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Deep Learning Technology: Sebastian Arnold, Betty van Aken, Paul Grundmann, Felix A. Gers and Alexander Löser. Learning Contextualized Document Representations for Healthcare Answer Retrieval. The Web Conference 2020 (WWW'20)
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Viral hepatitis is liver inflammation due to a viral infection. It may present in acute (recent infection, relatively rapid onset) or chronic forms.
The most common causes of viral hepatitis are the five unrelated hepatotropic viruses hepatitis A, hepatitis B, hepatitis C, hepatitis D, and hepatitis E. In addition to the nominal hepatitis viruses, other viruses that can also cause liver inflammation include cytomegalovirus, Epstein–Barr virus, and yellow fever. Up to 1997 there has been also 52 cases of viral hepatitis caused by herpes simplex virus.
There is the opportunity to prevent or treat the most common types. Hepatitis A and hepatitis B can be prevented by vaccination. Effective treatments for hepatitis C are available but expensive.
In 2013 about 1.5 million people died from viral hepatitis. Most deaths are due to hepatitis B and hepatitis C. East Asia is the region of the world most affected.
Acute viral hepatitis follows a pattern of infection that involves three distinct phases:
1. The initial prodromal phase (preceding symptoms) involves non-specific and flu-like symptoms common to many acute viral infections. These include fatigue, nausea, vomiting, poor appetite, joint pain, and headaches. Fever, when present, is most common in cases of hepatitis A and E. Late in this phase, people can experience liver-specific symptoms, including choluria (dark urine) and clay-colored stools.
2. Yellowing of the skin and whites of the eyes follow the prodrome after about 1–2 weeks and can last for up to 4 weeks. The non-specific symptoms seen in the prodromal typically resolve by this time, but people will develop an enlarged liver and right upper abdominal pain or discomfort. 10–20% of people will also experience an enlarged spleen, while some people will also experience a mild unintentional weight loss.
3. The recovery phase is characterized by resolution of the clinical symptoms of hepatitis with persistent elevations in liver lab values and potentially a persistently enlarged liver. All cases of hepatitis A and E are expected to fully resolve after 1–2 months. Most hepatitis B cases are also self-limiting and will resolve in 3–4 months. Few cases of hepatitis C will resolve completely.
Both drug-induced hepatitis and autoimmune hepatitis can present very similarly to acute viral hepatitis, with slight variations in symptoms depending on the cause. Cases of drug-induced hepatitis can manifest with systemic signs of an allergic reaction including rash, fever, serositis (inflammation of membranes lining certain organs), elevated eosinophils (a type of white blood cell), and suppression of bone marrow activity.
Hepatitis has a broad spectrum of presentations that range from a complete lack of symptoms to severe liver failure. The acute form of hepatitis, generally caused by viral infection, is characterized by constitutional symptoms that are typically self-limiting. Chronic hepatitis presents similarly, but can manifest signs and symptoms specific to liver dysfunction with long-standing inflammation and damage to the organ.
The most common cause of hepatitis is viral. Although they are classified under the disease hepatitis, these viruses are not all related.
An oncovirus is a virus that can cause cancer. This term originated from studies of acutely transforming retroviruses in the 1950–60s, often called oncornaviruses to denote their RNA virus origin.
It now refers to any virus with a DNA or RNA genome causing cancer and is synonymous with "tumor virus" or "cancer virus". The vast majority of human and animal viruses do not cause cancer, probably because of longstanding co-evolution between the virus and its host. Oncoviruses have been important not only in epidemiology, but also in investigations of cell cycle control mechanisms such as the Retinoblastoma protein.
The World Health Organization's International Agency for Research on Cancer estimated that in 2002, infection caused 17.8% of human cancers, with 11.9% caused by one of seven viruses. These cancers might be easily prevented through vaccination (e.g., papillomavirus vaccines), diagnosed with simple blood tests, and treated with less-toxic antiviral compounds.
There are several forms of Epstein–Barr virus infection. Infectious mononucleosis, nasopharyngeal carcinoma, and Burkitt's lymphoma can all be caused by the Epstein–Barr virus.
Epstein–Barr can cause infectious mononucleosis, also known as 'glandular fever', 'mono' and 'Pfeiffer's disease'. Infectious mononucleosis is caused when a person is first exposed to the virus during or after adolescence. It is predominantly found in the developing world, and most children in the developing world are found to have already been infected by around 18 months of age. Infection of children can occur when adults mouth feed or pre-chew food before giving it to the child. EBV antibody tests turn up almost universally positive. In the United States roughly half of five-year-olds have been infected.
Infectious mononucleosis mainly affects younger adults. When older adults do catch the disease, they less often have characteristic signs and symptoms such as the sore throat and lymphadenopathy. Instead, they may primarily experience prolonged fever, fatigue, malaise and body pains. They are more likely to have liver enlargement and jaundice. People over 40 years of age are more likely to develop serious illness. (See Prognosis.)
Viral cardiomyopathy occurs when viral infections cause myocarditis with a resulting thickening of the myocardium and dilation of the ventricles. These viruses include Coxsackie B and adenovirus, echoviruses, influenza H1N1, Epstein-Barr virus, rubella (German measles virus), varicella (chickenpox virus), mumps, measles, parvoviruses, yellow fever, dengue fever, polio, rabies and the viruses that cause hepatitis A and C.
In adolescence and young adulthood, the disease presents with a characteristic triad:
- Fever – usually lasting 14 days; often mild
- Sore throat – usually severe for 3–5 days, before resolving in the next 7–10 days.
- Swollen glands – mobile; usually located around the back of the neck (posterior cervical lymph nodes) and sometimes throughout the body.
Another major symptom is feeling tired. Headaches are common, and abdominal pains with nausea or vomiting sometimes also occur. Symptoms most often disappear after about 2–4 weeks. However, fatigue and a general feeling of being unwell (malaise) may sometimes last for months. Fatigue lasts more than one month in an estimated 28% of cases. Mild fever, swollen neck glands and body aches may also persist beyond 4 weeks. Most people are able to resume their usual activities within 2–3 months.
The most prominent sign of the disease is often the pharyngitis, which is frequently accompanied by enlarged tonsils with pus—an exudate similar to that seen in cases of strep throat. In about 50% of cases, small reddish-purple spots called petechiae can be seen on the roof of the mouth. Palatal enanthem can also occur, but is relatively uncommon.
Spleen enlargement is common in the second and third weeks, although this may not be apparent on physical examination. Rarely the spleen may rupture. There may also be some enlargement of the liver. Jaundice occurs only occasionally.
A small minority of people spontaneously present a rash, usually on the arms or trunk, which can be macular (morbilliform) or papular. Almost all people given amoxicillin or ampicillin eventually develop a generalized, itchy maculopapular rash, which however does not imply that the person will have adverse reactions to penicillins again in the future. Occasional cases of erythema nodosum and erythema multiforme have been reported.
About 95% of symptomatic cases report joint pain. This is typically symmetrical and with acute onset, affecting the fingers, toes, ankles, wrists, back, knees and elbows. Fatigue occurs in 90% and fever, myalgia and headache occur in 50–60%.
A rash occurs in 50% of patients and is widespread and maculopapular. Lymphadenopathy occurs commonly; sore throat and coryza less frequently. Diarrhea is rare. About 50% of people report needing time off work with the acute illness. If the rash is unnoticed, these symptoms are quite easily mistaken for more common illnesses like influenza or the common cold. Recovery from the flu symptoms is expected within a month, but, because the virus currently cannot be removed once infection has occurred secondary symptoms of joint and muscle inflammation, pain and stiffness can last for many years.
Less common manifestations include splenomegaly, hematuria and glomerulonephritis. Headache, neck stiffness, and photophobia may occur. There have been three case reports suggesting meningitis or encephalitis.
Reports from the 1980s and 1990s suggested RRV infection was associated with arthralgia, fatigue and depression lasting for years. More recent prospective studies have reported a steady improvement in symptoms over the first few months, with 15–66% of patients having ongoing arthralgia at 3 months. Arthralgias have resolved in the majority by 5–7 months. The incidence of chronic fatigue is 12% at 6 months and 9% at 12 months, similar to Epstein-Barr virus and Q fever. The only significant predictor of the likelihood of developing chronic symptoms is the severity of the acute illness itself. No other aspects of the patient's medical or psychiatric history have been found to be predictive. However, in those with the most persisting symptoms (12 months or more), comorbid rheumatologic conditions and/or depression are frequently observed .
Signs of chronic liver disease detectable on clinical examination can be divided into those that are associated with the diagnosis of chronic liver disease, associated with decompensation and associated with the cause.
Note that "other diseases can involve the liver" and cause hepatomegaly but would not be considered part of the spectrum of chronic liver disease. Some examples of this would include chronic cancers with liver metastases, infiltrative haematological disorders such as chronic lymphoproliferative conditions, chronic myeloid leukaemias, myelofibrosis and metabolic abnormalities such as Gaucher's disease and glycogen storage diseases.
The most common symptoms of CAEBV include:
- Fever
- Hepatitis
- Pancytopenia
- Spleen enlargement
- Hypersensitivity to mosquito bites
Complications include:
- Interstitial pneumonia
- Lymphoma, including B-cell, T-cell and NK-cell lymphomas
- Haemophagocytic syndrome
- Coronary artery aneurysms
- Liver failure
- Nasopharyngeal carcinoma
- Gastric adenocarcinoma
- CNS
- Intestinal perforation
- Myocarditis
- Peripheral neuropathy
Most individuals with HSE show a decrease in their level of consciousness and an altered mental state presenting as confusion, and changes in personality. Increased numbers of white blood cells can be found in patient's cerebrospinal fluid, without the presence of pathogenic bacteria and fungi. Patients typically have a fever and may have seizures. The electrical activity of the brain changes as the disease progresses, first showing abnormalities in one temporal lobe of the brain, which spread to the other temporal lobe 7–10 days later. Imaging by CT or MRI shows characteristic changes in the temporal lobes (see Figure). Definite diagnosis requires testing of the cerebrospinal fluid (CSF) by a lumbar puncture (spinal tap) for presence of the virus. The testing takes several days to perform, and patients with suspected Herpes encephalitis should be treated with acyclovir immediately while waiting for test results.
Herpesviral encephalitis is encephalitis due to herpes simplex virus.
Herpes simplex encephalitis (HSE) is a viral infection of the human central nervous system. It is estimated to affect at least 1 in 500,000 individuals per year and some studies suggest an incidence rate of 5.9 cases per 100,000 live births. The majority of cases of herpes encephalitis are caused by herpes simplex virus-1 (HSV-1), the same virus that causes cold sores. 57% of American adults are infected with HSV-1, which is spread through droplets, casual contact, and sometimes sexual contact, though most infected people never have cold sores. About 10% of cases of herpes encephalitis are due to HSV-2, which is typically spread through sexual contact. About 1 in 3 cases of HSE result from primary HSV-1 infection, predominantly occurring in individuals under the age of 18; 2 in 3 cases occur in seropositive persons, few of whom have history of recurrent orofacial herpes. Approximately 50% of individuals who develop HSE are over 50 years of age.
A subclinical infection (sometimes called a preinfection) is an infection that, being , is nearly or completely asymptomatic (no signs or symptoms). A subclinically infected person is thus an asymptomatic carrier of a microbe, intestinal parasite, or virus that usually is a pathogen causing illness, at least in some individuals. Many pathogens spread by being silently carried in this way by some of their host population. Such infections occur both in humans and nonhuman animals. An example of an asymptomatic infection is a mild common cold that is not noticed by the infected individual. Since subclinical infections often occur without eventual overt sign, their existence is only identified by microbiological culture or DNA techniques such as polymerase chain reaction.
Gianotti–Crosti syndrome mainly affects infants and young children. Children as young as 1.5 months and up to 12 years of age are reported to be affected. It is generally recognized as a papular or papulovesicular skin rash occurring mainly on the face and distal aspects of the four limbs. Purpura is generally not seen but may develop upon tourniquet test. However, extensive purpura without any hemorrhagic disorder has been reported. The presence of less lesions on the trunk does not exclude the diagnosis. Lymphadenopathy and hepatomegaly are sometimes noted. Raised AST and ALT levels with no rise in conjugated and unconjugated bilirubin levels are sometimes detectable, although the absence of such does not exclude the diagnosis. Spontaneous disappearance of the rash usually occurs after 15 to 60 days.
An individual may only develop signs of an infection after a period of subclinical infection, a duration that is called the incubation period. This is the case, for example, for subclinical sexually transmitted diseases such as AIDS and genital warts. Individuals with such subclinical infections, and those that never develop overt illness, creates a reserve of individuals that can transmit an infectious agent to infect other individuals. Because such cases of infections do not come to clinical attention, health statistics can often fail to measure the true prevalence of an infection in a population, and this prevents the accurate modeling of its infectious transmission.
Generally, tumor viruses cause little or no disease after infection in their hosts, or cause non-neoplastic diseases such as acute hepatitis for hepatitis B virus or mononucleosis for Epstein-Barr virus. A minority of persons (or animals) will go on to develop cancers after infection. This has complicated efforts to determine whether or not a given virus causes cancer. The well-known Koch's postulates, 19th-century constructs developed by Robert Koch to establish the likelihood that "Bacillus anthracis" will cause anthrax disease, are not applicable to viral diseases. (Firstly, this is because viruses cannot truly be isolated in pure culture—even stringent isolation techniques cannot exclude undetected contaminating viruses with similar density characteristics, and viruses must be grown on cells. Secondly, asymptomatic virus infection and carriage is the norm for most tumor viruses, which violates Koch's third principle. Relman and Fredericks have described the difficulties in applying Koch's postulates to virus-induced cancers. Finally, the host restriction for human viruses makes it unethical to experimentally transmit a suspected cancer virus.) Other measures, such as A.B. Hill's criteria, are more relevant to cancer virology but also have some limitations in determining causality.
Tumor viruses come in a variety of forms: Viruses with a DNA genome, such as adenovirus, and viruses with an RNA genome, like the Hepatitis C virus (HCV), can cause cancers, as can retroviruses having both DNA and RNA genomes (Human T-lymphotropic virus and hepatitis B virus, which normally replicates as a mixed double and single-stranded DNA virus but also has a retroviral replication component). In many cases, tumor viruses do not cause cancer in their native hosts but only in dead-end species. For example, adenoviruses do not cause cancer in humans but are instead responsible for colds, conjunctivitis and other acute illnesses. They only become tumorigenic when infected into certain rodent species, such as Syrian hamsters. Some viruses are tumorigenic when they infect a cell and persist as circular episomes or plasmids, replicating separately from host cell DNA (Epstein-Barr virus and Kaposi's sarcoma-associated herpesvirus). Other viruses are only carcinogenic when they integrate into the host cell genome as part of a biological accident, such as polyomaviruses and papillomaviruses.
A direct oncogenic viral mechanism involves either insertion of additional viral oncogenic genes into the host cell or to enhance already existing oncogenic genes (proto-oncogenes) in the genome. Indirect viral oncogenicity involves chronic nonspecific inflammation occurring over decades of infection, as is the case for HCV-induced liver cancer. These two mechanisms differ in their biology and epidemiology: direct tumor viruses must have at least one virus copy in every tumor cell expressing at least one protein or RNA that is causing the cell to become cancerous. Because foreign virus antigens are expressed in these tumors, persons who are immunosuppressed such as AIDS or transplant patients are at higher risk for these types of cancers. Chronic indirect tumor viruses, on the other hand, can be lost (at least theoretically) from a mature tumor that has accumulated sufficient mutations and growth conditions (hyperplasia) from the chronic inflammation of viral infection. In this latter case, it is controversial but at least theoretically possible that an indirect tumor virus could undergo "hit-and-run" and so the virus would be lost from the clinically diagnosed tumor. In practical terms, this is an uncommon occurrence if it does occur.
Gianotti–Crosti syndrome ( ), also known as infantile papular acrodermatitis, papular acrodermatitis of childhood, and papulovesicular acrolocated syndrome, is a reaction of the skin to a viral infection. Hepatitis B virus and Epstein–Barr virus are the most frequently reported pathogens. Other incriminated viruses are hepatitis A virus, hepatitis C virus, cytomegalovirus, coxsackievirus, adenovirus, enterovirus, rotavirus, rubella virus, HIV, and parainfluenza virus.
It is named for Ferdinando Gianotti and Agostino Crosti.
Chronic active EBV infection (CAEBV) or in its expanded form, chronic active Epstein-Barr virus infection is a very rare and often fatal complication of Epstein-Barr virus (EBV) infection that most often occurs in children or adolescents of Asian or South American lineage, although cases in Hispanics, Europeans and Africans have been reported.
Enlargement of the spleen is known as splenomegaly. It may be caused by sickle cell anemia, sarcoidosis, malaria, bacterial endocarditis, leukemia, pernicious anemia, Gaucher's disease, leishmaniasis, Hodgkin's disease, Banti's disease, hereditary spherocytosis, cysts, glandular fever (mononucleosis or 'Mono' caused by the Epstein-Barr Virus), and tumours. Primary tumors of the spleen include hemangiomas and hemangiosarcomas. Marked splenomegaly may result in the spleen occupying a large portion of the left side of the abdomen.
The spleen is the largest collection of lymphoid tissue in the body. It is normally palpable in preterm infants, in 30% of normal, full-term neonates, and in 5% to 10% of infants and toddlers. A spleen easily palpable below the costal margin in any child over the age of 3–4 years should be considered abnormal until proven otherwise.
Splenomegaly can result from antigenic stimulation (e.g., infection), obstruction of blood flow (e.g., portal vein obstruction), underlying functional abnormality (e.g., hemolytic anemia), or infiltration (e.g., leukemia or storage disease, such as Gaucher's disease). The most common cause of acute splenomegaly in children is viral infection, which is transient and usually moderate. Basic work-up for acute splenomegaly includes a complete blood count with differential, platelet count, and reticulocyte and atypical lymphocyte counts to exclude hemolytic anemia and leukemia. Assessment of IgM antibodies to viral capsid antigen (a rising titer) is indicated to confirm Epstein-Barr virus or cytomegalovirus. Other infections should be excluded if these tests are negative.
Acute PCH tends to be transient and self-limited, particularly in children. Chronic PCH associated with syphilis resolves after the syphilis is treated with appropriate antibiotics. Chronic idiopathic PCH is usually mild.