Patterns of hepatitis C virus RNA levels during acute infection: the InC3 study

Abstract

Background: Understanding the patterns of HCV RNA levels during acute hepatitis C virus (HCV) infection provides insights into immunopathogenesis and is important for vaccine design. This study evaluated patterns of HCV RNA levels and associated factors among individuals with acute infection.

Methods: Data were from an international collaboration of nine prospective cohorts of acute HCV (InC3 Study). Participants with well-characterized acute HCV infection (detected within three months post-infection and interval between the peak and subsequent HCV RNA levels ≤ 120 days) were categorised by a priori-defined patterns of HCV RNA levels: i) spontaneous clearance, ii) partial viral control with persistence (≥ 1 log IU/mL decline in HCV RNA levels following peak) and iii) viral plateau with persistence (increase or <1 log IU/mL decline in HCV RNA levels following peak). Factors associated with HCV RNA patterns were assessed using multinomial logistic regression.

Results: Among 643 individuals with acute HCV, 162 with well-characterized acute HCV were identified: spontaneous clearance (32%), partial viral control with persistence (27%), and viral plateau with persistence (41%). HCV RNA levels reached a high viraemic phase within two months following infection, with higher levels in the spontaneous clearance and partial viral control groups, compared to the viral plateau group (median: 6.0, 6.2, 5.3 log IU/mL, respectively; P = 0.018). In the two groups with persistence, Interferon lambda 3 (IFNL3) CC genotype was independently associated with partial viral control compared to viral plateau (adjusted odds ratio [AOR]: 2.75; 95%CI: 1.08, 7.02). In the two groups with viral control, female sex was independently associated with spontaneous clearance compared to partial viral control (AOR: 2.86; 95%CI: 1.04, 7.83).

Conclusions: Among individuals with acute HCV, a spectrum of HCV RNA patterns is evident. IFNL3 CC genotype is associated with initial viral control, while female sex is associated with ultimate spontaneous clearance.

Fig 1. Overview of InC³ study population.

Fig 2. Monthly medians of HCV RNA and ALT levels in individuals with acute HCV infection in the InC³ study (total n = 643).

(A) HCV RNA levels, by infection outcome (clearance vs. persistence); (B) ALT levels by infection outcome (clearance vs. persistence), tables underneath panel A and B represent number of participants with available HCV RNA/ALT levels measurements at each time point; (C) Fitted HCV RNA patterns, shaded areas in panel C represent the 95% confidence intervals.

Fig 3. Patterns of HCV RNA levels in individuals with well-characterized acute HCV infection in the InC³ study (total n = 162).

(A) Monthly medians of HCV RNA levels, table underneath represents number of participants with available HCV RNA level measurements at each time point; (B) Fitted HCV RNA patterns, shaded areas represent the 95% confidence intervals.

Fig 4. Distribution of sex, HCV genotype, IFNL3 genotype and peak HCV RNA levels by patterns of HCV RNA levels in individuals with acute HCV infection in the InC³ study.

(A) Sex, P = 0.09; (B) HCV genotype, P = 0.18; (C) IFNL3 genotype, P<0.01; (D) Peak HCV RNA levels, P<0.01; (E) IFNL3 genotype stratified by sex, male P = 0.03, female P = 0.02.