354A AASLD ABSTRACTS HEPATOLOGY October 1995

989 A STUDY OF UNEXPLAINED AMINOTRANSFERASES ELEVATIONS IN ANTI-HCV SERONEGATIVE HEMODIALYSIS PATIENTS. M Psichoaiou*. A Katsoulidou*. E Vaindirli*. S Moutafis**. G Skoutelis***. V Hadiiconstantinou****. A Hatzakis*. for the Multicentre Hemodialvsis Cohort Stuck, on VirelHeoatRis. *Athens Univ Medical School,**Kianous Stavros Clinic,***Athinaiki Clinic,****A. Fleming Hospital.

Patients undergoing chronic hemodialysis usually are immunocompromised and potentially have an increased risk of exposure to hepatotropic viruses. The aim of this study was to investigate the involvement of known hepatitis viruses in hemodialysis patients with unexplained elevations of aminotransferases. 420 anti-HCV (-) patients from 5 hemodialysis units were followed-up clinically with weekly or biweekly monitoring of ALT and serum storage, for a mean period of 17 months. Dudng this period, 21 patients showed a repeated (~4 measurements) abnormal (ALT >- 2 ULN) ALT elevation, in absence of drug or alcohol induced hepatitis and without a history of preexisting liver disease. Each sample was tested for antibodies to HCV by 2~ (EIA-2) and 3~(EIA-3) generation enzyme immunoassays. Serial serum samples obtained during the period of elevated transaminases were tested by EIA's for anti-HAV igM, HBsAg, anti-HBc IgM, IgM antibody to EBV and IgM antibody to CMV. During the same period, repeated (>_4) samples of each individual were tested for HCV-RNA and HBV-DNA by PCR. One patient (5%) who found to be CMV IgM (+) followed the typical pattern of initial igM rise with a later decline in IgM responce. None of the patients was found positive for anti-HCV. Seven patients (33 %) had detectable HCV-RNA during the pedod of ALT elevation, while three of them remained HCV-RNA (+) after ALT values normalization. None of these patients seroconverted to anti-HCV dudng 8 months of foliew-up. Thirteen of the 21(62%) patients lacked any of the previously mentioned markers. In conclusion, 1. HCV infection without anti-HCV seroconversion is involved in a substantial fraction of hemodialysis patients with unexplained elevations of aminotransferases; 2. In the majority of patients no apparent cause of ALT elevation was identified. It is possible that unknown hepatotrepic viruses are involved.

990 VIRAL HEPATITIS MARKERS AND EVALUATION OF ALT SCREENING AMONG SAUDI VOLUNTEERED BLOOD DONORS. I Allraif W Altarnimi M El~heikh A Alkh~han M .qohaihani Dept. of Liver Transplantation and Hepatobiliary Services, and Dept. of Pathology, King Fahad National Guard Hospital, Riyadh, Saudi Arabia. AIM: To assess the prevalence of hepatitis B and C and the utility of serum alanine aminotranferaee (ALT) screening among blood donors in Saudi Arabia. METHODS: We evaluated 15,006 volunteered blood donors between 1992 to 1995, for blood donation. RESULTS: 1247 (8.3%) of the blood donors were under weight and therefore were rejected from donation, of the 13759 remaining donors; 4161 (30.2%) had high ALT level, 1471 (I 0.7%) positive donors history, 259 (1.9%) low hematocrit level, and 855 (6.2%) other miscellaneous reasons and therefore were excluded from donation. Hepatitis serology of 7013 (51%) eligible donors with normal ALT revealed that 284 (4.0%) and 72 (1.0%) were reactive for HBsAg and Anti-HCV respectively. Among 100 consecutive donors who were found to have high ALT, 7 were reactive for HBsAg, 4 were Anti- HCV positive, and one was positive for both i.e. 87% have no clinical or serologic evidence of hepatitis B or C.

115'006 POTENTIAL BLOOD DONORS I ÷

REJECTED UNDERWEIGHT ~ SCREENED FOR ALT 1,247 (8.3%) 13,759 (91.7%)

+ REJECTED ACCEPTED FOR DONATION

1. High ALT 4,161 (30.2%) 7013 (51%) 2. Others 2,585 (18.8)

+ ÷" ÷ [POSITIVE HBsAg 284 (4.0%)[ [ POSITIVE Anti*HeY 71 (1.0%)

CONCLUSION: The prevalence of HBsAg and Anti HCV in healthy blood donors is 4% and 1% respectively in those with normal ALT level and 8% and 5% in those with elevated ALT. In addition, although ALT screening is a good discriminate to filter out most hepatitis infected blood donors, it results in elimination of large number of healthy blood donors (30.2%) and therefore should not be utilized in Saudi donors in the era of screening for hepatitis B and C.

991 THE SlONIFICANCE OF IgN ANTIBODY RESPONSE TO HEPATITIS C VIRUS CORE PROTEIN IN PATIENTS WITH CHRONIC HEPATITIS C. N Yuki T N Hayashi~ K Ohkawa r A Kasahara~ H Fusamoto . and T Kamada. First Department of Nedicine, Osaka University Nedical School, Osaka, Japan.

The significance of IgN antibody to hepatitis C virus core protein (IgN anti-HCVcore) was studied in chronic HCV infection. NETHODS IgN anti-NCVcore was tested with a solid-phase enzyme-linked immunoassay in 41 patients with chronic HCV infection diagnosed by the polymerase chain reaction. The results were correlated with clinical features, liver histological findings evaluated by the histological activity index, and virological features such as genotypes and vire=ic levels assessed by a branched DNA assay. Changes in IgN anti-NCVcore a f t e r a 28-vk i n t e r f e r o n - a course were f u r t h e r s tud ied . RESULTS IgR anti-HCVcore was found in 29 (71~) p a t i e n t s , and i t s occurrence was only r e l a t e d to viremic l e v e l s . A s i g n i f i c a n t r e l a t i o n s h i p was observed between viremic l e v e l s and IgM anti-HCVcore cu t -o f f index (r~ = 0.42, p<0.01). Of the e igh t low viremic (branched DNA-uegative) p a t i e n t s , two (25~) t e s t ed p o s i t i v e for IgM anti-HCVcore with a cu t -o f f index of <3, whereas 27 (82~) of the 33 h ighly viremic (branched DRA-pnsitive) p a t i e n t s had IgM anti-HCVcore (p<0.01). After i n t e r f e r o n - a therapy, sus ta ined aminotransferase normal iza t ion a f t e r therapy withdrawal was achieved by only two (13~) of the 16 p a t i e n t s with IgH anti-HCVcore cu t -o f f index >3 compared with 11 (44~) of the 25 p a t i e n t s with tha t <3 (p<0.05). IgM anti-NCVcore out -of f index decreased a f t e r therapy in p a t i e n t s who c leared the v i rus in sera but increased again fo l lowing reappearance of v i remia . CONCLUSIONS These f ind ings suggest tha t IgM anti-NCVcnre may serve as a simple s e r o l o g i c a l i n d i c a t o r of a c t i ve v i rus r e p l i c a t i o n and have re levance to the outcome of a n t i v i r a l therapy.

992 DIAGNOSTIC SIGNIFICANCE OF lgM ANTI-HCV CORE IN LIVER G R A F T RECIPIENTS. F Negro, E Giostra, L Rubbia-Brandt l, H Troenen 4, G Mentha z, M Albrecht 4, G Michel 4, L Perrin s, P Morel 2, and A Hadengne. Gastroenterology Division, Depts. of 1Pathology and 2Surgery, and SLaboratory of Virology, University Hospital, Geneva, Switzerland; 4Abbott GmbH Diagnostika, Wiesbaden, Germany.

The differential diagnosis between recurrent hepatitis C and rejection following orthotopie liver transplantation (OLT) is difficult due to the lack of suitable markers of HCV-induced liver damage. Immune-mediated mechanisms are believed to be important in the pathogenesis of hepatitis C. Thus, based on previous reports about the significance of IgM anti-HCV core in different clinical settings, we assessed the presence and kinetics of such antibodies in 16 patients undergoing OLT because ofanti-HCV- and HCV RNA-positive cirrhosis. Serial senun samples, collected at the time of OLT and for 3-73 months thereafter, were analysed for HCV RNA (by RT-PCR) and for lgM anti-HCV core (HCV- IgM EIA 2.0 [Abbott]). After OLT, patients were divided into four groups according to the liver histology and to the response to unmunosuppressive therapy: 1 had minimal lesions, 7 developed a definite rejection of variable intensity (grade 1-2), 4 suffered from a cleareut recurrent hepatitis C and 4 showed heterogeneous histopathological features, suggestive of both rejection and recurrent hepatitis. Recurrent HCV infection (defined as persistence or reappearance ofHCV RNA in serum following OLT) was seen in 13/14 patients (93%), irrespectively of the histological outcome. IgM anti-HCV core were detected in the patient with minimal lesions and normal ALT, in none of 7 patients undergoing liver rejection and in all 4 patients with recurrent hepatitis C. Among patients with heterogeneous histological features, IgM anti-HCV core persisted in 2/3 cases with early signs of recurrent hepatitis C; in the fourth patient, IgM anti-HCV became undetectable early after OLT in concomitance with an episode of rejection, but reappeared thereafter when the liver showed signs of recurrent hepatitis C. Therefore, in anti-HCV-positive transplanted patients, the absence (or disappearance) of IgM anti-HCV core may specifically identify the episodes of rejection of the liver (and, possibly, of liver damage unrelated to HCV), whereas its persistence is a harbinger of recurrent hepatitis C, even when serum ALT levels are normal.