Hepatitis A virus (HAV):
HAV belongs to the picornavirus group. HAV has diminished in importance over the past several decades in developed countires, but infection remains endemic in many regions of Central and Southeast Asia, Africa, and Central and South America.
structure
HAV has a relatively small ssRNA genome with a naked capsid with cubic symmetry.
Hepatitis A virus (HAV), an unusual member of the Picornaviridae family. Recent studies have shown that HAV exists in two forms—a regular, nonenveloped form and an enveloped form (eHAV), which is predominant in the sera of infected individuals. Although both forms are equally infectious, their means of cellular-membrane penetration—specifically, whether the two forms of HAV have separate pathways of entry into host cells or whether a unified pathway exists for this purpose—is unclear. While it is possible that eHAV has evolved its own separate mechanism for membrane fusion-based entry, no protein component analogous to glycoproteins of 9/11/25, 9:42 PM The VP4 Peptide of Hepatitis A Virus Ruptures Membranes through Formation of Discrete Pores – PMC enveloped viruses has been detected in the eHAV lipid envelope so far. Another plausible entry mechanism involves the conversion of eHAV into its nonenveloped counterpart during the initial encounter with host cells. The shedding of the lipid component would allow the viral capsid proteins to interact with the HAV cellular receptor 1 (HAVCR-1).
Transmission/prevention
HAV has a short incubation time (15-45 days) and is transmitted by the oral-fecal route or anal intercourse. Contaminated water supplies (e.g., wells near sewers) can also serve as a source.
Populations at most rick of HAV include (1) travelers who have visited endemnic areas of Africa, Asian and parts of central and south America, (2) men who have sex with men, (3) homeless (4) incarcerated and (5) drug users. See Koenig. India is considered to be a hyper endemic region for HAV. See Arora
The primary way to prevent infection is by way of vaccination. In the US, the vacination is a 2 dose series licensed for all persons above the age of 12 months. The HAV vaccine is composed of an inactivated virus. Persons with recent exposure to the HAV can be adminsitered the single agent HAV vaccine within two weeks of exposure to prevent infection.
Solar disinfection (SODIS) is a HWTS method that has been gaining popularity over the last 30 years. The SODIS technique consists of exposing small-volumes (up to 3 l) of contaminated water with low turbidity (<30 NTU) in transparent containers (usually polyethylene-terephthalate [PET] bottles) to direct sunlight for at least 6 h (or 2 consecutive days if there is more than 50% of cloud cover) during the maximum intensity of radiation. Biocidal effects of SODIS are attributed to optical (UVA) and solar mildheating mechanisms SODIS showed significant (P < 0.05) reductions from 4.0 (±0.56) ×104 to 3.15 (±0.69) × 103 RNA copies/100 ml (92.1%, 1.1 log) for HAV. SODIS conditions induced a loss of infectivity between 33.4% and 83.4% after 4 to 8 h in HAV trials, and between 33.4% and 66.7% after 6 h to 8 h in MNV-1 trials. See Polo
Populations at highest risk for HAV infection include travelers from high-income developed countries who visit endemic areas of Africa, Asia, and parts of Central and South America, men who have sex with men, close contacts (household or sexual) with infected persons, persons exposed to daycare centers, as well as the homeless, the incarcerated, and illicit drug users
Populations at highest risk for HAV infection include travelers from high-income developed countries who visit endemic areas of Africa, Asia, and parts of Central and South America, men who have sex with men, close contacts (household or sexual) with infected persons, persons exposed to daycare centers, as well as the homeless, the incarcerated, and illicit drug users
PPPopulations at highest risk for HAV infection include travelers from high-income developed countries who visit endemic areas of Africa, Asia, and parts of Central and South America, men who have sex with men, close contacts (household or sexual) with infected persons, persons exposed to daycare centers, as well as the homeless, the incarcerated, and illicit drug users
Populations at highest risk for HAV infection include travelers from high-income developed countries who visit endemic areas of Africa, Asia, and parts of Central and South America, men who have sex with men, close contacts (household or sexual) with infected persons, persons exposed to daycare centers, as well as the homeless, the incarcerated, and illicit drug usersPopulations at highest risk for HAV infection include travelers from high-income developed countries who visit endemic areas of Africa, Asia, and parts of Central and South America, men who have sex with men, close contacts (household or sexual) with infected persons, persons exposed to daycare centers, as well as the homeless, the incarcerated, and illicit drug usersPopulations at highest risk for HAV infection include travelers from high-income developed countries who visit endemic areas of Africa, Asia, and parts of Central and South America, men who have sex with men, close contacts (household or sexual) with infected persons, persons exposed to daycare centers, as well as the homeless, the incarcerated, and illicit drug usersPopulations at highest risk for HAV infection include travelers from high-income developed countries who visit endemic areas of Africa, Asia, and parts of Central and South America, men who have sex with men, close contacts (household or sexual) with infected persons, persons exposed to daycare centers, as well as the homeless, the incarcerated, and illicit drug users
Pathology/symptoms
Symptoms are usually mild and not chronic (lasts up to 2 weeks) and can include pain in upper right quadrant, nausea, jaundice, dark urine, clay colored stool, enlarged liver. Development of IgG provides long lasting immunity. Effective inactivated whole virus vaccines are available.
The liver pathology caused by HAV infection is indistinbuishable from that cuased by HBV. However, unlike HBV, HAV cannot initiate a chronic infection and is not associated with hepatic cancer.
Hepatitis B virus (HBV) (and Hepatitis D):
HBV belongs to the hepadnavirus group. HBV affects an estimated 300 million persons on a global basis. About 1.25 million people in the US are chronic carriers, defined as positive for hepatitis B surface antigen for more than at least 3 months. Although most carriers do not develop hepatic complicaitons form chronic HBV, 15-40 percent will develop serious sequelae during their lifetime.
structure
HBV has a ds/ss DNA genome and an envelope.
Hepatitis D is an enveloped RNA virus. It is actually a subivrus satellite of HBV, that is, it can propagate only in the presence of HBV.
Symptoms
In comparison with HAV, HAB has a long incubation time (70 days) and a gradual onset but more acute symptoms than HAV.
Transmission/prevention
The disease is blood borne and transmitted sexually or from the mother at birth. For sexual transmission, HBV is often transmitted trhough unprotected anal sex or receptive oral sex (giving oral sex). See Mayo Clinic
HBV enters the body through a break in the skin or mucous membrane or by injection into the bloodstream.
The primary prevention for HBV infection is vaccination. A vaccine called Pediarix contains protection agasint HBV, diphtheria, tetanus, pertussis and polio. It is recommended for children between 6 weeks and 7 years.
Disease Pathology
An important factor in the transmission pattern of HBV is that it multiples exclusively in the liver, which continously seeds the blood with viruses.
Persistance of hepatitus B surface and envelope antigens (HBsAg, HBeAg) is associated with poor prognosis whereas development of antibodies against these antigens is associated with recovery. HBV can be either “acute” or “chronic”. Acute HBV is a mild illness that can last a few weeks or months. While some people “clear” the virus, others go on to develop chronic HBV. HBV is a chronic disease in about 15% of the cases. A peculiarity of HBV infections is that the immune system often cannot completely resolve infections. Although “recovered” patients maintain protective immunity for the remainder of their lives, trace amounts of HBV DNA can still be detected sporadically. The basis for the apparent persistence is the covalently closed circular DNA (cccDNA) that persists in infected hepatocytes in the form of a minichromosome. See Tan
Replication:
HBV is a very small enveloped DNA virus that replicates via reverse transcription of an RNA intermediate, the pregenome. HBV replicates the following way: (1) HBV infects a liver cell and enzymes extend the short DNA strand of the viral genome. (2) the viral DNA migrates to the cell nucleus where it is copied into RNA. The RNA becomes the pregenome intermediate for further replication. (3) the pregenome is packaged in a newly made capsid. Polymerase enzymes begin to make a DNA copy of the pregenome. The new DNA strand is a duplicate of the original long strand in the viral genome. The pregenome disintegrates as the new DNA is completed. (4) polymerases begin reconstructing a complementary DNA strand from the long-strand template. (5) the viral DNA may persist in the cell long enough to become fully double stranded. It can then return to the nucleus for another round of replication. (6) if the new viral particle exits the cell instead of replicating again, the capsid is enclosed in a fresh envelope. The extension of the short DNA strand stops immediately.
Treatment:
Entecavir is a compound sold under the trade name Baraclude® as a treatment of hepatitis B. Entecavir is a nucleoside analog composed of two regions: a carbocylic ring and a guanine base. It is a modified version of the natural nucleoside 2′-deoxyguanosine (deoxyguanosine). Nucleoside analogs are designed to mimic the activity of natural nucleosides, the building blocks of DNA and RNA but are modified slighly from their natural counterparts to interfere with the replication of viral DNA – which means that they can serve as possible antiviral compounds. Entecavir is structurally identical to deoxyguanosine except that it has a carbon-carbon double bond (also known as an exocylci methylene group) at the 5′ position of the carbocylic ring wehreas deoxyguanosine has an oxygen atom.
Other Hepatitis Viruses
Hepatitis delta virus (HDV): have a small ssRNA genome. It is a defective virus in that it needs HBsAg for replication. So vacination for HAB will also protect one from HAD. HDV is transmitted via blood and blood products just like HVB. The occurrence is rare in the U.S. Interferon is the only licensed drug for treating chronic hepatitis D, but the relapse rate is high after discontinuation. HDV has two forms of viral proteins, large and small hepatitis D antigens (HDAg).
Hepatitis E virus (HEV): are classified in the genus Hepevirus and are a causative agent of human hepatitis. The virus capsid is non-enveloped and the nucleocapsid containing positive-sense singe-stranded RNA has a diameter of 27-34 nm. See ssRNA genome. Transmission (fecal-oral route) and disease is similar to HAV. HEV is seen mainly in 3rd world countries. HEV is endemic in humans, swine and several wild animals such as deers and boars. Four genetoypes of HEV that infect humans have been identified. The hepatitis E virus is transmitted mainly through the fecal-oral route due to fecal contamination of drinking water. This route accounts for a very large proportion of clinical cases with this disease. The risk factors for hepatitis E are related to poor sanitation, allowing virus excreted in the feces of infected people to reach drinking water supplies. The incubation period following exposure to HEV ranges from 2 to 10 weeks, with an average of 5 to 6 weeks. The infected persons excrete the virus beginning from a few days before to 3-4 weeks after onset of the disease. See WHO
Hepatitis G virus (HGV): is a flavivirus which can only be identified by PCR. Interestingly, there is an association with slower progression to AIDS in & HGV dual infection.
Hepatitis X virus: is disgnated for those patients with hepatitis where tests for all known hepatitis virsues are negative.
Fuminant viral hepatitis: is a condition that manifests only rarely in humans (less than about 0.01% of the hepatitis population. It has both non-viral (e.g., drug) and viral causes. Fulminant viral hepatitis can be cause by a number of different agents such as HepA and HepB, as well as the non-hepatitis ABCDE viruses.