Cost effectiveness of interferon alpha2b combined with ribavirin for the treatment of chronic hepatitis C.

Treatment of chronic hepatitis C with Interferon (IFN) alpha2b monotherapy results in 10% to 15% sustained virological response (SVR). Combining IFN with ribavirin increases this response. In this analysis, using the Markov model, 6 treatment strategies for chronic hepatitis C (previously untreated) were compared on the basis of incremental cost per additional quality-adjusted life years ($/QALY). Our results showed that the no treatment strategy was associated with a cost of $38,747 and 13.10 QALYs. The strategy using IFN alone for 48 weeks was associated with a cost of $35,642 and 14.05 QALYs. The strategy using IFN monotherapy followed by combination therapy for nonresponders and relapsers was associated with a cost of $34, 561 and 15.53 QALYs. A similar strategy, but limiting combination to relapsers only, was associated with a cost of $34,758 and 14.40 QALYs. The strategy using IFN with ribavirin as the initial therapy for all patients was associated with a cost of $34,792 and 15.31 QALYs. Finally, the strategy using viral genotyping first and then adjusting the duration of combination therapy based on genotype was associated with a cost of $37,263 and 15.89 QALYs. The strategy using genotyping to guide duration of combination therapy was the most cost-effective approach with an incremental cost-effectiveness ratio of $7,500 per QALY. Sensitivity analyses confirmed the robustness of these results. We conclude that combination of IFN and ribavirin with duration of therapy based on the viral genotype, is a cost-effective approach in treating patients with chronic hepatitis C.     

Interferon alpha-2B and ribavirin in combination for patients with chronic hepatitis C who failed to respond to, or relapsed after, interferon alpha therapy: a randomized trial.

PURPOSE: To assess the efficacy of interferon alpha-2b and ribavirin in combination in the treatment of patients with chronic hepatitis C who had either failed to respond to therapy with interferon alpha (nonresponders), or who had relapsed after interferon therapy (relapsers). SUBJECTS AND METHODS: Four hundred patients with chronic hepatitis C (200 nonresponders and 200 relapsers) were randomly assigned in equal numbers to receive either subcutaneous administration of recombinant interferon alpha-2b (3 million units three times per week) and ribavirin (1,000 to 1,200 mg/daily orally) or interferon alpha-2b alone (6 million units three times per week). Both ribavirin and interferon alpha-2b were given for 24 weeks. The patients were then followed for an additional 24 weeks. RESULTS: At the end of the treatment period, normalization of serum alanine aminotransferase levels and absence of hepatitis C virus RNA were seen in 21% of nonresponders and in 39% of relapsers who were treated with interferon alpha-2b and ribavirin, compared with 5% of nonresponders (P = 0.001) and 9% of relapsers treated with interferon alpha-2b alone (P <0.001). At the end of follow-up, 14% of nonresponders and 30% of relapsers treated with the combination therapy had a sustained response, compared with 1% of nonresponders (P = 0.001) and 5% of relapsers treated with interferon alpha alone (P <0.001). CONCLUSIONS: A 24-week course of treatment with interferon alpha-2b and ribavirin offers a chance of sustained response, whereas retreatment with interferon alpha-2b alone does not give satisfactory results. The role of long-term therapy in inducing prolonged remission remains to be explored.     

Treatment for hepatitis C virus in human immunodeficiency virus-infected patients: clinical benefits and cost-effectiveness

BACKGROUND: Hepatitis C virus (HCV) is an important cause of liver disease in human immunodeficiency virus (HIV)-infected patients. OBJECTIVE: To assess the cost-effectiveness of alternative management strategies for chronic HCV in co-infected patients with moderate hepatitis. METHODS: A state-transition model was used to simulate a cohort of HIV-infected patients with a mean CD4 cell count of 350 cells/ micro L and moderate chronic hepatitis C stratified by genotype. Strategies included interferon alfa (48 weeks), pegylated interferon alfa (48 weeks), interferon alfa and ribavirin (24 and 48 weeks), pegylated interferon alfa and ribavirin (48 weeks), and no treatment. Outcomes included life expectancy, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios. RESULTS: Treatment for moderate chronic HCV with combination therapy using an interferon-based regimen reduced the incidence of cirrhosis and provided gains in quality-adjusted life expectancy ranging from 6.2 to 13.9 months, depending on genotype. Regardless of genotype, the cost-effectiveness of interferon alfa and ribavirin for patients with moderate hepatitis was lower than $50 000 per QALY vs the next best strategy. With genotype 1, pegylated interferon alfa (vs interferon alfa) and ribavirin therapy provided an additional 1.6 quality-adjusted life-months for $40 000 per QALY. Because treatment is more effective with non-1 genotypes, pegylated interferon (vs interferon alfa) and ribavirin provided only 3 additional quality-adjusted life-months for $105 300 per QALY. For patients who were intolerant of ribavirin, monotherapy with pegylated interferon was always the most cost-effective option. CONCLUSIONS: Combination therapy for moderate hepatitis in coinfected patients will increase quality-adjusted life expectancy and have a cost-effectiveness ratio comparable to that of other well-accepted clinical interventions.     

Effects of adding ribavirin to interferon to treat chronic hepatitis C infection: a systematic review and meta-analysis of randomized trials

Evidence shows that a combination therapy of ribavirin plus interferon clears hepatitis C virus from the blood in about 40% of patients with chronic hepatitis C infection, but the effects on clinical outcomes are unclear. We evaluated the beneficial and harmful effects of ribavirin plus interferon vs interferon alone for treatment of patients with chronic hepatitis C infection. Randomized trials were included irrespective of blinding, language, or publication status. Trials were identified through the Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Library, MEDLINE, EMBASE, manual searches of bibliographies and journals, and correspondence with experts (in May 2004). Data were extracted independently by 2 reviewers. The primary outcomes were morbidity plus mortality and viral clearance. Secondary outcomes included histologic response, quality of life, and adverse events. Previous antiviral therapy (treatment-naive patients, relapsers, or nonresponders), patient characteristics, treatment regimen, methodological quality, and duration of follow-up were extracted. We included 72 trials with a total of 9991 enrolled patients. Treatment with ribavirin plus interferon significantly reduced morbidity plus mortality (Peto odds ratio, 0.46; 95% confidence interval [CI], 0.22-0.96) and significantly improved sustained viral clearance in treatment-naive patients (risk ratio, 0.72; 95% CI, 0.68-0.76), relapsers (risk ratio, 0.63; 95% CI, 0.54-0.73), and nonresponders (risk ratio, 0.89; 95% CI, 0.84-0.94). Combination therapy also significantly improved liver histologic response. The effects on quality of life are unclear. However, combination therapy significantly increased the risk of hematological, dermatological, gastrointestinal, and several other types of adverse events. In conclusion, the effect of ribavirin plus interferon on viral clearance may lead to reduced mortality and morbidity in patients with chronic hepatitis C infection. However, combination therapy is associated with increased risk for adverse events.     

Cost-effectiveness of peginterferon alfa-2b in combination with ribavirin as initial treatment for chronic hepatitis C in Sweden

The aim of the study was to assess the cost-effectiveness of peginterferon alfa-2b (pegIFN) compared to interferon alfa-2b (IFN), both in combination with ribavirin, as initial therapy for chronic hepatitis C in Sweden. A computer based Markov model describing the natural course of chronic hepatitis C was used to assess costs and quality-adjusted life-y (QALY) for the treatment strategies. Study population was a cohort of hepatitis C patients from the age of 43 y until death. Natural history and response data were obtained from the literature and from Swedish clinical experts. Costs were obtained from different health care providers in Sweden and based on Swedish clinical practice. In our base case analysis for genotype 1 patients, pegIFN plus ribavirin therapy generated 0.29 incremental QALYs and was cost saving (dominant strategy). Corresponding results for genotype 2/3 patients were 0.09 QALYs at an incremental cost of 941 euros (10,500 euros/QALY). A probabilistic sensitivity analysis was performed to study the stability of our results. From the results we conclude that for genotype 1 patients treatment with pegIFN and ribavirin increased quality-adjusted life expectancy and was cost-effective as initial therapy for hepatitis C. The cost-effectiveness for patients infected with genotype 2/3 was less obvious.     

Cost-effectiveness of combination peginterferon alpha-2a and ribavirin compared with interferon alpha-2b and ribavirin in patients with chronic hepatitis C

BACKGROUND: Sustained virological response (SVR) is the primary objective in the treatment of chronic hepatitis C (CHC). Results from a recent clinical trial of patients with previously untreated CHC demonstrate that the combination of peginterferon alpha-2a and ribavirin produces a greater SVR than interferon alpha-2b and ribavirin combination therapy. However, the cost-effectiveness of peginterferon alpha-2a plus ribavirin in the U.S. setting has not been investigated. METHODS: A Markov model was developed to investigate cost-effectiveness in patients with CHC using genotype to guide treatment duration. SVR and disease progression parameters were derived from the clinical trials and epidemiologic studies. The impact of treatment on life expectancy and costs were projected for a lifetime. Patients who had an SVR were assumed to remain virus-free for the rest of their lives. In genotype 1 patients, the SVRs were 46% for peginterferon alpha-2a plus ribavirin and 36% for interferon alpha-2b plus ribavirin. In genotype 2/3 patients, the SVRs were 76% for peginterferon alpha-2a plus ribavirin and 61% for interferon alpha-2b plus ribavirin. Quality of life and costs were based on estimates from the literature. All costs were based on published U.S. medical care costs and were adjusted to 2003 U.S. dollars. Costs and benefits beyond the first year were discounted at 3%. RESULTS: In genotype 1, peginterferon alpha-2a plus ribavirin increases quality-adjusted life expectancy (QALY) by 0.70 yr compared to interferon alpha-2b plus ribavirin, producing a cost-effectiveness ratio of $2,600 per QALY gained. In genotype 2/3 patients, peginterferon alpha-2a plus ribavirin increases QALY by 1.05 yr in comparison to interferon alpha-2b plus ribavirin. Peginterferon alpha-2a combination therapy in patients with HCV genotype 2 or 3 is dominant (more effective and cost saving) compared to interferon alpha-2b plus ribavirin. Results weighted by genotype prevalence (75% genotype 1; 25% genotype 2 or 3) also show that peginterferon alpha-2a plus ribavirin is dominant. Peginterferon alpha-2a and ribavirin remained cost-effective (below $16,500 per QALY gained) under sensitivity analyses on key clinical and cost parameters. CONCLUSION: Peginterferon alpha-2a in combination with ribavirin with duration of therapy based on genotype, is cost-effective compared with conventional interferon alpha-2b in combination with ribavirin when given to treatment-na?ve adults with CHC.     

Cost-effectiveness of hepatitis C virus antiviral treatment for injection drug user populations

Injecting drug use is the main risk of hepatitis C virus (HCV) transmission in most developed countries. HCV antiviral treatment (peginterferon-α + ribavirin) has been shown to be cost-effective for patients with no reinfection risk. We examined the cost-effectiveness of providing antiviral treatment for injecting drug users (IDUs) as compared with treating ex/non-IDUs or no treatment. A dynamic model of HCV transmission and disease progression was developed, incorporating: a fixed number of antiviral treatments allocated at the mild HCV stage over 10 years, no retreatment after treatment failure, potential reinfection, and three baseline IDU HCV chronic prevalence scenarios (20%, 40%, and 60%). We performed a probabilistic cost-utility analysis estimating long-term costs and outcomes measured in quality adjusted life years (QALYs) and calculating the incremental cost-effectiveness ratio (ICER) comparing treating IDUs, ex/non-IDUs, or no treatment. Antiviral treatment for IDUs is the most cost-effective option in the 20% and 40% baseline chronic prevalence settings, with ICERs compared with no treatment of ￡ 521 and ￡ 2,539 per QALY saved, respectively. Treatment of ex/non-IDUs is dominated in these scenarios. At 60% baseline prevalence, treating ex/non-IDUs is slightly more likely to be the more cost-effective option (with an ICER compared with no treatment of ￡ 6,803), and treating IDUs dominated due to high reinfection. A sensitivity analysis indicates these rankings hold even when IDU sustained viral response rates as compared with ex/non-IDUs are halved. CONCLUSION: Despite the possibility of reinfection, the model suggests providing antiviral treatment to IDUs is the most cost-effective policy option in chronic prevalence scenarios less than 60%. Further research on how HCV treatment for injectors can be scaled up and its impact on prevalence is warranted.     

Chronic hepatitis C: retreatment of relapsers. An evidence-based approach

Post-treatment relapse remains a major issue in the long-term management of chronic hepatitis C. Many studies have been conducted to identify the ideal therapy that would increase the cost-effectiveness of retreatment in the individual patient. Although the conclusions of two consensus conferences for the retreatment of relapse of chronic hepatitis C have been published recently, several important issues still remain unanswered. We reviewed the available data by an evidence-based approach and conclude the following: (1) patients should be retreated with a combination of interferon (IFN) and ribavirin for 6 months if there are no contraindications to ribavirin; (2) the excellent tolerability and the lesser expense of retreatment with IFN monotherapy makes it a low-cost option for patients who have transiently cleared HCV-RNA during the first IFN course, and a primary indication for those who are contraindications to ribavirin or are likely to experience adverse events under ribavirin; (3) relapsers retreated with monotherapy must receive a high dose of IFN; and (4) patients with cirrhosis should not be retreated with IFN alone. More data, particularly on the long-term course of patients retreated with combination therapy, are needed before setting guidelines for retreatment of relapsers.     

Clinical trial results of peginterferons in combination with ribavirin

Of the large number of patients chronically infected with hepatitis C virus (HCV), only about one third have progressive liver disease, and will eventually develop cirrhosis and hepatocellular carcinoma. These are the patients for whom effective antiviral treatment is most needed. Therapy is currently recommended for patients with chronic hepatitis C who have abnormal alanine aminotransferase (ALT) levels, detectable hepatitis C virus ribonucleic acid (HCV RNA) in the blood, and significant necroinflammatory changes and/or fibrosis on liver biopsy. The current gold standard in terms of treatment efficacy is the combination of peginterferon (PEG-IFN) and ribavirin. The overall sustained virological response rate (SVR) with these regimens is 54 to 61% following 48 weeks of therapy. Patients with genotype 1 infection have a 42 to 51% likelihood of response to 48 weeks of therapy. Those with genotypes 2 or 3 infection will respond to 24 weeks of therapy in 78 to 82% of cases. These SVR rates are 5 to 10 percentage points higher in all patient groups than in those obtained with standard doses of interferon (IFN) and ribavirin. Retreatment of nonresponders to standard IFN monotherapy using PEG-IFN and ribavirin has achieved SVR rates of 34 to 40%. Retreatment of patients who relapsed after IFN monotherapy has resulted in an SVR rate of about 60%. A SVR after retreatment of relapsers and nonresponders with PEG-IFN and ribavirin is more likely in patients previously treated with IFN monotherapy, those with HCV genotypes 2 or 3, patients with low viral load (<2 million copies/mL), and individuals who had a significant decrease in HCV RNA levels during the initial treatment. The potential benefits of long-term anti-HCV suppressive therapy in nonresponders are currently under investigation.     

Cost effectiveness of interferon alpha or peginterferon alpha with ribavirin for histologically mild chronic hepatitis C

BACKGROUND: For patients with mild chronic hepatitis C the cost effectiveness of antiviral therapy is unknown. AIMS: To assess whether antiviral therapy (either interferon alpha or peginterferon alpha combined with ribavirin) is cost effective at a mild stage compared with waiting and only treating those cases who progress to moderate disease. PATIENTS: Cases with mild chronic hepatitis C. METHODS: A cost effectiveness model which estimates long term costs and outcomes for patients with mild chronic hepatitis C. The model uses effectiveness and cost data from the UK mild hepatitis C randomised controlled trial, combined with estimates of disease progression and cost from observational studies. RESULTS: Antiviral treatment at a mild rather than a moderate stage improved outcomes measured by quality adjusted life years (QALYS) gained. The mean cost per QALY gained from antiviral treatment with interferon alpha-2b and ribavirin, compared with no treatment at a mild stage, was 4535 pounds sterling (7108 dollars) for patients with genotype non-1 and 25,188 pounds sterling (39,480 dollars) for patients with genotype 1. Providing peginterferon alpha-2b and ribavirin at a mild rather than a moderate stage was also associated with a gain in QALYS; the costs per QALY gained were 7821 pounds sterling (12,259 dollars) for patients with genotype non-1 and 28,409 pounds sterling (44,528 dollars) for patients with genotype 1. CONCLUSIONS: For patients with chronic hepatitis C, it is generally more cost effective to provide antiviral treatment at a mild rather than a moderate disease stage. For older patients (aged 65 years or over) with genotype 1, antiviral treatment at a mild stage is not cost effective.     

Impact of high‐dose interferon induction and ribavirin therapy in patients with chronic hepatitis C relapsing after or not responding to interferon monotherapy

Background/aims: Initial high‐dose interferon‐α induction therapy in combination with ribavirin improves sustained response rates in treatment‐naïve patients. This prospective, randomized, controlled study tested whether non‐responders or relapsers to interferon monotherapy also benefit from induction therapy. Methods: Patients with chronic hepatitis C who had not responded to (n=75) or relapsed (n=80) after previous interferon therapy were randomized to receive three different interferon doses during the first 14 weeks of therapy (A: 10 MU IntronA®/day for 2 weeks, followed by 10 MU/2 days for 12 weeks; B:5 MU/d for 14 weeks; C: 5 MU/2 days for 14 weeks) followed in all by 5 MU/2 days for 24 weeks. All patients received 1–1.2 g ribavirin/day throughout the whole study. Results: The rates of viral clearance at any time on treatment were similar in all groups. Sustained response rates were also not different among the groups in interferon nonresponders (A 32%, B 29%, C 31%) and relapsers (A 64%, B 68%, C 71%), respectively, as well as in patients with different genotypes. As expected, sustained response rates were higher in patients with genotype non‐1 than in those with genotype 1. Conclusion: High‐dose induction therapy does not improve the outcome of interferon/ribavirin therapy in interferon nonresponders or relapsers.     

A pragmatic and cost-effective strategy of a combination therapy of interferon alpha-2b and ribavirin for the treatment of chronic hepatitis C

BACKGROUND: Combination of interferon (IFN) alpha and ribavirin is considered the standard treatment for patients with chronic hepatitis C. While combination therapy is more effective than IFN alone, the optimal management of combination treatment remains uncertain. OBJECTIVE: To assess a pragmatic and cost-effective strategy for the therapy of treatment-naive patients with chronic hepatitis C. DESIGN: Markov model on original data of two randomized trials. METHODS: A validated computer simulation model was applied to non-cirrhotic hepatitis C virus (HCV)-infected patients. Patient characteristics and efficacy of treatment were extracted from two randomized trials reporting on 1,445 non-cirrhotic patients. Different strategies were compared separately for genotype 1 and genotype non-1 (mostly genotype 2/3) infections: (1) no treatment; (2) IFN for 48 weeks (if at 12 weeks HCV RNA undetectable); (3) IFN and ribavirin for 24 weeks; (4) IFN and ribavirin for 48 weeks; (5) IFN and ribavirin for 48 weeks (if at 24 weeks HCV RNA undetectable). All strategies were tested for different combinations of known response factors. RESULTS: In genotype non-1 infection, 24 weeks of combination therapy dominates all other strategies. In genotype 1 infection, 48 weeks of combination therapy for week-24 responders only prolongs life expectancy at a favourable cost-effectiveness ratio (CE) of 7,135 euros per quality-adjusted life year (QALY). Taking response factors other than genotype into account does not add to the effectiveness or cost effectiveness. CONCLUSION: Treating non-cirrhotic patients with chronic hepatitis C according to genotype only is most cost effective independent of the number of other known response factors.     

Economic and clinical effects of evaluating rapid viral response to peginterferon alfa-2b plus ribavirin for the initial treatment of chronic hepatitis C

OBJECTIVES: Evaluation of 12-wk viral response to initial antiviral therapy for chronic hepatitis C has been recommended to minimize antiviral-associated morbidity and costs. The aim of this study was to examine the economic and clinical effects of evaluating rapid viral response during antiviral therapy for treatment naive chronic hepatitis C patients. METHODS: We applied viral response and drug dosage from an international randomized clinical trial of ribavirin plus peginterferon alfa-2b or ribavirin plus interferon alfa-2b to a previously published computer cohort simulation to project lifelong clinical and economic outcomes. Natural history and economic estimates were based on published literature, expert panel estimates, and actual variable and reimbursement cost data. RESULTS: The assessment of 12-wk rapid viral response reduced antiviral treatment duration by 40-44% and antiviral costs by 44-45% (savings of $15,116-16,268 for peginterferon plus ribavirin and $8300 for interferon plus ribavirin) compared to full 48-wk dosing. With the 12-wk evaluation, the marginal cost-effectiveness of peginterferon plus ribavirin versus interferon plus ribavirin was $13,600-22,800 compared with $14,600-25,000 per discounted quality adjusted life-year gained with the 24-wk evaluation. For genotype 1, hepatitis C infected patients, 12-wk testing for peginterferon plus ribavirin remaining preferred and cost-effective compared with interferon plus ribavirin. For genotype 2 or 3, hepatitis C infected patients, 12-wk testing yielded similar results to those of 24-wk treatment. CONCLUSIONS: Assessment of 12-wk viral response in genotype 1, hepatitis C infected patients should reduce peginterferon plus ribavirin morbidity and costs and improve its cost-effectiveness; however, for genotype 2 and 3, hepatitis C infected patients, 12-wk testing and 24-wk treatment have similar outcomes. Decisions regarding continuation of antiviral treatment should also consider the variability in the accuracy of quantitative viral assays as well as patient preferences and other potential benefits of the same treatments.     

Treatment of nonresponders to standard hepatitis C therapy

Over 40% of patients with chronic hepatitis C fail to achieve sustained virologic response to treatment with pegylated interferon and ribavirin. They represent a growing population of patients with chronic hepatitis C. Those more likely to be nonresponders include patients with genotype 1 (especially with high viral load), advanced fibrosis, or HIV coinfection, as well as African Americans. Prior treatment history must be carefully reviewed and the pattern of nonresponse ascertained to formulate appropriate management strategies. Modi.-able factors associated with poor response should be identified prior to retreatment and addressed to improve the efficacy of retreatment. Patients with mild inflammation and mild fibrosis are at low risk of progression to cirrhosis and may reasonably be offered observation with periodic follow-up. The treatment of naïve patients needs to be optimized in order to minimize the growth of the population of “difficult to treat” nonresponders with chronic hepatitis C.     

Combined antiviral therapy of hepatitis C virus in dialysis patients: meta-analysis of clinical trials

Summary. The efficacy and safety of combined interferon (IFN) plus ribavirin in patients on long‐term dialysis and chronic hepatitis C remains unclear, although a number of small clinical trials have addressed this issue. We evaluated the efficacy and safety of combination antiviral therapy (conventional or pegylated interferon plus ribavirin) in dialysis patients with chronic hepatitis C by performing a systematic review of the literature with a meta‐analysis of clinical trials. The primary outcome was sustained virological response (SVR) (as a measure of efficacy); the secondary outcome was drop‐out rate (as a measure of tolerability). We used the random effects model of Der Simonian and Laird, with heterogeneity and sensitivity analyses. We identified 10 clinical studies (151 unique patients), one (10%) of which was a controlled clinical trial. Most (97.4%) patients were on long‐term haemodialysis. The summary estimate for SVR and drop‐out rate was 56% [95% Confidence Intervals (95% CI) 28–84] and 25% (95% CI, 10–40), respectively. The most frequent side effects requiring interruption of treatment were anaemia (26%) and heart failure (9%). These results occurred irrespective of type of interferon (conventional or peg‐IFN, peg‐IFNalfa‐2a or alfa‐2b), trial design (controlled or cohort study), or clinical characteristics of patients (naïve, nonresponders or relapsers). The studies were heterogeneous with regard to SVR and drop‐out rate. Combination antiviral therapy (interferon plus ribavirin) gives encouraging results in terms of efficacy and safety among dialysis patients even if the limited number of patients enrolled in our meta‐analysis hampers definitive conclusions.     

Management of chronic hepatitis C patients who have relapsed or not responded to pegylated interferon alfa plus ribavirin

Summary.  Development of therapeutic strategies for patients with chronic hepatitis C who experience virological breakthrough, relapse or nonresponse lag behind those for treatment-naïve patients. The probability of a previously treated patient responding to re-treatment depends on the nature of the previous regimen, the magnitude of the response to previous treatment and the patient's characteristics. Relapsers have higher sustained virological response rates than nonresponders when re-treated with pegylated interferon plus ribavirin. Re-treatment of nonresponders to pegylated interferon plus ribavirin with the standard 48-week regimen resulted in an approximate 6% sustained response rate in the EPIC-3 program. In the REPEAT trial, the sustained response rate was significantly higher in nonresponders to pegylated interferon alfa-2b (12 kD) plus ribavirin randomized to 72 weeks of peginterferon alfa-2a (40 kD) plus ribavirin, compared with a 48-week regimen (16% vs 8%, P  = 0.0006). Based on available data, extended treatment is the best option for these individuals. Undetectable viral RNA at week 12 is an important criterion for re-treatment in the REPEAT and EPIC studies. Maintenance therapy with pegylated interferon is generally ineffective in nonresponders and cannot be recommended. Directly acting antivirals may increase response rates and the burden of adverse events when combined with the standard of care, but will not be available for some years. In conclusion, after careful evaluation of an individual's benefit–risk ratio, a 72-week regimen is the preferred strategy for optimizing sustained response rates in patients who have not responded to the standard of care, provided that viral RNA is undetectable at week 12 of re-treatment.     

Treatment of relapsers after combination therapy for chronic hepatitis C

A significant number of patients with chronic hepatitis C relapse after treatment. As therapy for CHC has improved over the last decade, the issue of retreating patients who did not achieve a sustained virologic response with previous treatment regimens frequently arises. Several studies have assessed the efficacy of pegylated interferon (IFN) and ribavirin (RBV) combination therapy in IFN and RBV therapy relapsers. Patients who have relapsed after therapy have significantly higher SVR rates than those who are nonresponders to therapy and should be considered candidates for retreatment. Predictors of a favorable response to therapy in na?ve patients appear to also predict response to therapy in patients who have relapsed previously.     

Cost-effectiveness analysis of therapeutic options for chronic hepatitis C genotype 3 infected patients

Background: This study provides a cost-effectiveness analysis of therapeutic strategies for chronic hepatitis C genotype 3 infected patients in Spain.

Methods: A Markov model was designed to simulate the progression in a cohort of patients aged 50 years over a lifetime horizon.

Results: Sofosbuvir (SOF) plus peginterferon and ribavirin for 12 weeks was a cost-effective option when compared to standard of care (SoC) in the treatment of both ‘moderate fibrosis’ and ‘cirrhotic’ patients. Incremental cost-effectiveness ratios were €35,276/QALY and €18,374/QALY respectively. ICERs for SOF plus daclatasvir (DCV) regimens versus SoC were over the threshold limit considered, at €56,178/QALY and €77,378/QALY for ‘moderate fibrosis’ and ‘cirrhotic’ patients respectively.

Conclusion: Addition of SOF to IFN-based regimens for genotype 3 was cost-effective for both ‘moderate fibrosis’ and ‘cirrhotic’ patients. IFN-free options including SOF and DCV association required price reductions lower than the list prices to be considered cost-effective.     

Relapse to prior therapy is the most important factor for the retreatment response in patients with chronic hepatitis C virus infection.

BACKGROUND: Treatment options for hepatitis C have developed rapidly in the past decade. The current treatment of choice is a combination of pegylated-interferon-alpha (PEG-IFN-alpha) and ribavirin. With the development of more therapy options, patients who failed in prior therapy hope to clear hepatitis C virus by undergoing a more effective retreatment regime. In this report, we investigated response rates to combination therapy [standard IFN-alpha or PEG-IFN-alpha and ribavirin] in patients who relapsed or failed in prior therapy. METHODS: Ninety-three patients were included in this retrospective study. All patients failed to previous IFN-alpha monotherapy (n=55) or to a combination of standard IFN-alpha and ribavirin (n=38). Fifty-nine patients were nonresponders and 34 were relapsers. Thirty-five patients were retreated with standard IFN-alpha plus ribavirin and 58 received PEG-IFN-alpha combination therapy. RESULTS: Sustained virologic response (SVR) was induced in 31% of all patients. The highest SVR rate (58%) was observed in relapsers to standard IFN-alpha combination therapy who were retreated with PEG-IFN-alpha combination therapy. The SVR rate in relapsers to standard IFN-alpha monotherapy who received a standard IFN-alpha combination therapy was 50%. Relapsers responded in a significantly higher proportion to retreatment than nonresponders (56% vs. 17%, P<0.001). Relapse to previous therapy was identified as an independent predictor for therapy response. The lowest SVR rate was observed in nonresponders to standard IFN-alpha combination therapy who were retreated with PEG-IFN-alpha combination therapy (1/26; 4%). CONCLUSIONS: In relapsers, retreatment with the most effective therapy regime to date a combination of PEG-IFN-alpha and ribavirin, is promising. However, retreatment with PEG-IFN-alpha combination therapy in nonresponders to standard IFN combination therapy is not effective.     

Hepatitis C virus and liver transplantation.

Advances in immunosuppressive therapy, operative techniques, and perioperative management have resulted in long-term patient survival rates approaching 90% following liver transplantation for chronic viral hepatitis. The increasing number of referrals for liver transplantation reflects the impact of chronic HCV infection as a cause of end-stage liver disease. Unlike hepatitis B, there is still no effective treatment in preventing recurrent hepatitis C after liver transplantation. The spectrum of allograft injury related to universal HCV infection recurrence ranges from no evidence of histologic injury to mild inflammation to severe disease with allograft failure in small proportion of patients. Various factors may explain these differing outcomes, including degree of pretransplantation viremia, HLA compatibility, presence of more pathogenic HCV genotypes, integrity of cellular immune response, and type of immunosuppression. Fortunately, patient survival does not seem to be affected short-term; the long-term outcome of liver transplantation for chronic hepatitis C is unclear but is likely to be decreased. Combination therapy with interferon plus ribavirin seems to be a promising treatment strategy for posttransplantation recurrent hepatitis C, and the use of pegylated interferon plus ribavirin may improve these results. Patients with moderate to severe allograft hepatitis are appropriate candidates for combination antiviral therapy. Histopathologically documented recurrent hepatitis C in liver transplant recipients is associated with impaired quality of life, inferior physical condition, and a higher incidence of depression compared with patients who did not have HCV and in those without HCV recurrence. In conclusion, it is possible that the continued improvements in antiviral therapy against HCV infection may ultimately decrease the number of patients needing liver transplantation. Suitable candidates with chronic HCV infection thus warrant treatment with pegylated interferon plus ribavirin combination therapy in the hope of decreasing disease progression. Recent studies, which require confirmation, suggest that nonresponders to standard antiviral therapy may benefit from maintenance therapy. The donor pool for patients with chronic hepatitis C and decompensated cirrhosis can be improved by using HCV-positive donors and by increasing utilization of newer surgical techniques, including adult-to-adult living-donor liver transplantation and split-liver transplantation.