474A AASLD A B S T R A C T S HEPATOLOGY October 1995

1469 ARE ACUTE PHASE PROTEINS A NEW BIOLOGICAL MARKER OF HEPATOCELLULAR CARCINOMA IN CIRRHOTIC PATIENTS ? P Pernev*. MT Piva**. V Sieso*. P Fabbro-Perav*. F coste*. Y Le Bri~quir*. B Hanslik*. H Mion**, F Blanc*. *Service de M6decine Interne E, **Service de Biochimie B, H6pital Saint Eloi, Montpellier, France.

Biological markers, mainly a-fetopmtein (AFP) and des-'/-carboxylic prothrombin, have been evaluated for diagnosis of hepatocellular carcinoma (HCC) in cirrhotic patiems (pts), but the sensitivity of these markers remains insufficient. The pattern of acute phase proteins (APP) has been shown to change in different liver diseases (Meliconl et al, Liver 1988;8:65-74). The aim of our study was to assess if different patterns of APP could help for the diagnosis of HCC in cirrhotic pts. Methods : Sixty-seven cirrhotic pts without HCC (group 1), and 45 cirrhotic pts with HCC (group 2) were included in the study. The diagnosis of cirrhosis was performed by histologic examination. The diagnosis of HCC was proved by histologie examination or by association of abdominal US scanning and AFP minimal level of 500 ng/ml. In group 1, no HCC was detected during a 8 months follow-up after inclusion. Eleven APP (i.e; IgA; IgM; IgG; C3; orosomucoid (ORO); haptoglobin (HAP); cemloplasmin (CER); C reactive protein; transferin; albumin (ALB); prealbumin) have been measured in serum of the included pts. Results : According to the univariate analysis, significant difference between the 2 groups has been shown for 6 of the 11 measured proteins (data expressed as group 1 vs group 2, mean in g/L): lgM: 2.39 vs 1.76 (p<0.02), C3:0.90 vs 1.10 (t3<0.005), ORO: 0.44 vs 0.62 (p<0.005), HPT: 0.58 vs 0.97 (p<0.01), CER: 0.36 vs 0.42 (p<0.02), ALB: 30.9 vs 28.3 (p=0.05). In the multivariate analysis performed by logistic regression, independent risk factors for HCC were: C3 (p<0.02), ALB (p<0.01), IgM (p<0.05). Conclusion : Our results indicate that APP may be useful for diagnosis of HCC in cirrhotic pts. In this study, APP levels may correctly classify 75 % of the pts (HCC present or not). The interest of APP compared to other HCC diagnostic tests is presently on evaluation. Moreover, the usefulness of APP for prospective screening for HCC in cirrhotic pts must be investigate.

1470 VALIDATION OF A SCORING SYSTEM FOR THE DIAGNOSIS OF AUTOIMMUNE HEPATITIS (AIH) IN CHILDREN. ~M Peters and V Tolia. Children's Hospital of Michigan and Wayne State University School of Medicine, Detroit, MI.

The International AIH Group (IAIHG) has formulated a scoring system to distinguish AIH from other chronic liver diseases for use in adults (Hepatology, 18:998-1005,1993). We applied the IAIHG's scoring systemfor differentiating AIH from other causes of chronic liver disease in a pediatric population by a retrospective chart analysis on 26 patients. There were 13 males and 13 females, ranging in age at time of presentation from 5 days to 194 months (mean 98.46 months). Follow-up ranged from 6 to 102 months (mean 49.96 months). One or more liver biopsies were performed on 23 patients. Globulins, ANA, SMA, AMA and LKM-I were performed, but HLA typing was not done. Patients in whom Hepatitis A antibody testing was absent received a "+2" score if serological studies for Hepatitis B and C were both negativ e.

Initial clinical impressions of the patients were: cryptogenic Chronic Active Hepatitis- 9; "classical" AIH- 6; alpha-l-antitrypsin deficiency- 6; and miscellaneous- 5. Utilizing this modified IAIHG scoring, 2 of 6 children originally with "classical" AIH fell into the "probable" category. 3/9 patients with"cryptogenic" CAHsoored in the "probable" category for AIH. The rest of the group failed to achieve a significant score.

We conclude that the modified IAIHG scoring system may be a valid and helpful tool for the management of AIH in children with an equivocal diagnosis. A clearer under- standing of therapeutic implications for patients in the "probable" category will enhance its usefulness for clinicians providing care to pedia£ric patients with liver disease.

1471 EXPRESSION OF CYPIA1 AND CYPIA2 IN THE YELLOW PHOSPHOROUS INDUCED SWINE MODEL OF HEPATIC FIBROSIS AND THE BILE DUCT LIGATED RAT. T.C. Peterson. D.K. Chen and C.H. Cheung. Depts. of Medicine and Pharmacology. Dalhousie Univ., Halifax, N.S., Canada.

Recent studies suggest that cytochrome P-450 CYP1A family gone expression is altered in liver disease. In this study expression of CYP1AI and CYP1A2 was compared in two animal models of liver disease. Hepatic mRNA was isolated from a chronic swine model of hepatic fibrosis following 12 weeks of yellow phosphorous treatment and compared to controls. Hepatic mRNA was also isolated from the bile duct ligated rat model of liver disease following 4 wks of ligation and compared to sham-operated controls. CYP1A1 and CYP1A2 were analysed in Northern blots of mRNA from the two animal models using specific CYP1A1 and CYPIA2 probes (ATCC). Hepatic CYP1A1 mRNA (m.w. 2619) was expressed equally well in bile duct ligated and sham operated rats. Hepatic CYP1A1 mRNA was low or non- detectable in control pigs and appeared to be induced in fibrotic pigs. Hepatic CYP1A1 was expressed equally well in both normal and fibrotic pigs. These results suggest that expression of the CYP1A1 and CYP1A2 is different in the two animal models of hepatic fibrosis and unlike the human CYP1A (particularly CYP1A2) which is down regulated with liver disease, the CYPIA family is not affected in the bile duct ligated rat model compared to sham operated controls and CYP1A1 may be upregulated in the swine model of hepatic fibrosis compared to controls. (supported by Medical Research Council of Canada).

1472 FIBROPROLIFERATION IN SWINE AND RAT MODELS: EFFECT OF PENTOXIFYLLINE. T.C. Peterson and M. Neumeister. Depts of Medicine and Pharmacology. Dalhousie Univ. Halifax, N.S., Canada.

Fibroproliferation was studied in the yellow phosphorus induced swine model and bile duct ligated rat model of hepatic fibrosis. Fibroproliferation was assessed as uptake of 3H-thymidine into fibroblasts incubated with monocyte conditioned medium obtained from monocytes of pigs treated with yellow phosphorus or bile duct ligated rats and compared to controls. Fibrosis was assessed by collagen content of liver sections stained with Sirius red Fast green and in yellow phosphorus treated animals was significantly elevated (40± 2.7, n=15) compared to mineral oil treated controls (23 -+ 1.2, n=12). Collagen content of bile duct ligated rat model liver sections was elevated (31.2 -+ 1.6, n=6) compared to sham operated controls (21.6 -+ 0.7, n=6). Fibroproliferative factors were produced during development of fibrosis in the swine model. In contrast, no difference was observed in the production of fibroproliferative factors in the bile duct ligated rats compared to sham Operated controls. Pentoxifylline treatment of the swine model of hepatic fibrosis resulted in a marked improvement in liver function tests and in fibrosis as assessed by collagen content of liver sections and reduced fibroprnliferation in animals receiving yellow phosphorus treatment. This is in contrast to the bile duct ligated rat model where pentoxifylline treatment did not affect liver function tests, fibrosis or fibroproliferative activity of MCM obtained from these animals. These results suggest that fibroproliferation and increased synthesis of collagen are key events in the yellow phosphorus induced pig model of hepatic fibrosis and that pentoxifylline inhibits fibroproliferation and collagen synthesis. This is in contrast to the bile duct ligated rat model where fibroproliferation does not appear to be a key event in fibrosis and where pentoxifylline treatment does not alter fibroproliferative activity nor alter the course of fibrosis. (supported by the Medical Research Council of Canada).