Prevention and Management of CMV Infections after Liver Transplantation: Current Practice in German Transplant Centers.

Human cytomegalovirus (CMV) remains a major cause of mortality and morbidity in human liver transplant recipients. Anti-CMV therapeutics can be used to prevent or treat CMV in liver transplant recipients, but their toxicity needs to be balanced against the benefits. The choice of prevention strategy (prophylaxis or preemptive treatment) depends on the donor/recipient sero-status but may vary between institutions. We conducted a series of consultations and roundtable discussions with German liver transplant center representatives. Based on 20 out of 22 centers, we herein summarize the current approaches to CMV prevention and treatment in the context of liver transplantation in Germany. In 90% of centers, transient prophylaxis with ganciclovir or valganciclovir was standard of care in high-risk (donor CMV positive, recipient CMV naive) settings, while preemptive therapy (based on CMV viremia detected during (bi) weekly PCR testing for circulating CMV-DNA) was preferred in moderate- and low-risk settings. Duration of prophylaxis or intense surveillance was 3-6 months. In the case of CMV infection, immunosuppression was adapted. In most centers, antiviral treatment was initiated based on PCR results (median threshold value of 1000 copies/mL) with or without symptoms. Therefore, German transplant centers report similar approaches to the prevention and management of CMV infection in liver transplantation.

lncRNA KCNQ1OT1 Suppresses the Inflammation and Proliferation of Vascular Smooth Muscle Cells through IκBa in Intimal Hyperplasia.

Inflammation and proliferation of vascular smooth muscle cells (VSMCs) are the key events in intimal hyperplasia. This study aimed to explore the mechanism by which long non-coding RNA (lncRNA) KCNQ1OT1 affects VSMC inflammation and proliferation in this context. A vein graft (VG) model was established in mice to introduce intimal hyperplasia. Isolated normal VSMCs were induced with platelet-derived growth factor type BB (PDGF-BB), and the cell proliferation, migration, and secretion of inflammatory factors were determined. The results showed that KCNQ1OT1 was downregulated in the VSMCs from mice with intimal hyperplasia and in the PDGF-BB-treated VSMCs, and such downregulation of KCNQ1OT1 resulted from the increased methylation level in the KCNQ1OT1 promoter. Overexpressing KCNQ1OT1 suppressed PDFG-BB-induced VSMC proliferation, migration, and secretion of inflammatory factors. In VSMCs, KCNQ1OT1 bound to the nuclear transcription factor kappa Ba (IκBa) protein and increased the cellular IκBa level by reducing phosphorylation and promoting ubiquitination of the IκBa protein. Meanwhile, KCNQ1OT1 promoted the expression of IκBa by sponging miR-221. The effects of KCNQ1OT1 knockdown on promoting VSMC proliferation, migration, and secretion of inflammatory factors were abolished by IκBa overexpression. The roles of KCNQ1OT1 in reducing the intimal area and inhibiting IκBa expression were proved in the VG mouse model after KCNQ1OT1 overexpression. In conclusion, KCNQ1OT1 attenuated intimal hyperplasia by suppressing the inflammation and proliferation of VSMCs, in which the mechanism upregulated IκBa expression by binding to the IκBa protein and sponging miR-221.

How we do it: double in situ split for staged mesohepatectomy in patients with advanced gall bladder cancer and marginal future liver remnant.

PURPOSE: Associating liver partition with portal vein ligation for staged hepatectomy (ALPPS) has increased the rate of liver resections in patients with marginal future liver remnant. We here describe a modified ALPPS procedure with splitting-off the central liver segments for staged mesohepatectomy in patients with advanced gall bladder cancer. METHODS: A double in situ split for ALPPS (DALPPS) is performed with splitting-off the central liver segments (segments 1, 4, 5, and 8). This induces a rapid hypertrophy of the left lateral (segments 2/3) and right posterior sectors (segments 6/7). An intrahepatic right posterior approach during splitting-off the right posterior sector is introduced as a part of this new procedure. This approach facilitates the dissection and ligation of the right anterior branch of the portal vein (segments 5 and 8) while the liver hilum remains untouched during the first step of surgery. RESULTS: Two patients with advanced gall bladder cancer were treated with the DALPPS procedure till date. After a short interval (7-9 days), a rapid hypertrophy of the left lateral and right posterior sector was observed (hypertrophy up to 72.6 and 54.6 %, respectively). A staged mesohepatectomy including caudate lobectomy and resection of the extrahepatic bile duct was then performed safely. There was no surgical-technical morbidity. No signs of posthepatectomy liver failure according to the 50-50 criteria were seen. However, one patient died from severe ARDS attributed to the preoperative chemotherapy. Nevertheless, this complication is deemed to be surgery related. CONCLUSIONS: The DALPPS procedure is a new surgical technique for staged mesohepatectomy for patients with small future liver remnant in size or in function. However, appropriate patient selection is mandatory to avoid morbidity and mortality.

Intracellular Delivery of Molecular Cargo Using Cell-Penetrating Peptides and the Combination Strategies.

Cell-penetrating peptides (CPPs) can cross cellular membranes in a non-toxic fashion, improving the intracellular delivery of various molecular cargos such as nanoparticles, small molecules and plasmid DNA. Because CPPs provide a safe, efficient, and non-invasive mode of transport for various cargos into cells, they have been developed as vectors for the delivery of genetic and biologic products in recent years. Most common CPPs are positively charged peptides. While delivering negatively charged molecules (e.g., nucleic acids) to target cells, the internalization efficiency of CPPs is reduced and inhibited because the cationic charges on the CPPs are neutralized through the covering of CPPs by cargos on the structure. Even under these circumstances, the CPPs can still be non-covalently complexed with the negatively charged molecules. To address this issue, combination strategies of CPPs with other typical carriers provide a promising and novel delivery system. This review summarizes the latest research work in using CPPs combined with molecular cargos including liposomes, polymers, cationic peptides, nanoparticles, adeno-associated virus (AAV) and calcium for the delivery of genetic products, especially for small interfering RNA (siRNA). This combination strategy remedies the reduced internalization efficiency caused by neutralization.

Highly efficient delivery of siRNA to a heart transplant model by a novel cell penetrating peptide-dsRNA binding domain.

Small interfering RNAs (siRNAs) delivery remains a bottleneck for RNA interference (RNAi) - based therapies in the clinic. In the present study, a fusion protein with two cell-penetrating peptides (CPP), Hph1-Hph1, and a double-stranded RNA binding domain (dsRBD), was constructed for the siRNA delivery: dsRBD was designed to bind siRNA, and CPP would subsequently transport the dsRBD/siRNA complex into cells. We assessed the efficiency of the fusion protein, Hph1-Hph1-dsRBD, as a siRNA carrier. Calcium-condensed effects were assessed on GAPDH and green fluorescent protein (GFP) genes by western blot, real time polymerase chain reaction (RT-PCR), and flow cytometry analysis in vitro. Evaluations were also made in an in vivo heart transplantation model. The results demonstrated that the fusion protein, Hph1-Hph1-dsRBD, is highly efficient at delivering siRNA in vitro, and exhibits efficiency on GAPDH and GFP genes similar to or greater than lipofectamine. Interestingly, the calcium-condensed effects dramatically enhanced cellular uptake of the protein-siRNA complex. In vivo, Hph1-Hph1-dsRBD transferred and distributed ^ targeted siRNA throughout the whole mouse heart graft. Together, these results indicate that Hph1-Hph1-dsRBD has potential as an siRNA carrier for applications in the clinic or in biomedical research.

C-X-C motif receptor 2, endostatin and proteinase-activated receptor 1 polymorphisms as prognostic factors in NSCLC.

The progress of non-small cell lung cancer (NSCLC) is dependent on sufficient angiogenesis. Thrombin induced activation of proteinase-activated receptor 1 (PAR-1) on platelets leads to platelet secretion and aggregation. This influences cell survival, apoptosis and angiogenesis by the release of VEGF and Endostatin (ES), a potent angiogenesis inhibitor. Interleukin-8 (IL-8) induces tumor angiogenesis independent of the VEGF pathway through the chemokine C-X-C motif receptor 2 (CXCR-2). Our purpose was to evaluate germline polymorphisms of these potential therapy targets as prognostic markers for disease free survival (DFS) and overall survival (OS) in surgically treated NSCLC patients. In total 209 Caucasian patients, treated between 1996 and 2011, were included in this study. Genomic DNA was extracted from peripheral blood leucocytes. Genotyping of CXCR-2 +1208 C > T and +785 C > T, PAR-1 -506 Ins/del and -14 Ivs A > T and ES +4349 G > A was performed by TaqMan(®) genotyping assays or by polymerase chain reaction (PCR) followed by capillary electrophoresis. Chi-square test, Kaplan-Meier estimator and cox regression hazard model were used to assess the prognostic value of selected polymorphisms. The PAR-1 -14 Ivs A/A genotype was associated with advanced tumor stages (p = 0.024) and, in univariate analysis, with shorter median OS in squamous cell lung carcinoma (SqCC, p = 0.035). The CXCR-2 + 1208T/T genotype was associated with aggressive tumor biology (p = 0.038), and shorter DFS and OS (p = 0.018, p = 0.021) in NSCLC and especially in SqCC a negative predictor for DFS and OS (p = 0.045, p = 0.041). Genotyping of the CXCR-2 +1208 C >T polymorphism could be a useful tool to identify high-risk SqCC subgroups.

The T393C polymorphism of GNAS1 is a predictor for relapse and survival in resectable non-small cell lung cancer.

INTRODUCTION: The GNAS1 T393C single nucleotide polymorphism (T393C-SNP) correlates with Gαs mRNA stability and protein expression and augmented apoptosis. Genetic germ line variations as stable and reproducible markers potentially serve as prognostic marker in oncology. The aim of this study was to evaluate the potential prognostic value of T393C-SNP in complete resected non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: In total 163 Caucasian patients, who had been surgically treated for NSCLC between 1998 and 2010, were included in this study. Genotyping of peripheral blood cells was performed by polymerase chain reaction and digestion using the restriction enzyme FokI. The T393C-SNP was correlated with clinic-pathological parameters and survival. Chi-square test, Kaplan-Meier estimator and cox regression hazard model were used to assess the prognostic value of the T393C-SNP. RESULTS: C-allele carriers had a higher recurrence rate (p=0.018) and a shorter disease-free survival compared to homozygous T-allele carriers (12.26 months vs. 44.65 months, p=0.009). The overall survival in homozygous C allele carriers was shorter (19.10 months vs. 53.95 months, p=0.019). Multivariate Cox regression identified the CC genotype as a negative independent prognostic factor for recurrence (hazard ratio 2.36, p=0.007) and survival (hazard ratio 2.51, p=0.008). CONCLUSION: Determination of T393C-SNP preoperatively potentially allows allocation of NSCLC patients into different risk profiles and may influence the therapeutic strategy.

LigaSure™ vs. conventional dissection techniques in pancreatic surgery--a prospective randomised single-centre trial.

BACKGROUND: Surgical procedures in pancreatic surgery are well established, but still involve time-consuming manual dissection. We compared the use of LigaSure with conventional dissection techniques in pancreatic surgery in a prospective randomised single-centre trial (registration number: NCT00850291). METHODS: Patients with tumours of the pancreatic head that were assumed to be technically resectable were randomised to LigaSure or conventional surgery. The primary endpoint of this study was overall operation time. Secondary endpoints were preparation time until tumour resection, intraoperative blood loss, number of given units of packed red blood cells, costs of surgery, postoperative morbidity, length of hospital stay and mortality. RESULTS: There was no difference in overall operation time between the two groups (P = 0.227). Median costs for pancreatic surgery were significantly less in the conventional group with €3,047 (range 2,004-5,543) vs. €3,527 (range 2,516-5,056, P = 0.009). Preparation time, intraoperative blood loss, number of units of packed red blood cells, postoperative morbidity, length of hospital stay and mortality did not differ between the two groups. CONCLUSION: Our data indicate that the LigaSure device is equivalent to conventional dissection modalities in pancreatic surgery.

Carbon monoxide, a two-face for the protection of the liver.

Carbon monoxide is generally believed to be a 'toxic' gas molecule due to its binding capability with hemoglobin. Overexposure to carbon monoxide leads to a hypoxic state that may cause the death of a mammalian. In contrast, directly exposure of carbon monoxide may protect cells or organs from various disease insults. The paradox effects of carbon monoxide might vary on the ways of exposure and the amounts being exposed. Here we highlighted the characteristics of this gas molecule and summarized its protective effects and therapeutic potentials in liver diseases and liver transplantation.

Liver transplantation in patients with liver cirrhosis and active pneumonia: an observational study.

Patients with chronic liver disease are at high risk for severe infection because of increased bacterial translocation and immune suppression associated with liver dysfunction. Patients presenting with severe pneumonia and acute decompensation of cirrhosis are generally not considered for liver transplantation because it is unknown if these patients can recover from infection while under immunosuppression. We performed an observational study where patients with cirrhosis of the liver remained on the waiting list, although suffering from active pneumonia. Nine patients were included, but only six patients improved under goal-directed therapy and subsequently underwent liver transplantation. All six patients recovered quickly from infection; five patients recovered without sequelae and one patient died because of late complications. We propose that in patients with chronic liver disease and active pneumonia transplantation is a treatment option that should not hastily be abandoned.

Posterior cavoplasty: a new approach to avoid venous outflow obstruction and symptoms for small-for-size syndrome in right lobe living donor liver transplantation.

PURPOSE: A common and serious problem after living donor liver transplantation (LDLT) of small grafts is small-for-size syndrome (SFSS). Although hyperdynamic portal inflow and portal hypertension are cornerstones in the development of SFSS, inadequate outflow may aggravate SFSS. Therefore, enlargement of the portal outflow tract by incision of the anterior rim of the orifice of the right hepatic vein (RHV) has been advocated for right lobe LDLT. But backwards tilt of a small graft into a large abdominal cavity may lead to a choking of the otherwise large anastomosis and thus we propose posterior enlargement of the orifice of the RHV. METHOD: In this test-of-concept study, we evaluated portal vein pressure (PVP), clinical parameters, and laboratory measurements in 22 patients that underwent right lobe LDLT and either received standard end-to-end anastomosis of the RHV or posterior cavoplasty. RESULTS: In patients that underwent posterior cavoplasty, we observed significantly lower PVP and less hyperbilirubinemia. There was a non-significant trend to lower incidence of SFSS. Other laboratory measurements and clinical parameters were not significantly different. CONCLUSION: We recommend posterior cavoplasty for enlargement of the hepatic venous outflow tract in right lobe LDLT as a method to avoid portal hypertension, hyperbilirubinemia, and possibly SFSS, especially in patients that receive small grafts.

Prospective evaluation of biliary reconstruction with duct-to-duct continuous suture in adult live donor liver transplantation.

PURPOSE: Biliary reconstruction remains the Achilles' heel of adult live donor liver transplantation (LDLT). The study aims to investigate the feasibility of duct-to-duct hepaticocholedochostomy in LDLT. METHODS: Perioperative data from 30 consecutive LDLT aiming at duct-to-duct reconstruction of the biliary tract using a continuous suture technique were prospectively collected. Nineteen recipients (63.3%) had one graft bile duct. Eleven recipients (36.7%) had two or three graft bile ducts. The median follow-up was 50 months. RESULTS: The overall biliary complication rate was 23.3%. Two recipients developed biliary stricture (6.7%), and two recipients (6.7%) presented with biliary leakage in early posttransplant phase (<90 days). One recipient suffered from bilioma (3.3%), and two recipients (6.7%) presented with biliary stricture in later posttransplant phase (>90 days). No correlation was found between the number of graft bile ducts and the incidence of biliary complications. No biliary complication-associated necessity for re-transplantation or mortality was observed. On multivariate analysis, no single risk factor associated with biliary complication could be identified. All biliary complications were successfully treated with Roux-en-hepaticojejunostomy and/or with endoscopic interventions. CONCLUSION: Duct-to-duct hepaticocholedochostomy with continues suture represents a safe and feasible procedure for biliary reconstruction in LDLT. Recipients may benefit from aggressive management of biliary complications with Roux-en-hepaticojejunostomy as compared with repeated endoscopic interventions in early posttransplant phase.

Improved outcome after 'bottom-up' immunosuppression in liver transplant recipients with preoperative renal impairment.

BACKGROUND: Most patients with high MELD scores have impaired renal function prior to transplantation. PATIENT AND METHODS: A retrospective case control study was conducted with initial low immunosuppression, which was increased when patients rejected or were clinically stable beyond day 30 ('bottom-up'). RESULTS: Thirty patients with impaired renal function were included. Fifteen were treated with de novo cyclosporine A (CsA; group A), and 15 had 'bottom-up' immunosuppression (group B). Baseline renal function was similar: serum creatinine (SCr) median 1.8 mg/dl (range: 1.5-4.0 mg/dl; group A) versus 2.4 mg/dl (range: 1.5-4.0 mg/dl; group B; p = 0.24). The requirement for renal replacement therapy was significantly lower in group B (p = 0.032). Ten received 'bottom-up' immunosuppression [4 CsA/1 sirolimus (Sir) 'on demand' after rejection, 5 Sir (stable)] beyond day 30. By months 6 and 12 (1.6 mg/dl vs. 1.2 mg/dl), SCr values were significantly better in group B (p = 0.006). Renal function in group B did not differ between patients receiving CsA or Sir. Overall complication rates, survival and biopsy-proven acute rejection were similar, although BANFF scores were higher in group B (p = 0.004). CONCLUSION: Successful implementation of 'bottom-up' immunosuppression in liver transplant recipients with high lab-MELD scores and renal dysfunction at the time of transplantation has the potential to substantially improve short- and long-term outcomes.

"Rescue allocation offers" in liver transplantation: is there any reason to reject "unwanted" organs?

To increase the number of transplanted organs, the Eurotransplant foundation uses a so-called "rescue-organ-allocation" procedure for organs that had been rejected by at least three consecutive transplant centers for medical reasons. The transplant center that finally accepts such an organ can then freely choose a patient from its own waiting list, without being bound to regular allocation criteria. Almost 30% of deceased donor livers are now allocated through this process in the Eurotransplant region. We report our results of 38 "rescue-allocation" livers (RA livers) transplanted at our institution (2003-2007), compared to a group of 115 regularly allocated organs within the same period. From our data, RA livers have the same results as regularly allocated livers. Type and frequency of postoperative morbidity did not differ between both groups, though the analysis of subgroups showed a tendency toward reduced survival of RA livers in patients with viral hepatitis. Interestingly, the Donor Risk Index (DRI) showed no difference between RA livers and regularly allocated livers. Although preliminary due to small numbers, we conclude that RA livers can be safely transplanted without increased mortality or morbidity. However, no donor specific criteria which would justify rejecting a RA liver were found. This highly challenges the applicability of the RA procedure in its current form.

Adult Living Donor Liver Transplantation with ABO-Incompatible Grafts: A German Single Center Experience.

Adult living donor liver transplantations (ALDLTs) across the ABO blood group barrier have been reported in Asia, North Americas, and Europe, but not yet in Germany. Several strategies have been established to overcome the detrimental effects that are attached with such a disparity between donor and host, but no gold standard has yet emerged. Here, we present the first experiences with three ABO-incompatible adult living donor liver transplantations in Germany applying different immunosuppressive strategies. Four patient-donor couples were considered for ABO-incompatible ALDLT. In these patients, resident ABO blood group antibodies (isoagglutinins) were depleted by plasmapheresis or immunoadsorption and replenishment was inhibited by splenectomy and/or B-cell-targeted immunosuppression. Despite different treatments ALDLT could safely be performed in three patients and all patients had good initial graft function without signs for antibody-mediated rejection (AMR). Two patients had long-term graft survival with stable graft function. We thus propose the feasibility of ABO-incompatible ALDLT with these protocols and advocate further expansion of ABO incompatible ALDLT in multicenter trials to improve efficacy and safety.

Adult living donor liver transplantation: body mass index and MELD score of recipients are independent risk factors for hospital mortality.

BACKGROUND AND AIMS: Adult living donor liver transplantation (LDLT) has been established as elective procedure or urgent procedure to save the life of patients with terminal liver diseases. The outcome of LDLT varies between transplant centers. Here, we aim to evaluate the outcome of LDLT in our center and to identify the risk factors that are associated with hospital mortality of recipients. PATIENTS AND METHODS: A cohort study with 32 consecutive cases of adult living donor liver transplantation was conducted in two cooperated medical centers. Perioperative data, incidence of postoperative complications, and hospital mortality were analyzed. RESULTS: No major surgical complications and no hospital mortality were observed in all 32 donors. All donors were discharged with normal liver function with median intensive care unit (ICU) stay of 1 day and median hospital stay of 10 days. All recipients had normal liver function in early posttransplant period. Eighty-one percent of the recipient survived with normal liver function for more than 1 year. The pretransplant ICU stay, renal failure, international normalized ratio (>1.8), and Model for End-stage Liver Disease (MELD) score (>20) were independent risk factors for hospital mortality of recipients. CONCLUSIONS: Adult living donor liver transplantation should be reserved to less "sick" patients in the era of organ allocation based on MELD score.

Liver transplantation for sclerosing cholangitis in a polytraumatized patient.

BACKGROUND: Following a motorcycle accident, a 30-year-old male with multiple traumas-including liver rupture, traumatic fractures, cerebral hemorrhage, hepatic hematoma and respiratory failure-was referred to a university medical center. After initial stabilization, the patient developed pneumonia, acute kidney failure requiring intermittent hemodialysis, superinfection of the hepatic hematoma and systemic bacterial infection with multiple drug-resistant bacteria. The patient developed acute liver failure 8 weeks after the initial trauma. INVESTIGATIONS: Laboratory investigations, Doppler ultrasound, CT, ultrasound, angiography, endoscopic retrograde cholangiography, liver biopsy, bacteriology and X-ray. DIAGNOSIS: Sclerosing cholangitis in a critically ill patient. MANAGEMENT: Orthotopic liver transplantation.

Targeting of interleukin-10 is superior to cytotoxic T-lymphocyte associated antigen 4 with human immunoglobulin G(1) for the prevention of chronic allograft deterioration in organ transplantation.

BACKGROUND: Genetic manipulation of the allograft is an attractive approach to prevent the graft against chronic deterioration through stable expression of immunomodulatory or protective genes. However, the best strategy for prevention of chronic allograft deterioration remains unclear. METHODS: The efficacies of adeno-associated viral vector-mediated stable expression of indoleamine 2,3-dioxygenase (IDO), cytotoxic T-lymphocyte associated antigen 4 with human immunoglobulin G(1) (CTLA4Ig) or interleukin-10 (IL-10) in the prevention of chronic allograft deterioration were compared in a rat heart transplantation model. RESULTS: Transduction of grafts with IL-10 significantly prolonged allograft survival, whereas transduction of grafts with IDO did not improve graft survival compared to controls. Analysis of long-term survived heart allografts showed that both CTLA4Ig and IL-10 could significantly reduced the T cells and macrophage infiltration. However, stable expression of CTLA4Ig failed to prevent the development of transplant arteriosclerosis. By contrast, IL-10 suppressed the development of transplant arteriosclerosis effectively. The suppressive effects of IL-10 in preventing the development of chronic allograft deterioration were associated with lower transcript levels of transforming tumor growth factor beta 1 and macrophage migration inhibitory factor in the graft. In addition, higher transcript levels of heme oxygenase-1 were found in IL-10-transduced allograft. CONCLUSIONS: Targeting on IL-10 is superior to CTLA4Ig or IDO for the treatment of chronic allograft deterioration.

Living donor liver resection: a low-tech but highly efficient technique. The Regensburg experience.

BACKGROUND: To evaluate a low-tech blunt liver dissecting technique for living-liver-donor procedures. Thirty three adult-to-adult living-donor operations were performed at Regensburg University and Jordan Hospital, Amman. PATIENTS AND METHODS: For the technique of parenchymal dissection, dissecting scissors were used for blunt preparation; branches were closed, carefully pressing into the hepatic parenchyma. Donor, surgical procedure data, and data on liver function and recovery were analyzed and compared to literature. RESULTS: Median procedure time was 280 min (210 to 420 min). Median blood loss was 350 ml (0 to 650 ml). GOT levels decreased from 260 U/l (140 to 510 U/l) on day 1 to 65 U/l (31 to 220 U/l) on day 7. Bilirubin levels were at 2.0 mmol/l (1.29 to 5.99 mmol/l) on day 1 and 1.26 mmol/l (0.63 to 4.70 mmol/l) on day 7. After 12 days (6 to 23), all donors were discharged. There was no donor mortality. One major complication (biliary leakage) and seven minor complications occurred. CONCLUSION: This technique is a low-tech but efficient donor-dissection technique in living liver transplantation, which is comparable to other well established dissection techniques utilizing technical devices in regards to risk for the donor, performance, and recovery.

Liver transplantation as curative approach for advanced hepatocellular carcinoma: is it justified?

BACKGROUND: Liver transplantation is considered as one of therapeutic approaches to hepatocellular carcinoma (HCC). The present study aims to evaluate the efficacy of various therapeutic options for HCC. MATERIALS AND METHODS: One hundred twenty patients with known HCC in various tumour stages were evaluated in the present study. Patients were treated either with primary tumour resection, transarterial chemoembolisation (TACE) or liver transplantation (LTx) by an interdisciplinary team. RESULTS: The overall 1-year and 5-year survivals of patients in LTx group were 95 and 57%, respectively, which were significantly higher than those in primary tumour resection group (65 and 33%, P < 0.01) and those in TACE group (44 and 4%, P < 0.01). In parallel, 1-year and 5-year tumour-free survivals of patients in LTx group (75 and 62%) were significantly higher than those in primary tumour resection group (50 and 11%, P < 0.01). There were no significant differences in 1- and 5-year survivals of patients with early tumour stage received LTx or primary tumour resection, whereas patients in advanced tumour stage based on pathological findings of explanted liver significantly benefited from LTx as compared to primary resection. CONCLUSIONS: LTx can be a curative approach for patients with advanced HCC without extrahepatic metastasis. However, organ shortage is a major limiting factor in the selection of HCC patients for LTx.