Hepatic loss of miR-122 predisposes mice to hepatobiliary cyst and hepatocellular carcinoma upon diethylnitrosamine exposure.

Loss of miR-122 causes chronic steatohepatitis and spontaneous hepatocellular carcinoma. However, the consequence of miR-122 deficiency on genotoxic stress-induced liver pathogenesis is poorly understood. Here, we investigated the impact of miR-122 depletion on liver pathobiology by treating liver-specific miR-122 knockout (LKO) mice with the hepatocarcinogen diethylnitrosamine (DEN). At 25 weeks post-DEN injection, all LKO mice developed CK-19-positive hepatobiliary cysts, which correlated with DEN-induced transcriptional activation of Cdc25a mediated through E2f1. Additionally, LKO livers were more fibrotic and vascular, and developed larger microscopic tumors, possibly due to elevation of the Axl oncogene, a receptor tyrosine kinase as a novel target of miR-122, and several protumorigenic miR-122 targets. At 35 weeks following DEN exposure, LKO mice exhibited a higher incidence of macroscopic liver tumors (71%) and cysts (86%) compared to a 21.4% and 0% incidence of tumors and cysts, respectively, in control mice. The tumors in LKO mice were bigger (ninefold, P = 0.015) and predominantly hepatocellular carcinoma, whereas control mice mostly developed hepatocellular adenoma. DEN treatment also reduced survival of LKO mice compared to control mice (P = 0.03). Interestingly, induction of oxidative stress and proinflammatory cytokines in LKO liver shortly after DEN exposure indicates predisposition of a pro-tumorigenic microenvironment. Collectively, miR-122 depletion facilitates cystogenesis and hepatocarcinogenesis in mice on DEN challenge by up-regulating several genes involved in proliferation, growth factor signaling, neovascularization, and metastasis.

Rankings From US News and World Report Have Minimal Correlation With Kidney and Liver Transplant Recipient Survival Results From Retrospective Data.

OBJECTIVES: Increased demand for quality health care has led to lay-press ranking systems, such as the ranking from US News and World Report (US News). Their "Best Hospitals" publication advertises itself as the go-to resource for patients seeking care in a number of specialty areas. We sought to test the relationship between US News rankings and transplant outcomes. MATERIALS AND METHODS: Using data from 2014 to 2018, we compared outcomes from the Scientific Registry of Transplant Recipients database for liver and kidney transplants against US News-ranked centers using the categories "Nephrology" and "GI Surgery and Gastroenterology" as substitutes, as US News does not rank transplant centers specifically. P < .05 was set as significant. RESULTS: Using hazard ratio data, we found that kidney transplant center rank had only a small impact on postoperative outcomes in terms of patient survival (hazard ratio = 0.996, P = .049) but had no impact on graft survival (hazard ratio = 0.997, P = .077). In addition, liver transplant center rank had no impact on liver graft survival (hazard ratio = 1.003, P = .304). The impact of hospital ranking on survival was minimal compared with other variables. CONCLUSIONS: The US News rankings for "Nephrology" and "GI Surgery and Gastroenterology" have minimal values as a measure of liver and kidney transplant outcomes, highlighting that these lay press rankings are not useful to the unique transplant patient population and that providers should help guide patients to transplant-specific resources.