Defective T-cell functions play a role in the persistence of hepatitis C virus (HCV) infection. Activated T-cells express CD137, which co-stimulates anti-virus T-cell responses, and this activity is antagonized by soluble CD137 (sCD137). Here, we show that in sera of 81 patients with chronic HCV, sCD137 levels did not correlate with measures of viral infection, and did not decline after virus eradication using direct-acting antivirals. Thus, serum sCD137 was similar in patients infected with HCV and in uninfected controls. Of note, in HCV patients with liver cirrhosis and patients with mostly alcohol associated liver cirrhosis, sCD137 was increased. A negative association of sCD137 and albumin existed in both cohorts. sCD137 concentrations were similar in hepatic and portal vein blood excluding the liver as origin of higher levels. Recombinant sCD137 reduced T-helper (Th) 1 and Th2 but not Th17 cell polarization in-vitro, and accordingly lowered interferon-γ, tumor necrosis factor (TNF) and interleukin-13 in cell media. Serum sCD137 is associated with inflammatory states, and positively correlated with serum TNF in cirrhotic HCV patients following virus eradication. Our study argues against a role of sCD137 in HCV infection and suggests a function of sCD137 in liver cirrhosis, which yet has to be defined.

This article is protected by copyright. All rights reserved