April 1 9 9 5 AASLD A 1 0 9 1

ASSOCIATION OF RESPONSE TO INTERFERON WITH HEPATIC IRON CONTENT IN PATIENTS WITH HEPATITIS C : RELATIONSHIP TO GENOTYPES OF HCV N.Izumi. T.Nouchi*. N.Enomoto**. Y.Tanaka**. M,Idchihara, T.MurakamLK.Ono. O.Noouehi. S.Mivake. C.Sato***

Dept. of Int. Med., Musashino Red-Cross Hospital, *Dept. of Int. Med., Koritsu Shouwa Hospital, **2nd Dept. of Int. Med, ***Dept. of Health Science, Tokyo Meal. & Dent. Univ., Tokyo, Japan

Response to interferon therapy has been shown to be influneced by hepatic iron content in chronic viral hepatitis. However, in chronic hepatitis C, viral genotypes and serum HCVRNA levels have been reported to be closely associated with the response rate to interferon. The aim of the present study is to clarify the relationship of the iron content of the liver and response to interferon in chronic hepatitis C in each genotype. 65 patients with hepalits C were included in this study. The iron content of the liver was measured by atomic absorption after homogenizing the biopsied materials. Genotype of HCV was determined by mixed primer method, and serum HCVRNA levels were measured by competitive PCR and branched DNA probe assay. 10MU of recombinant alpha lib interferon was administered to each patinet every day for 2 weeks followed by 3 times per week for 22 weeks. Response to interferon was divided into two groups, i.e., responder: normal serum ALT during 6 months after finishing interferon therapy, non-responder: elevated ALT during the same period. Hepatic iron content was significantly higher in patients with history of excess amount of alcohol (80g/day) than those without, and it was significantly decreased in female patients before menopose. When excluded the patinets having history of excess amount of alcohol and female patients before menopose, hepatic iron content was significantly higher in patients with genotype 2 than in those with genotype 3 and 4. There was no significant correlation in hepatic iron content and serum RCVRNA levels. In the group of the patients with genolype 2, the iron content of the liver in responder to interferon was significantly lower than in non-responder (429+99.7 vs 875+110.4 mcg/g live/'). Conclusion: Response to interferon is influenced by hepatic iron content in chronic hepatitis C, even after dividing the patients with genotype of HCV.

• NATURAL HISTORY AND MORBIDITY OF CHRONIC HEPATITIS C (CHC) IN A TERTIARY REFERRAL PRACTICE. H. Jamal, R. Perrillo, F. Regenstein, Ochsner Medical Institutions, New Orleans, LA. BACKGROUND: Controversy exists regarding the frequency of serious liver disease and morbidity attendant to chronic hepatitis C virus (HCV) infection. A recently published trial, including only patients with transfusion-related HCV, suggests that CHC does not contribute to an excess of liver-related mortality when compared to transfused controls (N Engl J Med 327:1906, 1992). In an effort to assess the overall morbidity of CHC and to compare the presence of symptoms to disease duration, we reviewed our population of CHC patients in whom the approximate duration of disease could be determined. METHODS: We retrospectively reviewed the charts of 200 consecutively derived CHC patients (120 male, 80 female) for signs and symptoms of liver disease. All transplant referrals and 17 cases with incomplete information were excluded. In 155 patients (85%), the source of exposure (60% transfusion, 31% IVDU, 9% other) and approximate duration of disease could be ascertained. We related disease morbidity and liver biopsy results, when available, to duration from the time of exposure. RESULTS Histology Signs and Symptoms Dur in Mild Mod/Sev Circ. No Sx Fatigue Ascites/ Varices PSE Yrs* CAH(%) CAH(%) (%) (%) (%) edema(%) (%) (%) 1-10 5I 18 17 25 43 26 6 28 11-20 33 50 43 50 33 38 37 50 >20 15 31 39 25 23 34 56 21 N = 45 16 46 60 74 26 16 14 *Time from presumed exposure

Histologic changes were more severe and signs of advanced liver disease more frequent in patients with longer disease durations. Fatigue was the most common symptom (40%) but its presence did not appear to correlate with disease duration. Clinically evident depression occurred in 16% of our patients and may have contributed to the frequency of fatigue as a symptom. CONCLUSION: 1) Signs and symptoms of liver disease were frequent in CHC patients referred to our tertiary referral center, however, the presence of symptoms did not appear to correlate with disease duration. 2) Histologic changes tended to be more severe in patients with longer disease durations. 3) Depression was the most frequent co-existing illness in our population and represents an important co-morbidity in patients with CHC.

• IvIULTICEN'/NE TRIAL OF OCTREOTIDE VERSUS INJECTION SCLEROTHERAPY (IS) FOR ACUTE VARICEAL HAEMORRHAGE SA Jenkins ~, R Shields 1, R Sutton 1, AN Kingsnorth 1, M Davies z, E Elias z, AJ Turttbull 3, ~ Bassendine a, OFW JalTles 3, JP Ircdale '1, SK Vyas 4, MJP Arthur 4 Royal Liverpool University Hospital, Liverpool; Queen Elizabeth Hospital~ Birmingham, Freeman Hospital Newcastle-upon-Tyne; Southampton General Hospital Southampton

The role o f och'vofide in the management ofvariceal haemorrbage remains controversial. We conducted a mullicentre trial to assess the use of 50 ug/h intravenous octreotide for 4g h to control variceal haemorrhage. Consecutive patients with endosenpically confirmed variceal haemorrhage were randomised to either octreotide (n=73) or emergency IS (n=77). Overall control of bleeding was not signitioently different between octrvotida (85%) and IS (82%) over the 48 h trial period (rehtive risk of rebleedi.qg 0.g3; 95% (2I 0.38, 1.82). Oclrcolid¢ was as effective as IS irrespective of the severity of the liver disease, and in those actively bleeding at endoscopy. Mortality during the 4g h trial period was identical in the two groups, but more patients died in the octreotid¢ group during 60 days of follow-up, although this did not reach statistical sign/ficancc (relative risk of dying at 60 days 1.91; 95% CI 0.97, 3.78; p=0.06). The results of this study indicate that intravenous octreotide is as effective as IS in the control of acute variceal haemorrhage. Howev¢r, in view of the trend towards an increased 60 day mortality in the octreofide group, further trials are necessary to evaluate its safety in varieeal bleeding.

MORPHOMETRIC DEFINITION OF EPITHELIAL CELL HETEROGENEITY IN INTRA HEPATIC RATBILIARYTREE. A.M. Jezequel,C. Bassotti,L. Marucci and A. Benedetti. University of Ancona, Ancona, Italy. Morphological and functional heterogeneity of intrahepatic bile duct epithelial cells(BDC)has been shown in liver tissue and isola ted cholangiocytes(Hepatol,20,649,1994).Technique we devised to isolate intrahepatic bile ducts from rat liver allows to preserveh! sementmembraneandtightjunctions,maintaining,withrespectto solated BDC,polarity andmorphological features similar to arrange ment in situ.AIMof this study was to evaluate if(a)bile ducts,when isolated,maintain morphometricparameters similar to ducts in situ (b)cellularorganelles show heterogeneity in ducts of different si zeand (c)morphometricalfeaturespermitto distinguish different classes of bile ducts.METHODS:morphometric studies were conducted by point-counting on normal liver processed for light or electron mi croscopy.Data were also obtained from preparationsof biliarytree isolated from rat llver.Whole biliary tree was cut at different leve is to obtain bile ducts of different diameter.We evaluated:(a)diame ter of ducts,(b)number of lining eelle,(c)size and area of individu al cells,(d)nucleo/cytoplasmic (N/C)ratio,(e)voiume denslty(VD) of mit0chondria,endoplasmic reticulumandlysosomes.EESULTS:dia meter of intrahepatlc bile ducts ranged from 4 to i00 Dm and the area of lining cells ranged from 8 to i00 ~m2.A highly significant linear relationship existed between duct diameter and BDC area(r=0.78,p< 0.001)or number of lining cells(r=0.60,p<0.01).VDof mitochondria ranged from 8.13!3.2% of cytoplasmic volume in smallest ducts to 4.45±2.1%inlargest(NS).VDoflysosomeswasnotsignificantlychan ged in ducts of different size. In contrast,rough endoplasmicretic~ lumwas unconspicuous in smallest but increased significantly in largest ducts(p<0.01).Striking was the inverse relationship betw£ enN/C ratio and duct diameter(r=-0.60,p<O.O02).Allmorphometric data were equivalent if bile ducts were evaluated in situ orisola ted fragments. Taken together,these data allowed to classify bile ducts in 3 classes, Ji0,I0-50,~50 pm in dlameter.DISCUSSION:our d! tashowthat (a)isolated bile ducts maintain morphometricalchara! teristics similar to the tissue in situ,(b)a low grade of heteroge neity was evident for intracellular organelles in ducts of diffe- rent diameter and(c)diameter of ducts,number of lining cells and£ specially N/C ratio dndicate the origin of fragments examined where a study of functional heterogeneity is being considered.