Clinical Evidence Concise

A Publication of BMJ Publishing Group

Hepatitis C (Chronic)

Am Fam Physician. 2008 Jun 15;77(12):1724-1726.

This clinical content conforms to AAFP criteria for evidence-based continuing medical education (EB CME). See CME Quiz on page 1659.

Chronic hepatitis C virus infection is defined as persistent, detectable serum hepatitis C virus RNA for a period greater than six months, with or without derangement in liver function tests.

  • Sixty to 85 percent of persons who are infected with hepatitis C virus will develop chronic hepatitis C, which is now believed to affect 3 percent of the world's population.

  • Complications of chronic hepatitis C virus infection include cirrhosis, compensated and decompensated liver disease, and hepatocellular carcinoma.

  • Many persons with chronic hepatitis C virus remain asymptomatic, including a significant number of those who progress to cirrhosis. Therefore, routine screening of persons in high-risk groups is advisable.

Interferon monotherapy produces a sustained virologic response in treatment-naive persons and persons with cirrhosis or advanced fibrosis.

  • Interferon also improves liver histology, although it may not be effective in preventing hepatocellular carcinoma in persons with cirrhosis.

  • Effectiveness is dependent on duration of treatment, with 12-month treatments appearing to be more effective—but also more likely to produce adverse effects—than six-month treatments.

  • Six mU of interferon administered three times weekly seems to be no more effective at achieving sustained virologic response than 3 mU administered three times weekly, but is more likely to produce adverse effects.

  • Adding ribavirin to interferon regimens further increases the likelihood of achieving sustained virologic response, but it also increases the risk of anemia. Effectiveness of combination therapy depends on genotype. Persons with genotype 1 infections require 12 months of treatment, and persons with genotype 2 or 3 require only six months of treatment.

Peginterferon monotherapy increases the proportion of treatment-naive persons who achieve sustained virologic response compared with standard interferon monotherapy.

  • A dosage of 180 mcg once weekly seems more effective than a dosage of 135 mcg weekly.

  • Adding ribavirin to peginterferon increases the likelihood of achieving sustained virologic response compared with peginterferon alone or standard interferon plus ribavirin.

In persons who were previously nonresponsive to interferon monotherapy, treatment with interferon-alfa plus ribavirin increases the likelihood of achieving sustained virologic response.

  • This effect appears greater when the interferon dosage is higher than 3 mU three times weekly, or the duration of the treatment is 12 months or longer.

  • We did not find any studies examining the effectiveness of peginterferon monotherapy in this population; although, because interferon plus ribavirin is effective, there is consensus that peginterferon plus ribavirin is also likely to be beneficial.

  • In persons who relapse after interferon monotherapy, treatment with interferon plus ribavirin is more likely than interferon treatment alone to achieve sustained virologic response.

  • Again, although we found no studies, there is general consensus that peginterferon plus ribavirin is likely to improve the probability of achieving sustained virologic response.

In persons coinfected with hepatitis C virus and human immunodeficiency virus (HIV), peginterferon plus ribavirin is more likely than standard interferon plus ribavirin treatment to achieve sustained virologic response.

  • We do not know how effective interferon or peginterferon alone is in persons coinfected with hepatitis C virus and HIV.

Clinical Questions

What are the effects of interventions in treatment-naive persons with chronic infection but without liver decompensation?

Beneficial

Interferon

Interferon plus ribavirin

Peginterferon

Peginterferon plus ribavirin

What are the effects of interventions to treat persons with chronic infection, but without liver decompensation, who have not responded to interferon treatment?

Beneficial

Interferon-alfa plus ribavirin

Unknown effectiveness

Interferon retreatment

Peginterferon

Peginterferon plus ribavirin

What are the effects of interventions in persons with chronic infection, but without liver decompensation, who relapse after interferon treatment?

Beneficial

Interferon-alfa plus ribavirin

Interferon (less effective than interferon-alfa plus ribavirin at sustaining virologic response)

Likely to be beneficial

Peginterferon plus ribavirin*

Unknown effectiveness

Peginterferon

What are the effects of interventions in persons with chronic hepatitis C infection, who also have human immunodeficiency virus?

Likely to be beneficial

Interferon-alfa plus ribavirin (increased rates of sustained viral response from baseline, but less effective than peginterferon plus ribavirin) Peginterferon plus ribavirin

Unknown effectiveness

Interferon

Peginterferon


*— We found no randomized controlled trials. Categorization based on consensus.

Clinical Questions

View Table

Clinical Questions

What are the effects of interventions in treatment-naive persons with chronic infection but without liver decompensation?

Beneficial

Interferon

Interferon plus ribavirin

Peginterferon

Peginterferon plus ribavirin

What are the effects of interventions to treat persons with chronic infection, but without liver decompensation, who have not responded to interferon treatment?

Beneficial

Interferon-alfa plus ribavirin

Unknown effectiveness

Interferon retreatment

Peginterferon

Peginterferon plus ribavirin

What are the effects of interventions in persons with chronic infection, but without liver decompensation, who relapse after interferon treatment?

Beneficial

Interferon-alfa plus ribavirin

Interferon (less effective than interferon-alfa plus ribavirin at sustaining virologic response)

Likely to be beneficial

Peginterferon plus ribavirin*

Unknown effectiveness

Peginterferon

What are the effects of interventions in persons with chronic hepatitis C infection, who also have human immunodeficiency virus?

Likely to be beneficial

Interferon-alfa plus ribavirin (increased rates of sustained viral response from baseline, but less effective than peginterferon plus ribavirin) Peginterferon plus ribavirin

Unknown effectiveness

Interferon

Peginterferon


*— We found no randomized controlled trials. Categorization based on consensus.

Definition

Hepatitis C virus, identified in 1989, is a member of the Flaviviridae family of spherical, enveloped, positive-strand RNA viruses. There are six different hepatitis C virus genotypes. Genotype 1 is the most common and is also the most resistant to treatment. Chronic hepatitis C virus infection is defined as persistent, detectable serum hepatitis C virus RNA for a period greater than six months, with or without derangement in liver function tests. This is in contrast to acute hepatitis C virus infection, in which serum hepatitis C virus RNA clears within six months. Prospective studies have shown that 60 to 85 percent of persons infected with hepatitis C virus will develop chronic infection. This review discusses only interventions used to treat chronic hepatitis C virus infection without liver decompensation. The effect of treatment is measured by the presence or absence of detectable serum hepatitis C virus RNA. The loss of detectable hepatitis C virus RNA at the end of the treatment period is defined as the end of treatment virologic response. The loss of detectable hepatitis C virus RNA 24 weeks or more after the completion of treatment is termed the sustained virologic response. Response to treatment is defined as the loss of detectable serum hepatitis C virus RNA. Non-response is defined as a failure to clear serum hepatitis C virus RNA during the treatment period. A relapse from treatment is defined as loss of serum hepatitis C virus RNA during treatment, which reappears during the follow-up period, typically within 24 weeks of treatment episode.

Incidence and Prevalence

Hepatitis C virus has emerged as a major viral pandemic over the past two decades, with about 3 percent of the world's population chronically infected. The prevalence of hepatitis C virus varies throughout the world, with the highest number of infections reported in Egypt (6 to 28 percent). In the United States, an estimated 4 million persons are positive for hepatitis C virus antibodies, reflecting a prevalence rate of 2 percent; about 35,000 new hepatitis C virus infections are estimated to occur each year. In Europe, the prevalence of hepatitis C virus infection ranges from about 0.5 to 2 percent. Diagnosis of hepatitis C virus infection is often the result of active screening, because many persons with chronic infection remain asymptomatic, including a significant number of those who progress to cirrhosis. Therefore, the true incidence of hepatitis C virus is difficult to calculate accurately because it relates to the prevalence of risk factors for hepatitis C virus transmission, in particular injection drug use.

Etiology and Risk Factors

Hepatitis C virus is mainly bloodborne, and transmission occurs primarily through exposure to infected blood. This exposure may occur with injection drug use, blood transfusion or solid organ transplantation in the absence of universal screening procedures, maternal (vertical) transmission, unsafe medical practices, and occupational exposure to infected blood. As a result of hepatitis C virus screening, the absolute risk of acquiring infection through blood components or products is now low—less than 1 per 400,000 units of blood transfused. Vertical transmission is uncommon, with a transmission rate of less than 6 percent. Poverty, high-risk sexual behavior, and having fewer than 12 years of education are linked to an increased risk of infection. However, no risk factors can be identified in some patients.

Prognosis

The spectrum of liver disease and the rate of disease progression vary in persons with chronic hepatitis C virus infection. Complications include cirrhosis, compensated and decompensated liver disease, and hepatocellular carcinoma. Studies suggest that one third of persons with chronic hepatitis C virus infection are “rapid progressors” (time from infection to cirrhosis is less than 20 years); one third are “intermediate progressors” (time to cirrhosis is 20 to 50 years); and one third are “slow or nonprogressors” (time to cirrhosis is more than 50 years). Factors associated with disease progression include older age at acquisition; male sex; coinfection with HIV, hepatitis B virus, or both; coexisting liver disease; and excessive alcohol consumption. In persons who develop cirrhosis, the five-year risk of decompensation is 15 to 20 percent, the five-year risk of hepatocellular carcinoma is 10 percent, and in those who develop cirrhosis, the annual risk of hepatocellular carcinoma is 1 to 5 percent per year.

Author disclosure: Nothing to disclose.

Adapted with permission from Mohsen A, Norris S. Hepatitis C (chronic). Clin Evid Handbook. December 2007:262–264. Please visit http://www.clinicalevidence.bmj.com for full text and references.

search date: May 2006

 

This is one in a series of chapters excerpted from the Clinical Evidence Handbook, published by the BMJ Publishing Group, London, U.K. The medical information contained herein is the most accurate available at the date of publication. More updated and comprehensive information on this topic may be available in future print editions of the Clinical Evidence Handbook, as well as online at http://www.clinicalevidence.bmj.com (subscription required). Those who receive a complimentary print copy of the Clinical Evidence Handbook from United Health Foundation can gain complimentary online access by registering on the Web site using the ISBN number of their book.


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