ERα-associated translocations underlie oncogene amplifications in breast cancer.

Focal copy-number amplification is an oncogenic event. Although recent studies have revealed the complex structure1-3 and the evolutionary trajectories4 of oncogene amplicons, their origin remains poorly understood. Here we show that focal amplifications in breast cancer frequently derive from a mechanism-which we term translocation-bridge amplification-involving inter-chromosomal translocations that lead to dicentric chromosome bridge formation and breakage. In 780 breast cancer genomes, we observe that focal amplifications are frequently connected to each other by inter-chromosomal translocations at their boundaries. Subsequent analysis indicates the following model: the oncogene neighbourhood is translocated in G1 creating a dicentric chromosome, the dicentric chromosome is replicated, and as dicentric sister chromosomes segregate during mitosis, a chromosome bridge is formed and then broken, with fragments often being circularized in extrachromosomal DNAs. This model explains the amplifications of key oncogenes, including ERBB2 and CCND1. Recurrent amplification boundaries and rearrangement hotspots correlate with oestrogen receptor binding in breast cancer cells. Experimentally, oestrogen treatment induces DNA double-strand breaks in the oestrogen receptor target regions that are repaired by translocations, suggesting a role of oestrogen in generating the initial translocations. A pan-cancer analysis reveals tissue-specific biases in mechanisms initiating focal amplifications, with the breakage-fusion-bridge cycle prevalent in some and the translocation-bridge amplification in others, probably owing to the different timing of DNA break repair. Our results identify a common mode of oncogene amplification and propose oestrogen as its mechanistic origin in breast cancer.

The landscape of human SVA retrotransposons.

SINE-VNTR-Alu (SVA) retrotransposons are evolutionarily young and still-active transposable elements (TEs) in the human genome. Several pathogenic SVA insertions have been identified that directly mutate host genes to cause neurodegenerative and other types of diseases. However, due to their sequence heterogeneity and complex structures as well as limitations in sequencing techniques and analysis, SVA insertions have been less well studied compared to other mobile element insertions. Here, we identified polymorphic SVA insertions from 3646 whole-genome sequencing (WGS) samples of >150 diverse populations and constructed a polymorphic SVA insertion reference catalog. Using 20 long-read samples, we also assembled reference and polymorphic SVA sequences and characterized the internal hexamer/variable-number-tandem-repeat (VNTR) expansions as well as differing SVA activity for SVA subfamilies and human populations. In addition, we developed a module to annotate both reference and polymorphic SVA copies. By characterizing the landscape of both reference and polymorphic SVA retrotransposons, our study enables more accurate genotyping of these elements and facilitate the discovery of pathogenic SVA insertions.

BamSnap: a lightweight viewer for sequencing reads in BAM files.

SUMMARY: Despite the improvement in variant detection algorithms, visual inspection of the read-level data remains an essential step for accurate identification of variants in genome analysis. We developed BamSnap, an efficient BAM file viewer utilizing a graphics library and BAM indexing. In contrast to existing viewers, BamSnap can generate high-quality snapshots rapidly, with customized tracks and layout. As an example, we produced read-level images at 1000 genomic loci for >2500 whole-genomes. AVAILABILITY AND IMPLEMENTATION: BamSnap is freely available at https://github.com/parklab/bamsnap. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

HiTea: a computational pipeline to identify non-reference transposable element insertions in Hi-C data.

Hi-C is a common technique for assessing 3D chromatin conformation. Recent studies have shown that long-range interaction information in Hi-C data can be used to generate chromosome-length genome assemblies and identify large-scale structural variations. Here, we demonstrate the use of Hi-C data in detecting mobile transposable element (TE) insertions genome-wide. Our pipeline Hi-C-based TE analyzer (HiTea) capitalizes on clipped Hi-C reads and is aided by a high proportion of discordant read pairs in Hi-C data to detect insertions of three major families of active human TEs. Despite the uneven genome coverage in Hi-C data, HiTea is competitive with the existing callers based on whole-genome sequencing (WGS) data and can supplement the WGS-based characterization of the TE-insertion landscape. We employ the pipeline to identify TE-insertions from human cell-line Hi-C samples. AVAILABILITY AND IMPLEMENTATION: HiTea is available at https://github.com/parklab/HiTea and as a Docker image. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Global burden of lung cancer attributable to ambient fine particulate matter pollution in 204 countries and territories, 1990-2019.

INTRODUCTION: Understanding the latest global spatio-temporal pattern of lung cancer burden attributable to ambient fine particulate matter pollution (PM2.5) is crucial to prioritize global lung cancer prevention, as well as environment improvement. METHODS: Data on lung cancer attributable to ambient PM2.5 were downloaded from the Global Burden of Disease Study (GBD) 2019. The numbers and age-standardized rates on lung cancer mortality (ASMR) and disability-adjusted life years (ASDR) were estimated by age, sex, region, and country. We used estimated annual percentage change (EAPC) to quantify the temporal trends of ASMR and ASDR from 1990 to 2019. RESULTS: In 2019, the number of global lung cancer deaths and DALYs attributable to ambient PM2.5 was approximately 0.31 million and 7.02 million respectively, among which more deaths and DALYs occurred in males. At GBD region level, the heaviest burden occurred in East Asia, accounting for over 50% worldwide, with China ranked first worldwide. The number of ambient PM2.5 attributable lung cancer deaths and DALYs has over doubled from 1990 to 2019, but high sociodemographic index (SDI) region had a rapid decrease, with EAPC -2.21 in ASMR (95% CI: -2.32, -2.09). The age-specific mortality rate or DALY rate has increased in all age groups in low to middle SDI regions from 1990 to 2019. The ASMR or ASDR showed an inverted V-shaped association with SDI. The EAPC in ASMR or ASDR was highly negatively correlated with ASMR or ASDR in 1990 and SDI in 2019, with coefficients around 0.70. CONCLUSIONS: The number of ambient PM2.5-related lung cancer deaths and DALYs has largely increased because of the increase of exposure to PM2.5, population growth, and aging. Local governments should do economic activities under the consideration of public health, especially in high-burden areas.

The global burden of disease attributable to ambient fine particulate matter in 204 countries and territories, 1990-2019: A systematic analysis of the Global Burden of Disease Study 2019.

Understanding the spatio-temporal patterns of the disease burden attributable to ambient PM2.5 across the world is essential for the prevention of related diseases, as well as ambient PM2.5 control. Following the framework and methodology of the Global Burden of Disease Study (GBD) in 2019, the global, regional, and national data on ambient PM2.5-attributable death and disability-adjusted life years (DALYs), and the age-standardized rates of mortality (ASMR) and disability-adjusted life years (ASDR) were summarized based on age, gender, year, location and specific diseases. We calculated the average annual percentage change (AAPC) to depict the secular trends of ASMR and ASDR from 1990 to 2019. In 2019, the global ambient PM2.5-related deaths and DALYs were 4,140,970 and 118.2 million, respectively, with 1,702,150 deaths and 47.5 million DALYs for females and 2,438,820 deaths and 70.7 million DALYs for male. In the 13 level-three causes, ischemic heart disease, stroke, chronic obstructive and pulmonary disease (COPD) were the leading three causes of deaths and DALYs attributable to ambient PM2.5. The number of global deaths and DALYs attributable to ambient PM2.5 has increased by 102.3% and 67.7% from 1990 to 2019, respectively. However, ASMR and ASDR showed little change. In the 13 level-three diseases, ischemic heart disease, stroke, COPD, diabetes mellitus, and lung cancer were the top five contributors to the increase of global deaths or DALYs, among which diabetes mellitus had the fastest increase of ASMR and ASDR, with AAPC of 1.5 (95% CI: 1.43, 1.58) and 2.21 (95% CI: 2.15, 2.27), respectively. The population attributable fractions (PAF) of causes in ASMR or ASDR varied significantly across regions, of which PAF of COPD, stroke and lung cancer were the top three. Regarding the GBD region, high PAF mainly occurred in North Africa and Middle East, South Asia, and East Asia. The age-specific PAFs of ischemic heart disease and stroke deaths and DALYs due to ambient PM2.5 were negatively correlated with age. ASMR and ASDR of overall PM2.5 related-burden showed an inverted "V/U" relationship with the socio-demographic index (SDI). The AAPC of ASMR and ASDR of the overall causes showed a strong negative correlation with SDI in 2019, especially at the SDI larger than 0.5. The deaths and DALYs attributable to ambient PM2.5 continued to increase under the context of population growth and aging. Decision-makers should consider controlling the PM2.5 emission when developing the economy.

Induced Quantized Spin Current in Vacuum.

We uncover a fundamental effect of the QED vacuum in an external electromagnetic (EM) field. We show that the quantized vacuum of electrons is spin polarized by the EM field and manifests as a vacuum spin current. An experiment is proposed to measure the spin torque exerted by the spin current by measuring the twisted angle of the director axis of a nematic liquid crystal.

Clinicopathologic analysis of intraductal papillary neoplasm of bile duct: Korean multicenter cohort study.

BACKGROUND: IPNB is very rare disease and most previous studies on IPNB were case series with a small number due to low incidence. The aim of this study is to validate previously known clinicopathologic features of intraductal papillary neoplasm of bile duct (IPNB) based on the first largest multicenter cohort. METHODS: Among 587 patients previously diagnosed with IPNB and similar diseases from each center in Korea, 387 were included in this study after central pathologic review. We also reviewed all preoperative image data. RESULTS: Of 387 patients, 176 (45.5%) had invasive carcinoma and 21 (6.0%) lymph node metastasis. The 5-year overall survival was 80.9% for all patients, 88.8% for IPNB with mucosal dysplasia, and 70.5% for IPNB with invasive carcinoma. According to the "Jang & Kim's modified anatomical classification," 265 (68.5%) were intrahepatic, 103 (26.6%) extrahepatic, and 16 (4.1%) diffuse type. Multivariate analysis revealed that tumor invasiveness was a unique predictor for survival analysis. (p = 0.047 [hazard ratio = 2.116, 95% confidence interval 1.010-4.433]). CONCLUSIONS: This is the first Korean multicenter study on IPNB through central pathologic and radiologic review process. Although IPNB showed good long-term prognosis, relatively aggressive features were also found in invasive carcinoma and extrahepatic/diffuse type.

GAPPadder: a sensitive approach for closing gaps on draft genomes with short sequence reads.

BACKGROUND: Closing gaps in draft genomes is an important post processing step in genome assembly. It leads to more complete genomes, which benefits downstream genome analysis such as annotation and genotyping. Several tools have been developed for gap closing. However, these tools don't fully utilize the information contained in the sequence data. For example, while it is known that many gaps are caused by genomic repeats, existing tools often ignore many sequence reads that originate from a repeat-related gap. RESULTS: We compare GAPPadder with GapCloser, GapFiller and Sealer on one bacterial genome, human chromosome 14 and the human whole genome with paired-end and mate-paired reads with both short and long insert sizes. Empirical results show that GAPPadder can close more gaps than these existing tools. Besides closing gaps on draft genomes assembled only from short sequence reads, GAPPadder can also be used to close gaps for draft genomes assembled with long reads. We show GAPPadder can close gaps on the bed bug genome and the Asian sea bass genome that are assembled partially and fully with long reads respectively. We also show GAPPadder is efficient in both time and memory usage. CONCLUSION: In this paper, we propose a new approach called GAPPadder for gap closing. The main advantage of GAPPadder is that it uses more information in sequence data for gap closing. In particular, GAPPadder finds and uses reads that originate from repeat-related gaps. We show that these repeat-associated reads are useful for gap closing, even though they are ignored by all existing tools. Other main features of GAPPadder include utilizing the information in sequence reads with different insert sizes and performing two-stage local assembly of gap sequences. The results show that our method can close more gaps than several existing tools. The software tool, GAPPadder, is available for download at https://github.com/Reedwarbler/GAPPadder .

Genomic Takeover by Transposable Elements in the Strawberry Poison Frog.

We sequenced the genome of the strawberry poison frog, Oophaga pumilio, at a depth of 127.5× using variable insert size libraries. The total genome size is estimated to be 6.76 Gb, of which 4.76 Gb are from high copy number repetitive elements with low differentiation across copies. These repeats encompass DNA transposons, RNA transposons, and LTR retrotransposons, including at least 0.4 and 1.0 Gb of Mariner/Tc1 and Gypsy elements, respectively. Expression data indicate high levels of gypsy and Mariner/Tc1 expression in ova of O. pumilio compared with Xenopus laevis. We further observe phylogenetic evidence for horizontal transfer (HT) of Mariner elements, possibly between fish and frogs. The elements affected by HT are present in high copy number and are highly expressed, suggesting ongoing proliferation after HT. Our results suggest that the large amphibian genome sizes, at least partially, can be explained by a process of repeated invasion of new transposable elements that are not yet suppressed in the germline. We also find changes in the spliceosome that we hypothesize are related to permissiveness of O. pumilio to increases in intron length due to transposon proliferation. Finally, we identify the complement of ion channels in the first genomic sequenced poison frog and discuss its relation to the evolution of autoresistance to toxins sequestered in the skin.

An improved approach for reconstructing consensus repeats from short sequence reads.

BACKGROUND: Repeat elements are important components of most eukaryotic genomes. Most existing tools for repeat analysis rely either on high quality reference genomes or existing repeat libraries. Thus, it is still challenging to do repeat analysis for species with highly repetitive or complex genomes which often do not have good reference genomes or annotated repeat libraries. Recently we developed a computational method called REPdenovo that constructs consensus repeat sequences directly from short sequence reads, which outperforms an existing tool called RepARK. One major issue with REPdenovo is that it doesn't perform well for repeats with relatively high divergence rates or low copy numbers. In this paper, we present an improved approach for constructing consensus repeats directly from short reads. Comparing with the original REPdenovo, the improved approach uses more repeat-related k-mers and improves repeat assembly quality using a consensus-based k-mer processing method. RESULTS: We compare the performance of the new method with REPdenovo and RepARK on Human, Arabidopsis thaliana and Drosophila melanogaster short sequencing data. And the new method fully constructs more repeats in Repbase than the original REPdenovo and RepARK, especially for repeats of higher divergence rates and lower copy number. We also apply our new method on Hummingbird data which doesn't have a known repeat library, and it constructs many repeat elements that can be validated using PacBio long reads. CONCLUSION: We propose an improved method for reconstructing repeat elements directly from short sequence reads. The results show that our new method can assemble more complete repeats than REPdenovo (and also RepARK). Our new approach has been implemented as part of the REPdenovo software package, which is available for download at https://github.com/Reedwarbler/REPdenovo .

CircMarker: a fast and accurate algorithm for circular RNA detection.

BACKGROUND: While RNA is often created from linear splicing during transcription, recent studies have found that non-canonical splicing sometimes occurs. Non-canonical splicing joins 3' and 5' and forms the so-called circular RNA. It is now believed that circular RNA plays important biological roles such as affecting susceptibility of some diseases. During the past several years, multiple experimental methods have been developed to enrich circular RNA while degrade linear RNA. Although several useful software tools for circular RNA detection have been developed as well, these tools are based on reads mapping may miss many circular RNA. Also, existing tools are slow for large data due to their dependence on reads mapping. METHOD: In this paper, we present a new computational approach, named CircMarker, based on k-mers rather than reads mapping for circular RNA detection. CircMarker takes advantage of transcriptome annotation files to create the k-mer table for circular RNA detection. RESULTS: Empirical results show that CircMarker outperforms existing tools in circular RNA detection on accuracy and efficiency in many simulated and real datasets. CONCLUSIONS: We develop a new circular RNA detection method called CircMarker based on k-mer analysis. Our results on both simulation data and real data demonstrate that CircMarker runs much faster and can find more circular RNA with higher consensus-based sensitivity and high accuracy ratio compared with existing tools.

Metformin ameliorates TGF-ß1-induced osteoblastic differentiation of human aortic valve interstitial cells by inhibiting ß-catenin signaling.

Osteoblastic differentiation of aortic valve interstitial cells (AVICs) is the central process in the development of calcific aortic valve disease (CAVD). Metformin is a widely used first-line antidiabetic drug, and recently, pleiotropic benefits of metformin beyond hypoglycemia have been reported in the cardiovascular system. Here, we examined the effect of metformin on the osteoblastic differentiation of human AVICs. Our results showed that metformin ameliorated TGF-ß1-induced production of osteogenic proteins Runx2 and osteopontin as well as calcium deposition in the cultured human AVICs. Experiments using AICAR, Compound C and AMPKα siRNA showed that the beneficial effect of metformin on TGF-ß1-induced osteoblastic differentiation of human AVICs was mediated by AMPKα. Moreover, metformin inhibited the TGF-ß1-induced activation of ß-catenin, and ß-catenin siRNA blocked TGF-ß1-induced osteoblastic differentiation of AVICs. Smad2/3 and JNK were phosphorylated to promote the TGF-ß1-induced activation of ß-catenin and osteoblastic differentiation of AVICs, and metformin also alleviated TGF-ß1-induced activation of Smad2/3 and JNK. In conclusion, our results suggest a beneficial effect of metformin based on the prevention of osteoblastic differentiation of human AVICs via inhibition of ß-catenin, which indicates the therapeutic potential of metformin for CAVD.

Weyl Anomaly Induced Current in Boundary Quantum Field Theories.

We show that when an external magnetic field parallel to the boundary is applied, the Weyl anomaly gives rises to a new anomalous current in the vicinity of the boundary. The induced current is a magnetization current in origin: the movement of the virtual charges near the boundary give rise to a nonuniform magnetization of the vacuum and hence a magnetization current. Unlike other previously studied anomalous current phenomena such as the chiral magnetic effect or the chiral vortical effect, this induced current does not rely on the presence of a material system and can occur in vacuum. Similar to the Casimir effect, our discovered phenomenon arises from the effect of the boundary on the quantum fluctuations of the vacuum. However this induced current is purely quantum mechanical and has no classical limit. We briefly comment on how this induced current may be observed experimentally.

Enhanced Photosensing and Photodynamic Treatment of Colon Cancer Cells Using Methoxy Poly(ethylene glycol)-Conjugated Chlorin e6.

Nanophotosensitizer composed of methoxy poly(ethylene glycol) (MePEG) and chlorin e6 (Ce6) (abbreviated as Pe6) was synthesized for efficient delivery of Ce6 to the colon cancer cells. Pe6 nanophotosensitizer has small diameter less than 100 nm with spherical shape and core-shell structure. They were activated in aqueous solution while Ce6 was quenched due to its poor aqueous solubility. They showed no intrinsic cytotoxicity against normal cells and colon cancer cells. Pe6 nanophotosensitizers showed enhanced cellular uptake, phototoxicity, and reactive oxygen species (ROS) generation at in vitro cell culture experiment. Furthermore, they showed improved tumor tissue penetration and accumulation in vivo animal studies. We suggested Pe6 nanophotosensitizers as an ideal candidate for PDT of colon cancer.

Donor safety in living donor liver transplantation: The Korean organ transplantation registry study.

Major concerns about donor safety cause controversy and limit the use of living donor liver transplantation to overcome organ shortages. The Korean Organ Transplantation Registry established a nationwide organ transplantation registration system in 2014. We reviewed the prospectively collected data of all 832 living liver donors who underwent procedures between April 2014 and December 2015. We allocated the donors to a left lobe group (n = 59) and a right lobe group (n = 773) and analyzed the relations between graft types and remaining liver volumes and complications (graded using the Clavien 5-tier grading system). The median follow-up was 19 months (range, 10-31 months). During the study period, 553 men and 279 women donated livers, and there were no deaths after living liver donation. The overall, biliary, and major complication (grade ≥ III) rates were 9.3%, 1.7%, and 1.9%, respectively. The graft types and remaining liver volume were associated with significantly different overall, biliary, and major complication rates. Of the 16 patients with major complications, 9 (56.3%) involved biliary complications (2 biliary strictures [12.5%] and 7 bile leakages [43.8%]). Among the 832 donors, the mean aspartate transaminase, alanine aminotransferase, and total bilirubin levels were 23.9 ± 8.1 IU/L, 20.9 ± 11.3 IU/L, and 0.8 ± 0.4 mg/dL, respectively, 6 months after liver donation. In conclusion, biliary complications were the most common types of major morbidity in living liver donors. Donor hepatectomy can be performed successfully with minimal and easily controlled complications. Our study shows that prospective, nationwide cohort data provide an important means of investigating the safety in living liver donation. Liver Transplantation 23 999-1006 2017 AASLD.

Risk factors of early recurrence after curative hepatectomy in hepatocellular carcinoma.

Early recurrence is common after curative hepatectomy for hepatocellular carcinoma and is associated with poor prognosis. This study aimed to identify risk factors of early recurrence after curative hepatectomy in hepatocellular carcinoma. Overall, 63 patients who underwent curative hepatectomy for hepatocellular carcinoma were enrolled. Patients were divided into the early recurrence group, who developed recurrence within 12 months after hepatectomy (n = 10), and the non-early recurrence group (n = 53). Clinicopathological factors of early recurrence were retrospectively analyzed. Among the 63 patients, 10 (15.9%) patients experienced early recurrence. Univariate analysis showed tumor necrosis (p = 0.012), level of PIVKA-II (prothrombin induced by vitamin K absence or antagonist-II; p = 0.002), and microvascular invasion (p = 0.029) to be associated with early recurrence. By multivariate analysis, there were significant differences in high PIVKA-II (p < 0.001) and tumor necrosis (p = 0.012) in patients with early recurrence. The optimal cutoff values of PIVKA-II and tumor necrosis were 46 mAU/mL and 3% of total tumor volume, respectively. Patients with a high preoperative PIVKA-II level and extent of tumor necrosis, which are independent risk factors for early recurrence, should be actively treated and monitored closely after hepatectomy.

Increasing use of therapeutic apheresis as a liver-saving modality.

INTRODUCTION: Therapeutic plasma exchange (TPE) is used for temporary support of liver function in patients presenting with early graft dysfunction after liver transplantation (LT) or liver surgery. We analyzed the effect of therapeutic apheresis on patients with liver disease. METHODS: Between January 2011 and August 2016, 93 apheresis procedures were performed for 26 patients at our institution. Anti-ABO isoagglutination immunoglobulin (Ig) M titer was checked using a type A and type B 3% red blood cell (RBC) suspension in saline with two-fold serial dilutions of patient serum. Anti-ABO isoagglutination IgG titer was checked by a type A and B 0.8% RBC suspension using a low-ionic strength/Coombs card. RESULTS: ABO-incompatible (ABOi) LT was the most common (n=10, 38.5%) indication for apheresis; early graft dysfunction after LT (n=8, 30.7%) was the second most common. Median initial IgM and IgG anti-ABO titers for ABOi LT recipients were 1:16 (range, 1:8-1:128) and 1:48 (range, 1:8-1:2048). We performed preoperative TPE in 10 recipients (median number of sessions, 1.5; range, 1-11). Among patients with early graft dysfunction, those who underwent living donor LT had better survival (4/4; 100%) than those who underwent nonliving donor LT (0/3; 0%). Patients who underwent living donor LT first and then additional LT also survived after three TPE sessions. CONCLUSION: Therapeutic apheresis is associated with a good survival rate and is essential for liver support in patients with early graft dysfunction after LT or posthepatectomy liver failure and during preparation for ABOi LT.

Efficacy and patency of primary stenting for hepatic venous outflow obstruction after living donor liver transplantation.

BACKGROUND: Hepatic venous outflow is important for graft survival in living donor liver transplantation (LDLT). If hepatic venous outflow obstruction occurs, hepatic vein stenting is considered to restore the patency. PURPOSE: To retrospectively evaluate the efficacy and patency of primary hepatic vein stenting for hepatic venous outflow obstruction (HVOO) after LDLT. MATERIAL AND METHODS: Percutaneous interventions, including hepatic vein stent placement with or without balloon angioplasty, were performed in 21 patients who had undergone LDLT and had HVOO confirmed through hepatic venography or manometry, including the patients who had a structural abnormality. Two stents each were inserted in four patients; therefore, the total number of treated anastomoses was 25. Technical success, patency rates, and pressure gradients between hepatic veins and the right atrium were evaluated in 19 patients each. RESULTS: Technical success was achieved in 25 of 26 vessels (96%). The mean interval between operation and stenting was 43 days. After the procedure, the follow-up period was a mean 530 days. The mean pressure gradient decreased from 8.5 mmHg to 2.1 mmHg after treatment (P < 0.01). The patency rates of the 25 vessels were 80% at 1, 2, and 3 years after stent placement. However, middle hepatic vein stenting revealed a low patency rate (all were 36%). Three of seven stents (43%) in the middle hepatic vein occluded during follow-up. CONCLUSION: Percutaneous primary hepatic vein stent replacement is an effective treatment for HVOO after LDLT.

Clinical Impacts of Donor Types of Living vs. Deceased Donors: Predictors of One-Year Mortality in Patients with Liver Transplantation.

Transplantation studies about the clinical differences according to the type of donors are mostly conducted in western countries with rare reports from Asians. The aims of this study were to evaluate the clinical impacts of the type of donor, and the predictors of 1-year mortality in patients who underwent liver transplantation (LT). This study was performed for liver transplant recipients between May 2010 and December 2014 at the Pusan National University Yangsan Hospital. A total of 185 recipients who underwent LT were analyzed. Of the 185 recipients, 109 (58.9%) belonged to the living donor liver transplantation (LDLT) group. The median age was 52.4 years. LDLT recipients had lower model for end-stage liver disease (MELD) score compared with better liver function than deceased donor liver transplantation (DDLT) recipients (mean ± standard deviation [SD], 12.5 ± 8.3 vs. 24.9 ± 11.7, respectively; P < 0.001), and had more advanced hepatocellular carcinoma (HCC) (62.4% vs. 21.1%, respectively; P = 0.001). In complications and clinical outcomes, LDLT recipients showed shorter stay in intensive care unit (ICU) (mean ± SD, 10.8 ± 8.8 vs. 23.0 ± 13.8 days, respectively, P < 0.001), ventilator care days, and post-operative admission days, and lower 1-year mortality (11% vs. 27.6%, respectively, P = 0.004). Bleeding and infectious complications were less in LDLT recipients. Recipients with DDLT (P = 0.004) showed higher mortality in univariate analysis, and multi-logistic regression analysis found higher MELD score and higher pre-operative serum brain natriuretic peptide (BNP) were associated with 1-year mortality. This study may guide improved management before and after LT from donor selection to post-operation follow up.