Liver transplantation for iatrogenic bile duct injury: a systematic review.

BACKGROUND: Bile duct injury (BDI) is an infrequent but serious complication of cholecystectomy, often with life-changing consequences. Liver transplantation (LT) may be required following severe BDI, however given the rarity, few large studies exist to guide management for complex BDI. METHODS: A systematic review was performed to assess post-operative complications, 30-day mortality, retransplant rate and 1-year and 5-year survival following LT for BDI in Medline, EMBASE, Web of Science or Cochrane Clinical Trials Database. RESULTS: Seven articles met inclusion criteria, describing 179 patients that underwent LT for BDI. Secondary biliary cirrhosis (SBC) was the main indication for LT (82.2% of patients). Median model for end-stage liver disease (MELD) scores at time of LT ranged from 16 to 20.5. Median 30-day mortality was 20.0%. The 1-year and 5-year survival ranges were 55.0-84.3% and 30.0-83.3% respectively, and the overall retransplant rate was 11.5%. CONCLUSION: BDI is rarely indicated for LT, predominantly for SBC following multiple prior interventions. MELD scores poorly reflect underlying morbidity, and exception criteria for waitlisting may avoid prolonged LT waiting times. 30-day mortality was higher than for non-BDI indications, with comparable long term survival, suggesting that LT remains a viable but high risk salvage option for severe BDI.

Heterogeneity of management practices surrounding operable gallbladder cancer - results of the OMEGA-S international HPB surgical survey.

BACKGROUND: Gallbladder cancer (GBC) is an aggressive, uncommon malignancy, with variation in operative approaches adopted across centres and few large-scale studies to guide practice. We aimed to identify the extent of heterogeneity in GBC internationally to better inform the need for future multicentre studies. METHODS: A 34-question online survey was disseminated to members of the European-African Hepatopancreatobiliary Association (EAHPBA), American Hepatopancreatobiliary Association (AHPBA) and Asia-Pacific Hepatopancreatobiliary Association (A-PHPBA) regarding practices around diagnostic workup, operative approach, utilization of neoadjuvant and adjuvant therapies and surveillance strategies. RESULTS: Two hundred and three surgeons responded from 51 countries. High liver resection volume units (>50 resections/year) organised HPB multidisciplinary team discussion of GBCs more commonly than those with low volumes (p < 0.0001). Management practices exhibited areas of heterogeneity, particularly around operative extent. Contrary to consensus guidelines, anatomical liver resections were favoured over non-anatomical resections for T3 tumours and above, lymphadenectomy extent was lower than recommended, and a minority of respondents still routinely excised the common bile duct or port sites. CONCLUSION: Our findings suggest some similarities in the management of GBC internationally, but also specific areas of practice which differed from published guidelines. Transcontinental collaborative studies on GBC are necessary to establish evidence-based practice to minimise variation and optimise outcomes.

Negative predictive value of drain amylase concentration for development of pancreatic fistula after pancreaticoduodenectomy.

BACKGROUND: Post-operative pancreatic fistula (POPF) is the major source of morbidity following pancreaticoduodenectomy. A predictive indicator would be highly advantageous. One potential marker is drain amylase concentration (DAC). However, its predictive value has not been fully established. METHODS: 405 patients undergoing pancreaticoduodenectomy at our centre over a 10 year period were reviewed to determine the value of DAC as a predictive indicator for the development of POPF. RESULTS: POPF developed in 58 patients (14%). These patients suffered greater morbidity. Overall 30-day mortality was 1.5%. Male gender (OR: 5.1; p = 0.0082) and age > 70 (OR 2; p = 0.0372) were independent risk factors for POPF, whilst Type 2 diabetes (OR: 0.2321; p = 0.0090) and pancreatic ductal-adenocarcinoma (OR: 0.3721; p = 0.0039) decreased POPF risk. The DACs post-operatively were significantly higher in those developing POPF, but with significant overlap. ROC curves revealed optimal threshold values for differentiating POPF and non-POPF patients. A DAC°<°1400 U/ml on day 1 and <768 U/ml on day 2, although having a poor positive predictive value (32-44%), had a very strong negative predictive value (97-99%). CONCLUSION: Our data suggest that post-operative DAC below the determined optimal threshold values on day 1 and 2 following pancreaticoduodenectomy carries high negative predictive value for POPF development and identifies patients in whom early drain removal, and enhanced recovery may be considered, with simultaneous assessment of operative and clinical factors.

Surgical intervention for mediastinal pancreatic pseudocysts. A case series and review of the literature.

CONTEXT: Development of mediastinal pancreatic pseudocysts is a rare complication of pancreatitis. There is currently no consensus on the optimal management of this condition, options for which include conservative management with somatostatin analogues, endoscopic drainage procedures and surgery. CASE REPORT: Here we present two patients with mediastinal pancreatic pseudocysts which were initially managed endoscopically. However, in both cases, this led to complications secondary to the endoscopic procedures, recurrence or non-resolution of symptoms, requiring surgical cystogastrostomy and/or cystojejunostomy. CONCLUSION: These cases suggest that surgery may be ultimately necessary for mediastinal pancreatic pseudocysts where endoscopic procedures might have a high likelihood of failure.

The discard of deceased donor kidneys in the UK.

It is essential to minimize the unnecessary discard of procured deceased donor kidneys, but information on discard rates and the extent to which discard can be avoided are limited. Analysis of the UK Transplant Registry revealed that the discard rate of procured deceased donor kidneys has increased from 5% in 2002-3 to 12% in 2011-12. A national offering system for hard-to-place kidneys was introduced in the UK in 2006 (the Declined Kidney Scheme), but just 13% of kidneys that were subsequently discarded until 2012 were offered through the scheme. In order to examine the appropriateness of discard, 20 consecutive discarded kidneys from 13 deceased donors were assessed to determine if surgeons agreed with the decision that they were not implantable. Donors had a median (range) age of 67 (31-80) yr. Kidneys had been offered to a median of 3 (1-12) centers before discard. Four (20%) of the discarded kidneys were thought to be usable, and nine (45%) were possibly usable. As a result of these findings, major changes to the UK deceased donor kidney offering system have been implemented, including simultaneous offering and broader entry criteria for hard-to-place kidneys. Organizational changes are necessary to improve utilization of deceased donor kidneys.

Improved long-term survival after resection of colorectal liver metastases following staging with FDG positron emission tomography.

BACKGROUND AND OBJECTIVES: Actual long-term survival of patients with colorectal liver metastases staged by PET CT has not been reported. Objectives were to investigate whether PET CT staging results in actual improved long-term survival, to examine outcome in patients with 'equivocal' PET CT scans, and those excluded from hepatectomy by PET CT. METHODS: A retrospective analysis of patients undergoing hepatectomy for colorectal liver metastases between March 1998 and September 2008. RESULTS: Overall 5- and 10-year survival was 44.8% and 23.9%. PET CT staging resulted in management changes in 23% of patients. PET CT staged patients showed significantly better survival than those staged by CT alone at 3 years (79.8% vs. 54.1%) and at 5 years (54.1% vs. 37.3%) with median survivals of 6.4 years versus 3.9 years (log rank P = 0.018). Patients with equivocal PET CT scans showed worse median survival than those with favourable PET CT (log rank P = 0.002), but may include a subpopulation whose prognosis trends towards a more favourable outcome than those excluded from liver resection by PET CT, whose median survival remains limited to 21 months. CONCLUSIONS: Staging of patients with colorectal liver metastases by PET CT is associated with significantly improved actual long-term survival, and provides valuable prognostic information which guides surgical and oncological treatments.

Surgical outcomes of gallbladder cancer: the OMEGA retrospective, multicentre, international cohort study.

Background: Gallbladder cancer (GBC) is rare but aggressive. The extent of surgical intervention for different GBC stages is non-uniform, ranging from cholecystectomy alone to extended resections including major hepatectomy, resection of adjacent organs and routine extrahepatic bile duct resection (EBDR). Robust evidence here is lacking, however, and survival benefit poorly defined. This study assesses factors associated with recurrence-free survival (RFS), overall survival (OS) and morbidity and mortality following GBC surgery in high income countries (HIC) and low and middle income countries (LMIC). Methods: The multicentre, retrospective Operative Management of Gallbladder Cancer (OMEGA) cohort study included all patients who underwent GBC resection across 133 centres between 1st January 2010 and 31st December 2020. Regression analyses assessed factors associated with OS, RFS and morbidity. Findings: On multivariable analysis of all 3676 patients, wedge resection and segment IVb/V resection failed to improve RFS (HR 1.04 [0.84-1.29], p = 0.711 and HR 1.18 [0.95-1.46], p = 0.13 respectively) or OS (HR 0.96 [0.79-1.17], p = 0.67 and HR 1.48 [1.16-1.88], p = 0.49 respectively), while major hepatectomy was associated with worse RFS (HR 1.33 [1.02-1.74], p = 0.037) and OS (HR 1.26 [1.03-1.53], p = 0.022). Furthermore, EBDR (OR 2.86 [2.3-3.52], p < 0.0010), resection of additional organs (OR 2.22 [1.62-3.02], p < 0.0010) and major hepatectomy (OR 3.81 [2.55-5.73], p < 0.0010) were all associated with increased morbidity and mortality. Compared to LMIC, patients in HIC were associated with poorer RFS (HR 1.18 [1.02-1.37], p = 0.031) but not OS (HR 1.05 [0.91-1.22], p = 0.48). Adjuvant and neoadjuvant treatments were infrequently used. Interpretation: In this large, multicentre analysis of GBC surgical outcomes, liver resection was not conclusively associated with improved survival, and extended resections were associated with greater morbidity and mortality without oncological benefit. Aggressive upfront resections do not benefit higher stage GBC, and international collaborations are needed to develop evidence-based neoadjuvant and adjuvant treatment strategies to minimise surgical morbidity and prioritise prognostic benefit. Funding: Cambridge Hepatopancreatobiliary Department Research Fund.

Direct histological processing of EUS biopsies enables rapid molecular biomarker analysis for interventional pancreatic cancer trials.

OBJECTIVE: Current practice to diagnose pancreatic cancer is accomplished by endoscopic ultrasound guided fine needle aspiration (EUS-FNA) using a cytological approach. This method is time consuming and often fails to provide suitable specimens for modern molecular analyses. Here, we compare the cytological approach with direct formalin fixation of pancreatic EUS-FNA micro-cores and evaluate the potential to perform molecular biomarker analysis on these specimen. METHODS: 130 specimens obtained by EUS-FNA with a 22G needle were processed by the standard cytological approach and compared to a separate cohort of 130 specimens that were immediately formalin fixed to preserve micro-cores of tissue prior to routine histological processing. RESULTS: We found that direct formalin fixation significantly shortened the time required for diagnosis from 3.6 days to 2.9 days (p<0.05) by reducing the average time (140 vs 33 min/case) and number of slides (9.65 vs 4.67 slides/case) for histopathological processing. Specificity and sensitivity yielded comparable results between the two approaches (82.3% vs 77% and 90.9% vs 100%). Importantly, EUS-FNA histology preserved the tumour tissue architecture with neoplastic glands embedded in stroma in 67.89% of diagnostic cases compared to 27.55% with the standard cytological approach (p < 0.001). Furthermore, micro-core samples were suitable for molecular studies including the immunohistochemical detection of intranuclear Hes1 in malignant cells, and the laser-capture microdissection-mediated measurement of Gli-1 mRNA in tumour stromal myofibroblasts. CONCLUSIONS: Direct formalin fixation of pancreatic EUS-FNA micro-cores demonstrates superiority regarding diagnostic delay, costs, and specimen suitability for molecular studies. We advocate this approach for future investigational trials in pancreatic cancer patients.

Laparoscopic adrenalectomy: auditing the 10 year experience of a single centre.

BACKGROUND: Laparoscopic adrenalectomy (LA) is the gold standard for benign adrenal resection, and has been performed at our centre since 2000. We present a retrospective audit of our ten-year experience, and discuss the learning curve. METHODS: Creating a retrospective database, clinical and outcome data were collected for all resections performed over a ten-year period (2000-2010). Patients were chronologically divided into an 'early' (first 40 cases) and 'late' (subsequent cases) group to provide an insight into the learning curve. RESULTS: Over this period, 134 laparoscopic resections were performed, predominantly for benign adenomas (80.3%), with 48% of patients having primary hyperaldosteronism. There was almost equal sex distribution and mean age was 50.2 years, with a median BMI of 28.2. The mean operating time for left and right procedures were 127 and 124 min respectively, with 56.7% of resections being left sided. Our rate of conversion to open was 3.9%. Median length of stay was 4 days post-operatively. There was no mortality and 8.7% patients experienced a surgical complication. Analysis of the grouped data demonstrated a statistically significant reduction in open conversion rate (p = 0.017) and operative time (p = 0.011) in the 'late' group. Among the two groups there was no statistically significant difference in the length of stay and surgical complication rate. All results were comparable to published series in the literature. CONCLUSION: LA has proven to be a safe procedure with a low complication rate at our centre. Our data provide evidence that operative time and conversion rate improves with experience.

Radiation exposure during laparoscopic cholecystectomy with routine intraoperative cholangiography.

BACKGROUND: For many years, intraoperative cholangiography during cholecystectomy to aid definition of the biliary anatomy and to detect choledocholithiasis has been advocated. Although radiation exposure in fluoroscopic procedures is a concern, few available data exist regarding the radiation exposure incurred during intraoperative cholangiography. This study aimed to determine the average radiation exposure sustained during this procedure. METHODS: Radiation dose data were recorded between 5 September 2007 and 21 July 2008 for 108 consecutive patients undergoing laparoscopic cholecystectomy with intraoperative cholangiography. Dose area product values were used to calculate the entrance skin dose, an indicator of potential skin damage, and the effective dose, an indicator of long-term cancer risk, for each patient. RESULTS: The median age of the 108 patients (67% females) included in the data analysis was 51 years (range, 17-87 years). The mean entrance skin dose during intraoperative cholangiography was 0.0069 +/- 0.0066 Gy, and the mean effective dose was 0.18 +/- 0.17 mSv. No results exceeded the threshold of 2 Gy for skin damage, and the lifetime risk for the development of new cancer due to intraoperative cholangiography was less than 0.001%. CONCLUSION: Radiation doses administered during intraoperative cholangiography are safe and do not represent a contraindication to this procedure.

Current status of fast-track recovery pathways in pancreatic surgery.

CONTEXT: Pancreatic surgery is often associated with significant morbidity, thus requiring high level of peri-operative care and long hospital stay. Multi-modal "enhanced recovery" or "fast-track" pathways have recently been introduced, aiming to expedite patient recovery. OBJECTIVE: To evaluate the evidence underpinning the use of fast-track pathways in the peri-operative care of patients undergoing pancreatic cancer surgery. RESULTS: The available evidence is limited, consisting of three retrospective studies that report median length of hospital stay between 7 and 13 days. No significant difference has been noted in re-admission or 30-day mortality rates between fast-track patients and historical controls, but there is a trend for higher overall complication rate for the fast-track groups. CONCLUSION: Implementation of an enhanced recovery pathway is feasible and can achieve shorter hospital stay and reduced costs, with no increase in re-admission or peri-operative mortality rates. There is, however, conflicting evidence on the physiological mechanisms that contribute to accelerated patient recovery. Certain safety issues associated with post-operative morbidity warrant rigorous evaluation in further prospective studies.

Quality of life up to 30 years following liver transplantation.

Liver transplantation provides a return to a satisfactory quality of life (QOL) for the majority of patients in the short to medium term (first 5 years), but there is very little information on the QOL in the longer term and the factors influencing it. We therefore undertook a single-center cross-sectional analysis to determine QOL in patients 10 or more years after liver transplantation. All liver transplant recipients who were followed up at the Cambridge Transplant Unit for 10 or more years (transplanted between 1968 and 1994) and resident in the United Kingdom were asked to complete by post the Short Form 36 version 2 and the Ferrans and Powers questionnaires to evaluate their QOL. Univariate and multivariate analysis were performed to assess the relationship between a range of clinical parameters and QOL. One hundred two patients were invited to participate, and 61 (59.8%) responded. Overall, the patients reported a satisfactory QOL. On the Ferrans and Powers questionnaire, the patients had a mean Quality of Life Index score of 24.5. Factors associated with reduced physical functioning were age > 50 years at transplantation, female gender, and recurrence of the primary liver disease. On the Short Form 36 version 2 questionnaire, recipients had reduced physical functioning but normal mental health parameters in comparison with the normal population. Age > 60 years at the time of survey, female gender, and posttransplant complications were associated with reduced physical functioning. In conclusion, patients 10 or more years after liver transplantation generally have a good QOL, although physical functioning is reduced. Addressing issues such as recurrent disease and posttransplant problems such as osteoporosis may help to improve long-term QOL.

The role of arterial conduits for revascularisation in adult orthotopic liver transplantation.

The successful outcome in orthotopic liver transplantation (OLT) is critically dependent on the uncompromised hepatic graft blood inflow. Arterial conduits represent a good solution in cases where conventional revascularisation is not possible. The purpose of this systematic review is to analyse the published evidence on the use of arterial conduits in adult OLT. After review of the Pubmed and EMBASE databases, 19 relevant studies were identified and analysed. Even though patient survival was comparable, most large studies reported worse 1-, 3- and 5-year graft survival rates compared to grafts with standard arterial revascularisation. Primary grafts were more commonly affected than re-grafts. Early and late hepatic artery thrombosis occurred more commonly, while the use of an arterial conduit was identified as an independent risk factor. The overall biliary complications were comparable, however, ischaemic cholangiopathy was encountered about 3 times more in patients with arterial conduits and strongly correlated with the occurrence of late HAT. In conclusion, the use of arterial conduit is a useful option in adult OLT in cases that the conventional revascularisation technique cannot be used or results in suboptimal arterial inflow. More studies directly addressing issues such as pre-operative evaluation regarding the need for arterial conduit, the types of vessels used, positioning of the conduit and post-operative management are required.

Surgical management of hepato-pancreatic metastasis from renal cell carcinoma.

AIM: To investigate the outcomes of liver and pancreatic resections for renal cell carcinoma (RCC) metastatic disease. METHODS: This is a retrospective, single centre review of liver and/or pancreatic resections for RCC metastases between January 2003 and December 2015. Descriptive statistical analysis and survival analysis using the Kaplan-Meier estimation were performed. RESULTS: Thirteen patients had 7 pancreatic and 7 liver resections, with median follow-up 33 mo (range: 3-98). Postoperative complications were recorded in 5 cases, with no postoperative mortality. Three patients after hepatic and 5 after pancreatic resection developed recurrent disease. Median overall survival was 94 mo (range: 23-94) after liver and 98 mo (range: 3-98) after pancreatic resection. Disease-free survival was 10 mo (range 3-55) after liver and 28 mo (range 3-53) after pancreatic resection. CONCLUSION: Our study shows that despite the high incidence of recurrence, long term survival can be achieved with resection of hepatic and pancreatic RCC metastases in selected cases and should be considered as a management option in patients with oligometastatic disease.

Development of a Prognostic Model That Predicts Survival After Pancreaticoduodenectomy for Ampullary Cancer.

OBJECTIVES: The aims of this study were to (i) identify independent predictors of survival after pancreaticoduodenectomy for ampullary cancer and (ii) develop a prognostic model of survival. METHODS: Data were analyzed retrospectively on 110 consecutive patients who underwent pancreaticoduodenectomy between 2002 and 2013. Subjects were categorized into 3 nodal subgroups as per the recently proposed nodal subclassification: N0 (node negative), N1 (1-2 metastatic nodes), or N2 (≥3 metastatic nodes). Clinicopathological features and overall survival were compared by Kaplan-Meier and Cox regression analyses. RESULTS: The overall 1-, 3-, and 5-year survival rates were 79.8%, 42.2%, and 34.9%, respectively. The overall 1-, 3-, and 5-year survival rates for the N0 group were 85.2%, 71.9%, and 67.4%, respectively. The 1-, 3-, 5-year survival rates for the N1 and N2 subgroups were 81.5%, 49.4%, and 49.4% and 75%, 19.2%, and 6.4%, respectively (log rank, P < 0.0001). After performing a multivariate Cox regression analysis, vascular invasion and lymph node ratio were the only independent predictors of survival. Hence, a prediction model of survival was constructed based on those 2 variables. CONCLUSIONS: Using data from a carefully selected cohort of patients, we created a pilot prognostic model of postresectional survival. The proposed model may help clinicians to guide treatments in the adjuvant setting.

Human primary liver cancer-derived organoid cultures for disease modeling and drug screening.

Human liver cancer research currently lacks in vitro models that can faithfully recapitulate the pathophysiology of the original tumor. We recently described a novel, near-physiological organoid culture system, wherein primary human healthy liver cells form long-term expanding organoids that retain liver tissue function and genetic stability. Here we extend this culture system to the propagation of primary liver cancer (PLC) organoids from three of the most common PLC subtypes: hepatocellular carcinoma (HCC), cholangiocarcinoma (CC) and combined HCC/CC (CHC) tumors. PLC-derived organoid cultures preserve the histological architecture, gene expression and genomic landscape of the original tumor, allowing for discrimination between different tumor tissues and subtypes, even after long-term expansion in culture in the same medium conditions. Xenograft studies demonstrate that the tumorogenic potential, histological features and metastatic properties of PLC-derived organoids are preserved in vivo. PLC-derived organoids are amenable for biomarker identification and drug-screening testing and led to the identification of the ERK inhibitor SCH772984 as a potential therapeutic agent for primary liver cancer. We thus demonstrate the wide-ranging biomedical utilities of PLC-derived organoid models in furthering the understanding of liver cancer biology and in developing personalized-medicine approaches for the disease.

Time spent in hospital after liver transplantation: Effects of primary liver disease and comorbidity.

AIM: To explore the effect of primary liver disease and comorbidities on transplant length of stay (TLOS) and LOS in later admissions in the first two years after liver transplantation (LLOS). METHODS: A linked United Kingdom Liver Transplant Audit - Hospital Episode Statistics database of patients who received a first adult liver transplant between 1997 and 2010 in England was analysed. Patients who died within the first two years were excluded from the primary analysis, but a sensitivity analysis was also performed including all patients. Multivariable linear regression was used to evaluate the impact of primary liver disease and comorbidities on TLOS and LLOS. RESULTS: In 3772 patients, the mean (95%CI) TLOS was 24.8 (24.2 to 25.5) d, and the mean LLOS was 24.2 (22.9 to 25.5) d. Compared to patients with cancer, we found that the largest difference in TLOS was seen for acute hepatic failure group (6.1 d; 2.8 to 9.4) and the largest increase in LLOS was seen for other liver disease group (14.8 d; 8.1 to 21.5). Patients with cardiovascular disease had 8.5 d (5.7 to 11.3) longer TLOS and 6.0 d (0.2 to 11.9) longer LLOS, compare to those without. Patients with congestive cardiac failure had 7.6 d longer TLOS than those without. Other comorbidities did not significantly increase TLOS nor LLOS. CONCLUSION: The time patients spent in hospital varied according to their primary liver disease and some comorbidities. Time spent in hospital of patients with cancer was relatively short compared to most other indications. Cardiovascular disease and congestive cardiac failure were the comorbidities with a strong impact on increased LOS.

Incidental non-benign gallbladder histopathology after cholecystectomy in an United Kingdom population: Need for routine histological analysis?

AIM: To analyse the range of histopathology detected in the largest published United Kingdom series of cholecystectomy specimens and to evaluate the rational for selective histopathological analysis. METHODS: Incidental gallbladder malignancy is rare in the United Kingdom with recent literature supporting selective histological assessment of gallbladders after routine cholecystectomy. All cholecystectomy gallbladder specimens examined by the histopathology department at our hospital during a five year period between March 2008 and March 2013 were retrospectively analysed. Further data was collected on all specimens demonstrating carcinoma, dysplasia and polypoid growths. RESULTS: The study included 4027 patients. The majority (97%) of specimens exhibited gallstone or cholecystitis related disease. Polyps were demonstrated in 44 (1.09%), the majority of which were cholesterol based (41/44). Dysplasia, ranging from low to multifocal high-grade was demonstrated in 55 (1.37%). Incidental primary gallbladder adenocarcinoma was detected in 6 specimens (0.15%, 5 female and 1 male), and a single gallbladder revealed carcinoma in situ (0.02%). This large single centre study demonstrated a full range of gallbladder disease from cholecystectomy specimens, including more than 1% neoplastic histology and two cases of macroscopically occult gallbladder malignancies. CONCLUSION: Routine histological evaluation of all elective and emergency cholecystectomies is justified in a United Kingdom population as selective analysis has potential to miss potentially curable life threatening pathology.

Time-varying impact of comorbidities on mortality after liver transplantation: a national cohort study using linked clinical and administrative data.

OBJECTIVE: We assessed the impact of comorbidity on mortality in three periods after liver transplantation (first 90 days, 90 days-5 years and 5-10 years). DESIGN: Prospective cohort study using records from the UK Liver Transplant Audit (UKLTA) linked to Hospital Episode Statistics (HES), an administrative database of hospital admissions in the English National Health Service (NHS). Comorbidities relevant for liver transplantation were identified from the 10th revision of the International Classification of Diseases (ICD-10) codes in HES records of admissions in the year preceding their operation. Multivariable Cox regression was used to estimate HRs for three different time periods after liver transplantation. SETTING: All liver transplant centres in the NHS hospitals in England. PARTICIPANTS: Adults who received a first elective liver transplant between April 1997 and March 2010 in the linked UKLTA-HES database. OUTCOMES: Patient mortality in three different time periods after transplantation. RESULTS: Among 3837 recipients, 45.1% had comorbidities. Recipients with cardiovascular disease had statistically significantly higher mortality in all three periods after transplantation (first 90 days: HR=2.0; 95% CI 1.4 to 2.9, 90 days-5 years: 1.6; 1.2 to 2.2, beyond 5 years: 2.8; 1.7 to 4.4). Prior congestive cardiac failure (3.2; 2.1 to 4.9) significantly increased mortality only in the first 90 days. History of non-hepatic malignancy appeared to increase risk over all periods, but significantly only in the first 90 days (1.9; 1.0 to 3.6). A diagnosis of connective tissue disease, dementia, diabetes, chronic pulmonary and renal disease did not have a significant impact on mortality in any period. CONCLUSIONS: The impact of comorbidities present at the time of transplantation changes with time after transplantation. Renal disease, pulmonary disease and diabetes had no impact on mortality in contrast to previous reports.