Disease update: Hepatitis C

March 1, 2000
A lot has changed in the battle against the viruses that cause hepatitis. Are you and your staff up-to-date? Find out here.

A lot has changed in the battle against the viruses that cause hepatitis. Are you and your staff up-to-date? Find out here.

Hepatitis is an inflammation of the liver caused by several viruses (A, B, C, D, E, and G) and other factors, including chronic alcohol abuse, certain medications, and trauma. In its various forms, hepatitis affects millions of Americans each year. Although dental health-care workers have long been aware of the occupational risks associated with hepatitis B virus (HBV) - the most infectious of the hepatitis viruses - vaccines have eliminated the risk of infection for the vast majority of dental-care providers. Fairly recently, however, hepatitis C virus was identified and has emerged as a growing occupational and public health concern.

First identified in 1988 by molecular cloning, hepatitis C virus (HCV) was previously known as parenterally acquired non-A, non-B hepatitis. The enveloped, single-strand RNA virus has an average incubation period of six to seven weeks (range: two to 26 weeks). Virus replication may be detected as soon as one week after exposure, and HCV RNA appears as soon as two weeks after exposure to the virus. Because commercial tests to measure HCV RNA in serum are not licensed for use in the United States, diagnosis of HCV infection is generally made by detecting antibodies to HCV (anti-HCV) in the blood. In 80 percent of cases, anti-HCV is detectable five to six weeks postinfection; by 12 weeks, 90 percent of infected individuals have antibodies to HCV. Because currently available test methods cannot differentiate between acute and chronic infection, diagnosis of chronic hepatitis C in an anti-HCV-positive individual is generally based on the presence of elevated liver enzymes for more than six months.

HCV is responsible for an average of 28,000 to 180,000 infections each year. A leading cause of cirrhosis and liver cancer, HCV is now the principal reason for liver transplantation in the United States and is the causative agent in almost half of the viral hepatitis cases each year.

Approximately 25 to 35 percent of those infected with HCV will experience clinical illness commonly in the form of jaundice, fatigue, abdominal pain, loss of appetite, intermittent nausea, and vomiting. After the acute infection, only about 15 percent of infected persons appear to resolve their infections without any lasting sequelae. The remaining 85 percent progress to chronic hepatitis infections, with chronic liver disease (with persistently elevated liver enzymes) occurring in nearly 70 percent of infected persons. These extraordinarily high rates of chronic disease and persistent viremia indicate the absence of an effective neutralizing immune response.

Unfortunately, chronic hepatitis frequently remains unrecognized until symptoms appear with the development of advanced liver disease. Of those who develop chronic hepatitis, 10 to 20 percent develop cirrhosis over a period of 20 to 30 years.

HCV was traditionally transfusion-associated, but newer and more sensitive and effective commercial blood tests for the detection of HCV have reduced the risk of hepatitis C from transfusions from 1-in-200 units transfused to approximately 1-in-100,000 units. As a result, the annual number of newly acquired infections has declined by more than 80 percent over the past decade.

About 3.9 million Americans (1.8 percent of the country`s population) are chronically infected with HCV. According to the Centers for Disease Control and Prevention (CDC), chronic hepatitis C causes between 8,000 and 10,000 deaths and leads to about 1,000 liver transplants in the United States each year. Globally, the World Health Organization reports prevalences of 0.5 percent to more than 10 percent in population samples around the world, translating to more than 170 million infected individuals worldwide.

Transmission

HCV is spread primarily through direct contact with blood, most efficiently through large-volume or repeated percutaneous exposures. Although the risk that an HCV-infected individual will transmit the virus may be related to the type and size of the inoculum and the route of transmission as well as the titer of the virus, data on the threshold concentration of virus needed for transmission are insufficient.

Injection drug use is the most common risk factor, with 50 to 60 percent of all HCV cases associated with this practice. An additional 15 to 20 percent of recent cases have been reported among persons with a history of sexual exposure in the absence of other risk factors, and 4 percent have occurred in health-care workers who have contracted hepatitis C occupationally. Less common modes of transmission include hemodialysis and blood transfusions. In about 10 percent of cases, neither a specific risk factor nor the mode of transmission can be identified.

Perinatal transmission of HCV also is possible. CDC reports that five out of every 100 infants born to HCV-infected mothers become infected at the time of birth, and no effective preventive measures have been identified. Studies of infants born to anti-HCV-positive mothers have reported rates of perinatal transmission ranging from 0 to 13 percent; in two studies, only mothers with high titers of HCV RNA transmitted to their infants. Although infants infected with HCV at the time of birth appear to do very well in their first few years of life, additional studies are needed to determine whether these children will later develop health problems. Breast-feeding does not appear to be a route of transmission.

Occupational exposure

Occupational exposure by dental workers to HCV primarily involves parenteral contact with blood, although any mucous membrane or nonintact skin contact with patient fluids, including saliva, must be considered an exposure.

HCV acquisition is similar in nature to that of HBV, but the chances of infection following exposure are approximately 10 times higher for HBV. Research indicates that the probability of contracting hepatitis C after a needlestick injury from a seropositive source is approximately 3 percent, compared with 30 percent for HBV (calculated for oral surgeons) and 0.3 percent for the human immunodeficiency virus (HIV).

Risk factors for HCV transmission in the health-care setting are not well-defined, although a case-control study of patients with non-A, non-B hepatitis, conducted prior to the identification of HCV, found a significant association between acquiring disease and health-care employment, specifically patient care or laboratory work. Seroprevalence studies have reported antibody to HCV rates of 1 percent among hospital-based, health-care workers in Western countries. In one study, a history of accidental needlesticks was associated with antibodies to HCV, while other case reports have documented transmission of HCV infection from anti-HCV-positive patients to health-care workers via needlesticks, other sharps injury, or permucosal exposure of infected blood to the conjunctiva of the eye.

Follow-up studies of health-care workers who sustained percutaneous exposures to blood from anti-HCV-positive patients revealed an average seroconversion incidence of 3.5 percent. However, one study, which used polymerase chain reaction (PCR) to detect HCV infection by measuring HCV RNA in the blood, found an incidence of 10 percent. There is conflicting evidence as to the prevalence of HCV among dental professionals. For example, a 1991 case-controlled study by Klein and colleagues reported that dentists - in particular oral surgeons - were at increased risk for HCV infection. Overall, the authors noted a 1.75 percent prevalence rate of anti-HCV among dentists, compared with 0.14 percent of controls. When broken out by specialty, 9.3 percent of oral surgeons tested positive for anti-HCV, compared with only 0.97 percent of dentists who did not specialize in surgery.

Thomas et al, however, re-examined dentists` occupational risk of HCV infection using serum samples obtained through the American Dental Association`s Health Screening Program. Their data, which confirmed higher rates of HBV among dental personnel, suggest that the risk of HCV infection is considerably lower. They found anti-HCV in the blood of only 2 percent of oral surgeons and 0.7 percent of general dentists.

In contrast to HBV, HCV appears to be less infectious occupationally to dental staff. In fact, current evidence suggests that health-care workers are not at a notable risk of HCV acquisition as a result of occupational exposure, unless they sustain a needlestick injury from an infected patient. Nevertheless, infection with this virus can lead to significant morbidity. To minimize the potential for occupational exposure to any bloodborne pathogen, experts agree that universal precautions should be implemented in all instances where contact with blood or body fluids may occur.

Postexposure management

No vaccine is available for HCV, and postexposure prophylaxis with immune globulin does not appear to be effective in preventing hepatitis C infection. Because of the lack of information on the safety and efficacy of antiviral agents such as alpha interferon in postexposure management, CDC likewise discourages their use. Development of such products for postexposure management presents a significant challenge, because no protective antibody response has been observed following infection with HCV. Thus, primary preventive measures currently can only include serologic screening and programs that encourage high-risk behavior modification. For health-care workers, blood and body fluid precautions (i.e., universal precautions) help reduce exposure.

The most obvious benefit of a postexposure follow-up appears to be the opportunity for the health-care worker to seek evaluation for chronic liver disease and treatment, if eligible. Studies have shown that alpha interferon therapy may have a beneficial effect on some patients. In these studies, however, the patients were highly selected and therapy resulted in sustained improvement in 20 percent or fewer of those treated. No clinical, demographic, serum biochemical, serologic, or histologic features have been identified that reliably predict which patients will respond to treatment and sustain long-term remission.

According to CDC, even in the absence of available postexposure prophylaxis and with limited specific measures for disease prevention, individual institutions should consider implementing policies and procedures for follow-up after percutaneous or permucosal exposure to anti-HCV-positive blood to address the individual worker`s concern about risk and outcome. Above all, institutions should ensure education of health-care providers regarding the risk and prevention of bloodborne infections, including hepatitis C, in the occupational setting, and such information should be updated routinely to ensure accuracy.

Test methods

In 1992, the Food and Drug Administration (FDA) approved a new, more highly sensitive antibody test for screening blood against HCV that has significantly improved the safety of blood and prevented thousands of transfusion-related cases of hepatitis C each year. Capable of identifying up to 97 percent of infections, this improved blood-screening method is largely responsible for reducing the number of transfusion-associated HCV cases by 94 percent between 1965 and 1993, although a portion of this decline may be due to self-exclusion of high-risk donors.

Although their value in screening blood cannot be understated, HCV testing methods readily available in the clinical setting have some limitations. Currently available serologic tests detect only circulating antibodies to HCV, which only prove that an individual has been exposed to the pathogen. Serum testing cannot distinguish between acute, chronic, or resolved infection and is unable to determine whether the virus is circulating at the time of the test and, if so, in what amount. Furthermore, false positives can be commonplace in screening of low-risk populations, so confirmatory testing may be required to ascertain the presence of anti-HCV.

All anti-HCV-positive persons should be considered potentially infectious, since neither the presence of an antibody nor the presence of HCV RNA is a direct measure of infectivity when apparent parenteral or mucosal exposures occur.

CDC and other experts agree that testing, counseling, and appropriate medical follow-up should be offered to persons most likely to be infected with HCV who might require medical management, for example:

* persons who have ever injected illegal drugs

* persons who received clotting factor concentrates produced before 1987

* those who ever underwent chronic, long-term hemo-dialysis

* persons with persistently high liver enzyme levels

* individuals who were notified that they received blood from a donor who later tested positive for HCV

* recipients of blood transfusions or organ transplants prior to July 1992

Health-care professionals in primary care and other appropriate settings should routinely ask patients about their transfusion history and provide appropriate counseling and testing of persons potentially infected with HCV.

In addition, CDC and other experts agree that anyone interested in knowing his or her HCV status should be offered testing and counseling. Children born to HCV-positive women should be tested routinely based on this recognized exposure. Likewise, health-care, emergency medical, and public-safety workers should be routinely tested after needlesticks, sharps, or mucosal exposures to HCV-positive blood.

Treatment of HCV infection

Medical management of HCV infection is recommended for patients with chronic hepatitis C who are at greatest risk for progression to cirrhosis. These include patients with persistently elevated liver enzyme levels, detectable HCV RNA, and a liver biopsy indicating either portal or bridging fibrosis or at least moderate degrees of inflammation and necrosis. Primary treatment typically consists of alpha interferon, a natural human cell protein made by macrophages and B cells in response to viral infection. Dosage is 3 million units subcutaneously three times per week for 12 months. One year after therapy, approximately 15 to 25 percent of patients undergoing alpha interferon therapy demonstrate a sustained response. The antiviral agent ribavirin also is sometimes prescribed, but with modest results.

Recent studies, however, have suggested that dual ribavirin/alpha interferon therapy may be more effective than alpha interferon therapy alone. In fact, the combination therapy has received FDA approval in the treatment of hepatitis C relapse. Long-term studies are needed to determine whether this increase in response will decrease the rate of complications from infection.

Agency efforts to identify and inform

To reach those who may have been infected by blood transfusion in the past, Secretary of Health and Human Services Donna E. Shalala announced in January 1998 that HHS would implement measures to reach individuals who received a transfusion from a donor who tested positive for HCV, as well as a public and provider education effort to reach all people who received a transfusion before July 1992, as well as others at risk for hepatitis C. The plans will be carried out by CDC and FDA.

Two months after this directive, FDA published guidance for the blood-banking industry to use in notifying patients or medical facilities that received blood from a donor who subsequently tested positive for HCV. Originally requiring blood establishments to begin notifying patients by September 20, 1998, a reissued guidance states that notifications should have begun no later than March 1999.

In April 1998, CDC provided Shalala with a nationwide plan for the prevention and control of HCV infection and HCV-related chronic disease that supplemented the FDA guidance and included plans for identifying persons at risk for hepatitis C, including all persons transfused before July 1992. On October 16, 1998, CDC published formal recommendations for the prevention of transmission; the identification, counseling and testing of persons at risk for HCV infection; and the appropriate medical evaluation and management of HCV-infected persons.

At the National Institutes of Health, the National Institute of Allergy and Infectious Diseases has established a network of four Hepatitis C Cooperative Research Centers to pursue studies aimed at the prevention and treatment of HCV infection.

In addition, CDC has funded extramural studies into the risk of perinatal, sexual, and household transmission of HCV infection and has established cooperative agreements with non-governmental agencies to develop and distribute information for health-care providers and the public on the diagnosis, prevention, and medical management of hepatitis and related liver disease.

The Hepatitis Branch at CDC has implemented a toll-free number (888-4HEPCDC) and maintains a Web site ? http://www.cdc.gov/ncidod/diseases/hepatitis/ ? to allow access to information on viral hepatitis.

This resource was reprinted with the permission of OSAP. OSAP is a nonprofit organization providing information and education on dental infection control and office safety. For more information, please call (800) 298-6727.

Transmission of HCV associated with health care

* Health-care worker needlestick

* Blood splash into eyes

* Blood transfusion (rapidly declining)

* Infection of patients through IV administration of contaminated Immune Globulin

* Organ and tissue transplantation

* Transmission from HCV-positive cardiac surgeon to patients

* Patient-to-patient transmission from colonoscopy

Source: Molinari, JA. Lecture series.

Risk groups for HCV infection

* Injecting drug users

* Hemodialysis patients

* Health-care workers

* Sexual contacts of infected persons

* Persons with multiple sex partners

* Recipients of transfusions before July 1992

* Recipients of clotting factors before 1987

* Infants born to infected women

Source: CDC. Hepatitis C Fact Sheet. Available at http://www.cdc.gov/ncidod/diseases/hepatitis/c/hact.htm. Accessed August 28, 1998.

CDC summary recommendations for following health-care worker exposure to HCV

1. No postexposure prophylaxis is available for hepatitis C. Immune globulin is not recommended.

2. Institutions should provide health-care workers with accurate, up-to-date information on the risk and prevention of all bloodborne pathogens, including hepatitis C.

3. Institutions should consider implementing policies and procedures for follow-up of health-care workers after percutaneous or permucosal exposure to anti-HCV-positive blood. Such policies might include baseline testing of the source for anti-HCV as well as baseline and six-month follow-up testing of the worker exposed for anti-HCV and ALT activity. All anti-HCV results reported as repeatedly reactive by EIA should be confirmed by supplemental anti-HCV testing.

4. There are currently no recommendations regarding restriction of health-care workers with hepatitis C. The risk of transmission from an infected worker to a patient appears to be very low. Furthermore, there are no serologic assays that can determine infectivity, nor are there data to determine the threshold concentration of virus required for transmission. As recommended for all health-care workers, those who are anti-HCV-positive should follow strict aseptic techniques and standard (universal) precautions, including appropriate use of handwashing, protective barriers, and care in the use and disposal of needles and other sharp instruments.

Source: CDC. Hepatitis Surveillance Issues and Answers. Report No. 56, Issued April 1996. Available at http://www.cdc.gov/ncidod/diseases/hepatitis/h96issue.htm. Accessed August 28, 1998.

Recommendations for dental management of HCV-infected patients with impaired liver function

1. With invasive procedures, careful preoperative assessment of the coagulation status of the patient, including prothrombin time, partial prothrombin time, and platelet count.

2. Extreme caution in the prescription of medications-in particular, central nervous system depressants (barbiturates, opioids), hepatotoxic drugs (tetracyclines, erythromycin estolate, monoamine oxidase inhibitors, phenylbutazone), and drugs that may aggravate the hemorrhagic tendency (aspirin).

3. Consideration of possible HCV-associated medical conditions (mainly bloodborne conditions such as HIV, HBV, and hepatitis G virus).

4. Provision of effective oral hygiene prophylaxis to reduce the need for operative dentistry.

Source: Lodi G, Porter SR, Scully C. Hepatitis C virus infection: review and implication for the dentist.

Oral Surg Oral Med Oral Pathol, 1998;86(1):16.