Host and viral determinants of the outcome of exposure to HCV infection genotype 4: a large longitudinal study

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...

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Published in:	The American journal of gastroenterology Vol. 109; no. 2; pp. 199 - 211
Main Authors:	Kamal, Sanaa M, Kassim, Samar K, Ahmed, Amany I, Mahmoud, Sara, Bahnasy, Khaled A, Hafez, Tamer A, Aziz, Ibrahiem A, Fathelbab, Iman F, Mansour, Hoda M
Format:	Journal Article
Language:	English
Published:	United States Wolters Kluwer Health Medical Research, Lippincott Williams & Wilkins 01-02-2014
Subjects:	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 Egypt
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Summary:	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.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23
ISSN:	0002-9270 1572-0241
DOI:	10.1038/ajg.2013.427