Publications by authors named "Abid Suddle"

40 Publications

Statins: A Panacea to Reduce Mortality in Patients Undergoing Liver Transplantation for Hepatocellular Carcinoma?

Liver Transpl 2021 Nov 27. Epub 2021 Nov 27.

Institute of Liver Studies, King's College Hospital National Health Service Foundation Trust, London, UK.

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http://dx.doi.org/10.1002/lt.26381DOI Listing
November 2021

National time trends in mortality and graft survival following liver transplantation from circulatory death or brainstem death donors.

Br J Surg 2021 Dec;109(1):79-88

Department of Health Services Research and Policy, London School of Hygiene and Tropical Medicine, London, UK.

Background: Despite high waiting list mortality rates, concern still exists on the appropriateness of using livers donated after circulatory death (DCD). We compared mortality and graft loss in recipients of livers donated after circulatory or brainstem death (DBD) across two successive time periods.

Methods: Observational multinational data from the United Kingdom and Ireland were partitioned into two time periods (2008-2011 and 2012-2016). Cox regression methods were used to estimate hazard ratios (HRs) comparing the impact of periods on post-transplant mortality and graft failure.

Results: A total of 1176 DCD recipients and 3749 DBD recipients were included. Three-year patient mortality rates decreased markedly from 19.6 per cent in time period 1 to 10.4 per cent in time period 2 (adjusted HR 0.43, 95 per cent c.i. 0.30 to 0.62; P < 0.001) for DCD recipients but only decreased from 12.8 to 11.3 per cent (adjusted HR 0.96, 95 per cent c.i. 0.78 to 1.19; P = 0.732) in DBD recipients (P for interaction = 0.001). No time period-specific improvements in 3-year graft failure were observed for DCD (adjusted HR 0.80, 95% c.i. 0.61 to 1.05; P = 0.116) or DBD recipients (adjusted HR 0.95, 95% c.i. 0.79 to 1.14; P = 0.607). A slight increase in retransplantation rates occurred between time period 1 and 2 in those who received a DCD liver (from 7.3 to 11.8 per cent; P = 0.042), but there was no change in those receiving a DBD liver (from 4.9 to 4.5 per cent; P = 0.365). In time period 2, no difference in mortality rates between those receiving a DCD liver and those receiving a DBD liver was observed (adjusted HR 0.78, 95% c.i. 0.56 to 1.09; P = 0.142).

Conclusion: Mortality rates more than halved in recipients of a DCD liver over a decade and eventually compared similarly to mortality rates in recipients of a DBD liver. Regions with high waiting list mortality may mitigate this by use of DCD livers.
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http://dx.doi.org/10.1093/bjs/znab347DOI Listing
December 2021

Liver transplantation for HCC: validation of prognostic power of the RETREAT score for recurrence in a UK cohort.

HPB (Oxford) 2021 Sep 24. Epub 2021 Sep 24.

Liver Transplant Surgery, Institute of Liver Studies, King's College Hospital, London, SE5 9RS, United Kingdom. Electronic address:

Background: The Risk Estimation of Tumor Recurrence After Transplant (RETREAT) score as a prognostic index for recurrence has been reported previously and has not been validated outside the USA. Our study has validated the score in a single center UK cohort of patients being transplanted for HCC.

Methods: LT for HCC between 2008 and 2018 at our center were analyzed. Recurrence-free survival (RFS) was compared by the RETREAT score and validated using Net Reclassification Improvement (NRI) by comparing it to Milan criteria.

Results: 346 adult HCC patients were transplanted of whom 313 were included. 28 (8.9%) had a recurrence. Summation of largest diameter and total number of viable tumors (HR = 1.19, p < 0.001), micro-/macro-vascular invasion (HR = 3.74, p = 0.002) and AFP>20 ng/ml (HR = 3.03, p = 0.005) were associated with recurrence on multivariate analysis. RFS decreased with increasing RETREAT score (log-rank p = 0.016). RETREAT performed better than Milan with significant NRI at 1- and 2-years post-transplant (0.43 (p = 0.004) and 0.38 (p = 0.03) respectively).

Conclusion: LT outcomes using the revised UK criteria are equivalent to Milan criteria. Further, RETREAT score was validated as a prognostic index for the first time in a UK cohort and may assist risk stratification, selection for adjuvant therapies and guide surveillance.
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http://dx.doi.org/10.1016/j.hpb.2021.09.008DOI Listing
September 2021

Clinical management of sickle cell liver disease in children and young adults.

Arch Dis Child 2021 04 11;106(4):315-320. Epub 2020 Nov 11.

Paediatric Liver, GI and Nutrition Centre and MowatLabs, King's College Hospital NHS Foundation Trust, London, UK

Liver involvement in sickle cell disease (SCD) is often referred to as sickle cell hepatopathy (SCH) and is a complication of SCD which may be associated with significant mortality. This review is based on a round-table workshop between paediatric and adult hepatologists and haematologists and review of the literature. The discussion was prompted by the lack of substantial data and guidance in managing these sometimes very challenging cases. This review provides a structured approach for the diagnosis and management of SCH in children and young adults. The term SCH describes any hepatobiliary dysfunction in the context of SCD. Diagnosis and management of biliary complications, acute hepatic crisis, acute hepatic sequestration and other manifestations of SCH are discussed, as well as the role of liver transplantation and haemopoietic stem cell transplantation in the management of SCH.
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http://dx.doi.org/10.1136/archdischild-2020-319778DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7610372PMC
April 2021

The Impact of Performance Status on Length of Hospital Stay and Clinical Complications Following Liver Transplantation.

Transplantation 2021 09;105(9):2037-2044

Institute of Liver Studies, King's College Hospital NHS Foundation Trust, London, United Kingdom.

Background: Impaired pretransplant performance status (PS) is associated with chronic liver disease (CLD). We studied its impact on hospital length of stay (LOS), complications, and readmissions in the first year after liver transplantation.

Methods: The Standard National Liver Transplant Registry was linked to a hospital administrative dataset, and all first-time liver transplant recipients with CLD aged ≥18 years in England were identified. A modified 3-level Eastern Cooperative Oncology Group score was used to assess PS. Linear- and logistic-fixed effect regression models were used to estimate the effect of specific posttransplant complications and readmissions in the first year after transplantation.

Results: Six thousand nine hundred sixty-eight recipients were included. Impaired PS was associated with an increased LOS in the initial posttransplant period (comparing ECOG 1-3, adjusted difference 7.2 d; 95% confidence [CI], 4.8-9.6; P < 0.001) and in time spent on the ITU (adjusted difference 1.2 d; 95% CI, 0.4-2.0; P < 0.001). There was no significant association between ECOG status and total LOS of later admissions (adjusted difference, 2.5 d; 95% CI, -0.4-5.5; P = 0.23). Those with a poorer ECOG status had an increased incidence of renal failure (odds ratio, 1.5; 95% CI, 1.1-2.0; P = 0.004) and infection (odds ratio, 1.2; 95% CI, 1.1-1.4; P = 0.02) but not an increased incidence of readmission (odds ratio, 1.2; 95% CI, 0.9-1.5; P = 0.13).

Conclusions: In liver transplant recipients with CLD, impaired pretransplant PS is associated with prolonged LOS in the immediate posttransplant period but not with LOS of later admissions in the first year after transplantation. Impaired PS increased the risk of renal failure and infection.
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http://dx.doi.org/10.1097/TP.0000000000003484DOI Listing
September 2021

Kidney Rejection Following Simultaneous Liver-kidney Transplantation.

Transplant Direct 2020 Jul 11;6(7):e569. Epub 2020 Jun 11.

Institute of Liver Studies, King's College Hospital, London, United Kingdom.

Background: Donor-specific antibodies are reported to increase the risk of rejection and reduce allograft survival following simultaneous liver-kidney transplantation. Optimal immunosuppression regimens to reduce this risk and to treat rejection episodes are underinvestigated.

Methods: Cohort analysis of the first 27 simultaneous liver-kidney transplant recipients, between 2014 and 2018 at our unit, is performed under a new risk stratification policy. Those with donor-specific antibodies to class II HLA with a mean fluorescence intensity >10 000 are considered high risk for antibody-mediated rejection (AMR). These patients received immunosuppression, which consisted of induction therapy, tacrolimus, mycophenolate mofetil, and prednisolone. All other patients are considered low risk and received tacrolimus and prednisolone alone.

Results: Three patients were high risk for rejection, and 2 of these patients developed AMR, which was treated with plasma exchange and intravenous immunoglobulin. At 1 y, their estimated glomerular filtration rate (eGFR) were 50 and 59 mL/min. Two other patients developed AMR, which was similarly treated, and their 1-y eGFR was 31 and 50 mL/min. The overall histologically proven acute rejection rate within the first year was 33%, and median eGFR, for the 27 patients, at 1 y was 52 mL/min and at 2 y was 49 mL/min.

Conclusions: This study confirms that there is a risk of AMR following simultaneous liver-kidney transplantation despite increased immunosuppression. This can be effectively treated with plasma exchange and intravenous immunoglobulin.
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http://dx.doi.org/10.1097/TXD.0000000000001004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7339316PMC
July 2020

A Very Short Course of HBIg+NA Followed by Entecavir or Tenofovir Monotherapy Prevents HBV Recurrence in Low-Risk Liver Transplant Recipients.

Transplant Proc 2021 Jan-Feb;53(1):207-214. Epub 2020 Jun 28.

Institute of Liver Studies, King's College Hospital, London, United Kingdom.

Background: Monoprophylaxis with third-generation nucleos(t)ide analogues (NAs) can be safely adopted in hepatitis B virus (HBV)-positive, liver transplantation (LT) patients after at least 6 months of HBV immunoglobulin (HBIg)+NA. We investigated the efficacy of earlier initiation of post-LT entecavir (ETV) or tenofovir (TDF) monoprophylaxis.

Methods: Between September 2011 and January 2017, all consecutive hepatitis B surface antigen (HBsAg)-positive transplanted patients were scheduled to receive HBIg with ETV or TDF for a period related to the risk for HBV reinfection: 1. low-risk patients (HBeAg-negative and HBV DNA < 12 IU/mL before LT) were due to withdraw from HBIg once HBsAg had become negative after a minimum of 7 days of HBIg+NA; 2. high-risk patients were due to receive HBIg for at least 6 months, after which they continued with third-generation NA monotherapy, only.

Results: Twenty patients with a median interquartile range (IQR) follow-up of 46 (64-39) months were enrolled in the study (40% receiving ETV, 60% receiving TDF). Two low-risk patients refused early HBIg withdrawal and were therefore treated and analyzed along with the high-risk group. Eventually, there were 2 groups: group A, which included 12 low-risk patients, and group B, which included 8 patients (six high-risk, 2 low-risk). After transplantation, group A and B patients received HBIg+NA for a median (IQR) time of 7 (9-7) days and 9 (13-5) months, respectively. All 20 recipients demonstrated HBV DNA < 12 IU/mL and stable graft function during follow-up. Two patients (10%), 1 from each group, had HBsAg relapse. Notably, both patients who relapsed had hepatocellular carcinoma (HCC) diagnosed before LT and showed very low levels (< 0.25 IU/mL) of HBsAg after recurrence.

Conclusion: In low-risk HBsAg-positive recipients, HBIg may be safely discontinued within 2 weeks of LT and replaced by ETV or TDF monotherapy.
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http://dx.doi.org/10.1016/j.transproceed.2020.04.1822DOI Listing
April 2021

Low prevalence and disease severity of COVID-19 in post-liver transplant recipients-A single centre experience.

Liver Int 2020 08 17;40(8):1972-1976. Epub 2020 Jun 17.

Institute of Liver Studies, King's College Hospital, London, UK.

Coronavirus disease 2019 (COVID-19) caused by a novel coronavirus called severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is driving a present day global pandemic. Immunosuppressed patients are regarded as a high-risk cohort. The following is a short report on COVID-19 in liver transplant recipients (n = 5) from a high volume UK liver transplant unit with a large follow-up cohort (n = 4500). Based on this limited data, liver transplant recipients appear to have a low incidence of COVID-19, with less severe symptoms than expected, when compared with the general population and other solid organ recipients. This possibly could be related to self-isolation adherence and/or the 'ideal' level of immunosuppression that favourably modulates the immune response to COVID-19.
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http://dx.doi.org/10.1111/liv.14552DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7300707PMC
August 2020

Sequential Cohort Analysis After Liver Transplantation Shows de Novo Extended Release Tacrolimus Is Safe, Efficacious, and Minimizes Renal Dysfunction.

Transplant Direct 2020 Feb 17;6(2):e528. Epub 2020 Jan 17.

Institute of Liver Studies, King's College Hospital, Denmark Hill, London, United Kingdom.

The use of once-daily extended-release tacrolimus (ERT) is associated with improved long-term graft and patient survival when compared with twice-daily tacrolimus (BDT), but the underlying reasons for differential survival are unclear. The aim of the study was to compare clinical outcomes known to impact on posttransplant survival for de novo BDT and ERT in liver transplantation (LT) recipients.

Methods: We conducted a single-center, prospective sequential cohort analysis of adult patients undergoing LT during a change in protocol from de novo BDT to ERT, with a 6-month post-LT follow-up.

Results: A total of 160 transplanted patients were evaluated; 82 were in the BDT group and 78 were in the ERT group. The cohorts were matched for standard variables and a similar proportion in each group received induction interleukin-2 receptor antibody (36% and 31%). There were no significant differences in the measured outcomes of patient and graft survival, biopsy-proven acute rejection episodes, post LT diabetes, and toxicity. A significantly lower number of patients developed chronic kidney disease Stage3-4 in the ERT cohort compared with BDT cohort. In patients with pre-LT renal dysfunction who received antibody induction, estimated glomerular filtration rate decreased significantly in the BDT but not the ERT group.

Conclusions: We show that once-daily ERT is as safe and efficacious as BDT in de novo LT but optimally conserves renal function post-LT.
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http://dx.doi.org/10.1097/TXD.0000000000000970DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7004634PMC
February 2020

Successful simultaneous liver-kidney transplantation for renal failure associated with hereditary complement C3 deficiency.

Am J Transplant 2020 08 6;20(8):2260-2263. Epub 2020 Feb 6.

Institute of Liver Studies, King's College Hospital NHS Foundation Trust, London, UK.

Hereditary complement C3 deficiency is associated with recurrent bacterial infections and proliferative glomerulonephritis. We describe a case of an adult with complete deficiency of complement C3 due to homozygous mutations in C3 gene: c.1811delT (Val604Glyfs*2), recurrent bacterial infections, crescentic glomerulonephritis, and end-stage renal failure. Following isolated kidney transplantation he would remain C3 deficient with a similar, or increased, risk of infections and glomerulonephritis. As C3 is predominantly synthesized in the liver, with a small proportion of C3 monocyte derived and kidney derived, he proceeded to simultaneous liver-kidney transplantation. The procedure has been successful with restoration of his circulating C3 levels, normal liver and kidney function at 26 months of follow-up. Simultaneous liver-kidney transplant is a viable option to be considered in this rare setting.
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http://dx.doi.org/10.1111/ajt.15785DOI Listing
August 2020

Assessing the Time-Dependent Impact of Performance Status on Outcomes After Liver Transplantation.

Hepatology 2020 10 30;72(4):1341-1352. Epub 2020 Jun 30.

Institute of Liver Studies, King's College Hospital NHS Foundation Trust, London, United Kingdom.

Background And Aims: Identifying how the prognostic impact of performance status (PS) differs according to indication, era, and time period ("epoch") after liver transplantation (LT) could have implications for selection and treatment of patients on the waitlist. We used national data from the United Kingdom and Ireland to assess impact of PS on mortality separately for HCC and non-HCC recipients.

Approach And Results: We assessed pre-LT PS using the 5-point modified Eastern Cooperative Oncology Group scale and used Cox regression methods to estimate hazard ratios (HRs) that compared posttransplantation mortality in different epochs of follow-up (0-90 days and 90 days to 1 year) and in different eras of transplantation (1995-2005 and 2006-2016). 2107 HCC and 10,693 non-HCC patients were included. One-year survival decreased with worsening PS in non-HCC recipients where 1-year survival was 91.9% (95% confidence interval [CI], 88.3-94.4) in those able to carry out normal activity (PS1) compared to 78.7% (95% CI, 76.7-80.5) in those completely reliant on care (PS5). For HCC patients, these estimates were 89.9% (95% CI, 85.4-93.2) and 83.1% (95% CI, 61.0-93.3), respectively. Reduction in survival in non-HCC patients with poorer PS was in the first 90 days after transplant, with no major effect observed between 90 days and 1 year. Adjustment for donor and recipient characteristics did not change the findings. Comparing era, post-LT mortality improved for HCC (adjusted HR, 0.55; 95% CI, 0.40-0.74) and non-HCC recipients (0.48; 95% CI, 0.42-0.55), but this did not differ according to PS score (P = 0.39 and 0.61, respectively).

Conclusions: Impact on mortality of the recipient's pretransplant PS is principally limited to the first 3 months after LT. Over time, mortality has improved for both HCC and non-HCC recipients and across the full range of PS.
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http://dx.doi.org/10.1002/hep.31124DOI Listing
October 2020

Management of liver complications in sickle cell disease.

Authors:
Abid R Suddle

Hematology Am Soc Hematol Educ Program 2019 12;2019(1):345-350

Institute of Liver Studies, King's College Hospital, London, United Kingdom.

Liver disease is an important cause of morbidity and mortality in patients with sickle cell disease (SCD). Despite this, the natural history of liver disease is not well characterized and the evidence basis for specific therapeutic intervention is not robust. The spectrum of clinical liver disease encountered includes asymptomatic abnormalities of liver function; acute deteriorations in liver function, sometimes with a dramatic clinical phenotype; and decompensated chronic liver disease. In this paper, the pathophysiology and clinical presentation of patients with acute and chronic liver disease will be outlined. Advice will be given regarding initial assessment and investigation. The evidence for specific medical and surgical interventions will be reviewed, and management recommendations made for each specific clinical presentation. The potential role for liver transplantation will be considered in detail.
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http://dx.doi.org/10.1182/hematology.2019000037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6913458PMC
December 2019

Modern Outcomes Following Treatment of Hepatocellular Carcinoma in Hereditary Hemochromatosis: A Matched Cohort Study.

Am J Clin Oncol 2019 12;42(12):918-923

Institute of Liver Studies.

Objective: Hepatocellular carcinoma (HCC) is a complication of the common genetic condition hereditary hemochromatosis (HH). It is unknown whether HH as an etiology of liver disease impacts the outcome. We compared the results of liver transplantation (LT), surgical resection and locoregional therapies in a matched cohort study and investigated whether HH as an etiology has an impact on survival.

Materials And Methods: Consecutive patients with HH and HCC (2000 to 2015) were compared with age, sex and Barcelona Clinic Liver Cancer (BCLC) stage-matched non-HH HCC cases. Patients were offered curative or noncurative treatment according to BCLC stage and Milan criteria. The primary endpoint was all-cause mortality.

Results: A total of 102 patients (52 HH; total cohort median age: 67 [44 to 78] y, 97% male, Model for End-stage Liver Disease: 9 [5 to 31]) were studied with a median follow-up of 22 (3 to 126) months. Of the HH cases, the median serum ferritin at diagnosis of HCC was 326 (27 to 5718) μg/L and α-fetoprotein 33 (2 to 197,926) kIU/L. Five-year survival for HH patients receiving curative therapy was 77% (80% for LT, 67% for resection/radiofrequency ablation), and 15% (23% for transarterial chemoembolization) for those undergoing noncurative therapy. Survival for HH patients compared with controls was similar (hazard ratio=0.949; P=0.839). On multivariate Cox regression survival analysis, BCLC stage, and diagnosis of ischemic heart disease (but not HH diagnosis) were independently associated with reduced survival.

Conclusions: Patients with HCC and HH can achieve comparable survival rates following curative or LRT modalities to other liver diseases. The BCLC staging system accurately stratifies survival and excellent 5-year survival is possible following LT in selected patients.
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http://dx.doi.org/10.1097/COC.0000000000000583DOI Listing
December 2019

The Liver in Sickle Cell Disease.

Clin Liver Dis 2019 05 21;23(2):177-189. Epub 2019 Feb 21.

Institute of Liver Studies, King's College Hospital NHS Foundation Trust, Denmark Hill, London SE5 9RS, UK. Electronic address:

Patients with sickle cell disease can develop liver disease as a result of intrahepatic sickling of erythrocytes, viral hepatitis and iron overload secondary to multiple blood transfusions, and gallstone disease as a result of chronic hemolysis. The spectrum of clinical liver disease is wide and often multifactorial. Some patients develop cirrhosis that may progress to end-stage liver failure. Limited evidence exists for medical treatments. Exchange blood transfusions may improve outcomes in the acute liver syndromes. Liver transplantation may be an option for chronic liver disease. The role for prophylactic cholecystectomy in preventing complications of gallstone disease is controversial.
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http://dx.doi.org/10.1016/j.cld.2018.12.002DOI Listing
May 2019

Assessing the Impact of Suboptimal Donor Characteristics on Mortality After Liver Transplantation: A Time-dependent Analysis Comparing HCC With Non-HCC Patients.

Transplantation 2019 04;103(4):e89-e98

Department of Health Services Research and Policy, London School of Hygiene and Tropical Medicine, London, United Kingdom.

Background: Patients who receive a liver transplant for hepatocellular carcinoma (HCC) often receive poorer-quality livers. Tumor recurrence also has a negative effect on posttransplant outcomes. We compared mortality of HCC and non-HCC recipients in different posttransplant time periods (epochs) to separate the impact of these different risk factors on short-term and longer-term posttransplant survival.

Methods: We identified a population-based cohort of first-time liver transplant recipients (aged ≥16 years) between 2008 and 2016 in the United Kingdom. We used Cox regression to estimate hazard ratios (HRs) comparing posttransplant mortality between HCC and non-HCC patients in 3 posttransplant epochs: 0 to 90 days, 90 days to 2 years, and 2 to 5 years, with adjustment first for recipient and later also for donor characteristics.

Results: One thousand two hundred seventy HCC and 3657 non-HCC transplant recipients were included. Five-year posttransplant survival was 74.5% (95% confidence interval [CI] 71.2%-77.5%) in HCC patients and 84.6% (83.0%-86.1%) in non-HCC patients. With adjustment for recipient characteristics only, mortality of HCC patients was lower but not statistically significantly different in the first 90 days (HR, 0.76; 95% CI, 0.53-1.09; P = 0.11), but significantly higher thereafter (90 days to 2 years: HR, 1.99; 95% CI, 1.48-2.66; P < 0.001; 2 to 5 years HR, 1.77; 95% CI, 1.30-2.42; P < 0.001). Further adjustment for donor characteristics had little impact on these results.

Conclusions: HCC recipients have poorer 5-year posttransplant survival than non-HCC recipients, most likely because of tumor recurrence. The more frequent use of poorer-quality donor organs for HCC does not explain this difference.
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http://dx.doi.org/10.1097/TP.0000000000002559DOI Listing
April 2019

Day case 'treat and transfer' ERCP service under general anaesthesia.

Frontline Gastroenterol 2018 Oct 9;9(4):317-322. Epub 2018 Mar 9.

Institute of Liver Studies, King's College Hospital, London, UK.

Objective: General anaesthesia (GA) has been increasingly used for advanced endoscopic procedures in particular endoscopic retrograde cholangiopancreatography (ERCP). Given the increasing pressure on many hospitals, the delivery of such service on a regular basis may not always be possible. We established a new day case 'GA ERCP' service. We describe our experience in evaluating the safety and overall feasibility of this new service.

Design: Prospective database has been interrogated for the period from March 2015 to December 2016. We documented patients' demographics, ERCP indications, American Society of Anesthesiologists (ASA) status, Cotton grade and complications.

Results: 67 patients were referred to endoscopy unit at King's College Hospital (KCH), for urgent day case GA ERCP from nine referring hospitals. The main indications were failed ERCP under sedation 47.8% (32/67), and unavailability of ERCP locally 41.8% (28/67). A total of 64 patients were actually transferred to KCH; 57.8% (37/64) women with a median age 55.8 years (range 23-90). 78.1% (50/64) of patients had a virgin papilla, with 39% (25/64) were ASA ≥3. The Cotton grade was ≥ 3 in 50% (32/64) patients. ERCP was completed successfully in 87.5% (56/64). For patients with previous failed ERCP, repeat ERCP under GA was successful in 75% (24/32). All patients were safely discharged back to their referring hospitals after the short observation period post-ERCP.

Conclusions: Urgent inpatient transfers between hospitals for performing ERCP under GA as a day case is safe and feasible. The new GA ERCP pathway can be replicated by other UK centres.
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http://dx.doi.org/10.1136/flgastro-2017-100880DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6145430PMC
October 2018

Hepatocellular Carcinoma as a Complication of Vascular Disease of the Liver After Fontan Procedure.

Hepatology 2019 02 28;69(2):911-913. Epub 2018 Dec 28.

Institute of Liver Studies, King's College Hospital, London, United Kingdom.

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http://dx.doi.org/10.1002/hep.30194DOI Listing
February 2019

Efficacy and Tolerability of Direct-Acting Antivirals for Hepatitis C in Older Adults.

J Am Geriatr Soc 2018 07 25;66(7):1339-1345. Epub 2018 May 25.

Institute of Liver Studies, King's College Hospital, London, United Kingdom.

Objectives: To evaluate the efficacy and tolerability of direct-acting antiviral (DAA) therapy in individuals aged 65 and older.

Design: Retrospective review between June 2014 and January 2017.

Setting: Viral hepatitis outpatient clinic.

Participants: Individuals aged 65 and older treated with DAA therapy for hepatitis C virus (HCV) during the study period (N=113) divided into 2 cohorts: aged 65 to 74 (n=88) and aged 75 and older (n=25).

Measurements: Drug-drug interactions (DDIs), adverse events (AEs), and rates of sustained virologic response with DAA therapy were assessed.

Results: Sustained virologic response rate was 97.7% in individuals aged 65 to 74 and 95.8% in those aged 75 and older. Individuals aged 75 and older were more likely to be taking more than 2 medications per day for chronic conditions (84% vs 62%, p=.02) and more likely to have clinically significant DDIs necessitating cessation or adjustment of medications before commencement of DAA therapy (80% vs 36%, p=.001). Moreover, individuals aged 75 and older were more likely to experience an AE during therapy (50% vs 26%, p=.03) and were more susceptible to developing anemia secondary to ribavirin (60% vs 20%, p=.02).

Conclusion: DAA therapy is highly efficacious for the treatment of HCV in older adults, but those aged 75 and older are more likely to have clinically significant pretreatment DDIs and experience AEs, including ribavirin-induced anemia, during therapy.
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http://dx.doi.org/10.1111/jgs.15392DOI Listing
July 2018

Entecavir or tenofovir monotherapy prevents HBV recurrence in liver transplant recipients: A 5-year follow-up study after hepatitis B immunoglobulin withdrawal.

Dig Liver Dis 2018 Sep 13;50(9):944-953. Epub 2018 Apr 13.

Institute of Liver Studies, King's College Hospital, London, United Kingdom.

Background: Recent data suggest that oral third-generation nucleos(t)ide analogs (NA) monoprophylaxis following hepatitis B immunoglobulin (HBIg) withdrawal may be effective to prevent HBV reinfection after liver transplantation (LT).

Patients And Methods: Between 01/2010 and 03/2012, all HBV monoinfected and HBV/HDV co-infected LT patients followed in our centre withdrew HBIg ± NA and were commenced on either ETV or TDF as monotherapy.

Results: Seventy-seven patients were included in the study (55% TDF, 45% ETV). Group A comprised 69 HBV monoinfected patients and Group B 8 HBV/HDV co-infected patients. After HBIg withdrawal, Groups A and B patients were followed for 69 (range 13-83) months and 61 (range 31-78) months, respectively. No Group B patients had HBsAg or HBV DNA recurrence, while 6 (9%) Group A patients became HBsAg-positive after a median of 18 (range 1-40) months. The cumulative 5-year incidence of HBsAg recurrence was 9%. All 6 patients demonstrated undetectable HBV-DNA levels and stable graft function during 30 months of additional follow-up. In 3/6 patients, seroconversion was transitory, while the remaining 3 showed HBsAg levels <0.13 IU/mL over the entire period of observation. Pre-LT HCC emerged as the strongest predictor of HBsAg recurrence.

Conclusion: HBIG can be safely discontinued in HBsAgpositive LT recipients and replaced by ETV or TDF monotherapy.
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http://dx.doi.org/10.1016/j.dld.2018.03.032DOI Listing
September 2018

The Burden of Untreated Hepatitis C Virus Infection in Renal Patients in the United Kingdom.

Nephron 2018 5;139(2):170-171. Epub 2018 Apr 5.

Renal Unit, King's College Hospital, London, United Kingdom.

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http://dx.doi.org/10.1159/000488403DOI Listing
October 2019

A retrospective analysis of post-transplant lymphoproliferative disorder following liver transplantation.

Eur J Haematol 2018 Jan 4;100(1):98-103. Epub 2017 Dec 4.

Department of Haematology, King's College Hospital NHS Foundation Trust, London, UK.

Objective: To evaluate response rates and survival in adults developing post-transplant lymphoproliferative disorder (PTLD) following liver transplantation.

Methods: Patients were identified retrospectively and data collected through local liver and haematology electronic databases and pharmacy records.

Results: Forty-five patients were identified. The median age at first transplant and at development of PTLD was 48 and 54 years, respectively, with the median time from transplant to PTLD diagnosis of 56 months. The majority of cases (76%) were monomorphic B-cell lymphomas, and 36% of tumours were EBV positive. Treatment involved reduction in immune-suppression (RIS) in 30 (67%) with RIS the only treatment in 3. Ten (22%) patients were treated with rituximab alone, 13 (29%) with chemotherapy alone and 14 (31%) patients were treated with rituximab and chemotherapy. Twenty-six (58%) patients achieved a complete response (CR). At a median follow-up of 27 months, the median overall survival (OS) was 50 months. Response and OS were not associated with clinical factors or the use of rituximab.

Conclusion: Outcomes reported in this study are favourable and comparable to those reported previously. The addition of rituximab did not appear to have improved outcomes in this series, although a significant proportion of patients were able to avoid chemotherapy.
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http://dx.doi.org/10.1111/ejh.12988DOI Listing
January 2018

Dolutegravir-induced liver injury leading to sub-acute liver failure requiring transplantation: a case report and review of literature.

Int J STD AIDS 2018 03 23;29(4):414-417. Epub 2017 Oct 23.

1 Institute of Liver Studies, King's College Hospital, London, UK.

A patient with human immunodeficiency virus-1 infection presented with sub-acute liver failure, temporally related to commencement of an antiretroviral therapy regimen containing dolutegravir (Triumeq). The patient was not a carrier of HLA-B5701, and abacavir hypersensitivity was unlikely. We believe this is the first report of severe dolutegravir-related hepatotoxicity resulting in sub-acute liver failure and transplantation and highlights a potential need for closer monitoring after drug initiation.
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http://dx.doi.org/10.1177/0956462417734099DOI Listing
March 2018

Developing a donation after cardiac death risk index for adult and pediatric liver transplantation.

World J Transplant 2017 Jun;7(3):203-212

Shirin Elizabeth Khorsandi, Emmanouil Giorgakis, Hector Vilca-Melendez, John O'Grady, Michael Heneghan, Varuna Aluvihare, Abid Suddle, Kosh Agarwal, Krishna Menon, Andreas Prachalias, Parthi Srinivasan, Mohamed Rela, Wayel Jassem, Nigel Heaton, Institute of Liver Studies, King's College Hospital, London SE5 9RS, United Kingdom.

Aim: To identify objective predictive factors for donor after cardiac death (DCD) graft loss and using those factors, develop a donor recipient stratification risk predictive model that could be used to calculate a DCD risk index (DCD-RI) to help in prospective decision making on organ use.

Methods: The model included objective data from a single institute DCD database (2005-2013, = 261). Univariate survival analysis was followed by adjusted Cox-regressional hazard model. Covariates selected univariate regression were added to the model forward selection, significance level = 0.3. The warm ischemic threshold was clinically set at 30 min. Points were given to each predictor in proportion to their hazard ratio. Using this model, the DCD-RI was calculated. The cohort was stratified to predict graft loss risk and respective graft survival calculated.

Results: DCD graft survival predictors were primary indication for transplant ( = 0.066), retransplantation ( = 0.176), MELD > 25 ( = 0.05), cold ischemia > 10 h ( = 0.292) and donor hepatectomy time > 60 min ( = 0.028). According to the calculated DCD-RI score three risk classes could be defined of low (DCD-RI < 1), standard (DCD-RI 2-4) and high risk (DCD-RI > 5) with a 5 years graft survival of 86%, 78% and 34%, respectively.

Conclusion: The DCD-RI score independently predicted graft loss ( < 0.001) and the DCD-RI class predicted graft survival ( < 0.001).
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http://dx.doi.org/10.5500/wjt.v7.i3.203DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5487310PMC
June 2017

Hepatocellular Carcinoma in Perinatally Acquired HIV and HBV Coinfection: A Case Report.

Pediatr Infect Dis J 2017 Dec;36(12):1156-1158

From the *Imperial College London, London, United Kingdom; †King's College Hospital, London, United Kingdom; ‡King's College London, London, United Kingdom; and §Imperial College Healthcare NHS Trust, London, United Kingdom.

This report describes a case of hepatocellular carcinoma in an adolescent with perinatally acquired HIV and hepatitis B virus coinfection, arising despite more than a decade of suppressive antiretroviral therapy for both HIV and hepatitis B virus. This case raises important questions regarding optimal hepatocellular carcinoma screening in this high-risk group and the oncogenic potential of even very well-controlled viral infection.
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http://dx.doi.org/10.1097/INF.0000000000001662DOI Listing
December 2017

Interim assessment of liver damage in patients with sickle cell disease using new non-invasive techniques.

Br J Haematol 2017 02 16;176(4):643-650. Epub 2016 Dec 16.

Faculty of Life Sciences & Medicine, Molecular Haematology, King's College London, London, UK.

We explored transient elastography (TE) and enhanced liver fibrosis (ELF ) score with standard markers of liver function to assess liver damage in 193 well patients with sickle cell disease (SCD). Patients with HbSS or HbSβ thalassaemia (sickle cell anaemia, SCA; N = 134), had significantly higher TE results and ELF scores than those with HbSC (N = 49) disease (TE, 6·8 vs. 5·3, P < 0·0001 and ELF, 9·2 vs. 8·6 P < 0·0001). In SCA patients, TE and ELF correlated significantly with age and all serum liver function tests (LFTs). Additionally, (weak) positive correlation was found with lactate dehydrogenase (TE: r = 0·24, P = 0·004; ELF: r = 0·26 P = 0·002), and (weak) negative correlation with haemoglobin (TE: r = -0·25, P = 0·002; ELF: r = -0·25 P = 0·004). In HbSC patients, correlations were weaker or not significant between TE or ELF, and serum LFTs. All markers of iron loading correlated with TE values when corrected for sickle genotype (serum ferritin, β = 0·25, P < 0·0001, total blood transfusion units, β = 0·25, P < 0·0001 and LIC β = 0·32, P = 0·046). The exploratory study suggests that, while TE could have a role, the utility of ELF score in monitoring liver damage in SCD, needs further longitudinal studies.
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http://dx.doi.org/10.1111/bjh.14462DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5303160PMC
February 2017

Efficacy and safety of sorafenib in patients with advanced hepatocellular carcinoma: age is not a problem.

Eur J Gastroenterol Hepatol 2017 Jan;29(1):48-55

aDepartment of Oncology bInstitute of Liver Studies, King's College Hospital NHS Foundation Trust cDivision of Cancer Studies, King's College London, London, UK.

Objective: Sorafenib is the standard of care for patients with advanced hepatocellular carcinoma (HCC), but data on its use in the elderly are inconclusive.

Methods: All consecutive HCC patients who were treated in our institution with sorafenib since its licensing were included in the analysis. Patients were divided into two groups: (A) up to 75 and (B) older than 75 years old. Our endpoints were overall survival (OS) and time to treatment failure (TTF) because of disease progression or toxicity. Safety parameters and the prognostic effect of HCC characteristics were also investigated.

Results: Data from 190 patients (157 men), median age 66 (26-87) years, were studied (A=151 and B=39). No significant difference in OS and TTF was detected between the two groups [7.1 (5.5-8.7) vs. 10.4 (6.5-14.3) months, P=0.360 and 4.2 (2.3-6.2) vs. 5.6 (3.1-8.1) months, P=0.369, respectively]. Incidence of toxicities at all grades and dose reductions were comparable between groups A and B. In a multivariate setting, patients with Child-Pugh B score at baseline were associated with a higher risk of death (adjusted hazard ratio=2.17, 95% confidence interval:1.24-3.79, P=0.007) and treatment failure (adjusted hazard ratio=4.64, 95% confidence interval: 2.55-8.42, P=0.001) and had shorter OS and TTF compared with patients with a Child-Pugh A (P=0.004 and P<0.001, respectively).

Conclusion: Elderly patients with advanced HCC, when treated with sorafenib, have an equivalent clinical outcome with similar toxicity rates as their younger counterparts. Age alone should not be a discriminating factor for the management of advanced HCC with sorafenib.
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http://dx.doi.org/10.1097/MEG.0000000000000739DOI Listing
January 2017

Lymphoma and hematological conditions: II. Sickle cell hepatopathy and other hematological diseases.

Clin Liver Dis (Hoboken) 2016 Jul 26;8(1):6-9. Epub 2016 Jul 26.

Institute of Liver Studies King's College Hospital London SE5 9RS United Kingdom.

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http://dx.doi.org/10.1002/cld.557DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6490185PMC
July 2016

Lymphoma and hematological conditions: I. Lymphoma and liver complications of bone marrow transplant.

Clin Liver Dis (Hoboken) 2016 Jul 26;8(1):1-5. Epub 2016 Jul 26.

Institute of Liver Studies King's College Hospital London SE5 9RS United Kingdom.

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http://dx.doi.org/10.1002/cld.560DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6490187PMC
July 2016

Early Introduction of Subcutaneous Hepatitis B Immunoglobulin Following Liver Transplantation for Hepatitis B Virus Infection: A Prospective, Multicenter Study.

Transplantation 2016 Jul;100(7):1507-12

1 Hepatobiliary Surgery and Liver Transplantation, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy. 2 Liver Transplantation Center and General Surgery 2U, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, Torino, Italy. 3 Unità Operativa di Chirurgia Generale e dei Trapianti di Fegato e Multiorgano, Bologna, Italy. 4 Centro Trapianti di Fegato e Pancreas, Cagliari, Italy. 5 Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit, University of Modena and Reggio Emilia, Modena, Italy. 6 Chirurgia Epatobiliare e Trapianto Epatico Azienda Ospedaliera Universitaria di Padova-Unità Operativa di Chirurgia, Padova, Italy. 7 Struttura Complessa di Chirurgia Generale e dei Trapianti, Ospedale Niguarda, Milan, Italy. 8 Chirurgia Generale e Trapianto di Fegato, Bari, Italy. 9 Experimental Medicine and Surgery, Fondazione Policlinico Tor Vergata, Rome, Italy. 10 Unidad de Hepatología, Servicio de Medicina Digestiva, Hospital Universitari i Politècnic La Fe, Valencia, Spain. 11 Servicio de Cirugía General, Aparato Digestivo y Trasplante de Organos Abdominales, Hospital Universitario Doce de Octubre, Madrid, Spain. 12 Liver Unit, Hospital Clinic de Barcelona, Barcelona, Spain. 13 Institute of Liver Studies, King's College Hospital, London, United Kingdom. 14 NIHR Liver BRU, QE Hospital and Birmingham University, Birmingham, United Kingdom. 15 AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire, Villejuif, France. 16 University Paris-Sud, UMR-S 1193, Villejuif, France. 17 Biotest AG, Dreieich, Germany.

Background: Subcutaneous administration of hepatitis B immunoglobulin (HBIg) is effective in preventing hepatitis B virus (HBV) recurrence after liver transplantation, but early conversion to subcutaneous administration is undocumented.

Methods: In a prospective study, patients transplanted for terminal liver disease due to HBV infection who were HBV DNA-negative at transplant were switched by week 3 posttransplantation from intravenous to subcutaneous HBIg (500 or 1000 IU weekly or fortnightly, adjusted according to serum anti-HBs trough level) if they were HBsAg- and HBV-DNA negative at time of switch. All patients concomitantly received nucleos(t)ide analogue antiviral therapy. Primary endpoint was failure rate by month 6, defined as serum anti-HBs of 100 IU/L or less or HBV reinfection despite serum anti-HBs greater than 100 IU/L.

Results: Of 49 patients treated, 47 (95.9%) continued treatment until month 6. All patients achieved administration by a caregiver or self-injection by week 14. No treatment failures occurred. Mean anti-HBs declined progressively to month 6, plateauing at a protective titer of approximately 290 IU/L. All patients tested for HBV DNA remained negative (45/45). Only 1 adverse event (mild injection site hematoma) was assessed as treatment-related.

Conclusions: Introduction of subcutaneous HBIg administration by week 3 posttransplantation, combined with HBV virostatic prophylaxis, is effective and convenient for preventing HBV recurrence.
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http://dx.doi.org/10.1097/TP.0000000000001171DOI Listing
July 2016
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