L. Miglioresi

De novo malignancies following liver transplantation: results from a multicentric study in central and southern Italy, 1990-2008.

OBJECTIVE The objective of this study was to quantify incidence rates (IR) and risks of de novo tumors (except nonmelanoma skin cancers) in patients who underwent orthotopic liver transplantation (OLT) in central and southern Italy. METHODS Data were collected on 1675 patients (75.5% males) who underwent OLT in six Italian transplantation centers in central and southern Italy (1990-2008). The time at risk of cancer (person years [PY]) was computed from OLT to the date of cancer diagnosis, death, or last follow-up, whichever occurred first. The number of observed cancer cases were compared with the expected one using data from population-based cancer registries. We computed gender- and age-standardized incidence ratios (SIRs) and 95% confidence intervals (CIs). RESULTS During 10,104.3 PYs (median follow-up, 5.2 years), 98 patients (5.9% of the total) were diagnosed with a de novo malignancy (for a total of 100 diagnoses). Twenty-two of these cancers were post-transplantation lymphoproliferative disorders (PTLD; 18 non-Hodgkin lymphoma [NHL] and 2 Hodgkins lymphoma [HL]), 6 were Kaposis sarcoma (KS), and 72 were solid tumors (19 head and neck [H&N], 13 lung, 11 colon-rectum, 6 bladder, and 4 melanoma). The overall incidence was 9.9 cases/10(3) PYs, with a 1.4-fold significantly increased SIR (95% CI, l.2-1.7). Significantly increased SIRs were observed for KS (37.3), PTLD (3.9), larynx (5.7), melanoma (3.1), tongue (7.1), and H&N (4.5) cancers. CONCLUSIONS These results confirmed that OLT patients are at greater risk for cancer, mainly malignancies either virus-associated or related to pre-existent factors (eg, alcohols). These observations point to the need to improve cancer surveillance after OLT. The on-going enrollment of patients in the present cohort study will help to elucidate the burden of cancer after OLT and better identify risk factors associated with its development.

Validation of the AFP model as a predictor of HCC recurrence in patients with viral hepatitis-related cirrhosis who had received a liver transplant for HCC

BACKGROUND & AIMS The AFP model was shown to be superior to the Milan criteria for predicting hepatocellular carcinoma (HCC) recurrence after liver transplantation in a French population. Our aim was to test the AFP model in a non-French, post-hepatitic cirrhosis-based population of HCC candidates. METHODS 574 patients transplanted for HCC in four Italian centers were studied. AFP score was assessed at the last evaluation before liver transplantation (LT). Probabilities of recurrence and survival were estimated by the log-rank test or competing risk analysis and compared according to the AFP model. RESULTS 24.7% patients were beyond Milan criteria. HCC complicated hepatitis C virus (HCV) and hepatitis B virus (HBV) cirrhosis in 58.7% and 24% of the cases, respectively. Five-year probabilities of recurrence differed according to AFP score ⩽2 vs. >2 in the whole population (13.2±1.8% vs. 49.8±8.7%, p<0.001, HR=4.98), in patients within Milan criteria (12.8±2.0% vs. 32.4±12.1%, p=0.009, HR=3.51), beyond Milan criteria (14.9±4.2% vs. 58.9±11.5%, p<0.001, HR=4.26), HCV patients (14.9±2.5% vs. 67.6±14.7%, p<0.001, HR=6.56) and HBV patients (11.6±3.4% vs. 34.3±12.5%, p=0.012, HR=3.49). By net reclassification improvement analysis AFP score significantly improved prediction of non-recurrence compared to Milan criteria. Overall five-year survival rates according to AFP score ⩽2 or >2 were 71.7±2.2% vs. 42.2±8.3% (p<0.001, HR=2.14). CONCLUSIONS The AFP model identifies HCC candidates at low risk of recurrence, otherwise excluded by Milan criteria in a population with a predominance of post-hepatitic-related HCC. The AFP score can be proposed for selection of HCC candidates in programs with a high proportion of viral/HCV-related cirrhosis. LAY SUMMARY Selection criteria for liver transplantation of patients affected with hepatocellular carcinoma (HCC) are based on the Milan criteria, which have been shown to be too restrictive, precluding access to liver transplantation for some patients who might be cured by this operation. Recently, a French group of researchers developed a new selection model called the AFP model, or AFP score, allowing some patients with HCC not meeting Milan criteria to be transplanted with excellent results. In the present work, the AFP score was tested in a population of non-French patients transplanted for HCC occurring mainly on post-hepatitic (HCV or HBV) cirrhosis. The results confirm that in this specific population, as in the original French population of patients, the AFP model better selects patients with HCC eligible for transplantation, compared to Milan criteria. We conclude that the AFP score, which has been officially adopted by the French organization for Organ Sharing for HCC patients, can also be implemented in countries with an important burden of HCC occurring on post-hepatitic cirrhosis.

Experiences in Hepatic Surgery and Transplantation after Radioembolization

Yttrium-90 microspheres radioembolization has shown to be an effective modality of treatment in patients with primary or metastatic liver tumours [1-4]. It is usually offered to patients with advanced liver cancers. However, surgical experience after radioembolization is very limited to anecdotal cases mainly related to hepatocellular carcinoma. We have treated patients with hepatocellular carcinoma or liver metastasis mainly from colon, breast, melanoma and neuroendocrine tumours. In our experience after such treatment we were able to downstage the tumour to surgery only in the case of hepatocellular carcinoma. Five patients had liver transplantation and 1 had right hepatic resection after Yttrium-90 microspheres radioembolization. Of note 2 patients had neoplastic infiltration of a portal vein branch which resolved after treatment with Yttrium-90 microspheres radioembolization. The extra-hepatic spread was ruled out and later they were both transplanted. Here we report our initial single center experience with Yttrium-90 microspheres radioembolization as downstaging and bridging method for hepatocellular carcinoma prior liver surgery, resection or liver transplantation.

Treatment of hepatitis C recurrence is less successful in female than in male liver transplant recipients

It has been recently suggested that the risk of graft loss after liver transplantation (LT) may increase in female HCV patients. The aim of the study was to examine gender differences in HCV therapy tolerance and outcome in LT patients treated for HCV recurrence. A retrospective study was conducted on liver recipients with HCV recurrence, who were given antiviral therapy from 2001 to 2009 in 12 transplant centers in Italy. Sustained virological response (SVR), adherence‐to‐therapy, and side effects were evaluated. A multivariate logistic regression model was used after adjusting for possible confounders. The data regarding 342 treated patients were analyzed. SVR was reported in 38.8% of patients. At baseline, male and female did not differ in HCV viral load, histology, or rate of diabetes. SVR was lower in females than in males (29.5% vs. 42.1%; P = 0.03). Adherence‐to‐therapy was also lower in females than in males 43.4% vs. 23.8%; P = 0.001); anemia was the main reason for lower adherence. In a multivariate analysis in patients Genotype 1, female gender (P < 0.04), early virological response (P < 0.0001), and adherence to therapy (P < 0.0001) were independent predictors for SVR. In conclusion, female gender represents an independent negative prognostic factor for the outcome of HCV antiviral therapy after LT.

Treatment of genotype-1 hepatitis C recurrence after liver transplant improves survival in both sustained responders and relapsers

The aim of this study was to evaluate the factors affecting the response to treatment and how it could affect survival in a large series of genotype‐1 HCV‐transplanted patients. Three‐hundred and twenty six genotype‐1 HCV patients were enrolled. One hundred and ninety‐six patients (60.1%) were nonresponders and 130 (39.9%) showed negative HCV‐RNA at the end of treatment. Eighty‐four of them (25.8%) achieved sustained virological response, while 46 (14.1%) showed viral relapse. Five‐year cumulative survival was significantly worse in nonresponders (76.4%) compared with sustained viral response (93.2) or relapsers (94.9%). Sustained responders and relapsers were therefore considered as a single ‘response group’ in further analysis. Pretreatment variables significantly associated with virological response at multivariate regression analysis were the absence of ineffective pretransplant antiviral therapy, the recurrence of HCV‐hepatitis more than 1 year after transplant, an histological grading ≥4 at pretreatment liver biopsy, a pretreatment HCV‐RNA level <1.2 × 106 IU/ml, and the absence of diabetes. As expected, also on‐treatment variables (rapid and early virological response) were significantly associated to the response to antiviral treatment. In conclusion, this study shows that postliver transplant antiviral treatment results in beneficial effect on survival not only in sustained responders but also in relapsers.

427 TREATMENT OF HEPATITIS C RECURRENCE AFTER LIVER TRANSPLANTATION: GENDER ISSUE ON THERAPY OUTCOME

427 TREATMENT OF HEPATITIS C RECURRENCE AFTER LIVER TRANSPLANTATION: GENDER ISSUE ON THERAPY OUTCOME V. Giannelli, C. Lucidi, M. Giusto, F.R. Ponziani, M. Pompili, R. Vigano, R.M. Iemmolo, F.M. Donato, M. Rendina, P. Toniutto, L. Pasulo, S. Fagiuoli, M.C. Morelli, E. de Martin, L. Miglioresi, D. di Paolo, M. Merli, RECOLT-C. Sapienza University of Rome, Cattolica Sacro Cuore, Niguarda Ca’Granda Hospital, Rome, Modena University, Modena, Maggiore Hospital, Milan, Bari University, Bari, Udine University, Udine, Bergamo University, Bergamo, Sant’Orsola Malpighi Hospital, Bologna, Padua University Hospital, Padua, San Camillo-Spallanzani Hospital, Tor Vergata University Hospital, Rome, Italy E-mail: mr_valegiann84@hotmail.it

Best Matching for HCV Genotype 1 Liver Transplant Recipients is Predicted by Hcv1-Star. A Study From Aisf Recolt-C Database

561 BEST MATCHING FOR HCV GENOTYPE 1 LIVER TRANSPLANT RECIPIENTS IS PREDICTED BY HCV1-STAR. A STUDY FROM AISF RECOLT-C DATABASE F.R. Ponziani, A. Milani, A. Gasbarrini, R. Vigano, R.M. Iemmolo, M.F. Donato, M. Rendina, P. Toniutto, L. Pasulo, M. Cescon, E. De Martin, L. Miglioresi, V. Giannelli, D. Di Paolo, S. Fagiuoli, M. Pompili, AISF RECOLT-C Group. A. Gemelli Hospital, Rome, Niguarda Ca’Granda Hospital, Milan, University of Modena, Modena, Maggiore Hospital, Milan, University of Bari, Bari, University of Udine, Udine, Ospedali Riuniti, Bergamo, Sant’Orsola Malpighi Hospital, Bologna, University of Padua, Padua, San Camillo Spallanzani Hospital, Sapienza University, University of Torvergata, Rome, Italy E-mail: francesca.ponziani@yahoo.it

P.1.2: THE PERSISTENCE OF HCV REPLICATION IS ASSOCIATED WITH AN INCREASED MORTALITY RATE IN HCV RECURRENT TRANSPLANT PATIENTS: RESULTS FROM THE AISF-RECOLT-C GROUP

Background and aim: Sorafenib is a multikinase inhibitor approved for the treatment of advanced hepatocellular carcinoma (HCC). However, the predictive factors of outcome among treated patients have not been fully investigated. Aim of this study was to identify factors predictive for tumor control among patients with advanced HCC treated with sorafenib. Material and methods: All consecutive HCC patients treated with sorafenib at our Unit from October 2008 to October 2010 were evaluated. All patients received 800 mg/day of sorafenib until progression or unacceptable toxicities. Overall survival (OS) and time to progression (TTP) were estimated by using Kaplan-Meier curves. TTP was considered as a marker of tumor control. Univariate analysis included age, gender, etiology, AFP, Child-Pugh class, MELD, alanine aminotransferase (ALT), alkaline phosphatase, bilirubin, albumin, ascites, metastasis, portal vein thrombosis, oesophageal varices, effects related to VEGF inhibition: rash, arterial hypertension, bleeding, and hand-foot syndrome (HFS). To detect factors independently related to TTP, multivariate analysis by Cox’s model was done. Results: We treated 101 patients (median age 67 years; 81 males; 98 cirrhotics; Child A/B: 79/19; 55 macrovascular invasion; 39 extrahepatic spread). Median therapy duration was 4 (range 1-16) months. Median OS was 10 (95% CI 4.5-15.5) months. TTP was 9 (95%CI 3.7-14.3) months. Complete/partial response occurred in 21% of patients and stable disease in 19%. At univariate analysis, the variables significantly related to TTP were: female sex (14 months vs 6 months, p=.05), no portal thrombosis (13 months vs 6 months, p=.04), ALT =60UI (15 months vs 6 months, p=.02), no ascites (11 months vs 2 months, p=.003), and occurrence of HFS (16 months vs 5 months, p<0.000). At multivariate analysis, no ascites (p=.02; HR 2.7, 95%CI 1.2-6.0) and occurrence of HFS (p<.000; HR 8.9, 95%CI 3.3-23.8) were independently related to TTP. Conclusions: In sorafenib treated patients, the absence of ascites and the occurrence of HFS are predictive factors for longer TTP. HFS was the only symptom related to inhibition of VEGF predicting tumor control.