title: Individualized therapy for hepatitis C infection: focus on the interleukin-28B polymorphism in directing therapy.
abstract: Hepatitis C virus—a major global cause of chronic hepatitis, cirrhosis, and hepatocellular carcinoma—affects millions of people worldwide. Pegylated interferon (Peg-IFN) and ribavirin (RBV) had been the standard treatment for a decade until availability of the protease inhibitors in 2011. However, current antiviral therapy is still IFN-based and is associated with significant side effects and variable treatment response. Thus, various host and viral factors have been evaluated before and during treatment for the prediction of sustained virologic response to antiviral therapy. In 2009, genome-wide association studies found the single-nucleotide polymorphisms, located near the host interleukin-28B (IL28B) gene that encodes IFN-λ3, to be the best pretreatment predictor of virologic response to Peg-IFN and RBV therapy in chronic hepatitis C genotype 1 patients. Additionally, inosine triphosphatase (ITPA) gene variants were found to be associated with RBV-induced hemolytic anemia, which could affect treatment dose for selected patients. IL28B, ITPA, and other treatment predictors allowed for a potential individualized approach to treat hepatitis C. In the era of increased overall virologic response rates and good tolerability of the rapidly developing non-IFN oral direct-acting antiviral therapy regimens, the need for individualized treatment is likely to diminish. Various predictors of response, including IL28B will likely be of reduced importance in the near future.
authors.forename: Tzu-Hao
authors.initials: TH
authors.lastname: Lee
authors.forename: Hans L
authors.initials: HL
authors.lastname: Tillmann
authors.forename: Keyur
authors.initials: K
authors.lastname: Patel
mesh_terms: D000743:Anemia, Hemolytic / Q000139:chemically induced; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D004359:Drug Therapy, Combination; D005819:Genetic Markers; D014644:Genetic Variation; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics*; D006801:Humans; D007372:Interferons; D007378:Interleukins / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D057285:Precision Medicine / Q000379:methods*; D011480:Protease Inhibitors / Q000627:therapeutic use*; D011755:Pyrophosphatases / Q000235:genetics; D012254:Ribavirin / Q000009:adverse effects / Q000627:therapeutic use*; D000095022:Interferon Lambda; D000097630:Inosine Triphosphatase
chemical_list: D000998:Antiviral Agents; D005819:Genetic Markers; D007372:Interferons; D007378:Interleukins; D011480:Protease Inhibitors; D011755:Pyrophosphatases; D012254:Ribavirin; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C511829:ITPA protein, human; D000097630:Inosine Triphosphatase
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