Management of Hepatitis C Reviewed CME/CE

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News Author: Laurie Barclay, MD
CME Author: Laurie Barclay, MD

Authors and Disclosures

CME/CE Released: 06/09/2010; Valid for credit through 06/09/2011

June 9, 2010 — Recommendations for diagnosis and treatment of hepatitis C virus (HCV) infection in the family practice setting are provided in a review published in the June 1 issue of the American Family Physician. The review discusses chronic HCV infection in adults but does not cover special groups, such as children, pregnant women, transplant recipients, and persons coinfected with hepatitis B virus or HIV.

"An estimated 170 million persons, or 3 percent of the world's population, are chronically infected with the ...HCV," write Thad Wilkins, MD, and colleagues from Medical College of Georgia in Augusta. "In the United States, the prevalence of hepatitis C antibody is 2 percent in adults 20 years and older, but the prevalence is higher in groups at increased risk (e.g., 8 to 9 percent in persons undergoing hemodialysis). HCV, a single-stranded RNA virus, is transmitted through percutaneous exposure to infected blood."

Serious morbidity, including cirrhosis or hepatocellular carcinoma, and mortality may result from chronic HCV infection.

At-risk populations should be tested for hepatitis C, and positive test results should be confirmed using polymerase chain reaction to quantify virus. In the general population, namely asymptomatic adults who are not at increased risk for infection, the US Preventive Services Task Force (USPSTF) recommends against routine screening for HCV infection. The USPSTF also found insufficient evidence to recommend for or against routine screening of adults at high risk for HCV infection.

Current Treatment

Treatment goals in patients with HCV infection are to delay or prevent progression of fibrosis and to prevent the development of cirrhosis. Current treatment of chronic HCV infection is based on factors predicting sustained virologic response and includes pegylated interferon and ribavirin. The 2 formulations of pegylated interferon approved for treatment of HCV are pegylated interferon alfa-2a and pegylated interferon alfa-2b.

HCV genotype and virologic response to treatment determine the duration of treatment. Patients with genotypes 1 and 4 are treated for 48 weeks, and those with genotypes 2 and 3 are treated for 24 weeks. Multidrug regimens may be developed in the future, using new agents in combination with current therapies.

"The quantitative HCV RNA level is used to assess response to therapy and as a guide to discontinue treatment," the review authors write. "A negative viral load test after four weeks of therapy is predictive of sustained virologic response. In contrast, failure to achieve a 100-fold reduction in viral load by week 12 of therapy has a strong negative predictive value for sustained virologic response and suggests that treatment is likely ineffective and should be stopped."

Absolute contraindications to treatment of HCV infection include active alcohol or substance abuse, active autoimmune hepatitis or other condition known to be exacerbated by interferon and ribavirin, known hypersensitivity to medications used to treat HCV infection, and pregnancy or lack of compliance with adequate contraception. For ribavirin only, renal failure is an absolute contraindication.

Other absolute contraindications to treatment of HCV infection are severe concurrent cardiopulmonary disease; uncontrolled major depressive illness, psychosis, or bipolar disorder; and untreated hyperthyroidism. Relative contraindications to treatment of HCV infection include laboratory values suggesting decompensated cirrhosis, and baseline hematologic and biochemical indices.

Treatment of patients with chronic HCV infection should include counselling them to abstain from alcohol use. Although no vaccine currently exists to prevent HCV infection, persons infected with HCV should be vaccinated against hepatitis A and B. Persons with chronic HCV infection and cirrhosis should periodically undergo ultrasound imaging as surveillance for hepatocellular carcinoma, according to recommendations from the American Association for the Study of Liver Diseases.

Recommendations for Practice

Specific clinical recommendations for practice, and their accompanying level of evidence rating, are as follows:

    * Screening for HCV infection should not be performed in the general population of persons who are not at increased risk (level of evidence, A).
    * Persons with HCV infection should be vaccinated against hepatitis A and B (level of evidence, C).
    * Abstinence from alcohol is recommended for persons with chronic HCV infection (level of evidence, C).
    * Persons with chronic HCV infection and cirrhosis should avoid hepatotoxic drugs (level of evidence, C).
    * For persons with chronic HCV infection and cirrhosis, surveillance for hepatocellular carcinoma should be considered (level of evidence, C).
    * For chronic HCV infection, combination of pegylated interferon and ribavirin is the standard treatment (level of evidence, C, because the outcome is a surrogate marker, namely sustained virologic response, rather than mortality).

"Other interferons (consensus interferon and albinterferon alfa-2b) and ribavirin alternatives (taribavirin) are being developed to improve the effectiveness, safety, and tolerability of therapy for chronic HCV infection," the review authors conclude. "New protease inhibitors (telaprevir and boceprevir) are actively being investigated in phase 3 clinical trials. In the future, multidrug regimens will probably be used in combination with interferon and ribavirin."

The review authors have disclosed no relevant financial relationships.

Am Fam Physician. 2010;81:1351-1357. Abstract

Additional Resource

The Centers for Disease Control and Prevention has a helpful online resource on HCV called “Hepatitis C Information for Health Professionals.”
Clinical Context

Approximately 2% of US adults and 3% of the world's population are positive for antibody to HCV, a virus causing chronic bloodborne infection. In groups at increased risk, prevalence is higher and may be 8% to 9% in patients receiving hemodialysis.

The most common sources of HCV transmission include exposure to blood products before HCV testing procedures were routine; sharing contaminated needles used to inject illicit drugs; and reuse of incompletely sterilized needles, syringes, or other medical equipment. There are 9 genetically distinct genotypes of HCV. In the United States, genotype 1 accounts for 72% of patients with HCV infection; genotype 2 for 16% to 19%; and genotype 3 for 8% to 10%.
Study Highlights

    * The USPSTF recommends against routine screening for HCV infection in the general population of persons who are not at increased risk.
    * The USPSTF found insufficient evidence to recommend for or against routine screening of adults at high risk for HCV infection.
    * The review authors recommend testing at-risk populations for HCV and confirming positive test results using polymerase chain reaction to quantify virus.
    * Treatment of HCV aims to delay or prevent progression of fibrosis and to prevent cirrhosis.
    * Combination of pegylated interferon and ribavirin is the standard treatment of chronic HCV infection.
    * Pegylated interferon alfa-2a and pegylated interferon alfa-2b are the 2 formulations of pegylated interferon approved for treatment of HCV.
    * Treatment duration is determined by HCV genotype and virologic response to treatment.
    * For HCV genotypes 1 and 4, treatment duration is 48 weeks, and for genotypes 2 and 3, treatment duration is 24 weeks.
    * Response to treatment and indications to discontinue treatment are based on quantitative HCV RNA level.
    * Negative viral load test result after 4 weeks of treatment predicts sustained virologic response.
    * Failure to achieve a 100-fold reduction in viral load by week 12 of treatment has a strong negative predictive value for sustained virologic response and suggests that treatment is likely ineffective and should be stopped.
    * Persons with HCV infection should be vaccinated against hepatitis A and B.
    * Persons with chronic HCV infection should abstain from alcohol and avoid hepatotoxic drugs.
    * Surveillance for hepatocellular carcinoma with use of ultrasound imaging may be indicated for persons with chronic HCV infection and cirrhosis.

Clinical Implications

    * The USPSTF recommends against routinely screening for HCV infection in the general population of persons who are not at increased risk. The review authors recommend testing at-risk populations for HCV and confirming positive test results using polymerase chain reaction to quantify virus.
    * Combination of pegylated interferon and ribavirin is the standard treatment of chronic HCV infection. Response to treatment and indications to discontinue treatment are based on quantitative HCV RNA level. Multidrug regimens may be developed in the future, using new agents in combination with current therapies.

CME Test

Questions answered incorrectly will be highlighted.
According to the review by Wilkins and colleagues, which of the following statements about screening practices for HCV infection is correct?
The USPSTF recommends routine screening for HCV infection in the general population
The USPSTF found conclusive evidence to recommend for routine screening of adults at high risk for HCV infection
The review authors recommend against testing at-risk populations for HCV
Polymerase chain reaction testing can be used to quantify HCV virus
According to the review by Wilkins and colleagues, which of the following statements about treatment and management practices for HCV infection is not correct?
Treatment goals for HCV are to delay or prevent progression of fibrosis and to prevent cirrhosis
Combination of pegylated interferon and ribavirin is the standard treatment of chronic HCV infection
For HCV genotypes 1 and 4, treatment duration is 24 weeks
Negative viral load test result after 4 weeks of treatment predicts sustained virologic response

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Authors and Disclosures

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Medscape, LLC encourages Authors to identify investigational products or off-label uses of products regulated by the US Food and Drug Administration, at first mention and where appropriate in the content.
Author(s)
Laurie Barclay, MD

Freelance writer and reviewer, Medscape, LLC

Disclosure: Laurie Barclay, MD, has disclosed no relevant financial relationships.
Editor(s)
Brande Nicole Martin

CME Clinical Editor, Medscape, LLC

Disclosure: Brande Nicole Martin has disclosed no relevant financial relationships.
CME Author(s)
Laurie Barclay, MD

Freelance writer and reviewer, Medscape, LLC

Disclosure: Laurie Barclay, MD, has disclosed no relevant financial relationships.
CME Reviewer / Nurse Planner
Laurie E. Scudder, DNP, NP

Accreditation Coordinator, Continuing Professional Education Department, Medscape, LLC; Clinical Assistant Professor, School of Nursing and Allied Health, George Washington University, Washington, DC; Nurse Practitioner, School-Based Health Centers, Baltimore City Public Schools, Baltimore, Maryland

Disclosure: Laurie E. Scudder, DNP, NP, has disclosed no relevant financial relationships.
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CME/CE Information

CME/CE Released: 06/09/2010; Valid for credit through 06/09/2011
Target Audience

This article is intended for primary care clinicians, gastroenterologists, and other specialists caring for adults with hepatitis C virus infection.
Goal

The goal of this activity is to provide medical news to primary care clinicians and other healthcare professionals in order to enhance patient care.
Learning Objectives

Upon completion of this activity, participants will be able to:

   1. Describe screening practices for hepatitis C virus infection, based on a family-practice review.
   2. Describe treatment and management practices for hepatitis C virus infection, based on a family-practice review.

Credits Available

Physicians - maximum of 0.25 AMA PRA Category 1 Credit(s)™

Family Physicians - maximum of 0.25 AAFP Prescribed credit(s)

Nurses - 0.50 ANCC Contact Hour(s) (0 contact hours are in the area of pharmacology)

All other healthcare professionals completing continuing education credit for this activity will be issued a certificate of participation.

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