Journal Article

Host and Viral Determinants of the Outcome of Exposure to HCV Infection Genotype 4: A Large Longitudinal Study

Kamal, Sanaa M, Ahmed, Amany I, Mansour, Hoda M, Kassim, Samar K, Aziz, Ibrahiem A, Fathelbab, Iman F, Hafez, Tamer A, Mahmoud, Sara, Bahnasy, Khaled A

2014

Overview

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. 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. 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). 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.

• Publisher: Wolters Kluwer Health Medical Research, Lippincott Williams & Wilkins
• Subject: Acute Disease / Adult / Age Distribution / Antiviral Agents - therapeutic use / Case-Control Studies / Confidence Intervals / Disease Progression / Egypt - epidemiology / Female / Gastroenterology / GB virus C - genetics / GB virus C - isolation & purification / Genotype / Hepacivirus - drug effects / Hepacivirus - genetics / Hepatitis C - drug therapy / Hepatitis C - epidemiology / Hepatitis C - genetics / Hepatitis C virus / Humans / Incidence / Interferons / Interleukins - genetics / Kaplan-Meier Estimate / Longitudinal Studies / Male / Middle Aged / Polymorphism, Single Nucleotide / Prognosis / Prospective Studies / Ribavirin - therapeutic use / RNA, Viral - analysis / RNA, Viral - genetics / Sex Distribution / Statistics, Nonparametric / Treatment Outcome / Viral Load - genetics / Viremia - epidemiology / Viremia - genetics