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A SEER Database Analysis of the Survival Advantage of Transarterial Chemoembolization for Hepatocellular Carcinoma: An Underutilized Therapy.

Thu, 08/17/2017 - 18:48
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A SEER Database Analysis of the Survival Advantage of Transarterial Chemoembolization for Hepatocellular Carcinoma: An Underutilized Therapy.

J Vasc Interv Radiol. 2017 Feb;28(2):231-237.e2

Authors: Gray SH, White JA, Li P, Kilgore ML, Redden DT, Abdel Aal AK, Simpson HN, McGuire B, Eckhoff DE, Dubay DA

Abstract
PURPOSE: To measure transarterial chemoembolization utilization and survival benefit among patients with hepatocellular carcinoma (HCC) in the Surveillance, Epidemiology, and End Results (SEER) patient population.
MATERIALS AND METHODS: A retrospective study identified 37,832 patients with HCC diagnosed between 1991 and 2011. Survival was estimated by Kaplan-Meier method and compared by log-rank test. Propensity-score matching was used to address an imbalance of covariates.
RESULTS: More than 75% of patients with HCC did not receive any HCC-directed treatment. Transarterial chemoembolization was the most common initial therapy (15.9%). Factors associated with the use of chemoembolization included younger age, more HCC risk factors, more comorbidities, higher socioeconomic status, intrahepatic tumor, unifocal tumor, vascular invasion, and smaller tumor size (all P < .001). Median survival was improved in patients treated with chemoembolization compared with those not treated with chemoembolization (20.1 vs 4.3 mo; P < .0001). Similar findings were demonstrated in propensity-scoring analysis (14.5 vs 4.2 mo; P < .0001) and immortal time bias sensitivity analysis (9.5 vs 3.6 mo; P < .0001). There was a significantly improved survival hazard ratio (HR) in patients treated with chemoembolization (HR, 0.42; 95% confidence interval, 0.39-0.45).
CONCLUSIONS: Patients with HCC treated with transarterial chemoembolization experienced a significant survival advantage compared with those not treated with transarterial chemoembolization. More than 75% of SEER/Medicare patients diagnosed with HCC received no identifiable oncologic treatment. There is a significant public health need to increase awareness of efficacious HCC treatments such as transarterial chemoembolization.

PMID: 27939085 [PubMed - indexed for MEDLINE]

Adenoviral vector encoding soluble Flt-1 engineered human endometrial mesenchymal stem cells effectively regress endometriotic lesions in NOD/SCID mice.

Thu, 08/17/2017 - 18:48
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Adenoviral vector encoding soluble Flt-1 engineered human endometrial mesenchymal stem cells effectively regress endometriotic lesions in NOD/SCID mice.

Gene Ther. 2016 Jul;23(7):580-91

Authors: Koippallil Gopalakrishnan AR, Pandit H, Metkari SM, Warty N, Madan T

Abstract
This study was undertaken to study the efficiency of Adsflt-1 engineered human eutopic mesenchymal stem cells (MSCs) secreting anti-angiogenic sFlt-1 as a targeted cell-based therapy for endometriosis (EM). Eutopic MSCs were transduced with Adsflt-1/AdV0 viral vectors and were evaluated for expression and secretion of sFlt-1. EM was created in NOD/SCID mice using subcutaneous implantation techniques. Four doses of 10(6) MSC-Adsflt-1/MSC-AdV0 were administered to the model and therapeutic anti-angiogenic ability was analyzed by lesion size measurement, microvessel density, immunohistochemistry and real-time reverse transcriptase-PCR analysis. Approximately 86% of transduced MSCs expressed and secreted sFlt-1. MSC-Adsflt-1-treated animals exhibited significant reduction (52.8±1.8%) in size of endometriotic lesions. We observed a 2.3-fold decrease in the number and a 10-fold decrease in the size of endometrial glands in MSC-Adsflt-1-treated animals. A two-fold decrease in stromal cell densities was also observed in MSC-Adsflt-1-treated animals compared with the MSC-AdV0 group. Specific positive immunostaining for MSC marker, CD146 and sFlt-1 in the lesion sites of the MSC-Adsflt-1 group suggests possible homing of transduced MSCs, their survival and secretion of sFlt-1 at the target sites. A marked reduction in size of microvessels and microvessel density within endometriotic lesions and surrounding host subcutaneous layers was observed in MSC-Adsflt-1 group along with significantly downregulated expression of transcripts for vascular endothelial growth factor, fetal liver kinase 1 and matrix metalloproteinases (2 and 9). Our findings indicate the efficacy of a novel eutopic MSC-Adsflt-1 therapy in EM study models. Evaluating long-term effects of genetically modified MSCs in vivo is essential in translating MSC-Adsflt-1 therapy to the clinics.

PMID: 26990775 [PubMed - indexed for MEDLINE]

Curative Salvage Liver Transplantation in Cirrhotic patients with Hepatocellular Carcinoma: An intention-to-treat analysis.

Tue, 08/15/2017 - 12:45

Curative Salvage Liver Transplantation in Cirrhotic patients with Hepatocellular Carcinoma: An intention-to-treat analysis.

Hepatology. 2017 Aug 14;:

Authors: de Haas RJ, Lim C, Bhangui P, Salloum C, Compagnon P, Feray C, Calderaro J, Luciani A, Azoulay D

Abstract
The salvage liver transplantation (SLT) strategy was conceived for initially resectable and transplantable (R&T) hepatocellular carcinoma (HCC) patients, to try to obviate upfront LT, with the 'safety net' of SLT in case of post-resection recurrence. The SLT strategy is successful or curative when patients are recurrence-free following primary resection alone, or after SLT for recurrence. The aim of the current study was to determine the SLT strategy's potential for cure in R&T HCC patients, and to identify predictors for its success. From 1994-2012, all R&T cirrhotic HCC patients were enrolled in the SLT strategy. An intention-to-treat (ITT) analysis was used to determine this strategy's outcomes and predictors of success according to the above definition. In total, 110 patients were enrolled in the SLT strategy. Sixty-three patients (57%) had tumor recurrence after initial resection, and in 30 patients SLT could be performed (recurrence transplantability rate=48%). From the time of initial resection, ITT 5-year overall and disease-free survival rates were 69% and 60%, respectively. The SLT strategy was successful in 60 patients (56%), either by resection alone (36%), or by SLT for recurrence (19%). Pre-resection predictors of successful SLT strategy at multivariate analysis included model for end-stage liver disease (MELD) score >10, and absence of neoadjuvant transarterial chemoembolization (TACE). Additional post-resection predictive factors were absence of post-resection morbidity, and T-stage 1-2 at the resection specimen.
CONCLUSION: The SLT strategy is curative in only 56% of cases. Higher MELD score at inception of the strategy, and no pre-resection TACE are predictors of successful SLT strategy. This article is protected by copyright. All rights reserved.

PMID: 28806477 [PubMed - as supplied by publisher]

Risk Adjustment in ALPPS Is Associated With a Dramatic Decrease in Early Mortality and Morbidity.

Tue, 08/15/2017 - 12:45

Risk Adjustment in ALPPS Is Associated With a Dramatic Decrease in Early Mortality and Morbidity.

Ann Surg. 2017 Aug 11;:

Authors: Linecker M, Björnsson B, Stavrou GA, Oldhafer KJ, Lurje G, Neumann U, Adam R, Pruvot FR, Topp SA, Li J, Capobianco I, Nadalin S, Machado MA, Voskanyan S, Balci D, Hernandez-Alejandro R, Alvarez FA, De Santibañes E, Robles-Campos R, Malagó M, de Oliveira ML, Lesurtel M, Clavien PA, Petrowsky H

Abstract
OBJECTIVE: To longitudinally assess whether risk adjustment in Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS) occurred over time and is associated with postoperative outcome.
BACKGROUND: ALPPS is a novel 2-stage hepatectomy enabling resection of extensive hepatic tumors. ALPPS has been criticized for its high mortality, which is reported beyond accepted standards in liver surgery. Therefore, adjustments in patient selection and technique have been performed but have not yet been studied over time in relation to outcome.
METHODS: ALPPS centers of the International ALPPS Registry having performed ≥10 cases over a period of ≥3 years were assessed for 90-day mortality and major interstage complications (≥3b) of the longitudinal study period from 2009 to 2015. The predicted prestage 1 and 2 mortality risks were calculated for each patient. In addition, questionnaires were sent to all centers exploring center-specific risk adjustment strategies.
RESULTS: Among 437 patients from 16 centers, a shift in indications toward colorectal liver metastases from 53% to 77% and a reverse trend in biliary tumors from 24% to 9% were observed. Over time, 90-day mortality decreased from initially 17% to 4% in 2015 (P = 0.002). Similarly, major interstage complications decreased from 10% to 3% (P = 0.011). The reduction of 90-day mortality was independently associated with a risk adjustment in patient selection (P < 0.001; OR: 1.62; 95% CI: 1.36-1.93) and using less invasive techniques in stage-1 surgery (P = 0.019; OR: 0.39; 95% CI: 0.18-0.86). A survey indicated risk adjustment of patient selection in all centers and ALPPS technique in the majority (80%) of centers.
CONCLUSIONS: Risk adjustment of patient selection and technique in ALPPS resulted in a continuous drop of early mortality and major postoperative morbidity, which has meanwhile reached standard outcome measures accepted for major liver surgery.

PMID: 28806301 [PubMed - as supplied by publisher]

Nonmotor Manifestations of Wilson's Disease.

Tue, 08/15/2017 - 12:45

Nonmotor Manifestations of Wilson's Disease.

Int Rev Neurobiol. 2017;134:1443-1459

Authors: Biswas S, Paul N, Das SK

Abstract
Wilson disease (WD) is an autosomal genetic disorder characterized by excessive copper deposition initially in liver (hepatic variant) followed by brain (neuropsychiatric variant) and other organs such as cornea and kidney due to defect in biliary copper excretion. Predominant presentations of neuropsychiatric variant are extrapyramidal motor dysfunctions such as dystonias, Parkinsonism, choreoathetosis, tremor, and ataxias. Nonmotor symptoms (NMS) can appear before clinical disease expression and during ongoing disease process. NMS may cause confusion and delay in clinical diagnosis. In the early stage, presence of asymptomatic or symptomatic evidence of acute or chronic liver disease with or without KF ring in young subjects against the background of family history of liver disease may be indicative of underlying WD. In WD, common NMS are personality disorders, mood changes, psychosis, cognitive abnormalities, sleep disorders, and autonomic disturbances besides few systemic dysfunctions. Cognitive changes can be diagnosed by neuropsychological assessment, MRI, and SPECT study of brain. Nonmotor manifestations can be managed by metal chelator, antipsychotic agents, mood stabilizers, rarely electroconvulsive therapy, and occasional hepatic transplantation.

PMID: 28805579 [PubMed - in process]

Incidence and outcomes of primary central nervous system lymphoma in solid organ transplant recipients.

Tue, 08/15/2017 - 12:45

Incidence and outcomes of primary central nervous system lymphoma in solid organ transplant recipients.

Am J Transplant. 2017 Aug 14;:

Authors: Mahale P, Shiels MS, Lynch CF, Engels EA

Abstract
Primary central nervous system lymphoma (PCNSL) risk is greatly increased in immunosuppressed HIV-infected people. Using data from the United States transplant registry linked with 17 cancer registries (1987-2014), we studied PCNSL and systemic non-Hodgkin lymphoma (NHL) in 288,029 solid organ transplant recipients. Transplant recipients had elevated incidence for PCNSL compared with the general population (standardized incidence ratio=65.1; N=168), and this elevation was stronger than for systemic NHL (standardized incidence ratio=11.5; N=2,043). Compared to kidney recipients, PCNSL incidence was lower in liver recipients (adjusted incidence rate ratio [aIRR]=0.52), similar in heart and/or lung recipients, and higher in other/multiple organ recipients (aIRR=2.45). PCNSL incidence was higher in Asians/Pacific Islanders than non-Hispanic whites (aIRR=2.09); after induction immunosuppression with alemtuzumab (aIRR=3.12), monoclonal antibodies (aIRR=1.83), or polyclonal antibodies (aIRR=2.03); in recipients who were Epstein-Barr virus-seronegative at the time of transplant and at risk of primary infection (aIRR=1.95); and within the first 1.5 years after transplant (aIRR>2.00). Compared to other recipients, those with PCNSL had increased risk of death (adjusted hazard ratio [aHR]=11.79) or graft failure/retransplantation (aHR=3.24). Recipients with PCNSL also had higher mortality than those with systemic NHL (aHR=1.48). In conclusion, PCNSL risk is highly elevated among transplant recipients, and it carries a poor prognosis. This article is protected by copyright. All rights reserved.

PMID: 28805292 [PubMed - as supplied by publisher]

Impact of beta-blockers on cardiopulmonary exercise testing in patients with advanced liver disease.

Tue, 08/15/2017 - 12:45

Impact of beta-blockers on cardiopulmonary exercise testing in patients with advanced liver disease.

Aliment Pharmacol Ther. 2017 Aug 14;:

Authors: Wallen MP, Hall A, Dias KA, Ramos JS, Keating SE, Woodward AJ, Skinner TL, Macdonald GA, Arena R, Coombes JS

Abstract
BACKGROUND: Patients with advanced liver disease may develop portal hypertension that can result in variceal haemorrhage. Beta-blockers reduce portal pressure and minimise haemorrhage risk. These medications may attenuate measures of cardiopulmonary performance, such as the ventilatory threshold and peak oxygen uptake measured via cardiopulmonary exercise testing.
AIM: To determine the effect of beta-blockers on cardiopulmonary exercise testing variables in patients with advanced liver disease.
METHODS: This was a cross-sectional analysis of 72 participants who completed a cardiopulmonary exercise test before liver transplantation. All participants remained on their usual beta-blocker dose and timing prior to the test. Variables measured during cardiopulmonary exercise testing included the ventilatory threshold, peak oxygen uptake, heart rate, oxygen pulse, the oxygen uptake efficiency slope and the ventilatory equivalents for carbon dioxide slope.
RESULTS: Participants taking beta-blockers (n = 28) had a lower ventilatory threshold (P <.01) and peak oxygen uptake (P = .02), compared to participants not taking beta-blockers. After adjusting for age, the model of end-stage liver-disease score, liver-disease aetiology, presence of refractory ascites and ventilatory threshold remained significantly lower in the beta-blocker group (P = .04). The oxygen uptake efficiency slope was not impacted by beta-blocker use.
CONCLUSIONS: Ventilatory threshold is reduced in patients with advanced liver disease taking beta-blockers compared to those not taking the medication. This may incorrectly risk stratify patients on beta-blockers and has implications for patient management before and after liver transplantation. The oxygen uptake efficiency slope was not influenced by beta-blockers and may therefore be a better measure of cardiopulmonary performance in this patient population.

PMID: 28805258 [PubMed - as supplied by publisher]

The current therapeutic options for Crohn's disease: from medical therapy to intestinal transplantation.

Tue, 08/15/2017 - 12:45

The current therapeutic options for Crohn's disease: from medical therapy to intestinal transplantation.

Expert Rev Gastroenterol Hepatol. 2017 Aug 14;:

Authors: Lauro A, D'Amico F, Gondolesi G

Abstract
INTRODUCTION: Crohn's disease (CD) has an annual incidence per 100.000 person-year of 20.2 in North America and 12.7 in Europe, and the purpose of this review is to evaluate its medical management, from diagnosis to transplant. Pharmacologic manipulation with nutritional care aims to achieve and maintain remission, but more than half of patients will undergo an intestinal resection, very often repeated over time. They could experience short bowel syndrome (SBS) requiring total parenteral nutrition (TPN). Intestinal transplantation (ITx) represents an alternative in case of irreversible intestinal failure (IF) with life-threatening TPN complications. Patient survival after ITx is 79%, 53% and 43% at 1, 3 and 5 years respectively, with no differences among ITx for other disorders. Areas covered: The research discussed medical therapy with nutritional support, evaluating the role of endoscopy, surgery and transplant in CD. A systematic literature review was conducted using the PubMed search engine up to May 31(th), 2017 without restriction of the language. The decision on paper's eligibility was reached by consensus between the 3 screening authors. Expert commentary: CD treatment is mainly medical, leaving endoscopy and surgery for a complex course. ITx represents a therapeutic option if TPN complications with IF arise.

PMID: 28805088 [PubMed - as supplied by publisher]

Factors associated with cardiovascular target organ damage in children after renal transplantation.

Tue, 08/15/2017 - 12:45
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Factors associated with cardiovascular target organ damage in children after renal transplantation.

Pediatr Nephrol. 2017 Aug 13;:

Authors: Borchert-Mörlins B, Thurn D, Schmidt BMW, Büscher AK, Oh J, Kier T, Bauer E, Baig S, Kanzelmeyer N, Kemper MJ, Büscher R, Melk A

Abstract
BACKGROUND: Cardiovascular disease is the second-most common cause of death in pediatric renal transplant recipients. The aim of this study was to evaluate subclinical cardiovascular target organ damage defined as the presence of arterio- and atherosclerotic lesions and cardiac remodeling and to analyze contributing risk factors in a large cohort of children after renal transplantation (RT).
METHODS: A total of 109 children aged 13.1 ± 3.3 years who had undergone RT at one of three German transplant centers were enrolled in this study. Patients had been transplanted a mean of 5.5 (±4.0) years prior to being enrolled in the study. Anthropometric data, laboratory values and office- and 24-h ambulatory blood pressure monitoring (ABPM) were evaluated. Cardiovascular target organ damage was determined through non-invasive measurements of aortic pulse wave velocity (PWV), carotid intima-media thickness (IMT) and left ventricular mass (LVM).
RESULTS: Elevated PWV or IMT values were detected in 22 and 58% of patients, respectively. Left ventricular hypertrophy was found in as many as 43% of patients. The prevalence of uncontrolled or untreated hypertension was 41%, of which 16% of cases were only detected by ABPM measurements. In the multivariable analysis, higher diastolic blood pressure, everolimus intake and lower estimated glomerular filtration rate were independently associated with high PWV. Higher systolic blood pressure and body mass index were associated with elevated LVM.
CONCLUSIONS: Our results showed an alarming burden of cardiovascular subclinical organ damage in children after RT. Hypertension, obesity, immunosuppressive regimen and renal function emerged as independent risk factors of organ damage. Whereas the latter is not modifiable, the results of our study strongly indicate that the management of children after RT should focus on the control of blood pressure and weight.

PMID: 28804814 [PubMed - as supplied by publisher]

The pattern of IL-24/mda-7 and its cognate receptors expression following activation of human hepatic stellate cells.

Tue, 08/15/2017 - 12:45
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The pattern of IL-24/mda-7 and its cognate receptors expression following activation of human hepatic stellate cells.

Biomed Rep. 2017 Aug;7(2):173-178

Authors: Jamhiri I, Hosseini SY, Mehrabani D, Khodabandeh Z, Yaghobi R, Dowran R, Zahri S

Abstract
Activation of hepatic stellate cells (HSCs) is the pivotal event during liver fibrosis. Interleukin (IL)-24/melanoma differentiation-associated gene-7 (mda-7) has attracted attention in the pathophysiology of some diseases, while its role in activation/suppression of human HSCs is still unclear. It is important to elucidate whether the expression levels of the IL-24/mda-7 protein and its receptors in HSC cells are changed following activation. LX-2 cells, a human hepatic stellate cell line were activated by a combination of leptin and serum starvation. The activation state was evaluated through measuring the mRNA expression of profibrotic molecules, collagen-I, TIMP metalloproteinase inhibitor-1 and transforming growth factor-β. The expression of IL-24/mda-7 was assessed in mRNA and protein levels by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and ELISA methods, respectively. Hence, the amount of IL-22R1 and IL-20R2 subunit expression was also compared in activated and normal LX-2 cells by RT-qPCR. The expression level of IL-24/mda-7 and its cognate receptors was detectable both in the normal and activated LX-2 cell line. Furthermore, in activated LX-2, a significant increase of IL24 expression either on IL-22R1 and IL-20R2 subunits was also noticeable in comparison to normal cells. The activation state of LX-2 cells caused significant changes of IL-24/mda-7 and its receptors expression. In addition, the elevation in IL-24/mda-7 during LX-2 cell activation, suggested that IL-24/mda-7 and its cognate receptors serve a possible role in the development of the fibrosis process. Therefore, IL-24/mda-7 and relevant signaling pathways may be employed as a target for fibrosis treatment.

PMID: 28804632 [PubMed]

Changing landscape of hepatitis C virus-positive donors.

Tue, 08/15/2017 - 12:45
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Changing landscape of hepatitis C virus-positive donors.

World J Hepatol. 2017 Jul 18;9(20):905-906

Authors: Kling CE, Limaye AP, Sibulesky L

Abstract
With the introduction of the new highly effective antiviral therapies, there has been a dramatic increase in the use of the hepatitis C virus (HCV)-positive livers in HCV-positive recipients. In the majority of studies, HCV positivity was defined as a donor testing HCV Ab positive. In 2015, all Organ Procurement Organizations were mandated to perform and report HCV Nucleic Acid Amplification Testing (NAT) results on all deceased and living donors. Studies are not yet available on how organs are being utilized based on NAT status and whether NAT status affects recipient outcomes. Further studies are needed to maximize the use of these organs.

PMID: 28804573 [PubMed]

Bacterial infections post-living-donor liver transplantation in Egyptian hepatitis C virus-cirrhotic patients: A single-center study.

Tue, 08/15/2017 - 12:45
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Bacterial infections post-living-donor liver transplantation in Egyptian hepatitis C virus-cirrhotic patients: A single-center study.

World J Hepatol. 2017 Jul 18;9(20):896-904

Authors: Montasser MF, Abdelkader NA, Abdelhakam SM, Dabbous H, Montasser IF, Massoud YM, Abdelmoaty W, Saleh SA, Bahaa M, Said H, El-Meteini M

Abstract
AIM: To determine risk factors, causative organisms and antimicrobial resistance of bacterial infections following living-donor liver transplantation (LDLT) in cirrhotic patients.
METHODS: This prospective study included 45 patients with hepatitis C virus-related end-stage liver disease who underwent LDLT at Ain Shams Center for Organ Transplant, Cairo, Egypt from January 2014 to November 2015. Patients were followed-up for the first 3 mo after LDLT for detection of bacterial infections. All patients were examined for the possible risk factors suggestive of acquiring infection pre-, intra- and post-operatively. Positive cultures based on clinical suspicion and patterns of antimicrobial resistance were identified.
RESULTS: Thirty-three patients (73.3%) suffered from bacterial infections; 21 of them had a single infection episode, and 12 had repeated infection episodes. Bile was the most common site for both single and repeated episodes of infection (28.6% and 27.8%, respectively). The most common isolated organisms were gram-negative bacteria. Acinetobacter baumannii was the most common organism isolated from both single and repeated infection episodes (19% and 33.3%, respectively), followed by Escherichia coli for repeated infections (11.1%), and Pseudomonas aeruginosa for single infections (19%). Levofloxacin showed high sensitivity against repeated infection episodes (P = 0.03). Klebsiella, Acinetobacter and Pseudomonas were multi-drug resistant (MDR). Pre-transplant hepatocellular carcinoma (HCC) and duration of drain insertion (in days) were independent risk factors for the occurrence of repeated infection episodes (P = 0.024).
CONCLUSION: MDR gram-negative bacterial infections are common post-LDLT. Pre-transplant HCC and duration of drain insertion were independent risk factors for the occurrence of repeated infection episodes.

PMID: 28804572 [PubMed]

Impact of comorbidity on waiting list and post-transplant outcomes in patients undergoing liver retransplantation.

Tue, 08/15/2017 - 12:45
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Impact of comorbidity on waiting list and post-transplant outcomes in patients undergoing liver retransplantation.

World J Hepatol. 2017 Jul 18;9(20):884-895

Authors: Al-Freah MAB, Moran C, Foxton MR, Agarwal K, Wendon JA, Heaton ND, Heneghan MA

Abstract
AIM: To determine the impact of Charlson comorbidity index (CCI) on waiting list (WL) and post liver retransplantation (LRT) survival.
METHODS: Comparative study of all adult patients assessed for primary liver transplant (PLT) (n = 1090) and patients assessed for LRT (n = 150), 2000-2007 at our centre. Demographic, clinical and laboratory variables were recorded.
RESULTS: Median age for all patients was 53 years and 66% were men. Median model for end stage liver disease (MELD) score was 15. Median follow-up was 7-years. For retransplant patients, 84 (56%) had ≥ 1 comorbidity. The most common comorbidity was renal impairment in 66 (44.3%). WL mortality was higher in patients with ≥ 1 comorbidity (76% vs 53%, P = 0.044). CCI (OR = 2.688, 95%CI: 1.222-5.912, P = 0.014) was independently associated with WL mortality. Patients with MELD score ≥ 18 had inferior WL survival (Log-Rank 6.469, P = 0.011). On multivariate analysis, CCI (OR = 2.823, 95%CI: 1.563-5101, P = 0.001), MELD score ≥ 18 (OR 2.506, 95%CI: 1.044-6.018, P = 0.04), and requirement for organ support prior to LRT (P < 0.05) were associated with reduced post-LRT survival. Donor/graft parameters were not associated with survival (P = NS). Post-LRT mortality progressively increased according to the number of transplanted grafts (Log-Rank 18.455, P < 0.001). Post-LRT patient survival at 1-, 3- and 5-years were significantly inferior to those of PLT at 88% vs 73%, P < 0.001, 81% vs 71%, P = 0.018 and 69% vs 55%, P = 0.006, respectively.
CONCLUSION: Comorbidity increases WL and post-LRT mortality. Patients with MELD ≥ 18 have increased WL mortality. Patients with comorbidity or MELD ≥ 18 may benefit from earlier LRT. LRT for ≥ 3 grafts may not represent appropriate use of donated grafts.

PMID: 28804571 [PubMed]

The role of sebelipase alfa in the treatment of lysosomal acid lipase deficiency.

Tue, 08/15/2017 - 12:45
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The role of sebelipase alfa in the treatment of lysosomal acid lipase deficiency.

Therap Adv Gastroenterol. 2017 Jul;10(7):553-562

Authors: Erwin AL

Abstract
Lysosomal acid lipase deficiency (LALD) is a lysosomal storage disorder (LSD) characterized either by infantile onset with fulminant clinical course and very poor prognosis or childhood/adult-onset disease with an attenuated phenotype. The disorder is often misdiagnosed or remains undiagnosed in children and adults due to a rather unspecific clinical presentation with dyslipidemia and steatohepatitis. Until recently, no good treatment options were available for LALD. Despite supportive and symptomatic therapies, death occurred before 1 year of age in patients with infantile-onset disease and patients with childhood/adult-onset LALD suffered from significant complications, such as liver cirrhosis, requiring liver transplantation and early-onset cardiovascular disease. With the recent approval of sebelipase alfa for clinical use in infantile- as well as childhood/adult-onset LALD, a new treatment era for this disorder has begun. Sebelipase alfa is a recombinant human lysosomal acid lipase (LAL), which is administered via the intravenous route. Clinical trials have shown significant improvement of disease parameters such as liver transaminases, hepatomegaly, and dyslipidemia in childhood/adult-onset LALD patients. Treatment of infants with the severe infantile-onset form of the disease has led to improved survival beyond the age of 1 year, and also showed improvement of hepatic and gastrointestinal symptoms, as well as growth. Overall, sebelipase alfa has a favorable safety profile and promises to be a good long-term treatment option for patients with LALD, with significant reduction of disease burden and increased life expectancy.

PMID: 28804516 [PubMed]

Noncirrhotic hepatocellular carcinoma: etiology and occult hepatitis B virus infection in a hepatitis B virus-endemic area.

Tue, 08/15/2017 - 12:45
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Noncirrhotic hepatocellular carcinoma: etiology and occult hepatitis B virus infection in a hepatitis B virus-endemic area.

Therap Adv Gastroenterol. 2017 Jul;10(7):529-536

Authors: Shim CW, Park JW, Kim SH, Kim JS, Kim BH, Kim SH, Hong EK

Abstract
BACKGROUND: Although hepatocellular carcinoma (HCC) usually develops in cirrhotic livers, a minority of cases occur in noncirrhotic livers (NCLs). We investigated etiology, clinicopathological features, and occult hepatitis B virus (HBV) infection (OBI) in patients with NCL HCC in an HBV-endemic area.
METHODS: A total of 710 patients who underwent resection or transplantation for HCC at the National Cancer Center (NCC), Korea, were enrolled. HCC and fibrosis stage were diagnosed pathologically.
RESULTS: A total of 178 patients (25%) did not have cirrhosis (NCL group). The main cause of HCC was HBV infection (77.2%), followed by cryptogenic disease (11.0%). The prevalence of NCL was 19.2%, 32.5%, 50.0%, and 48.7% among patients with HBV, hepatitis C virus (HCV), alcoholic, and cryptogenic disease, respectively (p < 0.05); corresponding nonfibrosis rates were 8.1%, 0%, 19.0%, and 24.3%, respectively. The NCL group was significantly older, with a larger tumor size, smaller tumor number, lower tumor stage, and more frequent non-HBV etiology. Among non-HBV HCC cases, 130 (80.2%) had antibodies against HBV core (HBc) and 55 (38.5%) had OBI. OBI-positive rates of 0%, 31.8%, and 52.6% were detected among HCV, alcoholic, and cryptogenic HCC cases, respectively. OBI did not correlate with advanced fibrosis. The NCL and liver cirrhosis (LC) groups did not differ in median overall survival.
CONCLUSION: Regardless of etiology, a significant number of HCC patients, including half of nonviral cases, did not have LC. Half of cryptogenic HCC cases had OBI. This study promotes an understanding of fibrosis and OBI among patients with HCC in an HBV-endemic area.

PMID: 28804513 [PubMed]

Interferon-free therapy of hepatitis C during wait list and post-transplant risk of hepatocellular carcinoma recurrence.

Tue, 08/15/2017 - 12:45
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Interferon-free therapy of hepatitis C during wait list and post-transplant risk of hepatocellular carcinoma recurrence.

J Hepatol. 2017 Aug 10;:

Authors: Donato MF, Invernizzi F, Rossi G, Iavarone M

PMID: 28803950 [PubMed - as supplied by publisher]

The Vascular Niche Regulates Hematopoietic Stem and Progenitor Cell Lodgment and Expansion via klf6a-ccl25b.

Tue, 08/15/2017 - 12:45
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The Vascular Niche Regulates Hematopoietic Stem and Progenitor Cell Lodgment and Expansion via klf6a-ccl25b.

Dev Cell. 2017 Aug 09;:

Authors: Xue Y, Lv J, Zhang C, Wang L, Ma D, Liu F

Abstract
In mammals, hematopoietic stem and progenitor cells (HSPCs) rapidly expand in the fetal liver (FL), but the underlying mechanism remains unclear. Here, we characterize zebrafish caudal hematopoietic tissue (CHT) and identify an important cellular and molecular mechanism of HSPC expansion. Time-lapse imaging showed that HSPCs localize adjacent to vascular endothelial cells (ECs), and their migration and expansion display caudal vein-specific orientation in the CHT. RNA sequencing and functional analysis identified that an EC-expressed transcription factor, Krüppel-like factor 6a (Klf6a), is essential for the CHT niche. We further demonstrated that Klf6a directly regulates the expression of the chemokine (C-C motif) ligand 25b to modulate HSPC lodgment and proliferation. Ex vivo culture results support the conserved role of Ccl21/Ccr7 signaling in promoting HSPC expansion in mammals. Together, we identify the Klf6a-Ccl25b/Ccr7 axis in controlling the complex HSPC-CHT niche interaction, which may be applicable to in vitro expansion or engraftment of HSPCs after transplantation.

PMID: 28803829 [PubMed - as supplied by publisher]

The Clinical Spectrum of Hepatic Manifestations in Chronic Lymphocytic Leukemia.

Tue, 08/15/2017 - 12:45
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The Clinical Spectrum of Hepatic Manifestations in Chronic Lymphocytic Leukemia.

Clin Lymphoma Myeloma Leuk. 2017 Jul 23;:

Authors: Kreiniz N, Beyar Katz O, Polliack A, Tadmor T

Abstract
Chronic lymphocytic leukemia (CLL) is the most common leukemia in the Western world, characterized by the presence of long-lived circulating leukemic cells in the peripheral blood that may infiltrate all organs, particularly those of the reticulo-endothelial system. Liver enlargement and elevation of liver enzymes related to specific involvement by the underlying disease are well-recognized features in these patients. In CLL, the differential diagnosis of liver disorders is broad and includes liver infiltration by leukemic cells, immunologic manifestations associated with CLL, primary and secondary hepatic malignancies, drug-induced hepatotoxicity, infections, and Richter transformation. The above conditions can cause serious and even fatal complications such as acute liver failure. The aim of this study was to summarize all available published literature on hepatic manifestations encountered in CLL. This review contains sections on liver enlargement because of leukemic infiltration, autoimmune-induced hepatic dysfunction, acute liver failure, drug-induced liver toxicity, and associated malignancies. A high index of clinical suspicion and appropriate diagnostic evaluation, including liver biopsy in special circumstances, are important for both accurate diagnosis and deciding on the most appropriate treatment to prevent the development of fatal complications of acute liver failure.

PMID: 28803824 [PubMed - as supplied by publisher]

A mechanism based approach to management of children with end-stage liver disease.

Tue, 08/15/2017 - 12:45
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A mechanism based approach to management of children with end-stage liver disease.

Expert Rev Gastroenterol Hepatol. 2017 Aug 14;:

Authors: Haafiz AB

Abstract
INTRODUCTION: Due to parallel advances in surgical and acute care disciplines, liver transplantation (LT) has revolutionized the outlook for children with end-stage liver disease (ESLD). Contrary to advances in technical aspects of LT and the peri-operative care, pre-transplant management of ESLD remains quite a formidable challenge. Areas covered: This review provides mechanisms based management strategies to address common complications of ESLD including malnutrition, amended metabolic pathways, gastrointestinal dysfunction, and development of ascites. Clinically relevant discussion of each paradigm is followed by an account of high impact therapeutic interventions which can be used as guides for formulating management plans. A tabulated summary of the suggested interventions is also provided. Indeed, execution of a dynamic plan tailored to the evolution of pathophysiologic derangements can further enhance outcomes of pediatric LT. Expert commentary: LT has evolved as a dependable therapeutic option for a variety of fatal pediatric liver diseases. However, relative organ shortage remains a formidable challenge. Similarly, consumer expectations continue to grow for sustained improvement of graft and patient survival after LT. In this environment, the level of sophistication applied to the management ESLD before LT stands out as a major opportunity with lasting impact on the future of pediatric LT.

PMID: 28803487 [PubMed - as supplied by publisher]

Laparoscopic reversal of mini-gastric bypass to original anatomy for severe postoperative malnutrition.

Tue, 08/15/2017 - 12:45
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Laparoscopic reversal of mini-gastric bypass to original anatomy for severe postoperative malnutrition.

Langenbecks Arch Surg. 2017 Aug 12;:

Authors: Genser L, Soprani A, Tabbara M, Siksik JM, Cady J, Carandina S

Abstract
PURPOSE: Malnutrition after mini-gastric bypass (MGB) is a rare and dreaded complication with few data available regarding its surgical management. We aim to report the feasibility, safety, and results of laparoscopic reversal of MGB to normal anatomy (RMGB) in case of severe and refractory malnutrition syndrome after intensive nutritional support (SRMS).
METHODS: A 10-year retrospective chart review was performed on patients who underwent RMGB (video included) for SRMS following MGB.
RESULTS: Twenty-six of 2934 patients underwent a RMGB at a mean delay of 20.9 ± 13.4 months post-MGB. At presentation, mean body mass index (BMI), excess weight loss (%EWL), and albumin serum level were 22 ± 4.4 kg/m(2), 103.6 ± 22.5%, and 25.5 ± 3.6 gr/L, respectively. Seventeen (63.5%) patients had at least one severe malnutrition related complication including severe edema in 13 (50%), venous ulcers in 2 (7.7%), infectious complications in 7 (27%), deep venous thrombosis in 5 (19.2%), and motor deficit in 5 (19.2%) patients. At surgical exploration, 8 of 12 (66.5%) patients had a biliary limb longer than 200 cm and 9 (34.6%) had bile reflux symptoms. Overall morbidity was 30.8% but lower when resecting the entire previous gastrojejunostomy with creation of a new jejunojejunostomy (8.3 vs 50%, p = 0.03). After a mean follow-up of 8 ± 9.7 months, all patients experienced a complete clinical and biological regression of the SRMS after the RMGB despite a mean 13.9 kg weight regain in 16 (61.5%) patients.
CONCLUSIONS: Post-MGB SRMS and its related comorbidities are rare but dreaded conditions. Although burdened by a significant postoperative morbidity and weight regain, RMGB remains an effective option to consider, when intensive nutritional support fails.

PMID: 28803414 [PubMed - as supplied by publisher]

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