Viral Hepatitis

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Management and Treatment of Hepatitis C Viral Infection: Summary

for Health Care Providers

Summary of Current Recommendations

The management of HCV disease is evolving. We have attempted to provide a guide for the care of patients with hepatitis C. It is crucial to facilitate a multidisciplinary team who can respond to and provide HCV-specific care and treatment. Treatment should be provided to individuals who meet criteria for antiviral therapy and who are at greatest risk for progressive liver disease. The relative risks and benefits of beginning therapy immediately, delaying therapy, or deferring treatment indefinitely need to be carefully considered in each patient.

Recommendations in patients being considered for HCV therapy:

  1. All patients with chronic HCV infection should be evaluated as potential candidates for HCV antiviral treatment(III).
  2. Patients should undergo pretreatment assessments as summarized in Table 2 (III).
  3. Patients with more than portal fibrosis, including those with compensated cirrhosis, who lack contraindications, should be offered antiviral treatment (III).
  4. Patients with contraindications summarized in Table 3 should not begin HCV antiviral therapy (III).
  5. Patients should be counseled on their likelihood of achieving SVR prior to initiating therapy (III).

Recommendations for treatment in previously untreated patients:

  1. Peginterferon alfa plus ribavirin is the standard of care for treatment of chronic HCV (I).
  2. The peginterferon alfa-2a standard dose is 180 mcg/wk and the peginterferon alfa-2b standard dose is 1.5 mcg/kg/wk administered subcutaneously in combination with ribavirin (I).
  3. For patients with genotype 1 infection, the ribavirin dose is 1,000 mg/day if ≤75 kg or 1,200 mg/day if >75 kg in combination with peginterferon alfa (I).
  4. For patients with genotype 2 or 3 infection, the ribavirin dose is 800 mg/day in combination with peginterferon alfa (I).

Recommendation for monotherapy with peginterferon alfa:

  1. Peginterferon alfa monotherapy (Table 5) may be used to treat patients with contraindications to ribavirin (Table 3) (III).

Recommendations for virologic end points on treatment:

  1. RVR and EVR should be measured (II-2).
  2. Treatment may be discontinued in those failing to achieve an EVR (II-2).
  3. In patients with advanced liver disease, treatment may be continued even without an EVR, depending on tolerance of therapy (III).

Recommendations for treatment duration in genotype 1 infection:

  1. For patients who achieve RVR, 24 wk of treatment may be sufficient (III).
  2. For patients who fail to achieve RVR but achieve EVR, 48 wk is usually sufficient (I).
  3. For patients without an RVR and/or EVR, extending duration to 72 wk may be beneficial if virus is undetectable by 24 wk of therapy (III).
  4. For patients who continue to have detectable virus at 24 wk, treatment should be discontinued if the goal of therapy is viral eradication (I).

Recommendations for treatment duration in genotype 2 or 3 infection:

  1. Standard treatment duration is 24 wk (I).
  2. In patients with a low pretreatment RNA (≤600,000 IU/mL) who are not tolerating therapy, 16 wk of treatment may be sufficient (I).
  3. For patients with genotype 3 infection and a baseline HCV RNA >600,000 IU/mL or steatosis, treatment beyond 24 wk may improve response (III).

Recommendations in patients with cirrhosis:

  1. Patients with compensated cirrhosis and adequate neutrophil (ANC >1.5 k/mm3) and platelet (>70 k/mm3) counts to tolerate therapy should be treated with peginterferon alfa plus ribavirin at standard doses (II-2).
  2. In patients who do not achieve viral suppression with combination therapy, long-term maintenance therapy with low-dose peginterferon alfa may be considered on an individual basis (III).

Recommendations in nonresponders and relapsers:

  1. For nonresponders and relapsers to interferon with or without ribavirin, retreatment with peginterferon alfa and ribavirin should be considered on an individual basis (II-1).
  2. For nonresponders and relapsers to peginterferon alfa plus ribavirin, retreatment with peginterferon alfa and ribavirin may be considered only if substantial improvements in treatment dose or adherence can be made (III).
  3. If retreatment is undertaken, the duration is at least 48 wk in those who demonstrate viral response on therapy (III).

Recommendations in patients with mild disease:

  1. Treatment should be deferred in patients with minimal inflammation and/or minimal portal fibrosis on liver biopsy, unless the patient elects to undergo therapy with a goal of viral eradication (III).
  2. If treatment is deferred, liver biopsy may be repeated in 3-5 yr if results would change management (III).
  3. In patients with histological evidence of disease progression, treatment should be considered (III).

Recommendations in patients with normal ALT:

  1. Liver biopsy to stage fibrosis should be performed prior to starting treatment regardless of ALT level, especially in patients with genotype 1 infection (III).
  2. Treatment should be considered in patients with more than portal fibrosis on liver biopsy, regardless of ALT values (I).

Recommendation in patients with HCV genotype 4 infection:

  1. Appropriate candidates should be treated with peginterferon alfa-2a 180 mcg/wk or peginterferon alfa-2b 1.5 mcg/kg/wk plus ribavirin 1,000 or 1,200 mg/day for 48 wk (I).

Recommendations in patients >65 yr and/or with comorbid conditions:

  1. In patients with limited life expectancy from significant comorbid conditions, antiviral therapy should be deferred (III).
  2. In patients with significant comorbid conditions that will be exacerbated by peginterferon alfa and ribavirin, treatment should be deferred (III).
  3. In otherwise healthy patients, treatment should be considered regardless of age (III).

Recommendations for patients on methadone:

  1. Patients with ongoing injection drug use should be referred to a substance use specialist and reevaluated for HCV treatment at a later date (III).
  2. Antiviral therapy should be offered to patients enrolled in a methadone maintenance program who meet criteria for therapy (II-1).
  3. HCV treatment should be coordinated with substance abuse specialists (III).

Recommendations in patients with ongoing alcohol use:

  1. Patients should be encouraged to decrease consumption or to abstain (III).
  2. Patients should be referred for behavioral intervention to reduce alcohol use (III).
  3. Antiviral therapy should be offered to patients regardless of prior alcohol use who otherwise meet criteria for therapy (II-2).
  4. Alcohol consumption should be discouraged during antiviral treatment, because alcohol reduces adherence and treatment response (III).

Recommendations in African Americans, obese patients and those with hepatic steatosis:

  1. Antiviral therapy should be offered to patients regardless of race (III).
  2. Patients with a BMI >30 should be considered for antiviral treatment (III).
  3. Comorbid conditions common in obese patients such as diabetes, hypertension, and hyperlipidemia should be well controlled prior to initiation of antiviral therapy (III).

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 (III).
  2. Patients should be treated with peginterferon alfa and ribavirin at doses similar to those with HCV monoinfection (III).
  3. Patients should be treated with peginterferon alfa and ribavirin for at least 48 wk, regardless of genotype (III).
  4. Concomitant use of didanosine (ddI) and ribavirin should be avoided (II-3).
  5. Cytopenias related to HCV treatment are more common, and may require erythropoietin and granulocyte colony stimulating growth factors in order to continue therapy (III).
  6. HIV/HCV coinfected patients with cirrhosis and a Child-Pugh score ≥6 should not receive HCV antiviral therapy (II-3).

Recommendations in patients with renal disease:

  1. Patients should be considered for antiviral therapy with peginterferon alfa at doses modified for renal disease (Table 5) (II-2).
  2. Ribavirin should be avoided with a creatinine clearance <50 mL/min (II-3).

Recommendations in patients with acute HCV infection:

  1. Patients should be observed for a period of 8-12 wk from time of initial exposure in order to monitor for spontaneous resolution of infection (III).
  2. For those who fail to resolve infection spontaneously, treatment should be initiated with peginterferon alfa alone for 24 wk, regardless of genotype (II-1).

Recommendations in patients with decompensated cirrhosis:

  1. Liver transplantation is the optimal treatment in patients with decompensated cirrhosis (II-3).
  2. Antiviral therapy is contraindicated in most patients with decompensated cirrhosis (II-3).
  3. Interferon-based therapy in combination with ribavirin may be considered in patients awaiting liver transplantation with a Child-Pugh score ≤7 and a MELD score ≤18 (II-1).
  4. If antiviral therapy is undertaken, reduced interferon doses should be used and growth factors should be given to counteract treatment-associated cytopenias (III).

Recommendations in patients following solid organ transplantation:

  1. Interferon-based antiviral therapy is contraindicated following heart, lung, or kidney transplantation (II-3).
  2. In patients with biopsy-proven chronic HCV disease following liver transplantation, antiviral therapy with peginterferon alfa and ribavirin for 48 wk may be considered (II-1).
  3. If treatment is given following liver transplantation, peginterferon alfa and ribavirin should be initiated at reduced doses (II-3).
  4. Toxicities of antiviral therapy in liver transplant recipients should be managed with frequent monitoring, dose reductions, and growth factor support (III).
  5. Liver transplant recipients on antiviral therapy should be monitored closely for evidence of rejection and antiviral therapy should be stopped if rejection is documented (II-3).
  6. Preemptive antiviral therapy early posttransplantation in patients without histological recurrence should be avoided (II-3).

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).

Recommendations for dose modification:

  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).

Recommendations for growth factor use:

  1. Erythropoietin may be administered in patients with symptomatic anemia related to ribavirin therapy and/or to limit anemia-related ribavirin dose reductions or discontinuations, particularly in those who are cirrhotic, postliver transplantation, and HIV/HCV coinfected (I).
  2. Erythropoietin may be given preemptively in patients with pretreatment anemia (Hb <11 g/dL) in order to facilitate ribavirin dosing, particularly in those with advanced HCV disease (III).
  3. GCSF should not be given as primary therapy to prevent peginterferon alfa dose reductions (III).
  4. GCSF may be administered in patients who are cirrhotic, postliver transplantation, or HIV/HCV coinfected with an ANC <500/mm3, particularly if neutropenia persists despite peginterferon alfa dose reduction (III).