Abstract

Background: Gremlin 1 is a fibrotic protein that increases in the liver during fibrosis. There is also evidence that gremlin 1 expression is upregulated in the livers of patients with hepatitis C virus (HCV) infection. Since gremlin 1 is a secreted protein, this study is the first to examine whether serum gremlin 1 could serve as a noninvasive marker of liver fibrosis in patients with chronic HCV infection. The study also examined whether viral clearance with direct-acting antivirals (DAAs) affects circulating gremlin 1 levels. Methods: Serum gremlin 1 levels were measured in 30 controls and 114 patients with chronic HCV, as well as in 60 HCV patients for whom serum was available prior to therapy and at four and 12 weeks after therapy initiation and 12 weeks post-therapy. Results: Compared with 30 healthy controls, patients with HCV exhibited significantly higher serum gremlin 1 levels. Among patients with cirrhosis, defined by noninvasive scores or ultrasound, serum gremlin 1 levels were only modestly elevated. Serum gremlin 1 levels positively correlated with markers of inflammation and aminotransferase levels in HCV patients. During antiviral therapy, serum gremlin 1 levels transiently increased four weeks after therapy initiation and returned to pretreatment levels by week 12. Even though patients were effectively cured of the virus, patients still exhibited higher serum gremlin 1 levels compared with controls at 12 weeks post-therapy. Conclusions: Our findings indicate that chronic HCV infection is associated with elevated serum gremlin 1 levels, which do not return to normal shortly after viral cure. In contrast, serum gremlin 1 concentrations do not provide a reliable indicator of fibrosis stage in patients with chronic HCV infection.

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