Long-term efficacy of Peg-Interferon/Ribavirin with and without Lamivudine therapy for HBeAg-positive hepatitis B and C dual infection.

BACKGROUND: The optimal therapeutic strategy for hepatitis B virus (HBV) e antigen (HBeAg)-seropositive and hepatitis C virus (HCV) dually infected patients remains unknown. We aimed to elucidate the effectiveness of peginterferon (Peg-IFN)/ribavirin (RBV) with and without lamivudine (LAM) combination therapy in the clinical settings. PATIENTS AND METHODS: Nine patients seropositive for HBV surface antigen, HBeAg, antibodies to HCV and HCV RNA for >6 months were treated with Peg-IFN/RBV with (n = 5) and without (n = 4) a 12-month LAM add-on therapy at treatment week 12. The treatment duration of Peg-IFN/RBV was 24 weeks (HCV genotype 1 [HCV-1] with rapid virological response [RVR] or HCV-2) or 48 weeks (HCV-1 without RVR). Primary endpoints included HBeAg loss and HCV-sustained virological response (SVR). RESULTS: All of the nine patients had undetectable HCV RNA at treatment weeks 4 and 12 and end-of-Peg-IFN/RBV therapy. However, SVR was achieved in 100% of patients treated with triple therapy, compared with only 50% in those with Peg-IFN/RBV therapy (P = 0.167). The 3-year durability of HCV SVR was 100%. HBeAg loss and HBV DNA <2000 IU/mL at 6 months post-LAM treatment were found in 100% and 40% of patients treated with triple therapy, compared with none of the four patients with Peg-IFN/RBV therapy achieved any HBV responses. Of the five patients with triple therapy, four had persistent HBeAg loss during 3-year follow-up period; one developed HBeAg seroreversion 15 months after treatment. CONCLUSION: For HBeAg-positive HBV/HCV dually infected patients, Peg-IFN/RBV was effective for HCV eradication. Add-on LAM might promote HBeAg loss in the clinical setting.

Peginterferon alfa-2a with or without low-dose ribavirin for treatment-naive patients with hepatitis C virus genotype 2 receiving haemodialysis: a randomised trial.

OBJECTIVE: Data comparing the efficacy and safety of combination therapy with peginterferon plus low-dose ribavirin and peginterferon monotherapy in treatment-naive haemodialysis patients with hepatitis C virus genotype 2 (HCV-2) infection are limited. DESIGN: In this randomised trial, 172 patients received 24 weeks of peginterferon alfa-2a 135 µg/week plus ribavirin 200 mg/day (n=86) or peginterferon alfa-2a 135 µg/week (n=86). The efficacy and safety endpoints were sustained virological response (SVR) rate and adverse event (AE)-related withdrawal rate. RESULTS: Compared with monotherapy, combination therapy had a greater SVR rate (74% vs 44%, relative risk (RR): 1.68 [95% CI 1.29 to 2.20]; p<0.001). The beneficial effect of combination therapy was more pronounced in patients with baseline viral load ≥800,000 IU/mL than those with baseline viral load <800,000 IU/mL (RR: 3.08 [95% CI 1.80 to 5.29] vs. RR: 1.11 [95% CI 0.83 to 1.45]; interaction p=0.001). Patients receiving combination therapy were more likely to have a haemoglobin level of <8.5 g/dL (70% vs. 8%, risk difference (RD): 62% [95% CI 50% to 73%]; p<0.001) and required a higher dosage [mean: 13,417 vs. 6667 IU/week, p=0.027] of epoetin ß to manage anaemia than those receiving monotherapy. The AE-related withdrawal rates were 6% and 3% in combination therapy and monotherapy groups, respectively (RD: 2% [95% CI -4% to 9%]). CONCLUSIONS: In treatment-naive haemodialysis patients with HCV-2 infection, combination therapy with peginterferon plus low-dose ribavirin achieved a greater SVR rate than peginterferon monotherapy. Most haemodialysis patients can tolerate combination therapy. TRIAL REGISTRATION NUMBER: ClinicalTrial.gov number, NCT00491244.

The tertiary prevention of hepatocellular carcinoma in chronic hepatitis C patients.

BACKGROUND AND AIM: Pegylated interferon-alpha plus ribavirin combination (PegIFN/RBV) therapy possesses positive effect in the secondary prevention of hepatocellular carcinoma (HCC) in chronic hepatitis C (CHC) patients. The current study aimed to assess its efficacy in the tertiary prevention and to validate the performance of the MHC class I polypeptide-related chain A (MICA) level in the prediction of hepatocellular carcinoma (HCC) recurrence. METHODS: A multi-center study enrolling 105 consecutive HCC patients post curative therapies were prospectively recruited. The primary outcome measurement was recurrence of HCC. RESULTS: The mean observational period was 52.7 months (range = 3.9-121.5 months). Fifty-six (53.3%) patients achieved sustained virological response (SVR). After completion of treatment, 43 (41.0%) patients developed HCC recurrence, and 24 (55.8%) of them had their recurrence within 6 months after completion of therapy. Thirty-three (76.7%) of the patients with HCC recurrence were of de novo pattern. Those responders tended to have a lower cumulative incidence of recurrence than those non-responders (43.2 vs 84.8/100 person-month, log-rank P = 0.13). Those non-responders with a high MICA level (>100 pg/mL) carried the lowest cancer-free survival than those non-responders with a low MICA level and those responders (P = 0.002). Cox regression hazard analysis showed high baseline MICA level (Odds ratio [OR] = 4.8, 95% confidence interval [CI] = 1.1-20.8, P = 0.04) and a low platelet count (<100 000/mm(3) ) (OR = 5.4, 95% CI = 1.1-27.0, P = 0.04) predicted HCC recurrence. CONCLUSIONS: PegIFN/RBV therapy carried a limited effect in the tertiary prevention of HCC. A high MICA level predicted HCC recurrence, particularly among those non-responders.

Treatment efficacy of pegylated interferon plus ribavirin therapy in chronic hepatitis C patients with mixed genotype 1/2 infection.

BACKGROUND AND AIM: The treatment efficacy of patients with mixed hepatitis C virus (HCV) genotype 1/genotype 2 (HCV-1/2) remains unknown. We aimed to elucidate the sustained virological response (SVR) rate in patients with HCV-1/2 infection. METHODS: One hundred and ten HCV-1/2 patients treated with response-guided peginterferon/ribavirin therapy (24 weeks for patients with a rapid virological response [RVR] and low viral loads; 48 weeks for patients without a RVR or high viral loads) were allocated. Two hundred HCV-1 patients were selected as a historical control. Interleukin-28B (IL-28B) rs8099917 genotype was tested for the association with an SVR. RESULTS: The rates of RVR, sustained virologic response (SVR), and relapse rate were 71.8%, 87.3%, and 11.1%, respectively. The SVR rate was significantly higher in patients with an abbreviated regimen as compared with those with 48-week regimen (95.5% vs 75.0%, P = 0.002), and both were similar to the HCV-1 historical control. Stepwise logistic regression analysis revealed that lower baseline viral loads were the single factor predictive of an RVR (odds ratio/95% confidence intervals [OR/CI] of 41.62/9.72-178.19, P < 0.001). The achievement of an RVR was the single best factor predictive of an SVR (OR/CI: 7.5/1.33-42.27, P = 0.02). Nevertheless, an abbreviated regimen became the single factor associated with an SVR if treatment regimen was taken into consideration (OR/CI: 11.0/1.25-96.79, P = 0.03). The SVR rate did not differ between patients with rs8099917 TT and TG/GG genotype (91.7% vs 87.5%, P = 0.63). CONCLUSIONS: The treatment efficacy of patients with HCV-1/2 was satisfactory. The role of IL-28B genetic variants in the population with response-guided therapy was limited.

Pegylated interferon-α2a with or without low-dose ribavirin for treatment-naive patients with hepatitis C virus genotype 1 receiving hemodialysis: a randomized trial.

BACKGROUND: Data are limited on the efficacy and safety of pegylated interferon plus ribavirin for patients with hepatitis C virus genotype 1 (HCV-1) receiving hemodialysis. OBJECTIVE: To compare the efficacy and safety of combination therapy with pegylated interferon plus low-dose ribavirin and pegylated interferon monotherapy for treatment-naive patients with HCV-1 receiving hemodialysis. DESIGN: Open-label, randomized, controlled trial. (ClinicalTrials.gov: NCT00491244). SETTING: 8 centers in Taiwan. PATIENTS: 205 treatment-naive patients with HCV-1 receiving hemodialysis. INTERVENTION: 48 weeks of pegylated interferon-α2a, 135 µg weekly, plus ribavirin, 200 mg daily (n = 103), or pegylated interferon-α2a, 135 µg weekly (n = 102). MEASUREMENTS: Sustained virologic response rate and adverse event-related withdrawal rate. RESULTS: Compared with monotherapy, combination therapy had a greater sustained virologic response rate (64% vs. 33%; relative risk, 1.92 [95% CI, 1.41 to 2.62]; P < 0.001). More patients receiving combination therapy had hemoglobin levels less than 8.5 g/dL than those receiving monotherapy (72% vs. 6%; risk difference, 66% [CI, 56% to 76%]; P < 0.001). Patients receiving combination therapy required a higher dosage (mean, 13 946 IU per week [SD, 6449] vs. 5833 IU per week [SD, 1169]; P = 0.006) and longer duration (mean, 29 weeks [SD, 9] vs. 18 weeks [SD, 7]; P = 0.004) of epoetin-ß than patients receiving monotherapy. The adverse event-related withdrawal rates were 7% in the combination therapy group and 4% in the monotherapy group (risk difference, 3% [CI, -3% to 9%]). LIMITATION: Open-label trial; results may not be generalizable to patients on peritoneal dialysis. CONCLUSION: In treatment-naive patients with HCV-1 receiving hemodialysis, combination therapy with pegylated interferon plus low-dose ribavirin achieved a greater sustained virologic response rate than pegylated interferon monotherapy. PRIMARY FUNDING SOURCE: National Center of Excellence for Clinical Trial and Research.

Clinical utility of host genetic IL-28B variants in hepatitis C virus genotype 1 Asian patients retreated with pegylated interferon plus ribavirin.

BACKGROUND AND AIM: Host interleukin-28B (IL-28B) genetic variants determine a sustained virological response (SVR) in hepatitis C virus genotype 1 (HCV-1) treatment-naïve patients. Its impact on treatment-experienced Asian patients with peginterferon/ribavirin in is to be elucidated. METHODS: IL-28B rs8099917 genotype was determined in 70 HCV-1 treatment-experienced patients retreated with 48-week peginterferon/ribavirin. RESULTS: The SVR rate was 60.0% and was significantly higher in previous relapsers than in nonresponders (72.7% and 13.3%, P < 0.001). Multivariate analysis revealed that the most important factor predictive of an SVR was previous relapse (Odds ratio [OR]/95% confidence interval [CI]: 14.76/2.72-80.06, P = 0.002), followed by the carriage of rs8099917 TT genotype (OR/95% C.I.: 7.67/1.27-46.49, P = 0.03). Comparing to patients with TG/GG genotype, those with TT genotype had significantly higher rates of rapid virological response (29.3% vs 0%, P = 0.03), end-of-treatment virological response (86.2% vs 50.0%, P = 0.01), SVR (69.0% vs 16.7%, P = 0.002), and lower relapse rate (22.0 % vs 66.7%, P = 0.04). The SVR rate was similarly low between previous nonresponders with different rs8099917 genotypes (12.5% vs 14.3%, P = 1). On the contrary, previous relapsers with rs8099917 TT genotype had a significantly higher SVR rate than those who carried rs8099917 TG/GG genotype (78.0 % vs 20.0%, P = 0.02). Stepwise logistic regression analysis revealed that the only factor predictive of an SVR in previous relapsers was the carriage of rs809997 TT genotype (OR/95% CI:18.50/1.82-188.39, P = 0.014). CONCLUSIONS: Host IL-28B genetic variants played a role in Asian relapsers but not nonresponders retreated with peginterferon/ribavirin. Direct antiviral agents might be possibly avoidable in Asian relapsers with favorable IL-28B genotype.

Role of interleukin-28B polymorphisms in the treatment of hepatitis C virus genotype 2 infection in Asian patients.

UNLABELLED: Genome-wide association studies have linked single nucleotide polymorphisms (SNPs) near the interleukin-28B gene to the hepatitis C virus genotype 1 (HCV-1) response to peginterferon/ribavirin treatment. We aimed to explore the impact on the treatment outcomes of Asian HCV-2 patients. We determined rs8105790, rs8099917, rs4803219, and rs10853728 to be candidate SNPs in 482 Asian HCV-2 patients treated with the standard of care. Because the first three SNPs were in very strong linkage disequilibrium with one another (r2 = 0.94-0.96), rs8099917 and rs10853728 were selected for an analysis of their influence on the achievement of rapid virological response [RVR; seronegativity for hepatitis C virus (HCV) RNA in treatment week 4] and sustained virological response (SVR; seronegativity for HCV RNA throughout 24 weeks of posttreatment follow-up). The rs10853728 genotype did not predict RVR or SVR in HCV-2 patients. However, patients with the rs8099917 TT genotype, in comparison with patients with GT/GG genotypes, had a significantly higher rate of achieving RVR (85.2% versus 72.0%, P = 0.017) but did have not a significantly higher rate of achieving SVR (89.4% versus 86.0%). Multivariate analysis revealed that a baseline HCV viral load <400,000 IU/mL was the strongest predictor of RVR [odds ratio (OR) = 4.27, 95% confidence interval (CI) = 2.31-7.87, P < 0.001], and this was followed by advanced liver fibrosis (OR = 0.28, 95% CI = 0.15-0.53, P < 0.001), the carriage of the rs8099917 TT genotype (OR = 3.10, 95% CI = 1.34-7.21, P = 0.008), and the pretreatment level of aspartate aminotransferase (OR = 0.996, 95% CI = 0.99-1.00, P = 0.04). Nevertheless, the achievement of RVR was the single predictor of SVR with an OR of 19.37 (95% CI = 8.89-42.23, P < 0.001), whereas the rs8099917 genotypes played no role in achieving SVR with or without RVR. CONCLUSION: The rs8099917 TT genotype is significantly independently predictive of RVR, which is the single best predictor of SVR, in Asian HCV-2 patients.

The outcomes of glucose abnormalities in pre-diabetic chronic hepatitis C patients receiving peginterferon plus ribavirin therapy.

BACKGROUND/AIMS: Pre-diabetes is a risk factor for type 2 diabetes mellitus (DM) development. This study aimed to elucidate the impact of treatment response on sequential changes in glucose abnormalities in pre-diabetic chronic hepatitis C (CHC) patients. METHODS: Chronic Hepatitis C patients with a baseline haemoglobin A1C (A1C) range 5.7-6.4% who achieved 80/80/80 adherence were prospectively recruited. All patients received current peginterferon-based recommendations. The primary outcome measurement was their A1C level at the end of follow-up (EOF). The interaction between variants of the IL28B gene and outcomes of glucose metabolism was also measured. RESULTS: A total of 181 consecutive CHC patients were enrolled. The mean A1C at EOF was 5.82 ± 0.41%, which was significantly lower than the baseline level (5.93 ± 0.21%, P < 0.001). At EOF, 63 (34.8%) patients became normoglycaemic, whereas 10 (5.5%) patients developed DM. The sustained virological response (SVR) rates of 63 normoglycaemics, 108 pre-diabetics and 10 diabetic patients at the EOF were 92.1%, 84.3% and 50% respectively (normoglycaemics vs. diabetics P = 0.003; pre-diabetics vs. diabetics P = 0.02). Achievement of an SVR was the only predictive factor associated with normoglycaemia development at EOF by multivariate logistic regression analysis (Odds ratio = 2.6, P = 0.04). The prevalence of the interleukin 28B rs8099917 TT variant in patients who developed DM (70.0%) at EOF tended to be lower than that in patients with pre-diabetics (87.0%) or normoglycaemics (92.1%). CONCLUSION: Successful eradication of HCV improves glucose abnormalities in pre-diabetic CHC patients.

The efficacy and safety of pegylated interferon plus ribavirin combination therapy in chronic hepatitis c patients with hepatocellular carcinoma post curative therapies - a multicenter prospective trial.

BACKGROUND & AIMS: Evidence on the efficacy of antiviral treatment in chronic hepatitis C (CHC) patients with hepatocellular carcinoma (HCC) after curative treatment is scarce. We aimed to evaluate the efficacy and safety of pegylated interferon-alpha plus ribavirin (pegIFN/RBV) combination therapy in these patients, compared to cirrhotic patients. METHODS: This prospective, multicenter, case-control study recruited 82 consecutive CHC patients with HCC after curative management and 87 sex/age-matched cirrhotic patients. All patients received pegIFN-alpha-2a and weight-based RBV according to current treatment recommendations. The primary outcome measurement was sustained virological response (SVR, seronegative of hepatitis C virus RNA throughout the 6-month post-treatment follow-up period). RESULTS: The SVR rate was significantly lower in the HCC group compared to the cirrhosis group (48.8% vs 64.4%, p=0.04). However, the significantly lower rate of SVR in the HCC group was observed among genotype-1 patients (33.3% vs 60.7%, p=0.005) but not among genotype-2/3 patients (70.6% vs 71.0%, p=0.88). In patients who achieved 80/80/80 adherence, there was no significant difference of SVR rate between groups (50.7% vs 64.2%, p=0.12) Multivariate logistic regression analysis demonstrated that rapid virological response (viral clearance during the first 4 weeks of treatment, odds ratio=22.1, p<0.001) and adherence (odds ratio=3.1, p=0.05) were predictive factors associated with SVR, whilst previous occurrence of HCC was not associated with SVR (Odds ratio=0.4, p=0.09). The incidence of severe adverse events did not differ between the two groups. CONCLUSIONS: The study proved the feasibility of pegIFN/RBV therapy with current treatment guidelines in CHC patients after successful eradication of HCC, with careful monitoring.

Pegylated interferon plus ribavirin therapy improves pancreatic ß-cell function in chronic hepatitis C patients.

BACKGROUND/AIMS: Pretreatment insulin resistance (IR) is associated with treatment response to peginterferon plus ribavirin (PegIFN/RBV) combination therapy in chronic hepatitis C (CHC) infection. However, the impact of PegIFN/RBV therapy on both IR and ß-cell function in CHC patients has rarely been investigated. METHODS: A total of 277 non-diabetic patients treated with PegIFN-α and weight-based RBV, with 80/80/80 adherence, were recruited. Their IR and ß-cell function by homeostasis model assessment model (HOMA-IR and HOMA-%B) before treatment and at 24 week after treatment [end of follow-up (EOF)] was measured. RESULTS: A sustained virological response (SVR) was achieved by 79.4% (220/277) of all patients: 63.6% (75/118) of genotype-1 and 91.2% (145/159) of genotype-non-1 patients. There was no significant change of HOMA-IR post-therapy (2.25 ± 2.46 vs 2.04 ± 2.12, P=0.42). By contrast, there was a significant reduction of HOMA-%B of all patients at EOF (122.9 ± 145.2 vs 92.4 ± 73.2, P=0.001), particularly in those responders (119.1 ± 142.1 vs 89.6 ± 70.3, P=0.002). In 80 patients with high baseline HOMA-IR, both HOMA-IR and HOMA-%B decreased significantly at EOF, irrespective of SVR achievement. CONCLUSION: This study demonstrated pancreatic ß-cell function was ameliorated by PegIFN/RBV therapy in CHC patients, particularly in those responders.

Serum visfatin is correlated with disease severity and metabolic syndrome in chronic hepatitis C infection.

BACKGROUND AND AIM: Cytokines activation is a common feature in chronic hepatitis C (CHC) infection. Visfatin, as a recently-recognized adipocytokine, may correlate with metabolic abnormalities. We aimed to elucidate the characteristics of visfatin in CHC patients. METHODS: This retrospective study included 102 treatment-naïve CHC patients and 97 sex-/age-matched healthy adults. Serum visfatin levels were examined by an enzyme linked immunosorbent assay test. The correlation between visfatin and hepatitis C virus (HCV) infection in terms of virological, metabolic, and histopathological profiles was analyzed. The impact of visfatin on the treatment response to pegylated interferon plus ribavirin (PEGIFN/RBV) therapy was also assessed. RESULTS: The visfatin level was correlated significantly with fibrosis scores (r = 0.23, P = 0.02) in CHC patients. A significant higher visfatin level was observed in CHC patients with histological activity index scores of mild and more (P = 0.01) and advanced fibrosis (P = 0.04). The mean visfatin level (0.81 ± 0.28 log ng/mL) of 26 CHC patients with metabolic syndrome was significantly lower than their counterparts (0.95 ± 0.30 log ng/mL) (P = 0.03). There was no significant correlation between visfatin and HCV genotypes, viral load, and treatment response to PEGIFN/RBV therapy. Multiple logistic regression analyses demonstrated that metabolic syndrome was the leading negative variable (odds ratio = 0.09, 95% confidence interval = 0.02-0.46, P = 0.004) associated with high visfatin level, followed by advanced fibrosis (odds ratio = 2.88, 95% confidence interval = 1.06-6.78, P = 0.03). CONCLUSIONS: Serum visfatin was correlated with disease severity and metabolic syndrome in CHC patients.

Efficacy and safety of pegylated interferon combined with ribavirin for the treatment of older patients with chronic hepatitis C.

BACKGROUND: The present study evaluated the efficacy and safety of pegylated interferon (PegIFN)/ribavirin treatment in elderly patients with hepatitis C virus (HCV) infection. METHODS: Seventy elderly patients with hepatitis C virus (HCV) infection (group A; age, > or = 65 years) and 140 sex- and HCV genotype-matched controls (group B; age, 50-64 years) were allocated to receive a PegIFN-alpha-2a/ribavirin standard-of-care regimen. RESULTS: Group A had a significantly higher rate of treatment discontinuation (21.4% vs 6.4%; P = .001) and grade 3 or 4 adverse events (34.3% vs 20%; P = .002) than group B. In intention-to-treat analysis, the sustained virologic response (SVR) rate was substantially lower in group A than in group B (67.1% vs 78.6%; P = .07). The inferiority of the SVR rate in group A was observed among patients with HCV genotype 1 (HCV-1) (51.9% vs 75.9%; P = .03) but not among patients with HCV genotype 2 or 3 (HCV-2/3) (76.7% vs 80.2%; P = .65). Among patients in group A who had a rapid virologic response, those infected with HCV-1 and those infected with HCV-2/3 had similar SVR rates (80% and 87.9%, respectively). For patients receiving treatment for >80% of its expected duration, SVR rates were similar between the 2 groups (80.4% vs 82.6%, respectively), regardless of viral genotype. CONCLUSIONS: Older patients with HCV infection, especially those in the subgroup infected with HCV-1, had a greater frequency of adverse events and poorer adherence to the standard-of-care regimen, which may be the major reason for treatment inferiority. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT00629824 .

Early identification of achieving a sustained virological response in chronic hepatitis C patients without a rapid virological response.

BACKGROUND AND AIM: A number of hepatitis C virus (HCV) patients without a rapid virological response (RVR) achieved a sustained virological response (SVR) with peginterferon-alpha-2a/ribavirin. The aim of this study was to identify factors associated with SVR in non-RVR patients. METHODS: Baseline and on-treatment factors were used to explore the prognostic factors for SVR in 113 HCV genotype-1 (HCV-1) and 20 HCV-2 non-RVR patients in two randomized trials. RESULTS: The SVR rate in HCV-1 patients with a complete early virological response (cEVR) and partial early virological response was 91.9% versus 45% (P < 0.001) and 21.4% versus 10% (P = 0.62), respectively, after 48 and 24 weeks of treatment. The SVR rate in HCV-2 patients with a cEVR was 90.9% versus 57.1% (P = 0.25), respectively, after 24 and 16 weeks of treatment. Multivariate analysis showed that cEVR and standard regimen were independently associated with SVR. Viral kinetic study revealed that HCV viral loads < 10,000 IU/mL at week 4 were the best predictor of cEVR for both HCV-1 and HCV-2 non-RVR patients with the accuracy of 81% and 95%, respectively, and also of SVR with the accuracy of 78% and 92%, respectively, in patients receiving standard of care. The most important independent predictors for cEVR were HCV viral loads < 10(4) IU/mL at week 4, followed by increased ribavirin dose within 12 weeks of treatment. CONCLUSIONS: Achieving a cEVR with standard of care is the most important predictor of SVR in non-RVR patients. Week 4 viral loads < 10,000 IU/mL could accurately predict cEVR early and following SVR in non-SVR patients.

A real world cost effectiveness analysis of interferon-based therapy for HCV naïve super-responders.

BACKGROUND: A direct-acting antiviral (DAA) era in hepatitis C virus (HCV) treatment is fast approaching; unfortunately, the availability and affordability of DAAs in Asia-Pacific areas vary, making it difficult to develop universal HCV practice guidelines appropriate for the all Asian populations. This study aimed to evaluate the real-world cost-effectiveness of IFN-based therapy according to the current strategies with PegIFN/RBV for "easy-to-treat" to provide a reference for application of future DAA development for IFN-eligible, treatment naïve HCV patients. METHODS: A total of 1032 chronic hepatitis C treatment-naïve patients who corresponded to response-guided therapy (RGT) guidelines of PegIFN/RBV regimens were linked to the entire population of expenditures and order in the National Health Insurance Research Database of Taiwan. The average total cost per SVR achieved was calculated as the summation of the total cost for all treated patients/number of SVR cases. RESULTS: Current RGT suggested 24 weeks of PegIFN/RBV for G1 naïve patients with baseline LVL and RVR at treatment week 4 achieved an average treatment cost per SVR of $5090 ± 2400. This was of superior cost-effectiveness compared with those other subgroups of G1 patients. In terms of G2 patients, according to current RGT of 16 weeks of treatment duration, PegIFN/RBV treatment with RVR achieved was of a very competitive cost per SVR ($3237 ± 488). CONCLUSION: For a naïve patient in the new DAA era, the PegIFN/RBV treatment might be conserved for those with all favorable risk parameters, considering the treatment duration and cost per SVR, in the resource-constrained countries.

Long-term effects of interferon-based therapy for chronic hepatitis C.

Hepatitis C virus infection frequently causes chronic liver disease leading to cirrhosis and hepatocellular carcinoma (HCC) and has become the main indication for liver transplantation. Interferon (IFN)-based therapy has been used in the treatment of chronic hepatitis C (CHC) for viral clearance. Several earlier studies showed long-term beneficial effects of IFN monotherapy in reducing the progression of cirrhosis, hindering HCC development, and prolonging survival among both sustained virological responders and nonresponders. However, the benefits of preventing disease progression in CHC patients without sustained virological response (SVR) no longer existed over a longer observation period. Both IFN monotherapy and IFN-ribavirin combination therapy were shown to reduce significantly the complications of liver disease, in terms of development of cirrhosis, HCC and liver-related mortality. The significance disappeared after response to antiviral treatment was taken into account. The benefits were obtained mainly from successful antiviral treatment but were not related to the antiviral regimens, suggesting that the magnitude of this preventive effect could increase through the significant improvement of SVR rate by using a more effective regimen, such as interferon-ribavirin or peginterferon-ribavirin combination therapy. Nevertheless, about one-third of patients remain resistant to the current recommended antiviral regimens. More effective treatment is needed for the population.

Pegylated interferon plus ribavirin combination therapy in postliver transplant recipients with recurrent hepatitis C virus infection.

Posttransplant hepatitis C virus (HCV) recurrence is universal in chronic hepatitis C recipients. Antiviral therapy is suggested after liver transplant to halt disease progression. Pegylated interferon plus ribavirin therapy remains the standard of care in many areas where direct antiviral agents are poorly accessible. This study aimed to assess the treatment efficacy and safety of the regimen for Taiwanese patients with post-transplant HCV recurrence. Nine patients with HCV recurrence postliver transplantation were allocated. Patients received either pegylated interferon α-2a 180 µg/wk or pegylated interferon α-2b 1.5 mg/kg/wk plus ribavirin for 24-48 weeks. The primary endpoint was the achievement of sustained virological response (SVR), defined as undetectable HCV RNA throughout 6 months of follow-up after the end of treatment. The safety profiles were also documented. The rates of rapid virological response, early virological response, end-of-treatment virological response, and SVR were 33%, 63%, 75%, and 56% respectively. Of the four patients who failed antiviral treatment, the treatment responses were nonresponse (n = 1), loss of follow-up (n = 1), and relapse (n = 2). Three patients terminated therapy early due to severe adverse events, including severe anemia, intra-abdomen infection, and hepatocellular carcinoma recurrence. One of the three patients who terminated treatment early at Week 6 experienced rapid virological response followed by SVR. Pegylated interferon/ribavirin combination allowed a chance for cure with a fair SVR rate in Taiwanese chronic hepatitis C patients postliver transplantation. Early identification of side effects and careful monitoring during therapy might enhance the treatment efficacy.

A real-world impact of cost-effectiveness of pegylated interferon/ribavarin regimens on treatment-naïve chronic hepatitis C patients in Taiwan.

Treatments with pegylated interferon/ribavirin (PEG-IFN/RBV) has been standard-of-care in patients with chronic hepatitis C virus (HCV) (CHC) infection and reimbursed in Taiwan. However, the actual cost-effectiveness remains unclear. We aimed to evaluate a real-world cost-effectiveness for CHC patients treated with PEG-IFN/RBV by using a clinical cohort with linkage to the National Health Insurance Research Database of Taiwan. The total and itemized medical-care expenses of outpatient visits of 117 treatment-naïve CHC patients with linkage to the two million sampling of the National Health Insurance Research Database were collected. Four components of costs were assessed, including antiviral agents, nonantiviral agents, laboratory testing and consultation costs. The cost per sustained virological response (SVR) achieved was calculated to evaluate the cost-effectiveness. The average cost per treatment in 117 naïve Taiwanese CHC patients was $4620. With an overall SVR rate of 78.6%, the average cost per SVR was $5878. The average medical-care cost per treatment for 52 Genotype 1 (G1) patients was $5133, including $4420 for antivirals, $380 for nonantivirals, $302 for laboratory, and $78 for consultation, compared to $4209, $3635, $317, $233, and $56 for 65 Genotype 2 (G2) patients. With an SVR rate at 67.3% for G1 and 87.7% for G2 patients, the cost per SVR achieved was significantly higher in G1 patients than those in G2 patients ($7627 vs. $4799, p = 0.001). In the current study, we provided the real-world cost-effectiveness of PEG-IFN/RBV for treatment-naïve CHC patients. The genotype-specific cost-effectiveness could enhance decision-making for policy-makers in the coming era of directly acting antiviral therapy.

Identification of groups with poor cost-effectiveness of peginterferon plus ribavirin for naïve hepatitis C patients with a real-world cohort and database.

BACKGROUND: For decades, peginterferon and ribavirin (PegIFN/RBV) have been the standard-of-care for chronic hepatitis C virus (CHC) infection. However, the actual cost-effectiveness of this therapy remains unclear. We purposed to explore the real-world cost effectiveness for subgroups of treatment-naïve CHC patients with PegIFN/RBV therapy in a large real-world cohort using a whole population database. METHODS: A total of 1809 treatment-naïve chronic hepatitis C virus (HCV) patients (829 HCV genotype 1 [G1] and 980 HCV G2) treated with PegIFN/RBV therapies were linked to the National Health Insurance Research Database, covering the entire population of Taiwan from 1998 to 2013 to collect the total medical-care expenses of outpatient (antiviral agents, nonantiviral agents, laboratory, and consultation costs) and inpatient (medication, logistic, laboratory, and intervention costs) visits. The costs per treatment and the cost per sustained virological response (SVR) achieved were calculated. RESULTS: The average medical-care cost was USD $4823 (±$2984) per treatment and $6105 (±$3778) per SVR achieved. With SVR rates of 68.6% and 87.8%, the cost/SVR was significantly higher in G1 than those in G2 patients, respectively ($8285 vs $4663, P < .001). Treatment-naïve G1 patients of old ages, those with advanced fibrosis, high viral loads, or interleukin-28B unfavorable genotypes, or those without a rapid virological response (RVR: undetectable HCV RNA at week 4), or those with complete early virological response (cEVR: undetectable HCV RNA at week 12). Treatment-naïve G2 patients with high viral loads or without RVR or cEVR incurred significantly higher costs per SVR than their counterparts. The cost/SVR was extremely high among patients without RVR and in patients without cEVR. CONCLUSION: We investigated the real-world cost effectiveness data for different subgroups of treatment-naïve HCV patients with PegIFN/RBV therapies, which could provide useful, informative evidence for making decisions regarding future therapeutic strategies comprising costly direct-acting antivirals.