Background/Aims: Studies from Japan showed that HCV-lb isolates with at least four amino acid changes within NS5A(2209-2248), compared with the prototype sequence HCV-J are more sensitive to interferon than isolates with a prototype sequence. However, the data were not unequivocally confirmed in studies from other geographical areas, These discrepancies may be explained by differences in the prevalence of multiple mutations within the NS5A(2209-2248) andlor the treatment efficacy,Methods: In the present study, we therefore investigated the correlation between NS5A2209-2248 Sequences of HCV-lb isolates and sustained virological response in 72 European patients treated with 3x6 MU interferon-a per week with (n=26) and without (n=46) ribavirin (1000-1200 mg/day), Serum HCV RNA was amplified by reverse transcription-polymerase chain reaction (RT-PCR) and the NS5A(2209) (-2248) region was analyzed by sequencing of PCR products or individual clones,Results: Compared with HCV-1b prototype sequences, 19 patients (26%) had no amino acid changes prototype, 47 patients (65%) had 1-3 mutations (intermediate type) and six patients (8%) had at least 4 mutations in the NS5A(2209-2248) region (mutant type), Nine of the 12 patients with sustained virological response were infected with an intermediate type HCV-1b, the remaining three patients revealed a mutant type HCV-lb A sustained virological response was achieved in three of four patients with a mutant type HCV-1b treated with interferon-or and ribavirin, but in none of the mutant type HCV-lb infected patients treated with interferon-alpha alone, Quasispecies analysis of HCV in the NS5A(2209-2248) region showed only minor heterogeneity of the amino add seguence.Conclusions: The prevalence of mutant type HCV-lb isolates in European patients is low In patients treated with combination therapy interferon-a and ribavirin, a correlation between mutant type HCV-1b isolates and sustained virological response was observed. The discrepancies between previous studies appear to be related to the efficacy of antiviral treatment and to the low prevalence of mutant type HCV-1b isolates in Western countries.

Inflammatory processes in organs frequently lead to hyperplasia of regional lymph nodes. In the present study, we investigated whether lymph node enlargement within the hepatoduodenal ligament may reflect the inflammatory activity within the liver of patients chronically infected with the hepatitis C virus (HCV). In 114 patients with chronic hepatitis C and 49 healthy controls, the total lymph node volume within the hepatoduodenal ligament was prospectively investigated by ultrasound. In patients with chronic hepatitis C, a liver biopsy was taken at the same occasion, and specimens were semiquantitatively evaluated by the histological activity index (HAI). Hepatitis C viremia was assessed by quantitative reverse transcription-polymerase chain reaction (RT-PCR). Genotyping was performed by a reverse hybridization assay. In 104 of 114 patients (91.2%) and in 45 of 49 healthy controls (91.8%), adequate visualization of the region of the hepatoduodenal ligament was achieved by ultrasound. Lymph nodes were detected in all patients with chronic hepatitis C and in 33 of 45 controls. The mean perihepatic lymph node volume in healthy controls (2.2 +/- 1.8 mL) was lower than in HCV-infected patients with mild to moderate inflammatory activity, severe inflammatory activity, and patients with cirrhosis (5.8 +/- 2.2 mL, 18.1 +/- 10.4 mL, and 22.8 +/- 18.8 mL, respectively). In patients with HCV-RNA levels of less than 10(6) copies/mL, the total lymph node volume was 5.8 +/- 1.6 mL and was significantly increased in patients with higher viremia (20.3 +/- 13.8 mL; P < 10(-6)). No correlation was found between the total lymph node volume within the hepatoduodenal ligament, HCV genotypes, and liver function test results. In conclusion, enlargement of perihepatic lymph nodes in patients with chronic hepatitis C is predictive for the presence of severe inflammatory activity. The mechanism of portal lymphadenopathy in patients with chronic hepatitis is unknown but appears to be related to viral replication within the liver and the immune-mediated inflammatory response of the host.