Host and viral determinants of the outcome of exposure to HCV infection genotype 4: a large longitudinal study.
OBJECTIVE
The objective of this study was to characterize the factors that influence the outcome of exposure to hepatitis C virus (HCV) genotype 4 (HCV-G4) and the course of recent infection.


METHODS
In this longitudinal study, we prospectively assessed the clinical, genetic, virological, and immunological parameters and retrospectively determined single-nucleotide polymorphisms at interleukin-28B (IL-28B) rs12979860 in a well-characterized large cohort recently exposed to HCV-G4.


RESULTS
A total of 136 subjects with acute HCV (new viremia, seroconversion, and HCV-specific T-cell responses) were identified. Forty-eight subjects (35%) had spontaneous viral clearance and 88 subjects developed chronic HCV of which 42 subjects were treated with pegylated interferon monotherapy, with a sustained virologic response (SVR) rate of 88%. Twenty-six subjects developed HCV-specific T-cell immune responses without detectable viremia or seroconversion. IL-28B-CC (odds ratio (OR) 14.22; P<0.0001), multispecific T-cell responses (OR=11.66; P<0.0001), >300 IU/l alanine aminotransferase (ALT) decline within 4 weeks (OR=6.83; P<0.0001), jaundice (OR=3.54; P=0.001), female gender (OR=2.39; P=0.007), and >2.5 log10 HCV-RNA drop within 8 weeks (OR=2.48; P=0.016) were independently associated with spontaneous clearance. ALT normalization and undetectable HCV-RNA predicted SVR. Exposed apparently uninfected participants had a higher frequency of IL-28B-CC than patients with unresolved acute HCV (P<0.001). IL-28B-CC was associated with multispecific T-cell response (r(2)=0.0.835; P<0.001).


CONCLUSIONS
IL-28B-CC genotype, multispecific HCV T-cell responses, rapid decline in ALT, and viral load predict spontaneous clearance and response to acute HCV-G 4 therapy. IL-28B-CC genotype correlates with developing early multispecific T-cell responses. These findings have important implications for predicting the outcome of HCV exposure and acute infection and identifying patients likely to benefit from therapy.
Department of Infectious Diseases, Gastroenterology and Tropical Medicine, Ain Shams Faculty of Medicine, Cairo, Egypt.
Sanaa M
SM
Kamal
Department of Molecular Biology and Biochemistry, Ain Shams Faculty of Medicine, Cairo, Egypt.
Samar K
SK
Kassim
Department of Infectious Diseases, Gastroenterology and Tropical Medicine, Ain Shams Faculty of Medicine, Cairo, Egypt.
Amany I
AI
Ahmed
Department of Infectious Diseases, Gastroenterology and Tropical Medicine, Ain Shams Faculty of Medicine, Cairo, Egypt.
Sara
S
Mahmoud
Department of Biostatistics and Bioinformatics, Ain Shams University, Cairo, Egypt.
Khaled A
KA
Bahnasy
Department of Molecular Biology and Genetics, The American University in Cairo, Egypt.
Tamer A
TA
Hafez
Department of Tropical Medicine, Al Azhar Faculty of Medicine, Cairo, Egypt.
Ibrahiem A
IA
Aziz
Department of Immunology, Vacsera, Cairo, Egypt.
Iman F
IF
Fathelbab
Department of Immunology, Vacsera, Cairo, Egypt.
Hoda M
HM
Mansour
D000208:Acute Disease; D000328:Adult; D017677:Age Distribution; D000998:Antiviral Agents / Q000627:therapeutic use*; D016022:Case-Control Studies; D016001:Confidence Intervals; D018450:Disease Progression; D004534:Egypt / Q000453:epidemiology; D005260:Female; D029407:GB virus C / Q000235:genetics / Q000302:isolation & purification; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics*; D006526:Hepatitis C / Q000188:drug therapy / Q000453:epidemiology* / Q000235:genetics*; D006801:Humans; D015994:Incidence; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D053208:Kaplan-Meier Estimate; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D011446:Prospective Studies; D012367:RNA, Viral / Q000032:analysis / Q000235:genetics; D012254:Ribavirin / Q000627:therapeutic use; D017678:Sex Distribution; D018709:Statistics, Nonparametric; D016896:Treatment Outcome; D019562:Viral Load / Q000235:genetics; D014766:Viremia / Q000453:epidemiology* / Q000235:genetics; D000095022:Interferon Lambda
D000998:Antiviral Agents; D007372:Interferons; D007378:Interleukins; D012367:RNA, Viral; D012254:Ribavirin; C000624353:interferon-lambda, human; D000095022:Interferon Lambda