In the present study, we defined an “immediate virological response (IVR)” as the loss of serum HCV RNA 7 d after the first administration of PEG-IFN α. We then conducted a 12-wk treatment course of PEG-IFN α2a in a population of patients who had low pretreatment HCV RNA load and who achieved IVR. This short-term PEG-IFN α2a monotherapy without the addition of RBV exhibited an extremely high SVR rate.
The current standard therapy to eliminate HCV in patients with chronic hepatitis C is combination therapy with PEG-IFN α and RBV. While the SVR rate for 24 wk of PEG-IFN α/RBV therapy in patients with genotypes 2 and 3 is 78%-93%, the SVR rate for 48 wk of treatment for genotype 1 is 40%-51%[1,2,10-13
]. New methods of determining the adequate dose and duration of PEG-IFN α/RBV administration have been devised to increase the probability of SVR in the treatment for patients with genotype 1 and high pretreatment viral load[9,14
]. High dose and long-term IFN treatments, however, are expensive and contribute to additional risk for many adverse events.
Major contributory factors for SVR are viral genotype (except genotype 1), low pretreatment viral load (< 1.0 × 105
IU/mL) and early loss of serum HCV RNA[3-7
]. Early virological response (EVR) and rapid virological response (RVR), which are indicated by loss of serum HCV RNA at weeks 12 and 4, respectively, are closely related to the SVR rate[6,7,15,16
]. Furthermore, Mangia et al[8
] have reported that 12 wk of administration of PEG-IFN α/RBV to patients with HCV genotype 2 or 3 and who achieve RVR, results in a high probability of SVR. Tabaru et al[17
] reported that the SVR rate was 100% after treatment with IFN α2b for 6 wk for patients infected with HCV genotype 2a and low viral load. Establishing the minimum, and yet sufficient, IFN therapy period is important in terms of financial efficiency and for reduction of the risk of adverse events. Therefore, it is essential to establish a guideline to make the treatment period shorter than the standard length for patients who have a high probability of achieving SVR. For patients with low pretreatment HCV RNA load, the current standard IFN therapy which is allowed by Japanese National Medical Insurance, is 24-48 wk of PEG-IFN α2a monotherapy without the addition of RBV. RBV causes hemolytic anemia, and severe anemic symptoms sometimes appear in PEG-IFN α/RBV combination treatment[18
]. PEG-IFN α monotherapy can avoid these adverse events induced by RBV.
Thus, in the current study, we studied the efficacy of short-term PEG-IFN α2a monotherapy for patients who had a low pretreatment HCV RNA load and exhibited IVR. Remarkably, 35 (97.2%) out of 36 cases that we were able to follow up to 24 wk after the last administration, were categorized into the SVR group. With regard to the HCV RNA genotype, SVR rates were 100% (4/4) for genotype 1b, 95.7% (22/23) for genotype 2a and 100% (4/4) for genotype 2b (Figure ). These data might suggest that the efficacy of short-term PEG-IFN α2a monotherapy for patients exhibiting IVR is independent of HCV genotype. Further analyses with a large population of patients should be conducted for each genotype of HCV, because the number of patients enrolled in this study, especially for genotype 1b, was small.
The patient (Pt. 6) who relapsed during this treatment course subsequently received 24 wk of PEG-IFN α2a therapy and succeeded in achieving SVR. We consider that if short-term treatment failed to induce SVR, those non-SVR patients could be re-treated with long-term PEG-IFN α monotherapy (24-48 wk) or PEG-IFN α/RBV combination therapy. Thus, it is suggested that we should select short-term monotherapy at the first approach for patients with low pretreatment HCV RNA load and IVR.
Nine out of 35 cases who achieved SVR received less than 9 wk (4-8 wk) of drug administration. Therefore, there is the possibility that the treatment period could be shortened to less than 12 wk for a certain group of patients. Further analyses in randomized controlled trials with a large population of patients should be conducted to examine the efficacy of shorter treatment courses, such as 4 wk or 8 wk.
Frequent adverse events that generally appear during IFN therapy were seen in this study group of patients. However, no severe events were observed. None of the patients required discontinuation of therapy because of bone marrow suppression. While 1 case exhibited bacterial pneumonia as a severe complication, the patient recovered with antibiotic treatment. Thus, we consider that short-term monotherapy is safe.
PEG-IFN α monotherapy clearly has the advantage of avoiding adverse events induced by RBV. However, we have to consider the possibility that adding RBV to this short term PEG-IFN α therapy could offer shorter treatment duration or higher SVR rates. This option should be investigated in larger studies.
In conclusion, short-term PEG-IFN α2a monotherapy is highly effective for chronic hepatitis C patients who have low pretreatment HCV RNA load and exhibit IVR. IVR is a simple and useful indicator of early viral kinetics to predict the high probability of SVR.