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Identification of a flavonoid isolated from plum (Prunus domestica) as a potent inhibitor of Hepatitis C virus entry.

Sat, 06/24/2017 - 12:45
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Identification of a flavonoid isolated from plum (Prunus domestica) as a potent inhibitor of Hepatitis C virus entry.

Sci Rep. 2017 Jun 21;7(1):3965

Authors: Bose M, Kamra M, Mullick R, Bhattacharya S, Das S, Karande AA

Abstract
Hepatitis C virus (HCV) infection is a major cause of chronic liver diseases that often requires liver transplantation. The standard therapies are limited by severe side effects, resistance development, high expense and in a substantial proportion of cases, fail to clear the infection which bespeak the need for development of well-tolerated antivirals. Since most of the drug development strategies target the replication stage of viral lifecycle, the identification of entry inhibitors might be crucial especially in case of liver-transplant recipients. In the present study we have evaluated fruits which are known for their hepatoprotective effects in order to screen for entry inhibitors. We report the identification of a flavonoid, rutin, isolated from Prunus domestica as a new HCV entry inhibitor. Characterization and confirmation of the chemical structure was done by LC-ESI-MS, NMR and IR spectral analyses. Rutin significantly inhibited HCV-LP binding to hepatoma cells and inhibited cell-culture derived HCV (HCVcc) entry into hepatoma cells. Importantly, rutin was found to be non-toxic to hepatoma cells. Furthermore, rutin inhibits the early entry stage of HCV lifecycle possibly by directly acting on the viral particle. In conclusion, rutin is a promising candidate for development of anti-HCV therapeutics in the management of HCV infection.

PMID: 28638096 [PubMed - in process]

LincRNA-p21 Inhibits the Wnt/β-Catenin Pathway in Activated Hepatic Stellate Cells via Sponging MicroRNA-17-5p.

Sat, 06/24/2017 - 12:45
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LincRNA-p21 Inhibits the Wnt/β-Catenin Pathway in Activated Hepatic Stellate Cells via Sponging MicroRNA-17-5p.

Cell Physiol Biochem. 2017;41(5):1970-1980

Authors: Yu F, Guo Y, Chen B, Shi L, Dong P, Zhou M, Zheng J

Abstract
BACKGROUND/AIMS: It is known that the activation of hepatic stellate cells (HSCs) is a pivotal step in the initiation and progression of liver fibrosis. Aberrant activated Wnt/β-catenin pathway is known to accelerate the development of liver fibrosis. microRNAs (miRNAs)-mediated Wnt/β-catenin pathway has been reported to be involved in HSC activation during liver fibrosis. However, whether long noncoding RNAs (lncRNAs) regulate Wnt/β-catenin pathway during HSC activation still remains unclear.
METHODS: Long intergenic noncoding RNA-p21 (lincRNA-p21) expression was detected in Salvianolic acid B (Sal B)-treated cells. Effects of lincRNA-p21 knockdown on HSC activation and Wnt/β-catenin pathway activity were analyzed in Sal B-treated cells. In lincRNA-p21-overexpressing cells, effects of miR-17-5p on HSC activation and Wnt/β-catenin pathway activity were examined.
RESULTS: LincRNA-p21 expression was up-regulated in HSCs after Sal B treatment. In primary HSCs, lincRNA-p21 expression was down-regulated at Day 5 relative to Day 2. Sal B-inhibited HSC activation including the reduction of cell proliferation, α-smooth muscle actin (α-SMA) and type I collagen was inhibited by lincRNA-p21 knockdown. Sal B-induced Wnt/β-catenin pathway inactivation was blocked down by loss of lincRNA-p21. Notably, lincRNA-p21, confirmed as a target of miR-17-5p, suppresses miR-17-5p level. Lack of the miR-17-5p binding site in lincRNA-p21 prevents the suppression of miR-17-5p expression. In addition, the suppression of HSC activation and Wnt/β-catenin pathway induced by lincRNA-p21 overexpression was almost inhibited by miR-17-5p.
CONCLUSION: We demonstrate that lincRNA-p21-inhibited Wnt/β-catenin pathway is involved in the effects of Sal B on HSC activation and lincRNA-p21 suppresses HSC activation, at least in part, via miR-17-5p-mediated-Wnt/β-catenin pathway.

PMID: 28391277 [PubMed - indexed for MEDLINE]

Short- and Long-Term Mortality Rates of Elderly Acute Kidney Injury Patients Who Underwent Continuous Renal Replacement Therapy.

Sat, 06/24/2017 - 12:45
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Short- and Long-Term Mortality Rates of Elderly Acute Kidney Injury Patients Who Underwent Continuous Renal Replacement Therapy.

PLoS One. 2016;11(11):e0167067

Authors: Rhee H, Jang KS, Park JM, Kang JS, Hwang NK, Kim IY, Song SH, Seong EY, Lee DW, Lee SB, Kwak IS

Abstract
BACKGROUND: The world's population is aging faster and the incidence of acute kidney injury (AKI) needing continuous renal replacement therapy (CRRT) is increasing in elderly population. The outcome of AKI needing CRRT in elderly patients is known to be poor. However, the definitions of elderly used in the previous literatures were diverse and, there were few data that compared the long-term mortality rates of these patients with middle aged patients. This study was aimed to evaluate this issue.
METHODS: This study was a single-center, retrospective cohort study of patients who underwent CRRT from January 2013 to December 2015. The patients were divided into the following four age cohorts: middle-aged (55-64), young-old (65-74), middle-old (75-84), and old-old (≥85). The short- and long-term mortality rates for each age cohort were compared.
RESULTS: A total of 562 patients met the inclusion criteria. The short-term mortality rate was 57.3% in the entire cohort. Compared with the middle-aged cohort, the middle-old cohort (HR 1.48 (1.09-2.02), p = 0.012) and the old-old cohort (HR 2.33 (1.30-4.19), p = 0.005) showed an increased short-term mortality rate along with an increased SOFA score, acidemia and a prolonged prothrombin time. When we analyzed the long-term mortality rate of the 238 survived patients, the middle-old cohort (HR 3.76 (1.84-7.68), p<0.001), the old-old cohort (HR 4.40(1.20-16.10), p = 0.025), a lower BMI, the presence of liver cirrhosis, the presence of congestive heart failure and a history of sepsis were independent risk factors for the prediction of long-term mortality.
CONCLUSION: Compared with the middle-aged cohort, the middle-old and the old-old cohort showed an increased short-term and long-term mortality rate. However, in the young-old cohort, neither the short-term nor the long-term mortality rate was increased.

PMID: 27875571 [PubMed - indexed for MEDLINE]

Effect of Function-Enhanced Mesenchymal Stem Cells Infected With Decorin-Expressing Adenovirus on Hepatic Fibrosis.

Sat, 06/24/2017 - 12:45
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Effect of Function-Enhanced Mesenchymal Stem Cells Infected With Decorin-Expressing Adenovirus on Hepatic Fibrosis.

Stem Cells Transl Med. 2016 09;5(9):1247-56

Authors: Jang YO, Cho MY, Yun CO, Baik SK, Park KS, Cha SK, Chang SJ, Kim MY, Lim YL, Kwon SO

Abstract
UNLABELLED: : Bone marrow-derived mesenchymal stem cells (BM-MSCs) are known to have an antifibrotic effect and could be used as vehicles for targeted gene delivery. Decorin plays a protective role against fibrogenesis by modulating the degradation of the extracellular matrix. The aim of this study was to determine whether the antifibrotic effect of a combination treatment consisting of BM-MSCs and decorin on hepatic fibrosis is superior to BM-MSCs alone. The effects of BM-MSCs infected with decorin-expressing adenovirus (DCN-MSCs) on hepatic fibrosis were examined in a rat model of thioacetamide (TAA)-induced cirrhosis. The effects of infection with decorin-expressing adenovirus and of incubation with the conditioned medium of DCN-MSCs on transforming growth factor-β (TGF-β) signaling were analyzed in immortalized human hepatic stellate cells (HSCs). According to the Laennec fibrosis scoring system, cirrhotic livers from rats treated with DCN-MSCs exhibited histological improvement compared with cirrhotic livers from rats treated with control adenovirus-infected MSCs (CA-MSCs). DCN-MSC treatment reduced hepatic collagen distribution, lowered the hydroxyproline content, and rescued liver function impairment in rats with TAA-induced cirrhosis. These protective effects were more potent with DCN-MSCs than with CA-MSCs. The upregulation of collagen-1, α-smooth muscle actin (α-SMA), TGF-β1, and Smad3 phosphorylation in cirrhotic livers was prevented by DCN-MSC administration. Intriguingly, medium from cultured DCN-MSCs blocked both Smad3 phosphorylation and exogenous TGF-β1 stimulated α-SMA synthesis in HSCs. DCN-MSCs exert strong protective effects against hepatic fibrosis by suppressing TGF-β/Smad signaling. Thus, treatment with DCN-MSCs is a potentially novel and efficient therapeutic approach for patients with intractable cirrhosis.
SIGNIFICANCE: A combination treatment consisting of bone marrow-derived mesenchymal stem cells (BM-MSCs) and decorin strongly inhibited the progression of thioacetamide-induced hepatic fibrosis in rats, compared with BM-MSCs alone. Furthermore, the significant inhibitory effect of BM-MSCs infected with decorin-expressing adenovirus was attributed to suppressing transforming growth factor-β (TGF-β)/Smad signaling pathway, supported by attenuation of TGF-β1 expression and inhibition of Smad3 phosphorylation. Therefore, treatment with BM-MSCs infected with decorin-expressing adenovirus could constitute a novel and efficient therapeutic approach for patients with intractable cirrhosis.

PMID: 27365486 [PubMed - indexed for MEDLINE]

Long-Term Effects of Bone Marrow-Derived Mesenchymal Stem Cells in Dextran Sulfate Sodium-Induced Murine Chronic Colitis.

Sat, 06/24/2017 - 12:45
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Long-Term Effects of Bone Marrow-Derived Mesenchymal Stem Cells in Dextran Sulfate Sodium-Induced Murine Chronic Colitis.

Gut Liver. 2016 May 23;10(3):412-9

Authors: Lee HJ, Oh SH, Jang HW, Kwon JH, Lee KJ, Kim CH, Park SJ, Hong SP, Cheon JH, Kim TI, Kim WH

Abstract
BACKGROUND/AIMS: Bone marrow-derived mesenchymal stem cells (BM-MSCs) have shown beneficial effects in experimental colitis models, but the underlying mechanisms are not fully understood. We investigated the long-term effects of BM-MSCs, particularly in mice with chronic colitis.
METHODS: Chronic colitis was induced by administering 3% dextran sulfate sodium (DSS) in a series of three cycles. BMMSCs were injected intravenously into DSS-treated mice three times during the first cycle. On day 33, the therapeutic effects were evaluated with clinicopathologic profiles and histological scoring. Inflammatory mediators were measured with real-time polymerase chain reaction.
RESULTS: Systemic infusion of BM-MSCs ameliorated the severity of colitis, and body weight restoration was significantly promoted in the BMMSC- treated mice. In addition, BM-MSC treatment showed a sustained beneficial effect throughout the three cycles. Microscopic examination revealed that the mice treated with BM-MSCs had fewer inflammatory infiltrates, a lesser extent of inflammation, and less crypt structure damage compared with mice with DSS-induced colitis. Anti-inflammatory cytokine levels of interleukin-10 were significantly increased in the inflamed colons of BM-MSC-treated mice compared with DSS-induced colitis mice.
CONCLUSIONS: Systemic infusion of BM-MSCs at the onset of disease exerted preventive and rapid recovery effects, with long-term immunosuppressive action in mice with repeated DSS-induced chronic colitis.

PMID: 27114436 [PubMed - indexed for MEDLINE]

Therapeutic advances for primary biliary cholangitis: the old and the new.

Sat, 06/24/2017 - 12:45
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Therapeutic advances for primary biliary cholangitis: the old and the new.

Eur J Gastroenterol Hepatol. 2016 Jun;28(6):615-21

Authors: Wang L, Zhang FC, Zhang X

Abstract
Primary biliary cholangitis (PBC, primary biliary cirrhosis) is an autoimmune cholestatic liver disease characterized by chronic nonsuppurative destructive cholangitis and the presence of serum antimitochondrial antibodies. Ursodeoxycholic acid is the only drug approved by the US Food and Drug Administration to treat PBC. However, one-third of patients show incomplete responses to ursodeoxycholic acid and a poor prognosis. A number of old and new medications have been used in these patients, such as fibrates, glucocorticoids, immunosuppressants, obeticholic acid, mesenchymal stem cells, biological agents (anti-interleukin-12, cytotoxic T-lymphocyte antigen 4 immunoglobulin, anti-CD20), and antifibrotic drugs. This article reviews the therapeutic advances of these old and new medications in patients with PBC.

PMID: 26862931 [PubMed - indexed for MEDLINE]

Impact of insurance status on the survival of gallbladder cancer patients.

Thu, 06/22/2017 - 12:45
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Impact of insurance status on the survival of gallbladder cancer patients.

Oncotarget. 2017 Jun 06;:

Authors: Chen Z, Gao W, Pu L, Zhang L, Han G, Zhu Q, Li X, Wu J, Wang X

Abstract
The prognostic significance of insurance status has been investigated in many types of malignancies, however, its impact on gallbladder cancer is yet not known. The purpose of this study was to determine the relationship between insurance status and gallbladder cancer survival. We searched the Surveillance, Epidemiology, and End Results dataset, and identified 1,729 gallbladder cancer cases. Kaplan-Meier methods and multivariable Cox regression models were used to analyze survival outcomes and risk factors. We found that individuals who had non-Medicaid insurance were more likely to be male, older, from wealthier area, and better-educated. Insurance status was confirmed as an independent prognostic factor for gallbladder cancer patients. Stratified analysis revealed that the uninsured status independently predicted unfavorable survival outcome at localized tumor stage and in white individuals. To conclude, insurance status is an important predictive factor for gallbladder cancer, and uninsured individuals are at the highest risk of death.

PMID: 28636999 [PubMed - as supplied by publisher]

Analysis of Survival After Initiation of Continuous Renal Replacement Therapy in a Surgical Intensive Care Unit.

Thu, 06/22/2017 - 12:45
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Analysis of Survival After Initiation of Continuous Renal Replacement Therapy in a Surgical Intensive Care Unit.

JAMA Surg. 2017 Jun 21;:

Authors: Tatum JM, Barmparas G, Ko A, Dhillon N, Smith E, Margulies DR, Ley EJ

Abstract
Importance: Continuous renal replacement therapy (CRRT) benefits patients with renal failure who are too hemodynamically unstable for intermittent hemodialysis. The duration of therapy beyond which continued use is futile, particularly in a population of patients admitted to and primarily cared for by a surgical service (hereinafter referred to as surgical patients), is unclear.
Objective: To analyze proportions of and independent risk factors for survival to discharge after initiation of CRRT among patients in a surgical intensive care unit (SICU).
Design, Setting, and Participants: This retrospective cohort study included all patients undergoing CRRT from July 1, 2012, through January 31, 2016, in an SICU of an urban tertiary medical center. The population included patients treated before or after general surgery and patients admitted to a surgical service during inpatient evaluation and care before liver transplant. The pretransplant population was censored from further survival analysis on receipt of a transplant.
Exposures: Continuous renal replacement therapy.
Main Outcomes and Measures: Hospital mortality among patients in an SICU after initiation of CRRT.
Results: Of 108 patients (64 men [59.3%] and 44 women [40.7%]; mean [SD] age, 62.0 [12.7] years) admitted to the SICU, 53 were in the general surgical group and 55 in the pretransplant group. Thirteen of the 22 patients in the pretransplant group who required 7 or more days of CRRT died (in-hospital mortality, 59.1%); among the 12 patients in the general surgery group who required 7 or more days of CRRT, 12 died (in-hospital mortality, 100%). In the general surgical group, each day of CRRT was associated with an increased adjusted odds ratio of death of 1.39 (95% CI, 1.01-1.90; P = .04).
Conclusions and Relevance: Continuous renal replacement therapy is valuable for surgical patients with an acute and correctable indication; however, survival decreases significantly with increasing duration of CRRT. Duration of CRRT does not correlate with survival among patients awaiting liver transplant.

PMID: 28636702 [PubMed - as supplied by publisher]

Exosome-encapsulated microRNAs as circulating biomarkers for colorectal cancer.

Thu, 06/22/2017 - 12:45
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Exosome-encapsulated microRNAs as circulating biomarkers for colorectal cancer.

Oncotarget. 2017 Jun 16;:

Authors: Yan S, Han B, Gao S, Wang X, Wang Z, Wang F, Zhang J, Xu D, Sun B

Abstract
Currently available studies have suggested that a number of exosome-encapsulated microRNAs (miRNAs) are recognized as stable biomarkers for cancers. However, little is known about the effect of exosomal miRNAs on colorectal cancer (CRC). The aim of study is to identify specific miRNAs in serum exosomes, which may serve as potential diagnostic and prognostic biomarkers and therapeutic targets for CRC. Microarray analyses of miRNAs in serum exosomes from 3 primary CRC patients and 3 healthy controls were performed. Those differentially expressed exosome-encapsulated miRNAs were verified in exosome-enriched serum samples from 77 CRC patients and 20 healthy controls by quantitative real-time PCR (qRT-PCR). A total of 39 aberrantly expressed miRNAs in serum exosomes were identified by microarray analysis. After confirmation by qRT-PCR, we found that 5 exosome-encapsulated miRNAs (miR-638, miR-5787, miR-8075, miR-6869-5p and miR-548c-5p) were significantly down-regulated, while 2 exosome-encapsulated miRNAs (miR-486-5p and miR-3180-5p) were significantly up-regulated in serum. Decreased levels of miR-638 in serum exosomes were associated with increased risk of liver metastasis and later TNM stage of CRC. Networks analyses revealed that 5 aberrantly expressed miRNAs (miR-638, miR-5787, miR-8075, miR-6869-5p, and miR-548c-5p) might be involved in the process of glucose metabolism in CRC. The present study shows the specific serum profile of exosome-encapsulated miRNAs in CRC. Those specific miRNAs in serum exosomes may serve as disease biomarkers and novel therapeutic targets for CRC.

PMID: 28636562 [PubMed - as supplied by publisher]

Resolution of Donor Non-Alcoholic Fatty Liver Disease Following Liver Transplantation.

Thu, 06/22/2017 - 12:45
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Resolution of Donor Non-Alcoholic Fatty Liver Disease Following Liver Transplantation.

Clin Transplant. 2017 Jun 21;:

Authors: Posner AD, Sultan ST, Zaghloul NA, Twaddell WS, Bruno DA, Hanish SI, Hutson WR, Hebert L, Barth RN, LaMattina JC

Abstract
INTRODUCTION: Transplant surgeons conventionally select against livers displaying high degrees (>30%) of macrosteatosis (MaS), out of concern for primary non-function or severe graft dysfunction. As such, there is relatively limited experience with such livers, and the natural history remains incompletely characterized. We present our experience of transplanted livers with high degrees of MaS and microsteatosis (MiS), with a focus on the histopathologic and clinical outcomes.
METHODS: 29 cases were identified with liver biopsies available from both the donor and the corresponding liver transplant recipient. Donor liver biopsies displayed either MaS or MiS ≥ 15%, while all recipients received postoperative liver biopsies for cause.
RESULTS: The mean donor MaS and MiS were 15.6% (range 0-60%) and 41.3% (7.5-97.5%) respectively. MaS decreased significantly from donor (M=15.6%) to recipient postoperative biopsies (M=0.86%), p < 0.001. Similarly, MiS decreased significantly from donor biopsies (M=41.3%) to recipient postoperative biopsies (M=1.8%), p < 0.001. At a median of 68 days postoperatively (range 4-384), full resolution of MaS and MiS was observed in 27/29 recipients.
CONCLUSIONS: High degrees of MaS and MiS in donor livers resolve in recipients following liver transplantation. Further insight into the mechanisms responsible could translate to therapeutic targets for treating fatty liver diseases. This article is protected by copyright. All rights reserved.

PMID: 28636211 [PubMed - as supplied by publisher]

The Application of Heptamethine Cyanine Dye DZ-1 and Indocyanine Green for Imaging and Targeting in Xenograft Models of Hepatocellular Carcinoma.

Thu, 06/22/2017 - 12:45
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The Application of Heptamethine Cyanine Dye DZ-1 and Indocyanine Green for Imaging and Targeting in Xenograft Models of Hepatocellular Carcinoma.

Int J Mol Sci. 2017 Jun 21;18(6):

Authors: Zhang C, Zhao Y, Zhang H, Chen X, Zhao N, Tan D, Zhang H, Shi C

Abstract
Near infrared fluorescence (NIRF) imaging has strong potential for widespread use in noninvasive tumor imaging. Indocyanine green (ICG) is the only Food and Drug Administration (FDA) -approved NIRF dye for clinical diagnosis; however, it is unstable and poorly targets tumors. DZ-1 is a novel heptamethine cyanine NIRF dye, suitable for imaging and tumor targeting. Here, we compared the fluorescence intensity and metabolism of DZ-1 and ICG. Additionally, we assayed their specificities and abilities to target tumor cells, using cultured hepatocellular carcinoma (HCC) cell lines, a nude mouse subcutaneous xenograft model of liver cancer, and a rabbit orthotopic transplantation model. We found that DZ-1 accumulates in tumor tissue and specifically recognizes HCC in subcutaneous and orthotopic models. The NIRF intensity of DZ-1 was one order of magnitude stronger than that of ICG, and DZ-1 showed excellent intraoperative tumor targeting in the rabbit model. Importantly, ICG accumulated at tumor sites, as well as in the liver and kidney. Furthermore, DZ-1 analog-gemcitabine conjugate (NIRG) exhibited similar tumor-specific targeting and imaging properties, including inhibition of tumor growth, in HCC patient-derived xenograft (PDX) mice. DZ-1 and NIRG demonstrated superior tumor-targeting specificity, compared to ICG. We show that DZ-1 is an effective molecular probe for specific imaging, targeting, and therapy in HCC.

PMID: 28635650 [PubMed - in process]

Simultaneous ABO-incompatible living-donor liver transplantation and splenectomy without plasma exchange in China: Two case reports.

Thu, 06/22/2017 - 12:45
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Simultaneous ABO-incompatible living-donor liver transplantation and splenectomy without plasma exchange in China: Two case reports.

J Int Med Res. 2017 Jan 01;:300060517710407

Authors: Chen G, Sun J, Wei S, Chen Y, Tang G, Xie Z, Xu H, Chen J, Zhao H, Yuan Z, Wang W, Liu G, Wang B, Niu B

Abstract
ABO-incompatible (ABO-i) living-donor liver transplantation (LDLT) is performed if an ABO-compatible graft cannot be obtained. However, a perfect desensitization protocol has not been established worldwide, especially for simultaneous ABO-i LDLT and splenectomy. We herein report two cases of ABO-i LDLT. To the best of our knowledge, this is the first case report of ABO-i LDLT in an adult patient in China. Splenectomy and T-cell-targeted immunosuppression (basiliximab) was used to overcome the blood group barrier in these recipients. The patients had good graft function without signs of antibody-mediated rejection throughout the 12-month follow-up. Thus, ABO-i LDLT with splenectomy is undoubtedly life-saving when an ABO-compatible graft cannot be obtained for patients in critical condition.

PMID: 28635356 [PubMed - as supplied by publisher]

HBV reactivation after HCV eradication: Deja Vu.

Thu, 06/22/2017 - 12:45
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HBV reactivation after HCV eradication: Deja Vu.

Liver Int. 2017 Jul;37(7):1088

Authors: Reau N, Nelson DR

PMID: 28635166 [PubMed - in process]

Maternal coping with the prospect of liver transplant among their school-age children.

Thu, 06/22/2017 - 12:45
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Maternal coping with the prospect of liver transplant among their school-age children.

Int J Nurs Pract. 2017 Jun;23 Suppl 1:

Authors: Hiratsuka K, Nakamura N, Sato N

Abstract
The purpose of the current study was to describe the following: maternal coping with the prospect of becoming the living-donor liver transplant for their child; the daily lives of school-age children surviving biliary atresia with their native liver; and to explore the relationship between these individuals. Semistructured interviews were conducted with 6 school-age children surviving biliary atresia with their native liver and their mothers. The interviews were conducted from June to August 2014, and a qualitative content analysis was used. Results showed that mothers realized a possible need for transplantation in the future, which contributes to emotional and practical uncertainties. The mothers coexisted with this uncertainty and preferred to use a buffering strategy. In contrast, the children did not consider their illness and future and did not adhere to a therapeutic regimen. It is suggested that living with uncertainty about the health and survival of their children is advantageous for mothers. However, problems related to the psychosocial aspect and child's adherence may occur in the future. In addition, problem-solving coping strategies for mothers and the independence of chronically ill children with liver disease should be promoted.

PMID: 28635067 [PubMed - in process]

Liver transplantation for hepatocellular carcinoma.

Thu, 06/22/2017 - 12:45
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Liver transplantation for hepatocellular carcinoma.

Abdom Radiol (NY). 2017 Jun 20;:

Authors: Berumen J, Hemming A

Abstract
Over the last several years, liver transplantation has evolved to become a widely used treatment for hepatocellular carcinoma (HCC). The criteria used were developed in order to have acceptable outcomes for transplant with survival similar to other indications for transplant. These criteria are discussed in detail along with alternate options, including surgical resection and downstaging of HCC in cirrhotics. Technical considerations of liver transplantation must be considered, and living donor liver transplant is a possibility for treatment.

PMID: 28634617 [PubMed - as supplied by publisher]

Transarterial chemoembolization using 40 µm drug eluting beads for hepatocellular carcinoma.

Thu, 06/22/2017 - 12:45
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Transarterial chemoembolization using 40 µm drug eluting beads for hepatocellular carcinoma.

World J Radiol. 2017 May 28;9(5):245-252

Authors: Greco G, Cascella T, Facciorusso A, Nani R, Lanocita R, Morosi C, Vaiani M, Calareso G, Greco FG, Ragnanese A, Bongini MA, Marchianò AV, Mazzaferro V, Spreafico C

Abstract
AIM: To assess the safety and efficacy of transarterial chemoembolization (TACE) of hepatocellular carcinoma (HCC) using a new generation of 40 μm drug eluting beads in patients not eligible for curative treatment.
METHODS: Drug eluting bead TACE (DEB-TACE) using a new generation of microspheres (embozene tandem, 40 μm) preloaded with 100 mg of doxorubicin was performed on 48 early or intermediate HCC patients with compensated cirrhosis. Response to therapy was assessed with Response Evaluation Criteria in Solid Tumors (RECIST) and modified RECIST (mRECIST) guidelines applied to computed tomography or magnetic resonance imaging. Eleven out of the 48 treated patients treated progressed on to receive liver orthotopic transplantation (OLT). This allowed for histological analysis on the treated explanted nodules.
RESULTS: DEB-TACE with 40 μm showed a good safety profile without major complications or 30-d mortality. The objective response rate of treated tumors was 72.6% and 26.7% according to mRECIST and RECIST respectively. Histological examination in 11 patients assigned to OLT showed a necrosis degree > 90% in 78.6% of cases. The overall time to progression was 13 mo (11-21).
CONCLUSION: DEB-TACE with 40 μm particles is an effective treatment for the treatment of HCC in early-intermediate patients (Barcelona Clinic Liver Cancer stage A/B) with a good safety profile and good results in term of objective response rate and necrosis.

PMID: 28634515 [PubMed - in process]

Interrelations between 3-hydroxypropionate and propionate metabolism in rat liver: Relevance to disorders of propionyl-CoA metabolism.

Thu, 06/22/2017 - 12:45
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Interrelations between 3-hydroxypropionate and propionate metabolism in rat liver: Relevance to disorders of propionyl-CoA metabolism.

Am J Physiol Endocrinol Metab. 2017 Jun 20;:ajpendo.00105.2017

Authors: Wilson KA, Han Y, Zhang M, Hess J, Chapman KA, Cline GW, Tochtrop GP, Brunengraber H, Zhang GF

Abstract
Propionate, 3-hydroxypropionate (3HP), methylcitrate, related compounds and ammonium accumulate in body fluids of patients with disorders of propionyl-CoA metabolism, such as propionic acidemia. Although liver transplantation alleviates hyperammonemia, high concentrations of propionate, 3HP and methylcitrate persist in body fluids. We hypothesized that conserved metabolic perturbations occurring in transplanted patients result from the simultaneous presence of propionate and 3HP in body fluids. We investigated the interrelations of propionate and 3HP metabolism in perfused livers from normal rats using metabolomic and stable isotopic technologies. In the presence of propionate, 3HP or both, we observed the following metabolic perturbations. First, the citric acid cycle (CAC) is overloaded, but does not provide sufficient reducing equivalents to the respiratory chain to maintain the homeostasis of adenine nucleotides. Second, there is major CoA trapping in the propionyl-CoA pathway, and a tripling of liver total CoA within 1 hr. Third, liver proteolysis is stimulated. Fourth, propionate inhibits the conversion of 3HP to acetyl-CoA and its oxidation in the CAC. Fifth, some propionate and some 3HP are converted to nephrotoxic maleate by different processes. Our data have implication for the clinical management of propionic acidemia. They also emphasize the perturbations of liver intermediary metabolism induced by supraphysiological i.e., mM concentrations of labeled propionate used to trace intermediary metabolism, in particular inhibition of CAC flux and major decreases in the [ATP]/[ADP] and [ATP]/[AMP] ratios.

PMID: 28634175 [PubMed - as supplied by publisher]

Comparison of Patterns and Outcomes of Liver Resection for Hepatocellular Carcinoma: East versus West.

Thu, 06/22/2017 - 12:45
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Comparison of Patterns and Outcomes of Liver Resection for Hepatocellular Carcinoma: East versus West.

Clin Gastroenterol Hepatol. 2017 Jun 17;:

Authors: Yang T, Tabrizian P, Zhang H, Lau WY, Han J, Li ZL, Wang Z, Wu MC, Florman S, Schwartz ME, Shen F

PMID: 28634137 [PubMed - as supplied by publisher]

Cost-Effectiveness of Pre versus Post Liver Transplant Hepatitis C Treatment with Direct-Acting Antivirals.

Thu, 06/22/2017 - 12:45
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Cost-Effectiveness of Pre versus Post Liver Transplant Hepatitis C Treatment with Direct-Acting Antivirals.

Clin Gastroenterol Hepatol. 2017 Jun 17;:

Authors: Samur S, Kues B, Ayer T, Roberts MS, Kanwal F, Hur C, Donnell DMS, Chung RT, Chhatwal J

Abstract
BACKGROUND & AIMS: Oral direct-acting antivirals (DAAs) for hepatitis C virus (HCV) treatment offer new hope to both pre- and post-liver transplant (LT) patients. However, whether to treat HCV patients pre- versus post-LT is not clear, as treatment can improve liver function but could reduce the chance of receiving a LT while on the waiting list. Our objective was to evaluate the cost-effectiveness of pre-LT versus post-LT HCV treatment with oral DAAs in decompensated cirrhotic patients on the LT waiting list.
METHODS: We used a validated mathematical model that simulated a virtual trial comparing long-term clinical and cost outcomes of pre-LT versus post-LT HCV treatment with oral DAAs. Model parameters were estimated from United Network for Organ Sharing (UNOS) data, SOLAR-1 and 2 trials, and published studies. For each strategy, we estimated the quality-adjusted life year (QALY), life expectancy, cost, and the incremental cost-effectiveness ratio.
RESULTS: For lower MELD scores, QALYs were higher with pre-LT HCV treatment compared to post-LT treatment. Pre-LT HCV treatment was cost-saving in patients with MELD ≤15, and cost-effective in patients with MELD 16-21. In contrast, post-LT HCV treatment was cost-effective in patients with MELD 22-29 and cost-saving if MELD ≥30. Results varied by drug prices and by UNOS regions.
CONCLUSIONS: For cirrhotic patients awaiting LT, pre-LT HCV treatment with DAAs is cost-effective/saving in patients with MELD≤21, whereas post-LT HCV treatment is cost-effective/saving in patients with MELD≥22.

PMID: 28634131 [PubMed - as supplied by publisher]

Risk factors for pulmonary complications after hepatic resection: role of intraoperative hemodynamic instability and hepatic ischemia.

Thu, 06/22/2017 - 12:45
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Risk factors for pulmonary complications after hepatic resection: role of intraoperative hemodynamic instability and hepatic ischemia.

BMC Anesthesiol. 2017 Jun 20;17(1):84

Authors: Lepere V, Vanier A, Loncar Y, Lemoine L, Vaillant JC, Monsel A, Savier E, Coriat P, Eyraud D

Abstract
BACKGROUND: Postoperative operative pulmonary complications (PPCs) after hepatic surgery are associated with increased length of hospital stays. Intraoperative blood transfusion, extensive resection and different comorbidities have been identified. Other parameters, like time of hepatic ischemia, have neither been clinically studied, though experimental studies show that hepatic ischemia can provide lung injury. The objective of this study was to determinate the risk factors of postoperative pulmonary complications (PPCs) after hepatic resection within 7 postoperative days.
METHOD: Ninety-four patients consecutively who underwent elective hepatectomy between January and December 2013. Demographic data, pathological variables, and preoperative, intraoperative, and postoperative variables had been prospectively collected in a data base. The dependant variables studied were the occurrence of PPCs, defined before analysis of the data.
RESULTS: PPCs occurred in 32 (34%) patients. A multivariate analysis allowed identifying the risk factors for PPCs. On multivariate analysis, preoperative gamma-glutamyltransferase (GGT) elevation OR =5,12 [1,85-15,69] p = 0,002, liver ischemia duration OR = 1,03 [1,01-1,06] p = 0,01 and the intraoperative use of vasopressor OR = 4,40 [1,58-13,36] p = 0,006 were independently associated with PPCs. For every 10 min added in ischemia duration, the OR of the risk of PPCs was estimated to be 1.37 (CI95% = [1.08-1.81], p = 0.01).
CONCLUSION: Three risk factors for PPCs have been identified in a population undergoing liver resection: preoperative GGT elevation, ischemia duration and the intraoperative use of vasopressor. PPCs after liver surgery could be related to lung injury induced by liver ischemia reperfusion and not solely by direct infectious process. That could explain why factors influencing directly or indirectly liver ischemia were independently associated with PPCs.

PMID: 28633644 [PubMed - in process]

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