chronic transaminitis 07

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Chronic Transaminitis

Dr. Danny Panisko

UHN/MSH AIMGP Seminar Series

March 2007



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



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




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(

http://www.gastro.org/


http://www.nacb.org/

http://www.nacb.org/






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



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




Do these mysterio's (omen ha$e chronic

transaminitis1




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.




hy is the time frame of # months imortant F

3n (eneral terms/ 'hat is the sensitivity this definition for

chronic heatic in4ury F




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.



Cirrhosis




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.



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




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




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




8hich Imm'ne ca'ses o& )i$er %isease can )ea%

to chronic transaminitis 1




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



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




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.




)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



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




&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




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




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



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




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




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




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




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




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



Ch i T i iti




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.



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

chronic transaminitis 07

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