Viral Hepatitis

Quick Links

Veterans Crisis Line Badge
My healthevet badge

Update of the Management and Treatment of Hepatitis C Viral Infection, 2012: Appendix

for Health Care Providers

Appendix

Summary of Recommendations

Recommendation

  1. All patients with chronic HCV infection should be evaluated for HCV antiviral treatment. (Class IIa, Level B)

Recommendation for IL28 genotype testing:

  1. IL28B genotype testing can be performed before PegIFN-RBV therapy with or without a PI, if the information on the probability of treatment response or duration would alter treatment decisions (Class IIa, Level B).

Recommendations in patients being considered for HCV therapy:

  1. Patients should receive pretreatment assessments as summarized in Table 2 (Class I, Level B).
  2. Patients with more than portal fibrosis, including those with compensated cirrhosis, who lack contraindications, should be considered for treatment (Class I, Level B).
  3. Patients should be counseled on their likelihood of achieving SVR, based upon individual factors such as body mass index, genotype, race, stage of fibrosis, and viral load before initiating therapy (Class I, Level B).

Recommendations for therapy for treatment-naive patients with genotype 1 infection:

  1. PegIFN alfa and RBV, in combination with BOC (800 mg orally every 7-9 h with food) or TVR (750 mg orally every 7-9 h with 20 g of fat), is the standard of care for most treatment-naive genotype 1-infected patients (Class I, Level A).
  2. If a TVR-containing regimen is used in treatment-naive noncirrhotic patients who achieve eRVR, TVR should be discontinued at week 12 and PegIFN-RBV should be continued for an additional 12 weeks. If HCV RNA is detectable, but <1,000 IU/ml at treatment week 4, and remains <1,000 IU/ml or becomes undetectable by week 12, TVR should be discontinued at week 12, and PegIFN and RBV can be continued for another 36 weeks (refer to Figure 2; Class I, Level A).
  3. If a TVR-containing regimen is used in treatment-naive cirrhotics who achieve an HCV RNA that is undetectable or <1,000 IU/ml at treatment weeks 4 and 12, TVR should be discontinued at week 12, and PegIFN-RBV can be continued for another 36 weeks (refer to Figure 2; Class I, Level A).
  4. If a BOC-containing regimen is used in treatment-naive noncirrhotics, if HCV RNA declines by ≥ log 10 during the 4-week lead-in, and HCV RNA is undetectable at weeks 8-24, BOC-PegIFN-RBV for 24 weeks is sufficient. If HCV RNA is detectable at week 8, but <100 IU/ml at week 12 and negative at week 24, BOC-PegIFN-RBV should be continued until week 36, followed by PegIFN-RBV alone for 12 more weeks. If HCV RNA declines by <1 log 10 during the lead-in, BOC-PegIFN-RBV can be contined for 44 weeks (refer to Figure 3; Class I, Level A).
  5. If a BOC-containing regimen is used in treatment-naive cirrhotics, 44 weeks of BOC-PegIFN-RBV is required after the 4-week lead-in (refer to Figure 3; Class I, Level A).

Recommendations for treatment of nonresponders and relapsers with genotype 1 infection:

  1. For patients who previously failed PegIFN-RBV, retreatment with BOC or RBV and PegIFN-RBV may be considered, particularly in patients who were relapsers (Class I, Level A).
  2. If a BOC-containing regimen is used for re-treatment of noncirrhotic prior partial responders or relapsers, the recommended treatment duration is 36 weeks if HCV RNA is undetectable from weeks 8-24. If HCV RNA is detectable at week 12, but <100 IU/ml and is undetectable from weeks 24-36, BOC can be discontinued at week 36 and PegIFN-RBV can be continued for an additional 12 weeks (refer to Figure 3; Class I, Level B).
  3. If a BOC-containing regimen is used for re-treatment in cirrhotics, the treatment duration is 48 weeks if HCV RNA is detectable at week 12, but <100 IU/ml, and becomes undetectable from weeks 24-36 (refer to Figure 3; Class I, Level B).
  4. If a BOC-containing regimen is used for re-treatment of prior null responders, the treatment duration is 48 weeks if HCV RNA is detectable at week 12, but <100 IU/ml, and becomes undetectable from weeks 24-36 (refer to Figure 3; Class II, Level C).
  5. If a TVR-containing regimen is used for re-treatment of prior relapsers, and HCV RNA is undetectable from weeks 4 and 12, TVR should be discontinued at week 12 and PegIFN-RBV should be continued for an additional 12 weeks. If HCV RNA is detectable, but <1000 IU/ml at week 4 and/or 12, TVR can be discontinued at week 12, and PegIFN-RBV can be continued for an additional 36 weeks (refer to Figure 2; Class I, Level B).
  6. If a TVR-containing regimen is used for re-treatment of prior partial responders or null responders, and HCV RNA is <1000 IU/ml at weeks 4 and 12, TVR should be discontinued at week 12 and PegIFN alfa plus RBV should be continued for an additional 36 weeks (refer to Figure 2; Class I, Level B).

Recommendations for dose modification:

  1. PegIFN alfa and RBV doses should be reduced in response to decreases in white blood cells, neutrophils, hemoglobin or platelets, as outlined in Table 5 (Class I, Level A).
  2. If RBV is stopped for 7 days or more in patients who are concomitantly receiving BOC or TVR, then the PI also should be permanently discontinued (Class I, Level A).
  3. HCV PIs should be either continued at full dose or discontinued (Class I, Level A).
  4. Initial management of HCV treatment-related anemia should consist of RBV dose reduction in a symptomatic patient with a hemoglobin <10 g/dl, or as clinically indicated. Erythropoietin may be administered in patients with symptomatic anemia related to PegIFN - RBV therapy with or without BOC/TVR to limit anemia-related RBV dose reductions or dose discontinuations (Class II, Level C).
  5. Initial management of HCV treatment-related neutropenia should consist of PegIFN dose reduction for an ANC <750, or as clinically indicated. Granulocyte colony-stimulating factor should not be given as primary therapy to prevent PegIFN alfa dose reductions (Class I, Level C).

Recommendations for treatment monitoring:

  1. Patients should be monitored for treatment-related adverse effects at intervals of at least 2 weeks early in the course of therapy, and at intervals of 1-2 months during treatment as clinically indicated (Class I, Level C).
  2. Patient adherence to therapy should be assessed at every visit (Class I, Level C).
  3. Patients should be evaluated for depression, suicidal ideation, alcohol, and illicit drug use at each visit (Class I, Level C).
  4. Patients should be counseled about avoiding pregnancy by using two forms of contraception during treatment and for 6 months post-treatment, and pregnancy tests should be performed as indicated in (refer to Monitoring Table in Supplementary Materials). If a patient is receiving a BOC- or TVR-containing regimen, two alternative effective methods of contraception, such as intrauterine devices and barrier methods, should be used in at-risk patients and partners, during and for at least 6 months after treatment (Class I, Level B).
  5. Serum markers of biochemical and virologic response should be measured, and treatment-related adverse effects monitored at intervals as outlined (refer to Monitoring Table in Supplementary Materials; Class I, Level C).
  6. In patients receiving TVR-PegIFN-RBV, all treatment should be stopped if any of the following occur: (1) HCV RNA level >1,000 IU/ml at week 4 or 12; or (2) detectable HCV RNA levels at week 24 or at any timepoint thereafter; or (3) HCV RNA rebounds at any timepoint (≥ 1 log10 increase from the nadir HCV RNA) (Class I, Level C).
  7. In patients receiving BOC-PegIFN-RBV, all treatment should be stopped if any of the following occur: (1) HCV RNA level ≥ 100 IU/ml at week 12 with a BOC-containing regimen; or (2) detectable HCV RNA levels at week 24 or at any timepoint thereafter; or (3) HCV RNA rebounds at any timepoint (≥ 1 log10 increase from the nadir HCV RNA; Class I, Level C).
  8. If virologic failure occurs with a BOC- or TVR-containing regimen, the other PI must not be substituted (Class I, Level C).

Recommendations for PegIFN alfa with or without RBV treatment in genotype 1 patients:

  1. PegIFN alfa monotherapy may be used to treat patients with contraindications to RBV (Class I, Level A).
  2. For patients who achieve RVR and have a low baseline viral load (HCV RNA <400,000 IU/ml), 24-weeks of treatment with PegIFN - RBV may be sufficient (Class I, Level B).

Recommendations in patients with mild disease:

  1. Treatment can be deferred in patients with minimal inflammation and/or minimal portal fibrosis on liver biopsy (Class I, Level B).

Recommendations in patients with cirrhosis:

  1. HCV genotype 1-infected patients with compensated cirrhosis (Child-Pugh Class <7), adequate neutrophils (>1.5 k/mm3), and adequate platelet counts (>75 k/mm3) should be considered for treatment with BOC (for 44 weeks) or TVR (for 12 weeks) combined with PegIFN-RBV at standard doses for 48 weeks (Class I, Level B).
  2. Patients with cirrhosis remain at risk for HCC and should undergo routine screening regardless of viral clearance status, in accordance with current guidelines (Class I, Level B).

Recommendation in African Americans:

  1. BOC or TVR combined with PegIFN-RBV is the standard of care for genotype 1-infected African American patients (Class I, Level A).

Recommendations for treatment-naive and -experienced patients with genotype 2 or 3 infection:

  1. Treatment-naive patients should be treated with PegIFN-RBV for 24 weeks (Class I, Level A).
  2. For patients with low viral load (HCV RNA <600,000 IU/ml) and mild fibrosis who achieve a RVR, 12-18 weeks of treatment may be sufficient (Class I, Level A).
  3. For patients with genotype 3 infection and a high HCV RNA (>600,000 IU/ml), steatosis or advanced fibrosis, treatment beyond 24 weeks may improve response (Class I, Level B).
  4. Retreatment duration is 48 weeks (Class I, Level A).

Recommendations in patients with genotype 4 infection:

  1. Appropriate candidates with HCV genotype 4 infection should be treated with PegIFN alfa-2a 180 mcg per week or PegIFN alfa-2b 1.5 mcg/kg per week, plus RBV up to 1,400 mg per day for 48 weeks (Class I, Level A).

Recommendations in patients with decompensated cirrhosis:

  1. Liver transplantation is the treatment of choice in patients with decompensated cirrhosis (Class I, Level B).
  2. Antiviral therapy is contraindicated in most patients with decompensated cirrhosis (Class II, Level B).
  3. IFN-based therapy in combination with RBV may be considered in patients awaiting liver transplantation with a Child-Pugh score <7 and a MELD score ≤ 18 (Class I, Level A).
  4. If antiviral therapy is undertaken, reduced IFN doses should be used and growth factors can be given to counteract treatment-associated cytopenias (Class II, Level B).

Recommendations in patients following solid organ transplantation:

  1. IFN-based antiviral therapy is contraindicated following heart, lung or kidney transplantation (Class III, Level C).
  2. In patients with biopsy-proven chronic HCV disease following liver transplantation, PegIFN-RBV for 48 weeks may be considered (Class IIa, Level B).
  3. Toxicities of antiviral therapy should be managed with frequent monitoring, dose reductions, and growth factor support (Class IIa, Level B).
  4. Post-liver transplant patients on antiviral therapy should be monitored closely for evidence of rejection, and antiviral therapy should be stopped if rejection is documented (Class IIa, Level B).
  5. Pre-emptive antiviral therapy early post-transplantation in patients without histological recurrence should be avoided (Class IIa, Level B).

Recommendations in patients with renal disease:

  1. Patients should be considered for antiviral therapy with IFN (standard or pegylated) with RBV at modified doses (Table 3; Class IIa, Level C).
  2. Antiviral therapy for HCV treatment is not recommended in patients post-renal transplant; however, it may be considered if patients develop fibrosing cholestatic hepatitis (Class III, Level C).

Recommendations in patients with comorbid conditions:

  1. In patients with limited life expectancy from comorbid conditions, antiviral therapy is not recommended (Class I, Level C).
  2. In patients with significant comorbid conditions that will be exacerbated by PegIFN-RBV, treatment should be deferred (Class I, Level C).

Recommendations for patients on methadone:

  1. Antiviral therapy should be offered to patients enrolled in a methadone maintenance program who meet criteria for therapy (Class I, Level A).
  2. Treatment should be coordinated between HCV treatment providers and substance abuse specialists (Class I, Level B).

Recommendations in patients with ongoing alcohol use:

  1. Patients should be encouraged to decrease alcohol consumption or to abstain, and should be referred for behavioral intervention to reduce alcohol use (Class I, Level B).
  2. Antiviral therapy should be offered to patients who are otherwise appropriate candidates, regardless of prior alcohol use (Class I, Level B).
  3. Alcohol consumption should be discouraged during antiviral treatment because alcohol reduces adherence and treatment response (Class I, Level B).

Recommendations in obese patients and those with hepatic steatosis:

  1. Patients with a body mass index >30 should be considered for antiviral treatment (Class I, Level A).
  2. Comorbid conditions common in obese patients such as diabetes, hypertension, and hyperlipidemia should be controlled before initiation of antiviral therapy (Class I, Level C).

Recommendations in patients with HIV-HCV coinfection:

  1. Patients with controlled HIV infection and evidence of liver disease on biopsy should be considered for HCV antiviral therapy (Class I, Level B).
  2. Patients should be treated with PegIFN-RBV at doses similar to those with HCV monoinfection (Class I, Level B).
  3. Patients should be treated with PegIFN-RBV for 48 weeks, regardless of genotype (Class I, Level A).

Recommendations in patients with acute HCV infection:

  1. Patients should be observed for a period of 8-20 weeks from time of initial exposure to monitor for spontaneous resolution of infection (Class I, Level C).
  2. For those who fail to resolve infection spontaneously, treatment should be initiated with PegIFN alfa, with or without RBV for 24-48 weeks, based on genotype and HCV RNA response during therapy (Class I, Level B).