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Surgical Treatment of Colon Cancer of the Splenic Flexure: A Systematic Review and Meta-analysis.

Fri, 08/11/2017 - 12:45
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Surgical Treatment of Colon Cancer of the Splenic Flexure: A Systematic Review and Meta-analysis.

Surg Laparosc Endosc Percutan Tech. 2017 Aug 07;:

Authors: Martínez-Pérez A, Brunetti F, Vitali GC, Abdalla S, Ris F, de'Angelis N

Abstract
This is a systematic review and meta-analysis on the surgical treatments of splenic flexure carcinomas (SFCs). Medline, EMBASE, and Scopus were searched from January 1990 to May 2016. Studies of at least 5 patients comparing extended right colectomy (ERC) versus left colectomy (LC) and/or laparoscopy versus open surgery for SFCs were retrieved and analyzed. Overall, 12 retrospective studies were selected, including 569 patients. ERC was performed in 23.2% of patients, whereas LC in 76.8%. Pooled data suggested that ERC and LC had similar oncologic quality of resection and postoperative outcomes. Laparoscopy was used in 50.6% of patients (conversion rate: 2.5%) and it was associated with significantly shorter time to oral diet, fewer postoperative complications, and shorter hospital stay than open surgery. In conclusion, the optimal extent of SFC surgical resection, that is, ERC or LC remains under debate. However, laparoscopy provides better postoperative outcomes and fewer postoperative complications than open surgery.

PMID: 28796653 [PubMed - as supplied by publisher]

Inflammatory Bowel Disease with Primary Sclerosing Cholangitis: a Danish Population-based Cohort Study 1977-2011.

Fri, 08/11/2017 - 12:45
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Inflammatory Bowel Disease with Primary Sclerosing Cholangitis: a Danish Population-based Cohort Study 1977-2011.

Liver Int. 2017 Aug 10;:

Authors: Sørensen JØ, Nielsen OH, Andersson M, Ainsworth MA, Ytting H, Bélard E, Jess T

Abstract
BACKGROUND AND AIMS: Inflammatory bowel disease (IBD) may be complicated by primary sclerosing cholangitis (PSC). We aimed to assess the characteristics of Danish PSC-IBD patients and to compare their prognosis with IBD patients without PSC.
METHODS: A retrospective nationwide population-based cohort of 257 PSC-IBD patients was assessed through Danish national registries and manual scrutiny of patient files.
RESULTS: For all PSC-IBD patients diagnosed after 1976 (n=222) and 8,231 IBD controls (i.e. without PSC), the cumulative probability of resective surgery, liver transplantation, cancer, and survival from 1977 through 2011 was estimated and compared by log-rank test and Cox-regression. PSC-IBD patients primarily had ulcerative colitis (UC) (72%), were diagnosed in young adulthood (median age at IBD diagnosis, 23 years), and 9% were smokers. Among PSC-UC patients 78% had pancolitis at diagnosis. Among patients with PSC and Crohn's disease (CD) 91% had colonic involvement. The PSC-IBD patients had a significantly higher probability of receiving resective surgery (HR; 2.13, 95% CI: 1.50-3.03); of developing colorectal cancer (CRC) (HR; 21.4, 95% CI: 9.6-47.6), of cholangiocarcinoma (HR; 190, 95% CI: 54.8-660), and of dying (HR; 4.39, 95% CI: 3.22-6.00) as compared to non-PSC IBD controls. The 25-year cumulative risk of liver transplantation was high (53%).
CONCLUSIONS: This unselected population-based study shows that PSC-IBD patients not only have an extensive phenotype of IBD, they are also treated more intensively than other patients with IBD. However, the prognosis remains poor and without any apparent improvement over calendar time. This article is protected by copyright. All rights reserved.

PMID: 28796371 [PubMed - as supplied by publisher]

The Care of the Postliver Transplant Patient.

Fri, 08/11/2017 - 12:45
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The Care of the Postliver Transplant Patient.

J Clin Gastroenterol. 2017 Sep;51(8):683-692

Authors: Russo MW

Abstract
Since 1988 nearly 150,000 liver transplants have been performed in the United States. Over the past 3 decades the indications for liver transplant have changed from end-stage liver disease from alcohol and cholestatic liver diseases to hepatitis C and most recently nonalcoholic fatty liver disease. Liver transplant recipients are living longer with 10-year survival rates exceeding 60%. Gastroenterologists are likely to encounter or consult on postliver transplant recipients as they live longer and seek care closer to home. Complications after liver transplant are related to immunosuppression, malignancy, recurrent disease, and conditions associated with metabolic syndrome. This review will discuss postliver transplant care and complications in liver transplant recipients.

PMID: 28796003 [PubMed - in process]

Extrahepatic and Intrahepatic Malignancies in Patients With HCV Who Achieve an SVR With Directly Acting Antiviral Agents: Should We be Concerned that DAA Therapy Contributed to this Phenomenon?

Fri, 08/11/2017 - 12:45
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Extrahepatic and Intrahepatic Malignancies in Patients With HCV Who Achieve an SVR With Directly Acting Antiviral Agents: Should We be Concerned that DAA Therapy Contributed to this Phenomenon?

J Clin Gastroenterol. 2017 Sep;51(8):657-658

Authors: Gaglio PJ

PMID: 28796002 [PubMed - in process]

Celecoxib-induced Liver Injury: Analysis of Published Case Reports and Cases Reported to the Food and Drug Administration.

Fri, 08/11/2017 - 12:45
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Celecoxib-induced Liver Injury: Analysis of Published Case Reports and Cases Reported to the Food and Drug Administration.

J Clin Gastroenterol. 2017 Aug 08;:

Authors: Mukthinuthalapati PK, Fontana RJ, Vuppalanchi R, Chalasani N, Ghabril M

Abstract
BACKGROUND: Celecoxib is a widely prescribed nonsteroidal anti-inflammatory drug, and has been associated with rare instances of idiosyncratic drug-induced liver injury (DILI). The aim of this study is to describe and analyze the salient features of published cases of celecoxib DILI.
MATERIALS AND METHODS: A literature search using common terms for liver injury cross-referenced with celecoxib was undertaken from the year 2000 through June 2016. Identified cases were analyzed with respect to reported demographic and clinical data with descriptive.
RESULTS: Celecoxib DILI was reported in 18 patients with a median age of 54 years (range, 29 to 84) and 15 (88%) were female. The median daily dose was 200 mg (range, 200 to 533), and median duration and latency were 13 days (1 to 730) and 17 days (2 to 730), respectively. In 15 (83%) cases, DILI occurred after relatively short treatment duration, median of 12 days (1 to 42). Rash and immunoallergic features were noted in these patients, with peripheral or histologic findings of eosinophilia in 6 (40%). In 3 cases, DILI occurred after prolonged exposure (range, 152 to 730 d), none with immunoallergic features. The pattern of liver injury included hepatocellular (6), mixed (5), and cholestatic (4), and was unknown in 3 cases. Clinical outcomes included 2 (11%) requiring liver transplantation, 4 (22%) with chronic liver injury and recovery in 12 (67%) cases.
CONCLUSIONS: Women are overrepresented in published reports of celecoxib DILI. Latency was short (<3 mo) in most patients but some subjects may present with DILI following prolonged celecoxib use. Although rare, celecoxib-DILI can have potentially life threatening consequences.

PMID: 28795997 [PubMed - as supplied by publisher]

Toxic Myocarditis Caused by Acetaminophen in a Multidrug Overdose.

Fri, 08/11/2017 - 12:45
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Toxic Myocarditis Caused by Acetaminophen in a Multidrug Overdose.

Am J Forensic Med Pathol. 2017 Aug 09;:

Authors: Gosselin M, Dazé Y, Mireault P, Crahes M

Abstract
We report the case of an 18-year-old woman with personality disorders who was hospitalized a few hours after suicidal ingestion of acetaminophen, quetiapine, acetylsalicylic acid, and ethanol. Twelve hours after admission, severe liver damage was evident, but the patient was stable and awaiting hepatic transplantation. Electrolytes were successfully controlled. The condition of the liver stabilized. Cardiac biomarkers then deteriorated unexpectedly. Localized ST-segment elevations were noted on electrocardiogram, but angiography ruled out myocardial infarction. A computed tomographic scan ruled out cerebral edema. The patient died of irreversible cardiac arrest 40 hours after admission. Heart failure remained unexplained, and the body underwent forensic autopsy.At autopsy, histologic findings were indicative of acute toxic myocarditis and were concluded to be caused by acetaminophen intoxication. Acetaminophen overdose is common and typically leads to liver failure requiring supportive treatment and emergency liver transplantation. Toxic myocarditis is an extremely rare complication of acetaminophen overdose. It has only been reported 4 times in the literature despite the widespread use and misuse of acetaminophen. Toxic myocarditis remains a possibility in many cases of overdose but can be overlooked in a clinical picture dominated by hepatorenal failure and encephalopathy. Clinicians and forensic pathologists should be aware of this rare potential complication.

PMID: 28795995 [PubMed - as supplied by publisher]

Treatment of Patients With Hepatitis C Virus infection (Genotype 4) With Ledipasvir-Sofosbuvir in the Liver Transplant Setting.

Fri, 08/11/2017 - 12:45
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Treatment of Patients With Hepatitis C Virus infection (Genotype 4) With Ledipasvir-Sofosbuvir in the Liver Transplant Setting.

Transplantation. 2017 Aug 09;:

Authors: Abaalkhail F, Elsiesy H, Elbeshbeshy H, Shawkat M, Yousif S, Ullah W, Alabbad S, Al-Jedai A, Ajlan A, Broering D, Saab S, Al Sebayel M, Al-Hamoudi W

Abstract
BACKGROUND: Hepatitis C virus infection is a major cause of liver cirrhosis and hepatocellular carcinoma and the leading indication for liver transplantation. In the Middle East, genotype 4 HCV infection is the most common genotype. However, limited data exists on the treatment of genotype-4 in the liver transplant setting. We evaluated the safety and efficacy of ledipasvir-sofosbuvir (LDV/SOF) in treating HCV genotype-4 infected patients with cirrhosis or postliver transplantation.
METHODS: This prospective, single-arm, observational study includes cohort of patients with cirrhosis before liver transplantation (Cohort A) and a cohort of postliver transplantation patients (Cohort B). Patients received LDV/SOF (90 mg-400 mg) once daily for 12-24 weeks with or without ribavirin (RBV). Patients with creatinine clearance below 30 were excluded.
RESULTS: A total of 111 patients (61 cirrhotic; 50 postliver transplants) with HCV genotype 4 were treated in KFSH&RC; 55% cohort A and 44% cohort B received ribavirin. Sustained virological response SVR12 was 91.8% and 86% of cohorts A and B, respectively. There were no treatment-related mortality or serious adverse effects. RBV dose reduction occurred in 25% without any treatment discontinuation. SVR12 rates in cohort A were significantly higher in patients with a viral load below 800 000 (100% vs 83.9%, p value=0.022). Viral load did not impact SVR rates in cohort B. The use of RBV did not increase SVR12 and was associated with anemia.
CONCLUSIONS: Ledipasvir-sofosbuvir without ribavirin is an effective and safe treatment option for patients with HCV genotype 4 infection in pre and postliver transplant setting.

PMID: 28795982 [PubMed - as supplied by publisher]

Summary of the British Transplantation Society UK Guidelines for Hepatitis E and Solid Organ Transplantation.

Fri, 08/11/2017 - 12:45
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Summary of the British Transplantation Society UK Guidelines for Hepatitis E and Solid Organ Transplantation.

Transplantation. 2017 Aug 09;:

Authors: McPherson S, Elsharkawy AM, Ankcorn M, Ijaz S, Powell J, Rowe I, Tedder R, Andrews PA

Abstract
The incidence and prevalence of hepatitis E virus (HEV) infection has increased in many developed countries over the last decade, predominantly due to infection with genotype 3 (G3) HEV. Infection with HEV G3 is important in transplant recipients because it can persist in immunosuppressed individuals, leading if untreated to the development of chronic hepatitis and significant liver fibrosis. The British Transplantation Society (BTS) has developed Guidelines for "Hepatitis E & Solid Organ Transplantation" to inform clinical teams and patients about hepatitis E, to help increase the recognition of persistent hepatitis E infection, and to provide clear guidance on its management. This guideline was published on the BTS website in June 2017 and aims to review the evidence relating to the diagnosis and management of persistent hepatitis E in solid organ transplant recipients, and the methods of prevention of HEV infection. In line with previous guidelines published by the BTS, the guideline has used the GRADE system to rate the strength of evidence and recommendations. This article includes a summary overview of hepatitis E and transplantation with key references, and the statements of recommendation contained within the guideline. It is recommended that the full guideline document is consulted for complete details of the relevant references and evidence base. This may be accessed at https://bts.org.uk/guidelines-standards/.

PMID: 28795981 [PubMed - as supplied by publisher]

The Coagulation Profile of End-Stage Liver Disease and Considerations for Intraoperative Management.

Fri, 08/11/2017 - 12:45
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The Coagulation Profile of End-Stage Liver Disease and Considerations for Intraoperative Management.

Anesth Analg. 2017 Aug 08;:

Authors: Forkin KT, Colquhoun DA, Nemergut EC, Huffmyer JL

Abstract
The coagulopathy of end-stage liver disease results from a complex derangement in both anticoagulant and procoagulant processes. With even minor insults, cirrhotic patients experience either inappropriate bleeding or clotting, or even both simultaneously. The various phases of liver transplantation along with fluid and blood product administration may contribute to additional disturbances in coagulation. Thus, anesthetic management of patients undergoing liver transplantation to improve hemostasis and avoid inappropriate thrombosis in the perioperative environment can be challenging. To add to this challenge, traditional laboratory tests of coagulation are difficult to interpret in patients with end-stage liver disease. Viscoelastic coagulation tests such as thromboelastography (Haemonetics Corporation, Braintree, MA) and rotational thromboelastometry (TEM International, Munich, Germany) have helped to reduce transfusion of allogeneic blood products, especially fresh frozen plasma, but have also lead to the increased use of fibrinogen-containing products. In general, advancements in surgical techniques and anesthetic management have led to significant reduction in blood transfusion requirements during liver transplantation. Targeted transfusion protocols and pharmacologic prevention of fibrinolysis may further aid in the management of the complex coagulopathy of end-stage liver disease.

PMID: 28795966 [PubMed - as supplied by publisher]

Contribution of hepatobiliary scintigraphy in assessing ALPPS most suited timing.

Fri, 08/11/2017 - 12:45
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Contribution of hepatobiliary scintigraphy in assessing ALPPS most suited timing.

Updates Surg. 2017 Aug 09;:

Authors: Truant S, Baillet C, Deshorgue AC, El Amrani M, Huglo D, Pruvot FR

Abstract
To reduce post-hepatectomy liver failure (PHLF), associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) has been recently developed for patients with a limited future remnant liver (FRL). Nevertheless, high morbi-mortality rates have been reported . The current study aimed to analyze the kinetics of FRL function in patients who were offered ALPPS. Serial SPECT (99 m)Tc-mebrofenin hepatobiliary scintigraphy (HBS) was performed in all patients before and after surgery as well as at inter-stage to quantitatively assess hepatic function [total liver (TL) and FRL]. Patients were offered ALPPS for colorectal liver metastases (CLMs) (n = 6) and gallbladder carcinoma (n = 1). The data of delta of function or volume, expressed as (postoperative FRL - preoperative FRL/preoperative FRL) were compared to those derived from HBS of patients referred to the university hospital of Lille for one-stage major hepatectomy (n = 93). Additionally, the intrinsic liver function (i.e. function per unit of volume) was used to assess the regeneration rate. All but one patient had an anticipated FRL to body weight ratio (FRLBWR) ≤0.5%. Inter-stages HBS showed a progressive attenuation of the functional value of the excluded hepatic segments in favour of the FRL for all patients. Overall, there was a drop of total liver function contrasting with subnormal passive biochemical tests. Notably, the increase in FRL function between ALPPS stages [+12.5% (4.2-28.6%)] was lower than the volumetric gain [+42.6% (18.3-110.2%)] and inferior to that observed after one-stage major hepatectomy [+41.7% (-38.6 to +158.33%)]. This resulted in a drop of the FRL intrinsic liver function in ALPPS patients, of whom one died from PHLF. Our study enhances the importance of assessing liver function along with volume during ALPPS procedure and supports HBS as a suitable and reliable method, including a valuable contribution to determine most appropriate stage 2 surgical timing.

PMID: 28795384 [PubMed - as supplied by publisher]

The Effects of Tacrolimus on T-Cell Proliferation Are Short-Lived: A Pilot Analysis of Immune Function Testing.

Fri, 08/11/2017 - 12:45
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The Effects of Tacrolimus on T-Cell Proliferation Are Short-Lived: A Pilot Analysis of Immune Function Testing.

Transplant Direct. 2017 Aug;3(8):e199

Authors: Laskin BL, Jiao J, Baluarte HJ, Amaral S, Furth SL, Akimova T, Hancock WW, Levine MH, Reese PP, Beier UH

Abstract
BACKGROUND: Optimal immunosuppression after organ transplant should balance the risks of rejection, infection, and malignancy while minimizing barriers to adherence including frequent or time-sensitive dosing. There is currently no reliable immune function assay to directly measure the degree of immunosuppression after transplantation.
METHODS: We developed an immune function assay to mea//sure T-cell proliferation after exposure to immunosuppression in vivo. We tested the assay in mice, and then piloted the approach using single time point samples, 11 pediatric kidney transplant recipients prescribed tacrolimus, mycophenolate, and prednisone 6 months to 5 years posttransplant, with no history of rejection, opportunistic infection, or cancer. Twelve healthy adults were controls.
RESULTS: We demonstrated that our assay can quantify suppression of murine T-cell proliferation after tacrolimus treatment in vivo. In humans, we found a mean 25% reduction in CD4 and CD8 T-cell proliferation in pediatric renal transplant recipients on triple immunosuppression compared with adult healthy controls, but the pilot results were not statistically significant nor correlated with serum tacrolimus levels. We observed that cell processing and washing reduced the effects of tacrolimus on T-cell proliferation, as did discontinuation of tacrolimus treatment shortly before sampling.
CONCLUSIONS: T-cell proliferation is currently not suitable to measure immunosuppression because sample processing diminishes observable effects. Future immune function testing should focus on fresh samples with minimal washing steps. Our results also emphasize the importance of adherence to immunosuppressive treatment, because T-cell proliferation recovered substantially after even brief discontinuation of tacrolimus.

PMID: 28795150 [PubMed]

Impact of the Trough Level of Calcineurin Inhibitor on the Prevalence of Donor-Specific Human Leukocyte Antigen Antibodies During Long-Term Follow-Up After Pediatric Liver Transplantation: Antibody Strength and Complement-Binding Ability.

Fri, 08/11/2017 - 12:45
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Impact of the Trough Level of Calcineurin Inhibitor on the Prevalence of Donor-Specific Human Leukocyte Antigen Antibodies During Long-Term Follow-Up After Pediatric Liver Transplantation: Antibody Strength and Complement-Binding Ability.

Transplant Direct. 2017 Aug;3(8):e196

Authors: Tokodai K, Miyagi S, Nakanishi C, Hara Y, Nakanishi W, Goto M, Unno M, Kamei T

Abstract
BACKGROUND: In pediatric patients, long-term immunosuppression after liver transplantation (LT) is typically minimal. However, posttransplant donor-specific HLA antibodies (DSAs) may be prevalent under these conditions. Here, we evaluated the effects of minimized calcineurin inhibitor (CNI) on DSA development to assess the validity of minimized/withdrawn immunosuppression.
METHODS: We retrospectively examined 66 patients who underwent pediatric LT at our institution between July 1991 and October 2013. Patients were divided into 2 groups based on the CNI trough level. The cutoff trough levels were 3 and 30 ng/mL for tacrolimus and cyclosporine, respectively. Luminex single-antigen bead assays were performed, and the cutoff for a positive reaction was set at a mean fluorescence intensity (MFI) of at least 1000.
RESULTS: The mean recipient ages at the time of LT were 29.1 and 77.2 months for the low and regular CNI groups, respectively (P = 0.0007). Univariate logistic regression analysis revealed that recipient age at LT younger than 3 years (P = 0.0099) and low CNI (P < 0.0001) were significantly associated with DSA development. In multivariate analysis, low CNI was an independent risk factor of DSA development (P = 0.0011). Of 15 high-MFI DSAs, 3 were anti-DR, and 12 were anti-DQ. Two of 3 anti-DR DSAs and 11 of 12 anti-DQ DSAs had complement-binding ability and high MFIs.
CONCLUSIONS: CNI minimization was an independent risk factor for posttransplant DSA during long-term follow-up after pediatric LT. Adjusting CNI to appropriate levels is a safe first step to prevent the immunological effects of DSA.

PMID: 28795147 [PubMed]

Renal Outcomes in Patients With IgA Nephropathy Undergoing Liver Transplant: A Retrospective Cohort Study.

Fri, 08/11/2017 - 12:45
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Renal Outcomes in Patients With IgA Nephropathy Undergoing Liver Transplant: A Retrospective Cohort Study.

Transplant Direct. 2017 Aug;3(8):e193

Authors: Hommos MS, El-Zoghby ZM

Abstract
BACKGROUND: End-stage liver disease (ESLD) is the most common cause of secondary immunoglobulin A nephropathy (IgAN). Multiple mechanisms have been proposed to explain the association between liver disease and IgAN. Although some mechanisms are expected to reverse in patients after liver transplant, the long-term renal prognosis is unclear for these patients.
METHODS: This observational retrospective cohort study examined the renal outcomes of 14 patients who had IgAN with end-stage liver disease and subsequently underwent either liver transplant alone or combined liver and kidney transplant at a single tertiary care center.
RESULTS: Of the 7 patients who underwent liver transplant alone, hematuria persisted in 2, 4 had progressive loss of kidney function with worsening proteinuria in 3 but only 1 reached end-stage renal disease 5 years posttransplant. Among 7 combined liver and kidney transplant recipients, 1 had histologic and 1 had histologic and clinical recurrence of IgAN without kidney allograft loss.
CONCLUSIONS: IgAN in patients with advanced liver disease does not necessarily resolve after liver transplant but has overall favorable renal outcomes.

PMID: 28795144 [PubMed]

Resting and Exercise Energy Metabolism After Liver Transplantation for Nonalcoholic Steatohepatitis.

Fri, 08/11/2017 - 12:45
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Resting and Exercise Energy Metabolism After Liver Transplantation for Nonalcoholic Steatohepatitis.

Transplant Direct. 2017 Aug;3(8):e188

Authors: Levitsky J, Singhvi A, Sadowsky HS, Cohen A, Demzik A, VanWagner L, Rinella M

Abstract
BACKGROUND: Nonalcoholic steatohepatitis (NASH) is a leading indication for liver transplantation (LT). We hypothesized that weight gain after LT may be exacerbated by reduced metabolic rates due to the LT procedure, particularly during exercise. We aimed to compare resting and exercise energy expenditure between patients transplanted for NASH and nontransplant nonalcoholic fatty liver disease (NAFLD) subjects.
METHODS: NASH LT recipients (>1-year post, n = 14) and NAFLD controls (n = 13) underwent analysis of body composition, resting energy expenditure (REE), and exercise energy expenditure (VO2max), the latter using a ramped-Bruce protocol assessed by expired gas analysis and peak heart rate.
RESULTS: Participants were mean 61.5 ± 7.9 years, 48.1% men, and 66.7% white. Baseline comorbidities were similar between groups. Among men, mean REE adjusted for total (17.7 vs 18.8, P = 0.87) and lean body mass (23.5 vs 26.9, P = 0.26), as well as VO2 (20.1 vs 23.9, P = 0.29), was lower in NASH LT recipients compared with NAFLD controls, respectively, although not statistically significant. However, female NASH LT recipients had significantly lower mean REE than NAFLD controls when adjusted for total (14.2 vs 18.9, P = 0.01) and lean body mass (19.3 vs 26.5, P = 0.002), as well as significantly lower VO2max (14.4 vs 20.6, P = 0.017).
CONCLUSIONS: NASH LT recipients, particularly women, have lower REE and exercise energy expenditure compared with nontransplant NAFLD patients. More aggressive diet and exercise programs for post-LT NASH recipients to account for reduced resting and exercise metabolic rates may attenuate weight gain in this vulnerable population.

PMID: 28795140 [PubMed]

Elevated Preoperative Serum Bilirubin Improves Reperfusion Injury and Survival Postliver Transplantation.

Fri, 08/11/2017 - 12:45
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Elevated Preoperative Serum Bilirubin Improves Reperfusion Injury and Survival Postliver Transplantation.

Transplant Direct. 2017 Aug;3(8):e187

Authors: Spetzler V, Goldaracena N, Kaths JM, Marquez M, Selzner M, Selzner N

Abstract
BACKGROUND: The cytoprotective effects of hemeoxygenase-1 and its product biliverdin/bilirubin are widely acknowledged in experimental transplant medicine. However, its potentially beneficial effect during organ reperfusion is not established.
METHODS: In a matched study, we compared markers of reperfusion injury (alanine aminotransferase/aspartate aminotransferase) and transplantation outcome (complication rates, liver function, and survival) between recipient groups with "normal" versus "increased" preoperative bilirubin values. Groups were matched for donor and recipient age, liver disease, year of transplantation, and recipient's preoperative condition (modified model for end-stage liver disease score excluding bilirubin).
RESULTS: The postoperative transaminase peak was significantly higher when comparing the "normal" to the "increased" bilirubin group (maximum aspartate aminotransferase "normal" 2013 [325-13 210] U/L vs "increased" 1360 [221-15 460] U/L, P = 0.006; maximum alanine aminotransferase "normal" 1151 [82-6595] U/L vs "increased" 820 [66-5382] U/L, P = 0.01). Grafts in the "increased" bilirubin group had faster recovery of graft function with faster decrease in international normalized ratio at days 3 and 7 posttransplantation in the "increased" vs "normal" bilirubin group. Although long-term functional parameters (international normalized ratio and bilirubin posttransplantation) as well as surgical and biliary complication rates were similar in both groups, 1-year survival rates were significantly higher in the group with increased preoperative bilirubin (graft survival, "normal" 86% vs "increased" 97%; P = 0.006).
CONCLUSIONS: Increased bilirubin levels of liver graft recipients before transplantation are associated with reduced reperfusion injury and improved survival after transplantation.

PMID: 28795139 [PubMed]

Retransplantation in Late Hepatic Artery Thrombosis: Graft Access and Transplant Outcome.

Fri, 08/11/2017 - 12:45
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Retransplantation in Late Hepatic Artery Thrombosis: Graft Access and Transplant Outcome.

Transplant Direct. 2017 Aug;3(8):e186

Authors: Buchholz BM, Khan S, David MD, Gunson BK, Isaac JR, Roberts KJ, Muiesan P, Mirza DF, Tripathi D, Perera MTPR

Abstract
BACKGROUND: Definitive treatment for late hepatic artery thrombosis (L-HAT) is retransplantation (re-LT); however, the L-HAT-associated disease burden is poorly represented in allocation models.
METHODS: Graft access and transplant outcome of the re-LT experience between 2005 and 2016 was reviewed with specific focus on the L-HAT cohort in this single-center retrospective study.
RESULTS: Ninety-nine (5.7%) of 1725 liver transplantations were re-LT with HAT as the main indication (n = 43; 43%) distributed into early (n = 25) and late (n = 18) episodes. Model for end-stage liver disease as well as United Kingdom model for end-stage liver disease did not accurately reflect high disease burden of graft failure associated infections such as hepatic abscesses and biliary sepsis in L-HAT. Hence, re-LT candidates with L-HAT received low prioritization and waited longest until the allocation of an acceptable graft (median, 103 days; interquartile range, 28-291 days), allowing for progression of biliary sepsis. Balance of risk score and 3-month mortality score prognosticated good transplant outcome in L-HAT but, contrary to the prediction, the factual 1-year patient survival after re-LT was significantly inferior in L-HAT compared to early HAT, early non-HAT and late non-HAT (65% vs 82%, 92% and 95%) which was mainly caused by sepsis and multiorgan failure driving 3-month mortality (28% vs 11%, 16% and 0%). Access to a second graft after a median waitlist time of 6 weeks achieved the best short- and long-term outcome in re-LT for L-HAT (3-month mortality, 13%; 1-year survival, 77%).
CONCLUSIONS: Inequity in graft access and peritransplant sepsis are fundamental obstacles for successful re-LT in L-HAT. Offering a graft for those in need at the best window of opportunity could facilitate earlier engrafting with improved outcomes.

PMID: 28795138 [PubMed]

A case series on simultaneous liver and kidney transplantation: do we need intraoperative renal replacement therapy?

Fri, 08/11/2017 - 12:45
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A case series on simultaneous liver and kidney transplantation: do we need intraoperative renal replacement therapy?

Korean J Anesthesiol. 2017 Aug;70(4):467-476

Authors: Wi W, Hahm TS, Kim GS

Abstract
Since the implementation of the model for end-stage liver disease (MELD) scoring system in 2002, the liver transplantation (LT) society has observed a substantial increase in the number of recipients with renal dysfunction. Intraoperative renal replacement therapy (ioRRT) has emerged as one of the solutions available to manage high-MELD score recipients; however, its usefulness has not yet been proven. To date, we have experienced five cases of simultaneous liver and kidney transplantation (SLKT). Recipients of SLKT tend to have a lower pre-transplant kidney function and the longer operation time mandates a larger amount of fluid than LT alone. Hence, anesthetic care is more prone to be challenged by hyperkalemia, metabolic acidosis, and volume overload, making ioRRT a theoretically valuable intervention. However, in all five cases, recipients were managed without ioRRT, resulting in excellent graft and patient survival. As such, in this case series, we discuss current issues about ioRRT and SLKT.

PMID: 28794844 [PubMed]

Genetic variation at the CD28 locus and its impact on expansion of pro-inflammatory CD28 negative T cells in healthy individuals.

Fri, 08/11/2017 - 12:45
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Genetic variation at the CD28 locus and its impact on expansion of pro-inflammatory CD28 negative T cells in healthy individuals.

Sci Rep. 2017 Aug 09;7(1):7652

Authors: Liaskou E, Jeffery L, Chanouzas D, Soskic B, Seldin MF, Harper L, Sansom D, Hirschfield GM

Abstract
The CD28 locus is associated with susceptibility to a variety of autoimmune and immune-mediated inflammatory diseases including primary sclerosing cholangitis (PSC). Previously, we linked the CD28 pathway in PSC disease pathology and found that vitamin D could maintain CD28 expression. Here, we assessed whether the PSC-associated CD28 risk variant A (rs7426056) affects CD28 expression and T cell function in healthy individuals (n = 14 AA, n = 14 AG, n = 14 GG). Homozygotes for the PSC disease risk allele (AA) showed significantly lower CD28 mRNA expression ex-vivo than either GG or AG (p < 0.001) in total peripheral blood mononuclear cells. However, the CD28 risk variant alone was not sufficient to explain CD28 protein loss on CD4(+) T cells. All genotypes responded equally to vitamin D as indicated by induction of a regulatory phenotype and an increased anti-inflammatory/pro-inflammatory cytokine ratio. A genotypic effect on response to TNFα stimuli was detected, which was inhibited by vitamin D. Together our results show: (a) an altered gene expression in carriers of the susceptible CD28 variant, (b) no differences in protein levels on CD4(+) T cells, and

PMID: 28794437 [PubMed - in process]

Unexplained abnormal liver function in patients with primary antibody deficiency: could it be chronic hepatitis E infection?

Fri, 08/11/2017 - 12:45
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Unexplained abnormal liver function in patients with primary antibody deficiency: could it be chronic hepatitis E infection?

J Clin Pathol. 2017 Aug 09;:

Authors: Mohamed OE, Jones J, Osman H, Huissoon AP

Abstract
Data from recent studies suggest rising incidence rate of hepatitis E virus (HEV) infection in the UK. HEV infection may take a severe and persistent course in immunocompromised patients, including transplant recipients on immunosuppressives, patients with HIV, haematological malignancies and in idiopathic CD4(+) T lymphocytopenia. The prevalence of HEV in primary antibody deficiency (PAD) disorders is still unknown. The aim of this study was to investigate HEV infection in 27 patients with PAD with unexplained, persistently elevated liver enzymes. Although all the 27 patients tested negative for HEV-RNA, we would still strongly recommend that HEV should be considered in any immunodeficient patient with impaired liver function.

PMID: 28794125 [PubMed - as supplied by publisher]

A distinct role for Lgr5(+) stem cells in primary and metastatic colon cancer.

Fri, 08/11/2017 - 12:45
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A distinct role for Lgr5(+) stem cells in primary and metastatic colon cancer.

Nature. 2017 03 29;543(7647):676-680

Authors: de Sousa e Melo F, Kurtova AV, Harnoss JM, Kljavin N, Hoeck JD, Hung J, Anderson JE, Storm EE, Modrusan Z, Koeppen H, Dijkgraaf GJ, Piskol R, de Sauvage FJ

Abstract
Cancer stem cells (CSCs) have been hypothesized to represent the driving force behind tumour progression and metastasis, making them attractive cancer targets. However, conclusive experimental evidence for their functional relevance is still lacking for most malignancies. Here we show that the leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5) identifies intestinal CSCs in mouse tumours engineered to recapitulate the clinical progression of human colorectal cancer. We demonstrate that selective Lgr5(+) cell ablation restricts primary tumour growth, but does not result in tumour regression. Instead, tumours are maintained by proliferative Lgr5(-) cells that continuously attempt to replenish the Lgr5(+) CSC pool, leading to rapid re-initiation of tumour growth upon treatment cessation. Notably, CSCs are critical for the formation and maintenance of liver metastasis derived from colorectal cancers. Together, our data highlight distinct CSC dependencies for primary versus metastasic tumour growth, and suggest that targeting CSCs may represent a therapeutic opportunity for managing metastatic disease.

PMID: 28358093 [PubMed - indexed for MEDLINE]

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