Citations

AbstractPancreas transplantation alone (PTA) is a β cell replacement option for selected patients with type 1 diabetes mellitus; concerns have been raised regarding deterioration in kidney function (KF) after PTA. This retrospective multicenter study assessed actual impact of transplantation and immunosuppression on KF in PTA recipients at three Transplant Centers. The primary composite endpoint 10 years after PTA was >50% eGFR decline, eGFR < 30 mL/min/1.73 m2, and/or receiving a kidney transplant (KT). Overall, 822 PTA recipients met eligibility. Median baseline and 10‐year eGFR (mL/min/1.73 m2) were 76.3 (58.1–100.8) and 51.3 (35.3–65.9), respectively. Primary composite endpoint occurred in 98 patients (53.5%) with 45 experiencing a >50% decrease in eGFR by 10 years post‐transplant, 38 eGFR < 30 mL/min/1.73 m2 and 49 requiring KT. KF declined most significantly within 6 months post‐PTA, more often in females and patients with better preserved GFR up to 5 years with 11.6% kidney failure at 10 years. Patient survival and death‐censored graft survival were both 68% at 10 years with overall graft thrombosis rate 8%. KF declined initially after PTA but stabilized with further slow progression. In conclusion, prospective intervention studies are needed to test renal sparing interventions while gathering more granular data.

333 Background: Hepatitis B is a cause of hepatocellular carcinoma (HCC) globally, irrespective of viral loads. Interestingly, this process is not necessarily mediated through cirrhosis and may in fact involve oncogenic processes. Prior studies have suggested specific oncogenic gene expression pathways affected by viral regulatory proteins. Thus, identifying these genes and associated pathways could highlight predictive factors for HCC transformation, and has implications in early diagnosis and treatment. Methods: We employed our Search, Tag, Analyze, Resource (STARGEO) platform to conduct a meta-analysis of public data from NCBI's Gene Expression Omnibus. We performed meta-analysis consisting of 155 tumor samples compared against 185 adjacent non-tumor samples. We present the results from the meta-analysis in Ingenuity Pathway Analysis. Results:Our analysis revealed LXR/RXR activation, LPS-IL-1 mediation inhibition of RXR, and FXR/RXR activation as top canonical pathways amongst others. Top upstream regulators identified included the Ras family gene RABL6. The role of RABL6 in oncogenesis is beginning to unfold but its specific role in HBV-related HCC remains undefined. Our causal analysis suggests RABL6 mediates pathogenesis of HBV-related HCC through promotion of genes related to cell division, epigenetic regulation, and Akt signaling. Additionally, HOXA10 was a top upstream regulator and was strongly upregulated in our analysis. While described in other cancer, HOXA10 has not been well documented in HBV-related HCC and our causal analysis suggests it mediates pathogenesis through downregulation of tumor suppressors and its protective effect from oxidative stress. Conclusions: This meta-analysis describes possible role of viral regulatory proteins such as RABL6 and HOXA10 in the pathogenesis of HBV -related HCC. Further prospective studies are needed to confirm our findings.