E104 Apremilast, psoriasis and psoriatic arthritis and chronic liver disease

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Background: Several recent reports have shown a relationship between psoriasis and chronic liver disease using non–invasive imaging. While the aetiology remains uncertain, it has been suggested that inflammatory cytokines such as resistin, tumour necrosis factor alpha (TNF–α), IL–6 and IL1–β play a role in the development of insulin resistance and fatty liver as well as psoriasis and psoriatic arthritis. These connections imply a possible linked pathogenesis which is further supported by similarities between skin and liver inflammation. Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of disease states ranging from isolated fatty liver to nonalcoholic steatohepatitis (NASH), with increasing levels of fibrosis and ultimately cirrhosis. While NAFLD can be identified with ultrasound alone, liver biopsy is necessary in order to distinguish isolated steatosis from NASH and other liver disorders. Methods: 126 patients between ages of 18 and 80 years; 93 diagnosed with psoriasis and 33 with psoriatic arthritis who were treated with apremilast, were considered for enrollment in the study over a 6-18 month period. Ultrasound studies were done by standard protocol. Radiologists reviewed images and evaluated the presence of steatohepatitis. Blood was collected for evaluation of liver associated enzymes, HgbA1C and lipid studies. Iron studies, alpha–1 anti–trypsin, serum protein electrophoresis, a chronic viral hepatitis panel, anti–nuclear antibody, anti–smooth muscle antibody and ceruloplasmin were also collected from these participants. Results: 75 patients were diagnosed with chronic liver disease using an non–invasive technique: 40 NAFLD, 5 NASH (a biopsy was performed on 14 patients), 21 chronic liver disease (viral hepatitis or unknown origin) and 9 cirrhosis. 25 patients were followed by digestive medicine department. 57 patients were selected due to no change in medication or alcohol consumption. Their weight did not change during the process. FIB-4 was used as a predictor of fibrosis. The results were: 29 patients treated with apremilast improved, 11 worsened and 17 remained unchanged. Among patients who worsened, several were on co-treatment with methotrexate and consumed alcohol. In 3 patients values of FIB-4 were in discordance with an improvement of ultrasound studies. Conclusion: Although more studies with controls and a longer time interval are required, this preliminary study suggests that apremilast could offer clinical benefits in liver disease by reducing pro-inflammatory TNFα-mediated liver injury, most likely through downregulation of transcription factor NFκB. Apremilast also interferes with the production of nitric oxide synthase which is involved in the development of liver fibrosis. Furthermore, PDE4 is a cAMP-specific phosphodiesterase expressed in several brain regions that regulates the reinforcing effects of treatment of alcohol abuse. Disclosures: N. Palmou-Fontana: None. M. Marcellan: None. M. Drake: None. C. Gonzalez-Vela: None. J. Mayorga: None. A. Illaro: None. L. Reguero: None. M. Arias: None. J. Crespo: None. S. Armesto: None.

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