Low HCV replication levels in end-stage hepatitis C virus-related liver disease.
The relationship between HCV RNA levels and the severity of HCV-related liver disease has been addressed in a few studies, which has led to conflicting results. To clarify this point, we studied serum HCV RNA levels in patients with HCV liver disease at various stages, using a second-generation branched DNA (bDNA) assay. One hundred and forty-eight patients with chronic HCV infection were classified into 3 groups: group A included 92 patients with chronic active hepatitis (CAH) without cirrhosis; group B included 30 patients with CAH and compensated cirrhosis; group C included 26 patients with end-stage cirrhosis. In all patients, serum HCV RNA was sought by qualitative PCR and quantified using second-generation bDNA assay. HCV RNA was also quantified after liver transplantation in 22 patients from group C. HCV genotype was determined in all patients. HCV RNA was detected by PCR in 100%, l00% and 92% of the patients from groups A, B and C, respectively (NS). The proportion of patients with HCV RNA levels higher than the cut-off of bDNA assay was significantly lower in patients from group C than in patients from groups A and B (50% vs 94% and 93% respectively, p<0.0001). The mean HCV viremia was lower in group C than in groups A and B (1.35+/-0.24 MEq/ml vs 5.00+/-6.04 MEq/ml and 5.85+/-7.70 MEq/ml, respectively, p<0.0001). This difference was independent of HCV genotype. In the patients from group C, post-transplant HCV RNA levels were significantly higher than pretransplant HCV RNA levels (14.90+/-26.40 vs 1.35+/-0.24 MEq/ml, p=0.0065). HCV RNA levels do not appear to differ significantly among patients with CAH with or without compensated cirrhosis. In contrast, HCV RNA levels seem to be significantly lower in patients with end-stage HCV-related liver cirrhosis. In these patients, high levels of replication are restored after liver transplantation, suggesting that low pretransplant viral loads are not due to the intrinsic characteristics of the infective viral strains, but rather to the severity of liver disease.