Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related death in the world. The incidence of HCC in India is reportedly low and varies from 0.2 to 1.9 %. Aflatoxins, secondary metabolites produced by Aspergillus flavus and Aspergillus parasiticus, are potent human carcinogens implicated in HCC. The prevalence of aflatoxin B1 (AFB1) as co-carcinogen was analysed using an in-house immunoperoxidase test in 31 liver biopsies and 7 liver-resection specimens from histopathologically proven HCC, and in 15 liver biopsies from cirrhosis patients (control group). Serum was tested for hepatitis B and C serological markers using commercial assays, and for AFB1 using an in-house ELISA with a sensitivity of~1 ng ml "1 for AFB1. In spite of positive AFB1 immunostaining in HCC cases, all serum specimens, from both HCC and the control groups, were AFB1-negative. There were 18 (58.1 %) HCC cases that revealed AFB1 in liver biopsies; 68.8 % (n511) of non-B non-C hepatitis cases with HCC and 46.1 % (n56) of the hepatitis B surface-antigen-positive subjects were positive for AFB1. Out of the two hepatitis B/hepatitis C virus co-infected cases, one was positive for AFB1. Of seven tumour-resection samples, six were positive for AFB1. Only one case revealed AFB1 in the nontumour area of the resected material. Thus AFB1 staining was significantly associated with tumour tissue (P50.03). Aflatoxins proved to have a significant association with HCC in this peninsular part of the subcontinent. The impact seems to be a cumulative process, as revealed by the AFB1 deposits in HCC liver tissue, even though the serum levels were undetectable.

BackgroundType 1 Interferon (IFN) expression has been shown to correlate with disease severity in systemic lupus erythematosus (SLE) patients1 and anti-IFN biologics are being evaluated in a clinical setting.2 The 4-gene IFN response signature of IFI27, IFI44, IFI44L and RSAD22 is frequently used to determine IFN expression. However, numerous studies have reported on the use of different gene signatures.3, 4, 5 The impact of using different IFN gene signatures to stratify SLE patients is unclear.ObjectivesThe present study compares the relative performance of 4 IFN gene signatures in a cohort of 687 participants with self-reported SLE.MethodsA centralised site, IRB-approved, SLE cohort was recruited using social media. Qualified participants with self-reported SLE were consented electronically and asked to provide medical record review consent, complete an online questionnaire regarding their disease as well as provide 3 fingerstick blood samples over approximately a 6 week period. Blood samples from 687 participants were tested using a multi-modular gene expression assay containing 11 IFN response genes (primarily from the IFN-α response pathway). Normalised gene expression values were calculated, and the resulting data analysed to determine concordance between IFN gene signatures.Results10 of the 11 IFN response genes were highly correlated with one another (ρ ≥0.80). The 4-gene signature of IFI27, IFI44, IFI44L, and RSAD22 identified 36.5% of the participants as IFN high. Three other literature reported IFN signatures3, 4, 5 provided similar classification results with participants being assigned to the same IFN sub-group over 90% of the time, and nearly identical patient distributions.Abstract SAT0041 – Table 1SignatureGenesIFN High (%)IFN Low (%)% Agreement (95% CI) to Furie et al. Furie et al.2IFI27, IFI44, IFI44L, RSAD236.563.5N/ANiewold et al.3EIF2AK2, IFIT1, MX136.363.794.8% (93.4–95.9)Kirou et al.4EIK2AK2, IFIT1, IFI4436.064.095.1% (93.7–96.2)Westra et al.5IFI6, HERC5, IFIT1, MX136.064.094.8% (93.4–95.9)ConclusionsThe study demonstrated that commonly used IFN gene signatures provide similar IFN subtyping to the 90th percentile. The use of social media to engage patients directly along with self-collection of blood samples provides new opportunity for testing clinical study participants and potentially patients without requiring an office visit.References[1] Dall’Era M, et al. Type I interferon correlates with serological and clinical manifestations of SLE. Annals of the Rheumatic Diseases2005;64(12):1692–1697.[2] Furie R, et al. Anifrolumab, an Anti-Interferon-α Receptor Monoclonal Antibody, in Moderate-to-Severe Systemic Lupus Erythematosus. Arthritis Rheumatol2017;69(2): 376–386.[3] Niewold TB, et al. High serum IFN-alpha activity is a heritable risk factor for systemic lupus erythematosus. Genes Immun2007;8(6):492–502.[4] Kirou KA, et al. Activation of the Interferon-alpha Pathway Identifies a Subgroup of Systemic Lupus Erythematosus Patients with Distinct Serologic Features and Active Disease. Arthri...