The course of hepatitis C viraemia in transfusion recipients prior to availability of antiviral therapy

Abstract

Knowing the likely distribution of intervals from hepatitis C infection to first RNA-negativity is important in deciding about therapeutic intervention. Prospectively collected sera and data from the Transfusion-transmitted Viruses Study (1974-1980) provide specific dates of infection and pattern of alanine aminotransferase (ALT) elevations. We examined frequency, timing and correlates of spontaneous resolution for 94 acutely infected transfusion recipients followed for a median of 9.5 months. Later, follow-up sera (>10 years) were available for 27 of the 94 cases from a Veterans Administration (VA) Study (1989-1990). Twenty-five (27%) of the 94 cases were classified as probably resolved during the episode itself. First RNA negativity occurred at 6-50 weeks (median, 19.5 weeks) after infection, and 5-43 weeks (median, 11 weeks) after ALT elevation. Thirteen of the 25 cases remained RNA-negative subsequently; 12 others had 1-6 RNA-positive sera intercalated between first and last RNA-negative results. RNA negativity, therefore, began variably and was interrupted in 12 cases of 25 (48%) by transient RNA-positive sera. Five of these 25 patients who were RNA-negative in the last study specimen had late, Veterans Administration Study follow-up; none showed viraemia. Of the remaining 69 transfusion transmitted virus study recipients, whose last serum was RNA-positive, two cleared viraemia after the last study serum but before late follow-up. Eleven (16%) had 23 intercalated RNA-negative sera before last positivity. RNA status, therefore, needs monitoring for many months before judging the spontaneous outcome as transient negativity may occur. Resolution was significantly more common in women and symptomatic cases; it was not associated with viral load in the infectious donation, HCV genotype, or the recipient's age.

Hepatitis C Virus Reinfection and Spontaneous Clearance of Reinfection—the InC3Study

“…However, intercalation cases were also observed later in HCV infection and after lengthier periods of HCV RNA undetectability, as has previously been reported [6,12,38,39]. This highlights the importance of viral sequencing for classification of HCV reinfection.…”

“…The analysis of time to HCV reclearance versus primary clearance only included participants with reclearance during the study period. While the participants with persistent reinfection were all followed for at least 10 months, indicating that future reclearance would be unlikely, late clearance can occur, so there is a small risk of bias from excluding right-censored data (Supplementary Materials) [39]. This is the first study to investigate predictors of HCV reclearance.…”

Many hepatitis C reinfections that spontaneously clear may be undetected: Markov-chain Monte Carlo analysis of observational study data

“…Confirmed reinfections represent the gold standard, whereas analyses that include possible reinfections may be subject to misclassification errors, where some transient fluctuations in viral load may have been classified as possible reinfections. This has been shown to occur after more than six months of sustained viraemia [8,36], but is rare after 10 weeks of undetectability (as occurred for all spontaneous clearances in the Networks 2 study), making misclassification unlikely but still possible in the data used here. With respect to the reinfection duration estimates, the slightly longer durations estimated when including possible reinfections as well as confirmed reinfections may be due to such misclassification errors.…”

Current Treatment Approach in Acute Hepatitis C Infection

“…Most of the studies showed that spontaneous clearance usually occurs within the first 6 months of the infection. It has been reported that factors influencing spontaneous clearance positively were being under 30 years of age, female gender, symptomatic infection, IL 28BCC genotype and HCV genotype 1, while independent predictive factors have been determined to be female gender, IL 28 B CC genotype and HCV genotype 1 (10,11,12). Spontaneous clearance was reported in 46-67% of symptomatic cases, while no spontaneous clearance observed in asymptomatic patients (13,14).…”