Interleukin 28B genetic polymorphisms play a minor role in identifying optimal treatment duration in HCV genotype 1 slow responders to pegylated interferon plus ribavirin.
BACKGROUND
Pegylated interferon and ribavirin for 72 weeks improve sustained virological response (SVR) in HCV genotype 1 (HCV-1) slow viral responders. Whether interleukin 28B (IL28B) single nucleotide polymorphism (SNP) genotypes and on-treatment viral responses can identify non-rapid virological response (RVR) patients who benefit from 48 or 72 weeks of therapy remains unclear.


METHODS
Treatment-naive HCV-1 patients who failed to achieve RVR were randomly assigned to receive 48 (n=168) or 72 (n=167) weeks of therapy. Baseline factors and on-treatment virological responses at weeks 8 and 12 were evaluated for SVR in 289 compliant patients who received ≥80% of drug dosages and treatment duration, and had end of follow-up viral response. The stratified SVR rates for independent factors were compared by treatment duration.


RESULTS
Treatment duration, IL28B rs8099917 genotypes, cirrhosis, week-8 viral response (undetectable HCV RNA at treatment week 8) and complete early virological response (cEVR) predicted SVR. In week-8 viral response patients, the SVR rates of 72-week and 48-week treatment were similar (75-88%), regardless of IL28B SNP genotypes or cirrhosis. In non-week-8 viral response patients who achieved cEVR, the SVR rate of 72-week treatment was higher than that of 48-week treatment for non-cirrhotic patients, regardless of IL28B SNP genotypes (91-100% versus 13-44%; P=0.001).


CONCLUSIONS
Although IL28B SNP genotypes predict SVR, they play a minor role when on-treatment viral responses are taken into consideration. On-treatment viral responses at weeks 8 and 12 are the key determinants to decide the optimal treatment duration in HCV-1 patients without RVR.
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
Jou-Wei
JW
Lin
Jun-Herng
JH
Chen
Pei-Jer
PJ
Chen
Ding-Shinn
DS
Chen
Jia-Horng
JH
Kao
D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics / Q000472:pathogenicity*; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000235:genetics / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use*; D007372:Interferons / Q000627:therapeutic use; D007378:Interleukins / Q000235:genetics* / Q000378:metabolism; D008103:Liver Cirrhosis / Q000188:drug therapy / Q000235:genetics / Q000821:virology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012367:RNA, Viral / Q000097:blood; D012254:Ribavirin / Q000008:administration & dosage / Q000627:therapeutic use*; D013624:Taiwan; D013997:Time Factors; D016896:Treatment Outcome; D000095022:Interferon Lambda
D000998:Antiviral Agents; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D012367:RNA, Viral; D012254:Ribavirin; C000624353:interferon-lambda, human; D000095022:Interferon Lambda