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Chronic Transaminitis
Dr. Danny Panisko
UHN/MSH AIMGP Seminar Series
March 2007
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Chronic Transaminitis !"#ecti$es
At the en% o& this seminar yo' (i)) "e a")e to
De&ine chronic transaminitis
*ist an 'n%er)yin+ %i&&erentia) %ia+nosis
Un%erstan% re)e$ant &eat'res on History
Con%'ct a re)e$ant Physica) ,-am Descri"e a +'i%e)ine"ase% In$esti+ation
aroach
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Chronic Transaminitis !'t)ine
!"#ecti$es/!'t)ine an% G'i%e)ines/e&erences
Cases
Di&&erentia) Dia+nosis Me%ica) History
Physica) ,-amination
Initia) *a"oratory ,$a)'ation Dia+nostic A)+orithm
e$isit !"#ecti$es
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Chronic Transaminitis
G'i%e)ines
AGA Medical Position Statement: Evaluation of Liver Chemistry Tests.
Gastroenterology 2002 !2": !"#$%##. Also availa&le at
'''.(astro.or(
AGA Technical )evie' on the Evaluation of Liver Chemistry Tests.
Gastroenterology 2002 !2": !"#*%+$. At '''.(astro.or(
,ational Academy of Clinical -iochemistrys La&oratory Guidelines forthe Screenin(/ ia(nosis/ and Monitorin( of 1eatic 3n4ury 2000
Section $ Chronic 1eatic 3n4ury ."!%+. At '''.nac&.or(
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Chronic Transaminitis
Use&') e&erences
Pratt S and 5alan MM. Evaluation of a&normal liver%en6yme resultsin asymtomatic atients. N Eng J Med 2000 "$2: !2##%*!
)ole of PC) and liver &iosy in the evaluation of atients 'ithasymtomatic transaminitis: imlications in dia(nostic aroach. JGastroenterol Hepatol 200$ !78!!9: !27!%7
,eil ; and Po'ell L. Clinical asects of hemochromatosis. Sem
Liver Dis 200< 2<8$9: "+!%7!
Giannini EG et al. Liver en6yme alteration: A (uide for clinicians.CMAJ 200< !*2: "#*%*7
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Chronic Transaminitis Cases
Ms. A. =iral/ Miss -. 3mmune/ and Mrs. C. Metalto>in are threeasymtomatic "< year old 'omen coincidently referred to yourA3MGP clinic on the same day.
They 'ere noted to have elevated transaminases 8AST !00%!2</ALT !00%!2< ?,@"< and , ALP and T&ili9 &y their family Ms onroutine &lood'orB # months a(o. )eeat &lood'orB/ miraculouslyerformed on the same day/ revealed similar values 2 months a(oand also one 'eeB a(o.
The 'omen have &een 'ell 'ith no symtoms. They looBsurrisin(ly similar to you may&e identical trilets lost at &irth D
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Chronic Transaminitis Cases
Do these mysterio's (omen ha$e chronic
transaminitis1
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Chronic Transaminitis Cases
Do these mysterio's (omen ha$e chronic
transaminitis1
es. This entity is %e&ine% as ersistence o&
e)e$ate% A*T &or more than 3 months4 either
a&ter an eiso%e o& ac'te heatitis or (itho't
another e-)anation.
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Chronic Transaminitis Cases
hy is the time frame of # months imortant F
3n (eneral terms/ 'hat is the sensitivity this definition for
chronic heatic in4ury F
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Chronic Transaminitis Cases
hy is the time frame of # months imortant F
3t defines a clinical entity 'ith a limited differential and
eliminates a variety of short%lived causes of liver in4ury thatdo not have lon( term conseuences or considerations.
orB u of mild asymtomatic transaminitis that does notersist is not indicated in a atient 'ithout risB factors.
orB u of chronic asymtomatic transaminitis isconducted in the hoe of reventin( ro(ression tocirrhosis.
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Cirrhosis
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Chronic Transaminitis Cases
3n (eneral terms/ 'hat is the sensitivity of this definitionfor chronic heatic in4ury F
hile (enerally sensitive and secific/ it is not erfect.
Hor e>amle/ some atients 'ith chronic 1eatitis Cinfection do not mount elevated ALTs.
Also/ a atient 'ith rimary &iliary cirrhosis or sclerosin(cholan(itis may only have an elevated ALP earlier in thecourse of their disease.
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Chronic Transaminitis D-%-
In terms o& "roa% %isease cate+ories4 (hat is a
%i&&erentia) %ia+nosis o& otentia) etio)o+ies o&
chronic transaminitis 1
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Chronic Transaminitis D-%-
3n terms of &road disease cate(ories/ 'hat is a differentialdia(nosis of otential etiolo(ies of chronic transaminitis F
5ira)
Imm'ne
Meta) %eosition / To-ic
!ther 6 inc)'%in+ nonheatic
Can you rovide more detail for this differential &eforevie'in( the ans'ers on the ne>t slideF
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Chronic Transaminitis D-%-
8hich me%ications4 her"s4 street %r'+s can )ea%
to transaminitis an% )i$er in#'ry 1
8,ote: chronic recurrent use can lead to chronic
liver in4ury9
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Chronic Transaminitis D-%-
8hich Imm'ne ca'ses o& )i$er %isease can )ea%
to chronic transaminitis 1
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Chronic Transaminitis D-%-
8hich Imm'ne ca'ses o& )i$er %isease can )ea%
to chronic transaminitis 1
9Tr'e: A'toimm'ne heatitis
Primary ;i)iary Cirrhosis
Sc)erosin+ Cho)an+itis
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Chronic Transaminitis History
Gi$en the re$io's)y %isc'sse% %i&&erentia)
%ia+nosis4 (hat are imortant historica) &eat'res
to e-)ore in a atient (ith chronic transaminitis 1
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Chronic Transaminitis History
Symtoms of liver in4ury: fati(ue/ 'eaBness/ icterus/
ruritis/ darB urine/ ossi&le stool colour li(htenin(/
nausea/ vomitin(/ )IJ discomfort/ intolerance to dietary
rotein or ci(arette smoBe
Symtoms of the conseuences of cirrhosis: &leedin(/
cache>ia/ edema/ ascites/ encehaloathy/ sBin chan(es/
(ynecomastia etc.
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Chronic Transaminitis History
)isB factors K etiolo(y: fecalKoral and &loodK&ody fluid e>chan(e risBs for
viral heatitis
dru(s/ medications/ her&s/ to>ins/ alcohol ?CAGE/
acetaminohen 8rimary or co%to>in9
o&esity/ dietin(/ o&esity sur(ery/ &ullemia/ dia&etes as
risBs for non%alcoholic steatoheatitis 8,AS19
Hamily history: for diseases 'ith symtoms
consistent for hemochromatosis/ ilsons/ alha%!
antitrysin/ or autoimmune
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Chronic Transaminitis Physica)
8hat hysica) e-am &eat'res sho')% "e
emhasi<e% in a atient (ith chronic
transaminitis 1
8Can you identify the hysical si(ns on the follo'in( slides F9
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Chronic Transaminitis Physica)
&viously trivia..
ermatitis heretiformis: chronic heretiform lesions on
e>tensor surfaces 8in this case/ el&o's9 in atients 'ith
Celiac isease 5ayser%Hleischer )in(s/ &est areciated 'ith a slit
lam/ as &ro'n i(mentary deosits on the erihery of
the cornea/ in atients 'ith ilsons disease
Tendon >anthomata/ on the Achilles/ in atients 'ithhyerliidemia due to cholestasis in liver disease that
also can have chronic transaminitis such as rimary
&iliary cirrhosis
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Chronic Transaminitis Physica)
Hindin(s of liver in4ury and structural chan(e:heatome(aly/ )IJ tenderness
Hindin(s of liver dysfunction: icterusK4aundice/ edema/&leedin(/ &ruisin(/ edema/ encehaloathy/ asteri>is/fetor heaticus
Hindin(s of ortal hyertension: slenome(aly/ cautmedusa/ hemorrhoids/ ascites
Sti(mata of chronic liver disease
Hindin(s of Etiolo(ic disease rocesses: &ron6edia&etes/ mental status chan(esKsychoses/malnutritionKmala&sortion/ vasculitic urura 8'hat arethe connections 'ith these si(ns F9
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Chronic Transaminitis
Case History an% Physica)
No a%%itiona) history or hysica) e-am %ata (as
contri"'tory &or none o& the s'sicio's)y simi)ar Ms. A. 5ira)4 Miss ;. Imm'ne4 nor Mrs. C. Meta)to-in=.
e-cet that Ms. A. 5ira) recei$e% a trans&'sion o&2 'nits o& ;C>s a&ter a car acci%ent in ?@34an% Mrs. C. Meta)to-in 'n%er(ent a tota)
hysterectomy "eca'se o& &i"roi%s at a+e B0
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Chronic Transaminitis Initia) *a"s
8hat are consi%ere% re)e$ant initia) )a"oratory
in$esti+ations "y se$era) e-ert consens's
+'i%e)ines 1
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Chronic Transaminitis Initia) *a"s
8hat are consi%ere% re)e$ant initia) )a"oratory
in$esti+ations &or chronic transaminitis "y
se$era) e-ert consens's +'i%e)ines 1
*i$er en<ymes4 IN4 A)"'min4 C;C (ith
)ate)ets4 Heatitis ; S A+4 Heatitis ; S A"4
Heatitis C I+G4 Iron Sat'ration an%/or erritin
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Chronic Transaminitis Initia) *a"s
Ms. A. =iral 'as found to have 1eatitis C 3(Gositive. Therefore/ a dia(nosis of Chronic 1eatitisC 'as made. She 'as referred to a heatolo(ist for
consideration of antiviral theray.
Mrs. C. Metalto>in 'as found to have an ironsaturation of <+ 8n@$<9 and a ferritin of +<0 mc(Kl8n N 22%"229 hat is her dia(nosis F oes she need further dia(nostic testin( F hat are the &road rinciles in her mana(ement F
Ch i T i i i
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Chronic Transaminitis
Mrs. C. Meta)to-in
She liBely has hereditary hemochromatosis/ 'as not on iron
sulements/ O did not taBe alcohol to e>cess 8'hy is this relevant F9
Some hysicians liBe to confirm the de(ree of iron overload definitively'ith liver &iosy
She and her first de(ree relatives should receive (enetic screenin(/
'ith 1HE mutation analysis/ to facilitate decision maBin( for treatment
of family mem&ers and (enetic counselin(
Treat 'ith hle&otomy (et He saturation &elo' <0/ O assess for
cirrhosis and other systemic involvement of He overload
Ch i T i iti
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Chronic Transaminitis
Dia+nostic A)+orithm
Miss ;. Imm'ne ha% ENF initia) in$esti+ations
aart &rom a reeat o& the transaminases (hich
(ere minima))y e)e$ate% as "e&ore=
8hat sho')% "e %one no( 1
Ch i T i iti
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Chronic Transaminitis
Dia+nostic A)+orithm
The AGA al(orithm su((ests a&dominal ultrasound/A,A/ Cerulolasmin/ anti%smooth muscle anti&ody/ anti%(liadin anti&ody/ anti%endomysial anti&odies and alha%!antitrysin level.
8hat entities do these investi(ations test for F
see ans'er on ne>t slide9
The al(orithm also su((ests further confirmatory liver
&iosy if any of these results are a&normal. Manyheatolo(ists 'ould also do a liver &iosy at this oint ifthere 'as still no dia(nosis.8See al(orithm on 2nd slide follo'in(9
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Ch i T i iti
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Chronic Transaminitis
Miss ;. Imm'ne
Miss ;. Imm'ne ha% a ositi$e ANA at a titre o&
?30.
A )i$er "iosy con&irme% a'toimm'ne heatitis
(ith no e$i%ence o& cirrhosis.
She (as re&erre% to a heato)o+ist an% starte%
on Pre%nisone theray.
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Chronic Transaminitis !"#ecti$es
Hoe&'))y4 yo' are no( a")e to
De&ine chronic transaminitis
*ist an 'n%er)yin+ %i&&erentia) %ia+nosis
Un%erstan% re)e$ant &eat'res on History
Con%'ct a re)e$ant Physica) ,-am
Descri"e a +'i%e)ine"ase% In$esti+ation
aroach