Hepatic resection is the most curative treatment option for early-stage hepatocellular carcinoma, but is associated with a high recurrence rate, which exceeds 50% at 5 years after surgery. Understanding the genetic basis of hepatocellular carcinoma at surgically curable stages may enable the identification of new molecular biomarkers that accurately identify patients in need of additional early therapeutic interventions. Whole exome sequencing and copy number analysis was performed on 231 hepatocellular carcinomas (72% with hepatitis B viral infection) that were classified as early-stage hepatocellular carcinomas, candidates for surgical resection. Recurrent mutations were validated by Sanger sequencing. Unsupervised genomic analyses identified an association between specific genetic aberrations and postoperative clinical outcomes. Recurrent somatic mutations were identified in nine genes, including TP53, CTNNB1, AXIN1, RPS6KA3, and RB1. Recurrent homozygous deletions in FAM123A, RB1, and CDKN2A, and high-copy amplifications in MYC, RSPO2, CCND1, and FGF19 were detected. Pathway analyses of these genes revealed aberrations in the p53, Wnt, PIK3/Ras, cell cycle, and chromatin remodeling pathways. RB1 mutations were significantly associated with cancer-specific and recurrence-free survival after resection (multivariate P 5 0.038 and P 5 0.012, respectively). FGF19 amplifications, known to activate Wnt signaling, were mutually exclusive with CTNNB1 and AXIN1 mutations, and significantly associated with cirrhosis (P 5 0.017). Conclusion: RB1 mutations can be used as a prognostic molecular biomarker for resectable hepatocellular carcinoma. Further study is required to investigate the potential role of FGF19 amplification in driving hepatocarcinogenesis in patients with liver cirrhosis and to investigate the potential of anti-FGF19 treatment in these patients. (HEPATOLOGY 2014;60:1972-1982 See Editorial on Page 1812 H epatocellular carcinoma (HCC) is the sixth most common malignancy worldwide and exhibits the third highest mortality rate. Recent

Serious complications have occurred in a considerable proportion of living donors of liver transplants, but data from a single high-volume center has rarely been available. We analyzed the medical records of donors and recipients of the first 1,000 living donor liver transplants, performed at Asan Medical Center from December 1994 to June 2005, with a focus on donor safety. There were 107 pediatric and 893 adult transplants. The most common diagnoses were biliary atresia in pediatric recipients (63%) and hepatitis B-associated liver cirrhosis (80%) in adult recipients. Right lobe donors were strictly selected based on liver resection rate and steatosis. From 1,162 living donors, 588 right lobes, 6 extended right lobes, 7 right posterior segments, 464 left lobes, and 107 left lateral segments were obtained. Of these, 837 grafts were implanted singly, whereas 325, along with 1 cadaveric split graft, were implanted as dual grafts into 163 recipients. The 5-yr survival rates were 84.8% in pediatric recipients and 83.2% in adult recipients. There was no donor mortality, but 3.2% of donors experienced major complications. Until the end of 2001, the major donor complication rate was 6.7%, with most occurring in right liver donors. Since 2002, liver resection exceeding 65% of whole liver volume were avoided except for young donors with no hepatic steatosis, and the donor complication rate has been reduced to 1.3%. In conclusion, a majority of major living donor complications appear to be avoidable through the strict selection of living donor and graft type, intensive postoperative surveillance, and timely feedback of surgical techniques. Selection of right lobe graft should be very prudently considered if the donor right liver appears to be larger than 65% of the whole liver volume. Liver Transpl 12: 920-927, 2006.