CHAPTER 12

Hepatitis

Key Points:

Hepatitis A is one of the most common vaccine-preventable diseases in the world.
Hepatitis B is spread by infected blood and bodily fluids and is preventable by vaccination or lifestyle choices.
Travelers may be exposed to the hepatitis B virus by needle sharing and unprotected sex; from non-sterile medical or dental injections, and acupuncture; from unscreened blood transfusions; by direct contact with open skin lesions of an infected person.
You should avoid injections, dental procedures or skin piercing while traveling in a lesser-developed country. These can expose you not only to hepatitis B and C, but to HIV (human immunodeficiency virus) as well.
If you have a condition requiring injections, bring your own supply of needles and syringes.
A sterile needle/syringe kit or a sterile suture kit is also advisable in many countries where there is a risk of hepatitis and HIV. Give the kit to the health care provider to use if individually wrapped sterile equipment is not available.
The combination vaccine TwinRix (GSK) prevents both hepatitis A and B and is convenient to administer.
Countries with the highest risk of hepatitis E include Burma, Nepal, Pakistan, Sudan, China, and India.
Hepatitis E is fatal in up to 25% of women in late pregnancy. There is no vaccine to prevent hepatitis E, which is usually transmitted by contaminated drinking water.

What's New in 2008

Data from retrospective studies suggest that hepatitis C virus (HCV) genotype 1–positive patients who are slow responders to pegylated interferon plus fixed-dose ribavirin regimens have significantly higher rates of sustained virologic response (SVR) when they are treated for 72 weeks rather than the standard 48 weeks (Hepatology 2003; 37:1226).

Four Distinct Types

Hepatitis is a generic term for inflammations of the liver. It is caused by a number of viruses, other infectious agents, and toxins. There are four hepatitis viruses of which all travelers should be particularly aware: A, B, C, and E.* The means of transmission and long-term effects vary, depending on which virus causes the disease. For the traveler, viral hepatitis is a major concern—not only because of the potential health risks, but because many cases can be prevented by immunization.

Hepatitis A and E are transmitted primarily by contaminated food and water. High-risk areas are less developed countries where poor sanitation results in contamination of groundwater, tap water, and well water. Outbreaks of hepatitis A are also caused by food that has been contaminated by an infected food handler. Hepatitis B and C are spread by sexual contact, exchange of body fluids, injections from contaminated needles and syringes, and unscreened blood transfusions.

Hepatitis A

The symptoms can vary. Most cases of hepatitis, in fact, go completely unnoticed. In a textbook case, however, you would develop fever, fatigue, loss of appetite, jaundice (yellow skin), dark urine, abdominal pain, and aching joints.

Symptoms of acute hepatitis may occur weeks to months after exposure and typically last from 2 to 6 weeks. The likelihood of complete recovery depends on the particular viral infection and your underlying health. Complete recovery occurs in most cases of types A and E hepatitis, but 5% to 80% of types B and C may progress, causing chronic, sometimes fatal, liver disease.

Hepatitis A This is one of the most common vaccine-preventable viral illnesses in the world and the most frequently diagnosed form of hepatitis in travelers returning from developing countries. Hepatitis A is very widespread and close to 100% of people in less developed countries are infected with the hepatitis A virus (HAV) by 10 years of age. In some industrialized countries, however, no more than 10% of the population has been infected. In the United States, about 33% of the population has serologic evidence of previous HAV infection.

Figure 12.1 Geographic Distribution of Hepatitis A

Risk to Travelers The risk to a non-immune traveler of acquiring hepatitis A is estimated at 1 per 1,000 per month of exposure in resort areas, and 5 per 1,000 per month in remote areas of developing countries. Although the risk of hepatitis A is certainly higher in countries with substandard sanitation and hygiene, travel to developed or industrialized countries still carries some risk.

Symptoms usually appear 2 to 6 weeks after exposure. HAV infection is often mild or asymptomatic in children, but there are increased morbidity and mortality in adults. About 0.15% to 0.5% of infected adults develop fulminant liver failure, fatal in one half of these cases. In those older than age 50, mortality in the acute infection may reach 3%. In individuals with chronic hepatitis C or other forms of chronic liver disease, a superimposed HAV infection may carry even higher risks of severe disease and death.

Treatment

Treatment consists of supportive care. Eat a nutritious diet and avoid alcohol. Be aware that the combination of alcohol and acetaminophen (also called paracetamol in some countries) can cause direct hepatic toxicity. There is no specific treatment that will shorten your illness. Limiting exercise has no effect on the rate of recovery. Hospitalization is unnecessary unless you suffer more severe signs of acute liver failure or refractory nausea, vomiting, and dehydration. Close contacts such as family members or companion(s) who have not previously been infected or vaccinated should immediately receive immune globulin (if available) or hepatitis A vaccine.

Prevention

Hepatitis A vaccine—Several effective vaccines are available in the Unied States. These include: VAQTA (Merck), Havrix (GlaxoSmithKline), Avaxim (Aventis Pasteur MSD) and Apaxal (Berna). There is also TwinRix (GlaxoSmithKline)—a combination of hepatitis A and B vaccines. These vaccines give rise to measurable serum antibody levels within 2 weeks after a single injection to healthy people; a booster dose, recommended at 6 to 12 months, dramatically boosts antibody levels and provides virtually 100% immunity for at least 10 to 20 years, and probably for life. Hepatitis A vaccine is now recommended for all nonimmune travelers older >1 year of age going to lesser-developed countries.

Immune Globulin (IG)—Immune globulin (also known as immune serum globulin, ISG, or gamma globulin) is not a vaccine but rather a mixture of antibodies against a variety of infections, particularly hepatitis A. It confers short-lived passive immunity and is effective for preventing hepatitis A for 3 to 5 months, depending on the amount given. Because hepatitis A vaccine is not approved for children younger than 1 year of age, they are usually given immune globulin prior to travel.* Older persons, immunocompromised travelers, those with chronic liver disease and people with other chronic illnesses, who may not respond adequately to vaccination, are also candidates to receive IG.

Current Recommendations for Use of IG Travelers >40 years of age, immunocompromised persons, and those with chronic liver disease or other chronic medical conditions who have less than 2 weeks before departure may receive a single intramuscular dose of immune globulin (0.02 mL/kg) at a separate anatomic site, in addition to the initial dose of vaccine. This will ensure protection in case the vaccine is not entirely effective.

Vaccine alone, however, is sufficient when a healthy traveler is departing imminently and needs immediate protection. A single dose of vaccine can generate enough antibodies to provide clinical protection against hepatitis A, even when the traveler is exposed to the virus immediately thereafter.

*Vaccination of Children The hepatitis A vaccine is approved for children ≥1 year of age. Hepatitis A vaccine is safe in infants <1 year of age, but is effective only after the disappearance of maternal antibodies, which occurs at about 2 months of age. Infants vaccinated at 2, 4, and 6 months of age (or every 2 months x three doses) have shown 100% seroconversion, indicating that Hepatitis A vaccine (Havrix 720 Elisa Units) is highly immunogenic in seronegative infants and could obviate the need for immune globulin in this age bracket.

Children still officially too young for HAV are usually given immune globulin (IG), the dose determined by the weight of the child and the length of exposure to hepatitis A. The disadvantage of IG is that it protects for no longer than 6 months and immune globulin may also not be available. It also interferes with live attenuated virus vaccines such as measles, mumps, rubella, and varicella.

Safe Food and Drink Even if you have been immunized against hepatitis A, follow these rules to reduce your risks of acquiring other infections transmitted by contaminated food and water. This is especially important for pregnant women who may be exposed to hepatitis E:

Drink only boiled, commercially bottled, carbonated, or chemically treated water, soft drinks, fruit juices, beer, or wine.
Don’t put ice cubes in your drinks unless they have been made from safe water.
Eat only well-cooked foods. Avoid raw or undercooked meat, fish and shellfish, and raw fruits and vegetables, unless you peel them yourself. Stick to piping hot foods, if possible.
Avoid salads

Hand hygiene is also very important and effective. Hand washing before meals, or using a hand sanitizer gel such as Purell, not only reduces gastrointestinal disease, but also reduces the transmission of respiratory viruses.

Hepatitis B

Hepatitis B is important because of its potential severity and widespread occurrence worldwide. Although the hepatitis B virus is not as lethal as the AIDS virus, it is 100 times more infectious and is more easily spread by person-to-person contact.

Acute hepatitis B occurs from 6 weeks to 6 months after exposure, with an average of 75 days. The most common response to the virus is asymptomatic infection, so you may not even be aware of the illness. (Your chance of developing jaundice during the infection is less than 50%.) Whether you are symptomatic or not, your illness may last for several weeks, or even months, but if you are an adult you have a 90% to 95% chance of recovering completely and having lifelong immunity against any further attacks. Hepatitis B, though, differs in an important respect from hepatitis A: there is a 0.1% to 1% risk of death with the acute infection and an overall fatality rate of 1% to 3%. Five percent, or less, of infected adults (but up to 90% of infected newborns) become chronic carriers of the virus. Seniors who become infected also are at greater risk of becoming chronic carriers of the virus. If you do become a carrier of the virus, you can infect others, and you are also at risk for the development of chronic hepatitis, cirrhosis, and liver cancer. In fact, 10% of chronic carriers develop liver cancer.

High-Risk Countries and Exposure to the Virus

Areas where up to 5% to 20% of the population are carriers of the hepatitis B virus include all of sub-Saharan Africa, the Balkans, the Middle East, China, Southeast Asia, including Korea and Indonesia, the South Pacific Islands (Oceania), the interior Amazon Basin, Haiti, and the Dominican Republic. Travelers to these areas are at increased risk if they are exposed to the blood or body fluids of infected people. Sexual contact appears to be the most frequent mode of disease transmission, especially among expatriates staying long term in a risk area. The risk of hepatitis B in expatriates is 1:1,000 per month of stay abroad. Virus transmission also occurs from intravenous drug use, medical injections or vaccinations with contaminated needles and/or syringes, receipt of unscreened blood transfusions, or skin-to-skin contact with carriers of the virus who have open sores caused by tropical ulcers, impetigo, scabies, or infected insect bites. Fluid from these open sores can transmit the virus, and children especially may be at risk from playmates who have these open skin sores.

Figure 12.2 Geographic Distribution of Hepatitis B

Diagnosis of Acute and Chronic Hepatitis B Virus (HBV) Infection

Table 12.1 gives a summary of the serologic tests used to evaluate the status of a traveler who may be (1) acutely infected with HBV, (2) chronically infected and a carrier of HBV, or (3) nonimmune and susceptible to infection.

Table 12.1 Summary of Serologic Tests for Hepatitis B

Tests	Results	Interpretation
HBsAg	Negative
Anti-HBc	Negative	Susceptible
Anti-HBs	Negative
HBsAg	Negative
Anti-HBc	Negative or positive	Immune
Anti-HBs	Positive
HBsAg	Positive
Anti-HBc	Positive
IgM anti-HBc	Positive	Acutely infected
Anti-HBs	Negative
HBsAg	Positive
Anti-HBc	Positive
IgM anti-HBc	Negative	Chronically infected
Anti-HBs	Negative
HBsAg	Negative
Anti-HBc	Positive	Four interpretations possible*
Anti-HBs	Negative

*Possible interpretations:
1.    May be recovering from acute HBV infection
2.    May be distantly immune and test not sensitive enough to detect very low level of anti-HBs in serum
3.    May be susceptible with a false positive anti-HBc
4.    May be undetectable level of HBsAg present in the serum and the person is actually a carrier. HBsAg: If positive, obtain IgM anti-HBc to differentiate acute hepatitis B from chronic hepatitis B. Chronic hepatitis B is also defined by two HbsAg-positive tests separated by at least 6 months.

Treatment

The treatment of hepatitis B is summarized subsequently.

Prevention

Both hepatitis B immune globulin and vaccination will protect you against hepatitis B. The vaccines available in the United States, Recombivax-HB, Engerix-B, and TwinRix are genetically engineered vaccines derived from yeast. These vaccines are completely safe and virtually 100% effective in those who develop an antibody response after three doses have been administered. About 10% of recipients do not develop measurable antibody levels. Some recipients will develop measurable antibodies from additional, or increased, doses of vaccine.

If you have not been immunized, your risk of getting hepatitis B can also be reduced or eliminated by practicing safe sex or avoiding sexual contact. You should avoid medical injections or surgical procedures in less developed countries, if possible, because the equipment may not be sterile. Consider carrying a sterile needle and syringe kit.

Accelerated Immunization Because most travelers leave within a month after their first travel clinic visit, they may not have enough time to be fully immunized against hepatitis B if it is administered according to the standard schedule (0, 1, and 6 months). Studies have shown, however, that an accelerated vaccination schedule (0, 1, and 2 months or 0, 7, and 21 days) produces measurable antibodies in 80% of recipients by day 28 and more than 90% protection at 3 months. If you are departing on short notice the clinic can administer the vaccine on the accelerated schedule. Note: Even a single dose of hepatitis B vaccine may possibly “prime” your immune system and afford some protection. If you have time for only one injection of vaccine before departure, it seems worthwhile to receive it.

Immunization should be considered for the following groups: Frequent short-term travelers or any short-term traveler who engages in risk-taking activity; persons living for prolonged periods (more than 3 months) in endemic areas; adventure travelers; travelers with chronic diseases, especially chronic liver disease; older travelers; people who will have close, prolonged contact with the local population, such as health-care workers, missionaries, and relief workers; travelers who might have sexual contact with the local population; any risk-averse traveler desiring maximum preparation, especially if they are traveling in a country where the sterility of needles and syringes for medical injections cannot be guaranteed and there is the possibility of receiving a dental or medical injection.

Booster Doses Booster doses of vaccine are routinely not recommended for people with healthy immune systems. Studies suggest that about one third of those vaccinated against hepatitis B will no longer have measurable antibodies after 5 years, yet they are still considered to be protected against infection because of the body’s “immune memory.” For this reason the measurement of hepatitis B neutralizing antibody is not routinely recommended, except in people who are in high-risk occupations, such as health care, who are accidentally exposed to the virus.*

Prevention After Exposure If you are unvaccinated and have blood or body fluid exposure, you should receive hepatitis B immune globulin (HBIG), as well as the vaccine. This should be given within 24 to 48 hours following exposure to blood. If you have sexual exposure, you should receive HBIG plus the vaccine within 14 days of unsafe sexual contact.

Hepatitis C

Hepatitis C typically does not cause noticeable symptoms when initially acquired. It is usually diagnosed, often by chance years or even decades later. In 80% of those exposed, the infection becomes permanent, these people being “chronic carriers.” The carrier state is a persistent, active viral infection (chronic hepatitis C) that damages the liver, progressing over decades in 20% to 50% of carriers to cirrhosis (fibrous scarring of the liver) or, more rarely, liver cancer.

The number of new cases of hepatitis C in developed countries has decreased more than fivefold since the discovery of the hepatitis C virus (HCV). In the 1960s and 1970s, when there was a lot of experimentation with drugs, HCV got into the population that donated blood. Today, when all blood in developed countries is screened for HCV, the most common means of transmission is the sharing of needles by drug users.

In developed countries, HCV is acquired by:

Intravenous drug use (50% to 60% of cases)
Sexual contact (10% to 15%). HCV is not spread by sexual contact as efficiently as is HBV or HIV.
Miscellaneous or unknown causes: Some people are believed to have been exposed while working in a hospital, while receiving hemodialysis, during birth, or by sharing a toothbrush or razor or being exposed in some other way to infected blood. For 10% of people, there is simply no explanation for the infection. One possibility: intranasal cocaine use has recently been associated with HCV infection in persons without other risk factors.

Comparable information on trends of HCV incidence in less developed countries is unavailable. Some less developed countries don’t screen blood for HCV, so transfusions in these countries must be avoided, unless the situation is a dire emergency. Needles and syringes may also be contaminated, and you should avoid unnecessary medical injections or other forms of skin puncturing, e.g., acupuncture or tattooing, in these areas.

Treatment of Hepatitis B and C

With either hepatitis B or C, supportive treatment is indicated, but bed rest is neither necessary nor helpful. Your diet should be nutritious, but otherwise can be unrestricted. However, alcohol, the most important factor in disease progression, must be eliminated. Even more damaging is the combination of alcohol and acetaminophen. Even healthy persons who drink moderate amounts of alcohol, perhaps as little as three to four beers or mixed drinks per day for at least several weeks, and who take normally recommended doses of acetaminophen (6 to 8 extra-strength tablets) per day, are at risk for acute toxic hepatitis.

Interferon At this time, interferon a-2b (Intron A, Schering) as well as pegylated interferons are the FDA-approved drugs for the treatment of hepatitis B. About 40% of patients who are HBeAg(+) become HBeAg(-) after 6 months of treatment. Recently, the drug lamivudine has been associated with substantial histologic improvement in many patients with chronic hepatitis B.

Interferon and Ribavirin Three interferons have been approved for treatment of chronic hepatitis C: interferon a-2b (Intron-A, Schering-Plough); interferon a-2a (Roferon, Roche); alfacon-1 (Infergen, Amgen) as well as pegylated interferons (Pegasys and PegIntron). The combination of ribavirin and interferon a-2b (Rebetron, Schering-Plough) has been demonstrated to be superior to interferon a-2b alone. The genotype of hepatitis C determines the duration and response rates with combination treatment. Thirty percent of persons with genotype 1, which accounts for 70% to 80% of persons with HCV infection, remain virus free 6 months after completion of a 12-month course of treatment, whereas more than two thirds of persons with genotype 2 or 3 clear HCV after 6 months of therapy. Liver transplantation is the treatment of last resort for either disease.

Prevention of Hepatitis C

You should avoid unscreened blood transfusions in less developed countries. If a blood transfusion is required, locate a family member or colleague who would be a compatible donor. If a donor is not available, consider medical evacuation to a country with more advanced facilities. Also avoid unsafe sex and the use of potentially contaminated needles and syringes. Persons with hepatitis C should not share toothbrushes or grooming implements, should cover cuts and open sores, and should not donate blood or tissue.

There is no vaccine to prevent hepatitis C and immune globulin is not recommended after exposure. However, HCV carriers should be vaccinated against hepatitis A and hepatitis B because a superimposed infection with either virus can cause further liver damage.

Hepatitis E

Hepatitis E has many features in common with hepatitis A. They are both transmitted by the fecal-oral route, and in most cases the infection they cause is acute and self-limiting. The hepatitis E virus can be transmitted from person to person, but such secondary transmission is much less common, the incidence being 5% in hepatitis E compared with 50% for hepatitis A. This is probably because larger doses of virus are needed to transmit this disease.

Hepatitis E is endemic in many tropical and subtropical countries, with outbreaks being reported in India, Southeast Asia, China, and Russia. No outbreaks have been described in developed countries presumably because water supply and sanitary systems are more advanced..

Figure 12.3 Geographic Distribution of Hepatitis E

Most cases of hepatitis E are reported in young adults, who usually experience mild symptoms, followed by complete recovery. Chronic liver disease does not develop. However, fulminant liver failure, with a mortality rate of up to 20%, can occur in pregnant women, especially in the third trimester. Infected mothers can also transmit the hepatitis E virus to the fetus with significant consequences.

The risk to the average tourist is quite low, but the data are scarce. The risk to long-term expatriates appears to be higher. A recent study found an overall seroprevalence of 5.2% in development aid workers who lived in various underdeveloped countries for 9 years. The Indian subcontinent showed the highest incidence (10%) of infection. Infection rates for Latin America, East Africa, West and Central Africa, and Asia ranged between 6% and 9%. The Middle East had a prevalence of 2.1%. Individual countries with the highest risk of acquiring hepatitis E include Burma, Nepal, Pakistan, Sudan, China, and India.

Hepatitis E facts:

There are four infectious syndromes: asymptomatic, anicteric hepatitis, icteric hepatitis (with jaundice; most common) and fulminant hepatitis.
The incubation period lasts 2 to 10 weeks.
Asymptomatic and/or subclinical (anicteric) hepatitis may occur in 20% of Americans according to seroprevalence studies.
Typical symptoms of icteric hepatitis E include: jaundice, nausea, right-upper quadrant pain, hepatomegaly, elevated liver enzymes lasting 1-4 weeks.
Pregnancy is associated with the highest incidence of fulminant disease for unclear reasons.
Differential diagnosis of hepatitis E with jaundice includes hepatitis A, hepatitis B, hepatitis C, Epstein-Barr virus (EBV), cytomegalovirus (CMV), typhoid fever, and malaria.
Diagnosis: Antibody tests (positive IgM during symptomatic period or rising IgG titers are diagnostic) are available commercially in the United States but are not FDA approved. Can also be obtained through CDC by contacting your state health lab.

Diagnosis

Hepatitis E should be considered in returned travelers with fever and hepatitis. If tests for other forms of hepatitis are negative, serologic testing for HEV should be done. Information regarding serologic testing can be obtained from the CDC’s Hepatitis Branch in Decatur, Georgia (404-371-5910).

Treatment

No specific treatment is available. Follow the same advice as given in this chapter for hepatitis A.

Prevention

A vaccine is not available. If you are in an endemic area, especially a rural area where there is well water, strictly adhere to food and drink precautions, especially if you are pregnant. Avoid tap water, well water, and surface water. If you are treating water, remember to use a method that eliminates viruses, such as boiling, chemical disinfection, or purification with a water purifier, not a filter. Purifiers, unlike filters, eliminate viruses. Immune globulin is not protective against hepatitis E because the product in this country is not made from donors carrying sufficient antibodies to this virus.