Gastroenterology

Gastroenterology

Volume 142, Issue 1, January 2012, Pages 78-85.e2
Gastroenterology

Original Research
Clinical—Liver
Serum Level of IP-10 Increases Predictive Value of IL28B Polymorphisms for Spontaneous Clearance of Acute HCV Infection

https://doi.org/10.1053/j.gastro.2011.09.039Get rights and content

Background & Aims

Single nucleotide polymorphisms (SNPs) in IL28B and serum levels of interferon γ inducible protein 10 (IP-10) predict outcomes of antiviral therapy in patients with chronic hepatitis C. We associated IL28B SNPs rs12979860 and rs8099917, along with serum levels of IP-10, with outcomes of patients with acute hepatitis C (AHC).

Methods

We studied 120 patients with AHC (64 male; 37 ± 16 years old) and 96 healthy individuals (controls). The IL28B SNPs rs12979860 and rs8099917 were detected using real-time polymerase chain reaction; serum concentrations of IP-10 were measured by enzyme-linked immunosorbent assays of 62 patients with AHC.

Results

Hepatitis C virus was cleared spontaneously from 59 patients (49.2%). The IL28B rs12979860 C/C genotype was more frequent among patients with AHC than controls (62.5% vs 39.6%; P < .001) and among patients with spontaneous clearance than those without (74.6% vs 51.7%; P = .02) (positive predictive value, 60.3%). Patients with IL28B rs12979860 C/C more frequently developed jaundice (53.2% vs 27.6%; P = .022) than carriers of the T allele. The median level of IP-10 was lower among patients with AHC and spontaneous clearance (764 [113–2470] pg/mL) than those without spontaneous clearance (1481 [141–4412] pg/mL; P = .006). Based on receiver operating characteristic analysis, 540 pg/mL IP-10 was set as the cutoff for patients most likely to have spontaneous clearance (positive predictive value, 71.4%; negative predictive value, 65.9%). Including data on IP-10 levels increased the ability of the IL28B rs12979860 C/C to identify patients most likely to have spontaneous clearance (83% of those who had an IP-10 level <540 pg/mL and 32% who had an IP-10 level >540 pg/mL) (P < .01).

Conclusions

The combination of serum level of IP-10 and SNPs in IL28B can identify patients with AHC who are most likely to undergo spontaneous clearance and those in need of early antiviral therapy.

Section snippets

Patients

A total of 120 patients with AHC (64 male and 56 female; mean age, 37 ± 16 years) and 96 healthy controls were analyzed for IL28B SNPs rs12979860 and rs8099917. All patients as well as healthy controls were white. The 96 healthy controls were healthy voluntary blood donors and considered to be representative for normal frequencies of tested SNPs in the Austrian population.

AHC was defined either by an elevation of alanine aminotransferase (ALT) level of more than 5 times the upper limit of

Patient Characteristics

The mean age of patients with AHC was 37 ± 16 years and did not show any significant differences among patients with different IL28B genotypes. All patients were of European ancestry and diagnosed with AHC in Austrian referral centers. One hundred and six patients (88.3%) presented with ALT elevations of more than 5 times the upper limit of normal with or without jaundice and were diagnosed at the time point of acute presentation (Table 1). Fourteen patients (11.7%) had ALT levels less than 5

Discussion

In view of the high sustained virologic response rates by early antiviral therapy in acute HCV infection, identification of patients who may not clear HCV spontaneously is of importance. A delay of treatment of more than 3 months may diminish the efficacy of antiviral treatment.2, 3, 16, 17, 18, 19 On the other hand, due to high morbidity and costs, one should avoid unnecessary treatment, especially because a stringent allocation of increasingly limited economic resources is warranted. Thus,

Acknowledgments

The authors thank Kerstin Zinober, Elisabeth Eder, and Claudia Willheim for their help in sample collection and determination of IL28B SNPs and Dr Christoph Krall, from the Institute of Medical Statistics, Medical University of Vienna, Austria, for help in statistical analysis.

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  • Cited by (0)

    Conflicts of interest The authors disclose the following: Peter Ferenci is a member of the global advisory board and the speaker's bureau of Roche (Basel, Switzerland) and Rottapharm-Madaus (Monza, Italy); an advisor to Böhringer-Ingelheim, Vertex/Tibotec, Pfizer, and MSD Austria; and a recipient of an unrestricted research grant from Roche Austria. Harald Hofer, Andreas Maieron, Michael Strasser, and Rudolf Stauber serve as speakers for Roche Austria and MSD Austria. Petra Steindl-Munda and Christian Datz serve as speakers for Roche Austria. The remaining authors disclose no conflicts.

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