Diffusion and partitioning of different PFAS compounds through thermoplastic polyurethane and three different PVC-EIA liners.

Perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorobutane sulfonic acid (PFBS), 6:2 fluorotelomer sulfonic acid (6:2 FTS), and GenX are tested for diffusion and sorption through thermoplastic polyurethane (TPU) and three ethylene interpolymer alloy (PVC-EIA) liners (EIA1, EIA2, and EIA3) with decreasing ketone ethylene ester (KEE) contents. The tests were conducted at room temperature (23 °C), 35 °C, and 50 °C. The tests show significant diffusion through the TPU as manifested by a decrease in the source concentration and an increase in the receptor concentrations of PFOA and PFOS over time, especially at higher temperatures. On the other hand, the PVC-EIA liners show excellent diffusive resistance to the PFAS compounds especially at 23 °C. At higher temperatures, the diffusion resistance of the PVC-EIA liner with the lowest KEE content, EIA3, was best at 50 °C followed by EIA1 (highest KEE content) and finally EIA2. Sorption tests showed no measurable partitioning of any of the compounds to the liners examined. Based on 535 days of diffusion testing, permeation coefficients are provided for all the compounds considered for the four liners at three temperatures. In addition, the Pg values for PFOA and PFOS are provided for a linear low density polyethylene (LLDPE) and a coextruded LLDPE - ethylene vinyl alcohol (EVOH) geomembrane based on 1246 to 1331 days of testing and are compared to those estimated for EIA1, EIA2, and EIA3.

PFOA and PFOS diffusion through LLDPE and LLDPE coextruded with EVOH at 22 °C, 35 °C, and 50 °C.

Diffusion of perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) through 0.1 mm and 0.75 mm LLDPE and 0.1 mm and 0.75 mm LLDPE coextruded with ethyl vinyl alcohol (denoted as CoEx) at room temperature (23 °C), 35 °C, and 50 °C is examined. These tests had negligible source depletion throughout the monitoring period, indicating limited contaminant partitioning and diffusion through the LLDPE. At 483 days, 23 °C receptor PFOA and PFOS concentrations, cr, were <8 µg/L (cr/co < 3.2 × 10-4) for all tests, and at 399 days elevated temperature receptor concentrations were < 0.4 µg/L (cr/co < 1.6 × 10-5) at 35 °C and <0.5 µg/L (cr/co < 2.0 × 10-5) at 50 °C for both PFOA and PFOS. LLDPE partitioning coefficient, Sgf was 0.9-1.4 (PFOA) and 2.8-5.3 (PFOS) based on sorption tests at 23 °C. Based on the best estimates of permeation coefficient, PgCoEx, for CoEx was consistently lower than PgLLDPE. For PFOA, CoEx had PgCoEx < 0.26 × 10-16 m2/s at 23 °C, <11 × 10-16 m2/s (35 °C), and < 10 × 10-16 m2/s (50 °C) while LLDPE had PgLLDPE < 3.1 × 10-16 m2/s (23 °C), <13 × 10-16 m2/s (35 °C), and <19 × 10-16 m2/s (50 °C). For PFOS, CoEx and LLDPE had PgCoEx < 0.55 × 10-16 m2/s and PgLLDPE < 3.2 × 10-16 m2/s (23 °C), PgCoEx < 8.3 × 10-16 m2/s and PgLLDPE < 40 × 10-16 m2/s (35 °C), and PgCoEx < 8.2 × 10-16 m2/s and PgLLDPE < 52 × 10-16 m2/s (50 °C). These values are preliminary and may change (e.g., decrease) as more data comes available over time. The Pg values deduced for PFOA and PFOS are remarkably lower than those reported for other contaminants of concern, excepting BPA, which exhibits similar behaviour.

The Royal Free Hospital 'hub-and-spoke network model' delivers effective care and increased access to liver transplantation.

OBJECTIVES: 'Hub-and-spoke' networks may be one solution to reduce the geographical inequality in access to liver transplantation (LT) and the growing demands on, and saturation of, LT centres. It is not clear if such networks improve equity of access, deliver comparable patient outcomes or effect patient satisfaction. STUDY DESIGN: Retrospective evaluation of outcomes and patient satisfaction within the Royal Free liver transplant 'hub-and-spoke' network. METHODS: Patient outcomes in those assessed for LT between September 2011 and 2014 at spoke centres (n = 4) were compared retrospectively with those assessed at the LT hub centre. Patient satisfaction questionnaires were completed and changes in LT referral patterns were explored with data obtained directly from NHS Blood and Transplant (NHSBT). RESULTS: A total of 655 patients (180 spoke; 475 hub) were assessed for LT. Patients referred from spoke centres were more likely to have viral hepatitis as an underlying aetiology (72/180 vs 110/475; P < 0.001), or hepatocellular carcinoma (48/180 vs 60/475; P < 0.001) as an indication for LT and were more likely to be listed for LT when compared with hub patients (139/180 vs 312/475, P = 0.005). Mortality on the waiting list (9/123 vs 25/269, P = 0.57), waiting time to LT (64-days vs 78-days, P = 0.91) and Model for End-Stage liver disease (MELD)/United Kingdom End-Stage Liver Disease (UKELD) score (P = 0.24/0.26) in listed patients were equivalent as were 1- and 3-year patient and graft survival rates. Patient satisfaction rates were high at both types of centre, with significantly more patients preferring 'locally delivered care' at spoke vs hub (11/50 vs 70/73, P≤0.0001). Since the development of formal hub-and-spoke networks data from NHSBT based on postcode confirmed a significant increase in patients undergoing LT (153%) from spoke centres, whereas numbers assessed and transplanted from the hub centre have remained static. CONCLUSION: Hub-and-spoke LT networks are effective in offering equivalent clinical outcomes, high patient satisfaction and alleviate clinical pressure on the hub centre. They have to potential to help eliminate the geographical disparity in mortality rates from chronic liver disease.

De novo use of generic tacrolimus in liver transplantation - a single center experience with one-yr follow-up.

UNLABELLED: Use of generic tacrolimus in liver transplantation (LT) could result in cost savings. Generic tacrolimus has been shown to be bioequivalent to innovator tacrolimus in healthy volunteers and renal transplant patients. There are limited data on the de novo use of generic tacrolimus in LT. This study aimed to determine whether the de novo use of generic tacrolimus (Adoport, Sandoz,UK) was associated with differences in outcomes, safety, and cost compared with innovator tacrolimus (Prograf, Astellas, Japan). METHODS: Patients were studied before and after a programmatic change from de novo IS with Prograf to Adoport. Outcomes, tacrolimus levels, doses, and costs were compared for the first-yr post-LT. RESULTS: Ninety-four patients were studied, 46 Prograf, 48 Adoport. No significant differences in rejection, cytomegalovirus infection, acute kidney injury, sepsis, or graft loss were observed between groups. Tacrolimus costs were significantly reduced with the de novo use of Adoport. Day 14 dose normalized levels in Adoport patients showed significant variation but at the day 30 and one yr, there were no significant differences in the doses or levels of tacrolimus between groups. CONCLUSIONS: Adoport is safe and effective compared to Prograf when used de novo in LT patients. Tacrolimus costs were significantly reduced by the use of Adoport.

Nine scoring models for short-term mortality in alcoholic hepatitis: cross-validation in a biopsy-proven cohort.

BACKGROUND: Several prognostic models have emerged in alcoholic hepatitis (AH), but lack of external validation precludes their universal use. AIM: To validate the Maddrey Discriminant Function (DF); Glasgow Alcoholic Hepatitis Score (GAHS); Mayo End-stage Liver Disease (MELD); Age, Bilirubin, INR, Creatinine (ABIC); MELD-Na, UK End-stage Liver Disease (UKELD), and three scores of corticosteroid response at 1 week: an Early Change in Bilirubin Levels (ECBL), a 25% fall in bilirubin, and the Lille score. METHODS: Seventy-one consecutive patients with biopsy-proven AH, admitted between November 2007-September 2011, were evaluated. The clinical and biochemical parameters were analysed to assess prognostic models with respect to 30- and 90-day mortality. RESULTS: There were no significant differences in the areas under the receiver operating characteristics curve (AUROCs) relative to 30-day/90-day mortality: MELD 0.79/0.84, DF 0.71/0.74, GAHS 0.75/0.78, ABIC 0.71/0.78, MELD-Na 0.68/0.76, UKELD 0.56/0.68. One-week rescoring yielded a trend towards improved predictive accuracies (30-day/90-day AUROCs: 0.69­0.84/0.77­0.86). In patients with admission DF ≥ 32 (n = 31), response to corticosteroids according to ECBL, 25% fall in bilirubin and the Lille model yielded AUROCs of 0.73/0.73, 0.78/0.72 and 0.81/0.82 for a 30-day/90-day outcome respectively. All models showed excellent negative predictive values (NPVs; range: 86­100%), while the positive ones were low (range: 17­50%). CONCLUSIONS: MELD, DF, GAHS, ABIC and scores of corticosteroid response proved to be valid in an independent cohort of biopsy-proven alcoholic hepatitis. MELD modifications incorporating sodium did not confer any prognostic advantage over classical MELD. Based on excellent NPVs, the models are best to identify patients at low risk of death.

Reduced fibrosis in recurrent HCV with tacrolimus, azathioprine and steroids versus tacrolimus: randomised trial long term outcomes.

OBJECTIVE: Early results of a randomised trial showed reduced fibrosis due to recurrent HCV hepatitis with tacrolimus triple therapy (TT) versus monotherapy (MT) following transplantation for HCV cirrhosis. We evaluated the clinical outcomes after a median 8 years of follow-up, including differences in fibrosis assessed by collagen proportionate area (CPA). DESIGN: 103 consecutive liver transplant recipients with HCV cirrhosis receiving cadaveric grafts were randomised to tacrolimus MT (n=54) or TT (n=49) with daily tacrolimus (0.1 mg/kg divided dose), azathioprine (1 mg/kg) and prednisolone (20 mg), the last tailing off to zero by 6 months. Both groups had serial transjugular biopsies with hepatic venous pressure gradient (HVPG) measurement. Time to reach Ishak stage 4 was the predetermined endpoint. CPA was measured in all biopsies. Factors associated with HCV recurrence were evaluated. Clinical decompensation was the first occurrence of ascites/hydrothorax, variceal bleeding or encephalopathy. RESULTS: No significant preoperative, peri-operative or postoperative differences between groups were found. During 96 months median follow-up, stage 4 fibrosis was reached in 19 MT/11 TT with slower fibrosis progression in TT (p=0.009). CPA at last biopsy was 12% in MT and 8% in TT patients (p=0.004). 14 MT/ three TT patients reached HVPG≥10 mm Hg (p=0.002); 10 MT/three TT patients, decompensated. Multivariately, allocated MT (p=0.047, OR 3.23, 95% CI 1.01 to 10.3) was independently associated with decompensation: 14 MT/ seven TT died, and five MT/ four TT were retransplanted. CONCLUSIONS: Long term immunosuppression with tacrolimus, azathioprine and short term prednisolone in HCV cirrhosis recipients resulted in slower progression to severe fibrosis assessed by Ishak stage and CPA, less portal hypertension and decompensation, compared with tacrolimus alone. ISRCTN94834276--Randomised study for immunosuppression regimen in liver transplantation.

A randomised phase II/III trial of 3-weekly cisplatin-based sequential transarterial chemoembolisation vs embolisation alone for hepatocellular carcinoma.

BACKGROUND: Transarterial chemoembolisation (TACE) has not been shown to be superior to bland embolisation (TAE) for treatment of hepatocellular carcinoma (HCC). METHODS: We conducted a randomised phase II/III trial in patients with untreated HCC. Patients were randomised to TAE with polyvinyl alcohol (PVA) particles alone or sequential TACE (sTACE) in which cisplatin 50 mg was administered intrarterially 4-6 h before PVA embolisation. Treatment was repeated 3-weekly for up to three treatments. The primary endpoint was overall survival and secondary endpoints were progression-free survival, toxicity and response. Target sample sizes for phase II and III were 80 and 322. RESULTS: The trial was terminated at phase II after 86 patients had been randomised. Patients were well matched for prognostic criteria. All three planned treatments were given to 57.1% (TAE) and 56.8% (TACE) patients. Grade 3/4 toxicity occurred in 63.5% and 83.7%, respectively (P=0.019). End-of-treatment RECIST response (CR+PR) was 13.2 and 32.6% (P=0.04) (mRECIST 47.3% and 67.4) and median overall survival and progression-free survival was 17.3 vs 16.3 (P=0.74) months and 7.2 vs 7.5 (P=0.59), respectively. CONCLUSION: Transarterial chemoembolisation according this novel schedule is feasible and associated with a higher response rate than TAE alone. The survival benefit of TACE over TAE remains unproven.

A comparison of civilian (National Confidential Enquiry into Patient Outcome and Death) trauma standards with current practice in a deployed field hospital in Afghanistan.

BACKGROUND: The National Confidential Enquiry into Patient Outcome and Death (NCEPOD) report on trauma management, published in 2007, defined standards for United Kingdom (UK) hospitals dealing with trauma. This study compared the NCEPOD standards with the performance of a UK military field hospital in Afghanistan. SETTING: UK military field hospital, Camp Bastion, Helmand Province, Afghanistan. MATERIALS AND METHODS: Data were collected prospectively for all patients fulfilling the trauma team activation criteria during the 3 months of Operation Herrick IXa (from mid October 2008 to mid January 2009) and combined with a retrospective review of prehospital documentation, trauma resuscitation notes, operations notes and transfer notes for these patients. RESULTS: During the study period, there were 226 trauma team activations. Of those patients brought to the medical facility at Camp Bastion by UK assets, 93.7% were accompanied by a doctor with advanced airway skills, although only 6.2% of the patients required such an intervention. Consultants in emergency medicine and anaesthesia were present in 100% of cases and were directly involved (in either leading the team or performing airway management) in 63.5% and 77.6% of cases respectively. Of those patients requiring operative intervention, 98.1% had this performed by a consultant surgeon. Of those patients requiring CT, 93.6% of cases had this performed within 1 h of arrival. CONCLUSIONS: Trauma patients presenting to the medical facility at Camp Bastion during Operation Herrick IXa, irrespective of their nationality or background, received a high standard of medical care when compared with the NCEPOD standards.

Impact of tips preliver transplantation for the outcome posttransplantation.

The effects of transjugular intrahepatic portocaval shunt (TIPS) on the survival of grafts and patients after liver transplantation (LTx) have only been documented in small series and with only a comparative description with non-TIPS recipients. We evaluated 61 TIPS patients who had a subsequent LTx and compared these with 591 patients transplanted with cirrhosis without TIPS. Pretransplant characteristics were similar between groups. Graft survival at 1, 3 and 5 years post-LTx was 85.2%, 77% and 72.1% (TIPS) and 75.3%, 69.8% and 66.1% (controls). Patient survival at the same points was 91.7%, 85% and 81.7%, respectively (TIPS) and 85.4%, 80.3% and 76.2% (controls). Cox regression showed the absence of TIPS pre-LTx, transfusion of >5 units of blood during LTx, intensive care unit (ICU) stay post-LTx >3 days and earlier period of transplant to be significantly associated with a worse patient and graft survival at 1 year. Migration of the TIPS stent occurred in 28% of cases, increasing the time on bypass during LTx, but was not related to graft or patient survival. TIPS may improve portal supply to the graft and reduce collateral flow, improving function. This may account for the improved adjusted graft and patient survival by Cox regression at 12 months. Long-term survival was not affected.

The JAK2(V617F) tyrosine kinase mutation identifies clinically latent myeloproliferative disorders in patients presenting with hepatic or portal vein thrombosis.

Clinically latent myeloproliferative disorders (MPDs) are important causes of what would otherwise be considered idiopathic hepatic (HVT) or portal vein thrombosis (PVT). They may be difficult to diagnose initially because the peripheral blood count may be normal at the time of thrombosis. A strong association between an activating mutation of the gene encoding one of the Janus kinase family of tyrosine kinases (JAK2(V617F)) and the Philadelphia chromosome-negative MPDs has been identified. We have studied 19 patients with unexplained HVT or PVT and tested for JAK2(V617F). Fourteen (74%) of the 19 patients were heterozygous for JAK2(V617F) but did not meet diagnostic criteria for a MPD at the time of presentation with thrombosis. Prolonged follow-up established the presence of an overt MPD in 13 of the 14 patients after a median duration of 38 months. We recommend testing for JAK2(V617F) in all patients with unexplained HVT or PVT, to identify latent MPDs and prevent potential complications.

Tumour size and differentiation in predicting recurrence of hepatocellular carcinoma after liver transplantation: external validation of a new prognostic score.

BACKGROUND: A new prognostic score including tumour differentiation--establishing two groups of patients: group A with >3 points and group B with >4 points--improved the accuracy of the Milan criteria in predicting recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) in a large multicentre study (Decaens 2007). AIM: The aim of this study was to validate the new score in our HCC cohort. METHODS: The study involved 100 consecutive patients with mean age 55 years (range 31-68 years) (M/F: 88/22) transplanted for known HCC: 60 unifocal and 40 multifocal (2-3 nodules in 32 and >or=4 nodules in 8) at pre-LT imaging. Survival differences were analysed by log-rank test. Patient/tumour variables before LT and tumour differentiation at explant were assessed by univariate/multivariate analysis. RESULTS: Median follow-up was 29 months (range 1-145 months). HCC recurrence was recorded in 18 patients. Five-year recurrence-free survival rate was 67 +/- 7%. Patient survival at 3 months was 84 +/- 4% and at 5 years was 45 +/- 6%. Both recurrence-free survival and patient survival were not significantly different between groups A and B. Diameter of largest nodule was the sole pre-LT variable independently associated with recurrence [odd ratio (OR) 1.07; 95% confidence interval (CI) 1.01-1.12; P = 0.012]. Recurrence-free survival was significantly better in patients with diameter <30 mm compared with those with larger nodules (P = 0.0229). Number of nodules and tumour differentiation did not influence recurrence. There were three HCC recurrences with largest nodule size <30 mm, seven recurrences between 30-40 mm, and eight recurrences >40 mm. CONCLUSION: Tumour differentiation did not add significantly to prediction of HCC recurrence in our cohort. Conversely, diameter of the largest nodule remained a significant risk for recurrence.

Pegylated-interferon and ribavirin in liver transplant candidates and recipients with HCV cirrhosis: systematic review and meta-analysis of prospective controlled studies.

SUMMARY: Pegylated interferon with ribavirin (Peg/R) is the most effective therapy for chronic hepatitis C virus (HCV) but its utility and effectiveness after liver transplantation has been difficult to assess. We evaluated efficacy, tolerability, and safety of Peg/R in liver transplant candidates and recipients with HCV cirrhosis. We searched medical databases and conference proceedings between January 1999 and January 2008 selecting randomized and nonrandomized studies. Primary end points meta-analytically were: (1) sustained viral response (SVR) and (2) histological response. Secondary end points were: (1) treatment discontinuation, (2) mortality, and (3) rejection episodes. Pegylated interferons using either 1-1.5 mcg/kg of pegylated interferon alpha-2b or 180 microg (pegylated interferon alpha-2a combined with ribavirin 800-1200 mg/day were the most effective compared to any other regimen or no therapy. In three pretransplant studies the median SVR was 19.6% (19.6-50%). In six postransplant studies where a meta-analysis was done the cumulative risk difference in SVR was 0.31% (95% CI, 0.18-0.44, p < 0.001). However histological response was not significantly better compared to no therapy or other antiviral regimens. There were no significant differences in discontinuation of therapy, acute or chronic rejection or mortality between optimal Peg/R vs no treatment or other regimens. Hence pegylated interferon plus ribavirin in full doses is effective pre and post transplant but has a low SVR rate. To date no significant histological improvement has been reported.

Models for non-alcoholic fatty liver disease: a link with vascular risk.

Non alcoholic fatty liver disease (NAFLD) is often part of the metabolic syndrome which includes central obesity, dyslipidaemia, insulin resistance/type 2 diabetes mellitus and hypertension. In turn, NAFLD may be associated with an increased vascular risk. Several experimental models which express histological steatosis or steatohepatitis with fibrosis have been described. This review identifies those models of NAFLD with features of vascular risk.

Review article: renal function assessment in cirrhosis - difficulties and alternative measurements.

BACKGROUND: Renal function in patients with cirrhosis is important prognostically, both before and following liver transplantation. Its prognostic impact is reflected by the inclusion of serum creatinine in the model for end-stage liver disease score, which is now used for recipient prioritization on liver transplantation waiting lists in the USA. AIM: To review the accuracy of the surrogate markers for the assessment of renal function, i.e. glomerular filtration rate, particularly in patients with cirrhosis. METHOD: We reviewed the available literature in PubMed regarding the markers for GFR evaluation and the factors which affect their accuracy in cirrhosis. RESULTS: Although creatinine is widely available, it is an unreliable marker of glomerular filtration rate, particularly in patients with cirrhosis. Clearance of exogenous markers is considered the 'gold standard', but this methodology has many drawbacks, particularly poor applicability. Several mathematical formulae for estimated glomerular filtration rate are used to overcome some of these limitations: Cockcroft-Gault and Modification of Diet in Renal Disease formulae are the most frequently applied, but they are based on serum creatinine. CONCLUSIONS: Due to the inaccuracy of serum creatinine and its derived formulae in estimating glomerular filtration rate, alternative serum markers, such as cystatin C, and new formulae are desirable. These need formal evaluation in patients with cirrhosis so as to have a reliable surrogate of glomerular filtration rate, and to obviate many problems that are associated with using creatinine and estimated glomerular filtration rate.

Histopathology of graft versus host disease of the liver.

AIMS: To analyse the histological features of 33 patients (48 biopsy specimens) with a clinicopathological diagnosis of graft vs. host disease of the liver (L-GVHD). RESULTS: The time of biopsy post-haematopoietic stem cell transplantation (HSCT) ranged from 22 to 1082 days (median 144 days). Bile duct damage (BDD) was present in all biopsies except one. The bile duct to portal ratio ranged from 0.3 to 1 (median 0.8). Moderate/severe lobular hepatitis was present in 11 biopsies. Endotheliitis was present in four biopsies (8%). The majority of the biopsies showed none [25 (52%)] or mild [17 (35%)] fibrosis. The only significant difference between biopsies earlier ("acute") or later ("chronic" GVHD) than 100 days post-HSCT was the presence of portal inflammation in the "chronic" GVHD group. CONCLUSION: BDD is the predominant change in L-GVHD. In about a quarter of biopsies the appearance may be of a lobular hepatitis. L-GVHD is not a fibrogenic process. The significance of separating acute versus chronic L-GVHD based on a cut-off of 100 days post-HSCT is questionable. Further studies are needed to understand the relationships between the mechanisms of BDD, bile duct loss and regeneration.

Transjugular liver biopsy in patients with diffuse liver disease: comparison of three cores with one or two cores for accurate histological interpretation.

BACKGROUND: Transjugular liver biopsy (TJLB) can be performed to obtain more than two cores safely. This advantage has not been evaluated in terms of diagnostic accuracy or grading/staging evaluation. AIM: To evaluate whether three separate cores of TJLB provide more histological information compared with two or one cores. METHODS: Twenty-three patients, who had three separate passes, with each core >/=7mm in length using a 19G Tru-cut needle, were evaluated. Each TJLB was blindly coded; the pathologist randomly assessed: (a) each core separately covering the other two, (b) two cores simultaneously covering the third and (c) the three cores together for diagnostic yield, inflammation and fibrosis. RESULTS: The mean TJLB length was 32+/-5.5mm. In 12 one-core (52%) and 18 2-core (78%) assessments, diagnosis (mainly cirrhosis) was made correctly in each core. The within-patient standard deviations for one-core vs two-core assessment were similar for grading (0.42 and 0.47, respectively), but higher for staging (0.39 and 0.15, respectively). Staging was underestimated in assessing one-core and less for two cores compared to three cores. CONCLUSION: Three non-fragmented cores (each core >/=7mm in length) of TJLB can be considered a minimum requirement for histological assessment, giving better reproducibility in diagnosis as well as for inflammation and fibrosis.

Seeding following percutaneous diagnostic and therapeutic approaches for hepatocellular carcinoma. What is the risk and the outcome? Seeding risk for percutaneous approach of HCC.

BACKGROUND: Tumour biopsy is usually considered mandatory for patient management by oncologists. Currently percutaneous ablation is used therapeutically for cirrhotic patients with small hepatocellular carcinoma (HCC), not suitable for resection or waiting for liver transplantation. However malignant seeding is a recognized complication of both diagnostic and therapeutic procedures in patients with HCC. Although percutaneous therapy whether with or without biopsy of a suspected HCC nodule may minimize the risk of seeding, this has not been confirmed. AIM: To evaluate the risk of seeding, defined as new neoplastic disease occurring outside the liver capsule, either in the subcutaneous tissue or peritoneal cavity following needle biopsy and/or local ablation therapy (LAT). METHODS: A literature search resulted in 179 events in 99 articles between January 1983 and February 2007: 66 seedings followed liver biopsy, 26 percutaneous ethanol injection (PEI), 1 microwave, 22 radiofrequency ablation (RFA), and 64 after combined biopsy and percutaneous treatment (5 microwave; 33 PEI; 26 RFA). RESULTS: In 41 papers specifying the total number of patients biopsied and/or treated, the median risk of seeding was 2.29% (range 0-11%) for biopsy group; 1.4% (1.15-1.85%) for PEI when used with biopsy and 0.61% (0-5.56%) for RFA without biopsy, 0.95% (0-12.5%) for RFA with biopsy and 0.72% (0-10%) for liver nodules (including non-HCC nodules) biopsied and ablated. CONCLUSION: Risk of seeding with HCC is substantial and appears greater with using diagnostic biopsy alone compared to therapeutic percutaneous procedures. This risk is particularly relevant for patients being considered for liver transplantation.