Hepatitis viruses

There are five viruses – Hepatitis A, B, C, D & E, for which the liver is the principal target organ and the disease caused by them is generally referred to as “viral hepatitis”. Although the organ most affected by these viruses is the liver, they differ greatly in their structure, mode of replication, course of disease, and mode of transmission. Several other viruses are capable of causing clinical hepatitis including EBV and CMV.

Hepatitis A

Hepatitis A virus (HAV) causes “infectious hepatitis” and is spread by the fecal-oral route and, consequently, is much more prevalent in developing parts of the world. HAV infections result from consumption of contaminated food or water. Shellfish is a particular hazard. HAV is a picornavirus and has been renamed Enterovirus 72. Infections usually occur during warm weather.

Pathogenesis

HAV is ingested, replicates in the oropharynx and the epithelial lining of the intestines, initiates a transient viremia, and then targets parenchymal cells of the liver.

Clinical

The hallmark of hepatitis is jaundice – yellow discoloration of the skin due to accumulation of bile pigment. It is accompanied by fever, malaise and anorexia which are generally fairly mild in the case of Hepatitis A. It usually resolves without effecting chronic injury.

Laboratory diagnosis

The diagnosis is made serologically by the identification of the anti-HAV antibody of the IgM class.

Treatment and Prevention

There is no specific treatment. Spread is reduced by interrupting the fecal oral spread of the virus i.e., proper cooking of food, washing contaminated hands and treating drinking water. A vaccine is available and is recommended for those visiting endemic areas.

Hepatitis B

Classified as a Hepadnavirus, Hepatitis B virus is the prototypic parenterally transmitted (“blood borne”) virus. It has an unusual structure with several separate components that are important from both the diagnostic and pathogenic perspectives.

Structure

Circular DNA is enclosed by a 27 nm icosahedral capsid referred to as the “Core Antigen”(HBc) which is covered with a protein coat referred to as “Surface Antigen”(HBsAg). This surface antigen is generally produced in vast excess, and is found in the blood of infected individuals in the form of filamentous and spherical particles. Surface Antigen is the primary marker of infectivity.

A separate secreted protein of unknown function is referred to as “e antigen”. Designated HBeAg, it is a marker of high levels of infectivity. While all persons with HBsAg in their serum are infectious, those with HBeAg in their serum as well are highly infectious. It is measured infrequently.

Epidemiology

Hepatitis B virus is the most infectious blood-borne virus of humans. The infectious dose is extraordinarily small. It is transmitted through blood or body fluids such as semen, cervical secretions, and saliva. Blood contains the highest concentrations of virus; saliva contains the lowest. The HBV chronic carrier (defined as a person who is HBsAg-positive for 6 months) is the primary reservoir of infection. Modes of transmission include transfusion of blood or blood products (which is now rare in North America because of routine screening of donated blood and viral inactivating treatments of some blood products), sharing or reusing needles or syringes, percutaneous or mucous membrane exposure to blood or body fluids, and sexual activity. Percutaneous contact with contaminated inanimate objects may be a source of infection as HBV can survive for 1 week or longer on dry surfaces. Hepatitis B virus is not transmitted by the fecal-oral route.

A substantial proportion of persons with chronic HBV infection ultimately die of chronic liver disease (i.e., chronic active hepatitis or cirrhosis) or primary hepatocellular carcinoma (PHC). Persons infected as infants or young children are at higher risk of death due to liver disease than are those infected as adults. The risk of chronic infection with HBV is related inversely to the age at the time infection occurs. Transmission from mother to infant during the perinatal period (i.e., vertical transmission) occurs in infants born to HBsAg positive mothers. If not infected during the perinatal period, infants of HBsAg positive mothers remain at high risk of acquiring infection by person to person (i.e., horizontal transmission) during the first 5 years of life.

Most infected persons in North America acquire the infection as adolescents or adults. Groups at highest risk include users of injection drugs, persons with multiple sexual partners, in particular gay males. Others at increased risk include those with occupational exposure to blood or body fluids, staff of institutions and nonresidential child care programs for the developmentally disabled, patients receiving hemodialysis, and sexual or household contacts of persons with an acute or chronic infection. However, more than one third of infected persons do not have readily identifiable risk factor. Infection with HBV in adolescents and adults is associated with other sexually transmitted diseases. The frequency of HBV infection and patterns of transmission vary markedly throughout the world. In most areas of the United States, Canada, Western Europe, Australia, and southern South America, the infection is of low endemnicity and occurs primarily in adolescents and adults; 5% to 8% of the total population has been infected, and 0.2% to 0.9% have a chronic infection. In contrast, HBV infection is highly endemic in China, Southeast Asia, and Africa. In these areas, most infections occur in infants or children younger than 5 years, 70% to 90% of the adult population has been infected, and 8% to 15% have a chronic infection. Worldwide, HBV is a major cause of chronic liver disease and PHC.

Clinical Manifestations

Hepatitis B virus (HBV) causes a wide spectrum of manifestations, ranging from asymptomatic seroconversion, subacute illness with nonspecific symptoms (e.g., anorexia, nausea, or malaise), clinical hepatitis with jaundice (yellow skin) and icterus (yellow eyes), to fulminant fatal hepatitis. Anicteric or asymptomatic infection is most common in young children. Arthralgias, arthritis, or macular rashes can occur early in the course of the illness. Chronic HBV infection with persistence of hepatitis B surface antigen (HBsAg) occurs in as many as 90% of infants infected by perinatal transmission, in 30% of children 1 to 5 years old infected after birth, and in 5% to 10% of older children, adolescents, and adults.

Chronically infected persons are at increased risk for developing chronic liver disease (cirrhosis, chronic active hepatitis, or chronic persistent hepatitis) and primary hepatocellular carcinoma in later life.

Diagnosis

Hepatitis B is unusual in that several antigens and antibodies are routinely measured and used in the diagnosis of acute and chronic infection. Successful Immune Response Hepatitis B Surface Antigen (HBsAg)

Prevention

A very effective vaccine is routinely given to all Grade 4 children in Newfoundland. It is composed of genetically engineered Surface Antigen. Eventually it will be part of the routine early childhood schedule. Until such time as it is universal, its use should be advocated for all persons at increased risk, in particular health care workers.

Attention to the handling of sharp instruments (e.g. needles, scalpels) is also very important in minimizing risk in the health care setting. Hepatitis B is very efficiently transmitted via “needle stick” injury.

Hepatitis C

Hepatitis C virus is a small single stranded RNA flavivirus that was recently discovered to be the predominant cause of parenterally transmitted “non–A, non–B hepatitis”.

Epidemiology

Distributed worldwide, prevalence in any population is related to the prevalence of the practices of sharing injection drug equipment and the prevalence of poor healthcare practices (especially as relates to blood transfusion). Estimates of numbers of people infected in Europe and North America range from 0.5 – 2%.

Infection is spread primarily by parenteral exposure to blood and blood products from HCV–infected persons. The current risk of HCV infection following blood transfusion is very low in North America because of the exclusion of high–risk individuals from the pool of blood donors and by the screening of donors with assays for HCV antibody and nucleic acid amplification tests.

The highest seroprevalence rates of infection occur in persons with large or repeated direct percutaneous exposure to blood or blood products, such as injection drug users and patients with hemophilia who have received multiple blood transfusions. Rates are moderately high among those with smaller but repeated direct or inapparent percutaneous exposures, such as hemodialysis patients (20%); and lower rates are found among those with inapparent parenteral or mucosal exposures, such as persons with high–risk sexual behaviors and sexual and household contacts of infected persons (1% to 10%), as well as among those with sporadic percutaneous exposures, such as health care workers (1%).

Other body fluids contaminated with infected blood also can be sources of infection but far less efficiently than direct blood to blood contact. Sexual transmission has been described but is uncommon.

Seroprevalence among pregnant women in the United States has been estimated at 1% to 2%, but maternal–fetal (vertical transmission) is very uncommon.

All individuals with HCV antibody and/or HCV–RNA in their blood are considered to be infectious.

The incubation period for HCV infection averages 6 to 7 weeks with a range of 2 weeks to 6 months.

Clinical Symptoms

The signs and symptoms of hepatitis C infection are often indistinguishable from those of hepatitis A or B infection. Acute disease tends to be mild and insidious in onset and in children most infections are asymptomatic. Jaundice occurs in only 25% of patients, and abnormalities in liver function tests generally are less than those in patients with hepatitis B infection. Persistent infection occurs in at least 85%, even in the absence of biochemical evidence of liver disease. Most children with chronic infection are asymptomatic. Approximately 65% to 70% of patients develop chronic hepatitis and 20% develop cirrhosis; primary hepatocellular carcinoma can occur in these patients.

Prevention

There is no vaccine for HCV. Blood is currently screened in North American Blood Banks for HCV antibody and HCV RNA.

Treatment

Recent advances in therapy have made it possible to cure a proportion of infected individuals. Most success has occurred with a combination of interferon–alpha and ribavirin (an antiviral agent with ill–defined mechanism of action). Cost is a major issue.

Further reading – Health Canada Hepatitis C fact sheet

Hepatitis D

Approximately 15 million people in the world are infected with hepatitis D virus. It is a “defective satellite virus” that can replicate only in HBV–infected cells. Those coinfected with both Hepatitis B and D are more likely to have severe disease than those infected with Hepatitis B only.

Pathogenesis

The “delta agent” is spread in blood, semen, and vaginal secretions in a fashion similar to HBV. It can replicate and cause disease only in individuals with active HBV infections (surface antigen positive).

Clinical Syndromes

The delta agent increases the severity of hepatitis B infections. Individuals infected with delta agent are much more likely to develop fulminant hepatitis than are those with the other hepatitis viruses or hepatitis B alone. Chronic infection with delta agent can occur in individuals with chronic HBV.

Hepatitis E

The clinical course and mode of transmission of Hepatitis E virus (HEV) are very similar to Hepatitis A. It is a particular problem in developing countries where the mode of transmission is usually feces contaminated water. Very large outbreaks have been described in refugee camps. The mortality for HEV is 1% to 2%, approximately 10 times that of HAV. HEV infection is especially serious for pregnant women (mortality of approximately 20 %)

Heptatitis G

HGV is a recently defined virus that is also known as GB-C virus after the initials of the surgeon who was the source of the first isolate. It is unclear whether it is a cause of much liver disease. It is often found in people chronically infected with other hepatitis viruses making it difficult to define the effect.

Further reading – Health Canada Hepatitis G fact sheet

Category: Microorganisms

Other Notes