Hepatitis A, B and C: A Public Health Perspective

Generally, hepatitis is defined as inflammation of the liver. The inflammation can result from multiple sources such as infection, exposure to alcohol, certain medications, chemicals, or poisons, or an immune-compromising disorder. Although currently, there are five distinct hepatic viruses, for purposes of this chapter, I will only discuss the hepatitis A virus (HAV), hepatitis B virus (HBV), and hepatitis C virus (HCV).

Liver Overview

The liver is a large and vital organ that the body needs to stay alive. Its most important functions are detoxification of drugs and other poisonous chemicals (toxins), and storage of vitamins, sugars, fats and other nutrients. In addition, the liver manufactures proteins needed to sustain the body, makes bile to aid in food digestion, and produces clotting factors and other substances that fight infection.

The liver has an incredible ability to heal itself, but it can only heal itself if nothing is damaging it. Chronic or on-going inflammation can cause liver damage. If the damage is not stopped, the liver becomes hardened and scar-like. This is called cirrhosis, a condition traditionally associated with alcoholism. When this happens, the liver can no longer carry out its normal functions, a condition called liver failure. The only treatment for liver failure is liver transplant.

Hepatitis A Overview

The A virus is one of the three most common viruses in the United States. The other common viruses are B and C.

Whereas hepatitis B and hepatitis C viruses cause chronic inflammation, hepatitis A does not. A chronic condition means that it is on going, long-term or life-long. Although the liver does become inflamed and swollen, it heals completely in most people without any long-term damage. Once you have had hepatitis A, you develop lifelong immunity (antibodies) and cannot get the disease again.

Sources of infections

Hepatitis A is transmitted via a fecal-oral route. Generally, a person ingests something that has been contaminated with the feces of an affected person. This occurs with workers in the food preparation industry (poor hygiene), in children’s day care centers (overcrowding and poor hygiene) or underdeveloped countries with poor sanitation and sewage systems.

The virus can also be spread by eating raw or undercooked shellfish collected from water that has been contaminated by hepatitis A in the sewage. Additionally, although extremely rare, the hepatitis A virus can be transmitted through blood transfusions.

The incubation period for the virus is 15-50 days with an average of 28 days (1). This means that a person can be infected without presenting with any symptoms. Because of the way it is spread, the hepatitis A virus tends to occur in cyclical epidemics and outbreaks.

Symptoms of hepatitis A usually develop between 2 and 6 weeks after infection. The symptoms are usually not too severe and resolve themselves. Symptoms usually last less than 2 months, although they may last as long as 9 months. About 15% of people infected with hepatitis A have symptoms that come and go for 6-9 months (1).

Characteristics of At-risk Populations

Race: Because of the short incubation period, and the route of transmission, outbreaks in the United States tend to be cyclical occurring in certain well-defined populations: Americans Indians, Alaskan natives, and some Hispanic people. Epidemics occur in these groups every 5-10 years. However, between epidemics, hepatitis A still occurs at fairly high rates. For instance, the CDC reports that in 1997, 30,021 cases were reported to the National Notifiable Diseases Surveillance System (NNDSS)(2). When adjustments were made for underreporting, the number of cases reported in 1997 represented an estimated 90,000 symptomatic cases and 180,000 persons with HAV infection (2).

Sex: HAV infection has no sex predilection although homosexual males may have a higher risk of infection than heterosexual males (3).

Age: In the United States, the highest rate of infection occurs in children aged 5-14 years (3).

Other people at increased risk for hepatitis A infection are (2):

Household contacts of people infected with HAV
Sexual partners of people infected with HAV
International travelers, especially to developing countries
Military personnel stationed abroad, especially in developing countries
Men who have sex with other men
Users of illegal drugs (injected or non-injected)
People who may come into contact with HAV at work
Workers in professions such as health care, food preparation, and sewage and waste water management are not at greater risk of infection than the general public.
People who live or work in crowded conditions, such as dormitories, prisons, and residential facilities, or work in or attend daycare facilities are at increased risk if strict personal hygiene measures are not observed.

Economic Burden of Hepatitis A

According to the Centers for Disease Control and prevention (CDC), an estimated 100 persons die from acute liver failure due to the hepatitis A virus. In the 1999 Mortality and Morbidity Weekly Report, the CDC reported that between 11% and 22% of persons who have hepatitis A are hospitalized (2). Moreover, adults who become ill due to hepatitis A lose an average of 27 days of work. For adult cases, the average cost (direct and indirect) of hepatitis A ranged from $1,817 to $2,459 per case (2). For children, the average cost per case ranged from $433 to $1,492(2). The total cost in a recent common-source outbreak involving 43 persons was approximately $800,000. In the United States alone, according to a CDC data that is unpublished, in 1989, the estimated annual direct and indirect costs were more than $200 million (2).

Prevention of Hepatitis A

The hepatitis A virus is preventable. General measures consist of good personal hygiene, hand washing, ingestion of safe drinking water, and proper sanitation.

Additional measures consist of the HAV immune globulin (IG) and HAV vaccine.

· IG is a preparation of antibodies in the body. It can be safely given to children under age 2. It is given as an intramuscular injection is 80-90% effective in preventing HAV infection by means of passive immunity. It can be given within 2 weeks after exposure and is safe during pregnancy and breastfeeding (2).

· HAV vaccine is currently indicated for use in children aged 2 years or older. One dose of vaccine leads to the development of antibodies in 88% of adult patients by 15 days and in 99% by 1 month. The second dose, given 6 months later, leads to immunization in 100% of the adult patients (2).

· The CDC Advisory Committee on Immunization Practices has recommended universal vaccination against HAV for children. Currently, 11 states (AZ, AK, CA, ID, NV, NM, OK, OR, SD, UT, and WA) are implementing the immunization programs and several others are considering the recommendation (2).

The HAV vaccines are given in a series of 2 shots. The second is given 6-18 months after the first. Protection starts about 2-4 weeks after the first shot is given. The second dose is necessary to ensure long-term protection. The vaccines are thought to protect from infection for at least 20 years.

The vaccine must be given before exposure to the virus. They do not work after exposure. Not everyone needs to have the hepatitis A vaccines. However, the vaccines are recommended for the following groups (2):

· All children older than 2 years who live in communities where the number of HAV infections is unusually high or where there are periodic outbreaks of hepatitis A.

· People who are likely to be exposed to HAV at work (i.e. research laboratories where HAV is stored and handled).

· Travelers to developing countries (it must be given at least 4 weeks before travel)

· Adoptee from developing countries

· Men who have sex with men

· People who use illegal drugs

· People who have immune compromising diseases such as AIDS.

· People with blood-clotting disorders who receive clotting factors

From 1995-2001, Samandari et al. (2004) report that approximately 97,800 hepatitis A cases were averted because of the implementation of immunization programs(4). Moreover, sensitivity analysis indicates that the number of averted cases in this period could range from 45,500 to 172,900. Among children 2-18 years, vaccination coverage was estimated at 10% and is attributable to averting 51% cases of hepatitis A infection(4).

Outlook

Hepatitis A infections lead to life-long immunity against the virus. The symptoms are usually mild and tend to resolve on their own. Deaths due to hepatitis A are very rare. Moreover, complications such as hepatitis relapse or liver failure will rarely develop.

Hepatitis B Overview

Hepatitis B is caused by infection with the hepatitis B virus (HBV). This infection has 2 phases: acute and chronic. Acute (new, short-term) hepatitis B occurs shortly after exposure to the virus. A small number of people develop a very severe, life-threatening form of acute hepatitis called fulminant hepatitis.

Chronic hepatitis B infection with HBV can last longer than 6 months. Once the infection becomes chronic, it may never go away completely. About 90-95% of people who are infected are able to fight off the virus so their infection never becomes chronic (5). Only about 5-10 percent of adults infected with HBV go on to develop chronic infection (5)

People with chronic HBV infection are called chronic carriers. About two-thirds of these people do not themselves get sick or die of the virus, but they can transmit it to other people. The remaining one third of the people develop chronic hepatitis B.

Worldwide, about 350 million people are chronic carriers of HBV, of whom, more than 250,000 die from liver-related disease each year (6). In the United States, hepatitis B is largely a disease of young adults aged 20-50 years. About 1.25 million people are chronic carriers, and the disease causes about 5000 deaths each year. Mainly, these deaths occur from complications due to the development of hepatocellular carcinoma (HCC) or liver cancer.

Sources of Infections

Unlike HAV, the hepatitis B virus is transmitted from one person to another via an exchange in blood, also known as blood-borne transmission. Semen and saliva, which contain small amounts of blood, also carry the virus. The virus can be transmitted whenever any of these bodily fluids are in contact with broken skin or a mucous membrane (in the mouth, genital organs, or rectum) of an uninfected person. Half of all people infected with the hepatitis B virus have no symptoms.

According to the CDC, the incubation period for the Hepatitis B virus is between 45 – 160 days with an average of 120 days. Symptoms often develop within 30-180 days of exposure to the virus (1).

Characteristics of At-risk Populations for Hepatitis B

The prevalence of hepatitis B is low in persons younger than 12 years. It does, however, increase for older than 12 years. The increased prevalence could be attributable to the initiation of sexual contact which is the major mode of transmission, the number of sexual partners, and an early age of first intercourse. Additional risk factors identified in the National Health and Nutrition Examination Survey III survey are non-Hispanic black ethnicity, cocaine use, and high number of sexual partners, divorced or separated marital status, foreign birth, and low educational level (3).

Because of the implementation of routine vaccinations of infants in 1992 and adolescents in 1995, the prevalence of HBV is expected to decline.

Race: The prevalence of the disease is higher among African Americans (13.7%) than persons of Hispanic origin (5.3%) or white persons (3.0%)(3).

Sex: Between cohorts ranging in age from 20-59 years, there were more cases of HBV in men (6.5%) than in women (4.7%)(3).

Age: The longer that a person has the infection, the more likely it is to develop chronic inflammation. For instance, infants have a 90% chance, children have a 25-50% chance, adults have an approximately 5% chance, and persons who are elderly have an approximately 20-30% chance of developing chronic disease(7).

Other people who are at increased risk of being infected with the hepatitis B virus include the following (8):

· Men or women who have multiple sex partners, especially if they don't use a condom

· Men who have sex with men

· Men or women who have sex with a person infected with HBV

· People who are diagnosed with other sexually transmitted diseases

· Injection drug users who share needles

· People who receive transfusions of blood or blood products

· Hemodialysis patients undergoing dialysis for kidney disease

· Institutionalized mentally handicapped people and their attendants and family members

· Health care workers who are stuck with needles or other sharp instruments contaminated with infected blood

· Infants born to infected mothers

In some cases, the source of transmission is never known.

Economic Burden of Hepatitis B

The hepatitis B virus accounts for 5 -10% of chronic end-stage liver failure and 10-15% of the development of HCC. It is due to these complications that utilizes most of the health care expenditures. Margolis et al. estimated that, in 1981, expenditures due to acute and chronic HBV-related liver disease was at least $197 million in direct costs and $126 million for work-loss attributed to the illness (9).

Prevention

The good news is that infection with HBV is almost always preventable. According to the CDC, vaccination is recommended for the following groups (8):

· All infants regardless of the potential of exposure to HBV

· All adolescents at high risk of infection (i.e. injection drug users or multiple sex partners)

· People with occupational risk (i.e. medical employees who come in contact with blood or blood products)

· Patients and staff of institutions of the developmentally disabled

· Hemodialysis patients

· Chronic recipients of blood transfusions or certain other blood products

· Household contact and sexual partners of HBV carriers

· Adoptee from countries where HBV infections are endemic

· International travelers especially to countries where HBV is prevalent

· Men who have sex with men

· Sexually active men and women identified as already contracting a sexually transmitted disease

· Inmates of long-term correctional facilities

In an article published in JAMA, Hamilton (1983) found that a program to immunize high-risk medical personnel at the Duke University Medical Center to be cost-beneficial(10). According to the study, the program would cost $206,304 in the first year and by seven years, the cumulative cost of the program would equal those without the program(10). Hamilton also reports that at 10 years, there would be a cost saving ($746,742 with the programs versus $9191,950 without the program)(10).

Outlook

Global eradication of HBV is achievable (11). The hepatitis vaccine is effective and safe to use. According to McIntyre (2001) and Alter (2003), to accomplish such a goal, universal hepatitis B immunization needs to be integrated into existing childhood vaccination schedules. The dilemma is in establishing such a policy worldwide. In 2000, only 116 of 215 countries had such a policy (12). This number represents only 31% of the global birth cohorts (12). Complications arising from chronic HBV-related liver disease are another burden on the health care system. At-risk adults also need to be immunized to truly realize the benefits of the vaccine (12).

Hepatitis C Overview

Hepatitis C is an increasing public health concern in the United States and throughout the world. The World Health Organization estimates 170 million individuals worldwide are infected with hepatitis C virus (HCV) (13). Approximately 15-20% of people infected develop the acute form of the illness. The remaining cases develop chronic hepatitis leading to such complications as cirrhosis, end-stage liver disease, and HCC. Chronic liver disease because of hepatitis C causes 10,000 deaths each year in the United States.

Sources of Infections

HCV is not related to the other viruses that cause hepatitis. However, like the other hepatic viruses, it is contagious and spread via the exchange of blood or blood products. Since sharing of contaminated needles among IV drug users also involves exchange in blood products, the mode of transmission is the most common for the HCV.

Prior to 1992, blood transfusions during surgeries with infected blood, hemodialysis patients, and organ transplants from affected persons were common modes of transmission for the HCV. In 1992, a test became available for checking blood for HCV. Blood and blood products are now tested to ensure that they are not contaminated. Other less common transmissions of HCV include the following:

From mother to infant at the time of childbirth
Through sexual intercourse with an infected person. However, having multiple sex partners is a risk factor.
Needle sticks with HCV-contaminated blood: This is mostly seen in health care workers. The risk of developing HCV infection after a needle stick is about 5-10%.

The source of transmission is unknown in about 10% of people with acute hepatitis C and in about 30% of people with chronic hepatitis C.

Characteristics of At-risk Populations

Populations at high risk for contracting the HCV are similar to those of hepatitis B. HCV tends to be more prevalent in males than females. Other risk factors include persons living below the poverty level, age of first intercourse less than 18 years of age, having more than 50 sexual partners over a lifetime, lifetime use of cocaine, and more than 100 lifetime use of marijuana a(3).

Race: The prevalence of the disease is higher among African Americans (4.1%) than persons of Hispanic origin (3.4%) or white persons (2.0%)(3).

Sex: Between cohorts ranging in age from 20-59 years, there were more cases of HCV in men (3.4%) than in women (1.5%)(3). Again, when this data is stratified by race, more African American (5.8%) and Hispanic (4.1%) men are HCV-infected than their female counterparts (2.8% and 2.6%, respectively)(3).

Age: The age groups for hepatitis C infections are difficult to ascertain. Historically, 20-39 years have been known to have high incidence rate of HCV infections. Chronic hepatitis C has a long latency period, 10-20 years, so persons may be unknowing carriers. Groups under 15 years of age have very low incidence rate of infection (5).

Economic Burden of Hepatitis C (14)

The economic burden of hepatitis C is directly related to the complications such as cirrhosis and HCC. Hospitalization is a large proportion of the expenditures for HCV-related care. In 1995, approximately 27,000 hospitalizations in the US were attributed to liver disease due to HCV. This, in turn, corresponds to a crude incidence of one hospitalization per 1,000 persons infected. The estimated annual total expenditure for hospitalization due to HCV-related liver disease was between $129 and $514 million (14). This estimated cost does not factor in the cost of liver transplantation due to severe cirrhosis or HCC.

For physician services, there were an estimated 317,000 physician office visits incurring $23.9 million in expenditure during 1998. In addition, there were a total cost of $10.5 million emergency department costs and $530 million for pharmaceutical therapies in 1999. According to Alter’s report, in the late 1990’s, the total economic impact of HCV-related liver disease was estimated at $1 to $1.3 billion per year(14).

Prevention

One method to prevent the incidence of HCV is to modify the risky behaviors among those most at risk. The high prevalence of hepatitis C infection among injection drug users (IDU) indicates a need for such behavior modifying programs. The cost and illegality of purchasing syringes has made IDU more likely to share needles. To counter against this practice, many states have implemented syringe exchange programs (SEP). Data on the effectiveness of such programs is still inconclusive. In a study by Hahn et al., the investigators found that although sterile syringes are accessible to IDU, sharing of needles still persists. This finding does not suggest that SEP’s are not working. It does, however, suggest that additional measures are needed in an attempt to curb the spread of HCV. Several studies have found that SEP’s are the optimal settings for further intervention measures(15, 16). In fact, Pollack (2001) suggests that “more comprehensive harm reduction models, coupled with referral of active IDUs to treatment, must complement syringe exchange to successfully contain highly infectious blood-borne diseases”(17).

Another program evaluated by researchers is the medically supervised safer injecting facilities or SIF’s. Wood et al. in British Columbia, Canada found that IDU were willing to attend SIF’s (18). Although this program is not currently available in the US, Wood et al. suggest that the data “indicate a high potential for immediate community and public health benefits if SIF’s were presently available.

In an article by Boutwell et al. (2005), the authors estimate that 15%-40% of persons incarcerated in US prisons are infected with HCV (19). The authors suggest that “testing, education, and when appropriate, treatment of prisoners should be a cornerstone of the public health response to the hepatitis C epidemic in the United States.”

In a Medline search, I did not find much literature on programs educating the general public about the hepatitis epidemic in the US. However, there are many websites that contain educational materials on hepatitis both government-sponsored as well as industry-sponsored. Following is only a sample of the websites:

www.emedicine.com

www.cdc.gov

www.medscape.com

www.nlm.nih.gov/medlineplus/healthtopics.html

Outlook

Hepatitis C varies greatly in its long-term effects. Some people may be infected for 10-20 years before symptoms appear. Others may never develop the severe complications that go along with the disease. However, if the cirrhosis or other complications do develop, then special care is needed to safe-guard the liver. Persons infected with HCV should avoid alcohol or other toxins that may further exacerbate the damage to the liver. Cirrhosis from chronic hepatitis C can lead to liver failure. If damage is severe, liver transplantation is the only treatment.

The good news is, according to the CDC, rates of hepatitis C have been declining in all age groups. In fact, the greatest decline appears among 25-39 year olds, a group which historically had the highest incidence rates.

Support Groups and Counseling

American Liver Foundation

75 Maiden Lane, Suite 603

New York, NY 10038

(800) 465-4837

Hepatitis B Foundation

700 East Butler Avenue

Doylestown, PA 18901-2697

(215) 489-4900

Hepatitis Foundation International

30 Sunrise Terrace

Cedar Grove, NJ 07009-1423

(800) 891-0707

U.S. Centers for Disease Control and Prevention (CDC) Hepatitis Branch--National Information Hotline

(888) 443-7232

References

1. CDC. Protection Against Viral Hepatitis Recommendations of the Immunization Practices Advisory Committee (ACIP). MMWR 1990;39(RR-2):1-26.

2. CDC. Prevention of Hepatitis A Through Active or Passive Immunization: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 1999;48(RR-12):1-37.

3. Kruszon-Moran D, McQuillan G. Seroprevalence of six infectious diseases among adults in the United States by race/ethnicity: data from the third national health and nutrition examination survey, 1988--94. Adv Data 2005:1-9.

4. Samandari T, Bell B, Armstrong G. Quantifying the impact of hepatitis A immunization in the United States, 1995-2001. Vaccine 2004;22(31-32):4342-50.

5. CDC. Hepatitis Surveillance: CDC; 2004 September. Report No.: 59.

6. Lavanchy D. Hepatitis B virus epidemiology, disease burden, treatment, and current and emerging prevention and control measures. J Viral Hepat 2004;11(2):97-107.

7. WHO. Hepatitis B: World Health Organization October 2000. Report No.: 204.

8. CDC. Hepatitis B Virus: A Comprehensive Strategy for Eliminating Transmission in the United States Through Universal Childhood Vaccination: Recommendations of the Immunization Practices Advisory Committee (ACIP). MMWR 1991;40(RR-13):1-9.

9. Margolis H, Schatz G, Kane M. Development of recommendations for control of hepatitis B virus infections: the role of cost analysis. Vaccine 1990;8(Suppl S81-5):S93 - S94.

10. Hamilton J. Hepatitis B virus vaccine: an analysis of its potential use in medical workers. JAMA 1983;250(16):2145-50.

11. McIntyre C. Hepatitis B vaccine: risks and benefits of universal neonatal vaccination. J Pediatr Child Health 2001;37(3):215-7.

12. Alter M. Epidemiology and prevention of hepatitis B. Semin Liver Dis 2003;23(1):39-46.

13. CDC. NIH Consensus Statement on Management of Hepatitis C: National Institutes of Health; 2002 2002 Jun 10-12. Report No.: 19(3).

14. Alter M. Viral hepatitis: hepatitis C. In: Kim W, Brown Jr. R, Terrault N, El-Serag H, editors. Epidemiology and the impact of liver disease in the United States; 2001; Atlanta, GA; 2001.

15. Stancliff S, Agins B, Rich J, Burris S. Syringe access for the prevention of blood borne infections among injection drug users. BMC Public Health 2003;3(1):37.

16. Tortu S, McMahon J, Hamid R, Neaigus A. Women's drug injection practices in East Harlem: an event analysis in a high-risk community. AIDS Behav 2003;7(3):317-28.

17. Pollack H. Cost-effectiveness of harm reduction in preventing hepatitis C among injection drug users. Med Decis Making 2001;21(5):357-67.

18. Wood E, Kerr T, Spittal P, Li K, Small W, Tyndall M, et al. The potential public health and community impact of safer injecting facilities: evidence from a cohort of injection drug users. J Acquir Immune Defic Syndr 2003;32(1):2-8.

19. Boutwell A, Allen S, Rich J. Opportunities to address the hepatitis C epidemic in the correctional setting. Clin Infect Dis 2005;40(Suppl 5):S367-72.