Background and aims: Patients with chronic hepatitis C infection have high rates of major depressive disorder. The reasons for this are multifactorial, but social and demographic factors do not entirely explain the increased burden. Direct neuropathologic effect of the virus in the development of depression has been postulated but the mechanisms remain unclear. Single nucleotide polymorphisms (SNPs) in FKBP5 (protein product FKBP51), a co-chaperone of the glucocorticosteroid receptor, have been associated with greater severity of affective disorders. We examined the interaction between FKBP5 SNPs and chronic hepatitis C infection in patients with and without depressive symptoms. Methods: forty-one subjects completed quality of life and psychiatric questionnaires. Thirteen patients were classified as depressed on the Hospital Anxiety and Depression Scale depression sub-score (HADS-D ≥11). FKBP51 protein expression, FKBP5 mRNA and FKBP5 SNP analysis was compared between those with and without depression. Results: There were no statistically significant differences between the groups in demographics, medical co-morbidities or substance use. A moderate negative correlation (Spearman rho -0.53, p<0.001) was found between HADS-D sub-score and FKBP51 protein levels in serum. Correspondingly, the average expression fold change in peripheral blood FKBP5 mRNA relative to a reference gene was lower in the depressed group at 0.76 compared to controls at 1.40. There was no differential expression of FKBP5 SNPs between the groups. Conclusion: Levels of FKBP5 mRNA and FKBP51 are lower in hepatitis C patients with depression and further exploration of this interaction is required.
BACKGROUND Management of single small hepatocellular carcinoma (HCC) is straightforward with curative outcomes achieved by locoregional therapy or resection. Liver transplantation is often considered for multiple small or single large HCC. Management of two small HCC whether presenting synchronously or sequentially is less clear. AIM To define the outcomes of patients presenting with two small HCC. METHODS Retrospective review of HCC databases from multiple institutions of patients with either two synchronous or sequential HCC ≤ 3 cm between January 2000 and March 2018. Primary outcomes were overall survival (OS) and transplant-free survival (TFS). RESULTS 104 patients were identified (male n = 89). Median age was 63 years (interquartile range 58-67.75) and the most common aetiology of liver disease was hepatitis C (40.4%). 59 (56.7%) had synchronous HCC and 45 (43.3%) had sequential. 36 patients died (34.6%) and 25 were transplanted (24.0%). 1, 3 and 5-year OS was 93.0%, 66.1% and 62.3% and 5-year post-transplant survival was 95.8%. 1, 3 and 5-year TFS was 82.1%, 45.85% and 37.8%. When synchronous and sequential groups were compared, OS (1,3 and 5 year synchronous 91.3%, 63.8%, 61.1%, sequential 95.3%, 69.5%, 64.6%, P = 0.41) was similar but TFS was higher in the sequential group (1,3 and 5 year synchronous 68.5%, 37.3% and 29.7%, sequential 93.2%, 56.6%, 48.5%, P = 0.02) though this difference did not remain during multivariate analysis. CONCLUSION TFS in patients presenting with two HCC ≤ 3 cm is poor regardless of the timing of the second tumor. All patients presenting with two small HCC should be considered for transplantation.
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