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Donor and recipient P450 gene polymorphisms influence individual pharmacological effects of tacrolimus in Chinese liver transplantation patients.

Sun, 02/18/2018 - 13:45
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Donor and recipient P450 gene polymorphisms influence individual pharmacological effects of tacrolimus in Chinese liver transplantation patients.

Int Immunopharmacol. 2018 Feb 14;57:18-24

Authors: Liu J, Ouyang Y, Chen D, Yao B, Lin D, Li Z, Zang Y, Liu H, Fu X

Abstract
The immunosuppressant drug tacrolimus (Tac) used for the prevention of immunological rejection is a metabolic substrate of cytochrome P450 enzymes. This study was designed to evaluate the short-term and long-term potential influence of single-nucleotide polymorphisms (SNPs) in CYP450 genes of liver transplant (LT) recipients as well as the donors on individual pharmacological effects of Tac and to guide individualized-medication from the perspective of pharmacogenomics. Twenty-one SNPs of the CYP450 gene were genotyped for both recipients and donors in 373 LT patients receiving Tac-based immunosuppressants. The Tac concentration/dosage ratio (C/D) was evaluated from the initial medication until one year after LT. The C/D ratio was significantly higher when the donor and/or recipient genotype of CYP3A5 rs776746 was G/G or rs15524 was T/T or rs4646450 was C/C all through one year after transplantation. Comparing the effect of donor gene variants of rs776746, rs15524, and rs4646450 on Tac C/D ratios with the recipients, statistically significant differences were found between the donor T/T group and the recipient T/T group in rs15524 at 1 month and 6 months, and at 6 months, the donor C/C group differed from the recipient C/C group in rs4646450. In conclusion, rs776746, rs15524, and rs4646450 of CYP3A5 had a significant influence on Tac pharmacological effects for both the initial use and long-term use. The donor liver genotype and the recipient intestine genotype contribute almost equally in the short-term, but the donor genotype had a greater effect than the recipient genotype at 6 months. Personalized Tac treatment after LT should be based on the CYP3A5 genotype.

PMID: 29454235 [PubMed - as supplied by publisher]

Nanofibrous PLGA Electrospun Scaffolds Modified with Type I Collagen Influence Hepatocyte Function and Support Viability In Vitro.

Sun, 02/18/2018 - 13:45
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Nanofibrous PLGA Electrospun Scaffolds Modified with Type I Collagen Influence Hepatocyte Function and Support Viability In Vitro.

Acta Biomater. 2018 Feb 14;:

Authors: Brown JH, Das P, DiVito MD, Ivancic D, Poh Tan L, Wertheim JA

Abstract
A major challenge of maintaining primary hepatocytes in vitro is progressive loss of hepatocyte-specific functions, such as protein synthesis and cytochrome P450 (CYP450) catalytic activity. We developed a three-dimensional (3D) nanofibrous scaffold made from poly(L-lactide-co-glycolide) (PLGA) polymer using a newlyoptimizedwet electrospinning techniquethat resulted in a highly porous structure that accommodated inclusion of primary human hepatocytes. Extracellular matrix (ECM) proteins (type I collagen or fibronectin) at varying concentrations were chemically linked to electrospun PLGA using amine coupling to develop an in vitro culture system containing the minimal essential ECM components of the liver micro-environment that preserve hepatocyte function in vitro. Cell-laden nanofiber scaffolds were tested in vitro to maintain hepatocyte function over a two-week period. Incorporation of type I collagen onto PLGA scaffolds (PLGA-Chigh: 100 µg/mL) led to 10-fold greater albumin secretion, 4-fold higher urea synthesis, and elevated transcription of hepatocyte-specific CYP450 genes (CYP3A4, 3.5-fold increase and CYP2C9, 3-fold increase) in primary human hepatocytes compared to the same cells grown within unmodified PLGA scaffolds over two weeks. These indices, measured using collagen-bonded scaffolds, were also higher than scaffolds coupled to fibronectin or an ECM control sandwich culture composed of type I collagen and Matrigel. Induction of CYP2C9 activity was also higher in these same type I collagen PLGA scaffolds compared to other ECM-modified or unmodified PLGA constructs and was equivalent to the ECM control at 7 days. Together, we demonstrate a minimalist ECM-based 3D synthetic scaffold that accommodates primary human hepatocyte inclusion into the matrix, maintains long-term in vitro survival and stimulates function, which can be attributed to coupling of type I collagen.
STATEMENT OF SIGNIFICANCE: Culturing primary hepatocytes within a three-dimensional (3D) structure that mimics the natural liver environment is a promising strategy for extending the function and viability of hepatocytes in vitro. In the present study we generate porous PLGA nanofibers, that are chemically modified with extracellular matrix proteins, to serve as 3D scaffolds for the in vitro culture of primary human hepatocytes. Our findings demonstrate that the use of ECM proteins, especially type I collagen, in a porous 3D environment helps to improve the synthetic function of primary hepatocytes over time. We believe the work presented within will provide insights to readers for drug toxicity and tissue engineering applications.

PMID: 29454157 [PubMed - as supplied by publisher]

Quantitative Imaging Features and Postoperative Hepatic Insufficiency: A Multi-Institutional Expanded Cohort.

Sun, 02/18/2018 - 13:45
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Quantitative Imaging Features and Postoperative Hepatic Insufficiency: A Multi-Institutional Expanded Cohort.

J Am Coll Surg. 2018 Feb 14;:

Authors: Pak LM, Chakraborty J, Gonen M, Chapman WC, Do RK, Koerkamp BG, Verhoef K, Lee SY, Massani M, van der Stok EP, Simpson AL, Memorial Sloan Kettering Cancer Center Hepatopancreatobiliary Service

Abstract
BACKGROUND: Post-hepatectomy liver insufficiency (PHLI) is a significant cause of morbidity and mortality after liver resection. Quantitative imaging analysis using CT scans measures variations in pixel intensity related to perfusion. A preliminary study demonstrated a correlation between quantitative imaging features of the future liver remnant (FLR) parenchyma from preoperative CT scans and PHLI. The objective of the present study was to explore the potential application of quantitative imaging analysis in PHLI in an expanded, multi-institutional cohort.
STUDY DESIGN: Patients were retrospectively identified from five high-volume academic centers that developed PHLI after major hepatectomy and were matched to control patients without PHLI (by extent of resection, pre-operative chemotherapy treatment, age (±5 years), and sex). Quantitative imaging features were extracted from the FLR in the preoperative CT scan, and the most discriminatory features were identified using conditional logistic regression. %RLV was defined as follows: (FLR volume)/(total liver volume)x100. Significant clinical and imaging features were combined in a multivariate analysis using conditional logistic regression.
RESULTS: From 2000 to 2015, 74 patients with PHLI and 74 matched controls were identified. The most common indications for surgery were colorectal liver metastases (53%), hepatocellular carcinoma (37%), and cholangiocarcinoma (9%). Two CT imaging features (FD1_4: image complexity; ACM1_10: spatial distribution of pixel intensity) were strongly associated with PHLI and remained associated with PHLI on multivariate analysis (p=0.018 and p=0.023, respectively), independent of clinical variables, including preoperative bilirubin and %RLV.
CONCLUSIONS: Quantitative imaging features are independently associated with PHLI and are a promising preoperative risk stratification tool.

PMID: 29454098 [PubMed - as supplied by publisher]

Recipient characteristics and morbidity and mortality after liver transplantation.

Sun, 02/18/2018 - 13:45
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Recipient characteristics and morbidity and mortality after liver transplantation.

J Hepatol. 2018 Feb 14;:

Authors: Asrani SK, Saracino G, O'Leary JG, Gonzales S, Kim P, McKenna G, Klintmalm G, Trotter J

Abstract
BACKGROUND: Over the last decade, liver transplantation of sicker, older non-hepatitis C cirrhotics with multiple co-morbidities has increased in the United States.
METHODS: We sought to identify a parsimonious set of recipient factors among HCV negative adult transplant recipients associated with significant morbidity and mortality within 5 years after liver transplantation using national (n=31,829, 2002-2015) and center specific data. Coefficients of relevant recipient factors were converted to weighted points and scaled from 0-5. Recipient factors associated with graft failure included: ventilator support (5 pts; HR 1.59, 95% CI 1.48-1.72); recipient age >60 years (3 pts; HR 1.29, 95% CI 1.23-1.36); hemodialysis (3 pts; HR 1.26, 95% CI 1.16-1.37); diabetes (2 pts; HR 1.20, 95% CI 1.14-1.27); or serum creatinine ≥1.5mg/dL without hemodialysis (2 pts; HR 1.15, 95% CI 1.09-1.22).
RESULTS: Graft survival within 5 years based on points (any combination) was 77.2% (0-4), 69.1% (5-8) and 57.9% (>8). In recipients with > 8 points, graft survival was 42% (MELD<25) and 50% (MELD 25-35) in recipients receiving donors with donor risk index >1.7. In center specific data within the first year, subjects with ≥ 5 points (vs. 0-4) had longer hospitalization (11 vs. 8 days, p<0.01), higher admissions for rehabilitation (12.3% versus 2.7%, p<0.01), and higher incidence of cardiac disease (14.2% vs. 5.3%, p<0.01) and stage 3 chronic kidney disease (78.6% vs. 39.5%, p=0.03) within 5 years.
CONCLUSION: The impact of co-morbidities in a MELD based organ allocation system needs to be reassessed. The proposed clinical tool may be helpful for center specific assessment of risk of graft failure in non HCV patients and discussion regarding relevant morbidity in selected subsets.
LAY SUMMARY: Over the last decade, liver transplantation of sicker, older patient with multiple co-morbidities has increased. In this study, we show that a set of recipient factors (recipient age>60 years, ventilator status, diabetes, hemodialysis and creatinine>1.5mg/dL) can help identify patients that may not do well after transplant. Transplanting sicker organs in patients with certain combinations of these characteristics further leads to lower survival.

PMID: 29454069 [PubMed - as supplied by publisher]

Living-donor liver transplantation for mild Zellweger spectrum disorder: Up to 17 years follow-up.

Sun, 02/18/2018 - 13:45
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Living-donor liver transplantation for mild Zellweger spectrum disorder: Up to 17 years follow-up.

Pediatr Transplant. 2018 Feb 16;:

Authors: Demaret T, Varma S, Stephenne X, Smets F, Scheers I, Wanders R, Van Maldergem L, Reding R, Sokal E

Abstract
Mild Zellweger spectrum disorder, also described as Infantile Refsum disease, is attributable to mutations in PEX genes. Its clinical course is characterized by progressive hearing and vision loss, and neurodevelopmental regression. Supportive management is currently considered the standard of care, as no treatment has shown clinical benefits. LT was shown to correct levels of circulating toxic metabolites, partly responsible for chronic neurological impairment. Of three patients having undergone LT for mild ZSD, one died after LT, while the other two displayed significant neurodevelopmental improvement on both the long-term (17 years post-LT) and short-term (9 months post-LT) follow-up. We documented a sustained improvement of biochemical functions, with a complete normalization of plasma phytanic, pristanic, and pipecolic acid levels. This was associated with stabilization of hearing and visual functions, and improved neurodevelopmental status, which has enabled the older patient to lead a relatively autonomous lifestyle on the long term. The psychomotor acquisitions have been markedly improved as compared to their affected siblings, who did not undergo LT and exhibited a poor neurological outcome with severe disabilities. We speculate that LT performed before the onset of severe sensorineural defects in mild ZSD enables partial metabolic remission and improved long-term clinical outcomes.

PMID: 29453832 [PubMed - as supplied by publisher]

Proposal for new selection criteria considering pre-transplant muscularity and visceral adiposity in living donor liver transplantation.

Sun, 02/18/2018 - 13:45
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Proposal for new selection criteria considering pre-transplant muscularity and visceral adiposity in living donor liver transplantation.

J Cachexia Sarcopenia Muscle. 2018 Feb 17;:

Authors: Hamaguchi Y, Kaido T, Okumura S, Kobayashi A, Shirai H, Yao S, Yagi S, Kamo N, Okajima H, Uemoto S

Abstract
BACKGROUND: The significance of pre-operative body composition has recently attracted much attention in various diseases. However, cut-off values for these parameters remain undetermined, and these factors are not currently included in selection criteria for recipients of living donor liver transplantation (LDLT).
METHODS: Using computed tomography of 657 donors for LDLT, skeletal muscle mass, muscle quality, and visceral adiposity were evaluated by using skeletal muscle mass index (SMI), intramuscular adipose tissue content (IMAC), and visceral-to-subcutaneous adipose tissue area ratio (VSR). Sex-specific cut-offs for SMI, IMAC, and VSR were determined, and correlations with outcomes after LDLT in 277 recipients were examined with the aim of establishing new selection criteria for LDLT.
RESULTS: On the basis of younger donor data, we determined sex-specific cut-off values for low SMI, high IMAC, and high VSR (mean ± 2 standard deviations). Patients with all three factors showed the lowest survival rate after LDLT (1 year survival rate, 41.2%; P < 0.001). On multivariate analysis, low SMI (P = 0.002), high IMAC (P = 0.002), and high VSR (P = 0.001) were identified as independent risk factors for mortality after LDLT. Based on these findings, we have excluded patients showing all three factors (low SMI, high IMAC, and high VSR) as candidates for LDLT since October 2016.
CONCLUSIONS: Using cut-off values determined from healthy donors, we have established new selection criteria for LDLT including body composition, which should improve post-transplant outcomes.

PMID: 29453829 [PubMed - as supplied by publisher]

Unusual spontaneous porto-systemic shunt: The importance of diagnosing non-anatomical porto-systemic shunts to improve portal flow in pediatric living-related liver transplantation. Case report.

Sun, 02/18/2018 - 13:45
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Unusual spontaneous porto-systemic shunt: The importance of diagnosing non-anatomical porto-systemic shunts to improve portal flow in pediatric living-related liver transplantation. Case report.

Pediatr Transplant. 2018 Feb 16;:

Authors: Rubio JS, Rumbo C, Farinelli PA, Aguirre N, Ramisch DA, Paladini H, D Angelo P, Barros Schelotto P, Gondolesi GE

Abstract
Collateral circulation secondary to liver cirrhosis may cause the development of large PSSs that may steal flow from the main portal circulation. It is important to identify these shunts prior to, or during the transplant surgery because they might cause an insufficient portal flow to the implanted graft. There are few reports of "steal flow syndrome" cases in pediatrics, even in biliary atresia patients that may have portal hypoplasia as an associated malformation. We present a 12-month-old female who received an uneventful LDLT from her mother, and the GRWR was 4.8. During the early post-operative period, she became hemodynamically unstable, developed ascites, and altered LFT. The post-operative ultrasound identified reversed portal flow, finding a non-anatomical PSS. A 3D CT scan confirmed the presence of a mesocaval shunt through the territory of the right gonadal vein, draining into the right iliac vein, with no portal inflow into the liver. The patient was re-operated, and the shunt was ligated. An intraoperative Doppler ultrasound showed adequate portal inflow after the procedure; the patient evolved satisfactorily and was discharged home on day number 49. The aim was to report a case of post-operative steal syndrome in a pediatric recipient due to a mesocaval shunt not diagnosed during the pretransplant evaluation.

PMID: 29453782 [PubMed - as supplied by publisher]

Primary sclerosing cholangitis.

Sun, 02/18/2018 - 13:45
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Primary sclerosing cholangitis.

Lancet. 2018 Feb 13;:

Authors: Dyson JK, Beuers U, Jones DEJ, Lohse AW, Hudson M

Abstract
Primary sclerosing cholangitis is a rare, chronic cholestatic liver disease characterised by intrahepatic or extrahepatic stricturing, or both, with bile duct fibrosis. Inflammation and fibrosis of bile ducts and the liver are followed by impaired bile formation or flow and progressive liver dysfunction. Patients might be asymptomatic at presentation or might have pruritus, fatigue, right upper quadrant pain, recurrent cholangitis, or sequelae of portal hypertension. The key diagnostic elements are cholestatic liver biochemistry and bile duct stricturing on cholangiography. Genetic and environmental factors are important in the cause of the disease, with the intestinal microbiome increasingly thought to play a pathogenetic role. Approximately 70% of patients have concurrent inflammatory bowel disease and patients require colonoscopic screening and surveillance. Primary sclerosing cholangitis is associated with increased malignancy risk and surveillance strategies for early cholangiocarcinoma detection are limited. No single drug has been proven to improve transplant-free survival. Liver transplantation is effective for advanced disease but at least 25% of patients develop recurrent disease in the graft.

PMID: 29452711 [PubMed - as supplied by publisher]

Extraordinary disease-free survival in a rare malignant extrarenal rhabdoid tumor: a case report and review of the literature.

Sun, 02/18/2018 - 13:45
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Extraordinary disease-free survival in a rare malignant extrarenal rhabdoid tumor: a case report and review of the literature.

J Med Case Rep. 2018 Feb 17;12(1):39

Authors: D'Amico F, Bertacco A, Cesari M, Mescoli C, Caturegli G, Gondolesi G, Cillo U

Abstract
BACKGROUND: Malignant extrarenal rhabdoid tumor of the gastrointestinal tract is rarely reported in the literature. It is characterized by poor prognosis and aggressive metastatic features. A literature review evidenced only 19 cases, with poor outcome.
CASE PRESENTATION: We report a case of a colonic "pure" malignant extrarenal rhabdoid tumor with metastatic nodes in a 65-year-old Caucasian man. He was treated surgically with no recurrence, no adjuvant chemotherapy, and with 4-year survival without disease at the time of the submission of this article.
CONCLUSIONS: We present an extraordinary case of long-term survival due to the extended surgical treatment. We believe that the absence of organ metastasis at presentation is a positive prognostic factor, although pathology confirmed node involvement (13/38 positive) on microscopy.

PMID: 29452605 [PubMed - in process]

Outcome of ABO-incompatible adult living-donor liver transplantation for patients with hepatocellular carcinoma.

Sat, 02/17/2018 - 13:45

Outcome of ABO-incompatible adult living-donor liver transplantation for patients with hepatocellular carcinoma.

J Hepatol. 2018 Feb 13;:

Authors: Yoon YI, Song GW, Lee SG, Hwang S, Kim KH, Kim SH, Kang WH, Cho HD, Jwa EK, Kwon JH, Tak EY, Kirchner VA

Abstract
BACKGROUND & AIMS: Living-donor liver transplantation (LDLT) can simultaneously cure hepatocellular carcinoma (HCC) and underlying liver cirrhosis, improving long-term results in patients with HCC. ABO-incompatible LDLT could expand the living-donor pool, reduce waiting times for deceased-donor liver transplantation, and improve long-term survival for some patients with HCC.
METHODS: We retrospectively reviewed the medical records of patients undergoing LDLT for HCC from November 2008 to December 2015 at a single institution in Korea. In total, 165 patients underwent ABO-incompatible and 753 patients underwent ABO-compatible LDLT for HCC. ABO-incompatible recipients underwent desensitization to overcome the ABO blood-group barrier, including pre-transplant plasma exchange and rituximab administration (300-375 mg/m2 /body surface area).
RESULTS: We performed 1:1 propensity score matching and included 165 patients in each group. 82.4% of ABO-incompatible and 83.0% of -compatible LDLT groups had HCC within conventional Milan criteria, respectively, and 92.1 % and 92.7 % of patients in each group had a Child-Pugh score of A or B. ABO-incompatible and -compatible LDLT groups were followed up for 48.0 and 48.7 months, respectively, with both groups showing comparable recurrence-free survival rates (hazard ratio: 1.14, 95% confidence interval: 0.68-1.90; P = 0.630) and overall patient-survival outcomes (hazard ratio 1.10, 95% confidence interval: 0.60-2.00; P = 0.763).
CONCLUSIONS: These findings suggested that ABO-incompatible liver transplantation is a feasible option for patients with HCC, especially for those with compensated cirrhosis with HCC within conventional Milan criteria.
LAY SUMMARY: Despite hypothetical immunological concerns that the desensitization protocol for breaking through the ABO blood group barrier might have a negative impact on the recurrence of hepatocellular carcinoma (HCC), our experience demonstrated no significant differences in the long-term overall survival and recurrence-free survival rates between patients receiving ABO-compatible or ABO-incompatible liver transplantation. In conclusion, results from our institution indicated that ABO-incompatible living donor liver transplantation constitutes a potentially feasible option for patients with HCC, especially those with compensated cirrhosis with HCC within conventional Milan criteria.

PMID: 29452208 [PubMed - as supplied by publisher]

Glycogen synthase kinase 3β promotes liver innate immune activation by restraining AMP-activated protein kinase activation.

Sat, 02/17/2018 - 13:45

Glycogen synthase kinase 3β promotes liver innate immune activation by restraining AMP-activated protein kinase activation.

J Hepatol. 2018 Feb 13;:

Authors: Zhou H, Wang H, Ni M, Yue S, Xia Y, Busuttil RW, Kupiec-Weglinski JW, Lu L, Wang X, Zhai Y

Abstract
BACKGROUND & AIMS: Glycogen synthase kinase 3β (Gsk3β) is a ubiquitously expressed kinase with distinctive functions in different types of cells. Although its roles in regulating innate immune activation and ischemia and reperfusion injuries (IRI) have been well documented, underlying mechanisms remain ambiguous, due in part to the lack of cell-specific tools in vivo.
METHODS: We created a myeloid-specific Gsk3β KO strain to study its function in macrophages in a murine liver partial warm ischemia model.
RESULTS: Compared with controls, myeloid Gsk3β KO mice were protected from IRI with diminished pro-, but enhanced anti-inflammatory immune responses in livers. In bone marrow-derived macrophages (BMMs), Gsk3β deficiency resulted in an early reduction of TNF-α, but sustained increase of IL-10 gene transcription upon TLR4 stimulation in vitro. These were associated enhanced AMPK activation, which led to an accelerated and higher level of induction of the novel innate immune negative regulator small heterodimer partner (SHP). The regulatory function of Gsk3β on AMPK activation and SHP induction was confirmed in WT BMMs with Gsk3 inhibitor. Furthermore, we found that this immune regulatory mechanism was independent of Gsk3β S9 phosphorylation and the PI3K-AKT signaling pathway. In vivo, myeloid Gsk3β deficiency facilitated SHP upregulation by IR in liver macrophages. Treatments of Gsk3β KO mice with either AMPK inhibitor or SHP siRNA prior to the onset of liver ischemia restored liver pro-inflammatory immune activation and IRI in these otherwise protected hosts. Additionally, pharmacological activation of AMPK protected WT mice from liver IRI with reduced pro-inflammatory immune activation. Inhibition of the AMPK-SHP pathway by liver ischemia was demonstrated in tumor resection patients.
CONCLUSIONS: Gsk3β promotes innate pro-inflammatory immune activation by restraining AMPK activation.
LAY SUMMARY: Gsk3β promotes macrophage inflammatory activation by inhibiting the immune regulatory signaling of AMPK and the induction of small heterodimer partner. Therefore, therapeutic targeting of Gsk3β enhances innate immune regulation and protects livers from ischemia and reperfusion injury.

PMID: 29452207 [PubMed - as supplied by publisher]

Non invasive diagnosis of acute cellular rejection after liver transplantation - Current opinion.

Sat, 02/17/2018 - 13:45

Non invasive diagnosis of acute cellular rejection after liver transplantation - Current opinion.

Transpl Immunol. 2018 Feb 13;:

Authors: Kumar S, Mohapatra N, Borle DP, Choudhury A, Sarin S, Gupta E

PMID: 29452168 [PubMed - as supplied by publisher]

[Hepatitis C virus infection. From clinical guidelines to clinical practice and personalization of cure.]

Sat, 02/17/2018 - 13:45
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[Hepatitis C virus infection. From clinical guidelines to clinical practice and personalization of cure.]

Recenti Prog Med. 2018 Jan;109(1):33-37

Authors: Toniutto P

Abstract
Although clinical guidelines provide clear indications on the treatment of patients with chronic HCV related liver disease, there are still clinical situations in which clinicians experience and judgment remain essential in the proper patient management. These are mainly represented by antiviral therapy in patients with decompensated liver disease, especially if they are candidates for liver transplantation or with significant comorbidities and complex pharmacological therapies. Antiviral retreatment of patients who failed a regimen containing an NS5A protease inhibitor still appears to be a delicate context in which no solid recommendations are provided, especially in patients with HCV genotype 3 and decompensated cirrhosis. The follow-up of patients without cirrhosis who have obtained viral eradication is still controversial, in the absence of prospective clinical trials. With the advent of new drugs and shorter treatments in patients with mild liver disease, the subject of discussion and recommendations could become the evaluation of early HCV viral kinetics after the onset of treatment to decide in every patient when to stop antivirals.

PMID: 29451520 [PubMed - in process]

Reply to "Adequate portal vein flow after liver transplantation".

Sat, 02/17/2018 - 13:45
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Reply to "Adequate portal vein flow after liver transplantation".

Liver Transpl. 2018 Feb 16;:

Authors: Kim PTW, Klintmalm GB

PMID: 29451349 [PubMed - as supplied by publisher]

Methodological issues in constructing intention-to-treat transplant benefit models.

Sat, 02/17/2018 - 13:45
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Methodological issues in constructing intention-to-treat transplant benefit models.

Hepatology. 2018 Feb 16;:

Authors: Lai Q, Vitale A

PMID: 29451324 [PubMed - as supplied by publisher]

The long-term outcomes of cirrhotic patients with pleural effusion.

Sat, 02/17/2018 - 13:45
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The long-term outcomes of cirrhotic patients with pleural effusion.

Saudi J Gastroenterol. 2018 Jan-Feb;24(1):46-51

Authors: Hung TH, Tseng CW, Tsai CC, Tsai CC, Tseng KC, Hsieh YH

Abstract
Background/Aim: A pleural effusion is an abnormal collection of fluid in the pleural space and may cause related morbidity or mortality in cirrhotic patients. Currently, there are insufficient data to support the long-term prognosis for cirrhotic patients with pleural effusion. In this study, we investigated the short- and long-term effects of pleural effusion on mortality in cirrhotic patients and evaluated the benefit of liver transplantation in these patients.
Patients and Methods: The National Health Insurance Database, derived from the Taiwan National Health Insurance Program, was used to identify 3,487 cirrhotic patients with pleural effusion requiring drainage between January 1, 2007 and December 31, 2010. The proportional hazards Cox regression model was used to control for possible confounding factors.
Results: The 30-day, 90-day, 1-year, and 3-year mortalities were 20.1%, 40.2%, 59.1%, and 75.9%, respectively, in the cirrhotic patients with pleural effusion. After Cox proportional hazard regression analysis adjusted by patient gender, age, complications of cirrhosis and comorbid disorders, old age, esophageal variceal bleeding, hepatocellular carcinoma, hepatic encephalopathy, pneumonia, renal function impairment, and without liver transplantation conferred higher risks for 3-year mortality in the cirrhotic patients with pleura effusion. Liver transplantation is the most important factor to determine the 3-year mortalities (HR: 0.17, 95% CI 0.11- 0.26, P < 0.001). The 30-day, 30 to 90-day, 90-day to 1-year, and 1 to 3-year mortalities were 5.7%, 13.4%, 20.4%, and 21.7% respectively, in the liver transplantation group, and 20.5%, 41.0%, 61.2%, and 77.5%, respectively, in the non-liver transplantation group.
Conclusion: In cirrhotic patients, the presence of pleural effusion predicts poor long-term outcomes. Liver transplantation could dramatically improve the survival and should be suggested as soon as possible.

PMID: 29451184 [PubMed - in process]

Exosomal MicroRNA-10a Is Associated with Liver Regeneration in Rats through Downregulation of EphA4.

Sat, 02/17/2018 - 13:45
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Exosomal MicroRNA-10a Is Associated with Liver Regeneration in Rats through Downregulation of EphA4.

Chin Med J (Engl). 2018 Feb 20;131(4):454-460

Authors: Luo L, Yu ZP, Qin H, Zhu ZX, Liao MH, Liao HT, Yuan KF, Zeng Y

Abstract
Background: MicroRNAs (miRNAs) have been reported to play vital roles in liver regeneration. Previous studies mainly focused on the functions of intracellular miRNAs, while the functions of circulating exosomal miRNAs in liver regeneration remain largely unknown. The aim of this study was to identify the key exosomal miRNA that played vital roles in liver regeneration.
Methods: The Sprague-Dawley male rats were assigned to 70% partially hepatectomized group (n = 6) and sham surgery group (n = 6). The peripheral blood of both groups was collected 24 h after surgery. The exosomal miRNAs were extracted, and microarray was used to find out the key miRNA implicated in liver regeneration. Adenovirus was used to overexpress the key miRNA in rats, and proliferating cell nuclear antigen (PCNA) staining was applied to study the effect of key miRNA overexpression on liver regeneration. Western blotting was used to validate the predicted target of the key miRNA.
Results: Exosomal miR-10a was upregulated more than nine times in hepatectomized rats. The level of miR-10a was increased in the early phase of liver regeneration, reached the top at 72 h postsurgery, and decreased to perioperative level 168 h after surgery. Moreover, enforced expression of miR-10a by adenovirus facilitated the process of liver regeneration as evidenced by immunohistochemical staining of PCNA. Erythropoietin-producing hepatocellular receptor A4 (EphA4) has been predicted to be a target of miR-10a. The protein level of EphA4 was decreased in the early phase of liver regeneration, reached the bottom at 72 h postsurgery, and rose to perioperative level 168 h after surgery, which was negatively correlated with miR-10a, confirming that EphA4 served as a downstream target of miR-10a. Moreover, inhibition of EphA4 by rhynchophylline could promote the proliferation of hepatocytes by regulating the cell cycle.
Conclusion: Exosomal miR-10a might accelerate liver regeneration through downregulation of EphA4.

PMID: 29451151 [PubMed - in process]

Perioperative Single-Donor Platelet Apheresis and Red Blood Cell Transfusion Impact on 90-Day and Overall Survival in Living Donor Liver Transplantation.

Sat, 02/17/2018 - 13:45
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Perioperative Single-Donor Platelet Apheresis and Red Blood Cell Transfusion Impact on 90-Day and Overall Survival in Living Donor Liver Transplantation.

Chin Med J (Engl). 2018 Feb 20;131(4):426-434

Authors: Zheng W, Zhao KM, Luo LH, Yu Y, Zhu SM

Abstract
Background:: Although many previous studies have confirmed that perioperative blood transfusion is associated with poor outcomes after liver transplantation (LT), few studies described the influence of single-donor platelet apheresis transfusion in living donor LT (LDLT). This study aimed to assess the effect of blood products on outcomes for LDLT recipients, focusing on apheresis platelets.
Methods:: This retrospective study included 126 recipients who underwent their first adult-to-adult LDLT. Twenty-four variables including consumption of blood products of 126 LDLT recipients were assessed for their link to short-term outcomes and overall survival. Kaplan-Meier survival curve and the log-rank test were used for recipient survival analysis. A multivariate Cox proportional-hazard model and a propensity score analysis were applied to adjust confounders after potential risk factors were identified by a univariate Cox analysis.
Results: Patients who received apheresis platelet transfusion had a lower 90-day cumulative survival (78.9% vs. 94.2%, P = 0.009), but had no significant difference in overall survival in the Cox model, compared with those without apheresis platelet transfusion. Units of apheresis platelet transfusion (hazard ratio [HR] = 3.103, 95% confidence interval [CI]: 1.720-5.600, P < 0.001) and preoperative platelet count (HR = 0.170, 95% CI: 0.040-0.730, P = 0.017) impacted 90-day survival independently. Multivariate Cox regression analysis also found that units of red blood cell (RBC) transfusion (HR = 1.036, 95% CI: 1.006-1.067, P = 0.018), recipient's age (HR = 1.045, 95% CI: 1.005-1.086, P = 0.025), and ABO blood group comparison (HR = 2.990, 95% CI: 1.341-6.669, P = 0.007) were independent risk factors for overall survival after LDLT.
Conclusions:: This study suggested that apheresis platelets were only associated with early mortality but had no impact on overall survival in LDLT. Units of RBC, recipient's age, and ABO group comparison were independent predictors of long-term outcomes.

PMID: 29451147 [PubMed - in process]

Hepatocholangiocarcinoma/intrahepatic cholangiocarcinoma: are they contraindication or indication for liver transplantation? A propensity score-matched analysis.

Sat, 02/17/2018 - 13:45
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Hepatocholangiocarcinoma/intrahepatic cholangiocarcinoma: are they contraindication or indication for liver transplantation? A propensity score-matched analysis.

Hepatol Int. 2018 Feb 15;:

Authors: Ma KW, Chok KSH, She WH, Cheung TT, Chan ACY, Dai WC, Fung JYY, Lo CM

Abstract
BACKGROUND: Uncommon primary hepatic malignancies such as intrahepatic cholangiocarcinoma (ICC) and hepatocholangiocarcinoma (HCC-CC) were generally considered contraindications for liver transplantation(LT), and studies comparing the efficacy of LT and resection (LR) for ICC/HCC-CC were scarce.
OBJECTIVE: To compare the survival outcomes of ICC/HCC-CC patients treated by LT and LR in a propensity score-matched population.
METHOD: This is a retrospective study from 1995 to 2015. Consecutive patients with the pathological diagnosis of ICC or HCC-CC in the surgical specimens were included. All patients had either hepatectomy or LT with curative intent. Factors associated with survival were identified with multivariate analysis using cox-regression model. Propensity score-matched analysis was performed.
RESULT: There were 181 patients diagnosed to have ICC/HCC_CC. Nine patients received LT (all with incidental ICC/HCC-CC) and 172 received hepatectomy. The median follow-up period was 27.5 months. The median age was 60 years (range 3-86); Hepatitis B and C carrier status was found in 48.1 and 2.3% of the patients, respectively. The median tumor size was 6 cm and 71.3% of them had solitary tumor. Microvascular invasion was present in 47% of the patients. After propensity score matching, there were 54 (9 in LT and 45 in LR group) patients for analysis. Cox-regression analysis showed that early AJCC (7th) staging and LT were the independent factors associated with overall survival. Patients in the LT group had significantly better overall survival (5-year OS 77.8 vs 36.6%, log-rank p = 0.013).
CONCLUSION: ICC/HCC-CC are uncommon tumors with poor long-term oncological outcomes despite curative hepatectomy. Liver transplantation might be a better treatment option for patients with early ICC/HCC-CC.

PMID: 29450868 [PubMed - as supplied by publisher]

Racial and Socioeconomic Differences in the Use of High-Volume Commission on Cancer-Accredited Hospitals for Cancer Surgery in the United States.

Sat, 02/17/2018 - 13:45
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Racial and Socioeconomic Differences in the Use of High-Volume Commission on Cancer-Accredited Hospitals for Cancer Surgery in the United States.

Ann Surg Oncol. 2018 Feb 15;:

Authors: Wasif N, Etzioni D, Habermann EB, Mathur A, Pockaj BA, Gray RJ, Chang YH

Abstract
BACKGROUND: Although major cancer surgery at a high-volume hospital is associated with lower postoperative mortality, the use of such hospitals may not be equally distributed.
OBJECTIVE: Our aim was to study socioeconomic and racial differences in cancer surgery at Commission on Cancer (CoC)-accredited high-volume hospitals.
METHODS: The National Cancer Database (NCDB) was used to identify patients undergoing surgery for colon, esophageal, liver, and pancreatic cancer from 2003 to 2012. Annual hospital volume for each cancer was categorized using quartiles of patient volume. Patient-level predictors of surgery at a high-volume hospital, trends in the use of a high-volume hospital, and adjusted likelihood of surgery at a high-volume hospital in 2012 versus 2003 were analyzed.
RESULTS: African American patients were less likely to undergo surgery at a high-volume hospital for esophageal (odds ratio [OR] 0.59, 95% confidence interval [CI] 0.49-0.73) and pancreatic cancer (OR 0.83, 95% CI 0.74-0.92), while uninsured patients and those residing in low educational attainment zip codes were less likely to undergo surgery at a high-volume hospital for esophageal, liver, and pancreatic cancer. In 2012, African Americans, uninsured patients, and those from low educational attainment zip codes were no more likely to undergo surgery at a high-volume hospital than in 2003 for any cancer type. These differences were not seen in colon cancer patients, for whom significant regionalization was not seen.
CONCLUSIONS: Differences in the use of CoC-accredited high-volume hospitals for major cancer surgery were seen nationwide and persisted over the duration of the study. Strategies to increase referrals and/or access to high-volume hospitals for African American and socioeconomically disadvantaged patients should be explored.

PMID: 29450752 [PubMed - as supplied by publisher]

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