Therefore, down-regulation of mir302b and mir20a during early liver development may relieve the suppression of TGFβ signaling to promote hepatoblast proliferation. AZD5363 We thank Wenbo Xu and David Ho for technical assistance, and Dr. Nagarajan Kannan, Dr. Jeremy

Parker, and Jeff Lam for helpful discussion. P.A.H., M.A.M., and S.J.M.J. are Senior Scholars of the Michael Smith Foundation Health Research. Additional Supporting Information may be found in the online version of this article. “
“BACKGROUND AND AIM: Hepatocellular carcinoma (HCC) is an important complication of cirrhosis with an increasing incidence in the U.S. most likely due to hepatitis C virus (HCV). The only potentially curative treatment option for HCC is liver transplantation. METHODS: All adults (18+) who underwent liver transplantation for HCC were

included from the Scientific Registry of Transplant Recipients (1992-2013). Etiology of liver disease (LD) was grouped into HCV (anti-HCV-posi-tive), hepatitis find more B (HBV, HBsAg-positive), and other LD (negative viral hepatitis serology). RESULTS: Total 8,625 liver transplant recipients with HCC were included; 5,471 had HCV, 604 HBV, and 2,387 had other causes of LD. In comparison to hepatitis C, patients with hepatitis B were predominantly Asian (60.3%) and male (83.0%), had lower rates of pre-transplant obesity (HBV 11.4% vs. 30.1% in hepatitis C, 37.9% in other LD, p<0.0001), diabetes (HBV 14.2% vs. HCV 17.5% and other LD 30.5%, respectively, p<0.0001). Important comorbid-ities SPTLC1 were equally prevalent regardless of etiology (coronary artery disease, stroke, peripheral vascular disease, pulmonary embolism, cancer) (all p>0.05). In follow-up (43±38 months), 7.9% of HCC patients had graft failure and 27.8% died. HCV patients with HCC had highest average rate of graft failure: HBV 5.5% vs. HCV 8.9% vs. 6.4% in other LD (p<0.0001). After 1 year of follow-up, graft failure rates were similar in all HCC patients (4.8%-5.4%,

p=0.55). Despite this, starting year 3 post-transplant, the cumulative risk of graft failure in HCV patients became significantly higher (HCV 11.4% vs. HBV 6.6% vs. other LD 8.0%, p=0.0003) and remained high by follow-up year 5 (HCV 14.5% vs. HBV 8.1% vs. other LD 9.9%, 0.0007). The lowest post-transplant mortality rate was observed in HBV patients (HBV: 19.9% vs. HCV 29.1% and other LD 26.9%, p<0.0001). In fact, this difference was borderline significant starting as early as 1 year post-transplant (HBV 8.5% vs. HCV 12.0%, other LD 11.4%, p=0.0596), became highly significant by year 3 (HBV 15.5% vs. HCV 27.0% and other LD 22.7%, p<0.0001). In multivariate analysis of HCC patients, having hepatitis C was independently associated with an increased risk of both graft failure (aHR (95% CI) = 1.73 (1.35-2.21), p<0.0001) and mortality (1.34 (1.20-1.49), p<0.0001).