Biological dynamics of viral load in hemodialysis patients with hepatitis C virus

Abstract

The biological dynamics of hepatitis C virus (HCV) viremia in uremic patients with chronic infection have not been fully characterized. We prospectively studied fluctuations of HCV-RNA in sera from 52 patients with end-stage renal disease who were undergoing maintenance hemodialysis (HD) and had chronic HCV infection. We measured HCV viremia monthly over the course of 13 months with the branched-chain DNA (bDNA) signal amplification assay and prospectively analyzed liver function, expressed by monthly serum aspartate (AST) and alanine aminotransferase (ALT) determinations. We observed three different patterns of HCV viremia: (1) patients persistently positive by bDNA assay (persistent viremia; 23 of 52 patients; 44%), (2) individuals with alternatively positive and negative results (intermittent viremia; 17 of 52 patients; 33%), and (3) patients persistently negative by bDNA assay (12 of 52 patients; 23%). The HCV viral load over the follow-up was greater among patients with persistent compared with intermittent viremia (persistent, 31.7 x 10(5) Eq/mL; range, 6.3 x 10(5) to 16.03 x 10(6) Eq/mL versus intermittent, 10.4 x 10(5) Eq/mL; range, 1.1 x 10(5) to 9.4 x 10(6) Eq/mL; P = 0.0001). In addition, patients with persistent viremia had over time greater AST and/or ALT activities than the intermittent group (AST: persistent, 26.5 IU/L; range, 9.6 to 73.7 IU/L versus intermittent, 21.3 IU/L; range, 8 to 56.8 IU/L; P = 0.001 and ALT: persistent, 14.7 IU/L; range, 3.7 to 57.9 IU/L versus intermittent, 10.9 IU/L; range, 2.3 to 52.1 IU/L; P = 0.001). In the group with persistent viremia, the mean difference between maximum and minimum values of HCV-RNA observed in each individual patient was 2.09 +/- 0.7 natural logarithm (Log(n)) and in intermittent viremic patients, 1.55 +/- 1 Log(n) (P = 0.045). The HCV load at study entry (19.4 x 10(5) Eq/mL) was rather low and did not change versus the end of follow-up in all patients (P = not significant [NS]). In the entire group, the fluctuations in HCV-RNA levels over time between and within individuals were not significant (P = NS). No difference in variability of HCV-RNA values over time between patients infected with different HCV genotypes was seen. In conclusion, three different patterns of HCV viremia in HD over time were assessed; one third of viremic patients had intermittent viremia, and those patients had less HCV-RNA, enzyme-linked immunosorbent assay, and aminotransferase activity than did patients with persistent HCV load. Larger fluctuations in HCV RNA levels occurred in patients with persistent than with intermittent HCV viremia. However, the viremic HCV load was low and relatively stable over a 13-month follow-up in our population. Studies with longer observation periods are warranted to understand fully the natural history of HCV in these immunosuppressed individuals.