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UDC: 616.36-002-02-07-08-084-092
Melenko Svitlana Romanivna,
PhD, Associate Professor of the Department of Infectious Diseases and Epidemiology
Bukovinian State Medical University Berbenyuk Angelina Ivanovna, student
Bukovinian State Medical University
Zhytariuk Pavlo Ivanovych
student
Bukovinian State Medical University DOI: 10.24412/2520-6990-2023-6165-17-21 HEPATITIS A: ETIOLOGY, EPIDEMIOLOGY, DIAGNOSIS, TREATMENT AND PREVENTION
Abstract.
Hepatitis A is an acute infectious liver disease that is mostly asymptomatic in children, but its severity increases with age. Only in some patients can the infection have a prolonged or recurrent course. The reason for these different outcomes is unknown, but it is generally recognized that host factors, such as immunologic status, age, and the presence of concomitant liver disease, are the main determinants of severity. Each year, about 1.5 million clinical cases of hepatitis A infection are reported worldwide. The disease is most common in low-income countries, but outbreaks can also occur in developed countries. Globalization contributes to the spread of the disease worldwide, as the number of travels, imports and exports ofproducts from country to country is constantly increasing, while the virus is transmitted mainly through direct contact with infected patients or through the consumption of untreated water and food. Injecting drug users, travelers, homosexual men, etc. are at risk. The most effective method of prevention is personal hygiene and vaccination, and vaccination is especially recommended for people at risk.
Keywords: hepatitis A, vaccination, prevention, risk groups, epidemiology
Etiology
Hepatitis A virus (HAV) belongs to the genus Hepatovirus of the family Picornaviridae [1]. Hepatitis A virus has a single 7.5 kb positive-sense RNA genome with a single open reading frame (ORF) that encodes a single large polyprotein [2]. This polyprotein is processed by viral (protease 3C) and host cellular proteases to form structural (VP4, VP2, VP3 and VP1) and nonstructural mature proteins (2B, 2C, 3A, 3B, 3C (protease) and 3D (RNA-dependent RNA polymerase) [3-5]. Hepatitis A virus is currently classified into five genotypes (according to the latest report of the International Committee on Taxonomy of Viruses). Among them, only genotypes I, II and III, which are further subdivided into subtypes A and B, infect humans [6].
Epidemiology
The hepatitis A virus is very resistant to adverse physical conditions, such as high ambient temperature, acidity, and freezing for several hours or even several months [7-9]. At 100°C, the virus is destroyed only after 5 minutes, at room temperature it can survive for several weeks, and at 40°C - for several months, but it is killed rather quickly by UV light and conventional disinfectants. The high persistence of the virus in the environment and the high titer of virus excretion in the feces of infected people explains why virus transmission and infection with the virus correlates with contaminated water, consumption of unprocessed food, and poor sanitary and hygienic living conditions [10]. The route of transmission (fecal-oral) of hepatitis A virus can be direct, i.e. through contact with an infected person, and indirect, through the ingestion of the virus with contaminated water or food. Outbreaks in developed countries occur through human-to-human trans-
mission, and sporadic cases occur through food and water, although in some cases foodborne infections can also lead to outbreaks [11-12]. In addition to unprocessed food, seafood is the main source of infection [13,14], but we should not forget about outbreaks and sporadic cases that occur through imported frozen vegetables, berries and other fruits [15]. Blood-borne transmission is rarely observed. For a long time, it was believed that patients who have to take blood products, such as hemophilia, are at increased risk of infection, and vaccination was recommended for such patients. However, improvements in virus inactivation methods, the use of sterilized recombinant clotting factors, and plasma screening for HAV in the United States have yielded results, and patients are no longer at a greater risk than the general population [16]. The virus is also transmitted during organ transplantation [17].
According to the Global Burden of Disease (GBD) for 2019, hepatitis A virus is the most commonly diagnosed among the main acute forms of hepatitis (A, B, C and E) [18,19]. In general, about 100 million cases of HAV infection and 1.5 million symptomatic cases are reported worldwide each year, resulting in 15,00030,000 deaths from hepatitis A virus per year [20]. The endemic nature of HAV is classified according to age prevalence into high (90% under 10 years of age), intermediate (50% at age 15 years with <90% at age 10 years), low (50% at age 30 years with <50% at age 15 years) and very low (50% at age 30 years) [20]. The incidence rate varies significantly from country to country; the highest incidence rate is observed in low-income countries (Africa and South Asia) [13,21]. In countries with low socio-economic conditions and poor hygiene standards, young children are exposed to HAV from childhood, so they often remain asymptomatic,
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and there is a high proportion of immune individuals among the adult population. The paradox is that in developed countries, where sanitary and hygienic conditions are much better, the level of susceptible individuals is quite high, and asymptomatic cases are almost non-existent [22].
Children under 6 years of age who are exposed to the virus are usually asymptomatic, while older children, over 6 years of age, and adults will have symptoms of prolonged jaundice and subsequent long-term treatment, and are at risk of acute liver failure. Epidemiologic surveillance in regions with high incidence is difficult because young children are asymptomatic. However, even asymptomatic cases confer long-lasting immunity against HAV, which is detected by serologi-cal reactions. Studies conducted in low-income countries show that almost 100% of the population has anti-HAV IgG, which is serological evidence of an infection. Often, an outbreak begins after several patients have been identified, which is facilitated by a long incubation period.
Specific risk groups in developed countries
1. Increased level of infection with HAV:
1.1. International travelers
Hepatitis A can be prevented by vaccination among travelers. It affects travelers who travel from ep-idemiologically low-risk countries or areas to areas at high risk of infection. Between 2005 and 2007, travel-associated hepatitis A accounted for 46% of all cases, meaning that almost one in two cases was travel-related [22]; and between 2009 and 2015, travel was responsible for 30% of all hepatitis A cases in Europe [23].
1.2. Homosexual relations between men
Outbreaks of hepatitis A among homosexual men
are common in developed countries in Europe, America, and Australia [24-25]. The increased risk in this population group led to the recommendation of vaccination for men who have sex with men in 1996 [26]. A large outbreak of infection occurred in Europe after the EuroPride festival in Amsterdam, when more than 4000 confirmed cases were reported in 22 European countries [27]. The vaccination rate among this population ranges from 25-45%, which is low, given the numerous recommendations [28-30]...
1.3. People who use psychoactive substances and people who find themselves on the street (homeless)
It is well known that injecting drug users are more likely to have hepatitis B and C than other types of the disease, but research over the past decade has shown that this population is also susceptible to hepatitis A [31-33]. Although the transmissible route of transmission is not the main one for hepatitis A, this population group includes not only injecting drug users, but also non-injecting drug users, which leads to the idea that infection occurs due to non-compliance with sanitary and hygienic standards, these individuals may reuse disposable medical supplies (syringes), and they do not observe hygiene during drug preparation. That is, even among drug addicts and homeless people, infection occurs through the fecal-oral route, due to poor hygiene during and before cooking and preparing food and drugs; not washing hands after using the toilet [32,34]. Because many people in these populations suffer from
chronic hepatitis B and C, outbreaks of hepatitis A lead to high mortality.
A study of one outbreak of hepatitis A in Indiana found that 74% of 264 infected individuals were people who use psychoactive substances. As a result of the outbreak, 2% of the infected died and 30% developed chronic liver failure [35]. In addition, a study of the outbreak that began in 2016 in the United States and covered several states found that of the nearly 40,000 people infected (as of July 16, 2021), 73.2% were drug addicts, 14% had problems with permanent housing; it was also drug addicts, homosexual men, and homeless people who were most often hospitalized [36-37]. Vaccination is the best solution to prevent this problem in these populations, as they do not have access to adequate sanitation.
1.4. Homosexual men
High-risk behaviors among these individuals (oral sex, drug use) lead to more frequent outbreaks of hepatitis A virus among them [38]. This category of people also falls under the recommendations for vaccination.
2. Persons at increased risk of severe disease
The severity of disease and mortality from HAV is increased in people with HBV and HCV and other chronic liver diseases [42], such as alcoholic cirrhosis and fatty liver disease [43]. Individuals with HIV shed virus for a longer period of time and have higher titers [44]. Although patients with HAV have more severe disease, they are also associated with milder disease, as lower alanine aminotransferase activity is observed in patients with plasma RNA levels >1000 copies/mL [39,40].
In her 2018 paper "Globalization and the Changing Epidemiology of Viral Hepatitis A", Kathryn H. Ja-cobsen notes that in recent years there has been a downward trend in the incidence rate in most countries, with countries with very high rates moving to high rates and so on. This trend is due to several factors, namely increased access to clean drinking water and improved sanitation, where everyone in the community should have access to fresh drinking water, a toilet and a place to wash their hands after using the toilet. Also, people who care for young children who need help going to the toilet, people in the food industry, can help reduce the incidence of the disease by maintaining personal hygiene. Another important factor is socio-economic space, because even if we consider this factor at the level of ordinary households, families with higher incomes and fewer family members are less susceptible to infection because they are not as crowded, and everyone has more space of their own. Also, people with a higher social status will have less contact with possibly infected people. An equally important factor is the migration of the rural population to cities, industrial activities of the rural population in the city, etc., as villagers live in places with less sanitation, there is a high probability that they may be carriers or infected, and urban residents are more susceptible to infection, especially when villagers sell their own products in cities. In communities where a large percentage of the population is young children who may be asymptomatic, the infection rate remains consistently high because there is con-
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stant infection from child to child, meaning that the disease is endemic in such areas. While in areas where the majority of the population is older, the disease cannot become endemic, but its residents are more susceptible to hepatitis A virus infection [49].
Diagnosis
The differential diagnosis of viral hepatitis A, in addition to the differential diagnosis with other types of hepatitis, includes other diseases such as cytomegalo-virus, Epstein-Barr virus, leptospirosis, Rocky Mountain spotted fever, typhoid fever, parasitic infections, autoimmune hepatitis, lupus erythematosus, drug-induced liver damage, and liver damage due to self-injury, such as toxins and alcohol. Highly sensitive and specific serological tests for anti-HAV IgM have been available for over 40 years. Specific IgM remains positive for a long period of time, disappearing from patients' serum within 7 months after infection, but has the ability to persist for up to a year, while anti-HAV IgG remains positive for life [41].
Treatment
Most cases of acute hepatitis A do not require specific treatment. Some patients with liver failure require aggressive treatment and should consider liver transplantation [45].
Prevention
Prevention of viral hepatitis A is carried out by several main methods, namely: careful adherence to personal hygiene, adequate sanitation, contact tracing during outbreaks, isolation of patients, active and passive immunoprophylaxis. Immunization is carried out with a vaccine or immunoglobulin [46]. According to the Order of the Ministry of Health of Ukraine No. 595 of September 16, 2011, the vaccine against hepatitis A virus is one of the recommended vaccinations. The hepatitis A vaccine is administered intramuscularly starting at the age of 1-2 years. The vaccination course consists of two doses administered at intervals of 6-18 months. [48]. The U.S. Centers for Disease Control and Prevention provides recommendations for vaccination of healthy people aged 12 months to 40 years; immuno-globulin for those over 40 years, although vaccination is also acceptable; immunoglobulin is also administered to children under 12 months, immunocompro-mised individuals, patients with chronic liver disease, and anyone else who has contraindications to the vaccine [47].
Prevention also includes screening, which should be done by high-risk individuals, primarily homosexual men, injecting drug users, patients with HIV/AIDS or hepatitis C. Patients who are screened negative should be vaccinated [49].
The type of prevention may differ from region to region, or rather, the main focus of prevention may differ from region to region, for example, in regions where viral hepatitis A is endemic, the main focus of prevention is on improving sanitation, changing cooking conditions, and meat products, especially pork and game, should be cooked properly [45].
Conclusions
Hepatitis A virus is the most common among all types of hepatitis. The virus is spreading due to the globalization of all processes in the world, imports and
exports are increasing, people travel a lot, and due to insufficient hygiene, the incidence rate may increase. However, the improvement of sanitary conditions, due to increased public awareness and a number of other factors, have led to a significant decrease in the number of patients in the world. However, the reduction of the disease risk is not uniform globally, as there are many low-income countries where, despite certain attempts to change the situation for the better, there is a high incidence of hepatitis A, i.e. in certain regions the disease remains endemic. At the same time, in high-income countries with good living conditions, the incidence rate is decreasing, but outbreaks occur, because the population of these countries is very susceptible to hepatitis A virus infection. In general, the incidence rate is still quite high, which is quite surprising given the ease of prevention of this pathology, to some extent, the incidence rate is high due to the low level of vaccination against hepatitis A, especially among men who have same-sex relationships, injecting drug users and people without a permanent place of residence, globalization, and travelers. Prevention should be aimed at further improving sanitary conditions and increasing vaccination rates, especially among most-at-risk populations.
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