This new model using protein induced by vitamin K absence-II and alpha-fetoprotein provides refined prognostication. Among beyond-MC HCC patients, those with a MoRAL score ≤314.8 and without extrahepatic metastasis might be potential candidates for LDLT.
Hepatocellular carcinoma harbors numerous genomic and epigenomic aberrations of DNA copy numbers and DNA methylation. Transcriptomic deregulation by these aberrations plays key driver roles in heterogeneous progression of cancers. Here, we profile DNA copy numbers, DNA methylation, and messenger RNA expression levels from 64 cases of hepatocellular carcinoma specimens. We find that the frequencies of the aberrancies of the DNA copy-number-correlated (CNVcor) expression genes and the methylation-correlated expression (METcor) genes are co-regulated significantly. Multi-omics integration of the CNVcor and METcor genes reveal three prognostic subtypes of hepatocellular carcinoma, which can be validated by an independent data. The most aggressive subtype expressing stemness genes has frequent BAP1 mutations, implying its pivotal role in the aggressive tumor progression. In conclusion, our integrative analysis of genomic and epigenomic regulation provides new insights on the multi-layered pathobiology of hepatocellular carcinoma, which might be helpful in developing precision management for hepatocellular carcinoma patients.
TACE is an effective treatment that allows achievement of long-term survival rates comparable to those with HR and RFA in patients with small single-nodule hepatocellular carcinoma.
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.
Hypoxia-inducible factor-1 alpha (HIF-1α) is a transcription factor essential for cancer cell survival. The reprogramming of lipid metabolism has emerged as a hallmark of cancer, yet the relevance of HIF-1α to this process remains elusive. In this study, we profile HIF-1α-interacting proteins using proteomics analysis and identify fatty acid-binding protein 5 (FABP5) as a critical HIF-1α-binding partner. In hepatocellular carcinoma (HCC) tissues, both FABP5 and HIF-1α are upregulated, and their expression levels are associated with poor prognosis. FABP5 enhances HIF-1α activity by promoting HIF-1α synthesis while disrupting FIH/HIF-1α interaction at the same time. Oleic-acid treatment activates the FABP5/HIF-1α axis, thereby promoting lipid accumulation and cell proliferation in HCC cells. Our results indicate that fatty-acid-induced FABP5 upregulation drives HCC progression through HIF-1-driven lipid metabolism reprogramming.
Donor safety remains an important concern in living donor liver transplantation (LDLT). In the present study, we assessed recent advancements in the donor operation for LDLT through our experience with this procedure. A total of 886 donor hepatectomies performed between January 1999 and December 2012 were analyzed. Three chronological periods were investigated: the initial period (1999-2004, n 5 239), the period in which the right liver with middle hepatic vein reconstruction was primarily used (2005-2010, n 5 422), and the period in which the right liver with a standardized protocol, including a preoperative donor diet program, an evaluation of steatosis with magnetic resonance spectroscopy, no systemic heparin administration or central venous pressure monitoring, exact midplane dissection, and incremental application of minimal incisions, was exclusively used (2011-2012, n 5 225). The proportion of patients > 50 years old increased (2.5% versus 4.7% versus 8.9%), whereas the proportion of patients with a remnant liver volume 30% (6.5% versus 13.9% versus 6.3%) and with macrosteatosis 10% (7.9% versus 11.1% versus 4.4%) decreased throughout the periods. The operative time (292.7 versus 290.0 versus 272.8 minutes), hospital stay (12.4 versus 11.2 versus 8.5 days), and overall morbidity rate (26.4% versus 13.3% versus 5.8%), including major complications (>grade 3; 1.7% versus 1.9% versus 0.9%) and biliary complications (7.9% versus 5.0% versus 0.9%), were markedly reduced in the most recent period. No intraoperative transfusion was required. No cases of irreversible disability or mortality were noted. In conclusion, the quality of the donor operation has recently been standardized through a large volume of experience, and the operation has been proven to have minimal risk. However, a constant evaluation of our experience is critical for remaining prepared for any unavoidable crisis.
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