HEPATOLOGY Vol. 22, No. 4, Pt. 2, 1995 AASLD ABSTRACTS 135A

113 POOR PROGNOSIS OF PATIENTS RETRANSPLANTED FOR RECURRENT LIVER DISEASE DUE TO HEPATITIS C VIRUS C F~ray, A Habsanne, D Samuel, O Farges, M Reynes*, H Bismuth. Hepato-Biliary Surgery and Liver Transplant Center, Dpt Pathology*, Paul Brousse Hospital. Villejuif 94800, FRANCE.

Cirrhosis due to HCV is one of the first indication for liver transplantation. Recurrence of HCV after liver graft is constant and could account for long-terrr failure of liver graft. In order to appreciate i) the role of HCV in the indication of retransplantation and ii) the prognosis of retransplanted patients with HCV infection. we retrospectively studied all cases of first retransplantation performed al our institution. Patients and methods. From 1984 until 1994. 119 patients were retransplanted witln a mean of 465 days after first LT (1 day to 8 yearsJ. Assessment of HCV was done through second generation test and detection of HCV RNA in al] patients before and after reLT. Results. Causes of retransplantation were primary non function in 24 pts. chronic rejection (CR) in 44 pts, chronic hepatitis (CH) (cirrhosis or severe fibrosis) in 20. arterial thrombosis in 11. acute rejection fAR) in 10 and other causes in l0 pts. Among the 20 cases ofCH. HCV and HBV were detected in I 1 and 8 pts. Among the 54 cases of CR or AR. HCV and HBV were detected in 15 and 0 cases respectively (p<0.00II. ReLT was performed later in patients infected by HCV 6r HBV than in those without infection (2.2 vs 1.5 yrs; p<0,02). HCV related-liver diseases recurred in all patients after ReLT. One year graft survivals according etiology were the following:

cirrhosis C cirrhosis B anti-HCV anti-HCV positive and negative and re.iection

rejection 40 % 62 % 67 % 63 %

Among pauents retransplanted for cirrhosis C. loss of second graft was recurrent infection in three cases while 3 other patients had multiple organ failure.

Conclusions. HCV accounts for an increasing number of retransplantation. Prognosis of reLT was poor in pts retransplanted for chronic hepatitis C while those transplanted for rejection without or with infection by HCV had relatively good prognosts.

114 EARLY REINFECTION OF AND L A T E HCV RNA CLEARANCE FROM THE TRANSPLANT AFTER LIVER TRANSPLANTATION FOR CIRRHOSIS 'WITH CHRONIC HCV INFECTION. C. Sergi I, T. GOser ~, G. Otto 3, H.F. Otto ~, W.I. Hofiuann I . ~Institute of Pathology and Depts. of 2Internal Medicine and 3Surgery, University of Heidelberg, Germany.

Aims: HCV reinfection of a transplanted liver is reported to occur in up to 98% of transplantations performed for liver cirrhosis with chronic HCV infection. Little, however, is known about the time course of reinfection and the long term outcome. We, therefore, looked for HCV RNA in early and late post-transplant biopsies from livers after transplantation for liver cirrhosis with chronic HCV infection. Materials and Methods: 16 liver biopsies obtained from 6 transplanted livers from day 6 to day 1594 after trasnplantation of 5 patients and the corresponding explants were examined. HCV RNA was determined by nested RT-PCR after RNA extraction from snap frozen aliquots. A dot blot analysis with a high speci-fic probe to the amplified viral eDNA was used to confirm the PCR results, each step with positive and negative controls was always processed in duplicate. Results: All 5 explanted livers and the liver removed during retranspluntation of one patient on day 444 revealed to be HCV RNA positive. HCV RNA was found in the transplants as early as day 6 and as late as day 43 after transplantation. Thus, all transplants were reinfected during the first two months after transplantation. Surprisingly, clearance of HCV RNA was detected in one trans-plunt with a long observation time: the biopsy on day 1376 and the next two biopsies on days 1504 and 1594 did not contain HCV RNA anymore. Conclusions: HCV reinfection of the transplant after liver transplantation for cirrhosis with chronic HCV infection occurs as early as on the 6th postoperative day and seems to be completed within the first two months after transplantation. Thus, the clinical and histological follow up of a transplanted liver might be complicated by HCV reinfection in an early postoperative period already. The possibility of a clearance of HCV RNA as demonstrated for one transplanted liver in a vew late postoperative period (i.e. on day 1376) on the other hand might explain the relative benign postoperative course of HCV reinfection at least in some transplants.

1115 HEPATITIS C VIRUS (HCVI REINFECTION AFTER LIVER TRANSPLANTATION: OUTCOME AND FACTORS ASSOCIATED WITH SEVERE GRAFT DISEASE. M Salcedo. R Bafiaraa, E AIvarez#. CG Asanza. A de Dieoo, E Valdecantos, E Cos, and G Clemente. Liver Section and Department of Pathology#, Hospital General Universitario Gregorio Marafi6n, Universidad Complutense. Madrid. Spain,

Reinfection of the liver graft is almost universal after liver trasplantation (OLT) following HCV cirrhosis, However, the natural history of reinfection is poorly understood. Sometimes HVC reinfection is associated with severe liver disease and loss of the graft. The aim of this study is to analize the factors related with severe graft disease after HCV reinfection (SGRL PATIENTS AND METHODS: 34 OLT in 31 patients with HCV reinfection was revised. The mean histological follow-up was 21-+9 months (4-38). All the patients were immunosuppressed with a similar treatment including Cyciosporin, Azathioprine, and Prednisona. HCV reinfection was defined by the presence of HCV RNA after OLT in serum. Severe graft reinfection was defined by severe chronic active hepatitis (SCAH), cirrhosis (C) or severe cholestasis (SC) non related with other causes. Liver biopsies were performed at one month and every six months, and when liver test results were abnormal. RESULTS: Severe graft reinfection was found in 14 OLT (4 SCAH, 4 C, 6 SC) (41%). In univariate analysis the absence of etiologic cofactora other than HCV, preoperative serum HCV RNA positiviW, female, age below 52 years and the administration of more than two bolus of metil-prednisolone were associated with SGR. After stepwise logistic regresion only sex female (OR 6.9), viraemia preOLT (OR 9.74), age below 52 years (OR 10.6) and steroid treatment (OR 19.2) were associated with SGR, The actuarial probability of SGR was 7%, 22%, 26.6% and 47% at 6, 12, 24, 30 months after OLT. 3 patients needed retrasplantation. Six patiens died because of complications of liver disease, two of them after regrafting. CONCLUSIONS: Severe graft damage after HCV reinfection is not uncommon and may be associated with graft loss and death. The overimmunosupression induced by aditional doses of steroids is the most important predictive factor, suggesting the need for a careful management of rejection in patients with HCV infection and liver transplantation. Additional studies are required to ascertain the role of other factors.

116 INCREASED INFECTIONS IN LIVER TRANSPLANT RECIPIENTS WITH RECURRENT HEPATITIS C VIRUS (HCV) HEPATITIS. N Singh*, T Gavowski. MM Wa~ener, IR Marina. VA Medical Center, Pittsburgh, PA.

Recurrent HCV hepatitis has emerged as a significant cause of longterm hepatic dysfunction in liver transplant recipients. Association of HCV hepatitis with a higher risk of infections has been proposed in renal transplant recipients; this has not been assessed in liver transplant recipients.

Infections in liver transplant recipients with recurrent HCV hepatitis were prospectively assessed and compared with all other patients without HCV hepatitis, transplanted during the same period. Of 100 consecutive patients transplanted over a 5 year period, 52% (52/100) under,vent transplantation for HCV. Recurrent HCV hepatitis (diagnosed histopathologicelly) developed in 22% (100); mean followup was 903 days. Major infections occurred in 64% (14/22) of the patients with recurrent HCV hepatitis v s38% (30/78) of all other patients (p = .04) Patients with recurrent HCV hepatitis had significantly more episodes of major infections (mean 1.45 episodes/patient vs .51 episodes/patient, p = .003) and were more likely to have recurrent episodes of major infections (45%, 10/22 versus 10%, 8/78, p = .005) than all other patients, respectively. The incidence of major bacterial infections was not higher in patients with recurrent HCV hepatitis (41% versns 28%, p = NS), however fungal infections were higher (18% vs 6%, p = .10) and CMV disease was significantly higher (32% vs 9%, p = .012) in patients with recurrent HCV hepatitis as compared to other patients. Late infections (occurring > 6 months post-transplant) were significantly higher in patients with recurrent HCV (27% vs 6%, p = .011). Rejection episodes within 6 months posttransplant were higher in patients with recurrent HCV hepatitis (p = .03), however, the intensity of ilnmunosuppression (measured by corticosteroid boluses, recycles and OKT3) was not significantly different in these patients when compared with all other patients.

Recurrent HCV hepatitis after liver transplantation is associated with a high incidence of infections due to pathogens associated with depressed cell-mediated immunity. Future studies should assess the exact nature of the suppressive effect on host-defense in recurrent HCV hepatitis.