Pegylated interferon/ribavirin (peg-IFN/RBV) combination therapy is effective for chronic hepatitis C (CHC) but frequently causes adverse events, leading to early termination. Little is known about the outcome of CHC patients who required early termination.
Methods
Of 617 treatment-naive CHC patients prescribed a 24-week protocol of peg-IFN/RBV, 29 (4.7%) patients who terminated treatment early at <20 weeks were recruited to evaluate the rate of and the factors associated with sustained virological response (SVR), defined as seronegativity of hepatitis C virus (HCV) RNA throughout the 24-week off-treatment follow-up period.
Results
The reasons for early termination were flu-like symptoms/signs (n=9, 31.0%), irritability (n=1, 3.4%), severe urticaria (n=1, 3.4%), insomnia (n=2, 6.9%), pulmonary tuberculosis (n=1, 3.4%), suicide idea (n=2, 6.9%), poor response (n=2, 6.9%), depression (n=2, 6.9%), unwilling to continue (n=1, 3.4%), mortality (n=1, 3.4%), gastrointestinal upset (n=1, 3.4%), pancytopenia complicated with cellulitis (n=1, 3.4%), anaemia (n=3, 10.3%), overseas work (n=1, 3.4%) and an unknown cause (n=1, 3.4%). Five (17.2%) patients achieved an SVR, comprising none of 16 HCV genotype-1 and five of the 13 (38.5%) genotype-2 patients (P=0.001). All sustained responders were HCV RNA seronegative at week 4 of treatment. The SVR rate among HCV-2 patients was 0% (0/1), 0% (0/2), 25% (1/4), 33% (1/3) and 100% (3/3) in those who received peg-IFN/RBV for 1–3, 4–7, 8–11, 12–15 and 16–19 weeks, respectively (P=0.019, χ2 with linear trend).
Conclusions
Based on this limited study, we observed that an SVR might be achieved in patients who required early termination of a 24-week regimen of peg-IFN/RBV, especially for HCV-2 patients with HCV RNA seronegativity at week 4.
References
1.
YuM.L., DaiC.Y., LinZ.Y.A randomized trial of 24-vs. 48-week courses of PEG interferon alpha-2b plus ribavirin for genotype-1b-infected chronic hepatitis C patients: a pilot study in Taiwan.Liver Int2006; 26: 73–81.
2.
NIH Consensus Statement on Management of Hepatitis C: 2002.NIH Consens State Sci Statements2002; 19: 1–46.
3.
ChuangW.L., YuM.L., DaiC.Y., ChangW.Y.Treatment of chronic hepatitis C in southern Taiwan.Intervirology2006; 49: 99–106.
4.
FriedM.W., ShiffmanM.L., ReddyK.R.Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection.N Engl J Med2002; 347: 975–982.
5.
MannsM.P., McHutchisonJ.G., GordonS.C.Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial.Lancet2001; 358: 958–965.
6.
HadziyannisS.J., SetteH.Jr., MorganT.R., Peginterferon-alpha2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose.Ann Intern Med2004; 140: 346–355.
7.
LeeS.D., YuM.L., ChengP.N.Comparison of a 6-month course peginterferon alpha-2b plus ribavirin and interferon alpha-2b plus ribavirin in treating Chinese patients with chronic hepatitis C in Taiwan.J Viral Hepat2005; 12: 283–291.
8.
YuM.L., DaiC.Y., ChenS.C.A prospective study on treatment of chronic hepatitis C with tailored and extended interferon-alpha regimens according to pretreatment virological factors.Antiviral Res2004; 63: 25–32.
9.
ChuangW.L., DaiC.Y., ChenS.C.Randomized trial of three different regimens for 24 weeks for re-treatment of chronic hepatitis C patients who failed to respond to interferon-alpha monotherapy in Taiwan.Liver Int2004; 24: 595–602.
10.
ChuangW.L., DaiC.Y., ChangW.Y.Viral interaction and responses in chronic hepatitis C and B coinfected patients with interferon-alpha plus ribavirin combination therapy.Antivir Ther2005; 10: 125–133.
11.
McHutchisonJ.G., MannsM., PatelK.Adherence to combination therapy enhances sustained response in geno-type-1-infected patients with chronic hepatitis C.Gastroenterology2002; 123: 1061–1069.
12.
NousbaumJ.B., CadranelJ.F., SavaryO., LegrandM.C., DumouchelP., GouerouH.Sustained virological response after a short course of treatment with interferon and ribavirin in two chronic hepatitis C patients.J Hepatol2003; 39: 655–656.
13.
OkamotoH., TokitaH., SakamotoM.Characterization of the genomic sequence of type V (or 3a) hepatitis C virus isolates and PCR primers for specific detection.J Gen Virol1993; 74: 2385–2390.
14.
KnodellR.G., IshakK.G., BlackW.C.Formulation and application of a numerical scoring system for assessing histological activity in asymptomatic chronic active hepatitis.Hepatology1981; 1: 431–435.
15.
NeumannA.U., LamN.P., DahariH.Differences in viral dynamics between genotypes 1 and 2 of hepatitis C virus.J Infect Dis2000; 182: 28–35.
16.
ZeuzemS., HerrmannE., LeeJ.H.Viral kinetics in patients with chronic hepatitis C treated with standard or peginterferon alpha2a.Gastroenterology2001; 120: 1438–1447.
17.
FerenciP.Predicting the therapeutic response in patients with chronic hepatitis C: the role of viral kinetic studies.J Antimicrob Chemother2004; 53: 15–18.
18.
JessnerW., GschwantlerM., Steindl-MundaP.Primary interferon resistance and treatment response in chronic hepatitis C infection: a pilot study.Lancet2001; 358: 1241–1242.
19.
DalgardO., BjoroK., HellumK.B.Treatment with pegylated interferon and ribavirin in HCV infection with genotype 2 or 3 for 14 weeks: a pilot study.Hepatology2004; 40: 1260–1265.
20.
MangiaA., SantoroR., MinervaN.Peginterferon alfa-2b and ribavirin for 12 vs. 24 weeks in HCV genotype 2 or 3.N Engl J Med2005; 352: 2609–2617.
21.
von WagnerM., HuberM., BergT.Peginterferon-alpha-2a (40KD) and ribavirin for 16 or 24 weeks in patients with genotype 2 or 3 chronic hepatitis C.Gastroenterology2005; 129: 522–527.
