Hepatic HCV RNA before and after treatment with interferon alone or combined with ribavirin

Abstract

The clinical use of measuring hepatic hepatitis C virus (HCV) RNA before and after therapy in patients with chronic hepatitis C has been assessed in a number of small clinical trials. Viral clearance from the liver may be a better marker of long-term response than eradication of serum HCV RNA. The aim of this study was to evaluate quantitative hepatic HCV-RNA measurements before and after antiviral therapy. Two thousand eighty-nine chronic hepatitis C patients were enrolled in 3 published clinical trials evaluating interferon alfa-2b alone or with ribavirin either as initial therapy or for interferon relapse. Hepatic HCV-RNA quantitation was performed with a modified reverse-transcription polymerase chain reaction (RT-PCR) before and 24 weeks after therapy in 951 and 1,316 patients, respectively. Pretherapy hepatic HCV-RNA concentrations correlated best with serum HCV-RNA concentrations (R ‫؍‬ .236, P ‫؍‬ .0001) and negatively correlated with alanine transaminase (ALT) values (؊0.178, P ‫؍‬ .0001), duration of infection (؊0.09, P ‫؍‬ .02), parenchymal injury (؊0.135, P ‫؍‬ .0001), histologic activity index (HAI) inflammatory score (؊0.085, P ‫؍‬ .01), Knodell fibrosis score (؊0.072, P ‫؍‬ .03), and body weight (؊0.078, P ‫؍‬ .02). In paired liver biopsy specimens (n ‫؍‬ 534), change in hepatic HCV RNA correlated with the change in the HAI (R ‫؍‬ .346, P ‫؍‬ .0001). Of 400 sustained virologic responders (SVR), 393 (98%) had undetectable hepatic HCV RNA, whereas 7 (2%) had detectable hepatic HCV RNA; 5 have been followed and 2 have had reappearance of serum HCV RNA 12 months after therapy. In conclusion, measurement of hepatic HCV RNA before or after therapy reflects changes observed in serum HCV RNA, and correlates inversely with hepatic inflammation and fibrosis, but otherwise has minimal clinical use. (HEPATOLOGY 2002;35:688-693.)

Clearance of hepatitis C virus RNA from the peripheral blood mononuclear cells of blood donors who spontaneously or therapeutically control their plasma viremia

“…This conclusion is supported by a recent analysis that similarly failed to detect PBMC-associated HCV RNA in 9 spontaneous and 2 treatment-induced aviremic patients. 16 A greater than 90% rate of clearance of HCV RNA in the liver of sustained virological response also indicates that a long-lived hepatic reservoir is unlikely to exist, [37][38][39] although another report detected hepatic HCV RNA in 50% of spontaneously aviremic seropositive subjects. 22 The slow decrease in anti-HCV antibody titers in subjects with spontaneously cleared viremia [40][41][42][43][44] as well as the complete seroreversion detected in 7% of transfusion-transmitted infections 5 may also reflect an absence of ongoing antigenic stimulation, indirectly supporting clearance of infection in persons who test HCV RNA-negative in plasma.…”

Expertise of French Laboratories in Detection, Genotyping, and Quantification of Hepatitis C Virus RNA in Serum

“…Antiviral treatments are becoming more and more efficient, and monitoring of therapy requires reliable viral quantification tests. Hepatitis C virus (HCV) is an important cause of chronic liver disease, and recent studies have shown the efficiency of a combination of pegylated interferon and ribavirin in the treatment of patients with chronic hepatitis C (7,9). Furthermore, several studies have shown that the HCV genotype and viral load prior to treatment have predictive values for the response to antiviral therapy and that measurement of serum HCV RNA levels is useful in the monitoring of treated patients (2,5,8).…”

HCV RNA detection by TMA during the hepatitis C antiviral long-term treatment against cirrhosis (Halt-C) trial

“…1,2 Patients who test HCV RNA-negative by such assays at least 24 weeks after completion of therapy are considered to have a sustained virological response (SVR), a critical endpoint associated with durable eradication of infection and long-term remission, if not cure, of disease. [3][4][5][6] HCV RNA testing during therapy is also helpful for indicating whether a virological response has occurred and for predicting the likelihood of an eventual SVR with prolongation of therapy. Current management guidelines include the recommendation that patients treated with pegylated interferon alpha (peginterferon) and ribavirin have therapy stopped if HCV RNA is still present after 24 weeks of treatment.…”