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

Hajarizadeh B, Grady B, Page K, Kim AY, McGovern BH, Cox AL, Rice TM, Sacks-Davis R, Bruneau J, Morris M, Amin J, Schinkel J, Applegate T, Maher L, Hellard M, Lloyd AR, Prins M, Dore GJ, Grebely J, InC3 Study Gro - PLoS ONE (2015)

Bottom Line: 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).IFNL3 CC genotype is associated with initial viral control, while female sex is associated with ultimate spontaneous clearance.

View Article: PubMed Central - PubMed

Affiliation: The Kirby Institute, UNSW Australia (University of New South Wales), Sydney, NSW, Australia.

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.

No MeSH data available.


Related in: MedlinePlus

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.
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pone.0122232.g004: 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.

Mentions: Among individuals with well-characterized acute HCV, key baseline characteristics were compared among those with viral plateau with persistence (n = 66), partial viral control with persistence (n = 44) and spontaneous clearance (n = 52; Table 2, Fig. 4). Between the three groups, there was a significant difference in the proportion with IFNL3 CC genotype (29% vs. 51% vs. 63%, respectively; P<0.01), median peak HCV RNA level (5.3 log IU/mL vs. 6.0 log IU/mL vs. 6.5 log IU/mL, respectively; P<0.01) and the proportion with peak HCV RNA ≥5.6 log IU/mL (39% vs. 61% vs. 67%, respectively; P<0.01). There was also a trend towards a significant difference in sex across the three groups, with 54% of individuals with spontaneous HCV clearance being female, as compared to 37% in those with partial viral control with persistence and 35% in those with viral plateau with persistence (P = 0.09).


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

Hajarizadeh B, Grady B, Page K, Kim AY, McGovern BH, Cox AL, Rice TM, Sacks-Davis R, Bruneau J, Morris M, Amin J, Schinkel J, Applegate T, Maher L, Hellard M, Lloyd AR, Prins M, Dore GJ, Grebely J, InC3 Study Gro - PLoS ONE (2015)

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.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4383375&req=5

pone.0122232.g004: 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.
Mentions: Among individuals with well-characterized acute HCV, key baseline characteristics were compared among those with viral plateau with persistence (n = 66), partial viral control with persistence (n = 44) and spontaneous clearance (n = 52; Table 2, Fig. 4). Between the three groups, there was a significant difference in the proportion with IFNL3 CC genotype (29% vs. 51% vs. 63%, respectively; P<0.01), median peak HCV RNA level (5.3 log IU/mL vs. 6.0 log IU/mL vs. 6.5 log IU/mL, respectively; P<0.01) and the proportion with peak HCV RNA ≥5.6 log IU/mL (39% vs. 61% vs. 67%, respectively; P<0.01). There was also a trend towards a significant difference in sex across the three groups, with 54% of individuals with spontaneous HCV clearance being female, as compared to 37% in those with partial viral control with persistence and 35% in those with viral plateau with persistence (P = 0.09).

Bottom Line: 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).IFNL3 CC genotype is associated with initial viral control, while female sex is associated with ultimate spontaneous clearance.

View Article: PubMed Central - PubMed

Affiliation: The Kirby Institute, UNSW Australia (University of New South Wales), Sydney, NSW, Australia.

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.

No MeSH data available.


Related in: MedlinePlus