Post-hoc analysis of a randomized controlled trial on the impact of pre-transplant use of probiotics on outcomes after liver transplantation.

Perioperative use of probiotics serves as efficient prophylaxis against postoperative infections after liver transplantation, yet data on long-term effects of pre-transplant probiotic intake is lacking. The aim of this study was to assess the effects of pre-transplant probiotic administration on long-term results of liver transplantation. This was secondary analysis of a randomized trial. Patients were randomized to receive either 4-strain probiotic or placebo before liver transplantation. Five year graft survival was set as the primary end-point. Secondary end-points comprised serum bilirubin and C-reactive protein (CRP) concentration, international normalized ratio (INR), serum transaminases and gamma-glutamyl transferase (GGT) activity. Study group comprised 44 patients, of whom 21 received probiotics and 23 received placebo with 5-year graft survival of 81.0% and 87.0%, respectively (p = 0.591). Patients in the probiotic arm exhibited lower INR (p = 0.001) and CRP (p = 0.030) over the first 6 post-transplant months. In the absence of hepatitis B or C virus infection, pre-transplant administration of probiotics also reduced aspartate transaminase activity (p = 0.032). In the intervention arm, patients receiving probiotics for under and over 30 days had 5-year graft survival rates of 100% and 66.7%, respectively (p = 0.061). Duration of probiotic intake > 30 days was additionally associated with increased INR (p = 0.031), GGT (p = 0.032) and a tendency towards increased bilirubin (p = 0.074) over first 6 post-transplant months. Pre-transplant administration of probiotics has mild positive influence on 6-month allograft function, yet should not exceed 30 days due to potential negative effects on long-term outcomes. (ClinicalTrials.gov Identifier: NCT01735591).

Stereotactic body radiation therapy for early-stage hepatocellular carcinoma - a systematic review on outcome.

Background: Hepatocellular carcinoma (HCC) incidence is rising worldwide, especially due to increased detection of early-stage or small-sized tumors. Nevertheless, most of the patients are still not qualified for surgical resection at diagnosis due to the localization of the tumor, underlying liver disease or comorbidities. Stereotactic body radiation therapy (SBRT) is a radiotherapy modality which can deliver a high dose of radiation to the target tissue with a high degree of precision. It shows promise in terms of efficacy and morbidity.Material and methods: The aim of this systematic review is to summarize current knowledge on patient-specific outcomes of SBRT for small HCC including overall survival, local control, the effect of dose escalation and the toxicity of the treatment. The systematic review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). After a comprehensive database search, 16 studies (973 patients with 1034 lesions) were included in qualitative and quantitative analyses; 14 of them were retrospective.Results: Average tumor diameter was 23 mm and 95% of patients were in good general condition. Median BED10 (biologically equivalent dose calculated for α/ß ratio of 10 Gy) was 100 Gy (range 59.5-180 Gy). Mean weighted local control across studies was 94%, 92% and 93% at 1, 2, and 3 years, respectively. Mean weighted overall survival across studies was 90.9%, 67.5% and 73.4% at 1, 2, and 3 years, respectively. There were 171 grade 1-2 toxicities (17.5%) and 53 ≥ grade 3 toxicities (5.3%). There was no treatment-associated mortality.Conclusion: SBRT offers high local control with overall survival that is comparable with radiofrequency ablation and surgery. Quality of findings, especially on toxicities, is decreased by incomplete reporting and retrospective designs of published studies. Therefore, there is a need for better reporting and prospective studies to univocally recommend SBRT as a definitive treatment option in the guidelines for small HCCs.

Accuracy of Computed Tomography in the Assessment of Milan Criteria in Liver Transplantation for Hepatocellular Carcinoma.

BACKGROUND: Despite worldwide debate on optimal selection of patients with hepatocellular carcinoma (HCC) for liver transplantation, the Milan criteria remain the benchmark for comparisons. Moreover, morphologic tumor features are universally considered important in pretransplant patient evaluation. The aim of this study was to establish the diagnostic accuracy of multiphasic computed tomography (CT) in assessing HCC burden before liver transplantation with special reference to Milan criteria fulfillment. METHODS: This retrospective study was based on a data from 27 HCC patients after liver transplantation with available CT performed within 30 days pretransplant. CT results were compared with explant pathology with respect to Milan criteria fulfillment, tumor number, and diameter of the largest tumor. RESULTS: Out of 19 patients within the Milan criteria on CT, 3 fell beyond the criteria on explant pathology with a gross underestimation rate of 15.8%. Out of 8 patients beyond the Milan criteria on CT, 3 were within the criteria on explant pathology with a gross overestimation rate of 37.5%. Regarding tumor number, CT was accurate only in 14 patients (51.9%), while overestimation and underestimation occurred in 5 (18.5%) and 8 (29.6%) patients, respectively. Overestimation and underestimation of largest tumor size by at least 1 cm occurred in 4 (14.8%) and 7 (25.9%) patients, respectively. DISCUSSION: Multiphasic CT is associated with a remarkable risk of both under- and overestimation of HCC burden before transplantation. Transplant eligibility should not be solely based on CT results.

Impact of Donor Risk Index on Risk of Hepatic Artery Thrombosis in Patients After Orthotopic Liver Transplantation.

BACKGROUND: Hepatic artery thrombosis (HAT) is one of the most severe complications after liver transplantation (LT). HAT can lead to early graft loss and retransplantation or death of the recipient. METHODS: This retrospective cohort study was conducted using data from patients treated between January 2008 and December 2013 in the Department of General, Transplant and Liver Surgery at the Medical University of Warsaw. A total of 750 patients underwent LT over this period. RESULTS: HAT occurred in 27 patients (2.1%). The median DRI was 1.414 (IQR 1.103-1.578) points and median donor age was 47 (IQR 33-56) years. The optimal cut-off value of DRI in predicting HAT was ≥1.328 points. The cutoff point was characterized by sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 88.0%, 41.3%, 5.5% and 98.9%, respectively (AUC = 0.605, 95% CI 0.477-0.733). A DRI ≥1.328 was a significant risk factor for HAT (OR = 5.16, 95% confidence interval [CI] 1.529-17.48, P = .008). The optimal cutoff point for donor age was 50 years and was characterized by sensitivity, specificity, PPV, and NPV of 66.7%, 55.8%, 5.3%, and 97.8%, respectively. Donor age ≥50 years (OR = 2.53, 95% CI 1.123-5.714, P = .025) was a significant risk factor for HAT. CONCLUSION: DRI is a clinically relevant factor that allows estimating the risk of HAT after liver transplantation from a deceased donor. To reduce the incidence of this complication, the allocation of organs taken from donors at DRI exceeding 1.328 for recipients without other HAT risk factors should be considered.

Risk Factors of Prolonged ICU Stay in Liver Transplant Recipients in a Single-Center Experience.

BACKGROUND: Prolonged initial intensive care unit (ICU) stay after liver transplantation (LT) is associated with prolonged total hospitalization, increased hospital mortality, and impaired patient and graft survival. Recent data suggested that model for end-stage liver disease (MELD) score at the time of LT and the length of surgery were the two independent risk factors for an ICU stay longer than 3 days after LT. We further identified factors influencing prolonged ICU stay in single-center liver graft recipients. PATIENTS AND METHODS: One hundred fifty consecutive LT recipients (M/F 94/56, median age 55 (range, 39-60), 36% with viral hepatitis, were prospectively enrolled into the study. Associations between clinical factors and prolonged ICU stay were evaluated using logistic regression models. Receiver operating characteristic curves were analyzed to determine the appropriate cutoffs for continuous variables. Threshold for significance was P ≤ .05. RESULTS: Highly prolonged (≥8 days) and moderately prolonged (≥6 days) postoperative ICU stay was noted in 19 (12.7%) and 59 (39.3%) patients, respectively. Serum bilirubin (P = .001) and creatinine concentrations (P = .011), international normalized ratio (P = .004), and sodium-MELD (P < .001) were all significantly associated with postoperative intensive care unit stay over or equal to 75th percentile (6 days). Sodium-MELD was significantly associated with postoperative care unit stay greater or equal to the 90th percentile (8 days; P = .018). CONCLUSIONS: Sodium-MELD might be a novel risk factor of prolonged ICU stay in this single-center experience.

Is Elective Status a Predictor of Poor Survival in Liver Retransplantation?

BACKGROUND: Orthotopic liver retransplantation (reLT) is considered to have poorer outcomes than primary transplantation. The objective of this study was to analyze the impact of medical urgency status as a predictor of patient survival after reLT. METHODS: Forty-nine patients who underwent reLT were included in this retrospective study. Urgent or elective status was based on the judgment of the surgical team, selected variables, and the Model for End-Stage Liver Disease score. Multivariate analysis was performed to identify variables associated with patient survival following reLT. RESULTS: Overall survival of the patient cohort was 57% at 1 year and 54.3% at 3 years after reTL. Survival in urgent-status patients was 68.8% and 63.4% at 1 and 3 years, respectively, whereas the survival rate for elective patients was 40.0% at both time points. Mortality was significantly associated with elective status (hazard ratio [HR], 2.42; P = .046) at 1 year, but was no longer significant (HR, 2.19; P < .069) after 3 years of follow-up. CONCLUSIONS: Elective status is associated with poorer outcome. Patient selection determines long-term survival more than any other single factor, so for patients designated to an elective status, prompt retransplantation should be encouraged.

Profile of Gut Microbiota Associated With the Presence of Hepatocellular Cancer in Patients With Liver Cirrhosis.

BACKGROUND: Changes within the gut microbiota contribute to the progression of chronic liver diseases. According to the results of several studies performed in animal models, gut dysbiosis plays an important role in hepatocarcinogenesis. The aim of this study was to explore the characteristics of gut microbiota associated with the presence of hepatocellular cancer (HCC) in patients with cirrhosis of the liver undergoing liver transplantation. METHODS: A total of 15 patients with HCC and 15 non-HCC patients matched according to etiology of cirrhosis and Model for End-Stage Liver Disease (MELD) scores who underwent liver transplantations between 2012 and 2014 were included. Analysis of their gut microbial profile was based on prospectively collected stool samples from the pretransplant period. RESULTS: Patients with and without HCC were similar with respect to age (P = .506), sex (P = .700), hepatitis C virus (P > .999) and hepatitis B virus (P = .715) infection status, alcoholic liver disease (P > .999), and MELD score (P = .337). Notably, the presence of HCC was associated with significantly increased fecal counts of Escherichia coli (P = .025). Prediction of HCC presence based on E coli counts was associated with the area under the receiver-operating curve of 0.742 (95% confidence interval, 0.564-0.920), with the optimal cutoff on the level of 17.728 (natural logarithm of colony-forming units per 1 g of feces). Sensitivity and specificity rates for the established cutoff were 66.7% and 73.3%, respectively. CONCLUSIONS: The profile of gut microbiota associated with the presence of HCC in cirrhotic patients is characterized by increased fecal counts of E coli. Therefore, intestinal overgrowth of E coli may contribute to the process of hepatocarcinogenesis.

Outcomes of Patients With Poorly Differentiated Hepatocellular Carcinoma After Liver Transplantation.

BACKGROUND: Liver transplantation (LT) outcomes for patients with poorly differentiated (G3) hepatocellular carcinoma (HCC) are unsatisfactory. The aim of this study was to evaluate outcomes in patients with poorly differentiated HCC undergoing LT. PATIENTS AND METHODS: There were 192 HCC patients after LT in the Department of General, Transplant and Liver Surgery, Medical University of Warsaw, between January 2001 and April 2014. The study group comprised 24 patients with poorly differentiated tumors. RESULTS: Disease-free survival (DFS) for all patients was 49.5% at 5 years. The 5-year DFS for patients who met the Milan criteria (n = 9, 88.9%) was significantly better compared to those who did not (n = 15, 28.0%, P = .025). Multivariable analysis revealed that only the largest tumor diameter (P = .014) and α-fetoprotein (AFP) concentration (P = .001) were independent risk factors for DFS. The optimal cut-off AFP and tumor size that could distinguish patients with the highest risk were ≥500 ng/mL and ≥3.5 cm, respectively. DFS for patients with AFP <500 ng/mL and tumor size <3.5 cm was 100% after 2.8 years, and for those with ≥500 ng/mL or tumor size ≥3.5 cm was 46.9% after 5 years. However, the DFS for patients with AFP ≥500 ng/mL and tumor size ≥3.5 cm was only 12.5% after 4.7 years (P = .002). CONCLUSIONS: Outcomes of patients with poorly differentiated HCC treated with LT can be characterized with acceptable survival when applying criteria based on tumor size <3.5 cm and AFP <500 ng/mL.

Prognostic Factors and Outcomes of Patients After Liver Retransplantation.

BACKGROUND: Despite great progress and improvement in results of orthotopic liver transplantation (OLTx), 10%-20% of patients still require retransplantation (re-OLTx). The aim of the study was to present long-term results of liver retransplantation and to determine the factors influencing outcomes. PATIENTS AND METHODS: From December 1994 to July 2014, a total of 1461 liver transplantations were performed in the Department of General, Transplant and Liver Surgery of Medical University of Warsaw. There were 92 retransplantations (6.3%), including 40 early re-OLTx (up to 30 days). The most common indication for re-OLTx were vascular complications (41/92, 44.6%). Influence of clinical variables on short- and long-term outcomes was analyzed. RESULTS: Postoperative mortality was 30.4% (28/92). One-year, 3-year and 5-year survival for all patients was 59.8%, 56.5% and 54.1%, respectively. The best results were achieved in patients undergoing retransplantation due to chronic rejection and biliary complications, whose 5-year survival rates were 75.0% and 72.9% respectively. There was no difference in long-term survival after early and late retransplantations (60.9% and 49.3%, respectively; P = .158). Multivariable analysis revealed factors associated with longer survival of patients, namely, higher preoperative hemoglobin concentration (P = .001), increased blood transfusions (P = .048), and decreased fresh frozen plasma transfusions (P = .004). CONCLUSIONS: Liver retransplantation is a method providing satisfactory outcomes in selected patients. The perioperative period has a major impact on patient outcome.

Alveococcosis of the liver - strategy of surgical treatment with special focus on liver transplantation.

BACKGROUND: Echinococcosis is a zoonosis caused by infestation with any of 4 (of the 16) members of the Echinococcus genus, namely Echinococcus granulosus, Echinococcus multilocularis, Echinococcus oligarthus, and Echinococcus vogelii. The aim of this retrospective analysis was to present the outcomes of patients undergoing liver resection and liver transplantation (LT) for E. multilocularis infection. METHODS: A total of 44 patients who underwent surgical treatment of E. multilocularis infection in the period between 1989 and 2014 were included in the study cohort and retrospectively analyzed. RESULTS: LT was performed in 22 patients (50.0%), including 4 of 26 patients undergoing initial non-transplant management. Non-transplant procedures comprised liver resection in 23 patients (88.5%), diagnostic laparoscopy in 2 (7.7%), and left adrenalectomy in 1 patient (3.8%). Post-transplantation survival rates were 90%, 85%, and 75% at 1, 5, and 10 years, respectively. CONCLUSION: In conclusion, LT for E. multilocularis infection is a safe and effective treatment method.

The relevance of intestinal dysbiosis in liver transplant candidates.

BACKGROUND: The gut microbial ecosystem plays an important role in the pathogenesis of liver diseases. However, the association of microbial community structure with the severity of liver dysfunction is not completely understood. METHODS: Fecal microflora was assessed in 40 patients with liver cirrhosis listed for primary liver transplantation (LT). Independent associations between fecal microbial counts and serum bilirubin, serum creatinine, international normalized ratio (INR), and the Model for End-stage Liver Disease (MELD) score were established in multiple linear regression models. RESULTS: Bifidobacterium (standardized regression coefficient [sß] = -0.549; P < 0.001), Enterococcus (sß = 0.369; P = 0.004), and yeast (sß = 0.315; P = 0.018) numbers were independently associated with serum bilirubin, while Escherichia coli counts (sß = 0.318; P = 0.046) correlated with INR, and Bifidobacterium counts (sß = 0.410; P = 0.009) with serum creatinine. Only Bifidobacterium (sß = -0.468; P = 0.003) and Enterococcus (sß = 0.331; P = 0.029) counts were independent predictors of the MELD score. Bifidobacterium/Enterococcus ratio, proposed as a measure of pre-LT gut dysbiosis, was significantly related to the MELD score following the adjustment for the absolute Bifidobacterium (sß = -0.333; P = 0.029) and Enterococcus (sß = -0.966; P = 0.003) numbers. This pre-transplant dysbiosis ratio (PTDR) was significantly correlated with Enterococcus (R = -0.897; P < 0.001) but not with Bifidobacterium (R = 0.098; P = 0.546) counts. Among the other components of gut microflora, only hydrogen peroxide (H2 O2 )-producing Lactobacillus strains significantly influenced Enterococcus counts (sß = 0.349; P = 0.028) and PTDR (sß = -0.318; P = 0.046). CONCLUSION: While the abundance of both Bifidobacterium and Enterococcus is related to liver dysfunction, the size of the Enterococcus population seems to be the most important determinant of pre-LT gut dysbiosis in cirrhotic patients. The H2 O2 -producing Lactobacillus strains potentially ameliorate this dysbiotic state.

Reliability of frozen section in the assessment of allograft steatosis in liver transplantation.

BACKGROUND: Because liver allograft steatosis is an important risk factor of graft dysfunction after liver transplantation, it must be taken into consideration during graft acceptance. The aim of this study was to evaluate the reliability of frozen section in the assessment of liver steatosis before transplantation. METHODS: The retrospective analysis was based on data of 112 liver allograft procurements performed between 2003 and 2012. Hepatic steatosis was assessed in frozen and routine sections. Sensitivity, specificity, and positive and negative predictive values of the frozen section were evaluated with respect to detection of >30% and >50% steatosis. RESULTS: According to routine section assessment, there were 32 (28.6%) cases of steatosis >30% and 16 (14.3%) of >50%. The results of frozen section assessment were underestimated and overestimated in a similar low number of cases, both for the >30% (0.0% and 0.9%, respectively, P < 1.000) and the >50% (4.5% and 0.9%, respectively, P = .221) cutoff. Sensitivity, specificity, positive and negative predictive values of frozen section assessment were 100.0%, 98.8%, 97.0%, and 100.0%, respectively, for detection of >30% steatosis, and 68.8%, 99.0%, 91.7%, and 95.0%, respectively, for >50% steatosis. CONCLUSIONS: Considering high positive predictive value of frozen section assessment in detection of >50% steatosis, it may serve as a base to discard the use of graft for transplantation. However, according to the relatively moderate sensitivity of this method, decision of graft acceptance must also be made on consideration of other well-known factors for poor posttransplant function.

Outcomes following liver transplantation for metastatic neuroendocrine tumors.

INTRODUCTION: Metastatic disease is generally considered as an absolute contraindication for liver transplantation. However, due to relatively low aggressiveness and slow progression rates, liver metastases from neuroendocrine tumors (NETs) form an exception to this rule. Given the scarcity of available data, the purpose of this study was to evaluate long-term outcomes following liver transplantation for NET metastases. MATERIAL AND METHODS: There were 12 primary liver transplantations in patients with NET metastases out of 1334 liver transplantations performed in the Department of General, Transplant and Liver Surgery (Medical University of Warsaw) in the period between December 1989 and October 2013. Overall survival (OS) and disease-free survival (DFS) were set as primary and secondary outcome measures, respectively. RESULTS: Median follow-up was 7.9 years. For all patients, OS rate was 78.6% at 10 years and DFS rate was 15.5% at 9 years. Intraoperative transfusions of packed red blood cells (P = .021), Ki-67 proliferative index more than 2% (P = .048), and grade 2 tumors (P = .037) were identified as factors significantly associated with worse DFS. Notably, loss of E-cadherin expression (P = .444), mitotic rate (P = .771), extent of liver involvement (P = .548), primary tumor site (P = .983), and recipient age (P = .425) were not significantly associated with DFS. CONCLUSIONS: Excellent long-term OS rates support liver transplantation for unresectable NET metastases despite almost universal post-transplantation tumor recurrence. Selection of patients with G1 tumors with Ki-67 index not exceeding 2% and reducing the requirement for intraoperative blood transfusions might improve DFS rates.

Poor outcomes after liver transplantation in patients with incidental cholangiocarcinoma irrespective of tumor localization.

INTRODUCTION: After liver transplantation for cholangiocarcinoma (CCC), patients have a poor prognosis without use of specific therapeutic strategies. Accordingly, recipients with incidental CCC might have the highest risk of recurrent disease; however, sparse data on the long-term outcome of unselected patients with incidental CCC have been published. The aim of this study was to evaluate the post-transplantation outcomes of patients with incidental CCC with special focus on tumor localization. MATERIAL AND METHODS: There were 11 primary liver transplantations in patients with incidental CCC of 1310 liver transplantation procedures performed between December 1994 and August 2013. All patients with incidental CCC received a chemotherapy regiment including gemcitabine/5 fluorouracil, doxorubicin, and mitomycin. The patients were switched from calcineurin inhibitors to mammalian target of rapamycin inhibitor-based immunosuppression shortly after CCC diagnosis. RESULTS: Intra- and extrahepatic tumors were found in 6 and 5 patients, respectively. At median follow-up examination of 26.3 months there were 8 CCC recurrences and 7 patient deaths. Overall survival after liver transplantation for incidental CCC was 88.9% at 1 year, 44.4% at 2 years, and 14.8% at 3 years. The corresponding rates of recurrence-free survival were 45.7%, 45.7%, and 0.0%, respectively. Post-transplantation CCC recurrences were universal with 0% 3-year recurrence-free survival both in patients with intra- and extrahepatic tumors (P = .475). CONCLUSIONS: Incidental CCC in liver transplantation is associated with poor outcomes irrespective of tumor localization. Introduction of new adjuvant multimodal treatment concepts is necessary to improve the prognosis for this subgroup of patients.

Risk factors of acute renal failure after orthotopic liver transplantation: single-center experience.

BACKGROUND: Acute renal failure (ARF) is one of the most significant complications of orthotopic liver transplantation (OLT), associated with increased mortality rate and the development of chronic renal dysfunction. The aim of the study was to determine the perioperative risk factors for ARF in patients without previous history of renal disease who are undergoing OLT. MATERIALS AND METHODS: Forty-six patients who developed ARF after OLT performed in 1 transplant center were included in the study, and 52 consecutive patients without that complication served as a control group. Renal dysfunction was defined as a glomerular filtration rate <60 mL/min/1.73 m(2). The data concerning preoperative diseases, perioperative renal function, first-line immunosuppressive therapy, and blood transfusion requirement were retrospectively analyzed and compared among groups. Logistic regression modeling was used to determine risk factors for ARF. RESULTS: Patients who developed ARF were significantly older (mean age 53.3 vs 46.3 years, P = .057), had higher level of preoperative (0.79 vs 0.71 mg/dL, P = .0062) and intraoperative (0.85 vs 0.74 mg/dL, P = .0045) creatinine. The risk factors for ARF were intraoperative and 24-hour post-transplant creatinine level >0.9 mg/dL and high-dose tacrolimus-based immunosuppression. Transfusion of ≤6 units of red blood cells diminished the risk of ARF. Sex and preoperative diseases were not predictive to ARF in our regression models. CONCLUSION: Careful operative technique with low blood loss and immunosuppressive therapy of low nephrotoxic potential should be recommended in older patients to diminish the risk of renal dysfunction after orthotopic liver transplantation. Patients with higher levels of perioperative creatinine should be considered to have first-line immunosuppression without calcineurin inhibitors or with low-dose immunosuppressants of known nephrotoxic potential.

Evaluation of total tumor volume and pretransplantation α-fetoprotein level as selection criteria for liver transplantation in patients with hepatocellular cancer.

INTRODUCTION: Appropriate selection of hepatocellular cancer (HCC) patients for liver transplantation is crucial to minimize the risk of recurrence and provide long-term outcomes comparable with those for other indications. Selection criteria based on total tumor volume (TTV) and α-fetoprotein (AFP) concentrations were proposed in a recent large study. The aim of this study was to evaluate the results of liver transplantation for HCC within and beyond these criteria. MATERIAL AND METHODS: This retrospective study included 104 patients with HCC who underwent liver transplantation. Risk factors for overall survival and tumor recurrence were evaluated. Overall survival and cumulative tumor recurrence rate for patients with TTV <115 cm(3), AFP concentration <400 ng/mL, and no macrovascular invasion (76/104; 73.1%) were evaluated and compared with those for the remaining patients (28/104; 26.9%). RESULTS: Pretransplantation AFP concentration >400 ng/mL (P = .016; hazard ratio [HR], 3.36; 95% confidence intervals [CI], 1.25-9.03) was the only risk factor for overall survival. TTV >115 cm(3) (P = .021; HR 4.29; 95% CI, 1.24-14.81) and AFP concentration >400 ng/mL (P = .002; HR 6.97; 95% CI, 2.02-24.03) were independent risk factors for recurrence. The estimated 3-year tumor recurrence rate was 4.2% for patients with TTV <115 cm(3), AFP concentration <400 ng/mL, and no macrovascular invasion compared with 57.2% for the remaining patients (P < .00001). The 3-year overall survival rate of patients within and beyond this criteria was 81.7% and 64.6%, respectively (P = .0628). CONCLUSIONS: In contrast to other criteria, selection of HCC patients for liver transplantation on the basis of TTV and AFP concentration relates to both morphological features and tumor biology. Although fulfillment of these criteria was more than 1.5-fold higher than that of the Milan criteria, the rate of tumor recurrence was exceptionally low.