The influence of cryoprecipitate (CP) on liver histology and peripheral titers of hepatitis C virus (HCV) RNA was evaluated for 115 patients with chronic hepatitis. Fifty-four patients had measurable CP levels whereas 61 did not. Assessment of liver biopsies for grade of fibrosis revealed that patients with CP had increased fibrosis (P F .001) and incidence of cirrhosis (P ‫؍‬ .001) compared with those without CP. In contrast, there was not a significant difference in the inflammatory activity score between the 2 groups. HCV RNA in whole blood (WB) and plasma (Pl) was evaluated in patients with or without CP by end-pointlimiting dilution titer. Among patients with CP, WB titers were significantly higher than Pl titers (P F .001); however, there was no difference in WB or Pl titers in patients without CP (P ‫؍‬ .068). Histological activity and fibrosis scores of patients from either group were compared with peripheral viral titers of WB and Pl, percentage of CP, rheumatoid factor (RF) titer, and serum alanine transaminase (ALT). There were significant correlations between the amount of fibrosis and the percentage of CP and rheumatoid factor titer, yet neither of the latter parameters was correlated with inflammatory activity. These data suggest that patients with CP and chronic hepatitis owing to HCV are more likely to have progressive disease than patients without CP. Furthermore, the presence of CP in patients infected with HCV appears to influence the amount of virus detected in patient Pl, suggesting that WB assays may be more reliable for HCV-RNA quantitation in patients with CP. (HEPATOLOGY 2000;31:737-744.)

Fifty-two patients with chronic hepatitis C virus (HCV)infection were treated with standard doses of interferon alfa-2b. During treatment, HCV RNA detection was studied in samples of whole blood (WB), plasma (Pl), and peripheral blood mononuclear cells (PBMCs). Individuals were classified as sustained responders (SRs), complete responders with relapse (CRs), partial responders (PRs), or nonresponders (NRs) according to normalization of serum alanine transaminase (ALT) during treatment and follow-up. Before treatment, 100% of WB samples and more than 95% of Pl and PBMC samples were positive for HCV RNA. During treatment, there was progressive clearance of HCV RNA from Pl and PBMCs in SRs and CRs, but CRs had significantly more positive WB samples during and following treatment (P Ͻ.0001). At 6 months, only 10% of CR patients were positive by Pl assay, but 50% were positive by WB assay (P Ͻ.01). In the PR group, all WB samples remained positive throughout treatment, although 25% to 40% of PBMC and Pl samples became negative for HCV RNA during the first 2 months of therapy (WB Ͼ Pl or PBMC; P Ͻ .001). However, at later times during treatment most Pl and PBMC samples in the PR group were positive. Samples from the NR group showed no clearance of HCV RNA from WB, Pl, or PBMC fractions. These data document the increased sensitivity of WB assays for detecting HCV RNA in the peripheral blood of patients during interferon therapy. Furthermore, our findings suggest that WB analysis of HCV RNA may be a useful parameter to monitor in determining the end point of interferon therapy.(HEPATOL-OGY 1998;28:1110-1116.)Hepatitis C virus (HCV) is a small, enveloped RNA virus of approximately 9,500 nucleotides that is responsible for more than 90% of parenterally transmitted cases of non-A, non-B hepatitis. 1-3 Infection with HCV usually results in chronic active hepatitis, which may progress to cirrhosis. Currently, end-stage liver disease resulting from chronic HCV infection is a major reason for referral of patients for orthotopic liver transplantation in the United States. 4,5 Interferon therapy is the only approved treatment for chronic hepatitis C. Approximately 50% of patients who are treated respond with normalization of serum aminotransferase levels, although more than half of these responders will relapse after discontinuation of the drug. Thus, approximately 20% of treated patients have a durable, sustained response. 6,7 Although the reasons responsible for relapse are unclear, variables such as length of treatment, HCV genotype, and histological evidence of inflammation and fibrosis at the start of therapy appear to correlate with treatment outcomes. 3,[8][9][10][11] Reverse-transcription (RT) polymerase chain reaction (PCR) techniques to detect HCV RNA during interferon therapy have been widely employed and are considered to be important for optimum management. 12,13 A high level of HCV RNA in serum before treatment is a poor prognostic sign for sustained response; unfortunately, clearance of virus from serum or plasma ...

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