Interleukin 28B genetic polymorphisms and viral factors help identify HCV genotype-1 patients who benefit from 24-week pegylated interferon plus ribavirin therapy.
BACKGROUND
Interleukin 28B (IL28B) single nucleotide polymorphism (SNP) genotypes and viral factors can predict sustained virological response (SVR) in HCV genotype-1 (HCV-1) patients receiving 48 weeks of pegylated interferon and ribavirin. Whether these factors would identify those patients who can benefit from a shorter duration of therapy remains unclear.


METHODS
Treatment-naive HCV-1 patients (n=662) receiving 24 or 48 weeks of combination therapy were enrolled. Baseline demographic data, HCV viral load, IL28B SNP genotypes (rs8099917), duration of therapy and rapid virological response (RVR) were evaluated to predict SVR. The SVR rates were further stratified by the independent factors and compared.


RESULTS
The IL28B rs8099917 TT genotype, low baseline viral load (HCV RNA≤600,000 IU/ml), RVR and 48-week therapy independently predicted SVR. In RVR patients with the IL28B rs8099917 TT genotype, the SVR rate of 24-week therapy was comparable to 48-week therapy (95% versus 99%; P=0.21) at low baseline viral load, but was inferior to 48-week therapy (70% versus 97%; P<0.001) at high baseline viral load. In non-RVR patients, the SVR rate of 24-week therapy was inferior to 48-week therapy for those with the IL28B rs8099917 TT genotype but high baseline viral load (23% versus 62%; P<0.001), and those with the IL28B rs8099917 GT/GG genotype but low baseline viral load (0% versus 33%; P=0.02).


CONCLUSIONS
HCV-1 patients simultaneously bearing the IL28B rs8099917 TT genotype, low baseline viral load and RVR can benefit from a shorter duration of combination therapy.
Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
Chen-Hua
CH
Liu
Cheng-Chao
CC
Liang
Chun-Jen
CJ
Liu
Tai-Chung
TC
Tseng
Chih-Lin
CL
Lin
Sheng-Shun
SS
Yang
Tung-Hung
TH
Su
Shih-Jer
SJ
Hsu
Jou-Wei
JW
Lin
Jun-Herng
JH
Chen
Pei-Jer
PJ
Chen
Ding-Shinn
DS
Chen
Jia-Horng
JH
Kao
D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D044466:Asian People / Q000235:genetics; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000145:classification / Q000187:drug effects / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011237:Predictive Value of Tests; D011994:Recombinant Proteins / Q000627:therapeutic use; D012254:Ribavirin / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load; D000095022:Interferon Lambda
D000998:Antiviral Agents; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D012254:Ribavirin; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C100416:peginterferon alfa-2a