April 1995 AASLD A l 1 4 9

• HEPATOCELLULAR CARCINOMA IN PRIMARY BILIARY CIRRHOSIS: AN ITALIAN EXPERIENCE. M. Podda, E. Bertolini, P. Invernizzi, P.M. Battezzati, G. DeValle, M. Camisasca, A. Crosignani, *A. Sangiovanni, iV[. Zuin and *M. Colombo. Institute of Internal Medicine, School of Medicine Ospedale San Paolo, and *Institute of Internal Medicine I, University of Milan, Italy.

High incidence rates of Hepatocellular Carcinoma (HCC) have been reported in patients with liver cirrhosis, especially of viral etiology. On the basis of the few available data, HCC development has been considered to be a rare event in Primary Biliary Cirrhosis (PBC). To address this issue, starting from 1983 serial US scans and alpba-fetoprotein determinations at 6- month intervals were performed in all patients with PBC who were on regular follow up at our center. Patients showing occurrence of focal lesions underwent US-guided fine-needle biopsy. Since 1983, we enrolled 272 PBC patients (245 female; median age, 55 yrs; 15% anti-HCV +re; none HBsAg +ve or treated with immunosuppressant drugs). No HCC was detected at baseline examination. During a median follow-up of 47 mos, focal lesions consistent with HCC were found in 6 cases (4 females). HCC was histologically confirmed in 5 patients and, in one patient who had a severe impairment of haemostasis, HCC was diagnosed on the basis of a US pattern of invasive growth. All patients who developed HCC had liver cirrhosis and unifocal lesions. Of the patients who underwent liver biopsy, all had well differentiated, trabecular type HCC. Incidence of HCC was 0.5 cases per 100 patient year (0.4 and 1.9 in female and in male patients). Liver cirrhosis was documented at presentation or during follow-up in 167 patients (146 females; median age, 58 yrs) from the overall PBC series. Incidence of HCC in the cirrhotic patients (median follow up, 39 mos) was compared with that of a control group of 417 Italian patients (132 females) with cirrhosis of different origin (mainly HBV- and HCV-related). In PBC, incidence of HCC was 1 ease per I00 patient year (0.8 and 2.6 in female and in male patients), compared with 2.1 cases per 100 patient year (1.2 and 2.6 in female and in male patients) in the control group. Anti-HCV was positive in 4 of the 6 patients with PBC and HCC whose sera were tested by EtA2 or EIA3. In the 3 patients (2 EIA positive) with serum and liver tissue available for PCR analysis, serum and liver HCV RNA were detected in 1 and in all 3 cases, respectively. We conclude that the overall incidence of HCC in Italian patients with PBC who developed cirrhosis is lower than in patients with cirrhosis of different origin. The characteristic female preponderance among PBC patients mainly accounts for this difference. HCV infection may play a role in the development of HCC in PBC, probably by accelerating progression of the disease and/or through the addition of another mechanism of liver injury.

DIRECTION OF PORTAL VENOUS BLOOD FLOW AND SENSORY EVOKED POTENTIALS IN CIRRHOTICS WITH DISTAL SPLENORENAL SHUNT. B. Podesser, P. Moeschl, T. Payrits, B. Schneider, V. Metz, W. Yeganefar, A. Puespoek, E. Wolner, J. Miholic. Departements of Surgery, Internal Medicine, and Radiology, University of Vienna, AIIgemeines Krankenhaus, Vienna, Ausria Introduction. - Loss of selectivity of "selective" splenorenal shunt may occur in patients following elective distal splenorenal shunting for variceal hemorrhage. To assess the impact of portal venous blood flow direction on the risk of hepatic encephalopathy 15 patients were studied after a mean interval of 58 (8 - 187) months following surgery. Patients. - Mean age was 59 (35 - 75 ) years, and the male/female ratio was 2.0. The direction of portal venous blood flow was assessed using duplex sonography. As a measure of encephalopathy the long latency sensory evoked potentials (N 70 potentials) were measured. Results. - The N 70 - potentials were 71_+ 9 ms in normal controls. The N 70 potentials were significantly longer in cases with hepatofu@al portal venous blood flow. Direction of flow n interval N 70-potential

(months) (ms) Hepatopetal 9 56_+18 81+_2 Hepatofugal 6 4 5 _ + 2 8 112_+12* * p< 0.002 Conclusion. - It is concluded that abnormal hepatofugal portal blood flow is associated with prolonged sensory evoked potentials in cirrhotics with splenorenal shunts. There may be a causal relationship between direction of blood flow and encephalopathy in these patients.

• THE INHIBITORY EFFET OF BILE ACIDS ON INTERFERON-INDUCED

LYMPHOCYTE 2',5' OLIGO ADENYLATE SYNTHETASE (2'5' OAS) ACTIVITY IS NOT MEDIATED BY AN OXYDATIVE STRESS. podevin P*, Blanc MC**, Vaubourdolle M**, Bonnefis MT*, Veyrunes C*, et Poupon R***. INSERM U402", Laboratoire de biochimie A, Pr Giboudeau**,Unit~ d'B~patogastrcent~rologie***, H6pital Saint- Antoine, 75012 Paris, France.

We have previously reported an inhibitory effect of cholestasis and bile acids on interferon-induced lymphocyte 2'5' OAS activity(* l . Cholestasis and bile acids are known to induce an oxydative stress in hepatocytes; such an effect could be responsible for the inhibitory effect of bile acids on lymphocyte

interferon-induced 2'5' OAS activity. The aim of this study was to evaluate : (a) the effect of bile acids in vitro, on lyn~hocyte glutathione store and malonaldehyde (MDA) production;(b) the ability of various antioxydants agents N-Acetyl-cysteine NAC(500pM), superoxyde dimnutaee SOD(100U/mI), catalase CATII00U/ ml) to prevent the inhibitory effect of bile acids on interferon- induced 2'5' OAS activity.

Fresh human lyr~phocytes isolated on ficoll hypaque gradients were incubated 24h in complete medium in the presence of bile acids ICDCA, UDCA, and their conjugates) (0-200~M); or bile acids and ~00u/ml human recc~binant ~2b interferon ; or bile acids , interferon and the antioxydants agents. 2'5'OAS activity was measured in cell extracts using a radioenzymatic assay. Intracellular glutathione store and MDA production in the medium were measured by a colorimetric method.

In basal conditions, no sign/ficant difference in lymphocyte glutathione store and MDA production in the supernatants were observed. None of the antioxydant agents tested was able to prevent the inhibitory effect of bile acids on interferon-induced 2'5' OAS activity.

These results clearly show that the inhibitory effect of bile acids on interferon-induced 2'5' OAS activity is not related to an oxydative stress.

(*) Podevin et al, Gastroenterology in press

• ABSTINENCE FROM ALCOHOL DOES NOT AFFECT HCV REPLICATION. J. Poniaehik L.J. Jeffers, M. Bartholomew, L.A. Ocur, D. Bemstein, M. de Medina, H. O'Sullivan, E.R. Schiff. Div. of Hepatology, University of Miami School of Medicine and VA Medical Center, Miami, FL.

A high prevalence of antibodies to the hepatitis C virus (HCV) in patients with alcoholic liver disease has been documented. In addition, it has been reported that alcoholics with concomitant HCV infection tend to have more severe liver disease and it has been suggested that this may be due to an alcohol-induced augmentation of hepatitis C viral replication. If alcohol increases the level of HCV viremia, HCV-RNA levels should decrease with abstinence from alcohol. Objective: To determine the change in the levels of HCV-RNA in alcoholic pts with HCV infection aider they have become abstinent. Patients and Methods: Eight male alcoholic patients with a mean age of 43 years were admitted to a detoxification unit after actively "drinking (> 80 g alcohol/day). All pts were HCV-RNA positive. Pts who were HBsAg (+), HIV (+), or on immunosuppressive therapy were excluded. Clinical and laboratory evaluations (AST, ALT, CBC, prothrombin time and albumin) were performed. None of the patients had clinical or laboratory evidence of acute alcoholic hepatitis. Pts were followed until week 6 and HCV-RNA was quantitated by bDNA amplification (Chiton).

HCV-RNA (HCV Eq/mL x 105"1 Results: Pts Baseline Wk 2 Wk 4 Wk 6 I 170 ND 77 127 2 53 33 24 ND 3 32 ND 35 ND 4 11 < 3.5 16 < 3.5 5 39 ND 11 46 6 • 33 ND 88 76 7 < 3.5 I0 < 3.5 ND 8 13 8 13 ND ND = Not done. 7/8 (87%) pts did not have sustained decrease of HCV-RNA after abstinence. Conclusions: I) There is no evidence that abstinence from alcohol decreases HCV viremia. 2) Longer abstinence may be necessary to reduce viremia.