Can secukinumab improve liver fibrosis? A pilot prospective study of 10 psoriatic patients

Dear Editor, In recent years, there has been an increase in publications that relate psoriasis to non-alcoholic fatty liver disease (NAFLD), with the consequent risk of progression to liver fibrosis, cirrhosis and hepatocarcinoma. It has been speculated that both entities share common pathophysiological mechanisms. Among them, the overproduction of proinflammatory cytokines such as interleukin-17 could contribute to the development of psoriasis skin plaques and the progression of liver disease, so its blockage could be beneficial for both entities. In this study we investigated the possible antifibrotic effect of secukinumab in psoriasis patients treated for at least 2 years. We use secukinumab because it has shown favorable effects on metabolic and liver parameters. Liver elasticity was assessed by Transient Elastography (TE), using Fibroscan. Results reliability was defined by at least 10 valid measurements, success rate ≥60%, and interquartile range to median ratio ≤30%. A total of 10 psoriasis patients treated with secukinumab were collected. The clinical–epidemiological characteristics are summarized in Table 1. Only 2 of the 10 patients started lipid-lowering drugs after first Fibroscan performing. The Fibroscan value improved in all patients, including the two patients who started lipid-lowering treatment, while they maintained similar mean values of weight, body mass index (BMI), and analytical parameters. NAFLD, the most common chronic liver disease in the world, represents a spectrum of disorders that range from steatosis to steatohepatitis to fibrosis–cirrhosis, being obesity and insulin resistance its main risk factor. The association between psoriasis and liver fibrosis has been previously reported. Previous studies demonstrated that psoriasis was a predictor of advanced liver fibrosis independently of BMI, hypertension, and diabetes. Few studies have evaluated the prevalence of liver fibrosis in patients with psoriasis using TE, with results comparable to ours. IL-17 family of cytokines has been recently shown to play an important role in pathogenesis of variety of liver diseases, including NAFLD. For example, variety of mediators produced by Kupffer cells (e.g., TNF-α, TGFβ, and MCP-1), neutrophils (e.g., IL-17, ROS), and Th17 cells (e.g., IL-17) have been shown to induce cytokine production (e.g., IL-8, MCP-1, and TGF-β) and fibrogenic machinery in hepatic stellate cells, leading to aberrant production of liver extracellular matrix. Further, IL-17A-driven Kupffer cell activation played a critical role in hepatic neutrophil recruitment and injury in an ischemia reperfusion model and to exacerbate hepatic fibrosis in a mouse model of bile duct ligation. TABLE 1 Clinical–epidemiological characteristics of the patients