Skip directly to content

PubMed Liver Transplant

Subscribe to PubMed Liver Transplant feed PubMed Liver Transplant
NCBI: db=pubmed; Term=liver transplant
Updated: 1 hour 8 min ago

Treatment Options for Nonalcoholic Steatohepatitis - A Safety Evaluation.

Sat, 06/24/2017 - 12:45
Related Articles

Treatment Options for Nonalcoholic Steatohepatitis - A Safety Evaluation.

Expert Opin Drug Saf. 2017 Jun 22;:

Authors: Issa D, Wattacheril J, Sanyal AJ

Abstract
Introduction There is an urgent as yet unmet need to develop highly effective and safe therapeutics for nonalcoholic fatty liver disease (NAFLD). The remarkable progress in understanding NAFLD pathogenesis allowed the identification of injury pathways which may be recruited as therapy targets. Areas covered This article reviews the safety and tolerability data of the NAFLD therapies and explains the mechanistic basis for each of the established and investigational drugs. Treatment targets include: weight loss, anti-metabolic agents such as lipid lowering and anti-diabetic drugs, inflammation, fibrosis and others such as targeting gut microbiota, immune modulation and apoptosis. Expert Opinion Current therapies continue to remain suboptimal. Weight loss is effective but hard to achieve. Traditional and endoscopic bariatric procedures are promising although more randomized trials are needed and the long-term safety remains to be established. Clinical trials have demonstrated the efficacy of several drugs for the treatment of NASH. Of these, there remains some uncertainty about the long-term safety of vitamin E. Pioglitazone is associated with osteopenia, fluid retention and weight gain. Obeticholic acid causes pruritus in a substantial proportion of subjects and elafibranor has been associated with transient rises in creatinine. Several exciting therapies are under development and results of clinical and post-marketing trials will help elucidate their safety.

PMID: 28641031 [PubMed - as supplied by publisher]

Octogenarian Liver Grafts Reaching Centennial Age After Transplantation.

Sat, 06/24/2017 - 12:45
Related Articles

Octogenarian Liver Grafts Reaching Centennial Age After Transplantation.

Transplantation. 2017 Jul;101(7):e218-e219

Authors: Jiménez-Romero LC, Caso Maestro O, Cambra Molero F, Manrique Municio A, Calvo Pulido J, Marcacuzco Quinto A, Justo Alonso I

PMID: 28640791 [PubMed - in process]

MicroRNA-155 Deficiency in Kupffer Cells Ameliorates Liver Ischemia-Reperfusion Injury in Mice.

Sat, 06/24/2017 - 12:45
Related Articles

MicroRNA-155 Deficiency in Kupffer Cells Ameliorates Liver Ischemia-Reperfusion Injury in Mice.

Transplantation. 2017 Jul;101(7):1600-1608

Authors: Li Y, Ma D, Wang Z, Yang J

Abstract
BACKGROUND: MicroRNA-155 (miR-155) is known to be involved in autoimmune diseases, inflammation, and transplantation. However, its role in a warm hepatic ischemia-reperfusion (IR) model has not been fully elucidated.
METHODS: Partial hepatic IR was performed in wild-type and miR-155-deficient mice treated with or without GdCl3, and then the serum transaminase concentration and histology were analyzed. Kupffer cells (KCs) were isolated from the liver after IR, and immunohistochemistry was used to evaluate activation and polarization. In addition, the mRNA concentrations of various inflammatory cytokines were measured. Macrophages were obtained from the abdominal cavity and challenged with or without lipopolysaccharide to determine the influence of miR-155 deficiency on macrophage polarization in vitro. Furthermore, we used in vitro coculture assays to determine the effect of miR-155 deficiency on hepatocyte apoptosis induced directly by KCs.
RESULTS: miR-155 deficiency ameliorated liver IR injury, and inhibition of KCs by GdCl3 abolished this protective effect. miR-155 deficiency decreased CD80, CD86, and major histocompatibility complex class II expression in KCs after IR and tipped the M1/M2 balance toward an anti-inflammatory profile, where proinflammatory cytokine secretion was suppressed and IL-10 was enhanced. In addition, hepatocyte apoptosis was reduced in coculture with miR-155-deficient KCs in vitro.
CONCLUSIONS: miR-155 deficiency plays an effective role in attenuating liver IR injury likely by regulating the activation and inflammatory response, as well as modifying the polarization of KCs.

PMID: 28640790 [PubMed - in process]

Hepatocellular Carcinoma in South America: Evaluation of Risk Factors, Demographics, and Therapy.

Sat, 06/24/2017 - 12:45
Related Articles

Hepatocellular Carcinoma in South America: Evaluation of Risk Factors, Demographics, and Therapy.

Liver Int. 2017 Jun 22;:

Authors: Debes JD, Chan AJ, Balderramo D, Kikuchi L, Gonzalez Ballerga E, Prieto JE, Tapias M, Idrovo V, Davalos MB, Cairo F, Barreyro FJ, Paredes S, Hernandez N, Avendaño K, Diaz Ferrer J, Yang JD, Carrera E, Garcia JA, Mattos AZ, Hirsch BS, Gonçalves PT, Carrilho FJ, Roberts LR

Abstract
BACKGROUND AND AIMS: Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death worldwide. Most studies addressing the epidemiology of HCC originate from developed countries. This study reports the preliminary findings of a multinational approach to characterize HCC in South America.
METHODS: We evaluated 1336 HCC patients seen at 14 centers in six South American countries using a retrospective study design with participating centers completing a template chart of patient characteristics. The diagnosis of HCC was made radiographically or histologically for all cases according to institutional standards. Methodology of surveillance for each center was following AASLD or EASL recommendations.
RESULTS: Sixty-eight percent of individuals were male with a median age of 64 years at time of diagnosis. The most common risk factor for HCC was hepatitis C infection (HCV, 48%), followed by alcoholic cirrhosis (22%), Hepatitis B infection (HBV, 14%), and NAFLD (9%). We found that among individuals with HBV-related HCC, 38% were diagnosed before age 50. The most commonly provided therapy was Trans-arterial chemoembolization (35% of HCCs) with few individuals being considered for liver transplant (<20%). Only 47% of HCCs were diagnosed during surveillance and there was no difference in age of diagnosis between those diagnosed incidentally versus by surveillance. Nonetheless, being diagnosed during surveillance was associated with improved overall survival (p=0.01).
CONCLUSIONS: Our study represents the largest cohort to date reporting characteristics, and outcomes of HCC across South America. We found an important number of HCCs diagnosed outside of surveillance programs, with associated increased mortality in those patients. This article is protected by copyright. All rights reserved.

PMID: 28640517 [PubMed - as supplied by publisher]

A Liver-specific Gene Expression Panel Predicts the Differentiation Status of in vitro Hepatocyte Models.

Sat, 06/24/2017 - 12:45
Related Articles

A Liver-specific Gene Expression Panel Predicts the Differentiation Status of in vitro Hepatocyte Models.

Hepatology. 2017 Jun 22;:

Authors: Kim DS, Ryu JW, Son MY, Oh JH, Chung KS, Lee S, Lee JJ, Ahn JH, Min JS, Ahn J, Kang HM, Kim J, Jung CR, Kim NS, Cho HS

Abstract
Alternative cell sources, such as three-dimensional organoids and induced pluripotent stem cell-derived cells, might provide a potentially effective approach for both drug development applications and clinical transplantation. For example, the development of cell sources for liver cell-based therapy has been increasingly needed, and liver transplantation is performed for the treatment for patients with severe end-stage liver disease. Differentiated liver cells and three-dimensional (3D) organoids are expected to provide new cell sources for tissue models and revolutionary clinical therapies. However, conventional experimental methods confirming the expression levels of liver-specific lineage markers cannot provide complete information regarding the differentiation status or degree of similarity between liver and differentiated cell sources. Therefore, in this study, to overcome several issues associated with the assessment of differentiated liver cells and organoids, we developed a LiGEP (Liver-Specific Gene Expression Panel) algorithm that presents the degree of liver similarity as a "percentage". We demonstrated that the percentage calculated using the LiGEP algorithm was correlated with the developmental stages of in vivo liver tissues in mice, suggesting that LiGEP can correctly predict developmental stages. Moreover, 3D cultured HepaRG cells and human pluripotent stem cell (hPSC)-derived hepatocyte-like cells (HLCs) showed liver similarity scores of 59.14% and 32%, respectively, although general liver-specific markers were detected. Therefore, our study describes the first quantitative and predictive model for differentiated samples, particularly liver-specific cells or organoids, and this model can be further expanded to various tissue-specific organoids. Our LiGEP can provide useful information and insights regarding the differentiation status of in vitro liver models. This article is protected by copyright. All rights reserved.

PMID: 28640507 [PubMed - as supplied by publisher]

Sustained Post-Transplant Diabetes is Associated with Long-Term Major Cardiovascular Events Following Liver Transplantation.

Sat, 06/24/2017 - 12:45
Related Articles

Sustained Post-Transplant Diabetes is Associated with Long-Term Major Cardiovascular Events Following Liver Transplantation.

Am J Transplant. 2017 Jun 22;:

Authors: Roccaro GA, Goldberg DS, Hwang WT, Judy R, Thomasson A, Kimmel SE, Forde KA, Lewis JD, Yang YX

Abstract
Cardiovascular disease is a leading cause of death among liver transplant (LT) recipients. With a rising burden of post-transplant metabolic disease, increases in cardiovascular-related morbidity and mortality may reduce life expectancy following liver transplantation. It is unknown if the risk of long-term major cardiovascular events (MCE) differs among LT recipients with varying diabetic states. We performed a retrospective cohort study of LT recipients from 2003 to 2013, to compare the incidence of MCE among patients 1) without diabetes, 2) with pre-transplant diabetes 3) with de novo transient post-transplant diabetes, and 4) with de novo sustained post-transplant diabetes. We analyzed 994 eligible patients (39% normal, 24% pre-transplant diabetes, 16% transient post-transplant diabetes, and 20% sustained post-transplant diabetes). Median follow up was 54.7 months. Overall, 12% of patients experienced a MCE. Adjusting for demographic and clinical variables, sustained post-transplant diabetes was the only state associated with a significantly increased risk of MCE (SHR 1.95, 95% CI 1.20-3.18). Patients with sustained post-transplant diabetes mellitus had a 13% and 27% cumulative incidence of MCE at 5 and 10 years. While pre-transplant diabetes has traditionally been associated with cardiovascular disease, the long-term risk of MCE is greatest in LT recipients with sustained post-transplant diabetes mellitus. This article is protected by copyright. All rights reserved.

PMID: 28640504 [PubMed - as supplied by publisher]

Prognostic Factors for Transplant-Free Survival and Validation of Prognostic Models in Chinese Patients with Primary Biliary Cholangitis Receiving Ursodeoxycholic Acid.

Sat, 06/24/2017 - 12:45
Related Articles

Prognostic Factors for Transplant-Free Survival and Validation of Prognostic Models in Chinese Patients with Primary Biliary Cholangitis Receiving Ursodeoxycholic Acid.

Clin Transl Gastroenterol. 2017 Jun 22;8(6):e100

Authors: Cheung KS, Seto WK, Fung J, Lai CL, Yuen MF

Abstract
OBJECTIVES: We aimed to validate the prognostic models for primary biliary cholangitis (PBC) in Chinese patients receiving ursodeoxycholic acid (UCDA), and to compare their performances in predicting the long-term survival.
METHODS: Chinese patients with PBC from a tertiary center were identified via electronic search of hospital medical registry. Risk factors associated with adverse events (liver transplantation or death from liver-related causes including hepatocellular carcinoma (HCC) and liver decompensation) were determined. Transplant-free survival was defined as survival free of liver-related death or transplantation.
RESULTS: Of the 144 patients, 41 (28.5%) had baseline cirrhosis. The median age at diagnosis was 57.8 years. During a median follow-up of 7.0 years, 40 patients died (21 liver-related; 19 non-liver-related), 12 developed HCC, and 10 underwent transplantations. The 5-, 10-, and 15-year transplant-free survival probabilities were 91.0%, 78.1%, and 58.9%, respectively. Independent risk factors for adverse events were increasing age (hazard ratio (HR) 1.05), cirrhosis (HR 8.53), and suboptimal treatment response (HR 3.06). Aspartate aminotransferase/platelet ratio index at 1 year (APRI-r1) in combination with treatment response optimized the risk stratification. The performances of the GLOBE, UK-PBC scores, Rotterdam criteria, and APRI-r1 were comparable in predicting adverse events. The area under receiver operating curves within 5, 10, and 15 years were as follows-GLOBE score: 0.83, 0.85, and 0.85, respectively; UK-PBC score: 0.89, 0.83, and 0.79, respectively; Rotterdam criteria: 0.82, 0.76, and 0.80, respectively; APRI-r1: 0.80, 0.83, and 0.77, respectively.
CONCLUSIONS: The UK-PBC, GLOBE scores, Rotterdam criteria, and APRI-r1 had good and comparable prognostic prediction values for Chinese PBC patients receiving UCDA.

PMID: 28640288 [PubMed - in process]

Voluntary distance running prevents TNF-mediated liver injury in mice through alterations of the intrahepatic immune milieu.

Sat, 06/24/2017 - 12:45
Related Articles

Voluntary distance running prevents TNF-mediated liver injury in mice through alterations of the intrahepatic immune milieu.

Cell Death Dis. 2017 Jun 22;8(6):e2893

Authors: Huber Y, Gehrke N, Biedenbach J, Helmig S, Simon P, Straub BK, Bergheim I, Huber T, Schuppan D, Galle PR, Wörns MA, Schuchmann M, Schattenberg JM

Abstract
Physical activity confers a broad spectrum of health benefits. Beyond the obvious role in metabolically driven diseases, the role of physical activity in acute liver injury is poorly explored. To study the role of physical activity in acute liver injury, a novel model of voluntary distance running in mice was developed and mice were subjected to acute liver injury induced by N-galactosamine (GalN) and lipopolysaccharide (LPS). Analyses included histological stains, immunoblotting, qRT-PCR and FACS analysis. Voluntary distance running increased to an average of 10.3 km/day after a learning curve. Running lead to a decrease in the absolute numbers of intrahepatic CD4+ T and B lymphocytes and macrophages after 7 weeks. In parallel, hepatic mRNA expression of inflammatory cytokines including IL-6 and IL-1beta, TGF-beta and monocyte chemoattractant protein-1 (MCP-1/CCL2) were suppressed, while TNF-α was not affected by exercise. Likewise, expression of the macrophage-specific antigen F4/80 was downregulated 1.6-fold from exercise. Notably, acute liver injury from GaIN/LPS was significantly blunted following 7 weeks of voluntary exercise as determined by liver histology, a 84.6% reduction of alanine aminotransferase (P<0.01) and a 54.6% reduction of aspartate aminotransferase (P<0.05) compared with sedentary mice. Additionally, proinflammatory cytokines, activation of caspase 3 and JNK were significantly lower, while antiapoptotic protein A20 increased. Voluntary distance running alters the intrahepatic immune phenotype producing an environment that is less susceptible to acute liver injury.

PMID: 28640248 [PubMed - in process]

Treatment of mucopolysaccharidosis type II (Hunter syndrome): results from a systematic evidence review.

Sat, 06/24/2017 - 12:45
Related Articles

Treatment of mucopolysaccharidosis type II (Hunter syndrome): results from a systematic evidence review.

Genet Med. 2017 Jun 22;:

Authors: Bradley LA, Haddow HRM, Palomaki GE

Abstract
PurposeA pilot systematic evidence review to establish methodology utility in rare genetic diseases, support clinical recommendations, and identify important knowledge gaps.MethodsBroad-based published/gray-literature searches through December 2015 for studies of males with confirmed mucopolysaccharidosis type II (any age, phenotype, genotype, family history) treated with enzyme replacement therapy or hematopoietic stem cell transplantation. Preset inclusion criteria employed for abstract and full document selection, and standardized methods for data extraction and assessment of quality and strength of evidence.ResultsTwelve outcomes reported included benefits of urinary glycosaminoglycan and liver/spleen volume reductions and harms of immunoglobulin G/neutralizing antibody development (moderate strength of evidence). Less clear were benefits of improved 6-minute walk tests, height, early treatment, and harms of other adverse reactions (low strength of evidence). Benefits and harms of other outcomes were unclear (insufficient strength of evidence). Current benefits and harms of hematopoietic stem cell transplantation are unclear, based on dated, low-quality studies. A critical knowledge gap is long-term outcomes. Consensus on selection of critical outcomes and measures is needed to definitively evaluate treatment safety and effectiveness.ConclusionMinor methodology modifications and a focus on critical evidence can reduce review time and resources. Summarized evidence was sufficient to support guidance development and highlight important knowledge gaps.GENETICS in MEDICINE advance online publication, 22 June 2017; doi:10.1038/gim.2017.30.

PMID: 28640238 [PubMed - as supplied by publisher]

Case report of a modified Meso-Rex bypass as a treatment technique for late-onset portal vein cavernous transformation with portal hypertension after adult deceased-donor liver transplantation.

Sat, 06/24/2017 - 12:45
Related Articles

Case report of a modified Meso-Rex bypass as a treatment technique for late-onset portal vein cavernous transformation with portal hypertension after adult deceased-donor liver transplantation.

Medicine (Baltimore). 2017 Jun;96(25):e7208

Authors: Han D, Tang R, Wang L, Li A, Huang X, Shen S, Dong J

Abstract
RATIONALE: Portal vein thrombosis is a complication after liver transplantation and cavernous transformation of the portal vein (CTPV) is a result of portal vein thrombosis, with symptoms of portal hypertension revealed by an enhanced CT scan. Meso-Rex bypass is an artificial shunt connecting the left portal vein to the superior mesenteric vein and is mainly used for idiopathic cavernomas. This technique is also used for post-transplant portal vein thrombosis in pediatric patients thereby bypassing obstructed sites of the extrahepatic portal vein. Here we report about an adult patient who was treated by connecting the cystic part of the portal vein to the splenic vein instead of the superior mesenteric vein.
PATIENTS CONCERN: An adult male patient with post-liver transplantation portal vein cavernous transformation suffered from hypersplenism and elevated hepatic enzymes.
DIAGNOSIS: The last follow up revealed irregular and obvious hypersplenism, and splenomegaly had occurred, while an enhanced CT scan revealed serious esophagogastric varices and CTPV in addition to occluded right and common PV trunks.
INTERVENTION: The patient was treated by connecting the cystic part of the portal vein to the splenic vein instead of the superior mesenteric vein.
OUTCOME: After the operation, a satisfactory velocity was confirmed 1 month postoperatively and the shunt still remained patent at the 6-month postoperation follow-up.
LESSONS: A Meso-Rex bypass intervention connecting the left portal vein to the splenic vein instead of the superior mesenteric vein after liver transplantation in an adult patient with right and common portal vein occlusions has been successfully performed as an alternative approach.

PMID: 28640110 [PubMed - in process]

Correlation of HLA-DP/DQ polymorphisms with transplant etiologies and prognosis in liver transplant recipients.

Sat, 06/24/2017 - 12:45
Related Articles

Correlation of HLA-DP/DQ polymorphisms with transplant etiologies and prognosis in liver transplant recipients.

Medicine (Baltimore). 2017 Jun;96(25):e7205

Authors: Li Y, Huang Q, Tang JT, Wei TT, Yan L, Yang ZQ, Bai YJ, Wang LL, Shi YY

Abstract
Previous study has identified that the genetic variants in the human leukocyte antigen (HLA)-DP/DQ region were strongly associated with hepatitis B virus (HBV) infection. But their roles in liver function recovery after hepatic transplantation were still obscure. This study aimed to investigate whether HLA-DP/DQ polymorphisms were associated with post-transplant etiologies and prognosis in Chinese liver transplant recipients.A total of 144 liver transplant recipients were enrolled, which were divided into 2 groups according to the transplant etiology: HBV-related disease and non-HBV-related disease. HBV-related disease includes 3 subgroups: liver cirrhosis, hepatocellular carcinoma, and progressive HBV hepatitis. Three single-nucleotide polymorphisms HLA-DP (rs3077 and rs9277535) and HLA-DQ (rs7453920) were studied in all recipients by high-resolution melting curve analysis. Liver function indices (albumin, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyltranspeptidase, direct bilirubin, total bilirubin) and coagulation indices (prothrombin time, platelet, international normalized ratio, fibrinogen) were routinely tested. After transplant, 10 recipients who were positive for HBsAg or with elevation in HBV virus load were regarded as HBV recurrence.No significant association of HLA-DP/DQ polymorphisms with HBV recurrence or transplant etiology was observed (P < .05). Recipients with HLA-DQ (rs7453920) AG and AA genotype had lower direct bilirubin levels than GG genotype individuals, especially on the 14th day after surgery (17.80 vs. 5.35, P  =  .038). Patients with A alleles displayed earlier liver function recovery than patients with G alleles (7 vs. 6 months). No significant correlation was shown in HLA-DP rs3077 and rs9277535 with HBV infection or liver function recovery (P < .05).Our study concluded that HLA-DP (rs3077 and rs9277535) and HLA-DQ (rs7453920) were not significantly associated with HBV recurrence or HBV susceptibility, but HLA-DQ rs7453920 was related to prognosis of liver transplant recipients. HLA-DQ rs7453920 A might be used as an indicator of earlier recovery and better prognosis after transplantation.

PMID: 28640108 [PubMed - in process]

A nomogram prediction of postoperative surgical site infections in patients with perihilar cholangiocarcinoma.

Sat, 06/24/2017 - 12:45
Related Articles

A nomogram prediction of postoperative surgical site infections in patients with perihilar cholangiocarcinoma.

Medicine (Baltimore). 2017 Jun;96(25):e7198

Authors: Li L, Ding J, Han J, Wu H

Abstract
Surgical site infection (SSI) is one of the major morbidities after radical resection for perihilar cholangiocarcinoma (PHCC). This study aimed to clarify the risk factors and construct a nomogram to predict SSIs in patients with PHCC.A total of 335 consecutive patients who underwent hepatectomy combined with hepaticojejunostomy between January 2013 and December 2015 were analyzed retrospectively. SSIs, including incisional (superficial and deep) and space/organ infection, were defined according to the Centers for Disease Control and Prevention (CDC)'s National Nosocomial Infection Surveillance (NNIS) system. Risk factors associated with postoperative SSIs were analyzed by univariate and multivariate analyses. A nomogram was developed on the basis of results from the multivariate logistic model and the discriminatory ability of the model was analyzed.PHCC patients had higher organ/space SSI rate than incisional SSI rate after radical resection. Multivariate analysis showed that risk factors indicating postoperative overall SSIs (incisional and organ/space) included coexisting cholangiolithiasis [odds ratio (OR): 6.77; 95% confidence interval (95% CI): 2.40-19.11; P < .001], blood loss >1500 mL (OR: 4.77; 95% CI: 1.45-15.65; P  =  .010), having abdominal surgical history (OR: 5.85; 95% CI: 1.91-17.97; P  =  .002), and bile leakage (OR: 15.28; 95% CI: 5.90-39.62; P < .001). The β coefficients from the multivariate logistic model were used to construct the model for estimation of SSI risk. The scoring model was as follows: -4.12 +1.91 × (coexisting cholangiolithiasis  =  1) + 1.77 × (having previous abdominal surgical history  =  1) +1.56 × (blood loss >1500 mL  =  1) + 2.73 × (bile leakage  =  1). The discriminatory ability of the model was good and the area under the receiver operating characteristic (ROC) curve (AUC) was 0.851.In PHCC patients, there may be a relationship between postoperative SSIs and abdominal surgical history, coexisting cholangiolithiasis, bile leakage, and blood loss. The nomogram can be used to estimate the risk of postoperative SSIs in patients with PHCC.

PMID: 28640107 [PubMed - in process]

Authors' Reply: Does low Hepatic Artery Flow Increase Rate of Biliary Strictures in Deceased Donor Liver Transplantation?

Sat, 06/24/2017 - 12:45
Related Articles

Authors' Reply: Does low Hepatic Artery Flow Increase Rate of Biliary Strictures in Deceased Donor Liver Transplantation?

Transplantation. 2017 Jun 21;:

Authors: Kim PT, Klintmalm GB

PMID: 28640068 [PubMed - as supplied by publisher]

Molecular Adsorbent Recirculating System Can Reduce Short-Term Mortality Among Patients With Acute-on-Chronic Liver Failure-A Retrospective Analysis.

Sat, 06/24/2017 - 12:45
Related Articles

Molecular Adsorbent Recirculating System Can Reduce Short-Term Mortality Among Patients With Acute-on-Chronic Liver Failure-A Retrospective Analysis.

Crit Care Med. 2017 Jun 21;:

Authors: Gerth HU, Pohlen M, Thölking G, Pavenstädt H, Brand M, Hüsing-Kabar A, Wilms C, Maschmeier M, Kabar I, Torner J, Pavesi M, Arroyo V, Banares R, Schmidt HHJ

Abstract
OBJECTIVES: Acute-on-chronic liver failure is associated with numerous consecutive organ failures and a high short-term mortality rate. Molecular adsorbent recirculating system therapy has demonstrated beneficial effects on the distinct symptoms, but the associated mortality data remain controversial.
DESIGN: Retrospective analysis of acute-on-chronic liver failure patients receiving either standard medical treatment or standard medical treatment and molecular adsorbent recirculating system. Secondary analysis of data from the prospective randomized Recompensation of Exacerbated Liver Insufficiency with Hyperbilirubinemia and/or Encephalopathy and/or Renal Failure trial by applying the recently introduced Chronic Liver Failure-criteria.
SETTING: Medical Departments of University Hospital Muenster (Germany).
PATIENTS: This analysis was conducted in two parts. First, 101 patients with acute-on-chronic liver failure grades 1-3 and Chronic Liver Failure-C-Organ Failure liver subscore equals to 3 but stable pulmonary function were identified and received either standard medical treatment (standard medical treatment, n = 54) or standard medical treatment and molecular adsorbent recirculating system (n = 47) at the University Hospital Muenster. Second, the results of this retrospective analysis were tested against the Recompensation of Exacerbated Liver Insufficiency with Hyperbilirubinemia and/or Encephalopathy and/or Renal Failure trial.
INTERVENTIONS: Standard medical treatment and molecular adsorbent recirculating system.
MEASUREMENTS AND MAIN RESULTS: Additionally to improved laboratory variables (bilirubin and creatinine), the short-term mortality (up to day 14) of the molecular adsorbent recirculating system group was significantly reduced compared with standard medical treatment. A reduced 14-day mortality rate was observed in the molecular adsorbent recirculating system group (9.5% vs 50.0% with standard medical treatment; p = 0.004), especially in patients with multiple organ failure (acute-on-chronic liver failure grade 2-3). Concerning the affected organ system, this effect of molecular adsorbent recirculating system on mortality was particularly evident among patients with increased kidney, brain, or coagulation Chronic Liver Failure-C-Organ Failure subscores. Subsequent reanalysis of the Recompensation of Exacerbated Liver Insufficiency with Hyperbilirubinemia and/or Encephalopathy and/or Renal Failure dataset with adoption of the Chronic Liver Failure-classification resulted in similar findings.
CONCLUSIONS: Molecular adsorbent recirculating system treatment was associated with an improved short-term survival of patients with acute-on-chronic liver failure and multiple organ failure. Among these high-risk patients, molecular adsorbent recirculating system treatment might bridge to liver recovery or liver transplantation.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

PMID: 28640024 [PubMed - as supplied by publisher]

Living Donor Liver Transplantation in Pakistan.

Sat, 06/24/2017 - 12:45
Related Articles

Living Donor Liver Transplantation in Pakistan.

Transplantation. 2017 Jul;101(7):1507-1508

Authors: Hafeez Bhatti AB, Saud Dar F

PMID: 28640010 [PubMed - in process]

miRNA Signature of Hepatocellular Carcinoma Vascularization: How the Controls Can Influence the Signature.

Sat, 06/24/2017 - 12:45
Related Articles

miRNA Signature of Hepatocellular Carcinoma Vascularization: How the Controls Can Influence the Signature.

Dig Dis Sci. 2017 Jun 21;:

Authors: Fittipaldi S, Vasuri F, Bonora S, Degiovanni A, Santandrea G, Cucchetti A, Gramantieri L, Bolondi L, D'Errico A

Abstract
BACKGROUND: miRNA deregulation and vascular modifications constitute promising predictors in the study of hepatocellular carcinoma (HCC). In the literature, the relative miRNA abundance in HCC is usually determined using as control non-matched tumoral tissue, healthy liver, or cirrhotic liver. However, a common standard RNA control for the normalization toward the tissue gene expression was not settled yet.
AIM: To assess the differences existing in the quantitative miRNA gene expression in HCC on tissue according to two different liver controls.
METHODS: A wide array of miRNAs was analyzed on 22 HCCs arisen in cirrhotic and non-cirrhotic livers by means of microfluidic cards. Control samples included total RNA extracted from healthy and cirrhotic livers. Immunohistochemistry for CD34 and Nestin was performed to assess the pattern of intratumoral vascular modifications.
RESULTS: Six miRNAs were deregulated in HCCs using either controls: miR-532, miR-34a, miR-93, miR-149#, miR-7f-2#, and miR-30a-5p. Notably, the miRNA expression changed significantly between HCCs arisen in cirrhotic and non-cirrhotic livers, according to the control used for normalization. Different miRNA profiles were found also in HCCs with different vascular patterns, according to the control used for normalization.
CONCLUSIONS: Our data confirm that the choice of the methodology, and particularly the control used for normalization, represents the main concern in miRNA evaluation, particularly in a heterogeneous model such as liver pathology. Still we observed the deregulation of some common miRNAs as promising in HCC cancerogenesis and progression. A standardized control will be a crucial achievement to compare miRNA expression among different laboratories.

PMID: 28639131 [PubMed - as supplied by publisher]

Central Hepatectomy Still Plays an Important Role in Treatment of Early-Stage Centrally Located Hepatocellular Carcinoma.

Sat, 06/24/2017 - 12:45
Related Articles

Central Hepatectomy Still Plays an Important Role in Treatment of Early-Stage Centrally Located Hepatocellular Carcinoma.

World J Surg. 2017 Jun 21;:

Authors: Chen CH, Huang TH, Chang CC, Li WF, Lin TL, Wang CC

Abstract
BACKGROUND: Surgical management of centrally located hepatocellular carcinoma (CL-HCC) poses a great challenge. Major hepatectomy (MH) might compromise future remnant liver volume (FRLV), while the long-term benefits of central hepatectomy (CH) had not been well demonstrated.
METHODS: Consecutive patients with early-stage CL-HCC who underwent liver resection were enrolled. Fifteen patients underwent CH, while thirty-three were subjected to MH. All relevant clinicopathological variables were analyzed. Disease-free survival (DFS) and overall survival (OS) of both groups were compared.
RESULTS: There were no differences between CH and MH in terms of predisposing liver disease, tumor size, blood loss, complication rate and vascular invasion. Mean FRLV increased from 40.9 to 69.2% by using CH resection lines. The parenchymal transection time is longer in CH. There were no differences of DFS between two groups. The 5-year OS rates of CH and MH were 93.3 and 62.6%, respectively. MH was a poor prognostic factor.
CONCLUSIONS: CH is a relatively time-consuming and technique-demanding procedure, but excellent long-term survival could be achieved. CH could increase liver volume preservation without compromising intra-hepatic recurrence. In an endemic area of hepatitis and cirrhosis, CH should still play an important role in surgical treatment of CL-HCC.

PMID: 28639005 [PubMed - as supplied by publisher]

Evolving role of Sorafenib in the management of hepatocellular carcinoma.

Sat, 06/24/2017 - 12:45
Related Articles

Evolving role of Sorafenib in the management of hepatocellular carcinoma.

World J Clin Oncol. 2017 Jun 10;8(3):203-213

Authors: Ziogas IA, Tsoulfas G

Abstract
Hepatocellular carcinoma (HCC) is one of the most common malignant diseases worldwide and comes third in cancer-related mortality. Although there is a broad spectrum of treatment options to choose from, only a few patients are eligible candidates to receive a curative therapy according to their stage of disease, and thus palliative treatment is implemented in the majority of the patients suffering from liver cancer. Sorafenib, a multikinase inhibitor, is the only currently approved agent for systemic therapy in patients with advanced stage HCC and early stage liver disease. It has been shown to improve the overall survival, but with various side effects, while its cost is not negligible. Sorafenib has been in the market for a decade and has set the stage for personalized targeted therapy. Its role during this time has ranged from monotherapy to neoadjuvant and adjuvant treatment with surgical resection, liver transplantation and chemoembolization or even in combination with other chemotherapeutic agents. In this review our aim is to highlight in depth the current position of Sorafenib in the armamentarium against HCC and how that has evolved over time in its use either as a single agent or in combination with other therapies.

PMID: 28638790 [PubMed - in process]

Clinicopathological Study of Seronegative Celiac Disease in Adults in Pakistan: A Pilot Study.

Sat, 06/24/2017 - 12:45
Related Articles

Clinicopathological Study of Seronegative Celiac Disease in Adults in Pakistan: A Pilot Study.

Middle East J Dig Dis. 2017 Apr;9(2):94-99

Authors: Farina MH, Kumar Mandhwani R, Hassan Luck N, Abbas Z, Mubarak M, Laeeq SM, Tasneem AA

Abstract
BACKGROUND Celiac disease (CD) is usually missed, if the serology is negative. We aimed to evaluate the clinicopathological characteristics of seronegative CD (SNCD) and its response to gluten-free diet (GFD) in adult patients. METHODS This observational study was carried out at the Department of Hepatogastroenterology, Sindh Institute of Urology and Transplantation, Karachi, Pakistan from 2009 to 2015. All consecutive adult patients (≥17 years) with features of marked villous atrophy (Marsh class≥III) on duodenal biopsy, negative tissue transglutaminase IgA and IgG antibodies (anti-tTg IgA and IgG) and human leukocyte antigen (HLA) DQ2 or DQ8 serotypes were studied. Clinical characteristics, laboratory parameters, and response to GFD were analyzed by SPSS software version 20. Median and interquartile range (IQR) were used for summarizing quantitative data. Frequency (percentages) was used for qualitative data. RESULTS A total of 12 patients with median age of 31.5 years (IQR: 19.75-46.75 years), of whom five (41.6%) were men were studied. The presenting complaints were: weight loss in 11 (91.6%) and abdominal pain in 9 (75%) patients. Anemia was observed in 10 (83.3%) patients with median hemoglobin of 9.5 g/dL (IQR: 6.3-13.25 g/dL). Median alanine transaminase (ALT) was 21 U/L (IQR: 13-27 U/L) and median albumin was 3 g/dL (IQR: 2.4-3.6 g/dL). Anti-tTg IgA and IgG were negative in all patients. HLA DQ serotyping showed homozygous DQ2 and DQ8 in four and one patients, respectively; while heterozygous DQ2 and DQ8 in five and two patients, respectively. All patients were advised to receive GFD. Nine (75%) patients showed complete clinical response. Two patients were non-compliant and one with non-alcoholic fatty liver disease (NAFLD)-related cirrhosis had partial clinical response. Out of the nine responders, two patients showed response within 6 months while the remaining showed improvement over a year period. CONCLUSION The diagnosis of SNCD is rewarding as it responds favorably to GFD in most patients. HLA serology provides an important tool for diagnosis of this entity.

PMID: 28638585 [PubMed - in process]

Bright Polymer Dots Tracking Stem Cell Engraftment and Migration to Injured Mouse Liver.

Sat, 06/24/2017 - 12:45
Related Articles

Bright Polymer Dots Tracking Stem Cell Engraftment and Migration to Injured Mouse Liver.

Theranostics. 2017;7(7):1820-1834

Authors: Chen D, Li Q, Meng Z, Guo L, Tang Y, Liu Z, Yin S, Qin W, Yuan Z, Zhang X, Wu C

Abstract
Stem cell therapy holds promise for treatment of intractable diseases and injured organs. For clinical translation, it is pivotal to understand the homing, engraftment, and differentiation processes of stem cells in a living body. Here we report near-infrared (NIR) fluorescent semiconductor polymer dots (Pdots) for bright labeling and tracking of human mesenchymal stem cells (MSCs). The Pdots exhibit narrow-band emission at 775 nm with a quantum yield of 22%, among the highest value for various NIR probes. The Pdots together with a cell penetrating peptide are able to track stem cells over two weeks without disturbing their multipotent properties, as confirmed by the analyses on cell proliferation, differentiation, stem-cell markers, and immunophenotyping. The in vivo cell tracking was demonstrated in a liver-resection mouse model, which indicated that the Pdot-labeled MSCs after tail-vein transplantation were initially trapped in lung, gradually migrated to the injured liver, and then proliferated into cell clusters. Liver-function analysis and histological examination revealed that the inflammation induced by liver resection was apparently decreased after stem cell transplantation. With the bright labeling, superior biocompatibility, and long-term tracking performance, the Pdot probes are promising for stem cell research and regenerative medicine.

PMID: 28638470 [PubMed - in process]

Pages