Hepatitis A is a viral infection that causes inflammation of the liver. It is caused by the hepatitis A virus, also known as HAV. Hepatitis A is the most common form of viral hepatitis, with an estimated 1.4 million infections worldwide each year.

Hepatitis A is most common in developing areas including Central and South America, Africa, the Middle East and Asia. Whilst it used to be a common childhood infection in the United Kingdom, United States and other developed countries in the early 20th century, it is now infrequent due to improved sanitation and water treatment. In England and Wales, there were more than 7000 cases in the early 1990s, falling to just over 1000 in 2001. In the United States, about 7600 cases were reported in 2003. Because fewer people now become infected and gain immunity as children, more remain susceptible to hepatitis A as adults (Giammarino 2005).

Diagnosis and monitoring

A blood test that measures antibodies against the hepatitis A virus can show whether a person has been exposed to the virus. Some people with compromised immunity may not produce enough antibodies to be detected by the usual tests. The virus's genetic material may also be measured directly.

Other blood tests are used to detect and monitor liver problems. These include liver function tests, which measure levels of particular enzymes including alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the blood to determine how well the liver is working. Bilirubin, a by-product of the breakdown of red blood cells, is also commonly elevated in people with hepatitis A.

Symptoms and disease progression

Hepatitis A has an incubation period of between 15 and 50 days between infection and the development of symptoms. The hepatitis A virus replicates in liver cells, but liver injury is due to the bodys immune response rather the direct activity of the virus itself.

Most infants and young children have asymptomatic or mild disease, but the severity of illness increases with age. A majority of older children and adults experience symptoms, which may include:

• Feeling unwell.

• Fatigue.

• Nausea and vomiting.

• Diarrhoea.

• Loss of appetite.

• Fever.

• Upper abdominal pain.

• Muscle and joint aches.

After these initial symptoms, about 70% of older children and adults develop jaundice (yellowing of the skin and eyes) and about 80% experience hepatomegaly (liver enlargement).

Hepatitis A almost always clears up spontaneously. About 85% of infected individuals experience complete clinical recovery and normalisation of liver enzyme levels within three months, and most of the rest fully recover by six months (Koff 1992). Unlike hepatitis B and C, hepatitis A does not become chronic or lead to long-term liver damage such as cirrhosis or liver cancer. Once a person has had hepatitis A, they will not get it again.

Unusual symptoms

In less than 1% of cases, people infected with hepatitis A virus may develop an acute form of rapid liver failure called fulminant hepatitis, which can be severe or even fatal (Rezende 2003). Fulminant liver failure can lead to impaired blood clotting, metabolic disorders, brain dysfunction and coma. The risk of developing fulminant hepatitis is significantly higher amongst people with pre-existing liver disease, including chronic hepatitis B or C (Vento 1998).

Other atypical manifestations of hepatitis A virus infection include relapsing hepatitis, bile duct blockage, autoimmune hepatitis and a variety of other conditions unrelated to the liver. Relapsing hepatitis, characterised by prolonged or recurring symptoms and abnormal laboratory values occurs in an estimated 5 to 20% of cases (Schiff 1992; Glikson 1992). Manifestations due to effects outside the liver may include arthritis, skin rash, enlarged spleen, blood cell disorders, kidney dysfunction and blood vessel inflammation.

Treatment

The immune system typically clears the hepatitis A virus without treatment. During acute infection, supportive care is warranted, including rest, a healthy diet and avoidance of alcohol and medications that are harmful to the liver, such as paracetamol.

Individuals who develop fulminant liver failure should be managed in an intensive care unit, preferably at a facility capable of performing liver transplantation, as this is the only definitive treatment.

Transmission and prevention

Hepatitis A is most often transmitted from person-to-person via the faecal-oral route. It may be spread through close household or personal contact and through certain sexual practices, notably oral-anal sex (anilingus or rimming). The hepatitis A virus may also spread through contaminated water or food, most often undercooked shellfish or raw fruits or vegetables (Conaty 2000; Wheeler 2005).

Several hepatitis A outbreaks have been reported amongst gay and bisexual men (Centers for Disease Control and Prevention 1992; Henning 1999). For example, a cluster of 69 cases possibly attributable to sexual transmission between men was reported in Norway in 2004 (Blystad 2004). Likewise, in the autumn of 2004 the United Kingdom's Health Protection Agency identified a hepatitis A outbreak amongst nine gay men in London, most of whom frequented a particular pub with a darkroom where sexual activity took place (Health Protection Agency 2004). Other recent outbreaks have been reported in Denmark, France, Germany, the Netherlands and Sweden (Mazick 2005; Mø¬¢¡« 2004). Whilst some studies have associated hepatitis A virus transmission with a larger number of sex partners and specific sexual practices, other research has not found a link with homosexual activity (Coutinho 1983; Katz 1997; Ross 2002; Villano 1997).

Although hepatitis A virus is not considered primarily a blood-borne infection like hepatitis B and C viruses, cases have been attributed to blood product transfusion (Chudy 1999). Injecting and non-injecting drug users also have higher rates of hepatitis A infection (Villano 1997). Transmission from mother-to-child during pregnancy, birth or breast-feeding is rare. In about half of all cases, the transmission route is unknown.

Hepatitis A can be prevented by practicing good hygiene, including hand-washing after using the toilet or changing nappies, and before preparing or eating food. Avoid drinking untreated water when travelling in areas where hepatitis A is common. Also, avoid sharing items such as razors, toothbrushes or needles for injecting drugs. Safer sex practices, in particular use of barrier devices for oral-anal sex, can help reduce the risk of transmission.

Vaccine

Vaccination is the most reliable means of preventing hepatitis A. The hepatitis A vaccine is safe and effective for people over one year of age (Clemens 1995; Innis 1994; ). Two brands are available, Havrix, manufactured by GlaxoSmithKline and VAQTA, manufactured by Merck & Company, which appear similarly effective (Braconier 1999). There is also a combination hepatitis A and B vaccine called Twinrix (GlaxoSmithKline).

The hepatitis A vaccine is typically given in two doses, the second six to twelve months after the first. At least 95% of recipients develop antibodies within four weeks after the first dose. Protection has been shown to last at least ten years and may last as long as 30 years (Van Damme 2003; Van Herck 2004). The vaccine has not been associated with serious side-effects.

United Kingdom and United States guidelines recommend vaccination for at-risk individuals, including:

• Household contacts of people with hepatitis A.

• Sexual partners of people with hepatitis A.

• Men who have sex with men.

• International travellers to areas where hepatitis A infection is endemic.

• Injecting drug users. The United States guidelines also include users of non-injection recreational drugs.

• People with pre-existing liver disease.

People with chronic hepatitis B or C should be vaccinated because they are at increased risk for fulminant hepatitis A. The British HIV Association (BHIVA) and the United States Public Health Service recommend that all HIV-positive people should receive the hepatitis A vaccine unless they have already had hepatitis A or are known to have hepatitis A virus antibodies. As discussed below, vaccination is safe and generally effective in people with HIV.

Unvaccinated individuals who are exposed to hepatitis A may benefit from post-exposure prophylaxis using injected antibodies called 'human normal immunoglobulins' (HNIGs). HNIGs should be administered within two weeks of exposure and protection lasts three to six months.

Hepatitis A in HIV-positive people

The epidemiological and clinical manifestations of HIV / hepatitis A co-infection have not been well studied. Unlike with hepatitis B and C, research to date generally does not suggest that hepatitis A is more severe in HIV-positive individuals or vice versa.

The hepatitis A vaccine, which is made with inactivated virus, is safe and effective in people with HIV. However, severely immunocompromised individuals may not produce an adequate supply of antibodies and may be more likely to lose protective immunity over time (Bodsworth 1997; Kemper 2003; Santagostino 1994; Wallace 2004). This suggests that vaccination should be done early in the course of HIV disease, before immune function has declined. If a person presents with compromised immunity, use of antiretroviral therapy to raise the CD4 cell count may improve vaccine response.

Key research

Vento (1998) followed 163 patients with chronic HBV and 432 with chronic HCV for seven years. HAV co-infection occurred in 27 patients. 9 of 10 (90%) individuals with HBV had an uncomplicated course of hepatitis A (1 with pre-existing cirrhosis developed cholestasis), while 7 of 17 (41%) HCV-positive patients experienced fulminant liver failure, 6 of whom died.

Ida (2002) reported that HIV/HAV co-infection leads to higher and longer lasting HAV viraemia. Although the duration of hepatitis A symptoms was unaffected by HIV status, HIV-positive patients exhibited HAV viraemia for a median of 53 days, compared with 22 days amongst the HIV-negative individuals. HAV viral load was significantly higher in those with HIV, regardless of HIV viral load or CD4 cell count.

Mazick (2005) conducted a case-control study that included 18 cases of HAV predominantly among gay and bisexual men in Copenhagen in 2004, compared with 64 controls recruited at a gay pride festival. 16 of 18 (89%) cases and 36 of 63 (57%) controls had sex with casual partners (OR=5.6; 95% CI 1.2-26.9). 11 of 18 (61%) cases and 14 of 62 (23%) controls had sex in gay saunas (OR=4.2; 95% CI 1.5-11.5). Sex at private homes was associated with lower risk of HAV (OR=0.2; 95% CI 0.1-0.7).

Coutinho (1983) studied 689 gay men, 290 (42%) of whom had HAV antibodies at baseline. Among the 399 initially HAV-negative men, 35 contracted HAV during 690 days of follow-up. The incidence increased steadily, rather than in clusters. Exposure to HAV was significantly associated with duration of homosexual activity (p < 0.006), as well as having a larger number of sex partners in the prior 6 months.

Katz (1997) studied 411 young men (aged 17-22) surveyed at public venues in San Francisco and Berkeley, California. Baseline HAV seroprevalence was 28%, and 3.3% of susceptible men appeared to have recent infection. Independent predictors of HAV infection were Latino ethnicity (OR=5.3; 95% CI, 3.1-8.9), having 50 or more lifetime male sex partners (OR=1.8; 95% CI, 1.1-3.0) and having a lower education level. Insertive anal intercourse (OR=5.6; 95% CI, 1.0-32.8) and sharing dirty needles (OR=32.1; 95% CI, 3.0-346) predicted recent HAV infection.

Villano (1997) tested serum samples from 300 IDUs, 300 gay men and 300 blood donors. HAV antibodies were detected in 66% of IDUs, 32% of gay men and 14% of blood donors. HAV was not significantly associated with high-risk drug-using behaviour (p > 0.10), although this correlation was seen amongst low-income IDUs (p = .018). HAV incidence increased with the number of sex partners (p < .001) The researchers suggested that factors related to low socioeconomic status were more important as a risk factors for HAV than sex or drug use.

In a case-control study in the UK, Ross (2002) found an overall HAV seropositivity rate of 29%. Although ethnicity and age were strongly associated with higher rates of HAV, there was no significant difference in HAV seroprevalence between homosexual and heterosexual men. However, history of sex in a sauna was associated with increased HAV risk.

Ridolfo (1994) reported on 2 HIV/HAV co-infected patients in whom acute hepatitis A was associated with a marked and prolonged increase in HIV viral load. In one case, HAART interruption was a possible confounding factor. The researchers suggested that immune activation induced by HAV infection may trigger HIV replication.

In a study of 113 HAV-susceptible haemophiliacs (47 HIV-positive, 66 HIV-negative), Santagostino (1994) found that HAV vaccination induced antibody production in 89% of HIV-negative patients after one dose and 100% after the second does. Amongst the HIV-positive participants, 76% achieved HAV antibody titres of at least 20 mIU/ml after the second dose, dropping to 40% amongst those with evidence of HIV disease progression.

Kemper (2003) randomly assigned 133 HIV-positive patients to receive two doses of HAV vaccine or placebo 6 months apart. At month 9, HAV antibody production was seen in 68% of those with CD4 cell counts of 200 or more cells/mm³, compared with 9% of those with fewer than 200 CD4 cells/mm³ (p=.004).

Wallace (2004) administered the VAQTA HAV vaccine (2 doses, at week 0 and week 24) to 180 individuals, half of whom were HIV-positive. At week 28, 94% of the HIV-positive patients and 100% of the HIV-negative individuals had experienced HAV seroconversion. However, within the HIV-positive group, 87% of those with CD4 cell counts of 300 or fewer cells/mm³ produced HAV antibodies, compared with 100% of those with higher CD4 counts.

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