7 years.
• Among the ALFSG HAV patients, 4 readily available laboratory and clinical features at presentation may help identify patients in need of urgent liver transplantation but further validation is required.
• Since severe acute HAV infection is one of the few preventable etiologies of ALF, greaterfew preventable etiologies of ALF, greater vaccination of the general population and high‐risk subgroups may lead to further reductionsrisk subgroups may lead to further reductions in the associated morbidity and mortality.
EditorialEditorialHEPATOLOGY, Vol. 44, No. 6, 2006
RAYMOND S. KOFF, M.D.University of Connecticut Medical SchoolUniversity of Connecticut Medical SchoolFarmington, CT
HAVHAV
Conclusion of Edit
• Fulminant hepatitis A is disappearing. U f t t l it i t di i idl h t li i t• Unfortunately, it is not disappearing rapidly enough to eliminate the need for liver transplantation in acutely infected patients.
• Given the excellent immunogenicity and safety of the currently g y y yavailable inactivated HAV vaccines for more than a decade, the continuing occurrence of fulminant hepatitis A must be viewed as a failure of our health care system. y
• The ACIP’s recent recommendation for routine early childhood immunization beginning at age 12 to 23 months is a first step that needs immediate implementation throughout the countryneeds immediate implementation throughout the country.
• Ideally, it should have been accompanied by a recommendation for catch‐up vaccination for children, adolescents, and susceptible d ladults.
• This proposed recommendation accordingly may simply be too great an opportunity to miss.g pp y
Patients
OutcomesOutcomes
Conclusions of This StudyConclusions of This Study
• The association of undetectable viral load with poor outcome suggests a genetic p gg gpredisposition to a excessive host immune response contributes to the more severeresponse contributes to the more severe disease observed. h f h b h f• This is further supported by the occurrence of familial ALF case clustering
Hepatitis A epidemic in the elderlyHepatitis A epidemic in the elderly• 180 cases of HAV in patients more than 40 y op y• Hospitalization rate 3% (40‐49) 12% (50‐69)M k T Bil hi h i h i li d• Mean peak Tot Bil was higher in hospitalized patients ‐12.4 vs.7.2mg/dL
• Co‐morbid conditions – significant alcohol consumption‐8% diabetes ‐16 6% cardio‐consumption‐8%, diabetes ‐16.6%, cardio‐vascular disease 54%, COPD ‐21%
• Comlications – pancreatitis (4.1%), ascites (8.3%), prolonged cholestasis (7.6%), death (0.8%) p g ( ) ( )
Brown GR, Persley K South Med J. 2002 Aug;95(8):826‐33
SteroidsSteroids
Response to SteroidsResponse to Steroids
Re‐emerging Hepatitis ARe‐emerging Hepatitis A
Take Home PointsTake Home Points • Fulminant HAV declining but still exists• Possible predictors of the worst outcome besides KCC and Clishi criteria if ALF presents:
• Host factors : ALT, Creatinine, Pressors , intubation ( on day 1), Age ? Alcohol intake,intubation ( on day 1), Age ? Alcohol intake, co morbidity (HBV, NIDDM, COPD)
• Viral factors : HAV RNA Genotype?• Viral factors : HAV RNA, Genotype? , Genomic sequence ?
• HAV is a preventable disease !!! • Vaccination of susceptible adultsp
THANK YOUTHANK YOU
Fulminant HAVFulminant HAV
MARIA SJOGREN, M.D.Walter Reed Army Medical CenterWashington, DC
ALF due to HAV &HBVALF due to HAV &HBV
Conclusions of the Edit• Hepatitis A is a preventable infection Th t bidit d t lit fi d• The current morbidity and mortality figures and the high financial and societal costs of transplantation should make us reconsider ourtransplantation should make us reconsider our policies against universal vaccination against hepatitis Ahepatitis A.
• Excellent vaccines are commercially available to t h titi A it i th f diffi lt tprevent hepatitis A; it is therefore difficult to
comprehend why so many people are newly infected with the hepatitis A virus and why casesinfected with the hepatitis A virus and why cases of ALF cannot be prevented in the United States and abroadand abroad.
Outcomes
HAV ALF Decline
ALFSG vs.UNOS
Acute Cholestatic Hepatitis AAcute Cholestatic Hepatitis A
CholestasisCholestasis
CholestasisCholestasis