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.

CAN J GASTROENTFROI Vo1 l Nn 5 N

, • • • PT • • " ' C

ii • • ' •

Figure 9) Centrilobular balloon degencrarion in hepawcy1es from a mor· Figure 11) Same liver as in Figures 9 and 10. The bile ductulemetapla­ bidly obese patient. Nore rite Mallory bodies /arrows) within rite balloon sw (closed arrows) is illustrated in bo1h the periporral (PT) area and the cells. Also, note the absence of polymorphonuclear lmkocytes and the foci centrilobular (CV) area Normal bile ducts (open arrow) also stain /JOSI· of mononuclear inflammation and fibrosis ( x 330) tively for cytokeratins. The bile ductules sea in /1ositively for cycokerarins like bile ducts e11en though the bile ductules are 1ransformed liver cells. These meraplastic duc1ules s1imula1e periducralfibrosis. lmmunoperoxidase x 83

I

Figure 10) Same liver as Figure 9 stained/or normal liver cell cyrokeratins. Figure 12) Cenrrilobular scar shown in Figure J J. It is possible ro see rhar The balloon cells fail to swin positively like the adjacent normal hepaw­ the liver cells /irs1 develop increased cytokeratin around the edge of the cell cytes and 1he Mallory bodies (arroU1S) which are intensely seamed. This (open arrow). These liver cells seem ro become progressively smaller and failure to scain che cycof,lasm with antibodies to liver cell cytokeratin is express cyrokeratin throughout 1he cell. They 1hen form small nests (solid typical of cells which contain Mallory bodies. 1mmunoperoxidase x 330 arrows) which resemble bile ductules (bile duccular meraplasia). lmmuno­ peroxidase x 330

The polymorphonuclear leukocyte in· bodies were identified in 90% of the speci­ alcoholics at autopsy established a rela­ filtrate around hepatocytes that contain mens in both groups. Mallory bodies were tionship between the severity ofs ceatosis, Mallory bodies (satellitosis) (52) is miss· very numerous particularly in the alcoho­ Mallory bodies, fibrosis and the degree ing in fatty hepatitis, although there are lic patients (P<0.05). lntra-acinar inflam­ ofobesity in both groups (21). The preva­ exceptions (3, 7). mation (predominantly neutrophilic) lence of Mallory bodies and fibrosis was The pathologic changes of fatty hepa­ was more prominent in the alcoholics higher in type ll diabetes. ln alcoholic titis have been compared in detail with (P< 0.005). Centrilobular pericellular patients who were markedly obese, there those of alcoholic hepatitis in a study re­ fibrosis or cirrhosis was seen in both was a higher prevalence of Mallory bod­ ported by Diehl et al (7). They observed groups, but severe fibrosis or cirrhosis ies compared to nonobese alcoholics no qualitative differences in histology be­ was present more often in the alcoholic (68 versus 38%, P<0.001). tween two groups of patients (39 non­ group (63%) compared to the nonalco­ The frequency of fatty liver in obesity alcoholic and 68 alcoholic hepatitis). holic group (38%). Likewise, the clinical was 48% in a series of 50 patients hospi­ There were some differences in the aver­ stigmata of portal hypertension were talized for weight reduction ( 13). Fatty age severity of some of the features. found more often with marked fibrosis hepatitis was diagnosed in 26% of non­ Micro- and macrovesicular fat were more or cirrhosis in the alcoholic group. alcoholics. Fatty fibrosis was found in 8% often moderate to marked in severi ty in Another study of hepatic histology in­ and cirrhosis in 8%, but in these patients the nonalcoholics (P< 0.05). Mallory volving 320 alcoholics and 348 non- alcohol abuse was a factor. Protein defi-

192 CAN J GASTROENTEROL VOL 3 No 5 N0VEMB1:.Rl0tCEM6ER 1989 Fatty hepatitis

ciency correlated with steatosis, inflam­ in which the liver morphology of a com­ countered but were apparently periportal mation and fibrosis. Diabetes mellitus bination of 1515 morbidly obese patients in location. correlated with severe steatosis. Alcohol was summarized (34 ), the liver was nor­ Peters (29) reported serious hepatic intake correlated with severe steatosis, mal in 12% of the cases. Fatty change disease in I to 17% of patients who under­ fatty hepatitis, fatty fibrosis and fatty cir­ was the most frequent abnormality found went jejunoileal bypass. Most common rhosis in this series. (80%). Portal inflammation was seen in was acute hepatic fa ilure two-and-one­ Diabetes mellitus is sometimes com­ 33% and fibrosis, mainly portal or peri­ half to nine months after the bypass. This plicated by simple fatty liver and cirrho­ portal, was seen in 29%, while cirrhosis failure was associated with a large fatty sis. In a series of 62 patients with type II was seen in 3%. Mallory bodies were liver along with fibrosis and hepatoce l­ diabetes, I 7 had fatty hepatitis (3). The rarely found. A few reports describe cen­ lular necrosis. The fibrosis was both cen­ histology in nine biopsies studied system­ tral or pericellular fibrosis in nonalco­ tral and portal. The perivcnular hepato­ atically revealed fe atures of alcoholic holic patients (34 ). The same authors cytes were hydropic and surrounded by hepatitis. Fatty change and liver cell bal­ (53) studied the livers of 61 cases of mor­ collagen. Mallory bodies were found in looning were constant features. Neutro­ bid obesity (average 82% overweight). these swollen hepatocytes while neutro­ phils in association with Mallory bodies The patients' alcohol intake did not ex­ phils were sparse. The lesion was indis­ were found in five; mononuclear infil­ ceed a moderate amount and only one tinguishable from alcoholic hepatitis. A trate in four; acidophil bodies in five; patient was diabetic. Seven percent of simil ar lesion was encountered after fat granulomas in seven; pericellular fi­ the biopsies showed a normal liver. Fatty gastroplasty (32). Some of the patients brosis was mild. In six cases, there was change was the most common abnormal­ continued to drink alcohol while others bridging fibrosis between the portal and ity (85%). The degree of fatty change cor­ did not, however, the histological changes central ve in, but distortion of the lobu­ related with the presence of lipogran­ were id entical. This indicates that cau­ lar architecture was absent or slight. Cir­ uloma (54%), focal necrosis (33%) and tion must be exercised regarding valid­ rhosis was not encountered, although Kupffercell proliferation (49%). No Mal­ ity ofa negative history of alcohol abuse progression was discovered in one case lory bodies or cirrhosis were observed as the patien t may not be candid about on a subsequent biopsy. and alcoholic hepatitis was absent. These drinking habits. In a series of 29 obese patients with­ authors took the view that when Mallory Fatality in patients who underwent out alcohol abuse, fatty li ver was seen in bodies, fibrosis or cirrhosis arc encoun­ small bowel bypass su rgery was common. seven, fatty hepatitis in eight, fatty fibro­ tered in obese patients, it is likely that The second least common sequela to by­ sis in seven and fatty cirrhosis in seven the patient is abusing alcohol (3 4,53). pass was the insidious development of (6). Seven cases had Mallory bodies and When patients with morbid obesity are cirrhosis, discovered either accidendy or I 2 had central or perisi n usoidal fi bro­ treated with a small bowel bypass or after the development of ascites. Another sis. There was no correlation between gastroplasty, the liver morphology may important but uncommon complication the severity of liver damage and the de­ worsen, implying that malnutrition plays was the manifestation of tenuous hepatic gree of fatty change. Polymorphonuclear a role in the pathogenesis of fatty hepa­ reserve. In this condition, liver disease leukocytes were numerous in all of the titis (29 .30.32.35 ). This idea is strength­ developed rather suddenly as a conse­ patients with fatty hepatitis. In these pa­ ened by the observation that a massive quence of some o ther systemic insult, tients, diabetes and lipoprotein abnor­ small bowel resection can induce fatty similar to alcoholic liver disease. malities (mostly type IV) were common. hepatitis (37.38) although starvation ther­ The progression of liver disease in 34 In a second series of 20 cases of nonalco­ apy alone had no injurious effect on the patients who underwent jejunoileal by­ holic steatohepatitis (5), 90°/o were obese. liver of the morbidly obese (30); a mere pass for morbid obesity was studied via Moderate to severe macrovesicular fatty reduction in fat stores in the liver was follow-up biopsy five to nine months change and lobular inflammation were observed. Liver biopsies in 88 patients postoperatively. Twelve of 15 patients present in all cases as these were the cri­ taken one to two years after jejunoileal with no or slight steatosis progressed to teria for case selection. Fat was distri­ bypass showed that an increased num­ either moderate to severe steatosis, steato­ buted centrally or diffusely and fat cysts ber of patients had increased fat stores hepatitis or steatofibrosis. The six pa­ were always present. The inflammatory (30). However, portal fibrosis, inflamma­ tients wi th initial moderate to severe cells were mixed lymphocytes, mononu­ tion or biliary proliferation did not pre­ stcatosis all progressed co steatohepatitis clear cells and neutrophils located either dict progression to alcoholic hepatitis. or steatofibrosis, and one developed sep­ centrilobularly or in areas of focal ne­ O nly central or pericellular fibrosis pre­ ta! fibrosis. All of the patients with steato­ crosis. Mallory bodies located in zone 3 dicted progression to alcoholic hepati­ hepatitis (steatosis and a lobular lympho­ were present in 70%, Councilman bod­ tis. In 6.8%, central fibrosis progressed cytic inflammation) progressed to steato­ ies in 25%, perisinusoidal centrilobular to form central-portal bridging fibrosis. fibrosis. Of the five patients with steato­ or septa! fibrosis in 70% and cirrhosis in One half of these patients developed re­ fibrosis, three developed bridging fibro­ [5%. generative cirrhotic nodules. Only one sis. Mallory bodies appeared postoper­ The histopathology of the liver in mor­ case developed in to a morphologic pic­ atively in 11 patients (32%), all of whom bid obesity has been reported by numer­ ture resembling alcoholic hepatitis. Mal­ had had either severe steatosis, steato­ ous investigators. In a review of 4 l articles lory bodies were more frequently en- hepatitis or stcatofibrosis preoperatively.

CANJ GAS'fROEN TEROI Vo1 3 No 5 N OVEMIIER/DECEMllER 1989 193 FRENCH eta/

TABLE2 PATHOGENESIS Clinical features of nonalcoholic fatty hepatitis A variety of theo ries regarding the Number of patients having clinical pathogenesis of fatty hepatitis have been Total number of cases feature or medication(%) proposed, especially as it relates to pro­ Diabetes 88 44(50) gression after jejunoileal bypass ther­ Obesity 88 75(85) apy fo r morbid obesity. Protein calorie Hepatomegoly 49 31 (63) Cholecystectomy 49 14(29) malnutrition has been established four Portal hypertension 59 5( 8) months after bypass, but this reverts to­ Medications ward normal 12 to 36 months postoper­ Cardiac/hypertension 68 21 (31) atively (62), probably because of intest­ Diuretic 68 19(28) inal adaptation postoperatively ( 63 ). Hypoglycemics 68 17 (25) Thyroid 39 6(15) Other factors which may contribute to Estrogens 39 5(13) malnutrition after bypass are bacterial Corticosteroids 20 3(15) overgrowth in the blind loop and changes Doto ore derived from three reports(5-7t most senes specit,collyexctuded pot,ents with history of blood in the metabolism of bile acid (63,64). tronsfus,on. introvenous drug abuse. pos1t1ve hepatitis Bspecif1c ontlgen orontim,tochondriot ontibod­ Supporting this theory, Drenick et al ies: one senes(6J specificolly selected for obese potients The overoge pot,ent oge wos 50 yeors with 21 (24":,J motes ond 67(76'~,) temoles (65) reported that metronidazole, a d rug which suppresses the intestinal growth of anaerobes, prevented the progression TABLE 3 of liver disease after bypass. Laboratory features of nonalcoholic fatty hepatitis _____ Vy berg et al (66) ci te evidence that Total number of coses Number of abnormal values(%) bacteria in the blind loop produce acet­ AST/ ALT 88 48(55) aldehyde and suggest that since acetal­ Alkaline phosphatase 49 20(41) Bilirubin 59 11 (19) dehyde is also implicated in the patho­ Hyperllpldemo 49 19(39) genesis of alcohol liver d isease, it may Dote ore derived from three reports (5-7) AST Asportote ominotronsferose. ALT Alonine ominotronsferose also be the common denominator in the pathogenesis of both nonalcoholic faery hepatitis and alcoholic liver disease. They Only the patients with postoperative CLINICAL FEATURES argue that since both diseases are simi­ steatofibrosis and Mallory bodies devel­ Tables 2 and 3 summarize th.e clinical lar in their clinical and pathologic fea­ oped bridging fibrosis (six patients) or and laboratory features of patients with tures they may have a common etiology cirrhosis (three patients). The progres­ fatty hepatitis derived from three studies and that the common factor could be sion of liver disease resembled alcoholic (5-7). The patients are typically obese, acetaldehyde-related. Ethanol produc­ liver disease, ie, increasing steatosis, lob­ female. in their late 40s to early 50s, and tion through fermen tation could be the ular lymphocytic inflammation, pericel­ taking medication for, or having a vari­ source of acetaldehyde production; how­ lular fibrosis, Mallory bodies and de­ ety of, intercurrent conditions. The fore­ ever, alcohol is detected in th.e blood of ranged architecture, suggesting that the most of these conditions is diabetes; to a only one-third of patients followi ng by­ two diseases have the same mechanisms lesser extent, heart disease and hyper­ pass and only in low concentrations (67). (35). tension are also present. Most of the pa­ Hepatic free fatty acids increase in the One of the features of fatty liver in tients are asymptomatic with respect to liver in alcoholic liver disease and in mor­ alcoholics and morbidly obese patients liver disease, despite the fact that 15 to bid obesity (68). Similar changes occur is megamitochondria seen by light mi­ 38% have cirrhosis or severe fibrosis. in liver mitochondria in alloxan diabe­ croscopy or electron microscopy. The Jaundice, ascites, esophageal varices, en­ tes in rats. Thus, it is possible that the megamitochondria, which are elli ptical cephalopathy and hcpatorenal syndrome common factor responsible fo r the pro­ or cigar-shaped due to intramitochond­ occurred alone or in combination in only gression of fatty liver to fatty hepatitis ria l filaments (54), are located in peri­ a few patients ( 12%). The indications for and alcoholic hepatitis may be increased portal hepatocytes. These are nonspe­ liver biopsy in almost all of the patients free fatty acids. Fatty acids change the cific, but the globular mitochondria lo­ were hepatomegaly, abnormal liver func­ surface tension of membranes and act cated in centrilobular hepatocytes are a tion tests, or both. The latter had mostly as detergents to lyse membranes (69,70). useful marker of both alcoholic liver dis­ mild to moderate elevations of asparcate However. because free fatty acids in­ ease (55-59) and nonalcoholic fatty liver aminotransferase, alanine aminotrans­ crease in proportion to the severity of (60,61 ). There is no prognostic value in ferase, bilirubin or alkaline phosphatase. the disease process, it is difficult to de­ the presence of megamitochondna in The computerized axial tomography scan termine which is primary, the disease alcoholic liver disease (59); the prognostic and ultrasound of the liver may have a process or the increase in fatty acids. implication of the presence of mega mito­ heterogeneous appearance (Figures 13, Wanless et al (21) have reported evi­ chondria in fatty hepatitis in nonalco­ 14) due to the unven distribution of the dence that supports the hypothesis that holics is as yet unknown. increased fat stores (Figures 1,3 ). the pathogenesis of fatty hepatitis of

194 CAN J CASTROENTFROL V Ol 3 No 5 N

Figure 13) Computenzed axial tomography scan showing heterogeneity Figure 14) Ultrasound from the liver shown in Figures I to 3 Note the m the liver shown m Figures I to 3 Note that the density of the lwer is typical bright echo of/atty liver (arrow) focally decreased relative to the blood vessels ( arrow) morbid obesity with type ll diabetes, soned that insulin inhibited fatty acid II diabetes and morbid obesity treated and fatty hepatitis following jejunoileal oxidation in the liver, and that it caused with bypass surgery, but not in morbid bypass surgery for morbid o besity is the faery acids to be prefere~tially esterified obesity controlled by diet reduction ther­ same, ie, increased free fatty acids in and stored as triglycerides, resulting in a apy. This may explain why fatcy hepati­ the liver. They observed steatosis and fatty liver. Free fatcy acids thus accumu­ tis progresses after bypass surgery but steatonecrosis with Mallory bodies in the lated, causing membrane injury, swell­ reverts to a normal liver when diet calo­ subcapsular liver in patients on perito­ ing of hepatocytes and steatonecrosis rie restriction without surgery is success­ neal dialvsis with cype I diabetes receiv­ Generally, when insulin levels are ele­ ful in causing weight loss (30). It is likely ing intraperitoneal insulin on a regular vated enough to block fatty acid oxida­ that a similar mechanism is involved in basis. They suggested that this localized tion but not high enough to block free alcoholic liver disease with obesity, since fatty change was due to insulin and glu­ fatty acid mobilization, farcy liver and ne­ the metabolism of alcohol blocks fatcy cose diffusing from the peritoneum into crosis may result. Such a clinical situa­ acid oxidation by liver mitochondria the liver tissue. From this idea they rea- tion exists in obesity associated with cype (71)

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65. Drenick EJ, Fisler J, Johnson D Hepatic ethanol production and h,-pauc disease Lab lnvesi 197 1.25,427->4. stearos1s after mtcstinal hypass following 1e1unoileal bypas,, for morbid 70 French SW, TodoroffT. Norum ML. Prevenuon and reversal by mctronida obesity AmJ Clin Nurr 1975.28: 1277-83 Ihrig TJ Effect nf lipid hydrolysis zole, 1rrcsrect1vc of protcm-calmic 68. Mavrclis PG, Ammon HV, GleystcenJJ, and phosphate swellmg on the structural malnutntion Gastmcntcrology 1982, Komorowski RA. CharafUK. Hepatic and functional mtegnty of mtto­ 82 535-48 frel' forty acids in alcoholic liver disease chondna Exp Mol Pathol 1972. 66. Vyherg M. Ravn V, Andersen B Pattl'rn and morbid obestty Hepmoloi.:y 16:16- 12. of progression 111 liver mJury following 1983.3 226 >I. 71 Cedarbaum Al, Lieber CS. Beattle DS. JCJunoileal byra,s for morbid obcstty. 69 French SW. Norum ML, lhng TJ. Rubm E. Effect of chronic ethanol Liver 1987,7:271-6 TodoroffT Effect of phospholipi

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