['Perihepatic lymph node enlargement (PLNE) is a common ultrasound finding in chronic hepatitis C patients. Although PLNE is considered to reflect the inflammatory response to hepatitis C virus (HCV), its clinical significance remains unclear.', 'Between December 2004 and June 2005, we enrolled 846 chronic hepatitis C patients in whom adequate ultrasound examinations had been performed. PLNE was defined as a perihepatic lymph node that was at least 1 cm in the longest axis by ultrasonography. We analyzed the clinical features of patients with PLNE and prospectively investigated the association between PLNE and hepatocellular carcinoma (HCC) development.', 'We detected PLNE in 169 (20.0%) patients. Female sex, lower body mass index (BMI), and HCV serotype 1 were independently associated with the presence of PLNE. However, there were no significant differences in liver function tests, liver stiffness, and hepatitis C viral loads between patients with and without PLNE. During the follow-up period (mean 4.8 years), HCC developed in 121 patients. Unexpectedly, patients with PLNE revealed a significantly lower risk of HCC development than those without PLNE (p = 0.019, log rank test). Multivariate analysis revealed that the presence of PLNE was an independent negative predictor of HCC development (hazard ratio 0.551, p = 0.042). In addition, the sustained viral response rate in patients who received interferon (IFN) therapy was significantly lower in patients with PLNE than in patients without PLNE.'] Is perihepatic lymph node enlargement a negative predictor of liver cancer development in chronic hepatitis C patients?