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Am Fam Physician. 1999;59(2):349-354

See editorial on page 273.

This is Part II of a two-part article on hepatitis C. Part I, on serologic testing and diagnosis, appeared in the last issue (Am Fam Physician 1998;59:79–92.)

See related patient information handout on hepatitis C, written by the authors of this article.

An estimated 3.9 million Americans are infected with hepatitis C virus (HCV), and most do not know that they are infected. This group includes persons who are at risk for HCV–associated chronic liver disease and who also serve as reservoirs for transmission of HCV to others. Because there is no vaccine to prevent HCV infection and immune globulin is not effective for postexposure prophylaxis, prevention of HCV infection is paramount. Patients who are at risk of exposure to HCV should be advised on steps they might take to minimize their risk of infection. Patients who are infected with HCV should be counseled on ways to prevent transmission of HCV to others and to avoid hepatotoxins. They should also be examined for liver disease and referred for treatment, if indicated.

There is no vaccine to prevent hepatitis C virus (HCV) infection, and immune globulin is not effective for postexposure prophylaxis.1 In the absence of effective preventive measures and considering the long-term infectious nature of the disease, it is important that those who test positive for hepatitis C antibody (anti-HCV) be advised on how they can avoid infecting others. Because no tests are available to determine infectivity, it should be assumed that anyone testing positive for anti-HCV is potentially infectious.2 Primary health care professionals should obtain a history of high-risk exposures associated with the transmission of HCV and other blood-borne pathogens from all patients. HCV–specific information and prevention messages should be provided to infected patients by health care professionals who are knowledgeable about HCV transmission. All such patients should be told that HCV is transmitted primarily by exposure to blood, serum-derived body fluids and body fluids that are visibly contaminated with blood. They should be told what this information means in terms of their day-to-day living and in terminology that they can understand. Patients who are at risk of exposure to HCV should be advised about steps they might take to minimize their risk of becoming infected. The primary measures available to prevent HCV infection are screening of blood, organ and tissue donors; modification of high-risk practices; and use of blood and body-fluid precautions.2

What prevention messages should be given to patients with high-risk drug or sexual practices?

Persons who use or inject illegal drugs should be advised to stop using and injecting drugs. They should be strongly urged to enter and complete substance abuse treatment, including relapse prevention programs.3,4 If they continue to inject drugs, they should be advised never to reuse or share syringes, needles, water or drug preparation equipment. If injection equipment has been used by other persons, the equipment should be cleaned first with bleach and water. Only syringes obtained from a reliable source (e.g., pharmacies) should be used. A new, sterile syringe should be used to prepare and inject drugs. If possible, sterile water should be used to prepare drugs; otherwise, clean water from a reliable source, such as fresh tap water, can be used. A new or disinfected container (“cooker”) and a new filter (“cotton”) should also be used to prepare drugs. The injection site should be cleaned before the injection with a new alcohol swab. Syringes should be safely disposed of after one use.3,4 These persons should be advised to get vaccinated against hepatitis A5 and hepatitis B.6

Patients who are at risk for sexually transmitted diseases (STDs) should be advised that the surest way to prevent the spread of HIV infection and other STDs is to have sex with only one uninfected partner or not to have sex at all. Patients should be advised to use latex condoms correctly and every time to protect them and their partners from diseases spread by having sex. These patients should also be vaccinated against hepatitis B6 and, if appropriate, hepatitis A.5

What information should be given to patients who are HCV–positive?

To protect their liver from further harm, HCV–positive patients should be advised to avoid alcohol,7,8 not to start taking any new medicines, including over-the-counter and herbal medicines, without checking with their doctor and to get vaccinated against hepatitis A if liver disease is found to be present.5 To reduce the risk of transmission to others, HCV–positive patients should be advised not to donate blood, organs, tissue or semen, not to share toothbrushes, dental appliances, razors or other personal care articles that might have blood on them and to cover cuts and sores on the skin to keep from spreading infectious blood or secretions.2 HCV–positive patients with one long-term, steady sex partner do not need to change their sexual practices. They should, however, discuss the risk (which is low but not absent) with their partner. If they want to lower the small chance of spreading HCV to their partner, they may decide to use barrier precautions such as latex condoms. These patients should also discuss with their partner the need for counseling and testing.4

HCV–positive women do not need to avoid pregnancy or breast feeding. Potential, expectant and new parents should be advised that about five of every 100 infants born to HCV–infected women become infected. This infection occurs at the time of birth, and no treatment can prevent this from happening.4,9 Infants infected with HCV at the time of birth seem to do very well in the first few years of life. More studies are needed to find out if these children will be affected by the infection as they grow older. There is no evidence that mode of delivery is related to transmission; therefore, the need for cesarean section versus vaginal delivery should not be determined on the basis of HCV–infection status.

Limited data on breast feeding indicate that it does not transmit HCV, although it may be prudent for HCV–positive mothers to abstain from breast feeding if their nipples are cracked or bleeding. Infants born to HCV–positive women should be tested for HCV infection and, if positive, evaluated for the presence or development of chronic liver disease (see the section on testing of children born to HCV–positive women in part I of this article). If an HCV–positive woman has given birth to any children since becoming infected with HCV, she should consider having these children tested.4

Other messages should be given to all patients with HCV infection: that HCV is not spread by sneezing, hugging, coughing, food or water, sharing eating utensils or drinking glasses, or casual contact. Persons should not be excluded from work, school, play, child care or other settings on the basis of HCV infection status. Involvement with a support group may help patients cope with hepatitis C.4 HCV–positive persons should be evaluated (through referral or consultation, if appropriate) to assess for biochemical evidence of chronic liver disease. These patients should be assessed for severity of disease and possible treatment according to current practice guidelines in consultation with, or by referral to, a specialist knowledgeable in this field. The need for hepatitis A vaccination should be determined.4,5

What recommendations should be provided for follow-up care of a health care worker who has experienced a percutaneous or permucosal exposure to blood?

Individual institutions should establish policies and procedures for HCV testing of persons after such exposures. Institutions should ensure that all personnel are familiar with these policies and procedures. Health care professionals who provide care to persons exposed to HCV in the occupational setting should be knowledgeable about the risk for HCV infection and able to provide appropriate counseling, testing and medical follow-up.

Immune globulin and antiviral agents are not recommended for postexposure prophylaxis of hepatitis C. Limited data indicate that antiviral therapy might be beneficial when started early in the course of HCV infection, but no guidelines exist for administration of therapy during the acute phase of infection. When HCV infection is identified early, the patient should be referred for medical management to a specialist knowledgeable in this field. Recommendations for follow-up care for HCV infection in exposed health care providers are listed in Table 1.4,10

For the source patient—baseline testing for anti-HCV
For the person exposed to an HCV–positive source—baseline and follow-up testing, including the following:
Baseline testing for anti-HCV and ALT activity
Follow-up testing for anti-HCV (at four to six months) and ALT activity. (If earlier diagnosis of HCV infection is desired, testing for HCV RNA may be performed at four to six weeks.)
Confirmation by supplemental anti-HCV testing of all anti-HCV results reported as positive by enzyme immunoassay.

Are there recommended practice restrictions for anti-HCV–positive health care workers?

There are currently no recommendations regarding restriction of health care workers with hepatitis C. The risk of transmission from an infected employee to a patient appears to be very low.4,10

Should hepatitis A and hepatitis B vaccines be given to persons with chronic hepatitis C?

Susceptible patients with chronic liver disease should receive hepatitis A vaccine. Susceptible patients in a high-risk group for which hepatitis B vaccine is recommended should also receive hepatitis B vaccine.46

Treatment of HCV–Infected Patients

Treatment with interferon is generally recommended for patients with chronic hepatitis C who are at the greatest risk for progression to cirrhosis.1113 These patients have persistently elevated alanine aminotransferase (ALT) levels, detectable HCV RNA and liver biopsy results showing either portal or bridging fibrosis or at least moderate degrees of inflammation and necrosis. Indications for treatment in patients with persistently elevated ALT levels but with less severe histologic changes are less clear. In these patients, observation, including serial ALT measurements and a liver biopsy every three to five years, may be an acceptable alternative to treatment with interferon, because progression to cirrhosis is likely to be slow, if it occurs at all. Similarly, patients with compensated cirrhosis might not benefit from interferon therapy.

Interferon is not recommended in patients with persistently normal ALT values or advanced cirrhosis. Treatment of patients who drink significant amounts of alcohol or who inject illicit drugs should be delayed until these habits have been discontinued for at least six months. Interferon is contraindicated in patients with major depressive illness, cytopenias, hyperthyroidism, renal transplantation or evidence of autoimmune disease and in those who are pregnant.4,11

How should a patient be managed who is anti-HCV–positive (verified by supplemental test) and has normal liver enzyme levels?

Patients should be periodically assessed by monitoring serum ALT values several times over six to 12 months. If ALT values are persistently normal, it is then reasonable to assess ALT values annually.

When should a gastroenterologist or hepatologist be consulted in the management of HCV–infected patients?

A specialist in liver disease should be consulted for the management of anti-HCV–positive patients with elevated ALT values. Further evaluation may include determination of HCV RNA level and liver biopsy. Based on these findings, treatment with interferon may be recommended.

Do all patients who are considered for antiviral treatment need to have a liver biopsy?

Liver histology is the gold standard for assessing the severity of liver disease and the only means of diagnosing well-compensated cirrhosis. It is useful in determining not only inflammatory activity but also extent of fibrosis. Histologic grading of inflammatory activity and staging of fibrosis have also been shown to correlate with the risk of subsequent progression to cirrhosis. In addition, fibrosis score and cirrhosis have been identified as the most important independent predictive factors for response to interferon treatment.14

Should interferon treatment be considered for children with chronic hepatitis C?

Currently, interferon is only labeled for treatment of adults with chronic hepatitis C. It is not labeled by the U.S. Food and Drug Administration for use in children under 18 years of age; however, limited experience with interferon therapy for chronic hepatitis C suggests an efficacy similar to that observed in adults. Referral of a child with chronic hepatitis C to a pediatric hepatologist or gastroenterologist for management should be considered if serum ALT levels are persistently elevated and there is evidence of active viral replication, such as HCV RNA detected by polymerase chain reaction testing. Because of limited experience with interferon therapy in children, enrollment into a clinical trial, if available, should be considered if this step is contemplated.11

What is the recommended regimen for interferon therapy?

The recommended regimen for interferon therapy is 3 million U administered subcutaneously three times a week for 12 months. If patients have persistently abnormal ALT levels and detectable serum HCV RNA after three months of interferon therapy, treatment should be discontinued. The advisability of entering these patients into clinical trials for other treatments should be explored.11

What percentage of patients respond to interferon therapy?

Approximately 50 percent of treated patients have an initial response, with normalization of serum ALT activity and a loss or decrease of serum HCV RNA at the end of therapy. After interferon therapy is discontinued, however, more than one half of patients who responded to treatment relapse, with recurrence of elevated ALT levels and reappearance of serum HCV RNA. Thus, only 15 to 25 percent of treated patients have a sustained response one or more years after therapy ends.11,15

Are there other treatment options for patients with chronic hepatitis C?

Ribavirin (Virazole), a nucleoside analog, has been evaluated in clinical trials alone and in combination with interferon.16 In studies of patients treated with ribavirin alone, results demonstrated a decrease in ALT activity in about one third of patients, but no change in viral replication. In addition, when treatment was withdrawn, all patients relapsed, with recurrence of elevated ALT levels. Thus, monotherapy with ribavirin is not useful in the treatment of chronic hepatitis C.

The results of studies of patients treated with a combination of ribavirin and interferon, however, demonstrated a substantial increase in sustained response rates, reaching as high as 40 to 50 percent compared with interferon therapy alone. As with interferon-alone therapy, however, combination therapy in patients with genotype 1 (the most common strain of HCV in the United States) is not as successful; sustained response rates among these patients are still less than 30 percent. Combination therapy with interferon and ribavirin is now licensed for the treatment of chronic hepatitis C in patients who have relapsed following interferon treatment and for use in naive patients.

What are the side effects of interferon therapy?

Most patients experience flu-like symptoms early in treatment, but these symptoms diminish with continued therapy. Later side effects include fatigue, bone marrow suppression and neuropsychiatric effects such as apathy, cognitive changes, irritability and depression. The interferon dosage must be reduced in 10 to 40 percent of patients because of severity of side effects, and treatment must be discontinued in 5 to 15 percent.11,13

Can anything be done to reduce some of the side effects of interferon therapy?

Pretreatment with acetaminophen and administering interferon at night may help to alleviate the side effects.11,13

Are there additional side effects associated with ribavirin?

Yes. Ribavirin can induce hemolytic anemia, and use of this drug can be problematic in patients with preexisting anemia, bone marrow suppression or renal failure. Therefore, in these patients, combination therapy should be avoided, or attempts should be made to correct the anemia. Hemolytic anemia caused by ribavirin can also be life-threatening in patients with ischemic heart disease or cerebrovascular disease.16 Ribavirin is teratogenic, and female patients should avoid becoming pregnant during therapy.

Are there data on the efficacy of interferon or other antiviral treatment in preventing the long-term morbidity and mortality of hepatitis C?

No. Effects of antiviral treatment on important clinical outcomes, including quality of life and disease progression, have not been determined.

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