The present study examined 34 patients with CHC (18 men and 16 women; mean age, 62.8±10.1 for men and 63.6±10.4 years for women), who could be followed up long term, following triple treatment with PEG-IFN/RBV/TVR at Saiseikai Niigata Daini Hospital (Niigata, Japan) between November 2011 and March 2014. Written informed consent was obtained from all patients, and the Ethical Committee of Saiseikai Niigata Daini Hospital (Niigata, Japan) approved this study, which was conducted in accordance with the Declaration of Helsinki.

All patients received TVR (Mitsubishi Tanabe Pharma Corporation, Osaka, Japan) in combination with PEG-IFN α2b and RBV (both MSD, Tokyo, Japan) for 12 weeks. This was followed by an additional 12 weeks of PEG-IFN α2b and RBV alone. TVR (750 mg) was orally administered every 8 h, PEG-IFN α2b (1.5 µg/kg) was injected subcutaneously weekly and oral RBV was given daily at a dose of between 600 and 800 mg based on the body weight of the patient.

The association between the HRQOL of patients with CHC treated with TVR-based treatment and gender, age or treatment history was examined. The HRQOL of study participants was measured using a 36-item self-administered questionnaire, the SF-36. The SF-36 evaluates the following eight physical and mental health areas: Physical functioning (PF), physical role functioning (RP), bodily pain (BP), general health (GH), vitality (VT), social role functioning (SF), emotional role functioning (RE) and mental health (MH) (7). Each of the 8 areas was scored on a scale of 0–100, where a higher score indicated better health subjectively. These scores were calculated from the questionnaires as described previously (8–10). Briefly, a Japanese-validated version of SF-36 was used and the results were compared to a Japanese normative sample score of the SF-36 in 2,966 individuals (10,11). Scores were calculated based on the standard value (100 points) for the Japanese population.

Evaluation of HRQOL using the SF-36 was performed prior to treatment (0W), 2 weeks following the start of treatment (2W), 3 months following the start of treatment (12W), 6 months following the start of treatment (24W) and 1 year following the start of treatment (48W). In examination on the basis of treatment history, patients were classified as naïve (no prior CHC treatment; n=14), relapsed (recurrence of virus following treatment for CHC; n=19) or null responders (no change in viral load following CHC treatment; n=1, excluded from analysis due to low number).

Intergroup HRQOL was compared using the Student's t-test, the chi-squared test and the Mann-Whitney U test, while scores prior to and following the start of treatment were compared using a paired t-test. P<0.05 was considered to indicate a statistically significant difference. Statistical analysis was performed using StatView software (version 5.0; SAS Institute, Inc., Cary, NC, USA).

The clinical characteristics of patients were compared on the basis of gender (Table I). The men showed significantly higher values for height (P<0.01), weight (P<0.01), and body mass index (BMI; P<0.05), whereas the women exhibited a significantly higher serum concentration of RBV (12.6±2.1 mg/kg vs. 10.6±2.1 mg/kg; P<0.05) and TVR (39.8±7.7 mg/kg vs. 30.6±5.6 mg/kg; P<0.01). Hemoglobin (Hb) levels dropped in men and women during treatment as SF-36 scores fell (Fig. 1A). Mean Hb levels were 13.0±1.6 g/dl in men and 13.1±1.0 g/dl in women prior to starting treatment, but dropped significantly to 9.4±1.4 g/dl and 8.4±1.2 g/dl, respectively, by 12W (P<0.05; Fig. 1A). However, at 48W Hb values were 13.0±2.5 g/dl in men and 13.0±0.6 g/dl in women (Fig. 1A), indicating that baseline Hb levels had been recovered.

HRQOL improved markedly following completion of TVR-based triple treatment in complete-responders, with higher scores compared with those prior to treatment (data not shown). Interestingly, anemia (Hb <8 g/dl) and skin symptoms appeared frequently during treatment, corresponding to scores for physical functioning dropped (data not shown).

Comparison of PF scores revealed a downward trend for men (n=18) and women (n=16) following TVR-based triple treatment until 12W, with PF scores in men dropping significantly from 39.8±16.4 at 2W to 27.2±15.4 at 12W (P=0.037; Fig. 1B). In addition, PF improved from 12W, with a mean PF score in men of 53.9±3.0 at 48W, significantly higher than the pre-treatment score of 39.6±13.1 (P=0.0009; Fig. 2). In addition, scores for RP dropped significantly in women between 0W and 2W (P=0.0046; Fig. 2).

The score for MH in women was 42.5±10.8 prior to treatment (0W) and 35.5±9.8 at 12W (Fig. 3). Although a downward trend was seen, this difference was not significant. No significant differences in MH scores were seen between men and women, and no effects of TVR-based treatment on MH scores were observed (Fig. 3).

Patient characteristics were compared between patients ≥65 years old (elderly group, n=19) and those <65 years old (non-elderly group, n=15). The results of this comparison are presented in Table II. While significant differences in height (P<0.05) and treatment history (P<0.01) were seen between the elderly and non-elderly groups, no significant differences were seen in PEG-IFN, RBV or TVR dosage.

The non-elderly group exhibited significantly higher scores in PF (P<0.05) and RP (P<0.01) prior to treatment, which are correlated with physical health (Fig. 4). However, a drop in scores was seen the non-elderly and elderly groups during TVR treatment (Fig. 4). A significant rise in RP score was seen in the non-elderly group at 48W, following completion of treatment (P<0.01; Fig. 4).

A comparison of patient characteristics according to prior treatment history is presented in Table III. Patients were classified as naïve (n=14), relapsed (n=19) or null responders (n=1). However, the null responders group was excluded from this analysis. A tendency towards low PF scores, correlated with poor physical health, was seen in the naïve and relapse groups during TVR-based treatment. In the naïve group, the mean PF score was 44.0±13.7 prior to treatment and decreased significantly to 29.2±17.6 between 0W and 12W (P=0.02; Fig. 5). In the relapse group the decrease was not significant (Fig. 5). MH tended to decrease during TVR-based treatment, however, no significant difference was seen between groups (Fig. 5).