Hepatitis C medical therapy: Difference between revisions

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* [[Chronic renal disease]]
* [[Chronic renal disease]]
* [[HIV]] co-infection
* [[HIV]] co-infection
* [[Mixed cryoglobulinemic vasculitis]]:  
* [[Cryoglobulinemia|Mixed cryoglobulinemic vasculitis]]: <ref name="CacoubLongo2021">{{cite journal|last1=Cacoub|first1=Patrice|last2=Longo|first2=Dan L.|last3=Saadoun|first3=David|title=Extrahepatic Manifestations of Chronic HCV Infection|journal=New England Journal of Medicine|volume=384|issue=11|year=2021|pages=1038–1052|issn=0028-4793|doi=10.1056/NEJMra2033539}}</ref>
**Treatment of chronic [[Hepatitis C]] with [[mixed cryoglobulinemic vasculitis]] has to be individualized according to the severity.
**Treatment of chronic [[Hepatitis C]] with [[Cryoglobulinemia|mixed cryoglobulinemic vasculitis]] has to be individualized according to the severity.
**Patients with mild to moderate disease such as [[arthralgia]] and [[fatigue]] require just a direct-acting antiviral regimen.  
**Patients with mild to moderate disease such as [[arthralgia]] and [[fatigue]] require just a direct-acting antiviral regimen.  
**Severe cases such as [[glomerulonephritis]] and severe [[neuropathy]] require a combination of direct-acting [[antiviral]] agents with [[plasmapheresis]] (to clear out the [[cryoglobulin]]), [[rituximab]] (to deplete cryoglobulinproducing B cells).
**Severe cases such as [[glomerulonephritis]] and severe [[neuropathy]] require a combination of direct-acting [[antiviral]] agents with [[plasmapheresis]] (to clear out the [[cryoglobulin]]), [[rituximab]] (to deplete cryoglobulinproducing B cells).

Revision as of 17:48, 1 May 2021

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Serge Korjian, Yazan Daaboul, Mehrian Jafarizade, M.D [2]

Overview

The treatment of hepatitis C has changed dramatically over the past decade. Although protease inhibitors Telaprevir and Boceprevir are often combined with the regular regimen of IFN and Ribavirin to treat patients with genotype 1 HCV, Sofosbuvir and Simeprevir have demonstrated greater efficacy in viral clearance along with a better safety profile. Guidelines from the AASLD and the IDSA have recommended the use of these oral agents (particularly Sofosbuvir) as first line agents in the treatment of chronic HCV among both relapsers and treatment-naive patients.

Medical Therapy

Acute Hepatitis C

Since the majority of patients with acute hepatitis C are asymptomatic, the infection often goes unnoticed until the effects of chronic hepatitis begin to manifest. It is uncommon to closely monitor patients at risk to detect the development of acute hepatitis C. In the majority of patients, the response rate to treatment is higher in the acute phase rather than the chronic phase of infection. Moreover, treating patients with acute hepatitis has consistently shown high rates of viral clearance and significantly lower rates of chronicity. However, the best treatment regimen, the time of initiation, and the duration of therapy are still debatable.[1] If a patient is identified as having an acute hepatitis C infection, the initial approach includes a period of monitoring of 8 - 20 weeks (often 8 - 12 weeks) to detect spontaneous viral clearance.[1][2] New data suggests higher rates of viral clearance in untreated patients with acute clinical hepatitis C than previously reported.[3][4]For patients who fail to clear the infection spontaneously, treatment should be initiated with Peg-IFN alfa ± ribavirin for 24 to 48 weeks, based on HCV genotype and response to therapy determined by HCV RNA measurement.[2] Revised AASLD guidelines for the management of acute hepatitis C are expected in the summer of 2014.

Chronic Hepatitis C

Approach & Pre-treatment Assessment

Several key points need to be addressed in patients with chronic hepatitis C prior to the initiation of therapy. Every patient with documented infection requires evaluation to determine if he/she qualifies for medical therapy. Patients with clear indications for treatment require an extensive pre-treatment assessment. Important considerations include HCV genotype, extent of liver disease, concomitant alcohol abuse, psychiatric disorders, and pregnancy among others. With current regimens being physically and financially demanding, screening is essential to identify patients requiring therapy.

Pretreatment Assessment in Patients with Chronic Hepatitis C[2]
Necessary
  • Complete medical history, with emphasis on complications of liver disease, significant extrahepatic disease, and symptoms of chronic HCV that affect quality of life
  • Psychiatric history including past or ongoing disorders with screening for depression and alcohol use
  • Serum HBsAg, antiHBc, antiHBs, antiHAV
  • Quantitative HCV RNA measurement
  • HCV genotype
  • Previous antiviral therapies and response
  • Serum ALT, serum albumin, serum bilirubin (including direct bilirubin), and prothrombin time
  • CBCD
  • TSH
  • Creatinine
  • Glucose
  • Uric acid (receiving telaprevir)
  • Ferritin, iron saturation, and serum ANA
  • Pregnancy test
  • HIV serology
  • ECG in patients with known cardiac disease
Recommended
  • Liver biopsy only if results will influence management
  • IL28B genotype only if results will influence management
  • Urine toxicology screen for opiates, cocaine, and amphetamines
  • Eye exam for retinopathy in patients with diabetes or hypertension


Treatment Indications & Contraindications

Treatment accepted for patients with following characteristics: (should fulfill all characteristics)[1]


Treatment contraindicated for patients with any of the following characteristics:[1]


Treatment should be individualized for patients with any of the following characteristics:[1]

Monitoring Response to Treatment

Following viral kinetics and assessing the rate of viral clearance is useful to predict response to therapy and to determine the optimal duration of therapy. The following definitions relate to viral kinetics and are important in the management of hepatitis C.

Early Virologic Response (EVR):
It is defined as the decrease in HCV RNA in the serum by at least 2 logs at week 12 of treatment.[2] Absence of EVR is the most optimal means to identify non-responders to therapy. Almost all treatment-naive patients with HCV genotype 1 who do not have an EVR will not have a sustained virologic response. This may be used as an indication to discontinue treatment. EVR is not very useful in monitoring the treatment of other genotypes.[1]

Rapid Virologic Response (RVR):
It is defined as undetectable HCV RNA at week 4 of therapy.[2] RVR was investigated in order to limit useless exposure to therapy. RVR is a good prognostic sign with patients achieving an RVR usually going on to achieve a sustained virologic response regardless of the genotype or therapeutic regimen.[1]

Sustained Virologic Response (SVR):
It is defined as undetectable HCV RNA at 24 weeks after treatment completion.[2]

Partial Response
It is defined as greater than 2 log reduction from baseline HCV RNA at week 12, but virus remains detectable through week 24 or after the end of treatment.[2]

Relapse
It is defined as undetectable viremia during treatment and/or at the end of treatment, but subsequent viremia after cessation of treatment.[2] In most cases, virological relapse occurs in the first 12 weeks after discontinuation of therapy. Late relapses, beyond 24 weeks, are extremely uncommon.[1]

Non-response
It is defined as detectable HCV RNA throughout treatment.[2]

Different HCV subtype treatments:

The treatment of HCV has drastically changed in the past half-decade, and with more trials showing improved outcomes. With newer therapies, treatment recommendations have shifted away from older generation protease inhibitors, such as boceprevir and telaprevir, to simeprevir and sofosbuvir that are safer and more effective. The 2014 AASLD/IDSA recommendations for testing, managing, and treating hepatitis C have made these new agents first line therapies in the management of both treatment naive and relapsing patients.[6] The guidelines do not yet address the monitoring of patients who are on or have completed therapy. The treatment is according below tables.

HCV Guidance: Recommendations for Testing, Managing, and Treating Hepatitis C; by Infectious Disease Society of America [7]

Recommended and alternative regimens listed by evidence level and alphabetically for Treatment-Naive Genotype 1a Patients Without Cirrhosis
RECOMMENDED DURATION RATING 
Daily fixed-dose combination of elbasvir (50 mg)/grazoprevir (100 mg) for patients without baseline NS5A RASsa for elbasvir 12 weeks I, A
Daily fixed-dose combination of glecaprevir (300 mg)/pibrentasvir (120 mg)b 8 weeks I, A
Daily fixed-dose combination of ledipasvir (90 mg)/sofosbuvir (400 mg) 12 weeks I, A
Daily fixed-dose combination of ledipasvir (90 mg)/sofosbuvir (400 mg) for patients who are non-black, HIV-uninfected, and whose HCV RNA level is <6 million IU/mL 8 weeks I, B
Daily fixed-dose combination of sofosbuvir (400 mg)/velpatasvir (100 mg) 12 weeks I, A
ALTERNATIVE DURATION RATING 
Daily fixed-dose combination of paritaprevir (150 mg)/ritonavir (100 mg)/ombitasvir (25 mg) with dasabuvir (600 mg) as part of an extended-release regimen or plus twice-daily dosed dasabuvir (250 mg), with weight-based ribavirin 12 weeks I, A
Daily simeprevir (150 mg) plus sofosbuvir (400 mg) 12 weeks I, A
Daily daclatasvir (60 mg)c plus sofosbuvir (400 mg) 12 weeks I, B
Daily fixed-dose combination of elbasvir (50 mg)/grazoprevir (100 mg) with weight-based ribavirin for patients with baseline NS5A RASsa for elbasvir 16 weeks IIa, B
a Includes genotype 1a resistance-associated substitutions at amino acid positions 28, 30, 31, or 93 known to confer antiviral resistance.

b This is a 3-tablet coformulation.

c The dose of daclatasvir may need to increase or decrease when used concomitantly with cytochrome P450 3A/4 inducers and inhibitors, respectively.

Treatment-Naive Genotype 1a With Compensated Cirrhosis

Recommended and alternative regimens listed by evidence level and alphabetically for Treatment-Naive Genotype 1a Patients With Compensated Cirrhosis
RECOMMENDED DURATION RATING 
Daily fixed-dose combination of elbasvir (50 mg)/grazoprevir (100 mg) for patients without baseline NS5A RASsb for elbasvir 12 weeks I, A
Daily fixed-dose combination of glecaprevir (300 mg)/pibrentasvir (120 mg)c 12 weeks I, A
Daily fixed-dose combination of ledipasvir (90 mg)/sofosbuvir (400 mg) 12 weeks I, A
Daily fixed-dose combination of sofosbuvir (400 mg)/velpatasvir (100 mg) 12 weeks I, A
ALTERNATIVE DURATION RATING 
Daily fixed-dose combination of elbasvir (50 mg)/grazoprevir (100 mg) with weight-based ribavirin for patients with baseline NS5A RASsb for elbasvir 16 weeks IIa, B
a For decompensated cirrhosis, please refer to the appropriate section.

b Includes genotype 1a resistance-associated substitutions at amino acid positions 28, 30, 31, or 93 known to confer antiviral resistance.

c This is a 3-tablet coformulation.

Treatment-Naive Genotype 1b Without Cirrhosis

Recommended and alternative regimens listed by evidence level and alphabetically for Treatment-Naive Genotype 1b Patients Without Cirrhosis
RECOMMENDED DURATION RATING 
Daily fixed-dose combination of elbasvir (50 mg)/grazoprevir (100 mg) 12 weeks I, A
Daily fixed-dose combination of glecaprevir (300 mg)/pibrentasvir (120 mg)a 8 weeks I, A
Daily fixed-dose combination of ledipasvir (90 mg)/sofosbuvir (400 mg) 12 weeks I, A
Daily fixed-dose combination of ledipasvir (90 mg)/sofosbuvir (400 mg) for patients who are non-black, HIV-uninfected, and whose HCV RNA level is <6 million IU/mL 8 weeks I, B
Daily fixed-dose combination of sofosbuvir (400 mg)/velpatasvir (100 mg) 12 weeks I, A
ALTERNATIVE DURATION RATING 
Daily fixed-dose combination of paritaprevir (150 mg)/ritonavir (100 mg)/ombitasvir (25 mg) with dasabuvir (600 mg) as part of an extended-release regimen or plus twice-daily dosed dasabuvir (250 mg) 12 weeks I, A
Daily simeprevir (150 mg) plus sofosbuvir (400 mg) 12 weeks I, A
Daily daclatasvir (60 mg)b plus sofosbuvir (400 mg) 12 weeks I, B
a This is a 3-tablet coformulation.

b The dose of daclatasvir may need to increase or decrease when used concomitantly with cytochrome P450 3A/4 inducers and inhibitors, respectively.

Treatment-Naive Genotype 1b With Compensated Cirrhosis

Recommended and alternative regimens listed by evidence level and alphabetically for Treatment-Naive Genotype 1b Patients With Compensated Cirrhosis
RECOMMENDED DURATION RATING 
Daily fixed-dose combination of elbasvir (50 mg)/grazoprevir (100 mg) 12 weeks I, A
Daily fixed-dose combination of glecaprevir (300 mg)/pibrentasvir (120 mg)b 12 weeks I, A
Daily fixed-dose combination of ledipasvir (90 mg)/sofosbuvir (400 mg) 12 weeks I, A
Daily fixed-dose combination of sofosbuvir (400 mg)/velpatasvir (100 mg) 12 weeks I, A
ALTERNATIVE DURATION RATING 
Daily fixed-dose combination of paritaprevir (150 mg)/ritonavir (100 mg)/ombitasvir (25 mg) with dasabuvir (600 mg) as part of an extended-release regimen or plus twice-daily dosed dasabuvir (250 mg)c 12 weeks I, A
a For decompensated cirrhosis, please refer to the appropriate section.

b This is a 3-tablet coformulation.

c Please see statement on FDA warning regarding the use of paritaprevir/ritonavir/ombitasvir ± dasabuvir in patients with cirrhosis.

Treatment-Naive Genotype 2 Without Cirrhosis

Recommended and alternative regimens listed by evidence level and alphabetically for Treatment-Naive Genotype 2 Patients Without Cirrhosis
RECOMMENDED DURATION RATING 
Daily fixed-dose combination of glecaprevir (300 mg)/pibrentasvir (120 mg)a 8 weeks I, A
Daily fixed-dose combination of sofosbuvir (400 mg)/velpatasvir (100 mg) 12 weeks I, A
ALTERNATIVE DURATION RATING 
Daily daclatasvir (60 mg)b plus sofosbuvir (400 mg) 12 weeks IIa, B
a This is a 3-tablet coformulation.

b The dose of daclatasvir may need to increase or decrease when used concomitantly with cytochrome P450 3A/4 inducers and inhibitors, respectively.

Treatment-Naive Genotype 2 With Compensated Cirrhosis

Recommended and alternative regimens listed by evidence level and alphabetically for Treatment-Naive Genotype 2 Patients With Compensated Cirrhosis
RECOMMENDED DURATION RATING 
Daily fixed-dose combination of sofosbuvir (400 mg)/velpatasvir (100 mg) 12 weeks I, A
Daily fixed-dose combination of glecaprevir (300 mg)/

pibrentasvir (120 mg)b

12 weeks I, B
ALTERNATIVE DURATION RATING 
Daily daclatasvir (60 mg)c plus sofosbuvir (400 mg) 16 to 24 weeks IIa, B
a For decompensated cirrhosis, please refer to the appropriate section.

b This is a 3-tablet coformulation.

c The dose of daclatasvir may need to increase or decrease when used concomitantly with cytochrome P450 3A/4 inducers and inhibitors, respectively.

Treatment-Naive Genotype 3 Without Cirrhosis

Recommended and alternative regimens listed by evidence level and alphabetically for Treatment-Naive Genotype 3 Patients Without Cirrhosis
RECOMMENDED DURATION RATING 
Daily fixed-dose combination of glecaprevir (300 mg)/pibrentasvir (120 mg)a 8 weeks I, A
Daily fixed-dose combination of sofosbuvir (400 mg)/velpatasvir (100 mg) 12 weeks I, A
ALTERNATIVE DURATION RATING 
Daily daclatasvir (60 mg)b plus sofosbuvir (400 mg) 12 weeks I, A
a This is a 3-tablet coformulation. Please refer to the prescribing information.

b The dose of daclatasvir may need to increase or decrease when used concomitantly with cytochrome P450 3A/4 inducers and inhibitors, respectively.

Treatment-Naive Genotype 3 With Compensated Cirrhosis

Recommended and alternative regimens listed by evidence level and alphabetically for Treatment-Naive Genotype 3 Patients With Compensated Cirrhosis
RECOMMENDED DURATION RATING 
Daily fixed-dose combination of glecaprevir (300 mg)/pibrentasvir (120 mg)b 12 weeks I, A
Daily fixed-dose combination of sofosbuvir (400 mg)/velpatasvir (100 mg)c 12 weeks I, A
ALTERNATIVE DURATION RATING 
Daily fixed-dose combination of sofosbuvir (400 mg)/velpatasvir (100 mg)/voxilaprevir (100 mg) when Y93H is present 12 weeks IIa, B
Daily daclatasvir (60 mg)d plus sofosbuvir (400 mg) with or without weight-based ribavirinc 24 weeks IIa, B
a For decompensated cirrhosis, please refer to the appropriate section.

b This is a 3-tablet coformulation. Please refer to the prescribing information.

c RAS testing for Y93H is recommended for cirrhotic patients. If present, ribavirin should be included in the regimen or sofosbuvir/velpatasvir/voxilaprevir should be considered.

d The dose of daclatasvir may need to increase or decrease when used concomitantly with cytochrome P450 3A/4 inducers and inhibitors, respectively.

Treatment-Naive Genotype 4 Without Cirrhosis

Recommended and alternative regimens listed by evidence level and alphabetically for Treatment-Naive Genotype 4 Patients Without Cirrhosis
RECOMMENDED DURATION RATING 
Daily fixed-dose combination of glecaprevir (300 mg)/pibrentasvir (120 mg)a 8 weeks I, A
Daily fixed-dose combination of sofosbuvir (400 mg)/velpatasvir (100 mg) 12 weeks I, A
Daily fixed-dose combination of elbasvir (50 mg)/grazoprevir (100 mg) 12 weeks IIa, B
Daily fixed-dose combination of ledipasvir (90 mg)/sofosbuvir (400 mg) 12 weeks IIa, B
ALTERNATIVE DURATION RATING 
Daily fixed-dose combination of paritaprevir (150 mg)/ritonavir (100 mg)/ombitasvir (25 mg) and weight-based ribavirin 12 weeks I, A
a This is a 3-tablet coformulation.

 

Treatment-Naive Genotype 4 With Compensated Cirrhosis

Recommended and alternative regimens listed by evidence level and alphabetically for Treatment-Naive Genotype 4 Patients With Compensated Cirrhosis
RECOMMENDED DURATION RATING 
Daily fixed-dose combination of sofosbuvir (400 mg)/velpatasvir (100 mg) 12 weeks I, A
Daily fixed-dose combination of glecaprevir (300 mg)/pibrentasvir (120 mg)b 12 weeks I, B
Daily fixed-dose combination of elbasvir (50 mg)/grazoprevir (100 mg) 12 weeks IIa, B
Daily fixed-dose combination of ledipasvir (90 mg)/sofosbuvir (400 mg) 12 weeks IIa, B
ALTERNATIVE DURATION RATING 
Daily fixed-dose combination of paritaprevir (150 mg)/ritonavir (100 mg)/ombitasvir (25 mg) and weight-based ribavirinc 12 weeks I, A
a For decompensated cirrhosis.

b This is a 3-tablet coformulation.

c Please see statement on FDA warning regarding the use of paritaprevir/ritonavir/ombitasvir ± dasabuvir in patients with cirrhosis.

 

Treatment-Naive Genotype 5 or 6

Recommended and alternative regimens listed by evidence level and alphabetically for Treatment-Naive Genotype 5 or 6
RECOMMENDED DURATION RATING 
Daily fixed-dose combination of glecaprevir (300 mg)/

pibrentasvir (120 mg)b

8 weeks

(no cirrhosis)

I, A
Daily fixed-dose combination of glecaprevir (300 mg)/

pibrentasvir (120 mg)b

12 weeks

(cirrhosis)

I, A
Daily fixed-dose combination of sofosbuvir (400 mg)/velpatasvir (100 mg) 12 weeks I, B
Daily fixed-dose combination of ledipasvir (90 mg)/sofosbuvir (400 mg) 12 weeks IIa, B
a For decompensated cirrhosis, please refer to the appropriate section.

b This is a 3-tablet coformulation.

 


Antiviral Agents

Antiviral Agents Used in the Treatment of Hepatitis C
Agent Recommended Dose Adverse Effects
PegIFN alfa-2a (Pegasys™)

180 mcg subcutaneously once weekly[2]

Serious adverse events: <1%[8]

Common adverse events: 99% of patients experience at least one of the following[8]

  • Psychiatric reactions, including depression, insomnia, irritability, anxiety
  • Flu-like symptoms such as fatigue, pyrexia, myalgia, headache, and rigors
  • Anorexia
  • Nausea and vomiting
  • Diarrhea
  • Arthralgias
  • Injection site reactions
  • Alopecia
  • Pruritus
PegIFN alfa-2b (PEG-Intron™)

1.5 mc / kg SC once weekly[2]

Serious adverse events: <1%[9]

Common adverse events: 50% of patients have at least one of the following[9]

  • Injection site reaction
  • Mood instability and depression
  • Nausea
  • Fatigue/asthenia
  • Headache
  • Rigors and fevers
  • Myalgia
Ribavirin
(Rebetol™, Ribasphere™, Copegus™, RibaPak™)

Genotype 1
1,000 mg (if ≤ 75 kg) or 1,200 mg (if > 75 kg) PO daily divided into two doses[2]


Genotype 2 & 3
800 PO daily in two divided doses[2]

Ribavirin is teratogenic and may cause birth defects and/or death of the exposed fetus.

Serious adverse events:[10]

Common adverse events: [10]

  • Fatigue/asthenia
  • Fever
  • Myalgias
  • Headaches
Sofosbuvir (Sovaldi™)

400 mg orally daily

Common adverse events: 20%[11]

Simeprevir (Olysio™)

150 mg orally daily

Common adverse events: 20%[12]

Boceprevir [BOC] (Victrelis™)

800 mg (4 × 200 mg capsules) PO every 7 – 9h with food in combination with PegIFN – RBV following a 4-week lead-in with PegIFN – RBV [2]

No longer recommended given the safer profile of newer protease inhibitors

Serious adverse events:[13]

Common adverse events:[13]

  • Fatigue
  • Anemia
  • Nausea
  • Headache
  • Dysgeusia
Telaprevir [TVR] (Incivek™)

750 mg (2 × 375 mg tablets) PO every 7 – 9 h with food (20 grams fat) for 12 weeks, plus PegIFN – RBV 24 or 48 weeks [2]

No longer recommended given the safer profile of newer protease inhibitors

Serious adverse events:[14]

Common adverse events: [14]


References

  1. 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 Ghany MG, Strader DB, Thomas DL, Seeff LB, American Association for the Study of Liver Diseases (2009). "Diagnosis, management, and treatment of hepatitis C: an update". Hepatology. 49 (4): 1335–74. doi:10.1002/hep.22759. PMID 19330875.
  2. 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 2.11 2.12 2.13 2.14 Yee HS, Chang MF, Pocha C, Lim J, Ross D, Morgan TR; et al. (2012). "Update on the management and treatment of hepatitis C virus infection: recommendations from the Department of Veterans Affairs Hepatitis C Resource Center Program and the National Hepatitis C Program Office". Am J Gastroenterol. 107 (5): 669–89, quiz 690. doi:10.1038/ajg.2012.48. PMID 22525303.
  3. Gerlach JT, Diepolder HM, Zachoval R, Gruener NH, Jung MC, Ulsenheimer A; et al. (2003). "Acute hepatitis C: high rate of both spontaneous and treatment-induced viral clearance". Gastroenterology. 125 (1): 80–8. PMID 12851873.
  4. Micallef JM, Kaldor JM, Dore GJ (2006). "Spontaneous viral clearance following acute hepatitis C infection: a systematic review of longitudinal studies". J Viral Hepat. 13 (1): 34–41. doi:10.1111/j.1365-2893.2005.00651.x. PMID 16364080.
  5. 5.0 5.1 Cacoub, Patrice; Longo, Dan L.; Saadoun, David (2021). "Extrahepatic Manifestations of Chronic HCV Infection". New England Journal of Medicine. 384 (11): 1038–1052. doi:10.1056/NEJMra2033539. ISSN 0028-4793.
  6. AASLD/IDSA/IAS–USA. Recommendations for testing, managing, and treating hepatitis C. http://www.hcvguidelines.org. Accessed July 27, 2014.
  7. "Recommendations for Testing, Managing, and Treating Hepatitis C | HCV Guidance".
  8. 8.0 8.1 [| PEGASYS Prescribing Information. Genentech, Inc. 2013.]
  9. 9.0 9.1 [| PEGINTRON Prescribing Information. Merck & Co., Inc. 2013.]
  10. 10.0 10.1 [| COPEGUS Prescribing Information. Genentech, Inc. 2013.]
  11. [| SOVALDI Prescribing Information. Gilead Sciences, Inc. 2013]
  12. [| OLYSIO Prescribing Information. Janssen Products, LP 2013.]
  13. 13.0 13.1 [| VICTRELIS Prescribing Information. Merck & Co., Inc. 2013.]
  14. 14.0 14.1 [| INCIVEK Prescribing Information. Vertex Pharmaceuticals Incorporated, 2013.]