Spontaneous clearance of hepatitis C virus in an interleukin 28B favorable genotype highly prevalent area

Authors

  • Chao-Hung Hung M.D.,

    1. Division of Hepatogastroenterology Department of Internal Medicine Chang Gung Memorial Hospital-Kaohsiung Medical Center Chang Gung University College of Medicine Kaohsiung, Taiwan
    Search for more papers by this author
  • Kuo-Chin Chang M.D.,

    1. Division of Hepatogastroenterology Department of Internal Medicine Chang Gung Memorial Hospital-Kaohsiung Medical Center Chang Gung University College of Medicine Kaohsiung, Taiwan
    Search for more papers by this author
  • Sheng-Nan Lu M.D., M.P.H., Ph.D.,

    1. Division of Hepatogastroenterology Department of Internal Medicine Chang Gung Memorial Hospital-Kaohsiung Medical Center Chang Gung University College of Medicine Kaohsiung, Taiwan
    Search for more papers by this author
  • Jing-Houng Wang M.D.,

    1. Division of Hepatogastroenterology Department of Internal Medicine Chang Gung Memorial Hospital-Kaohsiung Medical Center Chang Gung University College of Medicine Kaohsiung, Taiwan
    Search for more papers by this author
  • Chien-Hung Chen M.D., Ph.D.,

    1. Division of Hepatogastroenterology Department of Internal Medicine Chang Gung Memorial Hospital-Kaohsiung Medical Center Chang Gung University College of Medicine Kaohsiung, Taiwan
    Search for more papers by this author
  • Chuan-Mo Lee M.D.,

    1. Division of Hepatogastroenterology Department of Internal Medicine Chang Gung Memorial Hospital-Kaohsiung Medical Center Chang Gung University College of Medicine Kaohsiung, Taiwan
    Search for more papers by this author
  • Tsung-Hui Hu M.D., Ph.D.

    1. Division of Hepatogastroenterology Department of Internal Medicine Chang Gung Memorial Hospital-Kaohsiung Medical Center Chang Gung University College of Medicine Kaohsiung, Taiwan
    Search for more papers by this author

  • Potential conflict of interest: Nothing to report.

To The Editor:

We read with great interest the article by Liu etal.,1 who studied the virus-host interaction and viral kinetics and evolution during the early phase of acute hepatitis C virus (HCV) infection in human subjects. They concluded that spontaneous clearance of acute HCV infection is predicted by high initial viremia as well as favorable interleukin (IL) 28B genotype and is associated with rapid envelope-sequence evolution.1 The authors noted that the initial viremia level in subjects with IL28B-C allele at rs12979860 and clearance was higher than that in subjects with IL28B-T allele and persistence (P = 0.001).1 However, these results require confirmation in a larger cohort and especially in Asian populations, in which IL28B favorable genotype is much more prevalent.2

To address the role of the rs12979860 single nucleotide polymorphism (SNP) in spontaneous HCV clearance among Asian populations, we genotyped 2,318 individuals comprised of individuals who cleared virus (n = 156) and those with persistent infection (n = 2,162). The distribution of the alleles of rs12979860 was in accordance with Hardy-Weinberg equilibrium in both individuals of HCV clearance and persistence (P = 1.0 and 0.32, respectively). Patients with HCV clearance and HCV persistence were similar regarding age and sex. However, the frequency of the C allele was significantly greater among individuals of HCV clearance (97%) than those of HCV persistence (93%) (P = 0.001) (Table 1). In addition, hepatitis B surface antigen (HBsAg) status was also associated with spontaneous HCV clearance. Multivariate logistic regression analysis demonstrated that rs12979860 CC genotype and HBV coinfection were independent factors associated with spontaneous HCV clearance, with odds ratios of 3.06 (95% confidence interval [CI] 1.47-6.37, P = 0.003) and 6.67 (95% CI 4.48-9.90, P < 0.001), respectively. Our data in agreement with Liu etal.'s finding confirmed a key role for IL28B genetic variation in determining spontaneous clearance.1 Alternatively, the frequency of the rs12979860 CC genotype in our study was substantially higher than that reported in Caucasians.2

Table 1. Characteristics of Study Subjects
 HCV Persistence (n=2,162)HCV Clearance (n=156) P-value
Age (years)55 (48-62)55 (43-64)0.702
Male gender (%)1138 (53%)79 (51%)0.345
HBsAg status (% positive)119 (6%)46 (29%)<0.001
ALT (U/L)113 (74-180)38 (22-66)<0.001
rs12979860 CC type (%)1868 (86%)148 (95%)0.001
Allele frequency (%)   
 C4023 (93%)304 (97%)0.001
 T301 (7%)8 (3%) 

The limited published data have indicated that 14%-42% of acute HCV-infected individuals recover spontaneously.3-6 Given the high prevalence of favorable IL28B genotype in Asian populations, it may be expected that spontaneous clearance of HCV is common in our patients. However, this is in contrast to our previous observation that a high percentage of subjects developed chronic disease following acute HCV infection.6 Also, this cannot explain that there are several HCV hyperendemic areas with an anti-HCV prevalence of up to 58% in southern Taiwan.7, 8 Based on the findings by Liu etal.,1 further investigation will be valuable to study the viral kinetics and evolution during the early phase of acute HCV infection in our populations.

Chao-Hung Hung X.X.*, Kuo-Chin Chang X.X.*, Sheng-Nan Lu X.X.*, Jing-Houng Wang X.X.*, Chien-Hung Chen X.X.*, Chuan-Mo Lee X.X.*, Tsung-Hui Hu X.X.*, * Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan.

Ancillary