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Update on the Management and Treatment of Hepatitis C Virus Infection, 2012: Tables

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Update on the Management and Treatment of Hepatitis C Virus Infection

Hepatitis C Resource Center Program
National Hepatitis C Program Office

May 2012

Table 1. Grading system for recommendations adapted from the AASLD Practice Guidelines for the Diagnosis, Management, and Treatment of Hepatitis C
Description
AASLD, American Association for the Study of Liver Diseases; RCT, randomized, controlled trials.
Classification
Class IConditions for which there is evidence and/or general agreement that a given diagnostic evaluation procedure or treatment is beneficial, useful, and effective
Class IIConditions for which there is conflicting evidence and/or a divergence of opinion about the usefulness/efficacy of a diagnostic evaluation, procedure, or treatment
Class IIaWeight of evidence/opinion is in favor of usefulness/efficacy Class IIb Usefulness/efficacy is less well established by evidence/opinion
Class IIbUsefulness/efficacy is less well established by evidence/opinion
IIIConditions for which there is evidence and/or general agreement that a diagnostic evaluation procedure/treatment is not useful/effective, and in some cases, may be harmful
Level of evidence
Level AData derived from multiple RCT or meta-analyses
Level BData derived from a single randomized trial, or nonrandomized studies
Level COnly consensus opinion of experts, case studies, or standard-of-care

Table 2. Pretreatment assessments in patients with chronic HCV infectiona

Necessary

  • Medical history, including complications of liver disease, presence of significant extrahepatic disease, and symptoms of chronic HCV that may diminish quality of life
  • Psychiatric history, including past or ongoing psychiatric, and substance use disorders
  • Screening for depression and alcohol use
  • Biochemical markers of liver injury and assessment of hepatic function, including serum ALT, serum albumin, serum bilirubin (including direct bilirubin), and prothrombin time
  • Hemoglobin, hematocrit, WBC with differential, and platelet count
  • TSH
  • Serum creatinine
  • Serum glucose
  • Uric acid (while receiving TVR)
  • Serum ferritin, iron saturation, and serum ANA
  • Pregnancy test (in women of childbearing age)
  • HIV serology
  • Serum HBsAg, antiHBc, antiHBs, antiHAV (total)
  • Quantitative HCV RNA measurement
  • HCV genotype
  • Previous antiviral therapies and response
  • ECG in patients with preexisting cardiac disease

Recommended

  • Liver biopsy (if results will influence management)
  • IL28B genotype (if results will influence management)
  • Eye exam for retinopathy in patients with diabetes or hypertension
  • Urine toxicology screen for opiates, cocaine, and amphetamines
a ALT, alanine transaminase; ANA, antinuclear antibodies; antiHAV, antibody to hepatitis A virus; antiHBs, antibodies to HBsAg; AntiHBc, antibody to hepatitis b core antigen; ECG, electrocardiogram; HbsAg, hepatitis B surface antigen; HCV, hepatitis C virus; TSH, thyroid-stimulating hormone; TVR, telaprevir; WBC, white blood cell.
Table 3. Antiviral treatment for chronic hepatitis C in adults (32, 33, 34, 35, 57, 58)
Generic
(Trade name)		Recommended doseRecommended dose in renal or hepatic dysfunction
BOC, boceprevir; Clcr, creatinine clearance; HCV, hepatitis C virus; PegIFN, peginterferon; PI, protease inhibitor; PO, orally; RBV, ribavirin; SC, subcutaneous; TVR, telaprevir.
PegIFN alfa-2a (Pegasys®) 180 mcg SC once weekly Clcr <30 ml/min: 135 mcg SC once weekly
Hemodialysis: 135 mcg SC once weekly
PegIFN alfa-2b (PEG-Intron®) 1.5 mc/kg SC once weekly Clcr 30-50 ml/min: reduce dose by 25%
Clcr 10-29 ml/min: reduce dose by 50%
RBV (Copegus®, Rebetol®, Ribasphere®, RibaPak®)

Genotype 1:
1,000 mg (if ≤ 75 kg) or 1,200 mg (if >75 kg) PO daily in two divided doses,

Or

<65 kg: 800 mg PO daily in two divided doses
65-85 kg: 1,000 mg PO daily in two divided doses
>85-105 kg: 1,200 mg PO daily in two divided doses
>105 kg: 1,400 mg PO dailsy in two divided doses

Genotype 2 or 3:
800 PO daily in two divided doses

Clcr 30-50 ml/min: 200 mg PO daily, alternating with 400 mg PO daily
Clcr <30 ml/min: 200 mg PO daily
PIs for treatment of HCV genotype 1
BOC (Victrelis™) 800 mg (4 x 200 mg capsules) PO every 7-9 apart with food in combination with PegIFN-RBV following a 4-week lead-in with PegIFN-RBV Dose adjustments not necessary for renal or hepatic impairment (Child-Pugh <7)
TVR (Incivek™) 750 mg (2 x 375 mg tablets) PO every 7-9 h with food (20 grams fat) for 12 weeks, plus PegIFN-RBV for 24 or 48 weeks Dose adjustments not necessary for renal or hepatic impairment (Child-Pugh <7)

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Table 4. SVR rates in genotype 1-infected patients treated with PegIFN/RBV ± BOC or TVR
Study cohort, NSVR to PI/PegIFN/RBV (arm 1 of trial)SVR to PI/PegIFN/RBV (arm 2 of trial)SVR with PegIFN/RBV
BOC, boceprevir; eRVR, extended rapid virologic response; HCV, hepatitis C virus; PegIFN, peginterferon alfa; PI, protease inhibitor; RBV, ribavirin; RGT, response-guided therapy; SVR, sustained virologic response; TVR, telaprevir.
Treatment-naive
BOC (SPRINT-2), SVR% 63 66 38
N = 1,099 (11) BOC/PegIFN/RBV RGT BOC/PegIFN/RBV 44 weeks PegIFN/RBV 48 weeks
TVR (ADVANCE), SVR% 69 75 44
N = 1,088 (12) TVR for 8 weeks/PegIFN/RBV RGT TVR for 12 weeks/PegIFN/RBV RGT PegIFN/RBV 48 weeks
TVR (ILLUMINATE), SVR% 71 73 NA
N = 540 (49) TVR for 12 weeks/PegIFN/RBV (24 total weeks) if eRVR TVR for 12 weeks/PegIFN/RBV(48 total weeks) if eRVR -
Treatment-experienced
TVR (REALIZE), SVR% overall - -
N = 662 (13) NA 64-66 17
TVR for 12 weeks/PegIFN/RBV (48 weeks total)
Prior relapsers (SVR%) - 83-88 24
Prior partial responders (SVR%) - 54-59 15
Prior null responders (SVR%) - 29-33 5
BOC (RESPOND-2), SVR% overall
N = 403 (14) 59 66 21
BOC/PegIFN/RBV (48 weeks total)
Prior relapsers (SVR%) 69 75 29
Prior partial responders (SVR%) 40 52 7

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Table 5. General guidelines for PegIFN-RBV dose reduction or discontinuation (32, 33, 57, 58)
PegIFN dose recommendationa

ANC, absolute neutrophil count; BOC, boceprevir; GCSF, granulocyte colony-stimulating factor; Hb, hemoglobin; HCV, hepatitis C virus; PegIFN, peginterferon; RBV, ribavirin; TVR, telaprevir; WBC, white blood cell counts.

a Manufacturer package insert recommendations.

b If dose is maintained outside of manufacturer recommendations, monitor ANC more frequently, and counsel patient on neutropenic precautions. In post-liver transplantation or HIV/HCV-coinfected patients who remain neutropenic despite dose reduction, consider starting GCSF until resolution.

c If dose is maintained outside of manufacturer recommendations, monitor platelet counts, and signs or symptoms of unusual bleeding or bruising more frequently.

WBC
<1.5 x 109/l PegIFN alfa-2b: reduce dose to 1 mcg/kg per week,
then to 0.5 mcg/kg per week if needed
<1.0 x 109/l Discontinue PegIFN alfa-2b until resolution
ANCb
<0.75 x 109/lPegIFN alfa-2a: reduce dose to 135 mcg per week
PegIFN alfa-2b: reduce dose to 1 mcg/kg per week,
then to 0.5 mcg/kg per week if needed
<0.50 x 109/l Discontinue PegIFN until resolution
Plateletsc
<50 k/mm3PegIFN alfa-2a: reduce dose to 90 mcg per week
PegIFN alfa-2b: reduce dose to 1 mcg/kg per week,
then to 0.5 mcg/kg per week if needed
<25 k/mm3Discontinue PegIFN until resolution
RBV dose recommendation
Hb
<11.0, but >10 g/dl No change in RBV dose if patient has minimal symptoms
In a symptomatic patient, consider RBV dose reduction
<10.0, but >8.5 g/dl Decrease RBV, consider starting an erythropoietic growth factor
In patients with a cardiac history, reduce RBV dose and reduce PegIFN alfa-2b dose by 50%
<8.5 g/dl Discontinue RBV until resolution
If RBV is stopped for ≥ 7 days or discontinued in patients who are concomitantly receiving BOC or TVR, then BOC or TVR must be permanently discontinued

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Table 6. HCV PI (BOC or TVR): RGT criteria and futility rules (34, 35)
BOC-PegIFN/RBVTVR-PegIFN/RBV
HCV, hepatitis C virus; PegIFN, peginterferon; PI, protease inhibitor; RBV, ribavirin; RGT, response-guided therapy; TVR, telaprevir.
Candidates for RGT Noncirrhotics:
Treatment-naive: 28 weeks
Prior relapser/partial responder: 36 weeks 		Noncirrhotics:
Treatment-naive: 24 weeks
Prior relapser: 24 weeks
Criteria for RGT HCV RNA undetectable (<10-15 IU/ml) weeks 8-24 HCV RNA undetectable (<10-15 IU/ml) weeks 4 and 12
Futility rules (stop all treatment if any of the following occur)

Week 12: HCV RNA ≥100 IU/ml

Or

Week 24: HCV RNA detectable

Or

HCV RNA rebounds at any timepoint (≥1 log10increase from the nadir HCV RNA)

Week 4 or 12: HCV RNA >1,000 IU/ml

Or

Week 24: HCV RNA detectable

Or

HCV RNA rebounds at any timepoint (≥1 log10 increase from the nadir HCV RNA)

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Supplemental Table 1: Treatment Monitoring Guidelines for Patients on Peginterferon-Ribavirin ± Protease Inhibitor (Boceprevir or Telaprevir)
Week

*Intervals may need to be increased based on patient tolerance and response to treatment in patients with significant declines in blood counts, renal insufficiency, diabetes, cirrhosis or other indications.

**Recommended for all patients at baseline and periodically during antiviral treatment in patients with diabetes, hypertension or as needed for visual complaints.

Necessary02481224Every 4-weeks ThereafterEnd-of-Treatment24 weeks Post-treatment
HCV RNA√ √√√√Follow Algorithm for additional timepoints√√
CBC with differential√√√√√√√*√
Liver function tests√√√√√√√*√
Psychiatric/Substance Use Screening√√√√√√√*
Renal panel√ √√*
Glucose√ √√*
TSH√ √√*
Uric acid (if on telaprevir)√√√√√√*√√
Pregnancy test√ √√√√√√√
Recommended
Fundoscopic Exam**√
Urine Toxicology Screen √

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Supplemental Table 2: Telaprevir and Boceprevir Drug-Drug Interactions

(See full table)

Adapted from earlier recommendations: Management and Treatment of Hepatitis C Viral Infection, 2006:

Table 3. Contraindications to HCV Therapy

  • Life-determining extrahepatic disease (malignancy, unstable angina, severe chronic obstructive pulmonary disease)
  • Clinically decompensated liver disease*
  • Uncontrolled autoimmune disorders
  • Pregnancy or planned pregnancy in a patient or the patient's sexual partner or unwillingness to use adequate birth control
  • Documented nonadherence to prior medical treatment or failure to complete HCV disease evaluation appointments and procedures
  • Inability to self-administer or to arrange appropriate administration of parenteral medication
  • Severe uncontrolled psychiatric disease, particularly depression with current suicidal risk~
  • Ongoing problematic injection drug use that interferes with adherence to medical treatment~, **
  • Ongoing heavy alcohol use that interferes with adherence to medical treatment~, **
*Select patients with clinically decompensated liver disease may be candidates for treatment.
~It is crucial that individuals deferred for HCV treatment due to psychiatric or substance use problems are referred for appropriate follow-up services and their eligibility for HCV treatment is reassessed within a reasonable time frame.
**There are no published data supporting a minimum length of abstinence as an inclusion criterion for HCV anti-viral treatment. Patients with active substance or an alcohol use disorder who are willing to participate in a substance use program should be considered for therapy on case-by-case basis.

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