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The role of the kidney in combined liver-kidney transplantation.

Sun, 12/10/2017 - 13:45

The role of the kidney in combined liver-kidney transplantation.

Liver Transpl. 2017 Dec 09;:

Authors: Formica RN

PMID: 29222928 [PubMed - as supplied by publisher]

Survival of children after liver transplantation for hepatocellular carcinoma.

Sun, 12/10/2017 - 13:45

Survival of children after liver transplantation for hepatocellular carcinoma.

Liver Transpl. 2017 Dec 09;:

Authors: Baumann U, Adam R, Duvoux C, Mikolajczyk R, Karam V, D'Antiga L, Chardot C, Coker A, Colledan M, Erizon BG, Line PD, Hadzic N, Isoniemi H, Klempnauer JL, Reding R, McKiernan PJ, McLin V, Paul A, Salizzoni M, Furtado ESB, Schneeberger S, Karch A

Abstract
Hepatocellular carcinoma (HCC) in childhood differs from adult HCC as it is often associated with inherited liver disease. It is, however, unclear whether liver transplantation (LT) for HCC in childhood with or without associated inherited disease has a comparable outcome to adult HCC. Based on data from the European Liver Transplant Registry (ELTR) we aimed to investigate if there are differences in patient and graft survival after LT for HCC between children and adults and between patients with underlying inherited versus non inherited liver disease respectively. We included all 175 children who underwent LT for HCC and were enrolled in ELTR between 1985 and 2012; of these, 38 had an associated inherited liver disease. Adult HCC patients with (n=79) and without (n=316, matched by age, sex and LT date) inherited liver disease served as an adult comparison population. We used multivariable piecewise Cox regression models with shared frailty terms (for LT center) to compare patient and graft survival between the different HCC groups. Survival analyses demonstrated a superior long-term survival of children with inherited liver disease when compared to children with HCC without inherited liver disease (HR:0.29; 95%CI:0.10-0.90; p=0.03) and adults with HCC with inherited liver disease (HR:0.27; 95%CI:0.06-1.25;p=0.09). There was no survival difference between adults with and without inherited disease (HR:1.05; 95%CI:0.66-1.66; p=0.84).
CONCLUSION: The potential survival advantage of children with an HCC based on inherited disease should be acknowledged when considering transplantation and prioritization for these patients. Further prospective studies accounting for tumor size and extension at LT are necessary to fully interpret our findings. This article is protected by copyright. All rights reserved.

PMID: 29222922 [PubMed - as supplied by publisher]

Transplanting HCV-positive livers into HCV-negative patients with preemptive antiviral treatment: A modeling study.

Sun, 12/10/2017 - 13:45

Transplanting HCV-positive livers into HCV-negative patients with preemptive antiviral treatment: A modeling study.

Hepatology. 2017 Dec 09;:

Authors: Chhatwal J, Samur S, Bethea ED, Ayer T, Kanwal F, Hur C, Roberts MS, Terrault N, Chung RT

Abstract
Under current guidelines hepatitis C virus (HCV)-positive livers are not transplanted into HCV-negative recipients because of adverse post-transplant outcomes associated with allograft HCV infection. However, HCV can now be cured post liver transplant (LT) using direct-acting antivirals (DAAs) with >90% success; therefore, HCV-negative patients on the liver transplant (LT) waiting list may benefit from accepting HCV-positive organs with preemptive treatment. Our objective was to evaluate if and in which HCV-negative patients the potential benefit of accepting an HCV-positive (i.e., viremic) organ outweighed the risks associated with HCV allograft infection. We developed a Markov-based mathematical model that simulated a virtual trial of HCV-negative patients on the LT waiting list to compare long-term outcomes in patients: 1) willing to accept any (HCV-negative or HCV-positive) liver versus 2) those willing to accept only HCV-negative livers. Patients receiving HCV-positive livers were treated preemptively with 12 weeks of DAA therapy and had a higher risk of graft failure than those receiving HCV-negative livers. The model incorporated data from published studies and the United Network for Organ Sharing (UNOS). We found that accepting any liver regardless of HCV status versus accepting only HCV-negative livers resulted in an increase in life expectancy when MELD was ≥ 20, and the benefit was highest at MELD 28 (0.172 additional life years). The magnitude of clinical benefit was greater in UNOS regions with higher HCV-positive donor organ rates, i.e. Regions 1, 2, 3, 10, and 11. Sensitivity analysis demonstrated that model outcomes were robust.
CONCLUSIONS: Transplanting HCV-positive livers into HCV-negative patients with preemptive DAA therapy could improve patient survival on the LT waiting list. Our analysis can help inform clinical trials and minimize patient harm. This article is protected by copyright. All rights reserved.

PMID: 29222916 [PubMed - as supplied by publisher]

Current and Future Therapeutic Regimens for Non-alcoholic Fatty Liver Disease (NAFLD) and Non-alcoholic Steatohepatitis (NASH).

Sun, 12/10/2017 - 13:45

Current and Future Therapeutic Regimens for Non-alcoholic Fatty Liver Disease (NAFLD) and Non-alcoholic Steatohepatitis (NASH).

Hepatology. 2017 Dec 09;:

Authors: Younossi ZM, Loomba R, Rinella ME, Bugianesi E, Marchesini G, Neuschwander-Tetri BA, Serfaty L, Negro F, Caldwell SH, Ratziu V, Corey KE, Friedman SL, Abdelmalek MF, Harrison SA, Sanyal AJ, Lavine JE, Mathurin P, Charlton MR, Chalasani NP, Anstee QM, Kowdley KV, George J, Goodman ZD, Lindor K

Abstract
NASH/NAFLD is rapidly becoming one of top causes of cirrhosis, hepatocellular carcinoma and indication for liver transplantation. Except for life style modification through diet and exercise, there are currently no other approved treatments for NASH/NAFLD. Although weight loss can be effective, it is hard to achieve and sustain. In contrast, bariatric surgery can improve metabolic conditions associated with NAFLD and has been shown to improve liver histology. In order to have approved regimens for treatment of NASH/NAFLD, a number of issues that must be addressed. First, all stakeholders must agree on the most appropriate clinical trial endpoints for NASH. Currently, resolution of NASH (without worsening fibrosis) or reduction of fibrosis stage (without worsening NASH) are the accepted endpoints by the regulatory authorities. It is important to recognize the prognostic implication of histologic features of NASH. In this context, although histologic NASH has been associated with advanced stage of fibrosis, it is not an independent predictor of long term mortality. In contrast, there is significant data to suggest that stage of fibrosis is the only robust and independent predictor of liver-related mortality. In addition to the primary endpoints, a number of important secondary endpoints, including non-invasive biomarkers, long term outcomes, and patient reported outcomes, must be considered. In 2017, a few phase 3 clinical trials for treatment of NASH are in progress. Additionally, a number of phase 2a and 2b clinical trials targeting different pathogenic pathways in NASH enriches the pipeline of emerging therapies.
CONCLUSION: Over the next 5 years, some of these regimens are expected to provide potential new treatment options for patients with NASH/NAFLD. This article is protected by copyright. All rights reserved.

PMID: 29222911 [PubMed - as supplied by publisher]

Obesity, lipid profiles and oxidative stress in children after liver transplantation.

Sun, 12/10/2017 - 13:45

Obesity, lipid profiles and oxidative stress in children after liver transplantation.

Acta Biochim Pol. 2017 Dec 10;:

Authors: Czubkowski P, Wierzbicka A, Pawłowska J, Jankowska I, Socha P

Abstract
PURPOSE: In adult liver transplant recipients, coronary artery disease and congestive heart failure are significant cause of morbidity and mortality. This may be attributed to the long-term immunosuppressive treatment, mostly with calcineurin inhibitors and steroids, which in long-term may be associated with hyperlipidemia, oxidative stress and cardiovascular complications. Since such data for children is sparse, the aim of this study was to assess the lipid and oxidative stress markers after pediatric liver transplantation (LTx).
METHOD: We performed prospective analysis of 74 children, at the median age of 7.9 (2.8-11.6) years, 3.2 (1.2-4.3) years after LTx. We assessed the BMI Z-scores, cholesterol fractions (LDLc, HDLc, VLDLc), triglicerides, apolipoproteins (ApoAI, ApoB, ApoE), LCAT, insulin resistance by HOMA-IR and markers of oxidative stress and atherosclerosis: glutathione (GSH), glutathione peroxidase (GPx), asymmetrical dimethyl arginine (ADMA) and oxidized low-density lipoprotein (oxyLDL). At baseline, the results were compared with a healthy age-and-sex matched control group. After 3.1±0.3 year follow-up we repeated all investigations and compared them with the baseline results.
RESULTS: At the baseline, we investigated 74 patients 3.2 (1.2-4.3) years after LTx, at the median age of 7.9 (2.8-11.6) years. The prevalence of overweight or obesity (BMI >85th percentile) was 23% and was more common in girls (24% vs 20%). Fourteen patients had TCH >200 mg%, 9 patients had LDLc >130 mg% and TG were at normal levels in all patients. Compared to the controls, there were no significant differences in lipid profiles but we found decreased GSH (p<0.001) and GPx (p<0.001) which play role as an antioxidant defense. OS markers were higher in the study group: ADMA (p<0.001), and oxyLDL (p<0.0001). Insulin resistance by HOMA-IR was increased in the study group (p=0.0002) but fasting glucose remained within normal ranges in all patients. After 3.1-year follow-up, the BMI >95th and >85Th percentile was present in 8% and 14% respectively. ADMA and oxyLDL decreased, whilst GSH and GPx increased when compared to the baseline. There was also significant decrease in apoB and Lp(a).
CONCLUSION: Children after LTx had normal lipid profiles when compared to controls, however there is a tendency for hypercholesterolemia and obesity, which may play a role in cardiovascular complications in the future. Some markers of oxidative stress were increased after LTx, however further investigations are required to establish its clinical significance.

PMID: 29222858 [PubMed - as supplied by publisher]

Decellularized Human Liver Extracellular Matrix (hDLM) Mediated Hepatic Differentiation of Human Induced Pluripotent Stem Cells (hIPSc).

Sun, 12/10/2017 - 13:45
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Decellularized Human Liver Extracellular Matrix (hDLM) Mediated Hepatic Differentiation of Human Induced Pluripotent Stem Cells (hIPSc).

J Tissue Eng Regen Med. 2017 Dec 08;:

Authors: Jaramillo M, Yeh H, Yarmush ML, Uygun BE

Abstract
Liver tissue engineering has emerged as a promising approach in organ transplantation, but has been hampered by the lack of a reliable and readily available cell source. Induced pluripotent cells (hiPSC) have been highlighted a desirable source, due to their differentiation potential, ability to self-renew and the possibility of making patient specific cells. We developed a decellularization protocol that efficiently removes cellular material, while retaining extracellular matrix components. Subsequently, hiPSC were differentiated on the decellularized human liver matrix (hDLM) scaffolds using an established hepatic differentiation protocol. We demonstrate that using hDLM leads to upregulation of functional hepatic markers when compared to standard differentiation conditions. In addition, expression of a number of hepatic transcription and nuclear factors were found to be within levels comparable to those of primary human adult hepatocytes. Analysis of progression of differentiation on hDLM demonstrated that hepatic developmental marker expression was consistent with hepatic development. The hDLM-derived cells exhibited key hepatic characteristics that were comparable to those observed in primary neonatal human hepatocytes. We investigated the optimal timing of introduction of hDLM into the differentiation protocol, and found that best results are obtained when cells are plated on hDLM since the earliest stages, and accompanied by a progressive loss of sensitivity to substrate composition at later stages. The significance of this work is that it allows for the development of differentiation protocols that take into account signals from ECM, closely recapitulating of the in-vivo microenvironment and resulting in cells that are phenotypically closer to mature hepatocytes.

PMID: 29222839 [PubMed - as supplied by publisher]

Indoxyl Sulfate Upregulates Liver P-Glycoprotein Expression and Activity through Aryl Hydrocarbon Receptor Signaling.

Sun, 12/10/2017 - 13:45
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Indoxyl Sulfate Upregulates Liver P-Glycoprotein Expression and Activity through Aryl Hydrocarbon Receptor Signaling.

J Am Soc Nephrol. 2017 Dec 08;:

Authors: Santana Machado T, Poitevin S, Paul P, McKay N, Jourde-Chiche N, Legris T, Mouly-Bandini A, Dignat-George F, Brunet P, Masereeuw R, Burtey S, Cerini C

Abstract
In patients with CKD, not only renal but also, nonrenal clearance of drugs is altered. Uremic toxins could modify the expression and/or activity of drug transporters in the liver. We tested whether the uremic toxin indoxyl sulfate (IS), an endogenous ligand of the transcription factor aryl hydrocarbon receptor, could change the expression of the following liver transporters involved in drug clearance: SLC10A1, SLC22A1, SLC22A7, SLC47A1, SLCO1B1, SLCO1B3, SLCO2B1, ABCB1, ABCB11, ABCC2, ABCC3, ABCC4, ABCC6, and ABCG2 We showed that IS increases the expression and activity of the efflux transporter P-glycoprotein (P-gp) encoded by ABCB1 in human hepatoma cells (HepG2) without modifying the expression of the other transporters. This effect depended on the aryl hydrocarbon receptor pathway. Presence of human albumin at physiologic concentration in the culture medium did not abolish the effect of IS. In two mouse models of CKD, the decline in renal function associated with the accumulation of IS in serum and the specific upregulation of Abcb1a in the liver. Additionally, among 109 heart or kidney transplant recipients with CKD, those with higher serum levels of IS needed higher doses of cyclosporin, a P-gp substrate, to obtain the cyclosporin target blood concentration. This need associated with serum levels of IS independent of renal function. These findings suggest that increased activity of P-gp could be responsible for increased hepatic cyclosporin clearance. Altogether, these results suggest that uremic toxins, such as IS, through effects on drug transporters, may modify the nonrenal clearance of drugs in patients with CKD.

PMID: 29222397 [PubMed - as supplied by publisher]

Treatment of inherited bone marrow failure syndromes beyond transplantation.

Sun, 12/10/2017 - 13:45
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Treatment of inherited bone marrow failure syndromes beyond transplantation.

Hematology Am Soc Hematol Educ Program. 2017 Dec 08;2017(1):96-101

Authors: Calado RT, Clé DV

Abstract
Despite significant progress in transplantation by the addition of alternative hematopoietic stem cell sources, many patients with inherited bone marrow failure syndromes are still not eligible for a transplant. In addition, the availability of sequencing panels has significantly improved diagnosis by identifying cryptic inherited cases. Androgens are the main nontransplant therapy for bone marrow failure in dyskeratosis congenita and Fanconi anemia, reaching responses in up to 80% of cases. Danazol and oxymetholone are more commonly used, but virilization and liver toxicity are major adverse events. Diamond-Blackfan anemia is commonly treated with corticosteroids, but most patients eventually become refractory to this treatment and toxicity is limiting. Growth factors still have a role in inherited cases, especially granulocyte colony-stimulating factor in congenital neutropenias. Novel therapies are warranted and thrombopoietin receptor agonists, leucine, quercetin, and novel gene therapy approaches may benefit inherited cases in the future.

PMID: 29222242 [PubMed - in process]

Combination of Neoadjuvant Transcatheter Arterial Chemoembolization and Orthotopic Liver Transplantation for the Treatment of Cirrhotomimetic Hepatocellular Carcinoma.

Sun, 12/10/2017 - 13:45
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Combination of Neoadjuvant Transcatheter Arterial Chemoembolization and Orthotopic Liver Transplantation for the Treatment of Cirrhotomimetic Hepatocellular Carcinoma.

J Vasc Interv Radiol. 2017 Dec 05;:

Authors: Habibollahi P, Shamchi SP, Tondon R, Ecker BL, Gade TP, Hunt S, Soulen MC, Furth EE, Levine MH, Nadolski G

Abstract
PURPOSE: To examine differences in outcome and response of cirrhotomimetic (CMM) hepatocellular carcinoma (HCC) to a combination of bridging transcatheter arterial chemoembolization and orthotopic liver transplantation (OLT) compared with non-CMM HCC.
MATERIALS AND METHODS: All patients with pathologically proven CMM HCC who underwent bridging transcatheter arterial chemoembolization before OLT between 2007 and 2013 (n = 23) were retrospectively compared with a control group of patients with pathologically proven non-CMM HCC (n = 46).
RESULTS: There were 29 tumors in the CMM HCC group and 64 tumors in the non-CMM group identified and treated. Objective response rate on MR imaging at 1 and 3 months after transcatheter arterial chemoembolization for CMM HCC tumors (including patients with complete and partial response) was 93.1% and 86.4% compared with 85.2% and 93.2% for non-CMM tumors without statistically significant difference (P = .54 and P = .09, respectively). Pathologic study of liver explants showed complete tumor necrosis in 62.3% of non-CMM tumors (38/61) compared with 10.3% of CMM tumors (3/29) (P < .0001). Overall 2-year survival after transcatheter arterial chemoembolization and OLT was significantly lower for patients with CMM HCC compared with patients non-CMM HCC (65.2% vs 87%, P = .03). Patients with CMM HCC with extranodular tumor extension involving > 50% of liver parenchyma had worse survival with mean 2-year survival of 402 days ± 102 vs 656 days ± 39 for the remaining patients with CMM HCC (P = .02).
CONCLUSIONS: Despite similar early imaging response rates, CMM HCC tumors had markedly lower rates of complete pathologic necrosis on liver explants and were associated with reduced survival after OLT compared with conventional HCCs.

PMID: 29221923 [PubMed - as supplied by publisher]

A Model including Sarcopenia Surpasses the MELD Score in Predicting Waiting List Mortality in Cirrhotic Liver Transplant Candidates.

Sun, 12/10/2017 - 13:45
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A Model including Sarcopenia Surpasses the MELD Score in Predicting Waiting List Mortality in Cirrhotic Liver Transplant Candidates.

J Hepatol. 2017 Dec 05;:

Authors: van Vugt JLA, Alferink LJM, Buettner S, Gaspersz MP, Bot D, Murad SD, Feshtali S, van Ooijen PMA, Polak WG, Porte RJ, van Hoek B, van den Berg AP, Metselaar HJ, IJzermans JNM

Abstract
BACKGROUND AND AIMS: Frail patients with low MELD scores may be underprioritised. Low skeletal muscle mass (i.e. sarcopenia) has been identified as risk factor for waiting list mortality and a recent study proposed to incorporate sarcopenia in the MELD score (i.e. MELD-Sarcopenia score). We aimed to investigate the association between sarcopenia and waiting list mortality, and to validate the MELD-Sarcopenia score (i.e. MELD+10.35∗Sarcopenia).
METHODS: We identified consecutive patients with cirrhosis listed for liver transplantation in the Eurotransplant registry between 2007-2014 and measured skeletal muscle mass on computed tomography (CT). A competing risk analysis was used to compare survival of patients with and without sarcopenia, and concordance (c) indices were calculated to assess performance of the MELD and MELD-Sarcopenia score. We created a nomogram of the best predictive model.
RESULTS: We included 585 patients with a median MELD score of 14 (IQR 9-19), of which 254 (43.4%) were identified as having sarcopenia. Median waiting list survival was shorter in patients with sarcopenia than those without (p<0.001). This effect was even more pronounced in patients with MELD ≤15. The discriminative performance of the MELD-Sarcopenia score (c-index 0.820) for 3-month mortality was lower than MELD score alone (c-index 0.839). Apart from sarcopenia and MELD score, other predictive variables were occurrence of hepatic encephalopathy before listing and recipient age. A model including all these variables yielded a c-index of 0.851.
CONCLUSIONS: Sarcopenia was associated with waiting list mortality in liver transplant candidates with cirrhosis, particularly in patients with lower MELD scores. The MELD-Sarcopenia score was successfully validated in this cohort. However, incorporating sarcopenia in the MELD score had limited added value in predicting waiting list mortality.
LAY SUMMARY: In this study among patients with liver cirrhosis listed for liver transplantation, low skeletal muscle mass was associated with mortality on the waiting list, particularly in patients who were listed with low priority based on a low MELD score. However, adding these measurements to the currently used system for donor and organ allocation showed no added value.

PMID: 29221886 [PubMed - as supplied by publisher]

Donor Polymorphisms of Toll-like Receptor 4 rs1927914 Associated with the Risk of Hepatocellular Carcinoma Recurrence Following Liver Transplantation.

Sun, 12/10/2017 - 13:45
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Donor Polymorphisms of Toll-like Receptor 4 rs1927914 Associated with the Risk of Hepatocellular Carcinoma Recurrence Following Liver Transplantation.

Arch Med Res. 2017 Dec 05;:

Authors: Shi G, Wang C, Zhang P, Ji L, Xu S, Tan X, Li H

Abstract
BACKGROUND: Hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT) severely restricts the long-term survival of patients. Toll-like receptor 4 (TLR4) has been considered to be involved in hepatocarcinogenesis and metastasis. Additionally, there is a study demonstrating the significant association between TLR4 gene rs1927914 polymorphism and HCC, but no study investigated the association of the TLR4 rs1927914 polymorphism with the risk of HCC recurrence following LT.
AIM: The purpose of this study was to assess the potential association between the TLR4 gene rs1927914 polymorphism of donors and recipients and hepatocellular carcinoma recurrence after LT.
METHODS: Eighty-three patients with HCC undergoing LT from July 2006-June 2015 were identified for this analysis. We genotyped a single-nucleotide polymorphism (rs1927914) in both donors and recipients and evaluated the association between the polymorphism and risk of tumor recurrence.
RESULTS: The donor TLR4 rs1927914 polymorphism was found to be significantly associated with HCC recurrence following LT. In multivariate logistic regression analysis, Milan criteria, microvascular invasion and donor TLR4 rs1927914 genotype were confirmed to be independent risk factors for HCC recurrence. Kaplan-Meier survival curves showed that patients carrying donors homozygous TT had a significantly lower recurrence-free survival and overall survival than CC/CT patients. Cox proportional hazards modeling indicated that TNM stage or Milan criteria, microvascular invasion, and donor TLR4 rs1927914 genotype were independent factors for the clinical outcomes of LT patients.
CONCLUSIONS: Donor TLR4 rs1927914 polymorphism is associated with an increased risk of HCC recurrence following LT and has a potential clinical value for the prediction of HCC recurrence after LT.

PMID: 29221801 [PubMed - as supplied by publisher]

Milder disease stage in patients with primary biliary cholangitis over a 44-year period: A changing natural history.

Sat, 12/09/2017 - 13:45

Milder disease stage in patients with primary biliary cholangitis over a 44-year period: A changing natural history.

Hepatology. 2017 Dec 08;:

Authors: Murillo Perez F, Goet JC, Lammers WJ, Gulamhusein A, van Buuren HR, Ponsioen CY, Carbone M, Mason A, Corpechot C, Invernizzi P, Mayo MJ, Battezzati PM, Floreani A, Pares A, Nevens F, Kowdley KV, Bruns T, Dalekos GN, Thorburn D, Hirschfield G, LaRusso NF, Lindor KD, Zachou K, Poupon R, Trivedi PJ, Verhelst X, Janssen HLA, Hansen BE, GLOBAL PBC Study Group

Abstract
Changes over time in the presenting features and clinical course of patients with primary biliary cholangitis (PBC) are poorly described. We sought to describe temporal trends in patient and disease characteristics over a 44-year period across a large international PBC cohort of 4805 patients diagnosed between 1970 and 2014, from 17 centers across Europe and North America. Patients were divided into five cohorts according to their year of diagnosis: 1970-1979 (n=143), 1980-1989 (n=858), 1990-1999 (n=1754), 2000-2009 (n=1815), ≥2010 (n=235). Age at diagnosis, disease stage, response to ursodeoxycholic acid (UDCA), and clinical outcomes were compared. Mean age at diagnosis increased incrementally by 2-3 years per decade from 46.9±10.1 years in the 1970s to 57.0±12.1 years from 2010 onward (p<0.001). The female to male ratio (9:1) and anti-mitochondrial antibody positivity (90%) were not significantly variable. The proportion of patients presenting with mild biochemical disease (according to Rotterdam staging) increased from 41.3% in the 1970s to 72.2% in the 1990s (p<0.001), and remained relatively stable thereafter. Patients with a mild histological stage at diagnosis increased from 60.4% (1970-1989) to 76.5% (1990-2014) (p<0.001). Correspondingly, response to UDCA according to Paris-I criteria increased; 51.7% in the 1970s and 70.5% in the 1990s (p<0.001). Recent decades were also characterized by lower decompensation rates (18.5% in the 1970s to 5.8% in the 2000s, p<0.001) and higher 10-year transplant-free survival (48.4%, 68.7%, 79.7%, and 80.1% for each respective cohort, p<0.001).
CONCLUSION: Over the last decades, there is a pattern of PBC presentation consistent with an older age at diagnosis alongside reduced disease severity. The observed trends may be explained by an increase in routine testing of liver function and/or a changing environmental trigger. This article is protected by copyright. All rights reserved.

PMID: 29220537 [PubMed - as supplied by publisher]

Donor-derived tuberculosis via orthotopic liver transplantation.

Sat, 12/09/2017 - 13:45

Donor-derived tuberculosis via orthotopic liver transplantation.

Neth J Med. 2017 Nov;75(9):415-417

Authors: Ruijter BN, van Wijngaarden AKS, van Hoek B, Mensen M, van Soolingen D, Arend SM

Abstract
We present a case of donor-derived tuberculosis after liver transplantation, in which the donor origin of the Mycobacterium tuberculosis isolate was made most likely by DNA fingerprinting. Screening for latent tuberculosis of transplant donors originating from high endemic areas with an ex-vivo interferon-gamma release assay should be considered.

PMID: 29219817 [PubMed - in process]

Hepatitis C Virus Infection in Kidney Transplant Patients: Current Treatment Options.

Sat, 12/09/2017 - 13:45

Hepatitis C Virus Infection in Kidney Transplant Patients: Current Treatment Options.

Exp Clin Transplant. 2017 Dec;15(6):587-593

Authors: Dzekova-Vidimliski P, Sikole A

Abstract
Hepatitis C virus infection is highly prevalent among kidney transplant recipients, occurring consequently to their previous treatment with hemodialysis. Hepatitis C virus infection has been associated with lower graft and patient survival compared with that shown in patients without infection. The lower survival has been associated with the posttransplant progression of liver disease and increased risk for development of extrahepatic complications. The choice of immunosuppressive drugs could significantly affect the course of the infection with an accelerated viral replication after kidney transplant. Eradicating hepatitis C virus infection with antiviral treatment is imperative to increasing graft and patient survival after transplant. Antiviral treatment options include standard interferon-based therapy and new directacting antiviral agents. Interferon-based treatment is rarely used in kidney transplant recipients because it has been associated with high risk of interferoninduced acute graft rejection. Several novel studies have shown that the new direct-acting antiviral agents are highly efficacious for treatment of hepatitis C infection in kidney transplant patients.

PMID: 29219790 [PubMed - in process]

Necrotizing enterocolitis in the setting of milk allergy after pediatric living donor liver transplantation.

Sat, 12/09/2017 - 13:45
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Necrotizing enterocolitis in the setting of milk allergy after pediatric living donor liver transplantation.

Pediatr Transplant. 2017 Dec 07;:

Authors: Narumoto S, Sakamoto S, Uchida H, Sasaki K, Shigeta T, Fukuda A, Nosaka S, Irie R, Yoshioka T, Kasahara M

Abstract
NEC is an idiopathic intestinal mucosal injury that may progress to transmural bowel necrosis without mesenteric ischemia. NEC usually affects 7- to 10-day-old neonates following enteral feeding. A 10-month-old girl with no history of laparotomy underwent LDLT for acute liver failure. After starting enteral feeding on postoperative day 5, she developed abdominal distention. Diffuse PVG and PI were detected by radiologic modalities. Exploratory laparotomy revealed patchy necrosis of the intestine without perforation. The microscopic findings of a resected specimen revealed transmural coagulative necrosis with multiple small thromboses compatible with neonatal NEC features, and eosinophil infiltration was also observed. Subsequently, after the resumption of enteral feeding with cow's milk, she developed severe diarrhea, the symptoms of which were eliminated after the administration of cow's milk was stopped. These clinical and pathological findings support the speculation that NEC might have been induced by a CMA. Food allergies, which can be induced by immunosuppressive agents, should be considered as a potential cause of NEC in the setting of pediatric liver transplantation.

PMID: 29218832 [PubMed - as supplied by publisher]

A systematic review of immunosuppressant adherence interventions in transplant recipients: Decoding the streetlight effect.

Sat, 12/09/2017 - 13:45
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A systematic review of immunosuppressant adherence interventions in transplant recipients: Decoding the streetlight effect.

Pediatr Transplant. 2017 Dec 07;:

Authors: Duncan S, Annunziato RA, Dunphy C, LaPointe Rudow D, Shneider BL, Shemesh E

Abstract
Non-adherence to immunosuppressant medications is an important risk factor for graft dysfunction. To evaluate the effectiveness of adherence-enhancing interventions, we reviewed adherence intervention studies in solid organ transplant recipients (all ages). Using the following databases: PsycINFO, PubMed, Scopus, and ScienceDirect, we identified 41 eligible studies. Only three non-randomized trials showed a possible positive effect on objective indicators of transplant outcomes (such as rejection, liver enzyme levels, kidney function). None of the 21 RCTs showed an improvement in transplant outcomes. Three studies showed a higher rate of adverse events in the intervention group as compared with controls, although this may be related to ascertainment bias. Improvement in adherence as measured indirectly (eg, with electronic monitoring devices) was not aligned with effects on transplant outcomes. We conclude that adherence interventions, to date, have largely been ineffective in improving transplant outcomes. To improve this track record, intervention efforts may wish to concentrate on non-adherent patients (rather than use convenience sampling, which excludes many of the patients who need the intervention), use direct measures of adherence to guide the interventions, and employ strategies that are intensive and yet engaging enough to ensure that non-adherent patients are able to participate.

PMID: 29218760 [PubMed - as supplied by publisher]

Successful liver transplantation for homozygous protein C deficiency with a Type II mutation using a heterozygous living related donor.

Sat, 12/09/2017 - 13:45
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Successful liver transplantation for homozygous protein C deficiency with a Type II mutation using a heterozygous living related donor.

Am J Hematol. 2017 Dec 08;:

Authors: Boucher AA, Luchtman-Jones L, Nathan JD, Palumbo JS

PMID: 29218739 [PubMed - as supplied by publisher]

Transition from laparoscopic to retroperitoneoscopic approach for live donor nephrectomy.

Sat, 12/09/2017 - 13:45
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Transition from laparoscopic to retroperitoneoscopic approach for live donor nephrectomy.

Surg Endosc. 2017 Dec 07;:

Authors: Ng ZQ, Musk G, Rea A, He B

Abstract
BACKGROUND: Laparoscopic donor nephrectomy has become the standard of care due to multiple benefits. Currently, there are various techniques employed with two different approaches: transperitoneal (TLDN) or retroperitoneoscopic (RLDN) approach. There is a lack of data to determine which technique is superior, although the RLDN offers an anatomical advantage by avoidance of manipulation of the intraperitoneal organs. The aims of this study were to explore the merits of RLDN to TLDN and assess the learning curve of transition from TLDN to RLDN.
METHODS: From January 2010 to February 2017, 106 live donor nephrectomies were performed: 56 by TLDN and 50 by RLDN. Data on patient demographics, perioperative parameters, analgesic consumption, pain scores, and kidney graft function were collected and analysed. Data were compared with a Student's t test or Mann-Whitney test. A CUSUM analysis was performed to investigate the learning curve.
RESULTS: All live donor nephrectomies were successful with no conversion to open surgery. There was no blood transfusion, readmission, or mortality. No postoperative complications were graded over Clavien II. Kidney function was comparable in both groups. The follow-up period ranged from 3 to 78 months.
CONCLUSION: Retroperitoneoscopic live donor nephrectomy is a safe approach with comparable results to TLDN. RLDN has an anatomical advantage as it avoids manipulating the intraperitoneal organs and retains a virgin abdomen and hence translates to a lower perioperative complication risk.

PMID: 29218666 [PubMed - as supplied by publisher]

Benefits of laparoscopic liver resection in patients with hepatocellular carcinoma and portal hypertension: a case-matched study.

Sat, 12/09/2017 - 13:45
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Benefits of laparoscopic liver resection in patients with hepatocellular carcinoma and portal hypertension: a case-matched study.

Surg Endosc. 2017 Dec 07;:

Authors: Molina V, Sampson-Dávila J, Ferrer J, Fondevila C, Díaz Del Gobbo R, Calatayud D, Bruix J, García-Valdecasas JC, Fuster J

Abstract
BACKGROUND: The advantages of laparoscopy over open liver resection in patients with cirrhosis have been widely demonstrated. On the other hand, information on the role of minimally invasive liver surgery in the presence of clinically significant portal hypertension (CSPH) is scarce. The aim of this study was to evaluate the role of laparoscopic liver resection in selected cirrhotic patients with CSPH.
METHODS: A retrospective case-control study of cirrhotic patients with hepatocellular carcinoma who were treated with laparoscopic liver resection was conducted from December 2005 to April 2016. A total of 45 patients were included. Patients were divided into two groups according to the presence or absence of clinically significant portal hypertension. Fifteen cirrhotic patients with CSPH were matched with 30 patients without CSPH.
RESULTS: Overall, there were no differences in intraoperative results. No conversion to open surgery occurred in the CSPH group, and 3 patients were converted in the Non-CSPH group (0 vs. 10% p = 0.57). Only 2 (7%) patients in the Non-CSPH group and 1 (7%) in the CSPH group had relevant complications (modified Clavien-Dindo classification III). Two patients in the Non-CSPH group and one in the CSPH group developed transient ascites (7 vs. 7%). Postoperative hospital stay was similar in both groups, with a median of 4 days in the CSPH group and 3 days in the Non-CSPH group (p = 0.37). The median follow-up of the entire cohort was 38 months (range 7-100). Overall survival rates at 1 and 3 years were 100 and 87%, respectively. There was no significant difference between the groups in terms of survival (p = 0.8).
CONCLUSION: This initial study showed that laparoscopic resection in patients with CSPH can be performed safely in well-selected patients and expand the current surgical indications in patients with CSPH. Prospective trials with a larger sample size are necessary to confirm these results.

PMID: 29218665 [PubMed - as supplied by publisher]

Mir-24 regulates hepatocyte apoptosis via BIM during acute liver failure.

Sat, 12/09/2017 - 13:45
Related Articles

Mir-24 regulates hepatocyte apoptosis via BIM during acute liver failure.

Am J Transl Res. 2017;9(11):4925-4935

Authors: Feng Z, Li Z, Zhu D, Ling W, Zheng L, Pu L, Kong L

Abstract
Acuteliver failure (ALF) has a high mortality rate and is characterized by massive hepatocyte destruction. Although microRNAs (miRNAs) play an important role in manyliver diseases, the role of miRNAs in ALF development is unknown. In this study, the murine ALF model was induced by intraperitoneal injection of D-galactosamine/lipopolysaccharide (D-GalN/LPS). Compared with saline-treated mice, miR-24 was distinctly down-regulated post D-GalN/LPS challenge in vivo and D-galactosamine/tumor necrosis factor (D-GalN/TNF) challenge in vitro, which was confirmed by quantitative real-time polymerase chain reaction. Meanwhile, the mRNA and protein levels of the BH3-only-domain-containing protein BIM were upregulated after challenge both in vivo and in vitro. Previous studies have demonstrated that hepatocyte apoptosis is a distinguishing feature of D-GalN/LPS-associated liver failure. In this study, D-GalN/LPS-challenged mice showed higher alanine aminotransferase and aspartate aminotransferase levels, more severe liver damage, increased numbers of apoptotic hepatocytes and higher levels of caspase-3 compared with saline-treated mice. In D-GalN/TNF-treated BNLCL2 cells, miR-24 overexpression attenuated apoptosis.Furthermore, miR-24 overexpression reduced BIM mRNA and protein levels in vitro. Taken together, these findings demonstrate that miR-24 regulates hepatocyte apoptosis via BIM during ALF development, suggesting that miR-24 is a novel onco-miRNA that may provide potential therapeutic targets for ALF.

PMID: 29218090 [PubMed]

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