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Patient Scenario

  1. Top of page
  2. Patient Scenario
  3. Introduction
  4. The Evidence
  5. Telaprevir Candidacy
  6. Assessment of Fibrosis
  7. Treatment Algorithm and Monitoring
  8. Management of Side Effects
  9. The Role of IL-28B in Telaprevir Therapy
  10. Recommendations
  11. References
  12. Supporting Information

A 52-year-old asymptomatic man is evaluated for chronic hepatitis C (CHC). The aspartate aminotransferase is 138 U/L and the alanine aminotransferase is 164 U/L, with normal bilirubin, alkaline phosphatase, albumin, and complete blood counts. The international normalized ratio is 1.1 and the serum creatinine is 0.9 mg/dL. Hepatitis C virus (HCV) RNA is 1.6 million IU/mL, and genotype is 1b. The patient has read about telaprevir and wants to know whether he is a candidate for treatment with this drug. He also wants to know whether he really requires a liver biopsy prior to initiation of treatment.

Would you use telaprevir with interferon and ribavirin in this patient? How will you determine whether he is responding to the drug regimen, how long will you give the medications, and how will you monitor for side effects? How do you determine whether treatment-related anemia is related to telaprevir and not ribavirin or interferon? Which of the side effects of telaprevir would warrant discontinuation of treatment?

Would your approach be different if the patient had genotype 2, genotype 3, or genotype 4 disease? Would your approach be different if he had the CC genotype for the interleukin-28 (IL-28) polymorphism?

Introduction

  1. Top of page
  2. Patient Scenario
  3. Introduction
  4. The Evidence
  5. Telaprevir Candidacy
  6. Assessment of Fibrosis
  7. Treatment Algorithm and Monitoring
  8. Management of Side Effects
  9. The Role of IL-28B in Telaprevir Therapy
  10. Recommendations
  11. References
  12. Supporting Information

HCV infection affects approximately 170 million persons worldwide and 4 million persons in the United States.1, 2 It is a significant public health challenge to identify and appropriately diagnose individuals with the HCV infection. The recent approval of the two new therapeutic protease inhibitors has engendered much interest from both patients and providers.3, 4

Telaprevir represents one of the first installments in the new arsenal of direct-acting antiviral (DAA) therapy. Telaprevir is a nonstructural protein 3/4A (NS3/4A) protease inhibitor approved by the FDA for use in adults with genotype 1 (G1) CHC. The genome of HCV encodes a single polyprotein of 3000 amino acids that requires further cleavage by host and viral proteases to render mature viral proteins. The NS3/4A protease cleaves the polyprotein at four sites and is responsible for generation of parts of the HCV RNA replication complex. Telaprevir is a peptidomimetic inhibitor that binds covalently yet reversibly to the protease-binding pocket.5 Results of phase 3 trials demonstrate that telaprevir, when added to the current standard of care (SOC) of pegylated interferon and ribavirin, is more effective than SOC and allows for a shorter treatment duration in many treatment-naive patients.6, 7 The patient in this scenario is representative of patients commonly encountered in hepatology and gastroenterology clinics across the United States, because more than 70% of patients with hepatitis C in the United States are infected with G1.

The Evidence

  1. Top of page
  2. Patient Scenario
  3. Introduction
  4. The Evidence
  5. Telaprevir Candidacy
  6. Assessment of Fibrosis
  7. Treatment Algorithm and Monitoring
  8. Management of Side Effects
  9. The Role of IL-28B in Telaprevir Therapy
  10. Recommendations
  11. References
  12. Supporting Information

Early phase studies demonstrated that telaprevir is a potent antiviral compound against HCV. However, it can not be used alone, because viral rebound due to selected mutants was universal during or after monotherapy with telaprevir.8 When combined with pegylated interferon, telaprevir effectively inhibits HCV without viral breakthrough even in patients with previously treated G1 CHC.9, 10 Subsequent phase 2b randomized, controlled trials (the so-called PROVE-1 and PROVE-2 trials) demonstrated superior sustained virologic response (SVR) rates in treatment-naive patients with G1 CHC treated with triple therapy (>60%) compared to pegylated interferon and ribavirin alone (41%).11, 12 The PROVE-2 trial also demonstrated the necessity of ribavirin as the regimen with telaprevir and pegylated interferon alone resulted in SVR = 36%.

Subsequent phase 3 trials have confirmed the efficacy of telaprevir. The ADVANCE study (n = 1088) examined 8- and 12-week courses of telaprevir plus peginterferon/ribavirin (PR) followed by response-guided therapy (RGT) with PR to complete 24 or 48 weeks in treatment-naive patients with G1 CHC.6 The control group received pegylated interferon and ribavirin for 48 weeks. Patients with an extended rapid virologic response (eRVR), defined as being negative for HCV RNA at both weeks 4 and 12, received additional PR until completion at 24 weeks, whereas those without eRVR received additional PR until week 48. SVR was achieved in 69% of the T8 group compared to 75% in the T12 group. Although both telaprevir treatment arms were superior to the SOC arm (P < 0.001), the T8 group experienced more treatment breakthrough (13%) than the T12 group (8%). Relapse was 9% for both telaprevir arms and 28% in the PR group.

A second phase 3 study, the ILLUMINATE trial, tested the efficacy of RGT for telaprevir.7 All patients (n = 540) received telaprevir and PR for 12 weeks and an additional 8 weeks of PR. Those patients who achieved eRVR were randomized to an additional 4 weeks (T12PR24) or an additional 28 weeks of PR (T12PR48). All patients without eRVR went on to receive an additional 28 weeks of PR (total = 48 weeks). The main finding of the trial was that shortened therapy (T12PR24) in patients achieving eRVR was as effective as T12PR48, in terms of SVR (SVR = 92% versus 88%). Patients who failed to achieve eRVR still had SVR in 64%. It is notable that among 61 patients with cirrhosis, 30 (49%) achieved eRVR; in those patients, SVR was higher with longer duration of therapy (SVR = 92% for T12PR48 versus 61% for T12PR24).

A recent randomized open label trial (n = 161) explored the use of twice daily (1150 mg q 12 hours) or thrice daily (750 mg q 8hr) telaprevir in RGT. There was a nearly identical SVR (≈82%) in the two arms.13 However, the current approved dosing schedule is 750 mg q 7-9 hours and more data are needed before endorsing the twice daily dosing schedule.

Finally, telaprevir is only indicated for patients with genotype 1 infection. Although there are limited phase 2 data that telaprevir could be effective against HCV genotype 2 or 4 infections, as well as in vitro data suggesting efficacy in genotypes 5a and 6a, there are insufficient data to support its use in non–genotype 1 patients.14, 15

Telaprevir Candidacy

  1. Top of page
  2. Patient Scenario
  3. Introduction
  4. The Evidence
  5. Telaprevir Candidacy
  6. Assessment of Fibrosis
  7. Treatment Algorithm and Monitoring
  8. Management of Side Effects
  9. The Role of IL-28B in Telaprevir Therapy
  10. Recommendations
  11. References
  12. Supporting Information

How does the evidence apply to the patient in the scenario? In general, participants for the phase 2 and 3 trials were between ages 18 and 70 years. Patients with cirrhosis were excluded from phase 2 studies but those with Child class A (compensated) cirrhosis were eligible for the phase 3 ILLUMINATE trial. Patients with hepatitis B, human immunodeficiency virus (HIV), and hepatocellular carcinoma (HCC) were also excluded. An ongoing phase 2 trial (NCT01332955) is recruiting patients coinfected with HIV and HCV.

An important factor to consider is the patient's medication list. Telaprevir is a significant inhibitor of cytochrome P450 isoenzyme CYP3A. Coadministration of telaprevir with other drugs that are metabolized by the enzyme may increase the half life of the latter drugs. Supporting Table 1 lists those medications, which should be surveyed in all telaprevir candidates.

The same general contraindications to pegylated interferon and ribavirin still apply when using a telaprevir-based regimen. Telaprevir is considered relatively safe in pregnancy (pregnancy category B) but oral contraceptives may be less effective when administered with telaprevir. In addition, pregnancy is to be avoided in patients taking PR and therefore two forms of contraception are required for females (or female partners of male patients) during treatment. An uncontrolled preexisting dermatologic condition would represent a potential relative contraindication.

More information is needed in order to determine whether the patient in question is a good candidate for telaprevir therapy. One of the most important factors in determining antiviral treatment candidacy has been the degree of fibrosis, which will be discussed in the next section.16 This patient has no history or overt features of cirrhosis, based on normal synthetic function and blood counts. Along that line, it is relevant to recall that significant cytopenias were an exclusion criteria in telaprevir studies. For example, the ILLUMINATE study, which allowed inclusion of patients with cirrhosis, enrolled patients with absolute neutrophils counts ≥1500 mm3, platelet ≥90,000 mm3, and hemoglobin ≥12 g/dL (females) or ≥13 g/dL (males). Finally, routine pretreatment evaluation for the SOC still needs to be carried out, including screening for coexistent HIV or HBV, and baseline psychiatric, renal, and cardiovascular assessment.

Assessment of Fibrosis

  1. Top of page
  2. Patient Scenario
  3. Introduction
  4. The Evidence
  5. Telaprevir Candidacy
  6. Assessment of Fibrosis
  7. Treatment Algorithm and Monitoring
  8. Management of Side Effects
  9. The Role of IL-28B in Telaprevir Therapy
  10. Recommendations
  11. References
  12. Supporting Information

There are four common reasons for assessment of fibrosis in patients with G1 CHC, including (1) patient counseling on prognosis, (2) diagnosis of cirrhosis to determine the need for surveillance for HCC and gastroesophageal varices, (3) evaluation for treatment candidacy, and (4) helping to determine treatment duration. Because of the common side effects, expense, and modest response rates with traditional SOC, histologic assessment was often used to evaluate whether the patient had enough fibrosis to warrant treatment.16 With the introduction of the first-generation protease inhibitors, there is no established consensus whether fibrosis stage needs to be assessed in the majority of patients.

On the one hand, with reported SVRs > 70%, the telaprevir containing triple therapy has become somewhat analogous to the standard dual therapy for patients infected with genotype 2 or 3. Because SVR can be achieved with a relatively short duration of therapy in a majority of treatment-naive and previous relapse patients, antiviral therapy may be justified independent of fibrosis stage.

Conversely, it is reasonable to consider observation in patients with early stage fibrosis. First, there are several new agents under development with a prospect of higher efficacy, fewer side effects, and shorter treatment duration. Because the progression of fibrosis in CHC occurs at a relatively predictable rate, patients with little fibrosis can afford to wait. Second, antiviral resistance to DAAs is now an important consideration, similar to treatment for HIV or HBV. Available data indicate that a majority of patients who fail to achieve SVR with protease inhibitors end up developing antiviral resistance. Although future consequences of resistance to protease inhibitors like telaprevir are uncertain, decreasing the effectiveness of a future therapy is a potential downside of ineffective therapy. Third, a 12-week course of telaprevir increases the cost of therapy by more than US $50,000.17 Therefore, more careful selection of treatment candidates might be justified so that it is preferentially directed toward patients who are more likely to develop problems in the relatively near future.

Given these considerations, we believe that patients who have no or little fibrosis and who do not have risk factors for rapid progression should continue to be provided the option of observation. Patients with stage 2 fibrosis or greater would generally be recommended for treatment. Other factors, such as age, extrahepatic comorbidity, concomitant liver disease, previous treatment experience including tolerance and result (e.g., relapse versus nonresponse), risk of disease transmission (e.g., health care provider) and the IL-28 genotype (discussed later), are taken into account. Affordability is always a concern, although manufacturers' patient assistance programs may ease the economic burden of the triple therapy.

Is a liver biopsy necessary to make these therapeutic decisions? Patients with hepatic decompensation, characterized by jaundice, hepatic encephalopathy, known gastroesophageal varices, or ascites, obviously have cirrhosis and are usually not candidates for treatment. Patients with overt clinical evidence of cirrhosis with or without portal hypertension, such as a small nodular liver on physical examination or ultrasound do not require a biopsy. In other patients without evidence of cirrhosis, noninvasive markers of liver fibrosis may be helpful. A detailed discussion of the performance characteristics of individual tests is beyond the scope of this review. Generally, most noninvasive tests including biomarker panels and transient elastography (if available) tend to have acceptable predictive values for little to no fibrosis and for well-established cirrhosis.18 Our practice has increasingly embraced noninvasive markers (magnetic resonance–based transient elastography in our case), reserving liver biopsies for patients with intermediate fibrosis assessment values where the prediction of fibrosis is less accurate.

Treatment Algorithm and Monitoring

  1. Top of page
  2. Patient Scenario
  3. Introduction
  4. The Evidence
  5. Telaprevir Candidacy
  6. Assessment of Fibrosis
  7. Treatment Algorithm and Monitoring
  8. Management of Side Effects
  9. The Role of IL-28B in Telaprevir Therapy
  10. Recommendations
  11. References
  12. Supporting Information

Provided that this adult patient presenting with G1 CHC meets the treatment eligibility, an anti-HCV regimen containing telaprevir would be recommended. Telaprevir is administered 750 mg by mouth every 7-9 hours with a 20 g/fat meal. The area under the plasma concentration curve (AUC) increases 330% when telaprevir is given with a meal containing 56 g of fat content, relative to the fasting state. Even a meal with 3.6 g of fat increases AUC by 110%, emphasizing the importance of taking 20 g fat meal. For reference, 4-5 pats of butter/margarine, 2 ounces of cheddar cheese, or 3 tablespoons of peanut butter would provide approximately 20 g of fat. Telaprevir must be administered with standard doses of pegylated interferon alfa and weight-based ribavirin (1000 mg/day for body weight <75 kg; 1200/day for body weight >75 kg) and is never to be prescribed as monotherapy. Timing and adherence of oral medications should be emphasized with patients. We recommend the following schedule to patients: 0600 hours (take telaprevir and first dose of ribavirin), 1400 hours (2nd dose telaprevir), 1800 hours (second dose of ribavirin), 2200 hours (third dose of telaprevir). In our early experience, most patients have found this to be the most reasonable schedule that allows taking medications with food. This schedule also allows patients 1 hour of flexibility either way to stay within a range of 7-9 hours.

Figure 1 depicts a treatment algorithm recommended for treatment-naive patients using a response-guided scheme, which should shorten the duration of therapy to 24 weeks in nearly 60% of patients. Once a patient is initiated on triple therapy in doses specified above, the first decision branch-point to guide therapy is the HCV RNA level at week 4. Of those who are negative for HCV RNA at week 4, patients who remain negative (note: detectable but below the limit of quantification does not qualify as undetectable) through week 12 have achieved eRVR. After completing 12 weeks of triple therapy, patients achieving eRVR should receive an additional 12 weeks of pegylated interferon and ribavirin. The expected probability of SVR in these patients is approximately 92%. However, given the relatively small number of patients with cirrhosis studied in the phase 3 program and the overall lower SVR in RGT treatment arm, the FDA label for both protease inhibitors has suggested that all patients with cirrhosis with an eRVR be treated for 48 weeks rather than undergo RGT. Thus, there may still be some role for accurate assessment for cirrhosis prior to initiating therapy.

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Figure 1. Telaprevir response-guided therapy algorithm for treatment-naive patients and relapsers. IFN, interferon; SE, side effect; TW, treatment week; Tx, treatment.

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In patients whose HCV RNA levels are detectable, but ≤1000 IU at week 4 and/or 12, the next decision branch-point is week 24. Patients who are HCV RNA negative at week 24, should receive an additional 24 weeks of PR (T12PR48) in order to achieve an expected SVR ≈ 60%. In patients who fail to reach these intermediate endpoints, all drugs should be discontinued, as further therapy is considered futile. Specifically, these futility rules include (1) HCV RNA > 1000 IU at any time between weeks 4 and 12; (2) HCV RNA detectable at week 24; and (3) permanent discontinuation of either pegylated interferon or ribavirin. A scenario not addressed by clinical trial data is the patient who achieves eRVR yet have detectable (but <1000 IU/mL) HCV RNA between weeks 12 and 23. We recommend that these patients receive a total of 48 weeks of PR, provided HCV RNA is undetectable at 24 weeks.

In order to assess these treatment milestones and to detect laboratory adverse events, patients must be carefully monitored. Our schedule for clinical visits and laboratories studies for patients on telaprevir is shown in Supporting Table 2. A highly sensitive real-time HCV RNA assay is recommended, with a low limit of HCV RNA quantification (e.g., ≤25 IU/mL) as well as limit of HCV RNA detection (e.g., 10-15 IU/mL).19 As with the current SOC, it is important to use the same test (and laboratory) each time in monitoring treatment response. Although not germane to the case being considered, we present our algorithm for previously treated patients for the reader's reference in Supporting Figures 1 and 2.

Management of Side Effects

  1. Top of page
  2. Patient Scenario
  3. Introduction
  4. The Evidence
  5. Telaprevir Candidacy
  6. Assessment of Fibrosis
  7. Treatment Algorithm and Monitoring
  8. Management of Side Effects
  9. The Role of IL-28B in Telaprevir Therapy
  10. Recommendations
  11. References
  12. Supporting Information

Common side effects in patients receiving telaprevir regimens can be broadly categorized as dermatologic (rash, 56%; pruritus, 47%), gastrointestinal (nausea, 39%; diarrhea, 26%; vomiting, 13%; dysgeusia, 10%), anorectal (hemorrhoids, 12%; anal discomfort, 11%; anal pruritus, 6%), hematologic (anemia, 36%), and metabolic (increased uric acid, 73%; increased bilirubin, 41%). Clinic visits are vital to monitor for rash and depression, because these potentially life-threatening adverse events can only be addressed in person.

Although most clinicians are familiar with side effects of pegylated interferon and ribavirin, two common side effects, namely anemia and rash, are more common when telaprevir is added. The rash experienced with telaprevir may appear eczematoid, is seen most often in first 4 weeks of treatment (median = 25 days), and is reversible with dose discontinuation. In the ADVANCE study, a protocol was developed to grade and manage rashes.6 A grade 1 rash is mild, localized to one or several isolated areas, and without epidermal disruption or mucous membrane involvement. Grade 1 rashes can be monitored, treated with class III topical corticosteroids (clobetasone or triamcinolone) in lotion or cream form for up to 2 weeks in conjunction with antihistamines such as diphenhydramine, hydroxyzine, levocetirizine, or desloratadine for pruritus. Grade 2 (moderate) rash is characterized as involving up to 50% of the integument, associated with possible superficial skin peeling, mucous membrane involvement without frank ulceration, and possible mild systemic symptoms. General measures listed for treatment of grade 1 rashes can be employed. If a grade 2 rash progresses despite these measures, it is recommended that telaprevir be discontinued. In a patient with stable grade 2 rash not responding to conservative measures, one could consider temporarily withdrawing ribavirin, as it may be difficult to confidently distinguish rash secondary to telaprevir from that induced by ribavirin or even interferon. Despite the long half-life of ribavirin, it has been reported that withdrawing it for as short as 48 hours may result in resolution of the rash.20 Grade 3 rash (severe) involves more than 50% of the integument or any of the following: vesicles/bullae, any ulceration of mucous membranes, epidermal detachment, targetoid lesion, or palpable purpura. Management of grade 3 rash includes immediate discontinuation of telaprevir, followed by ribavirin/pegylated interferon for nonresolution, and consideration of dermatology consultation. Stevens Johnson Syndrome, toxic epidermal necrolysis syndrome (TENS), erythema multiforme, and drug-related eosinophilia with systemic symptoms (DRESS) also constitute grade 3 rash, which merit discontinuation of all 3 agents. The DRESS syndrome rash may present with fever, facial edema, hypereosinophilia, and liver (elevated liver tests/hepatomegaly) or renal dysfunction.21, 22 Once telaprevir has been discontinued, it should not be restarted. Of note, systemic steroids to allow continued telaprevir dosing should be avoided for rash management, because its impact on rash progression and viral breakthrough have not been assessed.

The next most common side effect is anemia. On average, the addition of telaprevir to PR results in an additional 1 g/dL decline in hemoglobin, in addition to the mean maximal drop of 3 g/dL from pegylated interferon and ribavirin. In phase 3 studies, anemia with hemoglobin <10 g/dL occurred in 36% of patients on telaprevir versus 17% on SOC. The incidence of more severe anemia with a hemoglobin <8.5 g/dL was 14% with telaprevir compared to 5% with SOC. These resulted in dose reduction, interruption or discontinuation of ribavirin in approximately one-third of patients and discontinuation of telaprevir in 4%. The rate of decline of hemoglobin during weeks 1-4 is not any steeper with triple therapy than with SOC. In those receiving telaprevir, however, there is a continued decline between weeks 4 and 8. In theory, anemia of ribavirin should be distinguishable from that of telaprevir by markers of hemolysis. In practice, however, whether such a distinction is going to be helpful in clinical decision making remains uncertain. The most important principle to remember is that telaprevir cannot be dose-reduced or interrupted. Once it is stopped, it should not be restarted. Therefore, anemia should be initially managed with dose reductions in ribavirin of 200 mg increments or an initial reduction to 600 mg/day. If ribavirin is temporarily held, it can be restarted at 600 mg/day and titrated up by 200 mg as tolerated. If ribavirin is permanently discontinued, telaprevir must also be discontinued. Erythropoiesis-stimulating medications were not allowed in most phase 3 clinical trials but could be attempted to prevent RBV discontinuation, with blood transfusion used as the last resort. If all these measures are unsuccessful in recovering hemoglobin to above 8.5 g/dL, telaprevir must be discontinued permanently.

The Role of IL-28B in Telaprevir Therapy

  1. Top of page
  2. Patient Scenario
  3. Introduction
  4. The Evidence
  5. Telaprevir Candidacy
  6. Assessment of Fibrosis
  7. Treatment Algorithm and Monitoring
  8. Management of Side Effects
  9. The Role of IL-28B in Telaprevir Therapy
  10. Recommendations
  11. References
  12. Supporting Information

Variations in the IL-28B gene directly correlate with the probability of SVR in patients treated with pegylated interferon and ribavirin.23-25 The CC genotype has the highest likelihood of SVR, whereas patients with CT or TT genotypes have much lower response rates. IL-28B genotyping has been increasingly adopted in practice to help estimate the probability of successful treatment in G1 patients with CHC. To date, limited data are available regarding the impact of IL-28B genotype on treatment response to regimens containing telaprevir.

Retrospective subanalyses of trials with telaprevir have been presented as meeting abstracts. In the ADVANCE trial where a minority had available genotype data (42%), patients with the CC genotype fared better with SVR in 90% on telaprevir, whereas 71% and 73% of patients with the CT and TT genotypes achieved SVR, respectively.26 Thus, those on telaprevir attained higher SVR rates across all 3 IL-28B genotypes as compared to SOC, but the biggest differences were noted for patients with the CT and TT genotypes. In addition, IL-28B had the ability to predict the likelihood of eRVR in treatment-naive patients and thus the ability to shorten therapy to 24 weeks (CC: 72%, CT: 54%, TT: 48%). A similar subgroup analysis was conducted for the REALIZE trial, where genotype data were available in 80% (527 of 662 subjects).27 In a multivariate analysis, IL-28B genotype was not associated with SVR, whereas previous treatment response had a much stronger influence on SVR.

Currently, there is no consensus about the role for IL-28B status in the context of triple therapy with telaprevir. Although some experts have advocated that in patients with the CC genotype, the addition of telaprevir may not be cost-effective, further prospective studies on this issue are needed. Certainly in treatment-naive patients, IL-28B remains a powerful pretreatment predictor of SVR and likelihood for shortened duration of therapy. However, its role in the treatment experienced patient is less clear and does not appear to add clinical utility.

Recommendations

  1. Top of page
  2. Patient Scenario
  3. Introduction
  4. The Evidence
  5. Telaprevir Candidacy
  6. Assessment of Fibrosis
  7. Treatment Algorithm and Monitoring
  8. Management of Side Effects
  9. The Role of IL-28B in Telaprevir Therapy
  10. Recommendations
  11. References
  12. Supporting Information

The patient described in this scenario has chronic hepatitis C and requires assessment of fibrosis. If available, the initial evaluation may be conducted noninvasively, realizing a liver biopsy may be needed in a substantial proportion of cases. Treatment should be initiated for fibrosis stage of F2 or beyond, especially in patients judged to be at risk of disease progression in the near future, after confirming that the patient does not have contraindications to the three treatment agents. The clinician must be familiar with potential drug interactions and side effects of the three treatment agents, especially those of telaprevir. In order to ensure compliance and safety as well as response-guided treatment decisions, close monitoring is essential.

References

  1. Top of page
  2. Patient Scenario
  3. Introduction
  4. The Evidence
  5. Telaprevir Candidacy
  6. Assessment of Fibrosis
  7. Treatment Algorithm and Monitoring
  8. Management of Side Effects
  9. The Role of IL-28B in Telaprevir Therapy
  10. Recommendations
  11. References
  12. Supporting Information

Supporting Information

  1. Top of page
  2. Patient Scenario
  3. Introduction
  4. The Evidence
  5. Telaprevir Candidacy
  6. Assessment of Fibrosis
  7. Treatment Algorithm and Monitoring
  8. Management of Side Effects
  9. The Role of IL-28B in Telaprevir Therapy
  10. Recommendations
  11. References
  12. Supporting Information

Additional Supporting Information may be found in the online version of this article.

FilenameFormatSizeDescription
HEP_24660_sm_suppinfofig1.tif364KSupporting Information Figure 1
HEP_24660_sm_suppinfofig2.tif427KSupporting Information Figure 2
HEP_24660_sm_suppinfotab1.tif232KSupporting Information Table 1
HEP_24660_sm_suppinfotab2.tif178KSupporting Information Table 2

Please note: Wiley Blackwell is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.