Role of hepatic HCV–RNA level on the severity of chronic hepatitis C and response to antiviral therapy

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Abstract

Background

Correlation between hepatic HCV–RNA and serum HCV–RNA, severity of liver disease and response to therapy is poorly known.

Objectives

To assess the influence of hepatic HCV–RNA level on severity of liver disease and response to therapy in a large cohort of chronic hepatitis C (CHC) patients.

Study Design

HCV–RNA was measured in frozen liver biopsies and serum samples from 130 CHC patients the day of liver biopsy prior to treatment. Liver fibrosis was assessed by Ishaq scoring. A Sustained Virological Response (SVR) was observed in 52% of the patients, non-response (NR) in 34%.

Results

Mean ± standard deviation hepatic HCV–RNA level was 7.69 ± 0.67 log10 copies/mg of liver. Mean serum HCV–RNA level was 6.21 ± 0.72 log10 copies/ml. There was a correlation between hepatic and serum HCV–RNA in genotype 1 and 4 (p = 0.008 and p = 0.03) and age (p = 0.006). Mean hepatic HCV–RNA was 7.70 ± 0.69 vs 7.67 ± 0.68 log10 copies/mg of liver, in patients with significant fibrosis vs those with mild fibrosis, respectively (p = 0.7); 8.04 ± 0.68; 7.44 ± 0.47; 7.43 ± 0.49 and 7.44 ± 0.71 log10 copies/mg of liver in genotypes 1, 2, 3 and 4, respectively (p = 0.0001); higher in women than in men (p = 0.04); 7.60 ± 0.63, 7.71 ± 0.54 and 7.96 ± 0.73 log10 copies/mg in SVR, relapsers and NR, respectively (p = 0.1). Multivariate analysis showed that high hepatic HCV–RNA level was independently associated with genotype and response to therapy was associated with genotype independently from hepatic HCV–RNA level.

Conclusions

Hepatic HCV–RNA level was not associated with severity of liver disease. High level was strongly associated with HCV genotype independently from response to therapy.

Section snippets

Background

Seventy to 80% of patients infected with the hepatitis C virus (HCV) develop chronic hepatitis C.1 The combination of pegylated interferon and ribavirin induces a sustained virological response (SVR) rate of over 50%.2 Several viral and host related predictive factors for the response to interferon based therapy have been identified.3, 4, 5

The spectrum of liver disease in patients infected with HCV ranges from minimal lesions in HCV asymptomatic carriers to chronic hepatitis with minimal to

Objectives

The aim of our study was to assess the influence of hepatic HCV–RNA level on the severity of liver disease and on the response to antiviral therapy in a large cohort of chronic hepatitis C patients.

Patients selection

We retrospectively studied 130 consecutive patients seen at out patients liver units from 1994 to 2005 for CHC. The diagnosis of CHC was based on biopsy proven chronic hepatitis C and the presence of serum HCV–RNA.

The inclusion criteria were a frozen liver biopsy and a serum sample stored at −80 °C and collected the same day prior to antiviral therapy. The biopsy was performed for routine pathological assessment and a section was immediately frozen in liquid nitrogen and stored at −80 °C.

Results

The amount of liver tissue used for analysis weighed between 2.5 and 18 mg (mean 5.8 ± 3.1 mg) from which 3.4–14.5 μg (mean 7.1 ± 3.5 μg) of cellular RNA was extracted. For all the analyses, we used liver HCV–RNA concentration expressed in copies per mg of liver (supplemental data). Baseline characteristics of the 130 patients included in the study are shown in Table 1. Among the 130 patients included in the study 104 patients (80%) received the combination of pegylated interferon plus ribavirin (Table

Discussion

Our study performed in a large cohort of patients (130) with paired liver biopsy and serum shows a correlation between hepatic HCV–RNA and serum HCV–RNA in genotype 1 and 4. Liver HCV–RNA level was not associated with liver fibrosis and response to therapy. A high liver HCV–RNA level was independently associated with HCV genotype 1.

The possibility of sampling errors is the first element to be taken into account for liver parameters. As previously reported by Fanning et al. HCV–RNA is

Conflict of interest statement

None to declare.

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