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SMC1A recruits tumor-associated-fibroblasts (TAFs) and promotes colorectal cancer metastasis.

Wed, 08/09/2017 - 12:45
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SMC1A recruits tumor-associated-fibroblasts (TAFs) and promotes colorectal cancer metastasis.

Cancer Lett. 2017 Jan 28;385:39-45

Authors: Zhou P, Xiao N, Wang J, Wang Z, Zheng S, Shan S, Wang J, Du J, Wang J

Abstract
Tumor-associated-fibroblasts (TAFs) are the most important host cells in the stroma and take part in extracellular matrix construction and cancer colony development. During cancer colonization, seed cells from primary tumor can reconstruct the microenvironment by recruiting circulating cancer cells and TAFs to the metastasis site. Previous studies have established that SMC1A, a subunit of cohesin, is an important trigger signal for liver metastasis in colorectal cancer. We investigated the particular effects as well as the underlying mechanism of SMC1A on TAFs recruitment during liver metastasis of colorectal cancer. Here, We found that: first, the high expression of SMC1A in colorectal cancer cells promotes the invasiveness and the viability of these cells by recruiting circulating TAFs, facilitating early tumor construction and tumorigenesis; second, different expression levels of SMC1A influenced the reformation of fibroblasts, which assisted tumorigenesis, and third, expression of SMC1A stimulated the secretion of the inflammatory mediators of TNF-α and IL-1β, and up-regulated the transcriptional expression of MMP2 and VEGF-β, both of which were involved in the tumor-related gene pathway.

PMID: 27826041 [PubMed - indexed for MEDLINE]

Sclerosing peritonitis post liver transplantation: a rare condition where surgery is an important treatment option.

Tue, 08/08/2017 - 15:46
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Sclerosing peritonitis post liver transplantation: a rare condition where surgery is an important treatment option.

ANZ J Surg. 2017 Aug 07;:

Authors: Kong YX, Strasser SI, McCaughan GW, Crawford M, Verran DJ

Abstract
BACKGROUND: Sclerosing peritonitis (SP) is a rare but potentially fatal complication following orthotopic liver transplantation (OLT). The definitive surgical management is via a laparotomy peritonectomy and enterolysis procedure, but this carries risks particularly in the immunosuppressed transplant patient population. The natural history of SP is known from a handful of case reports and series, which mostly report de novo cases arising early on following OLT. The aim of this study was to identify all cases of de novo SP following OLT and the outcomes of management.
METHODS: Cases of SP post OLT were identified from the Australian National Liver Transplantation Unit (New South Wales) database of all 1393 adult patients.
RESULTS: Three cases of SP were diagnosed between 2 and over 9 years post-transplantation. Two patients proceeded to laparotomy and a peritonectomy and enterolysis procedure of the cocooned bowel. The third was managed conservatively due to a relatively indolent course and their medical co-morbidities.
CONCLUSION: SP should be considered in the differential diagnosis in patients post OLT presenting with symptoms of bowel obstruction, even years following transplantation. Surgery may be required in order to achieve a satisfactory outcome in some cases.

PMID: 28782907 [PubMed - as supplied by publisher]

Deleterious impact of C3d-binding donor-specific anti-HLA antibodies after pediatric liver transplantation.

Tue, 08/08/2017 - 15:46
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Deleterious impact of C3d-binding donor-specific anti-HLA antibodies after pediatric liver transplantation.

Transpl Immunol. 2017 Aug 03;:

Authors: Couchonnal E, Rivet C, Ducreux S, Dumortier J, Bosch A, Boillot O, Collardeau-Frachon S, Dubois R, Hervieu V, André P, Scoazec JY, Lachaux A, Dubois V, Guillaud O

Abstract
BACKGROUND: The prevalence and clinical impact of anti-HLA donor-specific antibodies (DSA) after liver transplantation (LT) have not been extensively studied, especially in pediatric population.
METHODS: The present cross-sectional study included 100 patients who underwent a first LT in childhood. Anti HLA immunization study was performed at a single time point during routine follow-up using Luminex® single antigen tests with classical anti-IgG conjugate and anti-C3d conjugate.
RESULTS: The main indication for LT was biliary atresia (52%) and median age at LT was 4.6years. The median time between LT and DSA assessment was 7.8years (range 1-21years). DSA was identified in twenty-four patients (24%) after LT, with a prevalence of 8%, 28%, 33%, 50%, respectively 0-5years, 5-10years, 10-15years and >15years after LT. DSA were mainly class II (23/24) with a mean MFI of 9.731±5.489 and 18 (79.3%) were C3d-binding DSA. Multivariate analysis disclosed that time elapsed since LT (p<0.01) and history of fulminant hepatitis (p=0.04) were significantly associated with a higher rate of DSA. Liver function tests (at time of DSA assessment) were not different according to the presence or not of DSA (or C3d-binding DSA). Regarding histology, the DSA group had a higher rate of chronic rejection, cirrhosis and centrilobular fibrosis or cirrhosis. In addition, patients with C3d-binding DSA and high MFI (>10,000) had a significant poorer long-term graft survival (p=0.03).
CONCLUSION: In our pediatric cohort of LT, prevalence of DSA was high and increased regularly with time. Presence of C3d positive-DSA with high MFI was associated with a higher rate of graft loss.

PMID: 28782692 [PubMed - as supplied by publisher]

The comparison of intelligence levels of children born to kidney or liver transplant women with children of healthy mothers.

Tue, 08/08/2017 - 15:46
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The comparison of intelligence levels of children born to kidney or liver transplant women with children of healthy mothers.

J Matern Fetal Neonatal Med. 2017 Aug 07;:1-13

Authors: Kociszewska-Najman B, Szpotanska-Sikorska M, Mazanowska N, Wielgos M, Pietrzak B

Abstract
BACKGROUND: Pregnancy after transplantation is associated with high risk of complications and prenatal exposure to immunosuppressants. The purpose of the study was to evaluate the intellectual development of children born to women after organ transplantation.
AIMS: A comparison of intelligence levels in 78 children of kidney or liver transplant women of 78 children born to healthy mothers. The assessment of intellectual level in children was conducted by psychologists and evaluated using age-adjusted intelligence tests (Psyche Cattell Infant Intelligence Scale, Terman-Merril Intelligence Scale or the Scales of Raven's Progressive Matrices).
RESULTS: No significant differences in the distribution of the quotient of intelligence between children born to kidney and liver transplant women were noted (chi(2) = 5.037; p = 0.284). Also no differences in the distribution of intelligence levels was noted between the children of transplanted and healthy mothers in infants and toddlers (chi(2) = 3.125; p = 0.537); preschool (chi(2) = 1.440; p = 0.692) and school age children (chi(2) = 4.079; p = 0.395).
CONCLUSIONS: The intellectual development of children of post-transplant women is similar to the general population. These results provide information on the low risk of intellectual disability in children of transplanted mothers and may improve counseling on the planning of pregnancy in this group of women.

PMID: 28782396 [PubMed - as supplied by publisher]

Eight weeks of ledipasvir/sofosbuvir is effective for selected patients with genotype 1 hepatitis C virus infection.

Tue, 08/08/2017 - 15:46
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Eight weeks of ledipasvir/sofosbuvir is effective for selected patients with genotype 1 hepatitis C virus infection.

Hepatology. 2017 Apr;65(4):1094-1103

Authors: Kowdley KV, Sundaram V, Jeon CY, Qureshi K, Latt NL, Sahota A, Lott S, Curry MP, Tsai N, Chaiyakunapruk N, Lee Y, Petersen J, Buggisch P

Abstract
Eight weeks duration of ledipasvir/sofosbuvir (LDV/SOF) can be considered in genotype 1 hepatitis C virus-infected patients who are treatment-naive, do not have cirrhosis, and have a pretreatment viral load <6,000,000 IU/mL. The effectiveness of this regimen, however, has not been fully confirmed by real-world experience. Using data from real-world cohorts, we aimed to determine the effectiveness of 8 weeks of LDV/SOF treatment, examine variables associated with relapse after treatment with this regimen, and compare the effectiveness of 8 weeks and 12 weeks of LDV/SOF treatment. To evaluate the effectiveness of 8 weeks of therapy and characteristics associated with relapse, we used individual patient data from the IFI (Institut für Interdisziplinäre Medizin), Burman's Pharmacy, and Kaiser Permanente Southern California. All patients had fibrosis staging assessed with biopsy, transient elastography, or serum biomarkers. We also performed a systematic review and meta-analysis of six additional real-world cohorts, to compare effectiveness of 8 weeks to 12 weeks duration. In our pooled data analysis, 634 patients were treated for 8 weeks with LDV/SOF, of whom all had outcomes of cure or relapse without loss to follow-up. Per protocol rates of sustained virologic response at 12 weeks were 98.1% (622/634) in the full cohort and 97.9% (571/583) among treatment-eligible patients. Exact logistic regression revealed no specific patient characteristics associated with relapse. Our meta-analysis of six additional real-world cohorts, comprised of 5,637 patients, demonstrated similar risk for relapse between 8 weeks and 12 weeks of LDV/SOF (relative risk = 0.99, 95% confidence interval 0.98-1.00).
CONCLUSION: An 8-week duration of treatment with LDV/SOF is highly effective in properly selected patients; greater use of this regimen is recommended. (Hepatology 2017;65:1094-1103).

PMID: 28027579 [PubMed - indexed for MEDLINE]

Treatment of Sepsis Pathogenesis with High Mobility Group Box Protein 1-Regulating Anti-inflammatory Agents.

Tue, 08/08/2017 - 15:46
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Treatment of Sepsis Pathogenesis with High Mobility Group Box Protein 1-Regulating Anti-inflammatory Agents.

J Med Chem. 2017 Jan 12;60(1):170-179

Authors: Cho W, Koo JY, Park Y, Oh K, Lee S, Song JS, Bae MA, Lim D, Lee DS, Park SB

Abstract
Sepsis is one of the major causes of death worldwide when associated with multiple organ failure. However, there is a critical lack of adequate sepsis therapies because of its diverse patterns of pathogenesis. The pro-inflammatory cytokine cascade mediates sepsis pathogenesis, and high mobility group box proteins (HMGBs) play an important role as late-stage cytokines. We previously reported the small-molecule modulator, inflachromene (1d), which inhibits the release of HMGBs and, thereby, reduces the production of pro-inflammatory cytokines. In this context, we intraperitoneally administered 1d to a cecal ligation and puncture (CLP)-induced mouse model of sepsis and confirmed that it successfully ameliorated sepsis pathogenesis. On the basis of a structure-activity relationship study, we discovered new candidate compounds, 2j and 2l, with improved therapeutic efficacy in vivo. Therefore, our study clearly demonstrates that the regulation of HMGB1 release using small molecules is a promising strategy for the treatment of sepsis.

PMID: 28001381 [PubMed - indexed for MEDLINE]

Impact of Facility Type and Surgical Volume on 10-Year Survival in Patients Undergoing Hepatic Resection for Hepatocellular Carcinoma.

Tue, 08/08/2017 - 15:46
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Impact of Facility Type and Surgical Volume on 10-Year Survival in Patients Undergoing Hepatic Resection for Hepatocellular Carcinoma.

J Am Coll Surg. 2017 Mar;224(3):362-372

Authors: Chapman BC, Paniccia A, Hosokawa PW, Henderson WG, Overbey DM, Messersmith W, McCarter MD, Gleisner A, Edil BH, Schulick RD, Gajdos C

Abstract
BACKGROUND: Previous studies have demonstrated improved in-hospital mortality after hepatic resection for hepatocellular carcinoma (HCC) at teaching hospitals. The objective of this study was to evaluate if resection of HCC at academic cancer programs (ACP) is associated with improved 10-year survival.
STUDY DESIGN: Using the National Cancer Data Base (NCDB) (1998 to 2011), we evaluated patients undergoing hepatic resection for HCC at ACPs, comprehensive community cancer programs (CCCPs), and community cancer programs (CCPs). High volume cancer programs (HVCPs) were defined as performing 10 or more hepatectomies per year. Multivariate Cox proportional hazard models by stepwise selection were applied to estimate hazard ratios (HR) of predictors of survival. The Kaplan-Meier method was used to generate survival curves at each facility type, and survival rates were compared using the log-rank test.
RESULTS: We identified 12,757 patients undergoing hepatic resection for HCC at ACPs (n = 8,404), CCPs (n = 483), and CCCPs (n = 3,870). Sixty-two percent (n = 5,191) of patients treated at ACPs were at high volume institutions compared with 11.6% (n = 446) and 0% of CCCPs and CCPs, respectively (p < 0.0001). On multivariable analysis, patients undergoing hepatic resection at transplant centers (p < 0.0001) and HVCPs had significantly improved survival (p < 0.0001). Adjusted 10-year survival rates were 28.7% at high volume ACPs, 28.2% at high volume CCCPs, 24.9% at low volume CCCPs, 25.1% at low volume ACPs, and 21.3% at CCPs (p ≤ 0.0001).
CONCLUSIONS: Patients undergoing hepatic resection for HCC at HVCPs had a significantly improved 10-year survival. Regionalization of HCC treatment to HVCPs may improve long-term survival.

PMID: 27923615 [PubMed - indexed for MEDLINE]

N-acetylcysteine and prednisolone treatment improved serum biochemistries in suspected flupirtine cases of severe idiosyncratic liver injury.

Mon, 08/07/2017 - 18:48
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N-acetylcysteine and prednisolone treatment improved serum biochemistries in suspected flupirtine cases of severe idiosyncratic liver injury.

Liver Int. 2017 Aug 07;:

Authors: Borlak J, van Bömmel F, Berg T

Abstract
BACKGROUND & AIMS: The analgesic flupirtine has been linked to cases of severe idiosyncratic drug-induced liver injury (sFILI). We therefore examined whether N-acetylcysteine (NAC) and glucocorticoid therapy is effective in the management of sFILI.
METHODS: In a retrospective cohort study efficacy of NAC-infusion and oral prednisolone treatments on liver-function-tests (LFTs) and clinical outcome of 21 sFILI cases was evaluated by comparing it to an external cohort of 30 sFILI cases not receiving the antidote. LFTs were also assayed in human hepatocyte cultures treated with flupirtine for 96h. Additionally, modulation of glutathione stores in cultures of human hepatocytes treated with 80 drugs was investigated.
RESULTS: Upon admission, patients presented ALT, AST and bilirubin elevations of up to 90, 35 and 30-fold of ULN, respectively. The average INR was 2.2 and 50% of patients had a high MELD score of ≥25 and included 5 cases of 28-32. The combined NAC/prednisolone treatment was well tolerated and led to significant ALT, AST and INR improvements within 2 weeks. However, the hyperbilirubinemia resolved slowly. Two patients with late start of NAC/prednisolone treatment developed hepatic encephalopathy and required liver transplantation; the remaining patients recovered without long-term sequela. Based on serum biochemistries sFILI cases resolved more rapidly (p<0.01) when compared to untreated sFILI patients and included a case with fatal outcome. Additionally, in-vitro studies revealed glutathione depletion as a common culprit for drugs with liver liabilities.
CONCLUSIONS: Based on these initial findings a prospective RCT is needed to confirm safety and efficacy of NAC/prednisolone treatment in sFILI. This article is protected by copyright. All rights reserved.

PMID: 28782153 [PubMed - as supplied by publisher]

Bilateral diaphragmatic paresis following pediatric liver transplantation.

Mon, 08/07/2017 - 18:48
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Bilateral diaphragmatic paresis following pediatric liver transplantation.

SAGE Open Med Case Rep. 2017;5:2050313X17719214

Authors: Olmscheid J, Molero H, Gershan W, Demirel N

Abstract
BACKGROUND: Although diaphragm paresis or paralysis is fairly common following cardiac procedures; it is a less common complication following liver transplantation. Unilateral diaphragm paresis, usually right sided, has been described following liver transplantation in adults and has been rarely described in children.
PURPOSE: Diaphragmatic injury following LT is often unrecognized and is typically unilateral, involving the right hemidiaphragm. Bilateral diaphragm dysfunction following liver transplantation in children is a rare complication.
METHODS: This is a case report of bilateral diaphragm paresis in a young child following a repeat liver transplantation.
CONCLUSION: Bilateral diaphragm paresis following liver transplantation in children is rare and spontaneous resolution is possible. A conservative approach with noninvasive ventilation as a first line treatment to allow the diaphragm to regain function should be considered.

PMID: 28781878 [PubMed]

Antitumoral effect of Ocoxin in hepatocellular carcinoma.

Mon, 08/07/2017 - 18:48
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Antitumoral effect of Ocoxin in hepatocellular carcinoma.

Oncol Lett. 2017 Aug;14(2):1950-1958

Authors: Díaz-Rodríguez E, El-Mallah AM, Sanz E, Pandiella A

Abstract
Hepatocellular carcinoma (HCC) is becoming one of the most prevalent types of cancer worldwide. The most efficient types of treatment at present include surgical resection and liver transplantation, but these treatments may only be used in a small percentage of patients. In order to identify novel therapeutic strategies for this disease, the present study explored the potential antitumoral effect of Ocoxin® oral solution (OOS) in HCC. OOS inhibited the proliferation of HCC cell lines in a time- and dose-dependent manner, being more efficient when used in combination with sorafenib, a standard of care treatment for patients diagnosed with advanced-stage disease. Mechanistic studies indicated that the effect of OOS was due to the induction of cell cycle arrest rather than the stimulation of apoptotic cell death. The cell cycle was slowed down in all phases in the HCC cell lines treated with OOS. Finally, when tested in animal models of HCC, OOS reduced tumor progression through the induction of necrosis in xenograft tumor models. Considering the poor prognosis and high resistance to antitumor treatments of HCC, the antiproliferative action of OOS, particularly in combination with sorafenib, provides the opportunity to investigate the effect of combined therapy in a clinical setting.

PMID: 28781639 [PubMed]

Influence of autologous blood transfusion in liver transplantation in patients with hepatitis B on the function and hemorheology of red blood cells.

Mon, 08/07/2017 - 18:48
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Influence of autologous blood transfusion in liver transplantation in patients with hepatitis B on the function and hemorheology of red blood cells.

Exp Ther Med. 2017 Aug;14(2):1205-1211

Authors: Liu X, Fan R, Lu Y, Kuang L, Yuan Q, Chen Y, Lin Z, Lin D

Abstract
The present study aimed to characterize the function and hemorheology of red blood cells (RBCs) recovered during liver transplantation surgery in patients with hepatitis B and decompensation. A total of 15 hepatitis B patients with decompensation who underwent liver transplantation surgery were included in the present study. Blood samples were recovered during the liver transplantation surgery using an Autologous Blood Recovery System. The morphology and structure of RBCs were characterized and compared between pre-operative and recovered blood samples. In addition, the physiological functions of RBCs were measured and compared between pre-operative and recovered blood samples. No significant differences in the morphological score, 2,3-diphosphoglycerate, Na(+)K(+)-ATPase, Ca(2+)-ATPase, Mg(2+)-ATPase, malondialdehyde and osmotic fragility were identified between RBCs in the pre-operative and recovered blood samples. The level of free hemoglobin in RBCs of the recovered blood samples was significantly higher than in the pre-operative blood samples (P<0.05). Medium- and high-shear blood viscosities in the recovered blood samples were significantly lower than those observed in the pre-operative blood samples (P<0.05). Casson viscosity in the recovered blood samples was significantly higher compared with the pre-operative blood samples. However, no significant differences (P>0.05) in the low-shear blood viscosity, plasma viscosity, relative blood viscosity, erythrocyte aggregation index or Casson yield stress were identified between recovered and pre-operative blood samples. These findings suggested that autologous blood transfusion in liver transplantation surgery in patients with hepatitis B and decompensation had no significant influence on the morphology, structure, function and hemorheology of RBCs.

PMID: 28781620 [PubMed]

Transplant-Free Survival Rates After Covered Transjugular Intrahepatic Portosystemic Shunt.

Mon, 08/07/2017 - 18:48
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Transplant-Free Survival Rates After Covered Transjugular Intrahepatic Portosystemic Shunt.

Gastroenterology. 2017 Aug 03;:

Authors: Schmidt-Martin D, Armstrong MJ, Rowe IA

PMID: 28781224 [PubMed - as supplied by publisher]

Reply.

Mon, 08/07/2017 - 18:48
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Reply.

Gastroenterology. 2017 Aug 03;:

Authors: Gane E

PMID: 28781221 [PubMed - as supplied by publisher]

Locoregional therapies for hepatocellular carcinoma and the new LI-RADS treatment response algorithm.

Mon, 08/07/2017 - 18:48
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Locoregional therapies for hepatocellular carcinoma and the new LI-RADS treatment response algorithm.

Abdom Radiol (NY). 2017 Aug 05;:

Authors: Kielar A, Fowler KJ, Lewis S, Yaghmai V, Miller FH, Yarmohammadi H, Kim C, Chernyak V, Yokoo T, Meyer J, Newton I, Do RK

Abstract
Radiologists play a central role in the assessment of patient response to locoregional therapies for hepatocellular carcinoma (HCC). The identification of viable tumor following treatment guides further management and potentially affects transplantation eligibility. Liver Imaging Reporting and Data Systems (LI-RADS) first introduced the concept of LR-treated in 2014, and a new treatment response algorithm is included in the 2017 update to assist radiologists in image interpretation of HCC after locoregional therapy. In addition to offering imaging criteria for viable and nonviable HCC, new concepts of nonevaluable tumors as well as tumors with equivocal viability are introduced. Existing guidelines provided by response evaluation criteria in solid tumors (RECIST) and modified RECIST address patient-level assessments and are routinely used in clinical trials but do not address the variable appearances following different locoregional therapies. The new LI-RADS treatment response algorithm addresses this gap and offers a comprehensive approach to assess treatment response for individual lesions after a variety of locoregional therapies, using either contrast-enhanced CT or MRI.

PMID: 28780679 [PubMed - as supplied by publisher]

Validation of Feasibility of Magnetic Resonance Imaging for the Measurement of Depth of Tumor Invasion in Distal Bile Duct Cancer According to the New American Joint Committee on Cancer Staging System.

Mon, 08/07/2017 - 18:48
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Validation of Feasibility of Magnetic Resonance Imaging for the Measurement of Depth of Tumor Invasion in Distal Bile Duct Cancer According to the New American Joint Committee on Cancer Staging System.

Acad Radiol. 2017 Aug 02;:

Authors: Han NY, Kim JY, Kim MJ, Park BJ, Sung DJ, Sim KC, Cho SB, Kim DS

Abstract
RATIONALE AND OBJECTIVES: This study aimed to develop and validate a method for measuring the depth of tumor invasion (DoI) using magnetic resonance imaging (MRI) and to investigate the diagnostic performance of the measured DoI for stratifying tumor (T) classification in patients with distal bile duct cancer according to the new American Joint Committee on Cancer staging system.
MATERIALS AND METHODS: Fifty-four patients (30 men and 24 women; age range, 43-81 years) with distal bile duct cancer were enrolled. A study coordinator first developed a "provisional method" for measuring DoI on T2-weighted MRI. Subsequently, after compensating for defects, the "improved method" was developed. Two reviewers independently measured DoI and assessed its correlations with the histopathologic reference standard using intraclass correlation coefficient (ICC). The study population was grouped according to the DoI for T classification based on the new staging system for evaluation of diagnostic predictive values.
RESULTS: The ICC values between the radiologic and the histopathologic DoI were calculated. Using the "improved method," the ICC for the coordinator's DoI was very good (ICC, 0.885), which was a significantly higher value than that obtained using the "provisional method" (ICC, 0.501, P = .00000); and for two reviewers' DoIs, the ICC values were good (ICC, 0.752 and 0.784, respectively). The overall accuracy of MRI for stratifying bile duct tumors using DoI was 87.0% and 85.2%, respectively.
CONCLUSIONS: This newly developed method reliably measured DoI on T2-weighted MRI and can be used for preoperative T classification of patients with distal bile duct cancer according to the new staging system.

PMID: 28780173 [PubMed - as supplied by publisher]

Intra-hepatic Depletion of Mucosal Associated Invariant T cells in Hepatitis C Virus-induced Liver Inflammation.

Mon, 08/07/2017 - 18:48
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Intra-hepatic Depletion of Mucosal Associated Invariant T cells in Hepatitis C Virus-induced Liver Inflammation.

Gastroenterology. 2017 Aug 02;:

Authors: Bolte FJ, O'Keefe AC, Webb LM, Serti E, Rivera E, Liang TJ, Ghany M, Rehermann B

Abstract
BACKGROUND & AIMS: Chronic hepatitis affects phenotypes of innate and adaptive immune cells. Mucosal associated invariant T (MAIT) cells are enriched in the liver as compared to the blood, respond to intra-hepatic cytokines, and (via the semi-invariant T-cell receptor) to bacteria translocated from the gut. Little is known about the role of MAIT cells in livers of patients with chronic hepatitis C virus (HCV) infection and their fate after antiviral therapy.
METHODS: We collected blood samples from 42 patients with chronic HCV infection who achieved a sustained virologic response after 12 weeks of treatment with sofosbuvir and velpatasvir. Mononuclear cells were isolated from blood before treatment, at weeks 4 and 12 during treatment, and 24 weeks after the end of treatment. Liver biopsies were collected from 37 of the patients prior to and at week 4 of treatment. Mononuclear cells from 56 blood donors and 10 livers that were not suitable for transplantation were used as controls. Liver samples were assessed histologically for inflammation and fibrosis. Mononuclear cells from liver and blood were studied by flow cytometry and analyzed for responses to cytokine and bacterial stimulation.
RESULTS: The frequency of MAIT cells among T cells was significantly lower in blood and liver samples of patients with HCV infection than of controls (median 1.31% vs 2.32% for blood samples, P=.0048 and median 4.34% vs 13.40% for liver samples, P=.001). There was an inverse correlation between the frequency of MAIT cells in the liver and histologically determined levels of liver inflammation (r=-.5437, P=.0006) and fibrosis (r=-.5829, P=.0002). MAIT cells from the liver had higher levels of activation and cytotoxicity than MAIT cells from blood (P<.0001). Production of interferon gamma (IFNG) by MAIT cells was dependent on monocyte-derived interleukin 18 (IL18), and was reduced in patients with HCV infection in response to T-cell receptor-mediated but not cytokine-mediated stimulation, as compared to controls. Anti-viral therapy rapidly decreased liver inflammation and MAIT cell activation and cytotoxicity, and increased the MAIT cell frequency among intra-hepatic but not blood T cells. The MAIT cell response to T-cell receptor-mediated stimulation did not change during the 12 weeks of antiviral therapy.
CONCLUSIONS: In analyses of paired blood and liver samples from patients with chronic HCV infection before, during and after antiviral therapy with sofosbuvir and velpatasvir, we found that intrahepatic MAIT cells are activated by monocyte-derived cytokines and depleted in HCV-induced liver inflammation.

PMID: 28780074 [PubMed - as supplied by publisher]

Validation of whole-slide imaging in the primary diagnosis of liver biopsies in a University Hospital.

Mon, 08/07/2017 - 18:48
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Validation of whole-slide imaging in the primary diagnosis of liver biopsies in a University Hospital.

Dig Liver Dis. 2017 Jul 19;:

Authors: Saco A, Diaz A, Hernandez M, Martinez D, Montironi C, Castillo P, Rakislova N, Del Pino M, Martinez A, Ordi J

Abstract
BACKGROUND: Experience in the use of whole slide imaging (WSI) for primary diagnosis is limited and there are no comprehensive reports evaluating this technology in liver biopsy specimens.
AIMS: To determine the accuracy of interpretation of WSI compared with conventional light microscopy (CLM) in the diagnosis of needle liver biopsies.
METHODS: Two experienced liver pathologists blindly analyzed 176 consecutive biopsies from the Pathology Department at the Hospital Clinic of Barcelona. One of the observers performed the initial evaluation with CLM, and the second evaluation with WSI, whereas the second observer performed the first evaluation with WSI and the second with CLM. All slides were digitized in a Ventana iScan HT at 400× and evaluated with the Virtuoso viewer (Roche diagnostics). We used kappa statistics (κ) for two observations.
RESULTS: Intra-observer agreement between WSI and CLM evaluations was almost perfect (96.6%, κ=0.9; 95% confidence interval [95% CI]: 0.9-1 for observer 1, and 90.3%, κ=0.9; 95%CI: 0.8-0.9 for observer 2). Both native and transplantation biopsies showed an almost perfect concordance in the diagnosis.
CONCLUSION: Diagnosis of needle liver biopsy specimens using WSI is accurate. This technology can reliably be introduced in routine diagnosis.

PMID: 28780052 [PubMed - as supplied by publisher]

Why Would a Patient Complain of Dysphagia and Heartburn After Multiple Bariatric Surgeries?

Mon, 08/07/2017 - 18:48
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Why Would a Patient Complain of Dysphagia and Heartburn After Multiple Bariatric Surgeries?

Gastroenterology. 2017 Aug 02;:

Authors: Debs T, Petrucciani N, Gugenheim J

PMID: 28780012 [PubMed - as supplied by publisher]

Management of renal dysfunction in patients with liver cirrhosis: role of pretransplantation hemodialysis and outcomes after liver transplantation.

Mon, 08/07/2017 - 18:48
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Management of renal dysfunction in patients with liver cirrhosis: role of pretransplantation hemodialysis and outcomes after liver transplantation.

Semin Vasc Surg. 2016 Dec;29(4):227-235

Authors: Thorat A, Jeng LB

Abstract
Patients with end-stage liver disease (ESLD) who develop hepatorenal syndrome (HRS) have very high mortality rates. For patients with HRS type I, median survival without specific therapy is only 2 weeks. Due to worsening clinical condition in such patients secondary to uremia and hepatic disease, some form of renal replacement therapy (RRT), either intermittent hemodialysis IHD or continuous veno-venous hemodialysis (CVVHD), must be instituted. However, the literature regarding the survival benefits of the hemodialysis for the worsening renal failure in liver cirrhotic patients remains limited. In this review, we performed a meta-analysis of nine different studies done in the last 2 decades that included 464 patients with end-stage liver disease with renal failure who received either pretransplantation or post-transplantation CVVHD. Survival of the patients was then analyzed with respect to patients with end-stage liver disease without renal failure that underwent liver transplantation (LT). Outcomes for the patients with pre-LT CVVHD were comparable with those of liver transplant recipients without renal failure. However, patients requiring post-LT hemodialysis for prolonged periods showed poor outcomes and a tendency to progress to chronic kidney disease. In all selected studies, patients with post-transplantation CVVHD for a prolonged period had a 3-year survival rate of ≤40%. This review highlights the role of pretransplantation CVVHD in selected patients with HRS who could achieve significantly better survival rates compared with patients without any renal replacement therapy or patients with post-transplantation CVVHD.

PMID: 28779790 [PubMed - in process]

A frailty index predicts post-liver transplant morbidity and mortality in HIV-positive patients.

Mon, 08/07/2017 - 18:48
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A frailty index predicts post-liver transplant morbidity and mortality in HIV-positive patients.

AIDS Res Ther. 2017 Aug 05;14(1):37

Authors: Guaraldi G, Dolci G, Zona S, Tarantino G, Serra V, Ballarin R, Franceschini E, Codeluppi M, Brothers TD, Mussini C, Di Benedetto F

Abstract
BACKGROUND: We hypothesized that frailty acts as a measure of health outcomes in the context of LT. The aim of this study was to explore frailty index across LT, as a measure of morbidity and mortality. This was a retrospective observational study including all consecutive 47 HIV+patients who received LT in Modena, Italy from 2003 to June 2015.
METHODS: frailty index (FI) was constructed from 30 health variables. It was used both as a continuous score and as a categorical variable, defining 'most frail' a FI > 0.45. FI change across transplant (deltaFI, ΔFI) was calculated as the difference between year 1 FI (FI-Y1) and pre-transplant FI (FI-t0). The outcomes measures were mortality and "otpimal LT" (defined as being alive without multi-morbidity).
RESULTS: Median value of FI-t0 was 0.48 (IQR 0.42-0.52), FI-Y1 was 0.31 (IQR 0.26-0.41). At year five mortality rate was 45%, "optimal transplant" rate at year 1 was 38%. All the patients who died in the post-LT were most frail in the pre-LT. ΔFI was a predictor of mortality after correction for age and MELD (HR = 1.10, p = 0.006) and was inversely associated with optimal transplant after correction for age (HR = 1.04, p = 0.01).
CONCLUSIONS: We validated FI as a valuable health measure in HIV transplant. In particular, we found a relevant correlation between FI strata at baseline and mortality and a statistically significant correlation between, ΔFI and survival rate.

PMID: 28779758 [PubMed - in process]

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