Early HCV-RNA kinetics after liver transplantation correlate with the outcome of recurrent hepatitis C

Category 1: Liver transplantation,

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EARLY HCV-RNA

KINETICS

TRANSPLANTATION RECURRENT

AFTER

CORRELATE

HEPATITIS

LIVER WITH THE OUTCOME

OF

C

A.M. Maina’, l? Ciccorossi’, F. Oliveri’, F. Filipponi2, l? Colombatto’, F. Bonino3, F. Mosca2, M.R. Brunetto I. ’Gastroenterologia E Epatologia, Azienda Ospedaliera Universitatia Pisana, Piss, Italy; 2Trapiantologia Epatica Universitatia, Azienda Ospedaliera Universitatia Pisana, Piss, Italy; ‘Ospedale Maggiore Di Milan0 IRCCS, Milano, Italy Recurrence of hepatitis C virus (HCV) infection and progressive liver disease are major problems after liver transplant (LT). We studied serum HCV-RNA kinetics during early viral recurrence (at LT, day 1, 7 and 30) and monthly thereafter (up to month 12) in 48 consecutive patients (33 males, 1.5 females, median age 5.5 y., range 34-66 y.) who underwent LT for end-stage cirrhosis (29) or hepatocellular carcinoma (19). We measured serum HCV RNA (by bDNA HCV RNA 2.0, Bayer; Cobas Monitor and Cobas Amplicor HCV test, Roche) and assess HCV genotypes by lineprobe assay (Inno-LiPA, Innogenetics). Liver tests were performed at the same time points and a liver biopsy at the time of serum transaminases flares (ALT > 2 times upper normal value) and at the end of 12-18 months post-LT follow-up in cases of persistently normal ALT. Histology was graded and staged according to Ishak et al. Ten pts refused the liver biopsy; 35 of 38 (92.1%) showed hepatitis recurrence l-18 months (median 12 m) after LT. Among 10 patients with severe disease 7 (70%) had an early (< 6 months) recurrence whereas only 6 of 25 (24%) in pts with mild-moderate disease. Median HCV RNA serum levels were 2.82~106 copies/ml (range: 8.5~102. 5.8~107) at LT; 3.54x 105 (8.5~102 -5.1~107) at day 1; 1.11x 106 (8.5x102-1.2x108) at day 7; 1.23 x107 (8.5x102-1.2x108) at day 30; 2.75~107 (7x104-1.2x108) at month 6; 1.94~107 (3.85~105-1.2~108) at month 12. Day l-30 HCV RNA levels were higher in the 10 pts with severe disease than in the remaining 28 pts (ANOVA comparing log10 means: day1 p=O.OOl, day7 p=O.O04 and day30 p=O.O2). In pts with < 6 months recurrence dayl-30 viremia was higher than in pts with after 6 months hepatitis recurrence (day1 p=O.O24, day7 p=O.O06 and day30 p=O.O18). HCV genotype did not influence disease recurrence and HCV RNA kinetics. These findings confirm that HCV infection recurrence is a highly dynamic process and suggest that its profile influences the severity of liver disease.

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PROLONGED

FOLLOW-UP

PATIENTS: RESULTS COMPARING PREVENTION

OF HBV LIVER TRANSPLANTED

FROM A RANDOMIZED

LAMIVUDINE

STUDY

VS. LAMIVUDINE+HBIG

OF HBV RECURRENCE

AFTER

IN THE

LIVER

TRANSPLANTATION

M. Buti’, A. Mas2, M. Prieto3, F. Casafont4, A. Gonzalez’, M. Miras6, A. Valdes7, .I. Herreros. ‘Liver Unit. Hospital Vail D‘Hebron., Barcelona, Spain; 2Liver Unit.Hospital Clinic., Barcelona, Spain; ‘Gastroenterology Deparment. Hospital La F ., Valencia, Spain; 4Gastroenterology Deparment. Hospital Marqu s De Valdecilla. SantandeK Spain, Santandes Spain; ‘Gastroenterology Deparment. Hospital Nuestra Senora De La Candelatia., Canarias, Spain; 6Gastroenterology Deparment.Hospital Virgen De La Arrixaca., Marcia, Spain; 7Liver Unit. Hospital Vail D‘Hebron, Barcelona, Spain; ‘Gastroenterology Deparment.Cl nica Universitatia De Navarra, Navarra, Spain Aim: To compare the long-term efficacy in preventing post-LTx (Liver transplantation) HBV recurrence of two therapies (LAM vs LAM +HBIg) in transplanted patients with chronic hepatitis B. Patients and Methods: 29 LTx patients were randomized to receive prophylaxis with lamivudine (LAM, 100 mg/daily) or LAM +HBIg (2000 UI/im/monthly) for 18 months after 4 weeks of LAM +HBIg. After month 18, patients were treated with the same schedule of LAM or HBIg+LAM following investigator criteria. The primary efficacy end-point was the absence of HBsAg and HBV DNA by hybridization test. Results: 29 patients have had a mean follow-up of 37~t9.1 months postLTx. Fifteen were randomized to receive HBIg+LAM and 14 LAM. At

surgery, acute liverfailure

37

month 18 post-LTx, no patients were reinfected. From month 18 on, 8 patients continued with HBIg+LAM and 21 with LAM. Up to now, all patients have survived except one (death unrelated to liver disease). HBV recurrence was detected in 3 (30%) patients at months 23, 25 and 48 (1 from LAM group and 2 from HBIg +LAM initially but all of them on LAM from month 18). One patient with HBV recurrence had acute hepatitis with YMDD mutants and 2 had mild liver disease. Conclusions: 1) Post-LTx patients with chronic hepatitis B on HBIg+LAM or LAM prophylaxis have excellent survival. 2) Late HBV recurrence occm-s, even with prophylaxis with LAM or HBIg+LAM 3) Prolonged and continuous monitoring is necessary to diagnose and treat late HBV recmrence.

I

106

IMMUNOSUPPRESSIVE FUNCTION

DURING

RECIPIENTS:

S.K.l? Cauduro,

REQUIREMENTS PREGNANCY

A SINGLE

CENTER

AND LIVER

IN LIVER TRANSPLANT EXPERIENCE

E. Hay. Transplant CtK, Mayo Clinic, Rochester MN, USA

Pregnancy in liver transplant recipients has increased risks for both mother and fetus, with particular concern about the allograft. Aims: To assess liver function, immunosuppressive adjustments and fetal and maternal outcome. Methods: All patients were kept on same previous immunosuppression with adjustments to maintain the therapeutic range (cyclosporin -Cya, 80. 120ng/ml; Tacrolimus-FK, 4-8nglml). Liver tests and drug levels were followed during all pregnancy up to 6 months after delivery. Pregnancies after Budd-Chiti syndrome (BCS) were maintained on subcutaneous heparin. Results: 12 patients had 22 pregnancies; mean age at the pregnancy 27 years. All patients had been amenorrheic before OLT and 10 were nulliparous. Of the 22 pregnancies, 6 (27%) ended in abortions at < 12 weeks (5 spontaneous) no statistically significant risk factors were found for these group; 2 of these 4 patients had subsequent successful pregnancies. Of the 16 pregnancies in 11 patients, 14 babies were born after 35 weeks (weight: median 31958, range 2600.41908) 2 babies were preterm (weights 2000 and 23208); all babies were healthy and with no fetal abnormalities. One fetal death occurred at 21 weeks gestation following maternal death from ruptured splenic artery aneurism (SAA) in the third postOLT pregnancy. Immunosuppression was prednisone with Cya (12), Cya (3), FK (1). There was no significant changes in the liver tests. In the third trimester albumin was significantly lower (mean 3.3g/dl) compared to previous levels (mean 4g/dl); Also the Cya levels were significantly lower (difference of mean 16.5ng/ml95% CI -44 to 11) requiring increment of the dose in a mean of 36mgldose. No rejection. With anticoagulation, pregnancy was successful in 2 patients transplanted for BCS. Conclusions: Patients require increasing doses of Cya during the second half of pregnancy. No rejection or allograft dysfunction was seen. Fetal and maternal outcome were good.

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THE STRESS CULTURES

RESPONSE -ADAPTIVE

IN J-DIMENSIONAL CHANGES

HEPGS

WITH FUNCTION

S. Choudhury’, M. Hubank2, H. Hodgson’, C. Selden’. ‘Department Of Medicine, Royal Free And University College Medical School, London, UK; 2Molecular Haematology, Institute Of Child Health, London, UK

Background: Alginate encapsulated HepG2s form 3-Dimensional spheroids with upregulated hepatocyte-specific functions. These are developed for potential use in a bioartificial liver for patients with fulminant liver failure. Compared with monolayer culture (M), per cell function rises over 8-10 days, but diminishes by d15, despite maintained viability and proliferation. Hypothesis: There is a stress response in both adverse conditions eg hypoxia, and as a result of increased cell performance, which involve different stress related genes. Methods: RNA from monolayer, d8 and d15 spheroids was subjected to microarray analysis (U95Av2 Affymetrix gene chip; n=9 (3x3). Candidate genes were further analysed by Western blot and functionally.