Matteo Zanello

Impact of model for end‐stage liver disease (MELD) score on prognosis after hepatectomy for hepatocellular carcinoma on cirrhosis

The objective of this study was to predict postoperative liver failure and morbidity after hepatectomy for hepatocellular carcinoma (HCC) with cirrhosis. The model for end‐stage liver disease (MELD) score is currently accepted as a disease severity index of cirrhotic patients awaiting liver transplantation; however, its impact on prognosis after resection of HCC on cirrhosis has never been investigated. One hundred fifty‐four cirrhotic patients resected in a tertiary care setting for HCC were retrospectively analyzed. For each patient, the MELD score was calculated and related to postoperative liver failure and complications (morbidity). Hospital stay and 1‐year survival was also investigated. MELD accuracy in predicting postoperative liver failure and morbidity of cirrhotic patients was assessed using receiver operating characteristic (ROC) analysis. Eleven patients (7.1%) experienced postoperative liver failure leading to death or transplantation. ROC analysis identified cirrhotic patients with a MELD score equal to or above 11 at high risk for postoperative liver failure (area under the curve [AUC] = 0.92, 95% confidence interval [CI] = 0.87‐0.96; sensitivity = 82%; specificity = 89%). Forty‐six patients (29.9%) developed at least 1 postoperative complication: ROC analysis identified patients with a MELD score equal to or above 9 at major risk for postoperative complications (AUC = 0.85, 95% CI = 0.78‐0.89; sensitivity = 87%; specificity = 63%). Cirrhotic patients with MELD score below 9 had no postoperative liver failure and low morbidity (8.1%). In conclusion, the MELD score can accurately predict postoperative liver failure and morbidity of cirrhotic patients referred for resection of HCC and should be used to select the best candidates for hepatectomy. Liver Transpl 12:966‐971, 2006.

Liver Transplantation for Recurrent Hepatocellular Carcinoma on Cirrhosis After Liver Resection : University of Bologna Experience

Liver resection (LR) for patients with small hepatocellular carcinoma (HCC) with preserved liver function, employing liver transplantation (LT) as a salvage procedure (SLT) in the event of HCC recurrence, is a debated strategy.

Effect of different immunosuppressive schedules on recurrence-free survival after liver transplantation for hepatocellular carcinoma

Background. Tumor recurrence represents the main limitation of liver transplantation in patients with hepatocellular carcinoma (HCC) and can be favored by exposure to calcineurin inhibitors. Methods. We investigated the effect of an immunosuppressant schedule that minimizes the exposure to calcineurin inhibitors on patients transplanted for HCC to ascertain whether this can reduce the tumor recurrence rate. For this purpose, we conducted a matched-cohort study: 31 patients with HCC transplanted between 2004 and 2007 who received sirolimus as part of their immunosuppression (group A) were compared with a control group of 31 patients (group B) transplanted in the same period who had the same prognostic factors but were given standard immunosuppression based on tacrolimus. Results. Three-year recurrence-free survival was 86% in group A and 56% in group B (P=0.04). Although the prevalence of microvascular invasion G3-G4 grading and alpha-fetoprotein more than 200 ng/mL was identical in the two groups, exposure to tacrolimus was significantly higher in patients of group B (median, 8.54; range, 5.5–13.5) in comparison with those of group A (median, 4.6; range, 1.8–9.1) (P=0.0001). Conclusions. By using sirolimus, exposure to calcineurin inhibitors can be minimized, reducing the risk of HCC recurrence.

Preoperative prediction of hepatocellular carcinoma tumour grade and micro-vascular invasion by means of artificial neural network: a pilot study.

BACKGROUND & AIMS Hepatocellular carcinoma (HCC) prognosis strongly depends upon nuclear grade and the presence of microscopic vascular invasion (MVI). The aim of this study was to develop an artificial neural network (ANN) that is able to predict tumour grade and MVI on the basis of non-invasive variables. METHODS Clinical, radiological, and histological data from 250 cirrhotic patients resected (n=200) or transplanted (n=50) for HCC were analyzed. ANN and logistic regression models were built on a training group of 175 randomly chosen patients and tested on the remaining testing group of 75. Receiver operating characteristics curve (ROC) and k-statistics were used to analyze model accuracy in the prediction of the final histological assessment of tumour grade (G1-G2 vs. G3-G4) and MVI (absent vs. present). RESULTS Pathologic examination showed G3-G4 in 69.6% of cases and MVI in 74.4%. Preoperative serum alpha-fetoprotein (AFP), tumour number, size, and volume were related to tumour grade and MVI (p<0.05) and were used for ANN building, whereas, tumour number did not enter into the logistic models. In the training group, ANN area under ROC curves (AUC) for tumour grade and MVI prediction were 0.94 and 0.92, both higher (p<0.001) than those of logistic models (0.85 for both). In the testing group, ANN correctly identified 93.3% of tumour grades (k=0.81) and 91% of MVI (k=0.73). Logistic models correctly identified 81% of tumour grades (k=0.55) and 85% of MVI (k=0.57). CONCLUSION ANN identifies HCC tumour grades and MVI on the basis of preoperative variables more accurately than the conventional linear model and should be used for tailoring clinical management.

Harm and Benefits of Primary Liver Resection and Salvage Transplantation for Hepatocellular Carcinoma

Primary transplantation offers longer life‐expectancy in comparison to hepatic resection (HR) for hepatocellular carcinoma (HCC) followed by salvage transplantation; however, livers not used for primary transplantation can be reallocated to the remaining waiting‐list patients, thus, the harm caused to resected patients could be balanced, or outweighed, by the benefit obtained from reallocation of livers originating from HCC patients first being resected. A Markov model was developed to investigate this issue based on literature data or estimated from the United Network for Organ Sharing database. Markov model shows that primary transplantation offers longer life‐expectancy in comparison to HR and salvage transplantation if 5‐year posttransplant survival remains higher than 60%. The balance between the harm for resected patients and the benefit for the remaining waiting list depends on (a) the proportion of HCC candidates, (b) the percentage shifted to HR and (c) the median expected time‐to‐transplant. Faced with a low proportion of HCC candidates, the harm caused to resected patients was higher than the benefit that could be obtained for the waiting‐list population from re‐allocation of extra livers. An increased proportion of HCC candidates and/or an increased median time‐to‐transplant could lead to a benefit for waiting‐list patients that outweighs this harm.

Liver Transplantation with the Meld System: A Prospective Study from a Single European Center

The efficacy of the Meld system to allocate livers has never been investigated in European centers. The outcome of 339 patients with chronic liver disease listed according to their Meld score between 2003 and 2005 (Meld era) was compared to 224 patients listed during the previous 2 years according to their Child score (Child era). During the Meld era, hepatocellular carcinomas (HCCs) had a ‘modified’ Meld based on their real Meld, waiting time and tumor stage. The dropouts were deaths, tumor progressions and too sick patients. The rate of removals from the list due to deaths and tumor progressions was significantly lower in the Meld than in the Child era: 10% and 1.2% versus 16.1% and 4.9%, p < 0.05. The 1‐year patient survival on the list was significantly higher in the Meld era (84% vs. 72%, p < 0.05). The prevalence of transplantation for HCC increased from 20.5% in the Child to 48.9% in the Meld era (p < 0.001), but between HCCs and non‐HCCs of this latter era the dropouts were comparable (9.4% vs. 14.9%, p = n.s.) as was the 1‐year patient survival on the list (83% vs. 84%, p = n.s.). The Meld allocation system improved the outcome of patients with or without HCC on the list.

A new priority policy for patients with hepatocellular carcinoma awaiting liver transplantation within the model for end-stage liver disease system

The best prioritization of patients with hepatocellular carcinoma (HCC) waiting for liver transplantation under the model for end‐stage liver disease (MELD) allocation system is still being debated. We analyzed the impact of a MELD adjustment for HCC, which consisted of the addition of an extra score (based on the HCC stage and waiting time) to the native MELD score. The outcome was analyzed for 301 patients with chronic liver disease listed for liver transplantation between March 1, 2001 and February 28, 2003 [United Network for Organ Sharing (UNOS)‐Child‐Turcotte‐Pugh (CTP) era, 163 patients, 28.8% with HCC] and between March 1, 2003 and February 28, 2004 (HCC‐MELD era, 138 patients, 29.7% with HCC). In the HCC‐MELD era, the cumulative dropout risk at 6 months was 17.6% for patients with HCC versus 22.3% for those patients without HCC (P = NS), similar to that in the UNOS‐CTP era. The cumulative probability of transplantation at 6 months was 70.3% versus 39.0% (P = 0.005), being higher than that in the UNOS‐CTP era for patients with HCC (P = 0.02). At the end of the HCC‐MELD era, 12 patients with HCC (29.3%) versus 57 without HCC (58.8%) were still on the list (P = 0.001). Both native and adjusted MELD scores were higher (P < 0.05) and progressed more in patients with HCC who dropped out than in those who underwent transplantation or remained on the list (the initial‐final native MELD scores were 17.3‐23.1, 15.5‐15.6, and 12.8‐14.1, respectively). The patients without HCC remaining on the list showed stable MELD scores (initial‐final: 15.1‐15.4). In conclusion, the present data support the strategy of including the native MELD scores in the allocation system for HCC. This model allows the timely transplantation of patients with HCC without severely affecting the outcome of patients without HCC. Liver Transpl 13:857–866, 2007.

Portal vein thrombosis and liver transplantation: evolution during 10 years of experience at the University of Bologna.

OBJECTIVE To evaluate the evolution of liver transplantation (LT) in cases with partial and total portal vein thrombosis (PVT). BACKGROUND Portal vein thrombosis and in particular total PVT are still surgically demanding conditions, which can exclude patients from LT or increase the postoperative complications after LT. METHODS We reviewed our 10-year experience (first era 1998–2002 and second era 2003–2008), comparing the outcome of patients with PVT to a group without PVT. RESULTS Among 889 LTs, we intraoperatively diagnosed 91 PVTs (10.2%):51 partial PVTs (56%) and 40 total PVTs (44%). The rate of complete PVTs increased from the first to the second era (2.2% vs. 6.7%, P < 0.005). Partial PVTs were mainly treated with thrombectomy while complete PVTs were managed with thrombectomy in 26 cases (63%), jumping graft in 6 (15%), portocaval hemitransposition in 6 (15%), and anastomosis to varix in 3 (7%). Among cases of PVT and no-PVT, the postoperative mortality was comparable (6.6% vs. 5.8%), as were the 1- and 5-year patient survival rates (85% and 68% PVT vs. 86% and 73% non-PVT). The postoperative outcome was similar in the PVT group between patients with partial and complete PVT, but in this last group, patient survival differed significantly between the 1st and 2nd era (57% vs. 89% at 1 year, P < 0.05). CONCLUSIONS Liver transplantation offers good survival in patients with partial PVT but also in selected cases with total PVT, where surgical innovation has improved the results.

Indication of the Extent of Hepatectomy for Hepatocellular Carcinoma on Cirrhosis by a Simple Algorithm Based on Preoperative Variables

OBJECTIVE To produce a model indicating the extent of hepatectomy for hepatocellular carcinoma on cirrhosis based on easily available preoperative data. DESIGN Retrospective study based on multicenter prospectively updated databases. SETTING Two tertiary referral centers specializing in hepatobiliary surgery. PATIENTS A total of 466 patients undergoing hepatectomy for hepatocellular carcinoma on cirrhosis between 1995 and 2006. MAIN OUTCOME MEASURES To create a decision tree for safe liver resection based on factors affecting irreversible postoperative liver failure (IPLF). RESULTS A total of 23 patients (4.9%) developed IPLF. The model for end-stage liver disease (MELD) score (categorized as <9, 9-10, and >10; P < .05 for all comparisons) and extent of hepatectomy were independent predictors of IPLF. In patients with a MELD score of less than 9, the IPLF rate was 0.4%. In patients with a MELD score of 9 or 10, the IPLF rate was 1.2% for resections of less than 1 segment, 5.1% for segmentectomies or bisegmentectomies, and 11.1% for major hepatectomies. In this category of MELD, serum sodium levels identified a low-risk group (sodium > or =140 mEq/L; to convert to millimoles per liter, multiply by 1.0) not experiencing IPLF and a high-risk group (sodium <140 mEq/L) in which resections of less than 1 segment led to an IPLF rate of 2.5% and resections of 1 segment or more led to an IPLF rate of more than 5% (P < .05). In patients with a MELD score of more than 10, the IPLF rate was more than 15% in all types of hepatectomies. CONCLUSION A simple algorithm based on the MELD score and serum sodium level can indicate the maximum tolerable extent of hepatectomy for hepatocellular carcinoma on cirrhosis.

Liver transplantations with donors aged 60 years and above: the low liver damage strategy

According to transplant registries, grafts from elderly donors have lower survival rates. During 1999–2005, we evaluated the outcomes of 89 patients who received a liver from a donor aged ≥ 60 years and managed with the low liver‐damage strategy (LLDS), based on the preoperative donor liver biopsy and the shortest possible ischemia time (group D ≥ 60‐LLDS). Group D ≥ 60‐LLDS was compared with 198 matched recipients, whose grafts were not managed with this strategy (89 donors < 60 years, group D < 60‐no‐LLDS and 89 donors aged ≥60 years, group D ≥ 60‐no‐LLDS). In the donors proposed from the age group of ≥60 years, the number of donors rejected decreased during the study period and the LLDS was found to be responsible for this in a significant manner (47% vs. 60%, respectively P < 0.01). Among the recipients transplanted, the clinical features (age, gender, viral infection, child and model for end‐stage liver disease score) were comparable among groups, but group D ≥ 60‐LLDS had a lower mean ischemia time: 415 ± 106 min vs. 465 ± 111 (D < 60‐no‐LLDS), P < 0.05 and vs. 476 ± 94 (D ≥ 60‐no‐LLDS), P < 0.05. After a median follow‐up of 3 years, the 1‐ and 3‐year graft survival rates of group D ≥ 60‐LLDS (84% and 76%) were comparable with group D < 60‐no‐LLDS (89% and 76%) and were significantly higher than group D ≥ 60‐no‐LLDS (71% and 54%), P < 0.005. In conclusion, the LLDS optimized the use of livers from elderly donors.