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Nonalcholic Fatty Hepatitis: an In1portant Clinical Condition

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Nonalcholic Fatty Hepatitis: an In1portant Clinical Condition REVIEW Nonalcholic fatty hepatitis: An in1portant clinical condition SAMU EL w. FRENCH. MO, LESLIE B. Emus. MD,] . FREEMAN, MD HE TERM FATIY HEPATIT IS HAS MANY ABSTRACT: The entity fatty hepatitis is defined and the li terature characteriz­ ing the clinical settings in which it develops is reviewed. The pathogenesis is T synonyms: fatty metamorphosis of discussed with emphasis on the common denominators shared by the various the liver in morbid obesity ( I), diabetic clinical conditions with which it is associated. The roles of alcohol, obesity and hepatitis (2,3), nonalcoholic stearohepa­ type II diabetes are stressed where inhibition of fatty acid oxidation by the liver is titis (4,5 ), fatty live r hepatitis (6), alcohol­ the basic defect in metabolism leading to fatty change, balloon degeneration and like liver disease in nonalcoholics (7 ), fast­ Mallory bod y for mation. le is concluded that this important entity is more com­ ing in obesity liver injury with alcoho lic mon than is generally appreciated . Can J Gastroenterol 1989;3(5): 189-197 hya line (8), stcatonecrosis (9) and non­ Key Words: Diabetes type TT , Fatty hepatitis, Mallory bodies, Obesity alcoholic Lacnncc's ( 10, 11 ). T he term fa tty hepatitis is preferred for its simplic­ L'hepatite graisseuse nonalcoolique: Une conditon clinique ity and for the concept that it conveys, importante one of fatty change with infla mmation in the li ver. T he disease process is im­ RESUME: L'hepatite graisseusc cstdefinie com me enrite morbide. La litterature po rtant to recognize clinically because it caracterisant les cadres cliniq ues ou cette affection se developpe est passee en revue. La pathogenese est exami nee et !'accent est pone sur les denominateurs can be mistaken fo r benign fa tty liver or com muns que partagent les diverses conditions cliniques auxquelles clle est asso­ alcoholic hepatitis. Fatty hepatitis is a per­ ciee. Le role de l'alcool, de l'obesire et du diabete de type 11 est souligne clans les nicious disease which may progress to cas ou !'inhibition d u processus d'oxydation hepatique des acides gras est la defi­ ci rrhosis without the physician real izing cience principale d u merabolisme entrainant !'accumulation de graisses, la dege­ it unless a liver bio psy is performed ( l ). nerescence graisseuse et la formation de corps de Mallo ry. On conclut que cette The clinical manifestations, associated entire importance est plus frequente qu'on ne l'estime generalement. diseases and pathology are the subject of this review. De/>artments of Pathology and S11rgery. Unrt,er.my of Ottau•a a nd Deparrmcn1 of Laboratory HISTORICAL BACKGROUND Medicine. 0 Hawa General Hospira /. Ot1awa . Onwrio Correspondence and reprints· Dr Samuel \,\I French. Professor and Chairman, Departmcnl of For many years, fa tty liver, regardless Pathology. Farnlcy of Hellhli Sciences, Univernry of Ouawa . 45 1 Smyth Road, Ottawa. Ontario of its cause, was considered a benign re­ KIH BM .5 versible process which did not progress Received for /m hli cauon July 21. / 989 Accepted Sc/>tcmber 19, 1989 to cirrhosis. This idea was based primar- CAN) GASTROENl rnoL Vo, 1 No 5 NO\ HIBtR/Dl:ClMB~R 1989 189 FRENCH era/ Figure 1) Gross photograph of a liver cross section taken ar autopsy from Figure 3) High power of Figure 2 showing the Junction between 4-1 faery an obe.1e patient diagnosed as having /atcy hepatitis on liver biopsy. The change on the left and minimal/acty change on the right ( x 83) liver appeared heterogeneous and partly nodular due to an uneven d1strr­ bution of/at. The light areas are/atcy and the dark areas are not.* Inciden­ tal bile duct cyst Figure 2) Low power view of a histologic section from the same liver Figure 4) Same liver as Figures 1 and 2 bur stained for collagen with shown in Figure I. The pale areas are /atty. The dark areas are nodular sinus red. Note the cencral-central bridging fibrosis (arrows) . This is in­ analogous to nodular regenernrive hyperplasia ( X 3) complete cirrhosis ( X 3) ily on the observation that the fatty liver cirrhosis in some ( 15). present authors have seen three cases of associated with Kwashiorkor in child­ Hepatitis of the fatty liver was first de­ methotrexate-induced nonalcoholic fatty hood did not progress to cirrhosis. A lso, scribed by Thaler ( 16). but the entity was hepatitis with Mallory body formation, the diabetic fatty liver, unlike the alco­ not widely appreciated until it became including one case in which typical cen­ holic fatty liver. did not progress to cir­ apparent that all of the morphologic fea­ tral sclerosing hyalin necrosis was found rhosis unless the patients were also al­ tures of alcoholic hepatitis, including in an elderly abstainer. coholics { l2). A similar result was re­ Mallory body formation and progression ported in the fatty li ver of obesity {13). to cirrhosis, were sometimes observed TABLE 1 Fibrosis or cirrhosis was not encountered in nonalcoholic patients. It has now been Nonalcoholic fatty hepatitis and fatty cir­ unless there was also a history of exces­ found to be associated with diabetes rhosis: Clinlcally associated conditions sive alcohol intake ( 13). The severity of (2-7,9, 13,17-21), obesity (3-7,13), mor­ Diobetes mellltus (2-7.9.13.17-2 1) fatty liver in alcoholics is predictive of bid obesity with or without intestinal Obesity(3-7.13) cirrhosis ( 14 ). However, in the study of bypass or gastroplasty ( 1, 15,22-36), fast­ Morbid obesity with or without intestinal fatty li ver associated with morbid obe­ ing in obese patients (8,22), massive re­ bypass or gostroplasty (1.15.22-36) Fasting in obese patients (8.22) section of the small intestine (3 7,38), sity, a few cases of liver fibrosis or cir­ Massive resection of small intestine (3 7 -38) rhosis were observed in which alcohol bulimia (39) and drug therapy (40-45) Bullmia(39) abuse was not a factor (I). Examination {Table 1). Fatty liver with fibrosis or cir­ Drug therapy: Glucocorticolds. amiodarone. of the liver biopsies taken before and rhosis caused by methotrexate may be perhexiline maleote (diuretics. hypoglyce­ after a small bowel bypass operation fo r hard to distinguish morphologically from mics. cardiac/hypertension. estrogens a nd thyroid)( 40-45) morbid obesity showed progression co nonalcoholic fatty he patitis ( 46). The 190 CAN J G ASTROENTEROL VOL 3 N O 5 N OVEMBER/DECEMllER 1989 Fatty hepatitis Figure 5) Lwer biopsy of a patienl wi1h morbid obesiry and /ally cirrho­ Figure 7) High power view ofa broJ,sy offaery hepa1icisfrom a morbidly sis. The bridging fibrosis incorpora1es central ,,eins and portal traces (ar­ obese pacienr. Note both 1he nucro-and macrovesicular fa1 The mrcrovesi­ row). SrriitS red X I 7 cular [a1 resembles the foamy degenera1ion seen rn alcoholic hepatitis ( x 330) - 'CV • Figure 6) View ofa porcal rracr ( PT) and centrilob11lar area (CV I show­ Figure 8) High power view of 1he same liver shown in Figure 6 showing a ing borh pmportal and centrilobular fibrosis. The .:eniral fibrosis is micro[octtS of 1he characteristic macrophage infiltrate seen in che lobule pericellular (arrows). This is/rom a biopsy offaery hepatitis from an obese (arrows/ The macrophages are iden1i/iable beca11se chey contain periodic patient. Sirn~1 red x 83 acid-Schiff positive {Jhagosomes. Digested penodrc acid-Schiff reagent x 330 The frequency of cirrhosis and fibro­ variable , being absent early and pro­ loon cells, and the intense staining of sis varies with different series, but in a gressing to incomplete cirrhosis (Figure 4) cycokeratin in the Mallory bodies (Fig­ review of 41 papers on liver morphol­ or cirrhosis (Figure 5 ). ure 10), analogous to that seen in alco­ ogy of 15 15 morbidly obese patients, Fibrous spurs extend from the portal holic hepatitis ( 4 7). Marked centrilobular 29% had fibrosis and 3°lo cirrhosis ( 34). tracts toward zone 3 of the lobule (Fig­ bile ductule metaplasia occurs in centri­ In a nine month follow-up of 34 cases of ure 6) whereas scars in zone 3 fo rm fi­ lobular scars (Figures 11, 12), as seen in jejunoileal bypass for morbid obesity, six brous bridges between the terminal hep­ alcoholic hepatitis ( 48-5 1). This prolif­ developed fibrosis a nd three cirrhosis atic venules (central veins) (Figure 4). eration of bile ductules induces a desmo­ (35). The earliest change is fatty change, both plastic response similar to that seen in microvesicular and macrovesicular (Fig­ the periporcal areas (Figures 11 , 12). This PATHOLOGY ure 7). The earliest infla mmatory change, phenomenon, in which liver cells express Hepatomegaly is the rule. Grossly, the which distinguishes fatty liver from fatty cytokera tins which are no rmally only liver is pale yellow or a mottled yellow hepatitis, is the development of foci of expressed by bile duct epithelium, is and brown , owing co a heterogeneous macrophages in the parenchyma (Figure known as bile duct metaplasia of hepa­ fatty change (Figure I). Fibrosis is vari­ 8). This is followed by balloon degener­ tocytes ( 49). The use of immunoperox­ able and irregularly distributed unless ation and Mallory body formation in the idase in the localization of these bile duct the liver has progressed to cirrhosis. centrilobular zone (Figure 9). This lesion cytokeratins is illustrated in Figures 11 Microscopically, the fatty ch ange may is accompanied by a mononuclear infil­ and 12. Thus, the evolution of fatty hep­ be diffuse early and more patchy in trate and fibrosis, and is associated with atitis to cirrhosis resembles that of alco­ late r stages (Figures 2, 3 ). Scarring is a loss of cytokeratin staining in the bal- holic hepatitis except for one feature.
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