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Management and Treatment of Hepatitis C Viral Infection: Monitoring Treatment Safety and Efficacy

for Health Care Providers

Monitoring Treatment Safety and Efficacy

Treatment Monitoring

Almost all patients receiving hepatitis C antiviral therapy will experience some treatment-related adverse effects. Common adverse effects of therapy include flu-like symptoms, fatigue, bone marrow suppression, mood disorders, gastrointestinal upset, dermatological reactions, and alopecia.

Close clinical and laboratory monitoring is crucial throughout treatment. Poor tolerability can lead to early treatment discontinuation. Clinicians can promote adherence by counseling patients on the recognition and management of treatment-related adverse effects. Patients should be reassured that most treatment-related adverse effects can be treated or minimized. (See Hepatitis C Treatment Side Effect Management Tips.)

Periodic laboratory monitoring is necessary in all patients on antiviral therapy (Table 4). Increasing the frequency of testing is advised in patients with significant reductions in white blood cell count, hematocrit, or platelet count or in those who experience significant clinical adverse events. Quantitative and/or qualitative HCV RNA should be performed at 4, 12, and 24 wk on treatment, at the end of treatment, and 24 wk after completion of therapy (section "On-Treatment Predictors"). Patients with a history of depression and substance use should be followed closely. Standardized screening instruments can be used to supplement the clinical exam (section "Psychiatric Assessment").

RECOMMENDATIONS FOR TREATMENT MONITORING

1. Patients should be monitored for HCV treatment-related adverse effects at intervals of 1-2 wk early in the course of therapy, and at intervals of 1-2 months during treatment once adverse effects stabilize (II-1).

2. Patient adherence to therapy should be assessed at every visit (III).

3. Serum markers of biochemical and virological response should be measured, and treatment-related adverse effects should be monitored at intervals as outlined in Table 4 (II-1).

4. Quantitative and/or qualitative virological assays should be performed at 4, 12, and 24 wk on therapy, end of treatment, and at 24 wk after treatment completion (II-1).

5. Patients should be evaluated for depression and suicidal ideations at each visit (II-3).

6. Patients should be counseled about avoiding pregnancy by using two forms of contraception during treatment as well as for 6 months posttreatment, and pregnancy tests should be performed as indicated in Table 4 (III).

7. Patients should be assessed for alcohol intake and illicit drug use at every visit (III).

Dose Modifications

Peginterferon alfa and ribavirin dose reductions are outlined in Table 8 and Table 9. In practice, peginterferon alfa dose reductions are done in a step-wise approach (e.g., for peginterferon alfa-2a from 180 mcg to 135 mcg to 90 mcg, and for peginterferon alfa-2b from 1.5 mcg/kg to 1.0 mcg/kg to 0.5 mcg/kg). In practice, ribavirin dose reductions often occur in 200-mg decrements (Table 9). Limiting dose reductions may improve SVR, especially for patients with genotype 1 infection. In a retrospective analysis, genotype 1-infected patients who received at least 80% of interferon and ribavirin doses for at least 80% of the intended duration were more likely to achieve SVR than those who did not fulfill these criteria (74) . The timing and degree of both peginterferon alfa and ribavirin dose reduction on SVR are under analysis (31) . Supportive therapies such as growth factors to minimize dose reduction may be considered (section "Growth Factors").

Table 8. General Guidelines for Peginterferon Dose Reduction or Discontinuation
LABORATORY VALUESMANUFACTURER PACKAGE INSERT RECOMMENDATIONS

ANC = absolute neutrophil count; WBC = white blood cell counts

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

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

WBC
<1.5 x 109/LReduce peginterferon alfa-2b dose by 50% and reevaluate
<1.0 x 109/LDiscontinue peginterferon alfa-2b until resolution
ANC*
<0.75 x 109/LPeginterferon alfa-2a: reduce dose to 135 mcg/wk and reevaluate
Peginterferon alfa-2b: reduce dose by 50% and reevaluate
<0.50 x 109/LDiscontinue peginterferon alfa until resolution
Platelets†
<80 k/mm3Peginterferon alfa-2b: reduce dose by 50% and reevaluate
<50 k/mm3Peginterferon alfa-2a: reduce dose to 90 mcg/wk and reevaluate
Peginterferon alfa-2b: discontinue until resolution
<25 k/mm3Peginterferon alfa-2a: discontinue until resolution

(Print table 8)

Table 9. General Guidelines for Ribavirin Dose Reduction or Discontinuation
PARAMETERRECOMMENDATION
In stable underlying cardiac disease, reduce ribavirin by 200 mg/day for ≥2 g/dL drop in Hb over a four-wk period. If the Hb level is <12 g/dL after four wk of dose reduction, discontinue ribavirin until resolution and reevaluation.
Hemoglobin (Hb)
<11.0 but >10 g/dLNo change in ribavirin dose if patient has minimal symptoms
In a symptomatic patient, consider ribavirin dose reduction by 200 mg/day and/or starting an erythropoietic growth factor
<10.0 but >8.5 g/dLDecrease ribavirin by 200 mg/day and/or consider starting an erythropoietic growth factor
Recheck Hb levels at least every 2 wk or more frequently if indicated
<8.5 g/dLDiscontinue until resolution

(Print table 9)

RECOMMENDATION FOR DOSE MODIFICATIONS

1. Peginterferon alfa and/or ribavirin doses should be reduced in response to decreases in white blood cells, neutrophils, platelets, or hemoglobin (Hb), as outlined in Table 8 and Table 9 (II-1).