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 36 min ago

The Liver Frailty Index Improves Mortality Prediction of the Subjective Clinician Assessment in Patients With Cirrhosis.

Wed, 12/13/2017 - 13:45
Related Articles

The Liver Frailty Index Improves Mortality Prediction of the Subjective Clinician Assessment in Patients With Cirrhosis.

Am J Gastroenterol. 2017 Dec 12;:

Authors: Lai JC, Covinsky KE, McCulloch CE, Feng S

Abstract
OBJECTIVES: Frailty, a critical determinant of health outcomes, is most commonly assessed in patients with cirrhosis by general clinician assessment that is limited by its subjectivity. We aimed to compare the objective Liver Frailty Index (LFI), consisting of three performance-based tests (grip, chair stands, balance), with a subjective hepatologist assessment.
METHODS: Outpatients with cirrhosis awaiting liver transplantation (LT) underwent: (1) objective measurement using the LFI and (2) subjective clinician assessment. Spearman's correlation assessed associations between the LFI and clinician assessment; Cox regression with waitlist mortality (death/delisting for sickness); discriminative ability with Concordance(C) statistics. The net reclassification index evaluated the percentage of patients correctly reclassified by adding the LFI to the clinician assessment.
RESULTS: Of the 529 patients with cirrhosis, median LFI was 3.8 (range 1.0-7.0) and clinician assessment was 3 (range 0-5). Correlation between LFI and the clinician assessment was modest (ρ=0.38) with high variability by hepatologist (ρ=0.26-0.70). At a median of 11 months, 102 (19%) died/were delisted. Both the LFI (hazard ratio (HR) 2.2, 95% confidence interval (CI) 1.7-2.9) and clinician assessment (HR 1.6, 95% CI 1.3-1.9) were associated with adjusted waitlist mortality risk (P<0.01). The addition of the LFI to the clinician assessment significantly improved mortality prediction over the clinician assessment alone (0.74 vs. 0.68; P=0.02). Compared with the clinician assessment alone, the addition of the LFI correctly reclassified 34% (95% CI 8-53%) of patients to their correct survival status.
CONCLUSION: The subjective clinician assessment can predict waitlist mortality in patients with cirrhosis but is subjective and variable by hepatologist. The addition of the LFI to the subjective clinician assessment significantly improved mortality risk prediction, reclassifying 34% of patients. Our data strongly support the incorporation of the objective LFI to anchor our assessments of patients with cirrhosis to enhance our decision-making.Am J Gastroenterol advance online publication, 12 December 2017; doi:10.1038/ajg.2017.443.

PMID: 29231189 [PubMed - as supplied by publisher]

Major Hepatic Complications in Ursodeoxycholic Acid-Treated Patients With Primary Biliary Cholangitis: Risk Factors and Time Trends in Incidence and Outcome.

Wed, 12/13/2017 - 13:45
Related Articles

Major Hepatic Complications in Ursodeoxycholic Acid-Treated Patients With Primary Biliary Cholangitis: Risk Factors and Time Trends in Incidence and Outcome.

Am J Gastroenterol. 2017 Dec 12;:

Authors: Harms MH, Lammers WJ, Thorburn D, Corpechot C, Invernizzi P, Janssen HLA, Battezzati PM, Nevens F, Lindor KD, Floreani A, Ponsioen CY, Mayo MJ, Dalekos GN, Bruns T, Parés A, Mason AL, Verhelst X, Kowdley KV, Goet JC, Hirschfield GM, Hansen BE, van Buuren HR

Abstract
OBJECTIVES: In this era of near universal ursodeoxycholic acid (UDCA) treatment for primary biliary cholangitis (PBC), progression to cirrhosis still occurs in an important proportion of patients. The aim of this study was to describe the incidence of cirrhosis-associated complications in patients with PBC and assess risk factors and impact on survival.
METHODS: Cohorts of UDCA-treated patients from 16 European and North-American liver centers were included. We used Cox proportional hazards assumptions and Kaplan-Meier estimates.
RESULTS: During 8.1 years' median follow-up, 278 of 3,224 patients developed ascites, variceal bleeding, and/or encephalopathy (incidence rate of 9.7 cases/1,000 patient years). The overall cumulative incidence was 9.1% after 10 years of follow-up, but decreased over time to 5.8% after the year 2000. Earlier calendar year of diagnosis (P<0.001), high aspartate aminotransferase to platelets ratio index (APRI; P<0.001) and biochemical non-response (P<0.001) were independently associated with future complications. Patients with both biochemical non-response and an APRI >0.54 after 12 months of UDCA had a 10-year complication rate of 37.4%, as compared to 3.2% in biochemical responders with an APRI ≤0.54. The 10-year transplantation-free survival after a complication was 9% (time-dependent hazard ratio 21.5; 20.1-22.8). Prognosis after variceal bleeding has improved over time.
CONCLUSIONS: In this large international cohort, up to 15% of UDCA-treated PBC patients developed major non-neoplastic, cirrhosis-associated hepatic complications within 15 years, but cumulative incidence has decreased over time. Biochemical non-response to UDCA and APRI were independent risk factors for these complications. Subsequent long-term outcome after complications is generally poor, but has improved over the past decades.Am J Gastroenterol advance online publication, 12 December 2017; doi:10.1038/ajg.2017.440.

PMID: 29231188 [PubMed - as supplied by publisher]

Gut microbial balance and liver transplantation: alteration, management, and prediction.

Wed, 12/13/2017 - 13:45
Related Articles

Gut microbial balance and liver transplantation: alteration, management, and prediction.

Front Med. 2017 Dec 12;:

Authors: Tian X, Yang Z, Luo F, Zheng S

Abstract
Liver transplantation is a conventional treatment for terminal stage liver diseases. However, several complications still hinder the survival rate. Intestinal barrier destruction is widely observed among patients receiving liver transplant and suffering from ischemia-reperfusion or rejection injuries because of the relationship between the intestine and the liver, both in anatomy and function. Importantly, the resulting alteration of gut microbiota aggravates graft dysfunctions during the process. This article reviews the research progress for gut microbial alterations and liver transplantation. Especially, this work also evaluates research on the management of gut microbial alteration and the prediction of possible injuries utilizing microbial alteration during liver transplantation. In addition, we propose possible directions for research on gut microbial alteration during liver transplantation and offer a hypothesis on the utilization of microbial alteration in liver transplantation. The aim is not only to predict perioperative injuries but also to function as a method of treatment or even inhibit the rejection of liver transplantation.

PMID: 29230676 [PubMed - as supplied by publisher]

Intraarterial Liver-Directed Therapies: The Role of Interventional Oncology.

Wed, 12/13/2017 - 13:45
Related Articles

Intraarterial Liver-Directed Therapies: The Role of Interventional Oncology.

Ochsner J. 2017;17(4):412-416

Authors: Ma J, Gimenez JM, Sandow T, Devun D, Kirsch D, Gulotta P, Gilbert P, Kay D

Abstract
Background: Since the early 1990s, the minimally invasive image-guided therapies used in interventional oncology to treat hepatocellular carcinoma have continued to evolve. Additionally, the range of applications has been expanded to the treatment of hepatic metastases from colorectal cancer, neuroendocrine tumors, cholangiocarcinoma, breast cancer, melanoma, and sarcoma.
Methods: We searched the literature to identify publications from 1990 to the present on various image-guided intraarterial therapies and their efficacy, as well as their role in the management of primary and secondary liver malignancies.
Results: Chemoembolization and radioembolization are considered a standard of care in treating, delaying progression of disease, and downstaging to bridge to liver transplantation. Progression-free survival and overall survival outcomes are promising in patients with colorectal cancer and neuroendocrine tumors with liver metastases. Applications in the treatment of hepatic metastases from cholangiocarcinoma, breast cancer, melanoma, and sarcoma also show potential.
Conclusion: Interventional oncology and its image-guided intraarterial therapies continue to gain recognition as treatment options for primary and secondary liver cancers. Growing evidence supports their role as a standard of care alongside medical oncology, surgery, and radiation oncology.

PMID: 29230127 [PubMed]

BOK promotes chemical-induced hepatocarcinogenesis in mice.

Wed, 12/13/2017 - 13:45
Related Articles

BOK promotes chemical-induced hepatocarcinogenesis in mice.

Cell Death Differ. 2017 Dec 11;:

Authors: Rabachini T, Fernandez-Marrero Y, Montani M, Loforese G, Sladky V, He Z, Bachmann D, Wicki S, Villunger A, Stroka D, Kaufmann T

Abstract
BCL-2-related ovarian killer (BOK) is a conserved and widely expressed BCL-2 family member with sequence homology to pro-apoptotic BAX and BAK, but with poorly understood pathophysiological function. Since several members of the BCL-2 family are critically involved in the regulation of hepatocellular apoptosis and carcinogenesis we aimed to establish whether loss of BOK affects diethylnitrosamine (DEN)-induced hepatocarcinogenesis in mice. Short-term exposure to DEN lead to upregulation of BOK mRNA and protein in the liver. Of note, induction of CHOP and the pro-apoptotic BH3-only proteins PUMA and BIM by DEN was strongly reduced in the absence of BOK. Accordingly, Bok -/- mice were significantly protected from DEN-induced acute hepatocellular apoptosis and associated inflammation. As a consequence, Bok -/- animals were partially protected against chemical-induced hepatocarcinogenesis showing fewer and, surprisingly, also smaller tumors than WT controls. Gene expression profiling revealed that downregulation of BOK results in upregulation of genes involved in cell cycle arrest. Bok -/- hepatocellular carcinoma (HCC) displayed higher expression levels of the cyclin kinase inhibitors p19INK4d and p21cip1. Accordingly, hepatocellular carcinoma in Bok -/- animals, BOK-deficient human HCC cell lines, as well as non-transformed cells, showed significantly less proliferation than BOK-proficient controls. We conclude that BOK is induced by DEN, contributes to DEN-induced hepatocellular apoptosis and resulting hepatocarcinogenesis. In line with its previously reported predominant localization at the endoplasmic reticulum, our findings support a role of BOK that links the cell cycle and cell death machineries upstream of mitochondrial damage.

PMID: 29229991 [PubMed - as supplied by publisher]

A Multicenter Phase III Study to Evaluate the Efficacy and Safety of Hepabulin, a New Hepatitis B Immunoglobulin, in Liver Transplantation Recipients with Hepatitis B.

Wed, 12/13/2017 - 13:45
Related Articles

A Multicenter Phase III Study to Evaluate the Efficacy and Safety of Hepabulin, a New Hepatitis B Immunoglobulin, in Liver Transplantation Recipients with Hepatitis B.

Ann Transplant. 2017 Dec 12;22:740-748

Authors: Choi HJ, Kim DG, Kim SI, Wang HJ, Joh JW, Suh KS, Kim SH

Abstract
BACKGROUND This study was performed to evaluate the effects and stability of the new hepatitis B immunoglobulin (HBIG), Hepabulin, in patients undergoing liver transplantation for hepatitis B. MATERIAL AND METHODS A total of 87 patients undergoing liver transplantation for hepatitis B-related liver disease were enrolled in this multicenter, phase III, open-label, single-arm study. Seventy (80.5%) of the 87 enrolled patients completed the study during the 52-week study period. Hepabulin (10,000 units) was intravenously injected intraoperatively, daily for 1 week, weekly for 1 month, and then once per month. Hepabulin was used as monotherapy without antiviral agents. Hepatitis B recurrence was defined as conversion from negativity for surface antigen after HBIG administration to positivity. RESULTS There were no cases of hepatitis B recurrence during the 52-week observation period. A total of 876 adverse events (AEs) that occurred during the study period were observed in 83 (95.4%) of 87 patients, and serious AEs were seen in 119 cases in 44 (50.6%) of the 87 patients. None of the AEs showed a relationship with this drug. Hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) rapidly disappeared within 1 week after HBIG administration, but hepatitis B virus (HBV) DNA persisted for up to 8 weeks after surgery, which was related to HBV viral load. Hepatitis B surface antibody (HBsAb) was correlated with HBIG (Hepabulin) dose. CONCLUSIONS The new HBIG, Hepabulin, was shown to be safe and effective in preventing the recurrence of HBV after liver transplantation.

PMID: 29229898 [PubMed - in process]

Liver transplantation for deterioration in native liver function after portoenterostomy for biliary atresia in Japan: Short- versus long-term survivors.

Wed, 12/13/2017 - 13:45
Related Articles

Liver transplantation for deterioration in native liver function after portoenterostomy for biliary atresia in Japan: Short- versus long-term survivors.

J Pediatr Surg. 2017 Nov 13;:

Authors: Ochi T, Nakamura H, Wada M, Tamura T, Koga H, Okazaki T, Urao M, Ishizaki Y, Kawasaki S, Kasahara M, Mizuta K, Lane GJ, Yamataka A

Abstract
PURPOSE: We reviewed our post-Kasai portoenterostomy biliary atresia (BA) patients who required liver transplantation (LTx) for deterioration in native liver (NL) function to investigate mortality in relation to age at LTx.
METHODS: BA patients indicated for LTx when less than 18years old (U18; n=17) and when 18 or older (18+; n=13) were compared. All achieved jaundice clearance postoperatively (TBil ≤1.2mg/dL (≈20μmol/L)).
RESULTS: In U18, living-donor (LD) LTxs were performed at a median of 6.1years (range: 0.5-16.7; n=14) and cadaveric (CD) LTxs at a median of 1.3years (1.1-1.5; n=3). In 18+, LDLTxs were performed at a median of 28years (18-37; n=8), and 1 case died from graft versus host disease. CDLTxs were indicated in 5, but 4 died at a median of 30years (26-32), a mean of 1.4years (0.7-1.8) after NL deterioration commenced. One case is awaiting CDLTx. At the time of review, all U18 and 7 LDLTx cases in 18+ were clinically stable. Mortality rates were 0% in U18 and 38% in 18+ (P=.006).
CONCLUSION: Our results highlight the extremely grave prognosis for long-term BA patients requiring LTx when 18 or older because of poor donor availability in Japan.
LEVEL OF EVIDENCE: Level III.

PMID: 29229480 [PubMed - as supplied by publisher]

Tumor Necrosis Factor-producing T-regulatory Cells are Associated With Severe Liver Injury in Patients With Acute Hepatitis A.

Wed, 12/13/2017 - 13:45
Related Articles

Tumor Necrosis Factor-producing T-regulatory Cells are Associated With Severe Liver Injury in Patients With Acute Hepatitis A.

Gastroenterology. 2017 Dec 08;:

Authors: Choi YS, Jung MK, Lee J, Choi SJ, Choi SH, Lee HW, Lee JJ, Kim HJ, Ahn SH, Lee DH, Kim W, Park SH, Huh JR, Kim HP, Park JY, Shin EC

Abstract
BACKGROUND AND AIMS: CD4+CD25+Foxp3+ T-regulatory (Treg) cells control immune responses and maintain immune homeostasis. However, under inflammatory conditions, Treg cells produce cytokines that promote inflammation. We investigated production of tumor necrosis factor (TNF) by Treg cells in patients with acute hepatitis A (AHA), and examined the characteristics of these cells and association with clinical factors.
METHODS: We analyzed blood samples collected from 63 patients with AHA at the time of hospitalization (and some at later time points) and 19 healthy donors in South Korea. Liver tissues were collected from patients with fulminant AHA during liver transplantation. Peripheral blood mononuclear cells (PBMCs) were isolated from whole blood and lymphocytes were isolated from liver tissues and analyzed by flow cytometry. Cytokine production from Treg cells (CD4+CD25+Foxp3+) was measured by immunofluorescence levels following stimulation with anti-CD3 and anti-CD28. Epigenetic stability of Treg cells was determined based on DNA methylation patters. Phenotypes of Treg cells were analyzed by flow cytometry, and an RORγt inhibitor, ML-209 was used to inhibit TNF production. Treg cell suppression assay was performed by co-culture of Treg-depleted PBMCs and isolated Treg cells.
RESULTS: A higher proportion of CD4+CD25+Foxp3+ Treg cells from patients with AHA, compared with controls, produced TNF upon stimulation with anti-CD3 and anti-CD28 (11.2% vs 2.8%). DNA methylation analysis confirmed the identity of the Treg cells. TNF-producing Treg cells had features of T-helper 17 cells, including upregulation of RORγt, which was required for TNF production. The Treg cells had reduced suppressive functions compared to Treg cells from controls. The frequency of TNF-producing Treg cells in AHA patients' blood correlated with their serum level of alanine aminotransferase.
CONCLUSIONS: Treg cells from patients with AHA have altered functions, compared with Treg cells from healthy individuals. Treg cells from patients with AHA produce higher levels of TNF, gain features of T-helper 17 cells, and have reduced suppressive activity. The presence of these cells is associated with severe liver injury in patients with AHA.

PMID: 29229400 [PubMed - as supplied by publisher]

Pretransplant coronary artery disease is a predictor for myocardial infarction and cardiac death after liver transplantation.

Wed, 12/13/2017 - 13:45
Related Articles

Pretransplant coronary artery disease is a predictor for myocardial infarction and cardiac death after liver transplantation.

Eur J Intern Med. 2017 Dec 08;:

Authors: Darstein F, Hoppe-Lotichius M, Vollmar J, Weyer-Elberich V, Zimmermann A, Mittler J, Otto G, Lang H, Galle PR, Zimmermann T

Abstract
BACKGROUND: Cardiovascular disease is a serious problem of liver transplant (LT) recipients because of increased cardiovascular risk due to immunosuppressive therapy, higher age, intraoperative risk and comorbidities (such as diabetes and nicotine abuse). Reported frequency of cardiovascular events after LT shows a high variability between different LT cohorts. Our aim was to analyze a cohort of LT recipients from a single center in Germany to evaluate frequency of the cardiovascular endpoints (CVE) myocardial infarction and/or cardiac death after LT and to investigate correlations of CVE post LT with pretransplant patient characteristics.
PATIENTS: In total, data from 352 LT patients were analyzed. Patients were identified from an administrative transplant database, and all data were retrieved from patients' charts and reports.
RESULTS: During the median follow-up of 4.0 (0-13) years, 10 cases of CVE were documented (six myocardial infarctions and four coronary deaths). The frequency of CVE did not differ according to classic cardiovascular risk factors such as body mass index (p=0.071), total cholesterol (p=0.533), hypertension (p=0.747), smoking (p=1.000) and pretransplant diabetes mellitus (p=0.146). In patients with pretransplant coronary heart disease (n=24; 6.8%) CVE were found more frequently (p=0.024).
CONCLUSION: In summary, we found a rate of 2.8% CVE after LT in a German transplant cohort. Pretransplant CHD was the only risk factor for CVE, but showed no significant impact on overall survival.

PMID: 29229303 [PubMed - as supplied by publisher]

Preliminary Experience in Combined Somatic and Cerebral Oximetry Monitoring in Liver Transplantation.

Wed, 12/13/2017 - 13:45
Related Articles

Preliminary Experience in Combined Somatic and Cerebral Oximetry Monitoring in Liver Transplantation.

J Cardiothorac Vasc Anesth. 2017 Jul 20;:

Authors: Hu T, Collin Y, Lapointe R, Carrier FM, Massicotte L, Fortier A, Lambert J, Vandenbroucke-Menu F, Denault AY

Abstract
OBJECTIVE: The use of cerebral near-infrared spectroscopy (NIRS) has become widespread in cardiac surgery after research demonstrated an association between perioperative cerebral desaturations and postoperative complications. Somatic NIRS desaturation also is associated with an increased risk of postoperative complications and mortality. The objective of this study was to explore the trends of both somatic and cerebral NIRS during liver transplantation.
DESIGN: A prospective, single-site, observational case series.
SETTING: Tertiary care center.
PARTICIPANTS: The study comprised 10 patients undergoing liver transplantation.
INTERVENTIONS: NIRS sensors were placed on the forehead (cerebral regional oxygen saturation [rSO2]) and on the right arm and right leg (somatic rSO2) to measure tissue perfusion. Desaturation was defined as a 20% decrease of baseline values for 15 seconds.
MEASUREMENTS AND MAIN RESULTS: In all patients, parallel changes in both cerebral and somatic rSO2 values were observed during phlebotomy, bleeding, transfusion, portal vein clamping, and the use of vasoactive agents. Induction of anesthesia increased cerebral rSO2 more than it did somatic values. However, ascites removal, abdominal manipulation, and clamping of the inferior vena cava (IVC) were associated with nonparallel changes in cerebral and somatic rSO2. Ascites removal was associated with increased somatic leg rSO2, and IVC clamping and abdominal hypertension were associated with a significant reduction in somatic leg rSO2. Somatic leg desaturation instead of arm or cerebral desaturation was associated with more postoperative complications.
CONCLUSIONS: The use of combined NIRS monitoring allows for the identification of the source of somatic or cerebral desaturation. Compromised venous flow from the IVC from clamping or abdominal compartment syndrome typically is associated with the appearance of more pronounced leg than arm desaturation.

PMID: 29229261 [PubMed - as supplied by publisher]

Unrecognized Esophageal Perforation After Liver Transplantation.

Wed, 12/13/2017 - 13:45
Related Articles

Unrecognized Esophageal Perforation After Liver Transplantation.

J Cardiothorac Vasc Anesth. 2017 Oct 31;:

Authors: Mazilescu LI, Bezinover D, Paul A, Saner FH

PMID: 29229256 [PubMed - as supplied by publisher]

Wisp2 disruption represses Cxcr4 expression and inhibits BMSCs homing to injured liver.

Wed, 12/13/2017 - 13:45
Related Articles

Wisp2 disruption represses Cxcr4 expression and inhibits BMSCs homing to injured liver.

Oncotarget. 2017 Nov 17;8(58):98823-98836

Authors: Qin D, Yan Y, Hu B, Zhang W, Li H, Li X, Liu S, Dai D, Hu X, Huang X, Zhang L

Abstract
Liver regeneration/repair is a compensatory regrowth following acute liver failure, and bone marrow-derived mesenchyme stem cell (BMSC) transplantation is an effective therapy that promotes liver regeneration/repair. Wnt1 inducible signaling pathway protein 2 (Wisp2) is highly expressed in BMSCs, however, its function remains unclear. In this work, we used clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein -9 nuclease (CRISPR/Cas9) genome editing technology to knockdown Wisp2 in BMSCs, and these modified cells were then transplanted into rats which were induced by the 2-AAF/PH. By linking the expression of Cas9 to green fluorescent protein (GFP), we tracked BMSCs in the rats. Disruption of Wisp2 inhibited the homing of BMSCs to injured liver and aggravated liver damage as indicated by remarkably high levels of ALT and AST. Moreover, the key factor in BMSC transplantation, C-X-C chemokine receptor type 4 (Cxcr4), was down-regulated in the Wisp2 depleted BMSCs and had a lower expression in the livers of the corresponding rats. By tracing the GFP marker, more BMSCs were observed to differentiate into CD31 positive endothelial cells in the functional Wisp2 cells but less in the Wisp2 gene disrupted cells. In summary, Wisp2 promotes the homing of BMSCs through Cxcr4 related signaling during liver repair in rats.

PMID: 29228730 [PubMed]

Comparison between liver resection and liver transplantation on outcomes in patients with solitary hepatocellular carcinoma meeting UNOS criteria: a population-based study of the SEER database.

Wed, 12/13/2017 - 13:45
Related Articles

Comparison between liver resection and liver transplantation on outcomes in patients with solitary hepatocellular carcinoma meeting UNOS criteria: a population-based study of the SEER database.

Oncotarget. 2017 Nov 14;8(57):97428-97438

Authors: Yang A, Ju W, Yuan X, Han M, Wang X, Guo Z, Wei X, Wang D, Zhu X, Wu L, He X

Abstract
Liver resection (LR) and liver transplantation (LT) are potential curative treatment methods for early hepatocellular carcinoma (HCC). However, it is controversial which treatment is more beneficial to patients with solitary HCC meeting the United Network for Organ Sharing (UNOS) criteria (single lesion, diameter≤50mm, no vascular invasion, no extrahepatic metastasis). We retrieved patients with solitary HCC meeting UNOS criteria diagnosed between 2004-2013 from the Surveillance Epidemiology and End Results (SEER) database. Multivariate Cox proportional hazards regression models were used to evaluate the impact of surgery type (LR/LT) on overall survival (OS) and disease-specific survival (DSS) in both the whole study group and subgroups. Our analyses show that LT Patients had significantly superior OS (Adjusted HR (95% CI): 0.39 [0.26-0.59]) and DSS (Adjusted HR (95% CI): 0.19 [0.10-0.35]) than those receiving LR, although compared with the 288 patients receiving LR, the 258 patients receiving LT had younger age, smaller tumor size, and higher fibrosis score (P<0.001). Subgroup analyses identified significant interactions between surgery type (LR/LT) and gender (Male/Female) in both OS (P=0.02) and DSS (P=0.02). Male patients benefit more from LT compared with LR in both OS (Adjusted HR (95% CI): 0.29 [0.18-0.47]) and DSS (Adjusted HR (95% CI): 0.10 [0.05-0.21]), but there is no difference between patients receiving LT and LR in female patients. In conclusion, LT is associated with superior survival than LR in patients with solitary HCC meeting UNOS criteria. Moreover, male patients benefits more from LT than LR, while female patients do not show different outcomes between the two procedures.

PMID: 29228622 [PubMed]

FGF19 Protects Hepatocellular Carcinoma Cells against Endoplasmic Reticulum Stress via Activation of FGFR4-GSK3β-Nrf2 Signaling.

Wed, 12/13/2017 - 13:45
Related Articles

FGF19 Protects Hepatocellular Carcinoma Cells against Endoplasmic Reticulum Stress via Activation of FGFR4-GSK3β-Nrf2 Signaling.

Cancer Res. 2017 Nov 15;77(22):6215-6225

Authors: Teng Y, Zhao H, Gao L, Zhang W, Shull AY, Shay C

Abstract
The tumor microenvironment induces endoplasmic reticulum (ER) stress in tumor cells, an event that can promote progression, but it is unknown how tumor cells adapt to this stress. In this study, we show that the fibroblast growth factor FGF19, a gene frequently amplified in hepatocellular carcinoma (HCC), facilitates a survival response to ER stress. Levels of FGF19 expression were increased in stressed HCC cells in culture and in a mouse xenograft model. Induction of ER stress required the transcription factor ATF4, which directly bound the FGF19 promoter. In cells where ER stress was induced, FGF19 overexpression promoted HCC cell survival and increased resistance to apoptosis, whereas FGF19 silencing counteracted these effects. Mechanistic investigations implicated glycogen synthase kinase-3β (GSK3β) in regulating nuclear accumulation of the stress-regulated transcription factor Nrf2 activated by FGF19. Our findings show how FGF19 provides a cytoprotective role against ER stress by activating a FGFR4-GSK3β-Nrf2 signaling cascade, with implications for targeting this signaling node as a candidate therapeutic regimen for HCC management. Cancer Res; 77(22); 6215-25. ©2017 AACR.

PMID: 28951455 [PubMed - indexed for MEDLINE]

Surgical management decreases disease recurrence risk in recurrent pyogenic cholangitis.

Tue, 12/12/2017 - 16:48

Surgical management decreases disease recurrence risk in recurrent pyogenic cholangitis.

ANZ J Surg. 2017 Dec 11;:

Authors: Tan HL, Koh YX, Lye WK, Lee SY, Goh BKP, Tan SS, Chiow AKH, Chan CY

Abstract
BACKGROUND: Recurrent pyogenic cholangitis (RPC) has a high risk of disease recurrence. We present our experience with RPC and examine the factors associated with disease recurrence.
METHODS: We performed a retrospective review of all patients with RPC treated at two tertiary institutions between January 1990 and December 2013. Patients with liver atrophy and/or abscess were categorized as being associated with parenchymal disease (PD).
RESULTS: We studied 157 patients with a median age of 59.0 (interquartile range (IQR): 47.0-70.0) years and a median follow-up duration of 71.0 (IQR: 26.0-109.0) months. There were 64 (40.8%) and 93 (59.2%) patients with and without associated PD, respectively. Disease recurrence rate was 43.9% in our overall cohort through the course of follow-up. Surgical treatment was an independent prognostic factor for decreased disease recurrence risk (hazard ratio (HR) 0.40, 95% confidence interval (CI) 0.18-0.87, P = 0.021). Stratified analysis revealed that liver resection was prognostic for lower risk of disease recurrence among patients with PD (HR 0.38, 95% CI 0.15-0.94, P = 0.036), while biliary bypass was prognostic for lower risk of disease recurrence among patients without PD (HR 0.30, 95% CI 0.15-0.61, P = 0.001). The overall post-operative complication rate among surgically treated patients was 31.1%, and the presence of bilobar stones was found to be independently associated with higher odds of post-operative complications (odds ratio 3.51, 95% CI 1.26-9.81, P = 0.017).
CONCLUSION: Surgical treatment is associated with decreased recurrence risk in RPC, but with significant post-operative morbidity. Where surgery is deemed appropriate, patients with and without PD are likely to benefit from liver resection and biliary bypass, respectively.

PMID: 29228512 [PubMed - as supplied by publisher]

Myeloid Neoplasms Following Solid Organ Transplantation: Clinicopathologic Studies of 23 Cases.

Tue, 12/12/2017 - 16:48

Myeloid Neoplasms Following Solid Organ Transplantation: Clinicopathologic Studies of 23 Cases.

Am J Clin Pathol. 2017 Dec 07;:

Authors: Wu B, Ingersoll K, Jug R, Yang LH, Luedke C, Lo A, Su P, Liu X, Rehder C, Gong J, Lu CM, Wang E

Abstract
Objectives: Myeloid neoplasms (MNs) after solid organ transplant are rare, and their clinicopathologic features have not been well characterized.
Methods: We retrospectively analyzed 23 such cases.
Results: The ages ranged from 2 to 76 years, with a median of 59 years at the diagnosis. The median interval between the transplant and diagnosis was 56 months (range, 8-384 months). The transplanted organs included liver in five, kidney in six, lung in five, heart in six, and heart/lung in one case(s). The types of MN included acute myeloid leukemia (AML) in 12, myelodysplastic syndrome (MDS) in five, chronic myelogenous leukemia (CML) in four, and myeloproliferative neoplasms (MPNs) in two cases. Cytogenetics demonstrated clonal abnormalities in 18 (78.3%) cases, including unbalanced changes in 10 (55.6%), Philadelphia chromosome in four (22.2%), and other balanced aberrations in four (22.2%) cases. Thirteen (56.5%) patients died, with an estimated median survival of 9 months. With disease stratification, AML and MDS have short median survivals (3.5 and 7 months, respectively), with an initial precipitous decline of the survival curve.
Conclusions: Posttransplant MNs have a latency period between that seen in AML/MDS related to alkylators and that associated with topoisomerase II inhibitors. The cytogenetic profile suggests a mutagenic effect on leukemogenesis. The clinical outcome for AML/MDS is dismal, with death occurring at an early phase of treatment.

PMID: 29228125 [PubMed - as supplied by publisher]

MicroRNA-146b-5p Identified in Porcine Liver Donation Model is Associated with Early Allograft Dysfunction in Human Liver Transplantation.

Tue, 12/12/2017 - 16:48

MicroRNA-146b-5p Identified in Porcine Liver Donation Model is Associated with Early Allograft Dysfunction in Human Liver Transplantation.

Med Sci Monit. 2017 Dec 11;23:5876-5884

Authors: Li C, Zhao Q, Zhang W, Chen M, Ju W, Wu L, Han M, Ma Y, Zhu X, Wang D, Guo Z, He X

Abstract
BACKGROUND Poor transplant outcome was observed in donation after brain death followed by circulatory death (DBCD), since the donor organs suffered both cytokine storm of brain death and warm ischemia injury. MicroRNAs (miRNAs) have emerged as promising disease biomarkers, so we sought to establish a miRNA signature of porcine DBCD and verify the findings in human liver transplantation. MATERIAL AND METHODS MiRNA expression was determined with miRNA sequencing in 3 types of the porcine model of organ donation, including donation after brain death (DBD) group, donation after circulatory death (DCD) group, and DBCD group. Bioinformatics analysis was performed to reveal the potential regulatory behavior of target miRNA. Human liver graft biopsy samples after reperfusion detected by fluorescence in situ hybridization were used to verify the expression of target miRNA. RESULTS We compared miRNA expression profiles of the 3 donation types. The porcine liver graft miR-146b was significantly increased and selected in the DBCD group versus in the DBD and DCD groups. The donor liver expression of human miR-146b-5p, which is homologous to porcine miR-146b, was further examined in 42 cases of human liver transplantations. High expression of miR-146b-5p successfully predicted the post-transplant early allograft dysfunction (EAD) with the area under the ROC curve (AUC) 0.759 (P=0.004). CONCLUSIONS Our results revealed the miRNA signature of DBCD liver grafts for the first time. The miR-146b-5p may have important clinical implications for monitoring liver graft function and predicating transplant outcomes.

PMID: 29227984 [PubMed - in process]

An ALOX12-12-HETE-GPR31 signaling axis is a key mediator of hepatic ischemia-reperfusion injury.

Tue, 12/12/2017 - 16:48

An ALOX12-12-HETE-GPR31 signaling axis is a key mediator of hepatic ischemia-reperfusion injury.

Nat Med. 2017 Dec 11;:

Authors: Zhang XJ, Cheng X, Yan ZZ, Fang J, Wang X, Wang W, Liu ZY, Shen LJ, Zhang P, Wang PX, Liao R, Ji YX, Wang JY, Tian S, Zhu XY, Zhang Y, Tian RF, Wang L, Ma XL, Huang Z, She ZG, Li H

Abstract
Hepatic ischemia-reperfusion (IR) injury is a common clinical issue lacking effective therapy and validated pharmacological targets. Here, using integrative 'omics' analysis, we identified an arachidonate 12-lipoxygenase (ALOX12)-12-hydroxyeicosatetraenoic acid (12-HETE)-G-protein-coupled receptor 31 (GPR31) signaling axis as a key determinant of the hepatic IR process. We found that ALOX12 was markedly upregulated in hepatocytes during ischemia to promote 12-HETE accumulation and that 12-HETE then directly binds to GPR31, triggering an inflammatory response that exacerbates liver damage. Notably, blocking 12-HETE production inhibits IR-induced liver dysfunction, inflammation and cell death in mice and pigs. Furthermore, we established a nonhuman primate hepatic IR model that closely recapitulates clinical liver dysfunction following liver resection. Most strikingly, blocking 12-HETE accumulation effectively attenuated all pathologies of hepatic IR in this model. Collectively, this study has revealed previously uncharacterized metabolic reprogramming involving an ALOX12-12-HETE-GPR31 axis that functionally determines hepatic IR procession. We have also provided proof of concept that blocking 12-HETE production is a promising strategy for preventing and treating IR-induced liver damage.

PMID: 29227475 [PubMed - as supplied by publisher]

A systematic review and meta-analysis of second-line immunosuppressants for autoimmune hepatitis treatment.

Tue, 12/12/2017 - 16:48

A systematic review and meta-analysis of second-line immunosuppressants for autoimmune hepatitis treatment.

Eur J Gastroenterol Hepatol. 2017 Dec 08;:

Authors: De Lemos-Bonotto M, Valle-Tovo C, Costabeber AM, Mattos AA, Azeredo-da-Silva ALF

Abstract
INTRODUCTION: The gold-standard treatment for autoimmune hepatitis (AIH) is a prednisone/azathioprine combination. However, subgroups of patients may be unresponsive to this treatment. The aim of this study is to evaluate the efficacy of second-line immunosuppressive therapies for AIH through a systematic review and meta-analysis in adult patients.
PATIENTS AND METHODS: The systematic review was registered at the PROSPERO platform under number 42015019831. Databases MEDLINE (PubMed), Lilacs, Cochrane, and Scielo were searched. The keywords used were 'Hepatitis, Autoimmune' and descriptors terms (MeSH and DeCS). These terms were linked with each immunosuppressant of interest.
RESULTS: A total of 1532 studies were identified. Of these, 1492 were excluded on the basis of title and abstract reading. Among the 40 studies retrieved for detailed full-text analysis, a total of 15 fulfilled the inclusion criteria for the analysis. The most studied second-line immunosuppressive was mycophenolate mofetil (MM). The mean reduction of aminotransferases was observed in 94.3% with tacrolimus/prednisone, 91.3% for cyclosporine/prednisone, 85.5% for budesonide, and 78.7% MM/prednisone. For MM/prednisone, the mean rate of histological remission was 88.6%, liver transplantation was indicated in 11.4%, and the mortality rate was 7.2%. Limitations were also present, such as the lack of randomized-controlled trials and prospective studies, the small number of patients, and the heterogeneity between remission criteria.
CONCLUSION: This is the first systematic review and meta-analysis to compare the second-line imunossupressant therapy for AIH. The most studied second-line immunosuppressive is the MM, with a reasonable histological remission. The use of combined tacrolimus/prednisone was the most effective for the normalization of aminotransferases.

PMID: 29227329 [PubMed - as supplied by publisher]

A systems-based approach to patient care after liver transplantation.

Tue, 12/12/2017 - 16:48

A systems-based approach to patient care after liver transplantation.

JAAPA. 2017 Dec 07;:

Authors: Gillespie M, Rizzolo D

Abstract
Liver transplantation is a cure to many devastating acute and end-stage liver diseases. In the immediate postoperative period, patients are prone to graft, end-organ, and immunosuppressive complications. This article reviews the causes, diagnosis, and treatment of acute postoperative liver transplant complications.

PMID: 29227319 [PubMed - as supplied by publisher]

Pages