The role of hypothermic machine perfusion in selecting renal grafts with advanced histological score.

BACKGROUND: Few studies explored the role of hypothermic machine perfusion (HMP) in the sub-group of non-standard renal grafts with a biopsy-proven advanced histological impairment. This study aimed to investigate the role of HMP in grafts with a Karpinski Score >3 in terms of the need for dialysis, creatinine reduction ratio at day-7 (CRR7), and 3-year graft survival. METHODS: Twenty-three perfused grafts with Karpinski Score >3 evaluated between November 2017 and December 2018 were retrospectively analyzed and compared with a control group of 32 non-perfused grafts transplanted between January 2014 and October 2017. RESULTS: After transplantation, perfused grafts had fewer cases requiring dialysis (8.7% vs. 34.4%; p = 0.051), a better reduction in serum creatinine (median at 7 days: 2.2 vs. 4.3 mg/dl; p = 0.045), and shorter length of hospital stay (median 11 vs. 15 days; p = 0.01). Three-year death-censored graft survival was better in the perfused cases (91.3% vs. 77.0%; p = 0.16). In perfused grafts, initial renal resistance (RR) had the best predictive value for renal function recovery after the first week, as defined by CRR7 ≤ 70% (AUC = 0.83; p = 0.02). A cut-off value of 0.5 mm Hg/ml/min showed a sensitivity of 82.4%, a specificity of 83.3%, and diagnostic odds ratio = 23.4. After dividing the entire population into a Low-RR (n = 8) and a High-RR Group (n = 15), more cases with CRR7 ≤ 70% were reported in the latter group (86.7 vs. 13.3%; p = 0.03). CONCLUSION: HMP yielded promising results in kidneys with Karpinski Score >3. Initial RR should be of interest in selecting non-standard organs for single kidney transplantation even in impaired histology.

Metformin exerts anti-cancerogenic effects and reverses epithelial-to-mesenchymal transition trait in primary human intrahepatic cholangiocarcinoma cells.

Intrahepatic cholangiocarcinoma (iCCA) is a highly aggressive cancer with marked resistance to chemotherapeutics without therapies. The tumour microenvironment of iCCA is enriched of Cancer-Stem-Cells expressing Epithelial-to-Mesenchymal Transition (EMT) traits, being these features associated with aggressiveness and drug resistance. Treatment with the anti-diabetic drug Metformin, has been recently associated with reduced incidence of iCCA. We aimed to evaluate the anti-cancerogenic effects of Metformin in vitro and in vivo on primary cultures of human iCCA. Our results showed that Metformin inhibited cell proliferation and induced dose- and time-dependent apoptosis of iCCA. The migration and invasion of iCCA cells in an extracellular bio-matrix was also significantly reduced upon treatments. Metformin increased the AMPK and FOXO3 and induced phosphorylation of activating FOXO3 in iCCA cells. After 12 days of treatment, a marked decrease of mesenchymal and EMT genes and an increase of epithelial genes were observed. After 2 months of treatment, in order to simulate chronic administration, Cytokeratin-19 positive cells constituted the majority of cell cultures paralleled by decreased Vimentin protein expression. Subcutaneous injection of iCCA cells previously treated with Metformin, in Balb/c-nude mice failed to induce tumour development. In conclusion, Metformin reverts the mesenchymal and EMT traits in iCCA by activating AMPK-FOXO3 related pathways suggesting it might have therapeutic implications.

Female gender and overestimation of glomerular filtration rate: Independent predictors of acute kidney injury after liver transplantation
.

Acute kidney injury (AKI) in liver transplant (LT) setting is a recognized complication and is related to increased morbidity and mortality. Pre-LT renal function is difficult to estimate, in particular for the female gender. The aim of the study was to evaluate the incidence of post-LT AKI, its relationship with survival, and related risk factors. In a single-center retrospective study of consecutive LT patients (2008 - 2015), we assessed patient characteristics and intra-LT events, and post-operative data were collected. The occurrence of AKI post-LT was also evaluated (KDIGO guidelines). Data of 145 LT patients were analyzed. 45 (31.0%) patients showed an overestimation of glomerular filtration rate (over-GFR), defined as GFR > 120 mL/min/1.73m2; 83 patients (57.2%) developed post-LT AKI. The patients (n = 145) were divided into two groups: 123 (84.8%) patients with no-AKI & AKI stage 1 and 22 (15.2%) patients with AKI stages 2 and 3. Patients with AKI stages 2 and 3 were characterized by a significantly decreased 5-year survival (p < 0.001). On the multivariable analysis, female gender and over-GFR were significantly predictive for development of AKI stages 2 and 3. Female gender has already been reported as a discriminant factor for LT candidates. Altered estimation of renal function also needs to be considered in this setting, as this could mask the presence of an unknown compromised renal function.

Esophageal carcinoma cuniculatum: systematic review of the literature and report of two cases.

BACKGROUND AND AIMS: Carcinoma cuniculatum (CC) is a rare variant of an extremely well-differentiated squamous cell carcinoma. The most commonly involved site is the skin, with a preference for the sole. Only 15 cases of esophageal CC have been reported so far. Based on published data, the clinical behavior of CC has not been clearly defined. We describe the clinical-pathologic features of two cases of esophageal CC, and provide a review of the available literature, to shed more light on this unusual tumor. METHODS: A detailed gross and histologic analysis was performed on two cases of surgically treated esophageal CC. The patients were followed-up after surgery. A systematic search was also done concerning studies focused on esophageal CC. A search of the electronic databases MEDLINE-PubMed was conducted using the following research terms: (esophagus) AND (cuniculatum carcinoma). RESULTS: Both patients were alive at last follow-up at six and nine months from surgery without any recurrence. Concerning the fifteen cases reported from the systematic review, median follow-up after surgery was very long as compared to common esophageal cancers (4.0 years), with only one recurrence observed. CONCLUSION: CC shows an indolent clinical behavior, with a low recurrence rate after radical surgery. The diagnosis of this rare tumor is typically made after surgery. An aggressive approach is required with curative intents.

Collaterals management during pancreatoduodenectomy in patients with celiac axis stenosis: A systematic review of the literature.

BACKGROUND/OBJECTIVES: Celiac axis stenosis (CAS) represents an uncommon and typically innocuous condition. However, when a pancreatic resection is required, a high risk for upper abdominal organs ischemia is observed. In presence of collaterals, such a risk is minimized if their preservation is realized. The aim of the present study is to systematically review the literature with the intent to address the routine management of collateral arteries in the case of CAS patients requiring pancreatoduodenectomy. METHODS: A systematic search was done in accordance with the PRISMA guidelines, using "celiac axis stenosis" AND "pancreatoduodenectomy" as MeSH terms. Seventy-four articles were initially screened: eventually, 30 articles were identified (n = 87). RESULTS: The main cause of CAS was median arcuate ligament (MAL) (n = 31; 35.6%), followed by atherosclerosis (n = 20; 23.0%). CAS was occasionally discovered during the Whipple procedure in 15 (17.2%) cases. Typically, MAL was divided during surgery (n = 24/31; 77.4%). In the great majority of cases (n = 83; 95.4%), vascular abnormalities involved the pancreatoduodenal arteries (i.e., dilatation, arcade, channels, aneurysms). Collateral arteries were typically preserved, being divided or reconstructed in only 14 (16.1%) cases, respectively. Severe ischemic complications were reported in six (6.9%) patients, 20.0% of whom were reported in patients with preoperatively unknown CAS (p-value 0.06). CONCLUSIONS: A correct pre-operative evaluation of anatomical conditions as well as a correct surgical planning represent the paramount targets in CAS patients with arterial collaterals. Vascular flow must be always safeguarded preserving/reconstructing the collaterals or resolving the CAS, with the final intent to avoid dreadful intra- and post-operative complications.

TGF-ß signaling is an effective target to impair survival and induce apoptosis of human cholangiocarcinoma cells: A study on human primary cell cultures.

Cholangiocarcinoma (CCA) and its subtypes (mucin- and mixed-CCA) arise from the neoplastic transformation of cholangiocytes, the epithelial cells lining the biliary tree. CCA has a high mortality rate owing to its aggressiveness, late diagnosis and high resistance to radiotherapy and chemotherapeutics. We have demonstrated that CCA is enriched for cancer stem cells which express epithelial to mesenchymal transition (EMT) traits, with these features being associated with aggressiveness and drug resistance. TGF-ß signaling is upregulated in CCA and involved in EMT. We have recently established primary cell cultures from human mucin- and mixed-intrahepatic CCA. In human CCA primary cultures with different levels of EMT trait expression, we evaluated the anticancer effects of: (i) CX-4945, a casein kinase-2 (CK2) inhibitor that blocks TGF-ß1-induced EMT; and (ii) LY2157299, a TGF-ß receptor I kinase inhibitor. We tested primary cell lines expressing EMT trait markers (vimentin, N-cadherin and nuclear catenin) but negative for epithelial markers, and cell lines expressing epithelial markers (CK19-positive) in association with EMT traits. Cell viability was evaluated by MTS assays, apoptosis by Annexin V FITC and cell migration by wound-healing assay. RESULTS: at a dose of 10 µM, CX4945 significantly decreased cell viability of primary human cell cultures from both mucin and mixed CCA, whereas in CK19-positive cell cultures, the effect of CX4945 on cell viability required higher concentrations (>30µM). At the same concentrations, CX4945 also induced apoptosis (3- fold increase vs controls) which correlated with the expression level of CK2 in the different CCA cell lines (mucin- and mixed-CCA). Indeed, no apoptotic effects were observed in CK19-positive cells expressing lower CK2 levels. The effects of CX4945 on viability and apoptosis were associated with an increased number of γ-H2ax (biomarker for DNA double-strand breaks) foci, suggesting the active role of CK2 as a repair mechanism in CCAs. LY2157299 failed to influence cell proliferation or apoptosis but significantly inhibited cell migration. At a 50 µM concentration, in fact, LY2157299 significantly impaired (at 24, 48 and 120 hrs) the wound-healing of primary cell cultures from both mucin-and mixed-CCA. In conclusion, we demonstrated that CX4945 and LY2157299 exert relevant but distinct anticancer effects against human CCA cells, with CX4945 acting on cell viability and apoptosis, and LY2157299 impairing cell migration. These results suggest that targeting the TGF-ß signaling with a combination of CX-4945 and LY2157299 could have potential benefits in the treatment of human CCA.

Portal vein thrombosis before liver transplant does not alter postoperative patient or graft survival.

OBJECTIVES: Portal vein thrombosis may complicate liver transplant. The purpose of this study was to analyze our cohort of transplanted recipients to evaluate the relation between preoperative portal vein thrombosis and patient and graft survival after liver transplant. MATERIALS AND METHODS: We retrospectively analyzed 209 patients who had liver transplant; 2 patients who had the diagnosis of portal vein thrombosis made during surgery were excluded. Patients were stratified in 2 groups according to whether they had (15 patients) or did not have portal vein thrombosis (192 patients) before liver transplant and were compared for early and late survival. RESULTS: In all 15 patients who had portal vein thrombosis, the Yerdel grade was I or II. Patients who had preoperative portal vein thrombosis had lower median survival (portal vein thrombosis, 47 mo; no portal vein thrombosis, 61 mo), frequency of total number of deaths (portal vein thrombosis, 4 [27%]; no portal vein thrombosis, 68 [35%]), and frequency of death within 3 months after transplant (portal vein thrombosis, 1 [7%]; no portal vein thrombosis, 23 [12%]). However, there was no significant difference between the 2 groups in patient or graft survival. CONCLUSIONS: Low-grade portal vein thrombosis detected before liver transplant is not an absolute contraindication for liver transplant. Radiographic screening before liver transplant is recommended to minimize surgical difficulty.

The Fas/Fas ligand apoptosis pathway underlies immunomodulatory properties of human biliary tree stem/progenitor cells.

BACKGROUND & AIMS: Human biliary tree stem/progenitor cells (hBTSCs) are multipotent epithelial stem cells, easily obtained from the biliary tree, with the potential for regenerative medicine in liver, biliary tree, and pancreas diseases. Recent reports indicate that human mesenchymal stem cells are able to modulate the T cell immune response. However, no information exists on the capabilities of hBTSCs to control the allogeneic response. The aims of this study were to evaluate FasL expression in hBTSCs, to study the in vitro interaction between hBTSCs and human lymphocytes, and the role of Fas/FasL modulation in inducing T cell apoptosis in hBTSCs/T cell co-cultures. METHODS: Fas and FasL expression were evaluated in situ and in vitro by immunofluorescence and western blotting. Co-cultures of hBTSCs with human leukocytes were used to analyze the influence of hBTSCs on lymphocytes activation and apoptosis. RESULTS: hBTSCs expressed HLA antigens and FasL in situ and in vitro. Western blot data demonstrated that hBTSCs constitutively expressed high levels of FasL that increased after co-culture with T cells. Confocal microscopy demonstrated that FasL expression was restricted to EpCAM(+)/LGR5(+) cells. FACS analysis of T cells co-cultured with hBTSCs indicated that hBTSCs were able to induce apoptosis in activated CD4(+) and CD8(+) T cell populations. Moreover, the Fas receptor appears to be more expressed in T cells co-cultured with hBTSCs than in resting T cells. CONCLUSIONS: Our data suggest that hBTSCs could modulate the T cell response through the production of FasL, which influences the lymphocyte Fas/FasL pathway by inducing "premature" apoptosis in CD4(+) and CD8(+) T cells.

Effects of unilateral ovariectomy on female fertility outcome.

PURPOSE: To compare the fertility outcome among women subjected to unilateral ovariectomy and other abdominal or non-gynaecologic pelvic surgery. METHODS: In this retrospective cohort study, 113 fertile women, surgically treated between 1990 and 2001 at Sapienza University of Rome with unilateral ovariectomy (UO), appendectomy (AP) or cholecystectomy (CO) for benign disease, were analysed for fertility outcome. Patients with assessed pre-surgical fertility defects, previous abdominal or pelvic surgeries and post-surgical contraception were not included. RESULTS: Thirty-five women underwent UO, 39 were subjected to AP and 39 were treated with CO. After a minimum 10-year post-surgical interval, the overall number of successful pregnancies was 75. The rate of women who experienced at least one post-operative successful pregnancy was: 48.5 % in UO, 41 % in AP and 53.8 % in CO (UO vs. AP, P = 0.55; UO vs. CO, P = 0.99; AP vs. CO, P = 0.53). One patient (2.8 %) in UO, one patient (2.6 %) in AP and two patients (5.1 %) in CO underwent Assisted Reproductive Technology to become pregnant. The rate of women who reported at least one miscarriage was: 10/35 (28.5 %) in UO, 11/39 (28.2 %) in AP, 12/39 (30.8 %) in CO (UO vs. AP, P = 0.93; UO vs. CO, P = 0.89; AP vs. CO, P = 0.81). One ectopic pregnancy was reported in CO group and one stillbirth occurred in one AP patient. CONCLUSIONS: No statistical difference in terms of post-operative fertility outcome between patients subjected to UO, AP or CO was found, thus allowing to suppose that the removal of one ovary does not significantly worsen the female fertility outcome respect to other abdominal or pelvic procedures.

Transjugular intrahepatic portosystemic shunt for a wait list patient is not a contraindication for orthotopic liver transplant outcomes.

OBJECTIVES: A transjugular intrahepatic portosystemic shunt for treating recurrent variceal bleeding or refractory ascites can be used as bridge therapy in patients awaiting a liver transplant. However, incorrect placement of the transjugular intrahepatic portosystemic shunt may complicate surgery during a liver transplant. This study sought to analyze a cohort of transplanted recipients to underscore whether transjugular intrahepatic portosystemic shunts can negatively affect liver transplant outcomes. MATERIALS AND METHODS: We retrospectively analyzed 207 patients who had undergone a liver transplant between January 2001 and December 2009 in the Rome "La Sapienza" center. Transjugular intrahepatic portosystemic shunt was performed before the liver transplant in 36 cases (17%). The analyzed population was stratified into 2 groups (no transjugular intrahepatic portosystemic shunt [n=171 ] and transjugular intrahepatic portosystemic shunt [n=36 ]), and patient survival outcomes were compared. RESULTS: In the no-transjugular intrahepatic portosystemic shunt group, 60 of 171 deaths (35%) were reported, 20 of which were seen in the first 3 months after the liver transplant. In the same group, 61 graft losses (36%) were observed, with 19 of which were seen in the first 3 months after the liver transplant. In transjugular intrahepatic portosystemic shunt group, 12 of the 36 deaths (33%) were seen; 5 patients died within 3 months of the liver transplant. In this latter group, 12 grafts (33%) were lost, 4 of which were reported during the first 3 months after surgery. The median patient survival was 64 months and 69 months in the 2 groups. On survival analysis, no significant differences were found between the 2 groups. CONCLUSIONS: Transjugular intrahepatic portosystemic shunt does not seem to affect outcomes after a liver transplant. We suggest that clinicians recognized the location of the stent to prevent any difficulty during surgery.

A case of portal vein arterialization after a liver transplant.

Hepatic artery thrombosis represents a potentially deadly complication after a liver transplant. Portal vein arterialization recently has been proposed as a bridge approach in patients with hepatic artery thrombosis needing a retransplant. We report the case of a 53-year-old man treated with a liver transplant for a cryptogenetic cirrhosis. One month after a liver transplant, a hepatic artery thrombosis was documented, and a portal vein arterialization as bridge therapy for another liver transplant was performed. After surgery, improvement in the patient's liver functioning was seen. No signs of portal hypertension or hepatic abscesses were documented. Unfortunately, 8 months after the liver transplant, the patient experienced a severe urinary infection caused by a multidrug-resistant Klebsiella and died. An increase in the oxygen supply to the liver parenchyma after portal vein arterializations represents rationale use for managing hepatic artery thromboses. Several cases of treating post liver transplant hepatic artery thromboses have been reported in the literature. Portal vein arterializations can be used as bridge therapy in well-selected situations of post-liver transplant hepatic artery thromboses. Strict surveillance should be used to prevent the onset of complications that can exclude a patient from a transplant. The correct timing for retransplant is not fully known, but we think the shorter the time to retransplant, the better is the patient survival.

Laparoscopy in Liver Transplantation: The Future has Arrived.

In the last two decades, laparoscopy has revolutionized the field of surgery. Many procedures previously performed with an open access are now routinely carried out with the laparoscopic approach. Several advantages are associated with laparoscopic surgery compared to open procedures: reduced pain due to smaller incisions and hemorrhaging, shorter hospital length of stay, and a lower incidence of wound infections. Liver transplantation (LT) brought a radical change in life expectancy of patients with hepatic end-stage disease. Today, LT represents the standard of care for more than fifty hepatic pathologies, with excellent results in terms of survival. Surely, with laparoscopy and LT being one of the most continuously evolving challenges in medicine, their recent combination has represented an astonishing scientific progress. The intent of the present paper is to underline the current role of diagnostic and therapeutic laparoscopy in patients waiting for LT, in the living donor LT and in LT recipients.

Alpha-fetoprotein and novel tumor biomarkers as predictors of hepatocellular carcinoma recurrence after surgery: a brilliant star raises again.

Alpha-fetoprotein (AFP), des-γ-carboxy prothrombin (DCP), and lens culinaris agglutinin-reactive fraction of AFP (AFP-L3) have been developed with the intent to detect hepatocellular carcinoma (HCC) and for the surveillance of at-risk patients. However, at present, none of these tests can be recommended to survey cirrhotic patients at risk for HCC development because of their suboptimal ability for routine clinical practice in HCC diagnosis. Starting from these considerations, these markers have been therefore routinely and successfully used as predictors of survival and HCC recurrence in patients treated with curative intent. All these markers have been largely used as predictors in patients treated with hepatic resection or locoregional therapies, mainly in Eastern countries. In recent studies, AFP has been proposed as predictor of recurrence after liver transplantation and as selector of patients in the waiting list. Use of AFP modification during the waiting list for LT is still under investigation, potentially representing a very interesting tool for patient selection. The development of a new predictive model combining radiological and biological features based on biological markers is strongly required. New genetic markers are continuously discovered, but they are not already fully available in the clinical practice.

Recurrence of hepatocellular cancer after liver transplantation: the role of primary resection and salvage transplantation in East and West.

BACKGROUND & AIMS: Greater tumor aggressiveness and different management modalities of hepatocellular cancer (HCC) before liver transplantation (LT) may explain the higher recurrence rates reported in Asia. This study investigates the prognostic factors for HCC recurrence in a Western and an Eastern HCC patient cohort in order to analyze the respective roles of tumor- and management-related factors on the incidence of post-LT HCC recurrence. METHODS: Data of 273 HCC patients, transplanted during the period January 1999-March 2009, were obtained from the Rome Inter-University Liver Transplant Consortium (n=157) and Hong Kong University (n=116) databases. Median follow-up was 4.3 years (range: 0.2-12). Recurrence rate and multivariate logistic regression analysis was performed on the entire population and on Milan criteria-in (MC-in) patients. RESULTS: Multivariate analysis on the entire population identified four independent risk factors for post-LT HCC recurrence: microvascular invasion (odds ratio, OR=4.88; p=0.001), poor tumor grading (OR=6.86; p=0.002), diameter of the largest tumor (OR=4.72; p=0.05), and previous liver resection (LR) (OR=3.34; p=0.04). After removal of LR, only tumor-related variables were independent risk factors for recurrence. When only MC-in patients were analyzed, no difference was observed between the two cohorts in terms of recurrence rate after LR patient removal. CONCLUSIONS: LR followed by salvage "for HCC recurrence" LT represents the main reason for a higher HCC recurrence rate in the Hong Kong patients, but not LR followed by salvage "for liver failure" LT in the Roman group. This approach towards HCC before LT may not be universally applicable. The precise patient background must be taken into account in order to identify the best pre-LT strategy.

[Adacolumn apheresis for hepatitis C virus in patients waiting for kidney transplant. Preliminary study]. / Trattamento con Adacolumn leucocitaferesi per la rimozione del virus C nei pazienti in lista per trapianto di rene. Studio preliminare.

Hepatitis C virus (HCV) infection occurs much more frequently in the hemodialysis population than in the general population. Patients with chronic kidney disease with persistent HCV infection may develop serious and progressive chronic liver disease, with associated long-term morbidity and mortality related to cirrhosis and hepatocellular carcinoma. Monocytes and macrophages are known to produce extrahepatic breeding sites and spread the disease. Our aim was to lower the levels of macrophages, granulocytes, monocytes, proinflammatory cells and viremia using an extracorporeal device: the Adacolumn ® leukocyte apheresis system (Otsuka). The Adacolumn is a direct hemoperfusion-type leukapheresis device. The column is a single-use (disposable) polycarbonate column with a capacity of about 335 mL, filled with 220-g cellulose acetate beads of 2 mm in diameter bathed in physiological saline. The carriers adsorb ''activated'' granulocytes and monocytes/macrophages that bear Fc and complement receptors. The patients underwent five 1-hour sessions for five consecutive days. The column was placed in an extracorporeal setting with a perfusion rate of 30 mL/min and a duration of 60 minutes. A reduction of viremia was observed in all patients in association with a decrease in cytokine levels and a proportional decrease in immune cells. Although this study investigated responses in a small number of patients, it was shown that the Adacolumn changed the cellular immunity and promoted early viral response.

Combination of biological and morphological parameters for the selection of patients with hepatocellular carcinoma waiting for liver transplantation.

BACKGROUND: In the last several years, there has been no agreement on how to possibly expand the Milan criteria (MC) in the selection of patients with hepatocellular carcinoma (HCC) for listing for liver transplant (LT). The aim of the study is to evaluate morphological and biological tumor parameters to identify new expanded criteria for the selection of patients with HCC as candidates for LT. METHODS: We retrospectively analyzed 158 consecutive patients with HCC who underwent LT. RESULTS: Twelve (7.6%) recurrences were observed. At multivariate analysis, alpha-fetoprotein (AFP) >400 ng/mL (odds ratio [OR] 8.4, p<0.01) and total tumor diameter (TTD) >8 cm (OR 7.4, p=0.01) were the strongest predictors for recurrence. AFP-TTD criteria resulted in a low five-yr recurrence rate (4.9%) and an increased number of LT compared with the MC (22.2% increase). The five-yr disease-free survival rate was 74.4% in AFP-TTD criteria in patients, with a higher effectiveness in stratifying the cohort with respect to the MC. CONCLUSIONS: Both AFP and TTD are good independent predictors of HCC recurrence. Their combination appears to obtain a better selection of candidates for LT without worsening patient survival and recurrence rates. This approach allows for an increase in the number of potentially transplantable patients.

Role of alpha-fetoprotein in selection of patients with hepatocellular carcinoma waiting for liver transplantation: must we reconsider it?

BACKGROUND: Milan criteria (MC) represent the most commonly adopted criteria for the selection of patients with hepatocellular carcinoma (HCC) waiting for liver transplantation (LT). However, MC are exclusively based on morphological aspects. The aim of the present study was to evaluate pre-LT-detectable biological parameters, to compare them with morphological ones in terms of tumor recurrence prediction and patient survival. METHODS: A cohort of 153 consecutive adult patients who underwent LT for HCC on cirrhosis from January 1999 to March 2009 was retrospectively analyzed. RESULTS: HCC recurrence was observed in 12 patients (7.8%). At multivariate logistic regression analysis, serum alpha-fetoprotein (AFP) was the unique independent negative risk factor for the development of HCC recurrence (odds ratio 2.0, p=0.03). Adopting a cutoff value of 210 ng/mL, patients who presented serum AFP =210 ng/mL showed a 5-year survival rate of 23.3% versus 76.2% observed in patients with pre-LT serum AFP <210 ng/mL (log-rank test: <0.0001). CONCLUSIONS: In our experience, AFP was the strongest predictor of HCC recurrence, stronger than tumor morphology. AFP could ameliorate the selection of LT candidates. Further studies to evaluate the combination of morphological and biological criteria are needed.