Fig. 16.16 Fattyliverdiseaseassociatedwithchronicalcoholuse.Amixofsmallandlargefatdroplets(seenasclearvacuoles)ismostprominentaroundthecentralveinandextendsoutwardtotheportaltracts.Somefibrosis(stained blue) ispresentinacharacteristicperisinusoidal“chickenwirefence”pattern(Massontrichromestain).(Courtesy of Dr. Elizabeth Brunt, Washington University, St. Louis, Missouri.) http://ebooksmedicine.net
Fig. 16.17 Hepatocyteinjuryinfattyliverdiseaseassociatedwithchronicalcoholuse.(A)Clusteredinflammatorycellsmarkingthesiteofanecrotichepatocyte.AMallory-Denkbodyispresentinanotherhepatocyte(arrow). (B)“Ballooned”hepatocytes(arrowheads) associatedwithclustersofinflammatorycells.Theinsetstainedforkeratins8and18(brown) showsaballoonedcell(dotted line) inwhichkeratinshavebeenubiquitinylatedandhavecollapsedintoanimmunoreactiveMallory-Denkbody,leavingthecytoplasm“empty.”(Courtesy of Dr. Elizabeth Brunt,Washington University, St. Louis, Missouri.)
Macroscopically,fattyliverswithwidespreadsteatosisarelarge(weighing4–6kgormore),soft,yellow,andgreasy.
Steatohepatitis. ThesechangestypicallyaremorepronouncedwithalcoholusethaninNAFLD,butcanbeseenineither:
Hepatocyte ballooning. Singleorscatteredfociofcellsundergoswellingandnecrosis;aswithsteatosis,thesefeaturesaremostprominentinthecentrilobularregions(
Fig.16.17A
Mallory-Denk bodies. Theseconsistoftangledskeinsofintermediatefilaments(includingubiquitinylatedkeratins8and
Fig.16.17B •Neutrophil infiltration. Predominantlyneutrophilicinfiltrationmaypermeatethelobuleandaccumulatearounddegeneratinghepatocytes,particularlythosecontainingMallory-Denkbodies.Lymphocytesandmacrophagesalsomaybeseeninportaltractsorparenchyma.
Steatofibrosis. Fattyliverdiseaseofallkindshasadistinctivepatternofscarring.Likeotherchanges,fibrosisappearsfirstinthecentrilobularregionascentral vein sclerosis. PerisinusoidalscarringappearsnextinthespaceofDisseofthecentrilobularregionandthenspreadsoutward,encirclingindividualorsmallclustersofhepatocytesinachicken wire fence pattern (see
Fig.16.16 ).Tendrilsoffibrosiseventuallylinktoportaltractsandthencondensetocreatecentral portal fibrous septa. Asthesebecomemoreprominent,thelivertakesonanodular,cirrhoticappearance.Becauseinmostcasestheunderlyingcausepersists,thecontinualsubdivisionofestablishednodulesbynew,perisinusoidalscarringleadstoaclassicmicronodular orLaennec cirrhosis. Earlyinthecourse,theliverisyellow-tan,fatty,andenlarged,butwithpersistentdamageoverthecourseofyearstheliveristransformedintoabrown,shrunken,nonfattyorgancomposedofcirrhoticnodulesthatareusuallylessthan 0.3cmindiameter—smallerthanistypicalformostchronicviralhepatitis.Theend-stagecirrhoticlivermayenterintoa“burnedout”phasedevoidoffattychangeandothertypicalfeatures.Amajorityofcasesofcryptogenic cirrhosis, withoutclearetiology,arenowrecognizedas“burned-out”NAFLD.