HEPATOLOGY Vol . 22, N o . 4, P t . 2, 1995 A A S L D A B S T R A C T S 4 7 1 A

1 4 5 7 T H E EFFECT OF URSODEOXYCHOLIC ACID ( U D C A ) O N LIVER SERUM E N Z Y M E S IN H E M O D I A L Y S E D PATIENTS WITH CHRONIC C VIRAL INFECTION. Ouzan D(lk Chanas Mtlt. Baldini Etl l . Haffon P(2k Marmin Lf2L Brichetli A(lt. Salvadori dM(lk (1) Institut,Arnauit TZANCK -St Laurent du Var - (2) Alpha Bio - Marseille,

Ten to fourty five percent of french 'hemodialysed patient~ have~ anti HCV ;which are associated with HCV-RNA In. 85% Of them and with chroqic hepatitis in 95% despiste few liver enzymes abnormalities. This calls for treatment. A reduction in serum enzymes has been already observed by. admini~rating ursodeoxycholic to patients with chronic hepatitis. The aim of this pilot study was to access the tolerance and the efficacy of' UDCA in 25~ hemodialysedpatients anti HCV and HCV-RNA (Amplicor) positive with elevated liver enzymes : ALT ~ ! 4 patients, AST : 13 patients, GGT : 17 patients and APL : 4 patients. The'se patients (16 M, 9F) had been receiving hernodialysis for 1(}2 + 67 months. They received UDCA 500 mg/day (250 mg bid) the first week, then 75~ rag/day (250 mg tid) during Six months. The t01erance'was correct. Treatment was interrupted in one case because of digestive, side ef!ects. Serum enzymes before and during the fOllow-up are reported in the following tab~:

Mean Baseline 3 Months 6 Months

AST 44±24 37-+25 35±26 AL l 62-+67 39-+28 39-+38 APL 246±181 200-+124 218±128 GGT 134-+218 52±37 42-+27

UDC administration is follow by a significant reduction in AST, p<0,05; in ALT p<0,01 and in GGT p<0,001 at 3 an~ 6 months in hemodialysed anti HCV- RNApositive patients with a fair tolerance.

1458 THE INTEREST OF MEASURING PLASMA GST IN PATIENTS ON DIALYSIS, INFECTED WITH THE HEPATITIS C VIRUS (HCV). Ouzan Of 1 ), I<hiri H(2k Bal(;Ijni E l lk Fervn JM(2). Brichetti A{1). Halfon P(2t (1) Institut Amault Tzanck - St Laurent du Var (2) Alpha Bio - Marseille.

Alpha GST (ligandin) is a detoxifying enzyme which catalyses the nuclsophili¢ attack of glutathione on toxic hydrophiles. It is found in high concentrations in the cytosol el hepatocytes. When monitoring drug-induced or auto-immune hepatitis, the sensitivity and correlation with the histological picture are higher for plasma GST than for the transaminases. The aim of our study was to demonstrate the clinical value of the Enzyme Immune-Assay el, GST in a population of chronic renal dialysis patients, with or without HCV infection. In fact, in this population, infection with hepatitis C is characterised by normal or intermittantly increased levels of transaminases. 147 patients on dialysis were included in the study, anti-HCV (Elisa III Ortho) was present in 65 patients and HCV-RNA (Ampiicor Roche) was detected amongst 53 of these. A sample of heparin blood was obtained form fasting patients, in the absence of all treatment. The plasma was stored at -20 ° prior to the assay of ASAT, AI.~T and GST. (Elisa Hepkit Biotrin International, Dublin): The results are eummarised as follows :

Patients Normal Values % Cases with abnormal values

Diaiysed Dialysed Dialysed HCV -ve HCV +ve RNA +re

ALAT 13.1-+9.9 <30 14.2 6.3 7.5 ASAT 25.5+173 <30 3.5 34.9 39.6 GST(ng/ml) 3.7+6.9 <4 20.2 39.7 41.5 ALAT+ASAT 14.2 34,9 39.6 ALAT+GST 21.4 41.3 43.4 ASAT+GST 27.3 50.8 58.4

Elevated values o| GST are lound in 37% of HCV positive patients on dialysis, with normal ALAT levels. There is a significant correlation between the plasma concentration of GST, of ASAT and the presence of anti-HCV-RNA (p<0,01). Conc lus ion : The addition of the assay of GST ot the transarninases increases the sensitivity of the assay of ALT for the diagnostic el hepatitis C virus. GST could also be an interesting parameterin the evaluation of the efficacy of treatment of chronic hepatitis C in patients on renal dialysis.

1459 THE MITOCHONDRON IS THE KEY ORGANELLE FOR HEPATITIS B VIRUS INFECTION. K-H Paik. K Park. Y-I Yank. M Kim, B-W Lee. and S-H Lee. Paik-Inje Memorial Institute for Biomedical Science, Inje University, Pusan, Korea.

The hepatitis B virus (HBV) can be easily found in the organs with a large quantity of mitochondria, which include the liver, the pancrease, and the salivary gland. However, the mitochondria are often damaged in the conventional culture systems. Recently, we infected non-human animal livers with human HBV using Inje University physiologic culture system (Leema Phurmed, Seoul Korea). With the electron microscopic examination, a large quantity of the surface (HBs) antigens were identified in the organelles with double membrane as well as some s~ctures that resembles damaged crisme. Considering the fact that the mitechondrion has a separate translation system, we hypothesized that the antigens replicated in mitochondria are different from antigens replicated in nuclei. To confirm our hypothesis, the following investigations were undertaken. METHODS 1) The animal kidneys were infected with HBV, where there are far more mitochondria existed in the proximal tubles than in the distal tubles, thereafter, investigated with imumnohistochemislry. 2) The HBs and envelope (HBe) antigens were investigated using ELISA technique (Abbott), after sepemdng the mitechondrial fraction from the infected liver tissues by centrifugation. 3) The surface antigens in the vaccines obtained with recombinant DNA technology were compared to those from natural plasma using SDS-PAGE. RESULTS 1 ) The infected renal tissues were stained unevenly with the anti-ItBs antibody. The proximal tubles were stained far more than the distal tebles. With the electron microscopic examination, significantly higher concentration of mitochondria containing surface antigens were observed in the proximal tubules than distal tables. 2) The mitochondrial fraction contains at least 10 folds more HBs antigens than cytoplasmic, or nuclear fractions. Also, the titers of HBe antigen were positive, only in mitochondrial fraction. 3) The vaccines made from recombinant DNA technology showed only one band whereas the plasma-delived vaccines revealed a wide spectrum of the surface antigens. CONCLUSIONS 1) Conttary to the current cencept, HBV can be infected and replicate in any organ which contains substantial number of the michnndria. 2) HBV replicates usually in the mitochondria. Only a limited number of HBV replicate in the nuclei. 3) That is the reason why the natural antigens in the serum of patients with antigenemia are different from the antigens in the serum of transgenic mice. 4) The conventional recombinant DNA techology may not be a viable option for HBV vaccine. 5) The HBe antigens may be replicated in mitochnndria with core antigen genes, rather than the proteolytic self-cleavage of the core antigens. 6)The concept of the receptor for HBV should be reassessed.

1460 Etiology of Acute Sporadic Viral Hepatitis in Bahia-Brazil R.Parana; H.Cotrim; F.Silva; L.Lyra; M.L.Boenec-McCurtey; C.Trepo Hepatology Unit-Hospital of Bahia-Brazil;INSERM U.271 Lyon,France

The etlology of acute sporadic viral hepatitls(ASVH)shows regional variations.The data

available from Brazil are scarce,and make no reference to HEV, In order to study the

etiology of acute Non-A,Non-B hepatitis in Bahia,we studied 133 patients over 16 years

of age with ASHV at the University Hospital. Patients with high alcohol intake~previous

IVDU or Blood transfusion,and suspected drug related disease were excluded. Serological

analyses were carried out for antiHBe-lgM,antiV~L~-IgM,~IBsAg. Those testing negative for

all the above mentioned markers were tested for antiaCV(B-llj confirmed by RIBA Ill),

HCV-RNA(PCR),antiHEV-IgG,EBV,CMV. The patients who reported a history of blood trans-

fusion or intravenous drug use were excluded. A follow-up 6 months later was done for all

N~NB patients. Of the 133 patients,63(47.3%)~re positive for HAv~Bg(29.3%)for BBV and

none for HDV.

31(23.3%)were considered Non-A,Non-B. From these,5(16.1%)presented initially positive

serology for antiHCV,and 7(22.5%)seroconverted to antiHCV within 90 days of the follow-

-up,performing a total of 12(3B.7%)eases related to HCV, Five(16.1%)patients reacted to

antiHEV and none were positive for EBV and CMV. Fourteen(45.i%)tested negative for all

the viral markers studied and were considered as having an unknown agent.

Among the 12 patients BCV related,7(SB%)reported a possible hidden s~rce of

contamination: 4 were health worker; 2 reported dental treatment and i sexual promiscuity

After 6 months,6/12(50%)patients with hepatitis C maintained elevated ALT~all were HCV-

-RNA positive. Of the other 6 patients with normal ALT, 2 were BCV-RNA positive,

suggesting that 8/12(66%) became chronic carriers. A liver Biopsy was performed in 6 of

them,presenting: CAH and CPH in 4 and 2 patients,respectively.

Among the 14 patients with hepatitis of unknown agent only 2(14.2%)had elevated ALT after

6 months o~ follow-up,and both of the~ did not consent liver biopsy. We concluded that

even in the adult population the hepatitis A virus is the predominant etiological agent

of ASVH in Bahia. However~the hepatitis C virus seems to be an important agent in eases

of gon-A,Non-g hepatitls,with a high chronicity rate. Based on preliminary results,we

believe hepatitis E virus should be the subject of further study in this region. Finally,

seronegative eases are common among Non-A,Non-B,ABVH cases in Bahia-Brazil,and deserve

longitudinal studies in order to better understand the natural hls~ory of the dlsease~