Correlation of interferon-lambda 4 ss469415590 with the hepatitis C virus treatment response and its comparison with interleukin 28b polymorphisms in predicting a sustained virological response: a meta-analysis.
BACKGROUND
Interferon-lambda 4 (IFNL4) ss469415590 is a newly discovered polymorphism that could predict the treatment response in hepatitis C virus (HCV)-infected patients. This meta-analysis was performed in order to clarify its specific effect on the treatment response and to compare it with interleukin 28b (IL28B).


METHODS
The commonly used literature databases were searched. Meta-analyses were performed with fixed/random-effects models using Stata 12.0. The sustained virological response (SVR) rate was summarized using R software. Publication bias was examined through Egger's test.


RESULTS
A total of seven studies were finally included in this meta-analysis. IFNL4 ss469415590 was demonstrated to be associated with SVR (odds ratio (OR) 3.83, 95% confidence interval (CI) 3.22-4.56, p<0.001). Asians had a higher likelihood of achieving SVR than Caucasians (OR=7.36 vs. 3.54). When stratifying all the patients according to HCV genotype, a significant association was observed in HCV genotype 1 patients (OR 4.5, 95% CI 2.91-6.95, p<0.001). In HCV genotype 2/3 patients, the favorable TT/TT genotype patients tended to have a statistically higher SVR rate than the non-TT/TT genotype patients (84.4% vs. 78.3%, p=0.058). Compared with IL28B rs12979860 (OR 3.45) and rs8099917 (OR 3.50), ss469415590 TT/TT genotype patients showed a slightly higher probability of achieving a SVR (OR 3.61 calculated from studies investigating both IFNL4 and rs12979860; OR 4.86 for studies investigating both IFNL4 and rs8099917). Furthermore, ss469415590 showed a slightly higher predictive value than rs12979860 using the diagnostic test tool (area under the curve=0.71 vs. 0.70). IFNL4 was also correlated with rapid virological response (RVR) (OR 4.35, 95% CI 1.43-13.20, p=0.01), viral clearance (OR 0.31, 95% CI 0.24-0.39, p<0.001), and HCV susceptibility (OR 0.76, 95% CI 0.65-0.89, p=0.001).


CONCLUSIONS
IFNL4 ss469415590 is significantly associated with SVR in HCV genotype 1 patients, irrespective of race; there is a tendency towards an association in HCV genotype 2/3 patients. Comparable to IL28B, IFNL4 is correlated with natural viral clearance and HCV susceptibility, additionally IFNL4 ss469415590 has a slightly higher predictive performance over IL28B polymorphisms in regard to SVR.
Department of Infectious Diseases, Binzhou Medical University Hospital, No. 661 Huanghe 2(nd) Road, Binzhou, Shandong 256603, China. Electronic address: liyh_binzhou@126.com.
Yunhua
Y
Li
Binzhou Medical University Hospital Outpatient Department, Binzhou Medical University Hospital, Binzhou, Shandong, China.
Luhua
L
Yang
Binzhou Medical University School of Nursing, Binzhou, Shandong, China.
Kaihui
K
Sha
Department of Infectious Diseases, Binzhou Medical University Hospital, No. 661 Huanghe 2(nd) Road, Binzhou, Shandong 256603, China.
Tonggang
T
Liu
Department of Infectious Diseases, Binzhou Medical University Hospital, No. 661 Huanghe 2(nd) Road, Binzhou, Shandong 256603, China.
Liguo
L
Zhang
D000998:Antiviral Agents / Q000627:therapeutic use*; D044466:Asian People; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D000072230:Sustained Virologic Response; D016896:Treatment Outcome; D044465:White People; D000095022:Interferon Lambda
D000998:Antiviral Agents; D007372:Interferons; D007378:Interleukins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C579163:IFNL4 protein, human
Hepatitis C virus; Interferon-lambda 4; Interleukin 28b; Meta-analysis; Sustained virological response