Persistently Low Brain-Derived Neurotrophic Factor Levels in Patients with Hepatitis C-Related Liver Cirrhosis Following Viral Eradication

Brain-derived neurotrophic factor (BDNF) has been linked to hepatitis C virus (HCV) infection and to liver function. This study evaluated associations between serum BDNF and hepatic steatosis, fibrosis, cirrhosis, viral genotype, and viral clearance after direct-acting antiviral (DAA) therapy. Serum BDNF was measured in 92 patients with chronic HCV infection and 30 healthy controls. In 58 patients, samples were obtained before therapy, at weeks 4 and 12, and at sustained virologic response 12 (SVR12); 81 patients had SVR12 samples. Before therapy, serum BDNF was lower in patients than in controls (median 4.9 vs. 7.3 ng/mL; p < 0.001) and was lowest in the 36 patients with ultrasound-diagnosed cirrhosis (median 3.4 ng/mL; p < 0.001 vs. non-cirrhotic patients). In non-cirrhotic patients, BDNF was modestly reduced (median BDNF: 6.0 ng/mL) compared with controls (p = 0.027) and was not associated with steatosis, fibrosis stage, or genotype. In cirrhosis, BDNF correlated positively with albumin and platelet count. At SVR12, BDNF levels were modestly higher in non-cirrhotic patients than at pretreatment and were no longer different from those in controls, whereas they remained low in patients with cirrhosis. In the entire cohort, platelet count significantly predicted serum BDNF levels. The lack of difference between cirrhosis and non-cirrhotic patients after adjustment for platelet count and log10 transformation to normalize BDNF distribution suggests that the altered BDNF levels observed in patients with cirrhosis may be partly attributable to changes in platelet count rather than reflecting a disease-specific alteration in hepatic BDNF synthesis.