e n GI Grand Rounds Johanna Chan PGY5 Fellow Baylor College of Medicine 10312013 Mentor Dr Norman Sussman No conflicts of interest No financial disclosures HPI 58yo healthy Hispanic man ID: 777225
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Slide1
Happy Halloween!
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Slide2GI Grand RoundsJohanna Chan, PGY-5 FellowBaylor College of Medicine10/31/2013Mentor: Dr. Norman Sussman
Slide3No conflicts of interestNo financial disclosures
Slide4HPI58yo healthy Hispanic manMinimal primary care2-3 weeks of worsening jaundice, increasing abdominal distention, and worsening lower extremity swellingNo known liver diseaseNo other complaints
Slide5PMHxEtOH abuseNo known prior liver diseaseMedications: nonePSHx: none
FamHxMother: heart disease, DM2Father: HTN
Brother: DM2No liver disease or autoimmune disease
SocHx
10 beers/wk
x
30 yrs
Last
EtOH
2 months prior
No prior IVDA, nasal cocaine, blood transfusions, tattoos
Quit smoking 4 weeks ago
No military service
Works as a railroad foreman
Slide6Physical ExamT 98.1, BP 109/65, HR 86, RR 12, O2 sat 98% RAGen: NAD, AAOx4, conversational, nontoxic, jaundicedHEENT: +scleral icterus, PERRL, EOMI, MMM, OP clearCV: RRR no m/r/g
Chest: CTAB no wheezes, slight crackles at basesAbd
: distended, +ascites, soft, nontender
, NABSExt: 2+ pitting edema BLE, WWP
Neuro: nonfocal
Slide7Labs on admission
MCV
104
63%
PMNs
136
4.8
21
109
8
1.0
73
18.8
50.7
16.5
207
INR 2.1
Blood cultures (−)
Urine cultures (−)
CXR unremarkable
Ascites
100
WBCs
, 37%
PMNs
Total
prot
8.4
Albumin 2.6
Total
bili
21.6
Direct
bili
16.3
Alk
phos
210
ALT 675
AST 888
Slide8Additional labsHep A total Ab (+)Hep A IgM (−) Hep B sAb 816.5
Hep B cAb reactiveHBV DNA <20
Hep C Ab (−)
HIV (−)CMV IgG (+)CMV
IgM (−)EBV IgG
(+)
EBV
IgM
(−)
T-spot TB (−)
ANA +1:2560 homogeneous
ASMA 56
IgG
3339
IgG1 2153
IgG2 774
IgG3 271
IgG4 142.2
AMA (−)
LKM-1
Ab
<20
A
lpha 1 AT normal
Ceruloplasmin
30
Ferritin 1790HFE mutations C282Y/H63D not detected
Slide9Slide10Transjugular liver biopsyHepatic venous pressure gradient 20mmHg
Slide11Courtesy of Dr. Laura Sulak and Dr. Rhonda Shannon
Slide12Courtesy of Dr. Laura Sulak and Dr. Rhonda Shannon
Slide13Courtesy of Dr. Laura Sulak and Dr. Rhonda Shannon
Slide14Liver biopsy (HD #2)Extensive fibrosis with marked cholangiolar proliferation and chronic inflammationInflammation predominantly composed of lymphocytes with focal areas showing increased numbers of plasma cellsScattered iron deposition, no alpha-1 antitrypsin depositionNo definite hepatocytes, granulomas
, or malignancy identified
Slide15Clinical courseDiagnosed with autoimmune hepatitisHD #3: prednisone 60mg PO daily
Slide16Lab trendHD #2HD #3HD #4HD #5
HD #6Total
bili22.2
20.324.023.4
21.1Alk
phos
180
159
173
182
173
ALT
547
484
483
416
301
AST
723
767
778
664
339
WBC
12.3
10.3
10.2
9.6
9.4
Platelets157158
167173177
INR2.12.22.0
2.22.4Creat
1.111.151.00
1.161.14
Slide17Clinical courseHD #3: prednisone 60mg PO dailyHD #6: mild asterixis, solumedrol 1g IV OLT evaluation, status 1AHD #7: obtunded, transferred to ICUHD #8: underwent liver transplant
Slide18Courtesy of Dr. Laura Sulak and Dr. Rhonda Shannon
Slide19Courtesy of Dr. Laura Sulak and Dr. Rhonda Shannon
Slide20Courtesy of Dr. Laura Sulak and Dr. Rhonda Shannon
Slide21ExplantGROSS: cut surface discolored in diffuse patchy pattern with yellow-green mottling, ~40% of the right lobe has areas of tan-pink normal parenchymaSubacute panlobular necrosis, severe, with multilobular
parenchymal collapse and early fibrosisGallbladder, no gallstones identified
Negative for malignancy
Slide22Acute liver failure due to autoimmune hepatitis
Slide23Clinical questionsWhat is the role for autoimmune hepatitis (AIH) diagnostic criteria in acute liver failure?Is there a typical histologic pattern in autoimmune acute liver failure (AI-ALF)?What is the role for steroids in AI-ALF?
Slide24Clinical questionsWhat is the role for autoimmune hepatitis (AIH) diagnostic criteria in acute liver failure?Is there a typical histologic pattern in autoimmune acute liver failure (AI-ALF)?What is the role for steroids in AI-ALF?
Slide25International AIH GroupAlvarez F et al. J Hepatol 1999; 31:929-938.
Slide26Simplified Diagnostic Criteria for AIHHennes EM et al. Hepatology 2008;48:169-176.
Slide27These criteria were designed to differentiate AIH from other causes of chronic liver diseaseIn contrast to classical AIH, no consensus guidelines distinguish AI-ALF from other ALF etiologies
Slide28AASLD guidelines: Management of ALFWhen autoimmune hepatitis is suspected as the cause for acute liver failure, liver biopsy should be considered to establish the diagnosis (III)Patients with acute liver failure due to autoimmune hepatitis should be treated with corticosteroids (prednisone, 40-60 mg/day) (I)Patients should be placed on the list for transplantation
even while corticosteroids are being administered (III)
Polson J et al. 2005;41:1179-1197.
Slide29Clinical questionsWhat is the role for autoimmune hepatitis (AIH) diagnostic criteria in acute liver failure?Is there a typical histologic pattern in autoimmune acute liver failure (AI-ALF)?What is the role for steroids in AI-ALF?
Slide30Histology of AIH vs. AI-ALFClassical AIH histology:Portal tract-based necroinflammationInterface hepatitisLobular (zone 2 and 3) involvement possibleCentrilobular predominance distinctly unusualCentrilobular variant of AIH?
Stravitz RT et al.
Hepatology 2011; 53(2): 517-26.Pratt DS et al. Gastroenterology 1997;113:664-668.
Slide31AIH histologic variantPratt et al. first reported a centrilobular variant of AIH in 1997Other case series followedCentrilobular zone 3 necrosis pattern typical for acute de novo autoimmune hepatitismore often presented as acute hepatitis, less fibrosis, or severe AIH presentationMay evolve into classical portal-based hepatitis or remain
centrilobular
Pratt DS et al. Gastroenterology 1997;113:664-668.Hofer H et al. J Clin
Pathol 2006; 59:246-249.Kessler WR et al. Clin
Gastroenterol Hepatol. 2004; 2(7):625-31.
Singh R et al. Am J
Gastroenterol
. 2002; 97(10): 2670-3.
Slide32Singh R et al. Am J Gastroenterol. 2002; 97(10): 2670-3.
Slide33Lee WM et al. Hepatology 2008; 47: 1401-15.
Slide34Liver sections (biopsies & explants) from 72 patient subset with “indeterminate” ALFSubset of ALF study group registry 1998-2008Developed histologic criteria for probable AI-ALF:Massive hepatic necrosisPresence of lymphoid folliclesPlasma cell-enriched inflammatory infiltrateCentral perivenulitis
Stravitz RT et al. Hepatology
2011; 53(2): 517-26.
Slide35Stravitz RT et al. Hepatology 2011; 53(2): 517-26.
Slide36Liver sections (biopsies & explants) from 72 patient subset with “indeterminate” ALFSubset of ALF study group registry 1998-2008Developed histologic criteria for probable AI-ALF:Massive hepatic necrosisPresence of lymphoid folliclesPlasma cell-enriched inflammatory infiltrate
Central perivenulitis
42/72 sections “probable” AI-ALF; higher serum globulins (P = 0.037), higher prevalence of ANA and/or ASMA (P = 0.034)
Stravitz RT et al.
Hepatology 2011; 53(2): 517-26.
Slide37Clinical questionsWhat is the role for autoimmune hepatitis (AIH) diagnostic criteria in acute liver failure?Is there a typical histologic pattern in autoimmune acute liver failure (AI-ALF)?What is the role for steroids in AI-ALF?
Slide38Steroid use in acute liver failureRetrospective analysis of autoimmune, indeterminate, and drug-induced ALF66 autoimmune (25 steroids, 41 no steroids)164 indeterminate (21 steroids, 143 no steroids)131 drug-induced (16 steroids, 115 no steroids)Karkhanis J et al and the Acute Liver Failure Study Group.
Hepatology 2013 Aug 8. [Epub ahead of print]
Slide39Karkhanis J et al and the Acute Liver Failure Study Group. Hepatology
2013 Aug 8. [Epub ahead of print]
Slide40Karkhanis J et al and the Acute Liver Failure Study Group. Hepatology 2013 Aug 8. [Epub ahead of print]
Slide41Steroid use in acute liver failureRetrospective analysis of autoimmune, indeterminate, and drug-induced ALF66 autoimmune (25 steroids, 41 no steroids)164 indeterminate (21 steroids, 143 no steroids)131 drug-induced (16 steroids, 115 no steroids)Steroids not associated with survival benefit, not significant in multivariable analysisSteroids associated with worse survival in MELD >40 subgroup (30% vs. 57%,
p = 0.03)
Karkhanis J et al and the Acute Liver Failure Study Group.
Hepatology 2013 Aug 8. [Epub ahead of print]Polson J et al. 2005;41:1179-1197.
Slide42Patient follow upSeen in transplant clinic 10/21/13Doing well
Slide43Take home pointsNo consensus diagnostic criteria for AI-ALFAI-ALF remains a diagnosis based on excluding viral and drug etiologies first, then requires histologic and serologic evaluationHistology of AI-ALF differs from typical AIH and is complicated by massive hepatic necrosisSteroids do not show a survival benefit in AI-ALF, and may be harmful in a subset of patients with MELD >40
Slide44ReferencesAbe M et al. Clinicopathologic features of the severe form of acute type 1 autoimmune hepatitis. Clin Gastroenterol Hepatol 2007; 5:255-8.Alvarez F et al. International Autoimmune Hepatitis Group Report: review of criteria for diagnosis of autoimmune hepatitis. J
Hepatol 1999; 31:929-938.Czaja
AJ. Acute and acute severe (fulminant) autoimmune hepatitis. Dig Dis
Sci (2013) 58:897-914.Czaja AJ. Performance parameters of the diagnostic scoring systems for autoimmune hepatitis.
Hepatology. 2008;48:1540-1548.Fujiwara K et al. Advanced histology and impaired liver regeneration are associated with disease severity in acute-onset autoimmune hepatitis. Histopathology 2011, 58, 693-704.
Fujiwara K et al. Diagnostic value and utility of the simplified International
Autoimmmune
Hepatitis Group criteria in acute-onset autoimmune hepatitis. Liver Int. 2011; 31(7):1013-20.
Hennes
EM et al. Simplified criteria for the diagnosis of autoimmune hepatitis.
Hepatology
2008;48:169-176.
Hofer H et al.
Centrilobular
necrosis in autoimmune hepatitis: a
histologic
feature associated with acute clinical presentation. J
Clin
Pathol
2006; 59: 246-249.
Karkhanis
J et al. Steroid use in acute liver failure.
Hepatology
2013 Aug 8.
doi
: 10.1002/hep.26678. [Epub ahead of print]Kessler WR et al. Fulminant hepatic failure as the initial presentation of acute autoimmune hepatitis.
Clin Gastroenterol Hepatol. 2004; 2(7):625-31.Lee WM et al. Acute liver failure: summary of a workshop.
Hepatology 2008; 47: 1401-15.
Slide45References (continued)Lee WM, Stravitz RT, Larson AM. Introduction to the revised American Association for the Study of Liver Diseases Position Paper on acute liver failure 2011. Hepatology. 2012;55:965-967.Manns MP, Strassburg CP. Autoimmune hepatitis: clinical challenges. Gastroenterology 2001;120:1502-1517.
Miyake Y et al. Clinical characteristics of fulminant-type autoimmune hepatitis: an analysis of eleven cases. Aliment
Pharmacol Ther 2006; 23: 1347-53.
Montano-Loza AJ, Carpenter HA, Czaja AJ. Features associated with treatment failure in type 1 autoimmune hepatitis and predictive value of the model of end-stage liver disease.
Hepatology. 2007;46:1138-1145.Nikias
GA,
Batts
KP,
Czaja
AJ. The nature and prognostic implications of autoimmune hepatitis with an acute presentation. J
Hepatol
1994; 21:866-71.
Polson J, Lee WM. AASLD position paper: the management of acute liver failure.
Hepatology
. 2005;41:1179-1197.
Pratt DS et al. A novel
histologic
lesion in
glucocorticoid
-responsive chronic hepatitis. Gastroenterology 1997;113:664-668.
Singh R et al. Acute autoimmune hepatitis presenting with
centrizonal
liver disease: case report and review of the literature. Am J
Gastroenterol
. 2002; 97(10): 2670-3.
Stravitz
RT et al. and the Acute Liver Failure Study Group. Autoimmune acute liver failure: proposed clinical and histological criteria. Hepatology 2011; 53(2): 517-26.Yasui S et al. Clinicopathological
features of severe and fulminant forms of autoimmune hepatitis. J Gastroenterol (2011) 46:378-390.
Slide46Questions or comments?