Q. What treatments are available for HCV?

A. Current treatment for HCV is either standard interferon or PEG-Intron (pegylated interferon alfa-2b) given subcutaneously with ribavirin orally for 24-48 weeks. Combination therapy with PEG-Intron and ribavirin is the current standard of care for the treatment of HCV. Despite PEG-Intron’s increased effectiveness over the standard formulation, some insurance providers will not reimburse for its use due to increased cost. Plasma levels of interferon tend to fluctuate more with standard-of-care therapy, resulting in less ability to suppress viral activity. Side effects associated with PEG-Intron and standard interferon are similar. However, patients may experience more application site reactions with PEG-Intron. 

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Ribavirin alone is not effective for the treatment of chronic HCV. The FDA-approved dosage of ribavirin when administered with pegylated interferon is 800 mg per day in divided doses. However, studies have indicated that a weight-based approach yields a better response rate in patients with genotype 1.7 Recommended dosing of ribavirin with standard interferon therapy is 1,000 mg for those <165 lb and 1200 mg for those >165 lb.

Q. Who should receive treatment?

A. The decision to treat is based on consideration of several factors, including patient age, comorbid factors, risk of cirrhosis, likelihood of response, liver biopsy, and patient’s willingness to undergo therapy. Treatment is not approved for individuals <18 years of age, and patients >60 years should be managed on an individual basis. Many patients may be excluded from therapy because of contraindications. Absolute contraindications to PEG-Intron include past or present psychosis or severe depression, neutropenia and/or thrombocytopenia, organ transplant except for liver, symptomatic heart disease, decompensated cirrhosis, and uncontrolled seizure disorder. Relative contraindications include uncontrolled diabetes mellitus and autoimmune disorders, especially thyroiditis. Absolute contraindications to ribavirin include end-stage renal failure, anemia, hemoglobinopathies, severe heart disease, pregnancy, and unreliable methods of contraception. 

Only patients with detectable serum HCV RNA are candidates for treatment. The histologic results of the liver biopsy should be considered in relation to the supposed duration of disease, clinical status, and biochemical abnormalities when making a therapeutic decision regarding treatment.5 Individuals with moderate or severe necroinflammatory activity and/or fibrosis should be treated. Treatment should not be based on genotype or viral load. However, favorable factors include genotypes 2 and 3, viral load <3.5 million copies/mL, minimal or no fibrosis, female gender, and age <40 years.5 Treatment is strongly favored for patients with HCV who have stage 2 fibrosis and/or fairly recent acquisition of the disease.

Patients with compensated cirrhosis secondary to HCV have a good prognosis and can benefit from treatment with PEG-Intron and ribavirin. Those who do not respond to combination treatment or are not candidates for ribavirin should receive PEG-Intron monotherapy to help reduce the risks of developing hepatocellular carcinoma.

Individuals with cirrhosis should be screened for hepatocellular carcinoma with abdominal ultrasound and
a-fetoprotein. Those with decompensated cirrhosis, as evidenced by biochemical markers, ascites, jaundice, wasting, variceal hemorrhage, or hepatic encephalopathy, should not undergo liver biopsy or be treated. They should be monitored for signs of clinical decompensation and appropriately referred to a liver transplant center. 

Patients with HIV coinfection require a more aggressive approach because of rapid progression of advanced liver disease. No large studies are available on the treatment of chronic HCV in children. Some research has suggested that the response rate in children is similar to that in adults. Treatment of young patients requires further research.

Many clinicians will not treat patients who persist with IV drug use and/or alcohol consumption. Patients who are heavy consumers of alcohol   should not be treated because of alcohol’s propensity to increase viremia and interfere with treatment response. However, limited experience demonstrates feasibility and effectiveness of treating HCV in IV drug users.4 Active IV drug users should be considered for treatment on an individual basis; they should not be excluded automatically from treatment.4

Q. What are the side effects of HCV treatment?

A. Many patients may forgo therapy after learning of the side effects, while others may discontinue therapy after finding the side effects difficult to tolerate. Side effects are usually worse during the first weeks of therapy. Most patients experience flulike symptoms, such as fever, rigors, myalgias, and headache, which can be relieved with acetaminophen. Significant psychiatric side effects have been associated with interferon, including depression, anxiety, insomnia, irritability, impaired concentration, and suicidal ideations. Patients should be evaluated on a regular basis for neuropsychiatric side effects; some may require an antidepressant. Patients with existing depression may need additional treatment by a mental-health professional. 

Diabetes symptoms may worsen with interferon therapy, and some patients may become glucose-intolerant for the first time. Myelosuppression in the form of neutropenia and thrombocytopenia is also associated with interferon-based therapy. Neutropenia is often encountered with PEG-Intron use; it can be treated with granulocyte-stimulating factors. Regardless of which form of interferon is utilized, CBCs should be obtained on a regular basis.

Thyroid dysfunction associated with interferon may occur, usually three to six months after initiation of treatment, and may be irreversible even after treatment is discontinued.8 Thyroid-stimulating hormone determinations are recommended at baseline and every three months thereafter. 

Additional side effects include taste perversion, anorexia, nausea, and reversible alopecia. Patients may also experience such injection site reactions as induration and erythema.

Ribavirin has been associated with significant teratogenic side effects. Two methods of contraception should be used while undergoing treatment and for six months following the cessation of therapy. Regular pregnancy tests should be performed on women of childbearing age. Ribavirin can also cause severe hemolytic anemia. Anemia, the primary dose-limiting toxicity associated with ribavirin, may occur during the first few weeks of treatment. Ribavirin or interferon should be decreased if myelosuppression becomes a significant problem. Other side effects include nausea, nasal congestion, pruritus, and fatigue.

Q. How is treatment success measured?

A. Sustained undetectability of HCV RNA in serum by PCR testing at 24 weeks after the completion of therapy is the gold standard for measuring treatment response. Several major studies have been conducted on response rates, each with varying results. Response rates in genotype 1 with standard and pegylated interferon therapy are 33% and 41%, respectively; in genotypes 2-6, response rates are 73% and 75%. This sustained virologic response appears to be >95% for up to 10 years. Independent predictors of sustained virologic response to interferon/ribavirin therapy include a genotype other than 1, viral load <3.5 million/mL, age <40 years, female gender, and no or mild fibrosis.9 Genotype appears to be the most important factor.

Sustained virologic response is associated with a decreasing incidence of further liver disease.6 The risk of hepatocellular carcinoma is also decreased. Virologic response should be assessed between weeks 12 and 24. If HCV RNA is still detectable, treatment should be discontinued. These patients are considered nonresponders, and further treatment would not likely produce a response. 

Only 15%-20% of nonresponders treated with standard interferon-ribavirin combination therapy achieve a sustained virologic response on re-treatment with PEG-Intron and ribavirin. Patients with genotype 2 or 3 have improved response rates compared with re-treatment rates of genotype 1.4 Extending treatment time does not reduce the relapse rate. Several trials are evaluating the role of maintenance therapy with PEG-Intron in the prevention of progressive liver disease. However, until these results are known, maintenance therapy in nonresponders is considered experimental.

Q. How should patients with HCV be educated?

A. Patients with HCV should be educated on the need to prevent further harm to the liver and reduce the risk of transmitting the virus to others. Patients should not drink alcohol because it can accelerate liver damage. Vaccination against hepatitis A and B is recommended for HCV patients because superinfection can accelerate existing damage. Nonsteroidal anti-inflammatory drugs can contribute to idiosyncratic liver toxicity and should be avoided. Because of its predictable hepatotoxicity in a dose-dependent manner, acetaminophen can be used safely in dosages not exceeding 2 g/day. Patients should not donate blood, organs, tissue, and/or semen. Toothbrushes, razors, and other personal-care articles that may harbor blood should not be shared. Cuts should be covered to prevent spreading infectious blood. Patients should be encouraged to discuss the risk, albeit low, with their sexual partner, and patients with multiple partners should use condoms. 

Women with HCV do not need to avoid pregnancy or breast-feeding. They should, however, be informed of the five percent risk of perinatal transmission. The mode of delivery does not appear to be related to transmission of the virus.

Q. What is the future of HCV treatment?

A. A longer-acting pegylated interferon (Pegasys) was approved for the treatment of adults with chronic HCV in October 2002. In December 2002, the FDA approved Pegasys in combination with Copegus (ribavirin) for the treatment of adults with chronic HCV who have compensated liver disease and have not been previously treated with interferon-α. 

Compared with PEG-Intron’s half-life of 30-50 hours, Pegasys has a half-life of 50-80 hours. It demonstrated improvement in sustained virologic response rates of 51 percent over current therapy in those individuals with genotype 1 and those with cirrhosis. 

The development of an HCV vaccination is also under investigation. Research has met with much difficulty, partly because of the virus’ rapid ability to mutate and the lack of anti-infective protection offered by anti-HCV antibodies. 


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 8. Physicians’ Desk Reference. 56th ed. Montvale, N.J.: Medical Economics Company Inc; 2001:3153.
 9. Poynard T, McHutchison JG, Goodman Z, et al. Is an “a la carte” combination of interferon alfa-2b plus ribavirin regimen possible for the first line treatment in patients with chronic hepatitis C? The ALGOVIR Project Group. Hepatology 31:211, 2000.