L. Caccamo

European collaborative study on factors influencing outcome after liver transplantation for hepatitis C

BACKGROUND & AIMSnLiver transplantation for hepatitis C virus (HCV)-related liver disease is characterized by frequent graft infection by HCV. The prognosis and risk factors for morbidity and mortality in this condition were determined.nnnMETHODSnA retrospective study of 652 consecutive anti-HCV-positive patients undergoing liver transplantation between 1984 and 1995 in 15 European centers was conducted; 102 patients coinfected with hepatitis B virus (HBV) received immunoglobulin prophylaxis for antibody to hepatitis B surface antigen.nnnRESULTSnOverall, 5-year survival was 72%. Five-year actuarial rates of hepatitis and cirrhosis were 80% and 10%. Genotypes 1b, 1a, and 2 were detected in 214 (80%), 24 (9%), and 24 (9%) of 268 patients analyzed. The only discriminant factor for patient or graft survival was hepatocellular carcinoma as primary indication. Independent risk factors for recurrent hepatitis included the absence of HBV coinfection before transplantation (relative risk [RR], 1.7; 95% confidence interval [CI], 1.2-2.6; P = 0.005), genotype 1b (RR, 2; 95% CI, 1.3-2.9; P = 0.01), and age > 49 years (RR, 1.4; 95% CI, 1.1-1.8; P = 0.01).nnnCONCLUSIONSnThe results of transplantation for HCV-related disease are compromised by a significant risk of cirrhosis, although 5-year survival is satisfactory. Genotype 1b, age, and absence of pretransplantation coinfection by HBV are risk factors for recurrent HCV.

Randomized trial of lamivudine versus hepatitis B immunoglobulin for long-term prophylaxis of hepatitis B recurrence after liver transplantation

BACKGROUND/AIMSnThe long-term prophylaxis of hepatitis B after liver transplantation requires further optimization. In a randomized trial we investigated a regimen where the initially given hepatitis B immunoglobulin (HBIg) is replaced by long-term lamivudine treatment.nnnMETHODSnTwenty-four liver transplant recipients (all HBsAg-positive/HBV DNA-negative before transplantation), who had received HBIg for at least 6 months without HBV recurrence, were randomized to receive lamivudine (n = 12) or HBIg (n = 12) for 52 weeks. The efficacy criteria involved seronegativity for HBsAg and undetectable HBsAg/ HBcAg in the liver.nnnRESULTSnTwenty-one of 24 patients completed the study without hepatitis B virus (HBV) recurrence (11 on HBIg, ten on lamivudine), while three patients became HBsAg-positive. Amongst those without HBV recurrence HBV DNA was detectable only by polymerase chain reaction, intermittently in serum and lymphocytes, and in liver specimens from six of eight patients receiving HBIg and five of seven receiving lamivudine. YMDD variant was found in four cases with no viral antigen expression. Eight patients continued lamivudine after the study and during an additional 6-22 months remained HBsAg-negative with normal graft function.nnnCONCLUSIONSnSubstitution of HBIg with lamivudine is effective for prevention of HBV recurrence in low-risk liver transplant recipients and offers a convenient and cost-effective alternative for long-term HBV prophylaxis.

Balancing Donor and Recipient Risk Factors in Liver Transplantation: The Value of D‐MELD With Particular Reference to HCV Recipients

Donor–recipient match is a matter of debate in liver transplantation. D‐MELD (donor age × recipient biochemical model for end‐stage liver disease [MELD]) and other factors were analyzed on a national Italian database recording 5946 liver transplants. Primary endpoint was to determine factors predictive of 3‐year patient survival. D‐MELD cutoff predictive of 5‐year patient survival <50% (5yrsPS<50%) was investigated. A prognosis calculator was implemented (http://www.D‐MELD.com). Differences among D‐MELD deciles allowed their regrouping into three D‐MELD classes (A < 338, B 338–1628, C >1628). At 3 years, the odds ratio (OR) for death was 2.03 (95% confidence interval [CI], 1.44–2.85) in D‐MELD class C versus B. The OR was 0.40 (95% CI, 0.24–0.66) in class A versus class B. Other predictors were hepatitis C virus (HCV; OR = 1.42; 95% CI, 1.11–1.81), hepatitis B virus (HBV; OR = 0.69; 95% CI, 0.51–0.93), retransplant (OR = 1.82; 95% CI, 1.16–2.87) and low‐volume center (OR = 1.48; 95% CI, 1.11–1.99). Cox regressions up to 90 months confirmed results. The hazard ratio was 1.97 (95% CI, 1.59–2.43) for D‐MELD class C versus class B and 0.42 (95% CI, 0.29–0.60) for D‐MELD class A versus class B. Recipient age, HCV, HBV and retransplant were also significant. The 5yrsPS<50% cutoff was identified only in HCV patients (D‐MELD ≥ 1750). The innovative approach offered by D‐MELD and covariates is helpful in predicting outcome after liver transplantation, especially in HCV recipients.

Hepatitis B-core antibody positive donors in liver transplantation and their impact on graft survival: Evidence from the Liver Match cohort study

BACKGROUND & AIMSnThe appropriate allocation of grafts from HBcAb positive donors in liver transplantation is crucial, yet a consensus is still lacking.nnnMETHODSnWe evaluated this issue within Liver Match, a prospective observational Italian study. Data from 1437 consecutive, first transplants performed in 2007-2009 using grafts from deceased heart beating donors were analyzed (median follow-up: 1040 days). Of these, 219 (15.2%) were HBcAb positive. Sixty-six HBcAb positive grafts were allocated to HBsAg positive and 153 to HBsAg negative recipients.nnnRESULTSn329 graft losses occurred (22.9%): 66 (30.1%) among 219 recipients of HBcAb positive grafts, and 263 (21.6%) among 1218 recipients of HBcAb negative grafts. Graft survival was lower in recipients of HBcAb positive compared to HBcAb negative donors, with unadjusted 3-year graft survival of 0.69 (s.e. 0.032) and 0.77 (0.013), respectively (log-rank, p=0.0047). After stratifying for recipient HBsAg status, this difference was only observed among HBsAg negative recipients (log rank, p=0.0007), 3-year graft survival being excellent (0.88, s.e. 0.020) among HBsAg positive recipients, regardless of the HBcAb donor status (log rank, p=0.4478). Graft loss due to de novo HBV hepatitis occurred only in one patient. At Cox regression, hazard ratios for graft loss were: MELD (1.30 per 10 units, p=0.0002), donor HBcAb positivity (1.56, p=0.0015), recipient HBsAg positivity (0.43, p <0.0001), portal vein thrombosis (1.99, p=0.0156), and DRI (1.41 per unit, p=0.0325).nnnCONCLUSIONSnHBcAb positive donor grafts have better outcomes when transplanted into HBsAg positive than HBsAg negative recipients. These findings suggest that donor HBcAb positivity requires more stringent allocation strategies.

Liver Transplantation for Hepatitis B Virus Patients : Long-Term Results of Three Therapeutic Approaches

The indications for liver transplantation among patients with post-hepatitis B virus (HBV)-related cirrhosis have changed over the past 35 years. We reviewed the long-term results of 47 patients treated with liver transplantation for HBV-related cirrhosis. Patients were classified into 3 groups according to the perioperative regimen. In the initial experience, no immunoprophylaxis was adopted (no-IP; n=5). From 1988-1996, an immunoprophylaxis scheme was adopted (HBIg; n=16). From 1997-2007, we adopted the combination of lamivudine and HBIg (LAM-HBIg; n=26). We calculated the prevalence of serological reinfection and patient survival at 1 to 20 years, using the 3 regimens. The recurrence rate was 75% in the group of untreated patients; 30% in the HBIg group; and 9% in the LAM-HBIg group. The overall survival was 67% at 5 years, and 64% at 10 and 20 years. The long-term survival for each of the 3 therapeutic approaches, namely, for the patients who did not receive any treatment, for the HBIg group, and for the LAM-HBIg group, were 20%, 50%, and 84%, respectively. We suggest to use the LAM-HBIg combination.

No hepatitis recurrence using combination prophylaxis in HBV-positive liver transplant recipients with YMDD mutants

Recurrence of hepatitis B impairs the outcome of liver transplantation (OLT). In serum hepatitis B virus (HBV)‐DNA‐positive recipients, prophylaxis using lamivudine and immunoglobulins (HBIg) reduces the risk of recurrence, but it is undefined whether this regimen also protects candidates with YMDD mutants. Seventeen OLT viraemic candidates received pre‐emptive lamivudine followed by post‐OLT prophylaxis with lamivudine and HBIg. Both sera and liver biopsies were prospectively collected and high‐sensitive polymerase chain reaction (PCR) assay was applied for HBV‐DNA detection. Finally, the presence of YMDD mutants was explored in all PCR‐positive samples. All patients remained hepatitis B recurrence‐free after a mean follow up of 32u2003months. By PCR, serum HBV‐DNA was detectable in 64.3% of cases at OLT‐baseline, in 64.7% under combined prophylaxis and in 58.8% in patients (70.5% of the total) with a minimum follow up of 24u2003months. At OLT‐baseline, YMDD mutants were found in 44.4% of patients. After OLT, mutants were present in 50% of patients but only in 16.6% of cases in the long period. Although 41% of the native livers and 42.8% of the analysed grafts harboured HBV‐DNA, YMDD mutants were detected in 57% of the native positive livers. YMDD mutants were largely detected both at OLT‐baseline and post‐OLT, but their presence decreased over time. Regardless of the presence of YMDD mutants, no hepatitis B recurrence was observed in our OLT recipients using pre‐emptive lamivudine followed by continuous prophylaxis with lamivudine and HBIg.

OC-20 Prophylaxis of hepatitis B after liver transplantation: report of an Italian survey in a cohort of 2260 patients

s of the 46th A.I.S.F. Annual Meeting 2013 / Digestive and Liver Disease 45S (2013), S1–S48 S7 the increase of HRR. The analysis of survival benefit comparing the risk of waiting list drop-out with the mortality of the 170 transplanted patients with same HRR, showed an important benefit for LT in patients with HRR>16.3. Conclusions: In patients with MELD<18, the combination of ascites, sodium, albumin, bilirubin and renal function in a new score (HRR) is superior than MELD in identifying both patients at a high risk of waitlist drop-out and patients in whom LT may be safely deferred.

206 THE UN-SUSTAINABLE MATCH IN HCV LIVER TRANSPLANT PATIENTS

206 THE UN-SUSTAINABLE MATCH IN HCV LIVER TRANSPLANT PATIENTS A.W. Avolio, S. Agnes, M.C. Lirosi, M. Salizzoni, A. Pinna, B. Gridelli, L. De Carlis, M. Colledan, G. Gerunda, U. Valente, G. Rossi, G. Ettorre, A. Risaliti, V. Mazzaferro, F. Bresadola, M. Rossi, G. Tisone, F. Zamboni, L. Lupo, O. Cuomo, F. Calise, A. Vitale, N. Nicolotti, R. Romagnoli, A. Cucchetti, S. Gruttadauria, I. Mangoni, D. Pinelli, R. Montalti, M. Gelli, L. Caccamo, G. Vennarecci, D. Nicolini, E. Regalia, U. Baccarani, Q. Lai, T. Manzia, E. Tondolo, M. Rendina, A. Perrella, E. Scuderi, B. Antonelli, C. de Waure, M. Angelico, P. Burra, A. Gasbarrini, U. Cillo, Donor-to-Recipient Italian Liver Transplant (DR2-ILTx) Study Group. Liver Transplant Center, “A.Gemelli”Hospital, Catholic University, Rome, Liver Transplant Center, “S. Giovanni Battista” Hospital, University of Turin, Turin, Liver Transplant Center, “S. Orsola” Hospital, University of Bologna, Bologna, Liver Transplant Center, IsMeTT-UPMC, Palermo, Liver TransplantCenter, “Niguarda” Hospital, Milan, Liver Transplant Center, “Ospedali Riuniti”, Bergamo, Liver Transplant Center, University of Modena and Reggio Emilia, Modena, Liver Transplant Center, “S. Martino” Hospital, University of Genoa, Genoa, Liver Transpantation Center, IRCCS Foundation, “Maggiore” Hospital, Milan, Liver Transplant Center, “San Camillo-Forlanini” Hospital, Rome, Liver Transplant Center, “Umberto I” Hospital, Polytechnic University of Marche, Ancona, Liver Transplant Center, National Cancer Institute, IRCCS Foundation, Milan, Liver Transplant Center, University of Udine, Udine, Liver Transplant Center, “Umberto I” Hospital, “La Sapienza” University, Liver Transplant Center, “Tor Vergata” University Hospital, Rome, Liver Transplant Center, “G. Brotzu” University Hospital, Cagliari, Liver Transplant Center, Department of Emergency and Organ Transplant, University of Bari, Bari, Liver Transplant Center, Laparoscopic Hepatobiliary Surgical Unit, “A. Cardarelli” University Hospital, Liver Transplant Center, Hepatobiliary Surgical Unit, “A. Cardarelli” University Hospital, Naples, Liver Transplant Center, Department of Surgical and Gastroenterological Sciences, University of Padua, Padova, Epidemiology and Biostatistics Unit, Institute of Hygiene, Catholic University, Rome, Italy E-mail: alfonso.avolio@tin.it

93 THE USE OF MYCHOPHENOLATE MOFETIL IS A MAJOR DETERMINANT OF ONE YEAR GRAFT SURVIVAL AFTER LIVER TRANSPLANTATION: RESULTS FROM THE LIVER MATCH PROSPECTIVE STUDY

93 THE USE OF MYCHOPHENOLATE MOFETIL IS A MAJOR DETERMINANT OF ONE YEAR GRAFT SURVIVAL AFTER LIVER TRANSPLANTATION: RESULTS FROM THE LIVER MATCH PROSPECTIVE STUDY M. Angelico, T. Marianelli, L. Caccamo, A. Gasbarrini, C. Gavrila, A. Ricci, A. Nardi, on behalf of Liver Match Investigators: AISF and CNT Governing Boards, Directors of Liver Transplant Programs and AISF Fellowship Recipients. Hepatology & Liver Transplantation, Tor Vergata University, Rome, Liver Transplantation, Milan University, Milan, Gastroenterology, Catholic University, Biomathematics, Tor Vergata University, Biostatistics, National Transplant Center, Rome, Italy E-mail: angelico@med.uniroma2.it