Hepatitis C medical therapy: Difference between revisions

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Latest revision as of 23:09, 12 June 2021

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], Javaria Anwer M.D.[3]

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]^[5]
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 complete blood count, comprehensive metabolic panel Laboratory testing should include total that includes estimated glomerular filtration rate 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 (as all current direct-acting antiviral therapies are pregnancy category C) 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]

Age ≥ 18 years
HCV RNA positive
Liver biopsy showing chronic hepatitis with bridging fibrosis or higher
Compensated liver disease:
- Total bilirubin ≤ 1.5 g/dL
- INR ≤ 1.5
- Serum albumin > 3.4
- Platelet count ≥ 75,000 mm3
- No evidence of hepatic decompensation (hepatic encephalopathy or ascites)
Acceptable hematological and biochemical profile:
- Hemoglobin ≥ 13 g/dL for men; 12 g/dL for women
- Neutrophil count ≥ 1500 /mm3
- Serum creatinine ≤ 1.5 mg/dL
Willing to adhere to therapy
No contraindications to therapy

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

Age ≤ 2 years
Uncontrolled major depressive disorder
Any solid organ transplant
Autoimmune hepatitis or other autoimmune condition known to be exacerbated by peg-interferon and ribavirin
Untreated thyroid disease
Pregnant or unwilling to comply with adequate contraception
Severe comorbidities such as severe hypertension, heart failure, significant coronary heart disease, poorly controlled diabetes, chronic obstructive pulmonary disease
Known hypersensitivity to drugs used

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

Age < 18 years of age
Failed initial treatment (non-responder or relapser)
Decompensated cirrhosis
Liver transplant recipients
Liver biopsy demonstrating mild or no fibrosis
Current illicit drug or alcohol abusers willing to enroll in a substance abuse program. Abstinence for a minimum of 6 months is required
Chronic renal disease
HIV co-infection
Mixed cryoglobulinemic vasculitis: ^[6]
- Treatment of chronic Hepatitis C with 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.
- 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).
- Refractory cases (associated with underlying, low-grade lymphoma) may require immunosuppressants. Low-dose glucocorticoids can help control minor inflammatory symptoms.

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.^[7] 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 ^[8]

International guidelines recommend direct-acting antiviral treatment to be initiated without delay among patients with clinically significant extrahepatic manifestations of chronic hepatitis C.^[6]

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 ribavirin^c	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 ribavirin^c	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%^[9] Depression with suicide Relapse of drug abuse/overdose Severe bacterial infections (osteomyelitis, endocarditis, pyelonephritis, pneumonia, and sepsis) Hepatic decompensation (2% of patients with HIV coinfection) Common adverse events: 99% of patients experience at least one of the following^[9] 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%^[10] Suicidal/homicidal thoughts Cardiovascular events Loss of vision, retinopathy including macular edema, retinal artery or vein thrombosis Stroke Bone marrow toxicity Development or exacerbation of autoimmune disorders Colitis Pancreatitis Pulmonary disorders including dyspnea, pulmonary infiltrates, pneumonia, bronchiolitis obliterans Liver failure especially with HIV coinfection Common adverse events: 50% of patients have at least one of the following^[10] 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:^[11] Bacterial infection (sepsis, osteomyelitis, endocarditis, pyelonephritis, pneumonia) (3-5%) Hemolytic anemia (13%) Pancreatitis Liver failure Pulmonary disease Common adverse events: ^[11] Fatigue/asthenia Fever Myalgias Headaches
Sofosbuvir (Sovaldi™)	400 mg orally daily	Common adverse events: 20%^[12] Fatigue Headache Insomnia Anemia
Simeprevir (Olysio™)	150 mg orally daily	Common adverse events: 20%^[13] Rash Photosensitivity Pruritus Nausea Dyspnea
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:^[14] Anemia Neutropenia Pancytopenia Common adverse events:^[14] 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:^[15] Stevens-Johnson Syndrome (SJS) Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Toxic Epidermal Necrolysis (TEN) Profound anemia Common adverse events: ^[15] Rash Pruritus Fatigue Anemia Nausea and vomiting Hemorrhoids Diarrhea Anorectal discomfort Dysgeusia Anal pruritus

References

↑ ^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.
↑ ^2.00 ^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.
↑ 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.
↑ 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.
↑ Cacoub P, Desbois AC, Comarmond C, Saadoun D (November 2018). "Impact of sustained virological response on the extrahepatic manifestations of chronic hepatitis C: a meta-analysis". Gut. 67 (11): 2025–2034. doi:10.1136/gutjnl-2018-316234. PMID 29703790.
↑ ^6.0 ^6.1 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.
↑ AASLD/IDSA/IAS–USA. Recommendations for testing, managing, and treating hepatitis C. http://www.hcvguidelines.org. Accessed July 27, 2014.
↑ "Recommendations for Testing, Managing, and Treating Hepatitis C | HCV Guidance".
↑ ^9.0 ^9.1 [| PEGASYS Prescribing Information. Genentech, Inc. 2013.]
↑ ^10.0 ^10.1 [| PEGINTRON Prescribing Information. Merck & Co., Inc. 2013.]
↑ ^11.0 ^11.1 [| COPEGUS Prescribing Information. Genentech, Inc. 2013.]
↑ [| SOVALDI Prescribing Information. Gilead Sciences, Inc. 2013]
↑ [| OLYSIO Prescribing Information. Janssen Products, LP 2013.]
↑ ^14.0 ^14.1 [| VICTRELIS Prescribing Information. Merck & Co., Inc. 2013.]
↑ ^15.0 ^15.1 [| INCIVEK Prescribing Information. Vertex Pharmaceuticals Incorporated, 2013.]

[pmid19330875-1] 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.

[pmid22525303-2] 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.

[pmid12851873-3] 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.

[pmid16364080-4] 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.

[pmid29703790-5] Cacoub P, Desbois AC, Comarmond C, Saadoun D (November 2018). "Impact of sustained virological response on the extrahepatic manifestations of chronic hepatitis C: a meta-analysis". Gut. 67 (11): 2025–2034. doi:10.1136/gutjnl-2018-316234. PMID 29703790.

[CacoubLongo2021-6] 6.0 ^6.1 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.

[aasld2014-7] AASLD/IDSA/IAS–USA. Recommendations for testing, managing, and treating hepatitis C. http://www.hcvguidelines.org. Accessed July 27, 2014.

[urlRecommendations_for_Testing,_Managing,_and_Treating_Hepatitis_C_|_HCV_Guidance-8] "Recommendations for Testing, Managing, and Treating Hepatitis C | HCV Guidance".

[pegasys-9] 9.0 ^9.1 [| PEGASYS Prescribing Information. Genentech, Inc. 2013.]

[pegintron-10] 10.0 ^10.1 [| PEGINTRON Prescribing Information. Merck & Co., Inc. 2013.]

[COPEGUS-11] 11.0 ^11.1 [| COPEGUS Prescribing Information. Genentech, Inc. 2013.]

[sofosbuvir-12] [| SOVALDI Prescribing Information. Gilead Sciences, Inc. 2013]

[simeprevir-13] [| OLYSIO Prescribing Information. Janssen Products, LP 2013.]

[victrelis-14] 14.0 ^14.1 [| VICTRELIS Prescribing Information. Merck & Co., Inc. 2013.]

[incivek-15] 15.0 ^15.1 [| INCIVEK Prescribing Information. Vertex Pharmaceuticals Incorporated, 2013.]

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+__NOTOC__
 {{Hepatitis C}}
-{{CMG}}; '''Assistant Editor-In-Chief:''' Nina Axiotakis [mailto:naxiotak@oberlin.edu]
+{{CMG}}; '''Associate Editor(s)-In-Chief:''' [[User:Sergekorjian|Serge Korjian]], [[User:YazanDaaboul|Yazan Daaboul]], {{MJ}}, {{JA}}
-== Treatment==
+==Overview==
+The treatment of [[hepatitis C]] has changed dramatically over the past decade.  Although [[protease inhibitor]]s [[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.
-Treatment during the acute infection phase has much higher success rates (greater than 90%) with a shorter duration of treatment (but balance this against the 80% chance of spontaneous clearance without treatment).
+== Medical Therapy==
-Those with low initial viral loads respond much better to treatment than those with higher viral loads (greater than 2 million virons/ml). Current combination therapy is usually supervised by physicians in the fields of [[gastroenterology]], [[hepatology]] or [[infectious disease]].
+===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.<ref name="pmid19330875">{{cite journal| author=Ghany MG, Strader DB, Thomas DL, Seeff LB, American Association for the Study of Liver Diseases| title=Diagnosis, management, and treatment of hepatitis C: an update. | journal=Hepatology | year= 2009 | volume= 49 | issue= 4 | pages= 1335-74 | pmid=19330875 | doi=10.1002/hep.22759 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19330875  }} </ref> 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.<ref name="pmid19330875">{{cite journal| author=Ghany MG, Strader DB, Thomas DL, Seeff LB, American Association for the Study of Liver Diseases| title=Diagnosis, management, and treatment of hepatitis C: an update. | journal=Hepatology | year= 2009 | volume= 49 | issue= 4 | pages= 1335-74 | pmid=19330875 | doi=10.1002/hep.22759 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19330875  }} </ref><ref name="pmid22525303">{{cite journal| author=Yee HS, Chang MF, Pocha C, Lim J, Ross D, Morgan TR et al.| title=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. | journal=Am J Gastroenterol | year= 2012 | volume= 107 | issue= 5 | pages= 669-89; quiz 690 | pmid=22525303 | doi=10.1038/ajg.2012.48 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22525303  }} </ref>  New data suggests higher rates of viral clearance in untreated patients with acute clinical hepatitis C than previously reported.<ref name="pmid12851873">{{cite journal| author=Gerlach JT, Diepolder HM, Zachoval R, Gruener NH, Jung MC, Ulsenheimer A et al.| title=Acute hepatitis C: high rate of both spontaneous and treatment-induced viral clearance. | journal=Gastroenterology | year= 2003 | volume= 125 | issue= 1 | pages= 80-8 | pmid=12851873 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12851873  }} </ref><ref name="pmid16364080">{{cite journal| author=Micallef JM, Kaldor JM, Dore GJ| title=Spontaneous viral clearance following acute hepatitis C infection: a systematic review of longitudinal studies. | journal=J Viral Hepat | year= 2006 | volume= 13 | issue= 1 | pages= 34-41 | pmid=16364080 | doi=10.1111/j.1365-2893.2005.00651.x | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16364080  }} </ref>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.<ref name="pmid22525303">{{cite journal| author=Yee HS, Chang MF, Pocha C, Lim J, Ross D, Morgan TR et al.| title=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. | journal=Am J Gastroenterol | year= 2012 | volume= 107 | issue= 5 | pages= 669-89; quiz 690 | pmid=22525303 | doi=10.1038/ajg.2012.48 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22525303  }} </ref> Revised AASLD guidelines for the management of acute hepatitis C are expected in the summer of 2014.
-The treatment may be physically demanding, particularly those with a prior history of drug or alcohol abuse. It can qualify for temporary [[disability]] in some cases. A substantial proportion of patients will experience a panoply of side effects ranging from a 'flu-like' syndrome (the most common, experienced for a few days after the weekly injection of interferon) to severe adverse events including [[anemia]], [[cardiovascular disease|cardiovascular events]] and psychiatric problems such as [[suicide]] or suicidal ideation. The latter are exacerbated by the general physiological stress experienced by the patient.
+===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.
-In addition to the standard treatment with interferon and ribavirin, some studies have shown a higher success rates when the antiviral drug [[amantadine]] (Symmetrel) is added to the regimen. Sometimes called "triple therapy", it involves the addition of 100mg of amantadine twice a day. Studies indicate that this may be especially helpful for "nonresponders" - patients who have not been successful in previous treatments using interferon and ribavirin only.<!--
+{| style="border: 0px; font-size: 100%; margin: 3px; align:center;" align="center" width="900px"
-  --><ref name="Maynard">{{cite journal | author = Maynard M, Pradat P, Bailly F, Rozier F, Nemoz C, Si Ahmed S, Adeleine P, Trépo C | title = Amantadine triple therapy for non-responder hepatitis C patients. Clues for controversies (ANRS HC 03 BITRI). | journal = J Hepatol | volume = 44 | issue = 3 | pages = 484-90 | year = 2006 | id = PMID 16426697}}</ref>
+|+'''''Pretreatment Assessment in Patients with Chronic Hepatitis C'''''<ref name="pmid22525303">{{cite journal| author=Yee HS, Chang MF, Pocha C, Lim J, Ross D, Morgan TR et al.| title=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. | journal=Am J Gastroenterol | year= 2012 | volume= 107 | issue= 5 | pages= 669-89; quiz 690 | pmid=22525303 | doi=10.1038/ajg.2012.48 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22525303  }} </ref><ref name="pmid29703790">{{cite journal |vauthors=Cacoub P, Desbois AC, Comarmond C, Saadoun D |title=Impact of sustained virological response on the extrahepatic manifestations of chronic hepatitis C: a meta-analysis |journal=Gut |volume=67 |issue=11 |pages=2025–2034 |date=November 2018 |pmid=29703790 |doi=10.1136/gutjnl-2018-316234 |url=}}</ref>
-Currently, amantadine is not approved for treatment of Hepatitis C, and studies are ongoing to determine when it is most likely to benefit the patient.  Followup studies have shown no benefit to adding this drug and currently it is not commonly used by experienced hepatologists.
+! style="background: #4479BA; width: 550px;" | {{fontcolor|#FFF|'''Necessary'''}}
+|-
+| style="padding: 5px 5px; background: #DCDCDC;" |
+* 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
+*[[complete blood count]], [[comprehensive metabolic panel]]
+*Laboratory testing should include total  that includes estimated [[glomerular filtration rate]]
+* 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 (as all current direct-acting [[antiviral]] therapies are [[pregnancy]] category C)
+* [[HIV]] serology
+* [[ECG]] in patients with known cardiac disease
+      |-
-Current guidelines strongly recommend that hepatitis C patients be vaccinated for hepatitis A and B if they have not yet been exposed to these viruses, as this would radically worsen their liver disease.
+! style="background: #4479BA; width: 550px;" | {{fontcolor|#FFF|'''Recommended'''}}
+|-
+| style="padding: 5px 5px; background: #DCDCDC;" |
+* 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]]
-[[Alcoholic beverage]] consumption accelerates HCV associated fibrosis and cirrhosis, and makes liver cancer more likely; [[insulin resistance]] and [[metabolic syndrome]] may similarly worsen the hepatic prognosis.  There is also evidence that smoking increases the fibrosis (scarring) rate.
+|-
+|}
+<br>
-=== Treatment Indications ===
+==== Treatment Indications & Contraindications ====
-* '''Clearly Indicated'''
+<u>'''Treatment {{fontcolor|#4479BA|accepted}} for patients with following characteristics''':</u> (should fulfill all characteristics)<ref name="pmid19330875">{{cite journal| author=Ghany MG, Strader DB, Thomas DL, Seeff LB, American Association for the Study of Liver Diseases| title=Diagnosis, management, and treatment of hepatitis C: an update. | journal=Hepatology | year= 2009 | volume= 49 | issue= 4 | pages= 1335-74 | pmid=19330875 | doi=10.1002/hep.22759 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19330875  }} </ref>
-*:* Detectable HCV RNA and persistently elevated alanine aminotransferase (ALT)
+* Age ≥ 18 years
-*:* Liver biopsy with fibrosis or moderate necrosis/inflammation
+* HCV RNA positive
-*:*:* High risk disease progression
+* Liver biopsy showing chronic hepatitis with bridging fibrosis or higher
-* '''Possibly Beneficial'''
+* Compensated liver disease:
-*:* Detectable HCV RNA and elevated ALT
+** ''[[Total bilirubin]]'' ≤ 1.5 g/dL
-*:* Liver biopsy with minimal or mild inflammatory changes
+** ''[[INR]]'' ≤ 1.5
-*:*:* Lower risk disease progression
+** ''[[Serum albumin]]'' > 3.4
-*:*:* Alternative = follow ALT and re-biopsy at 3-5 years
+** ''[[Platelet count]]'' ≥ 75,000 mm3
-* '''Not Indicated'''
+** ''No evidence of hepatic decompensation'' ([[hepatic encephalopathy]] or [[ascites]])
-*:* Detectable HCV RNA with persistently normal ALT
+* Acceptable hematological and biochemical profile:
-*:* Liver biopsy with minimal or no inflammatory changes
+** ''[[Hemoglobin]]'' ≥ 13 g/dL for men; 12 g/dL for women
-*:*:* Excellent prognosis without therapy
+** ''[[Neutrophil count]]'' ≥ 1500 /mm3
-*:*:* May consider therapy if extrahepatic hepatic manifestations
+** ''Serum [[creatinine]]'' ≤ 1.5 mg/dL
-* '''Contraindicated'''
+* Willing to adhere to therapy
-*:* IFN-alfa
+* No contraindications to therapy
-*:*:* Severe depression, psychosis
+<br>
-*:*:* Decompensated cirrhosis
+<u>'''Treatment {{fontcolor|#4479BA|contraindicated}} for patients with any of the following characteristics''':</u><ref name="pmid19330875">{{cite journal| author=Ghany MG, Strader DB, Thomas DL, Seeff LB, American Association for the Study of Liver Diseases| title=Diagnosis, management, and treatment of hepatitis C: an update. | journal=Hepatology | year= 2009 | volume= 49 | issue= 4 | pages= 1335-74 | pmid=19330875 | doi=10.1002/hep.22759 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19330875  }} </ref>
-*:*:* Neutropenia or thrombocytopenia
+* Age ≤ 2 years
-*:*:* Uncontrolled seizures
+* Uncontrolled [[major depressive disorder]]
-*:*:* Organ transplant (other than liver)
+* Any solid organ transplant
-*:*:* Symptomatic heart disease
+* Autoimmune hepatitis or other autoimmune condition known to be exacerbated by peg-interferon and [[ribavirin]]
-*:* Ribavirin
+* Untreated thyroid disease
-*:*:* Pregnancy or inadequate contraception
+* Pregnant or unwilling to comply with adequate contraception
-*:*:* Anemia, hemoglobinopathy
+* Severe comorbidities such as ''severe [[hypertension]], [[heart failure]], significant coronary heart disease, poorly controlled [[diabetes]], [[chronic obstructive pulmonary disease]]''
-*:*:* Severe cardiac disease or end-stage renal disease (ESRD)
+* Known [[hypersensitivity to drugs]] used
+<br>
+<u>'''Treatment should be {{fontcolor|#4479BA|individualized}} for patients with any of the following characteristics''':</u><ref name="pmid19330875">{{cite journal| author=Ghany MG, Strader DB, Thomas DL, Seeff LB, American Association for the Study of Liver Diseases| title=Diagnosis, management, and treatment of hepatitis C: an update. | journal=Hepatology | year= 2009 | volume= 49 | issue= 4 | pages= 1335-74 | pmid=19330875 | doi=10.1002/hep.22759 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19330875  }} </ref>
+* Age < 18 years of [[age]]
+* Failed initial [[treatment]] (non-responder or relapser)
+* Decompensated [[cirrhosis]]
+* [[Liver]] [[transplant]] recipients
+* Liver [[biopsy]] demonstrating mild or no [[fibrosis]]
+* Current illicit drug or [[alcohol]] abusers willing to enroll in a substance abuse program. Abstinence for a minimum of 6 months is required
+* [[Chronic renal disease]]
+* [[HIV]] co-infection
+* [[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 [[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.
+**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).
+** Refractory cases (associated with underlying, low-grade [[lymphoma]]) may require [[immunosuppressants]]. Low-dose [[glucocorticoids]] can help control minor [[inflammation|inflammatory]] [[symptoms]].
-=== Chronic Pharmacotherapies ===
+===Monitoring Response to Treatment===
-* '''Interferon alfa monoRx'''
+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.
-*:* Sustained response 16%
-*:* Genotype 1a or 1b--lowest response rate
-* '''IFN-alfa + ribavirin'''
-*:* Sustained response 40%
-*:* Genotype 1 or high HCV RNA--max response at 48 weeks
-*:* Genotype 2 or 3--maximal response at 24 weeks
-*:* Doses = IFN 3 mU sc tiw + ribavirin 600 mg po bid
-*:* If HCV RNA+ at 24 weeks, discontinue therapy (no response)
-* '''Pegylated Interferon'''
-*:* Higher response rate than conventional IFN monoRx
-*:* Weight-based dose given every week
-*:* Combination with ribavirin currently in clinical trials
-=== During pregnancy and breastfeeding ===
+'''''{{fontcolor|#4479BA|Early Virologic Response (EVR):}}'''''<br>
+It is defined as the decrease in HCV RNA in the serum by at least 2 logs at week 12 of treatment.<ref name="pmid22525303">{{cite journal| author=Yee HS, Chang MF, Pocha C, Lim J, Ross D, Morgan TR et al.| title=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. | journal=Am J Gastroenterol | year= 2012 | volume= 107 | issue= 5 | pages= 669-89; quiz 690 | pmid=22525303 | doi=10.1038/ajg.2012.48 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22525303  }} </ref> 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.<ref name="pmid19330875">{{cite journal| author=Ghany MG, Strader DB, Thomas DL, Seeff LB, American Association for the Study of Liver Diseases| title=Diagnosis, management, and treatment of hepatitis C: an update. | journal=Hepatology | year= 2009 | volume= 49 | issue= 4 | pages= 1335-74 | pmid=19330875 | doi=10.1002/hep.22759 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19330875  }} </ref>
-If a [[pregnant]] woman has risk factors for hepatitis C, she should be tested for antibodies against HCV. About four out of every hundred infants born to HCV infected women become infected. The virus is spread to the baby at the time of birth. There is no treatment that can prevent this from happening.
+'''''{{fontcolor|#4479BA|Rapid Virologic Response (RVR):}}'''''<br>
+It is defined as undetectable HCV RNA at week 4 of therapy.<ref name="pmid22525303">{{cite journal| author=Yee HS, Chang MF, Pocha C, Lim J, Ross D, Morgan TR et al.| title=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. | journal=Am J Gastroenterol | year= 2012 | volume= 107 | issue= 5 | pages= 669-89; quiz 690 | pmid=22525303 | doi=10.1038/ajg.2012.48 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22525303  }} </ref> 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.<ref name="pmid19330875">{{cite journal| author=Ghany MG, Strader DB, Thomas DL, Seeff LB, American Association for the Study of Liver Diseases| title=Diagnosis, management, and treatment of hepatitis C: an update. | journal=Hepatology | year= 2009 | volume= 49 | issue= 4 | pages= 1335-74 | pmid=19330875 | doi=10.1002/hep.22759 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19330875  }} </ref>
-In a mother that also has HIV, the rate of transmission can be as high as 19%. There is currently no data to determine whether antiviral therapy reduces perinatal transmission. [[Ribavirin]] and [[interferon]]s are contraindicated during pregnancy. However, avoiding fetal scalp monitoring and prolonged labor after [[rupture of membranes]] may reduce the risk of transmission to the infant.
+'''''{{fontcolor|#4479BA|Sustained Virologic Response (SVR):}}'''''<br>
+It is defined as undetectable HCV RNA at 24 weeks after treatment completion.<ref name="pmid22525303">{{cite journal| author=Yee HS, Chang MF, Pocha C, Lim J, Ross D, Morgan TR et al.| title=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. | journal=Am J Gastroenterol | year= 2012 | volume= 107 | issue= 5 | pages= 669-89; quiz 690 | pmid=22525303 | doi=10.1038/ajg.2012.48 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22525303  }} </ref>
-HCV antibodies from the mother may persist in infants until 15 months of age. If an early [[diagnosis]] is desired, testing for HCV RNA can be performed between the ages of 2 and 6 months, with a repeat test done independent of the first test result. If a later diagnosis is preferred, an anti-HCV test can performed after 15 months of age. Most infants infected with HCV at the time of birth have no [[symptoms]] and do well during childhood. There is no evidence that [[breast-feeding]] spreads HCV. To be cautious, an infected mother should avoid breastfeeding if her nipples are cracked and bleeding.<ref>{{cite journal | author = Mast E | title = Mother-to-infant hepatitis C virus transmission and breastfeeding. | journal = Adv Exp Med Biol | volume = 554 | issue = | pages = 211-6 | year = | id = PMID 15384578}}</ref>
+'''''{{fontcolor|#4479BA|Partial Response}}'''''<br>
+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.<ref name="pmid22525303">{{cite journal| author=Yee HS, Chang MF, Pocha C, Lim J, Ross D, Morgan TR et al.| title=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. | journal=Am J Gastroenterol | year= 2012 | volume= 107 | issue= 5 | pages= 669-89; quiz 690 | pmid=22525303 | doi=10.1038/ajg.2012.48 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22525303  }} </ref>
-==Adverse Effects==
+'''''{{fontcolor|#4479BA|Relapse}}'''''<br>
-===Interferon therapy===
+It is defined as undetectable viremia during treatment and/or at the end of treatment, but subsequent viremia after cessation of treatment.<ref name="pmid22525303">{{cite journal| author=Yee HS, Chang MF, Pocha C, Lim J, Ross D, Morgan TR et al.| title=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. | journal=Am J Gastroenterol | year= 2012 | volume= 107 | issue= 5 | pages= 669-89; quiz 690 | pmid=22525303 | doi=10.1038/ajg.2012.48 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22525303  }} </ref> In most cases, virological relapse occurs in the first 12 weeks after discontinuation of therapy. Late relapses, beyond 24 weeks, are extremely uncommon.<ref name="pmid19330875">{{cite journal| author=Ghany MG, Strader DB, Thomas DL, Seeff LB, American Association for the Study of Liver Diseases| title=Diagnosis, management, and treatment of hepatitis C: an update. | journal=Hepatology | year= 2009 | volume= 49 | issue= 4 | pages= 1335-74 | pmid=19330875 | doi=10.1002/hep.22759 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19330875  }} </ref>
-Most persons have flu-like symptoms (fever, chills, headache, muscle and joint aches, fast heart rate) early in treatment, but these lessen with continued treatment. Later side effects may include tiredness, hair loss, low blood count, trouble with thinking, moodiness, and depression. Severe side effects are rare (seen in less than 2 out of 100 persons). These include thyroid disease, depression with suicidal thoughts, seizures, acute heart or kidney failure, eye and lung problems, hearing loss, and blood infection. Although rare, deaths have occurred due to liver failure or blood infection, mostly in persons with cirrhosis. An important side effect of interferon is worsening of liver disease with treatment, which can be severe and even fatal. Interferon dosage must be reduced in up to 40 out of 100 persons because of severity of side effects, and treatment must be stopped in up to 15 out of 100 persons. Pregnant women should not be treated with interferon.
+'''''{{fontcolor|#4479BA|Non-response}}'''''<br>
+It is defined as detectable HCV RNA throughout treatment.<ref name="pmid22525303">{{cite journal| author=Yee HS, Chang MF, Pocha C, Lim J, Ross D, Morgan TR et al.| title=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. | journal=Am J Gastroenterol | year= 2012 | volume= 107 | issue= 5 | pages= 669-89; quiz 690 | pmid=22525303 | doi=10.1038/ajg.2012.48 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22525303  }} </ref><br><br>
-===Combination (ribavirin + interferon) treatment===
+===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.<ref name="aasld2014">AASLD/IDSA/IAS–USA. Recommendations for testing, managing, and treating hepatitis C. http://www.hcvguidelines.org. Accessed July 27, 2014.</ref> The guidelines do not yet address the monitoring of patients who are on or have completed therapy. The treatment is according below tables.<br>
-In addition to the side effects due to interferon described above, ribavirin can cause serious anemia (low red blood cell count) and can be a serious problem for persons with conditions that cause anemia, such as kidney failure. In these persons, combination therapy should be avoided or attempts should be made to correct the anemia. Anemia caused by ribavirin can be life-threatening for persons with certain types of heart or blood vessel disease. Ribavirin causes birth defects and pregnancy should be avoided during treatment. Patients and their healthcare providers should carefully review the product manufacturer information prior to treatment.
+=== HCV Guidance: Recommendations for Testing, Managing, and Treating Hepatitis C; by Infectious Disease Society of America <ref name="urlRecommendations for Testing, Managing, and Treating Hepatitis C | HCV Guidance">{{cite web |url=https://www.hcvguidelines.org/ |title=Recommendations for Testing, Managing, and Treating Hepatitis C &#124; HCV Guidance |format= |work= |accessdate=}}</ref> ===
+*International guidelines recommend direct-acting antiviral [[treatment]] to be initiated without delay among [[patients]] with clinically significant extra[[liver|hepatic]] manifestations of [[chronic]] [[hepatitis C]].<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>
+{| class="wikitable" style="width: 80%;"
+|-
+| colspan="3" align="center" style="background:#4479BA; color: #FFFFFF;" + |'''Recommended and alternative regimens listed by evidence level and alphabetically for Treatment-Naive Genotype 1a Patients Without Cirrhosis'''
+|-
+| bgcolor="#bbbbbb" |RECOMMENDED
+| bgcolor="#bbbbbb" |DURATION
+| bgcolor="#bbbbbb" |RATING
+|-
+| Daily fixed-dose combination of [[Elbasvir and grazoprevir|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)<sup>b</sup>
+| 8 weeks
+| I, A
+|-
+| Daily fixed-dose combination of [[Ledipasvir / sofosbuvir|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 / velpatasvir|sofosbuvir (400 mg)/velpatasvir (100 mg)]]
+| 12 weeks
+| I, A
+|-
+| bgcolor="#bbbbbb" |ALTERNATIVE
+| bgcolor="#bbbbbb" |DURATION
+| bgcolor="#bbbbbb" |RATING
+|-
+| Daily fixed-dose combination of [[Ombitasvir, paritaprevir, and ritonavir|paritaprevir]] (150 mg)/[[ritonavir]] (100 mg)/[[Ombitasvir, paritaprevir, and ritonavir|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 and grazoprevir|elbasvir]] (50 mg)/[[Elbasvir and grazoprevir|grazoprevir]] (100 mg) with weight-based ribavirin for patients with baseline NS5A RASsa for [[Elbasvir and grazoprevir|elbasvir]]
+| 16 weeks
+| IIa, B
+|-
+| colspan="3" bgcolor="#bbbbbb" |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.
-===Treatment for symptoms or side effects due to antiviral treatment===
+c The dose of daclatasvir may need to increase or decrease when used concomitantly with cytochrome P450 3A/4 inducers and inhibitors, respectively.
+|}
-You should report what you are feeling to your doctor. Some side effects may be reduced by giving interferon at night or lowering the dosage of the drug. In addition, flu-like symptoms can be reduced by taking acetaminophen before treatment.
+=== Treatment-Naive Genotype 1a With Compensated Cirrhosis ===
+{| class="wikitable"
+| colspan="3" align="center" style="background:#4479BA; color: #FFFFFF;" + |'''Recommended and alternative regimens listed by evidence level and alphabetically for Treatment-Naive Genotype 1a Patients With Compensated Cirrhosis'''
+|-
+| bgcolor="#bbbbbb" |RECOMMENDED
+| bgcolor="#bbbbbb" |DURATION
+| bgcolor="#bbbbbb" |RATING
+|-
+| Daily fixed-dose combination of [[Elbasvir and grazoprevir|elbasvir]] (50 mg)/[[Elbasvir and grazoprevir|grazoprevir]] (100 mg) for patients without baseline NS5A RASsb for [[Elbasvir and grazoprevir|elbasvir]]
+| 12 weeks
+| I, A
+|-
+| Daily fixed-dose combination of glecaprevir (300 mg)/pibrentasvir (120 mg)<sup>c</sup>
+| 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
+|-
+| bgcolor="#bbbbbb" |ALTERNATIVE
+| bgcolor="#bbbbbb" |DURATION
+| bgcolor="#bbbbbb" |RATING
+|-
+| Daily fixed-dose combination of [[Elbasvir and grazoprevir|elbasvir]] (50 mg)/[[Elbasvir and grazoprevir|grazoprevir]] (100 mg) with weight-based [[ribavirin]] for patients with baseline NS5A RASsb for [[elbasvir]]
+| 16 weeks
+| IIa, B
+|-
+| colspan="3" bgcolor="#bbbbbb" |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.
-The Food and Drug Administration has approved the use of the combination anti-viral therapy for the treatment of hepatitis C in children 3 to 17 years old.
+c This is a 3-tablet coformulation.
+|}
-==Recommendations for Assessment Prior to Treatment and Monitoring During and After Therapy: AASLD Practice Guidelines 2009<ref name="pmid19554546">{{cite journal |author=Swan T, Curry J |title=Comment on the updated AASLD practice guidelines for the diagnosis, management, and treatment of hepatitis C: treating active drug users |journal=[[Hepatology (Baltimore, Md.)]] |volume=50 |issue=1 |pages=323–4; author reply 324–5 |year=2009 |month=July |pmid=19554546 |doi=10.1002/hep.23077 |url=http://dx.doi.org/10.1002/hep.23077 |accessdate=2012-02-21}}</ref>==
+=== Treatment-Naive Genotype 1b Without Cirrhosis ===
-{{cquote|
+{| class="wikitable"
-'''1.''' Treatment decisions should be individualized based on the severity of liver disease, the potential for serious side effects, the likelihood of treatment response, the presence of comorbid conditions, and the patient’s readiness for treatment ''(Class IIa, Level C)''.
+| colspan="3" align="center" style="background:#4479BA; color: #FFFFFF;" + |'''Recommended and alternative regimens listed by evidence level and alphabetically for Treatment-Naive Genotype 1b Patients Without Cirrhosis'''
-'''2.''' For patients in whom liver histology is available, treatment is indicated in those with bridging ﬁbrosis or compensated cirrhosis provided they do not have contraindications to therapy ''(Class I, Level B)''.
+|-
+| bgcolor="#bbbbbb" |RECOMMENDED
+| bgcolor="#bbbbbb" |DURATION
+| bgcolor="#bbbbbb" |RATING
+|-
+| Daily fixed-dose combination of [[Elbasvir and grazoprevir|elbasvir]] (50 mg)/[[Elbasvir and grazoprevir|grazoprevir]] (100 mg)
+| 12 weeks
+| I, A
+|-
+| Daily fixed-dose combination of [[Elbasvir and grazoprevir|glecaprevir]] (300 mg)/pibrentasvir (120 mg)<sup>a</sup>
+| 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
+|-
+| bgcolor="#bbbbbb" |ALTERNATIVE
+| bgcolor="#bbbbbb" |DURATION
+| bgcolor="#bbbbbb" |RATING
+|-
+| Daily fixed-dose combination of [[Ombitasvir, paritaprevir, and ritonavir|paritaprevir]] (150 mg)/[[ritonavir]] (100 mg)/[[Ombitasvir, paritaprevir, and ritonavir|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
+|-
+| colspan="3" bgcolor="#bbbbbb" | 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.
+|}
-'''3.''' The optimal therapy for chronic HCV infection is the combination of peginterferon alfa and ribavirin ''(Class I, Level A)''.
+=== Treatment-Naive Genotype 1b With Compensated Cirrhosis ===
+{| class="wikitable"
+| colspan="3" align="center" style="background:#4479BA; color: #FFFFFF;" + |'''Recommended and alternative regimens listed by evidence level and alphabetically for Treatment-Naive Genotype 1b Patients With Compensated Cirrhosis'''
+|-
+| bgcolor="#bbbbbb" |RECOMMENDED
+| bgcolor="#bbbbbb" |DURATION
+| bgcolor="#bbbbbb" |RATING
+|-
+| Daily fixed-dose combination of [[Elbasvir and grazoprevir|elbasvir]] (50 mg)/[[Elbasvir and grazoprevir|grazoprevir]] (100 mg)
+| 12 weeks
+| I, A
+|-
+| Daily fixed-dose combination of [[Elbasvir and grazoprevir|glecaprevir]] (300 mg)/pibrentasvir (120 mg)<sup>b</sup>
+| 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
+|-
+| bgcolor="#bbbbbb" |ALTERNATIVE
+| bgcolor="#bbbbbb" |DURATION
+| bgcolor="#bbbbbb" |RATING
+|-
+| Daily fixed-dose combination of [[Ombitasvir, paritaprevir, and ritonavir|paritaprevir]] (150 mg)/[[ritonavir]] (100 mg)/[[Ombitasvir, paritaprevir, and ritonavir|ombitasvir]] (25 mg) with dasabuvir (600 mg) as part of an extended-release regimen or plus twice-daily dosed dasabuvir (250 mg)<sup>c</sup>
+| 12 weeks
+| I, A
+|-
+| colspan="3" bgcolor="#bbbbbb" |a For decompensated cirrhosis, please refer to the appropriate section.
+b This is a 3-tablet coformulation.
-'''4.''' HCV RNA should be tested by a highly sensitive quantitative assay at the initiation of or shortly before treatment and at week 12 of therapy, ''(Class I, Level A)''.
+c Please see statement on FDA warning regarding the use of paritaprevir/ritonavir/ombitasvir ± dasabuvir in patients with cirrhosis.
+|}
-===Genotypes 1 and 4 HCV infection===
+=== Treatment-Naive Genotype 2 Without Cirrhosis ===
-'''1.''' Treatment with peginterferon plus ribavirin should be planned for 48 weeks; the dose for peginterferon alfa-2a is 180 µg subcutaneously per week together with ribavirin using doses of 1,000 mg for those <75 kg in weight and 1,200 mg for those >75 kg; the dose for peginterferon alfa-2b is 1.5 µg/kg subcutaneously per week together with ribavirin using doses of 800 mg for those weighing <65 kg; 1,000 mg for those weighing >65 kg to 85 kg, 1,200 mg for >85 kg to 105 kg, and 1,400 mg for >105 kg ''(Class I, Level A)''.
+{| class="wikitable"
+| colspan="3" align="center" style="background:#4479BA; color: #FFFFFF;" + |'''Recommended and alternative regimens listed by evidence level and alphabetically for Treatment-Naive Genotype 2 Patients Without Cirrhosis'''
-'''2.''' Treatment may be discontinued in patients who do not achieve an early virological response (EVR; >2 log reduction in HCV RNA at week 12 of treatment) ''(Class I, Level A)''.
+|-
+| bgcolor="#bbbbbb" |RECOMMENDED
+| bgcolor="#bbbbbb" |DURATION
+| bgcolor="#bbbbbb" |RATING
+|-
+| Daily fixed-dose combination of [[Elbasvir and grazoprevir|glecaprevir]] (300 mg)/pibrentasvir (120 mg)<sup>a</sup>
+| 8 weeks
+| I, A
+|-
+| Daily fixed-dose combination of [[sofosbuvir]] (400 mg)/velpatasvir (100 mg)
+| 12 weeks
+| I, A
+|-
+| bgcolor="#bbbbbb" |ALTERNATIVE
+| bgcolor="#bbbbbb" |DURATION
+| bgcolor="#bbbbbb" |RATING
+|-
+| Daily [[daclatasvir]] (60 mg)<sup>b</sup> plus [[sofosbuvir]] (400 mg)
+| 12 weeks
+| IIa, B
+|-
+| colspan="3" bgcolor="#bbbbbb" |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.
+|}
-'''3.''' Patients who do not achieve a complete EVR (undetectable HCV RNA at week 12 of treatment) should be re-tested at week 24, and if HCV RNA remains positive, treatment should be discontinued ''(Class I, Level A)''.
+=== Treatment-Naive Genotype 2 With Compensated Cirrhosis ===
+{| class="wikitable"
+| colspan="3" align="center" style="background:#4479BA; color: #FFFFFF;" + |'''Recommended and alternative regimens listed by evidence level and alphabetically for Treatment-Naive Genotype 2 Patients With Compensated Cirrhosis'''
-'''4.''' For patients with genotype 1 infection who have delayed virus clearance (HCV RNA test becomes negative between weeks 12 and 24), consideration should be given to extending therapy to 72 weeks ''(Class IIa, Level B)''.
+|-
+| bgcolor="#bbbbbb" |RECOMMENDED
+| bgcolor="#bbbbbb" |DURATION
+| bgcolor="#bbbbbb" |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)<sup>b</sup>
+| 12 weeks
+| I, B
+|-
+| bgcolor="#bbbbbb" |ALTERNATIVE
+| bgcolor="#bbbbbb" |DURATION
+| bgcolor="#bbbbbb" |RATING
+|-
+| Daily daclatasvir (60 mg)c plus sofosbuvir (400 mg)
+| 16 to 24 weeks
+| IIa, B
+|-
+| colspan="3" bgcolor="#bbbbbb" |a For decompensated cirrhosis, please refer to the appropriate section.
+b This is a 3-tablet coformulation.
-'''5.''' Patients with genotype 1 infection whose treatment continues through 48 to 72 weeks and whose measurement of HCV RNA with a highly sensitive assay is negative at the end of treatment should be retested for HCV RNA 24 weeks later to evaluate for a sustained virological response (SVR; HCV RNA negative 24 weeks after cessation of treatment) ''(Class I, Level A)''
+c The dose of daclatasvir may need to increase or decrease when used concomitantly with cytochrome P450 3A/4 inducers and inhibitors, respectively.
+|}
-===Genotype 2 or Genotype 3 HCV Infection===
+=== Treatment-Naive Genotype 3 Without Cirrhosis ===
-'''1.''' Treatment with peginterferon plus ribavirin should be administered for 24 weeks, using a ribavirin dose of 800 mg ''(Class I, Level A)''.
+{| class="wikitable"
+| colspan="3" align="center" style="background:#4479BA; color: #FFFFFF;" + |'''Recommended and alternative regimens listed by evidence level and alphabetically for Treatment-Naive Genotype 3 Patients Without Cirrhosis'''
+|-
+| bgcolor="#bbbbbb" |RECOMMENDED
+| bgcolor="#bbbbbb" |DURATION
+| bgcolor="#bbbbbb" |RATING
+|-
+| Daily fixed-dose combination of glecaprevir (300 mg)/pibrentasvir (120 mg)<sup>a</sup>
+| 8 weeks
+| I, A
+|-
+| Daily fixed-dose combination of [[sofosbuvir]] (400 mg)/velpatasvir (100 mg)
+| 12 weeks
+| I, A
+|-
+|-
+| bgcolor="#bbbbbb" |ALTERNATIVE
+| bgcolor="#bbbbbb" |DURATION
+| bgcolor="#bbbbbb" |RATING
+|-
+| Daily daclatasvir (60 mg)<sup>b</sup> plus [[sofosbuvir]] (400 mg)
+| 12 weeks
+| I, A
+|-
+| colspan="3" bgcolor="#bbbbbb" |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.
+|}
-'''2.''' Patients whose treatment continues through 24 weeks and whose measurement of HCV RNA with a highly sensitive assay is negative should be retested for HCV RNA 24 weeks later to evaluate for an SVR ''(Class I, Level A)''.
+=== Treatment-Naive Genotype 3 With Compensated Cirrhosis ===
+{| class="wikitable"
+| colspan="3" align="center" style="background:#4479BA; color: #FFFFFF;" + |'''Recommended and alternative regimens listed by evidence level and alphabetically for Treatment-Naive Genotype 3 Patients With Compensated Cirrhosis'''
-'''3.''' Patients with HCV-related cirrhosis who achieve an SVR, regardless of the genotype, should continue to be monitored at 6 to 12 month intervals for the development of HCC ''(Class I'''Bold text'''Ia, Level C)''.}}
+|-
+| bgcolor="#bbbbbb" |RECOMMENDED
+| bgcolor="#bbbbbb" |DURATION
+| bgcolor="#bbbbbb" |RATING
+|-
+| Daily fixed-dose combination of glecaprevir (300 mg)/pibrentasvir (120 mg)<sup>b</sup>
+| 12 weeks
+| I, A
+|-
+| Daily fixed-dose combination of sofosbuvir (400 mg)/velpatasvir (100 mg)<sup>c</sup>
+| 12 weeks
+| I, A
+|-
+| bgcolor="#bbbbbb" |ALTERNATIVE
+| bgcolor="#bbbbbb" |DURATION
+| bgcolor="#bbbbbb" |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 ribavirin<sup>c</sup>
+| 24 weeks
+| IIa, B
+|-
+| colspan="3" bgcolor="#bbbbbb" |a For decompensated cirrhosis, please refer to the appropriate section.
+b This is a 3-tablet coformulation. Please refer to the prescribing information.
-==Recommendations for Retreatment of Persons Who Failed to Respond to Previous Treatment : AASLD Practice Guidelines 2009<ref name="pmid19554546">{{cite journal |author=Swan T, Curry J |title=Comment on the updated AASLD practice guidelines for the diagnosis, management, and treatment of hepatitis C: treating active drug users |journal=[[Hepatology (Baltimore, Md.)]] |volume=50 |issue=1 |pages=323–4; author reply 324–5 |year=2009 |month=July |pmid=19554546 |doi=10.1002/hep.23077 |url=http://dx.doi.org/10.1002/hep.23077 |accessdate=2012-02-21}}</ref>==
+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.
-{{cquote|
-'''1.''' Retreatment with peginterferon plus ribavirin in patients who did not achieve an SVR after a prior full course of peginterferon plus ribavirin is not recommended, even if a different type of peginterferon is administered ''(for relapsers, Class III, Level C; for non-responders, Class III, Level B)''.
-'''2.''' Retreatment with peginterferon plus ribavirin can be considered for non-responders or relapsers who have previously been treated with non-pegylated interferon with or without
+d The dose of daclatasvir may need to increase or decrease when used concomitantly with cytochrome P450 3A/4 inducers and inhibitors, respectively.
-ribavirin, or with peginterferon monotherapy, particularly if they have bridging ﬁbrosis or [[cirrhosis]] ''(Class IIa, Level B)''.
+|}
-'''3.''' Maintenance therapy is not recommended for patients with bridging ﬁbrosis or cirrhosis who have failed a prior course of peginterferon and [[ribavirin]] ''(Class III, Level B)''}}.
+=== Treatment-Naive Genotype 4 Without Cirrhosis ===
+{| class="wikitable"
+| colspan="3" align="center" style="background:#4479BA; color: #FFFFFF;" + |'''Recommended and alternative regimens listed by evidence level and alphabetically for Treatment-Naive Genotype 4 Patients Without Cirrhosis'''
-==Recommendations for Treatment of Persons with Normal Serum Aminotransferase Values: AASLD Practice Guidelines 2009<ref name="pmid19554546">{{cite journal |author=Swan T, Curry J |title=Comment on the updated AASLD practice guidelines for the diagnosis, management, and treatment of hepatitis C: treating active drug users |journal=[[Hepatology (Baltimore, Md.)]] |volume=50 |issue=1 |pages=323–4; author reply 324–5 |year=2009 |month=July |pmid=19554546 |doi=10.1002/hep.23077 |url=http://dx.doi.org/10.1002/hep.23077 |accessdate=2012-02-21}}</ref>==
+|-
-{{cquote|
+| bgcolor="#bbbbbb" |RECOMMENDED
-'''1.''' Regardless of the serum alanine aminotransferase level, the decision to initiate therapy with pegylated interferon and ribavirin should be individualized based on the severity of liver disease by liver biopsy, the potential for serious side effects, the likelihood of response, and the presence of comorbid conditions ''(Class I, Level B)''.
+| bgcolor="#bbbbbb" |DURATION
+| bgcolor="#bbbbbb" |RATING
+|-
+| Daily fixed-dose combination of glecaprevir (300 mg)/pibrentasvir (120 mg)<sup>a</sup>
+| 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 and grazoprevir|elbasvir]] (50 mg)/[[Elbasvir and grazoprevir|grazoprevir]] (100 mg)
+| 12 weeks
+| IIa, B
+|-
+| Daily fixed-dose combination of ledipasvir (90 mg)/[[sofosbuvir]] (400 mg)
+| 12 weeks
+| IIa, B
+|-
+| bgcolor="#bbbbbb" |ALTERNATIVE
+| bgcolor="#bbbbbb" |DURATION
+| bgcolor="#bbbbbb" |RATING
+|-
+| Daily fixed-dose combination of paritaprevir (150 mg)/ritonavir (100 mg)/ombitasvir (25 mg) and weight-based ribavirin
+| 12 weeks
+| I, A
+|-
+| colspan="3" bgcolor="#bbbbbb" |a This is a 3-tablet coformulation.
+|}
-'''2.''' The treatment regimen for HCV-infected persons with normal aminotransferase levels should be the same as that used for persons with elevated serum aminotransferase levels ''(Class I, Level B)''.}}
+=== Treatment-Naive Genotype 4 With Compensated Cirrhosis ===
+{| class="wikitable"
+| colspan="3" align="center" style="background:#4479BA; color: #FFFFFF;" + |'''Recommended and alternative regimens listed by evidence level and alphabetically for Treatment-Naive Genotype 4 Patients With Compensated Cirrhosis'''
+|-
+| bgcolor="#bbbbbb" |RECOMMENDED
+| bgcolor="#bbbbbb" |DURATION
+| bgcolor="#bbbbbb" |RATING
+|-
+| Daily fixed-dose combination of [[sofosbuvir]] (400 mg)/velpatasvir (100 mg)
+| 12 weeks
+| I, A
+|-
+| Daily fixed-dose combination of [[Elbasvir and grazoprevir|glecaprevir]] (300 mg)/pibrentasvir (120 mg)<sup>b</sup>
+| 12 weeks
+| I, B
+|-
+| Daily fixed-dose combination of [[Elbasvir and grazoprevir|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
+|-
+| bgcolor="#bbbbbb" |ALTERNATIVE
+| bgcolor="#bbbbbb" |DURATION
+| bgcolor="#bbbbbb" |RATING
+|-
+| Daily fixed-dose combination of paritaprevir (150 mg)/ritonavir (100 mg)/ombitasvir (25 mg) and weight-based ribavirin<sup>c</sup>
+| 12 weeks
+| I, A
+|-
+| colspan="3" bgcolor="#bbbbbb" |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 ===
+{| class="wikitable"
+| colspan="3" align="center" style="background:#4479BA; color: #FFFFFF;" + |'''Recommended and alternative regimens listed by evidence level and alphabetically for Treatment-Naive Genotype 5 or 6'''
+|-
+| bgcolor="#bbbbbb" |RECOMMENDED
+| bgcolor="#bbbbbb" |DURATION
+| bgcolor="#bbbbbb" |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
+|-
+| colspan="3" bgcolor="#bbbbbb" |a For decompensated cirrhosis, please refer to the appropriate section.
+b This is a 3-tablet coformulation.
+|}
+===Antiviral Agents===
+{| style="border: 0px; font-size: 90%; margin: 3px;" align="center"
+|+'''''Antiviral Agents Used in the Treatment of Hepatitis C'''''
+! style="background: #4479BA; width: 120px;" | {{fontcolor|#FFF|Agent}}
+! style="background: #4479BA; width: 550px;" | {{fontcolor|#FFF|Recommended Dose}}
+! style="background: #4479BA; width: 550px;" | {{fontcolor|#FFF|Adverse Effects}}
+|-
+| style="padding: 5px 5px; background: #DCDCDC;" |'''PegIFN alfa-2a (Pegasys™)'''
+| style="padding: 5px 5px; background: #F5F5F5;" |
+mcg subcutaneously once weekly<ref name="pmid22525303">{{cite journal| author=Yee HS, Chang MF, Pocha C, Lim J, Ross D, Morgan TR et al.| title=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. | journal=Am J Gastroenterol | year= 2012 | volume= 107 | issue= 5 | pages= 669-89; quiz 690 | pmid=22525303 | doi=10.1038/ajg.2012.48 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22525303  }} </ref>
+| style="padding: 5px 5px; background: #F5F5F5;" |
+''Serious adverse events'': <1%<ref name="pegasys">[[http://www.pegasys.com/hcp/about-pegasys/what?cid=peg_we_F001113_P000517&c=MVPEHCF479P0533&gclid=CPC0iO_U5r8CFc1i7AodqzUAhQ | PEGASYS Prescribing Information. Genentech, Inc. 2013.]]</ref>
+* [[Depression]] with suicide
+* Relapse of drug abuse/overdose
+* Severe bacterial infections ([[osteomyelitis]], [[endocarditis]], [[pyelonephritis]], [[pneumonia]], and [[sepsis]])
+* Hepatic decompensation (2% of patients with HIV coinfection)
+''Common adverse events'': 99% of patients experience at least one of the following<ref name="pegasys">[[http://www.pegasys.com/hcp/about-pegasys/what?cid=peg_we_F001113_P000517&c=MVPEHCF479P0533&gclid=CPC0iO_U5r8CFc1i7AodqzUAhQ | PEGASYS Prescribing Information. Genentech, Inc. 2013.]]</ref>
+* 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]]
+|-
+| style="padding: 5px 5px; background: #DCDCDC;" |'''PegIFN alfa-2b (PEG-Intron™)'''
+| style="padding: 5px 5px; background: #F5F5F5;" |
+.5 mc / kg SC once weekly<ref name="pmid22525303">{{cite journal| author=Yee HS, Chang MF, Pocha C, Lim J, Ross D, Morgan TR et al.| title=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. | journal=Am J Gastroenterol | year= 2012 | volume= 107 | issue= 5 | pages= 669-89; quiz 690 | pmid=22525303 | doi=10.1038/ajg.2012.48 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22525303  }} </ref>
+| style="padding: 5px 5px; background: #F5F5F5;" |
+''Serious adverse events'': <1%<ref name="pegintron">[[http://www.merck.com/product/usa/pi_circulars/p/pegintron/pegintron_pi.pdf | PEGINTRON Prescribing Information. Merck & Co., Inc. 2013.]]</ref>
+* Suicidal/homicidal thoughts
+* Cardiovascular events
+* Loss of vision, [[retinopathy]] including [[macular edema]], retinal artery or vein thrombosis
+* [[Stroke]]
+* Bone marrow toxicity
+* Development or exacerbation of autoimmune disorders
+* [[Colitis]]
+* [[Pancreatitis]]
+* Pulmonary disorders including dyspnea, pulmonary infiltrates, [[pneumonia]], [[bronchiolitis obliterans]]
+* Liver failure especially with [[HIV]] coinfection
+''Common adverse events'': 50% of patients have at least one of the following<ref name="pegintron">[[http://www.merck.com/product/usa/pi_circulars/p/pegintron/pegintron_pi.pdf | PEGINTRON Prescribing Information. Merck & Co., Inc. 2013.]]</ref>
+* Injection site reaction
+* Mood instability and [[depression]]
+* Nausea
+* Fatigue/asthenia
+* Headache
+* Rigors and fevers
+* [[Myalgia]]
+|-
+| style="padding: 5px 5px; background: #DCDCDC;" |'''Ribavirin <br>(Rebetol™, Ribasphere™, Copegus™, RibaPak™)'''
+| style="padding: 5px 5px; background: #F5F5F5;" |
+'''''Genotype 1'''''<br>
+,000 mg (if ≤ 75 kg) or 1,200 mg (if > 75 kg) PO daily divided into two doses<ref name="pmid22525303">{{cite journal| author=Yee HS, Chang MF, Pocha C, Lim J, Ross D, Morgan TR et al.| title=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. | journal=Am J Gastroenterol | year= 2012 | volume= 107 | issue= 5 | pages= 669-89; quiz 690 | pmid=22525303 | doi=10.1038/ajg.2012.48 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22525303  }} </ref>
+'''''Genotype 2 & 3'''''<br>
+PO daily in two divided doses<ref name="pmid22525303">{{cite journal| author=Yee HS, Chang MF, Pocha C, Lim J, Ross D, Morgan TR et al.| title=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. | journal=Am J Gastroenterol | year= 2012 | volume= 107 | issue= 5 | pages= 669-89; quiz 690 | pmid=22525303 | doi=10.1038/ajg.2012.48 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22525303  }} </ref>
+| style="padding: 5px 5px; background: #F5F5F5;" |
+'''Ribavirin is teratogenic and may cause birth defects and/or death of the exposed fetus.'''
+''Serious adverse events'':<ref name="COPEGUS">[[http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021511s023lbl.pdf | COPEGUS Prescribing Information. Genentech, Inc. 2013.]]</ref>
+* Bacterial infection ([[sepsis]], [[osteomyelitis]], [[endocarditis]], [[pyelonephritis]], [[pneumonia]]) (3-5%)
+* Hemolytic anemia (13%)
+* [[Pancreatitis]]
+* Liver failure
+* Pulmonary disease
+''Common adverse events'': <ref name="COPEGUS">[[http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021511s023lbl.pdf | COPEGUS Prescribing Information. Genentech, Inc. 2013.]]</ref>
+* Fatigue/asthenia
+* [[Fever]]
+* Myalgias
+* Headaches
+|-
+| style="padding: 5px 5px; background: #DCDCDC;" |'''Sofosbuvir (Sovaldi™)'''
+| style="padding: 5px 5px; background: #F5F5F5;" |
+mg orally daily
+| style="padding: 5px 5px; background: #F5F5F5;" |
+''Common adverse events'': 20%<ref name="sofosbuvir">[[http://www.gilead.com/~/media/Files/pdfs/medicines/liver-disease/sovaldi/sovaldi_pi.pdf | SOVALDI Prescribing Information. Gilead Sciences, Inc. 2013]]</ref>
+* Fatigue
+* Headache
+* [[Insomnia]]
+* [[Anemia]]
+|-
+| style="padding: 5px 5px; background: #DCDCDC;" |'''Simeprevir (Olysio™)'''
+| style="padding: 5px 5px; background: #F5F5F5;" |
+mg orally daily
+| style="padding: 5px 5px; background: #F5F5F5;" |
+''Common adverse events'': 20%<ref name="simeprevir">[[http://www.olysio.com/shared/product/olysio/prescribing-information.pdf | OLYSIO Prescribing Information. Janssen Products, LP 2013.]]</ref>
+* Rash
+* [[Photosensitivity]]
+* Pruritus
+* Nausea
+* Dyspnea
+|-
+| style="padding: 5px 5px; background: #DCDCDC;" |'''Boceprevir [BOC] (Victrelis™)'''
+| style="padding: 5px 5px; background: #F5F5F5;" |
+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      <ref name="pmid22525303">{{cite journal| author=Yee HS, Chang MF, Pocha C, Lim J, Ross D, Morgan TR et al.| title=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. | journal=Am J Gastroenterol | year= 2012 | volume= 107 | issue= 5 | pages= 669-89; quiz 690 | pmid=22525303 | doi=10.1038/ajg.2012.48 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22525303  }} </ref>
+'''{{fontcolor|red|No longer recommended given the safer profile of newer protease inhibitors}}'''
+| style="padding: 5px 5px; background: #F5F5F5;" |
+Serious adverse events:<ref name="victrelis">[[http://www.merck.com/product/usa/pi_circulars/v/victrelis/victrelis_pi.pdf | VICTRELIS Prescribing Information. Merck & Co., Inc. 2013.]]</ref>
+* Anemia
+* [[Neutropenia]]
+* Pancytopenia<br>
+''Common adverse events'':<ref name="victrelis">[[http://www.merck.com/product/usa/pi_circulars/v/victrelis/victrelis_pi.pdf | VICTRELIS Prescribing Information. Merck & Co., Inc. 2013.]]</ref>
+* [[Fatigue]]
+* Anemia
+* Nausea
+* Headache
+* Dysgeusia
+|-
+| style="padding: 5px 5px; background: #DCDCDC;" |'''Telaprevir [TVR] (Incivek™)'''
+| style="padding: 5px 5px; background: #F5F5F5;" |
+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      <ref name="pmid22525303">{{cite journal| author=Yee HS, Chang MF, Pocha C, Lim J, Ross D, Morgan TR et al.| title=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. | journal=Am J Gastroenterol | year= 2012 | volume= 107 | issue= 5 | pages= 669-89; quiz 690 | pmid=22525303 | doi=10.1038/ajg.2012.48 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22525303  }} </ref>
+'''{{fontcolor|red|No longer recommended given the safer profile of newer protease inhibitors}}'''
+| style="padding: 5px 5px; background: #F5F5F5;" |
+''Serious adverse events'':<ref name="incivek">[[http://pi.vrtx.com/files/uspi_telaprevir.pdf | INCIVEK Prescribing Information. Vertex Pharmaceuticals Incorporated, 2013.]]</ref>
+* [[Stevens-Johnson Syndrome]] (SJS)
+* [[DRESS syndrome|Drug Reaction with Eosinophilia and Systemic Symptoms]] (DRESS)
+* [[Toxic Epidermal Necrolysis]] (TEN)
+* Profound anemia<br>
+''Common adverse events'':
+<ref name="incivek">[[http://pi.vrtx.com/files/uspi_telaprevir.pdf | INCIVEK Prescribing Information. Vertex Pharmaceuticals Incorporated, 2013.]]</ref>
+* Rash
+* Pruritus
+* Fatigue
+* Anemia
+* Nausea and vomiting
+* [[Hemorrhoids]]
+* [[Diarrhea]]
+* Anorectal discomfort
+* [[Dysgeusia]]
+* Anal pruritus
+|-
+|}
+<br>
 ==References==
-{{Reflist|2}}
+{{reflist|2}}
-[[Category:Hepatitis|C]]
 [[Category:Gastroenterology]]
+[[Category:Emergency mdicine]]
 [[Category:Infectious disease]]
+[[Category:Hepatology]]
-{{WH}}
-{{WS}}