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on methodical conference
department of infectious diseases and epidemiology
„____” ____________ 200 р.
Protocol № _____
Chief of Dept., professor __________ V.D. Moskaliuk
METHODOLOGICAL INSTRUCTIONS
to a fifth year student of the Faculty of Medicine
on independent preparation for practical training
Topic: VIRAL HEPATITES (VHA, VHВ, VHС, VHD, VHE)
Subject:
Major:
Educational degree and qualification degree:
Year of study:
Hours:
Prepared by assistant professor
Infectious Diseases
Medicine
Specialist
5
6
Sydorchuk A.S.
Topic: Viral hepatites (VHA, VHВ, VHС, VHD, VHE)
1. Lesson duration: 6 hours
2. Aims of the lesson:
3.1. Students are to know:
• etiology of viral hepatites A, B, C, D, E, types of pathogens, their principal properties;
• epidemiology of viral hepatites A, B, C, D, E;
• pathogenesis of viral hepatites A, B, C, D, E and morphology of organs afflicted by VHA,
VHВ, VHС, VHD, VHE;
• symptoms and development of typical and atypical viral hepatites A, B, C, D, E ;
• clinical characteristic of viral hepatites A, B, C, D, E ;
• complications of viral hepatites A, B, C, D, E ;
• diagnosis of viral hepatites A, B, C, D, E ;
• laboratory methods of examination at viral hepatites A, B, C, D, E ;
• differential diagnosis of viral hepatites A, B, C, D, E including distinguishing between similar
diseases;
• treatment of viral hepatites A, B, C, D, E with taking into account of course severity;
• prophylactic and antiepidemic measures at viral hepatites A, B, C, D, E .
3.2. Students are to be able:
• to question a patient in order for obtaining of information on disease history and
epidemiologic anamnesis;
• to perform clinical examination of a patient;
• to formulate and to substantiate the diagnosis of viral hepatites A, B, C, D, E ;
• to prepare a plan of additional patient examination;
• to evaluate results of laboratory examination;
• to determinate a jaundice stage;
• to make differential diagnosis to distinguish between similar diseases;
• to prescribe adequate pathogen and etiotropic treatment;
• to prepare a plan and organize prophylactic and antiepidemic measures.
3.3. Students are to acquire the following skills:
• to conduct clinical examination of a viral hepatites A, B, C, D, E patient and other acute
intestinal diseases;
• to formulate and substantiate a clinical diagnosis;
• to prepare a plan of paraclinic patient examination;
• to take samples of material (feces, vomit) for bacterioscopy and other quick analysis methods
and bacteriological examination for revealing of VHA, VHE;
and to take samples of material (blood, serum, cervical secret, sperm, amniotic water) for PCR
(polimerase chain reaction) and other quick analysis methods (ELISA) and serological
examination for revealing of VHВ, VHС, VHD,
• to evaluate results of paraclinic patient examination;
• to organize hospitalization and treatment of a viral hepatites A, B, C, D, E patient (of a
person suspected to have viral hepatites A, B, C, D, E );
• to provide emergency aid at acute liver failure;
• to plan and organize prophylactic measures against viral hepatites A, B, C, D, E ;
• to plan and organize antiepidemic measures to localize and liquidate a viral hepatites A, B, C,
D, E source.
4. Advice to students.
VHA is stable during pH 3.0-9.0. sensitive to formaldehyde, may remain preserved for a
period of few months or even years during temperature + 4 °C, f o r weeks - during room
temperature. Complete inactivation of virus takes place during 85 °C in a period of 5 minutes.
VHA is resistant to chlorine, in comparison with other viruses of this group and may enter
through barriers ol water cleaning stations. Complete inactivation of virus steps on during
concentration of chlorine 2.0 - 2.5 mg/L with exposition for a period of 15 minutes, of lime
chloride - 10 mg/L during 15 minutes.
Virus of hepatitis A may reproduce in number of human and monkey cellular cultures, from
where viral antigen is obtained. It is necessary to remark, that successful adaptation of VHA
towards culture of cells is very much necessary for study of biological properties, for obtaining of
source of reagents for diagnostics (antigen, antiserurn), as well as for construction of vaccines
(live, killed).
Viral hepatitis A is an antroponosis. The source of disease is sick person in prejaundice
period and during 15-20 days of climax period of the disease and virus carrier. Primary
localization of virus is gastrointestinal tract. Mechanism of transmission is fecal-oral. Virus is
excreted from the organism of sick person with feces. Specific factors of hepatitis A virus
transmission are water and blood. Character of water infection depends upon conditions of
water supply and its relation with fecal contamination. Intermediate factors of transmission are
flies, transferring virus with feces on products of nutrition, dishes.
Preliminary diagnosis of viral hepatitis is based on epidemiological anamnesis, finding of the
development of the disease, clinical picture with account of peculiarities of the ways of the
transmission, duration of incubation period, presence of prejaundice period, presence of typical
subjective and objective signs with account of the patients age.
Diagnosis is confirmed by routine and specific laboratory tests. In routine blood test of the
patients with viral hepatitis lymphocytosis is observed with moderately expressed course and
in serious course of the disease - anemia and leucopenia. ESR is slightly decreased. In urine
urobilin and bile pigments are observed. During climax period, particularly during medium
serious and serious forms, there are no stercobilin in stool.
Increased content of general bilirubin, primarily on account of its direct fraction is
observed in blood serum during all jaundice period. Ratio of direct and indirect fraction
composes 3:1. In all patients already in pre-jaundice period of the disease, during all jaundice period
and in the period of early reconvalescence increased activity of ALT, AST is observed, testifying
about the presence of cytolytic processes in liver.
Treatment is used in complex and depends on the clinical form and gravity of disease
course. At mild course of a viral hepatitis in the acute period it is possible to prescribe only
semi-bed regime, diet NO 5, polyvitamines and desensitizing preparations: calcium
gluconate, diazolin, diprazin or tavegil. In case of meteorism, feeling of gravity in epigastrium
area after the meal, unstable feces - festal, pancurmen, allochol, cholenzym are indicated.
Medical Care: You will usually be treated at home. Resting and eating healthy food
will help you get better. You should drink 8 (soda pop can size) glasses of water each day. But
you may need to be put in the hospital for tests and treatment. There is no special medicine
used to treat hepatitis A. Avoid the use of acetaminophen, ibuprofen and aspirin unless
absolutely necessary. Friends and family may get a shot to keep them from getting hepatitis A.
If the patient is hospitalized, he should be placed in a private room with separate toilet
facilities. The major reason for such isolation is to prevent the spread of type A hepatitis. Even
with lax precautions, such spread is very rare; most patients with type A hepatitis are no longer
excreting virus once they have become symptomatic. Nevertheless, there are exceptions, and
isolation is prudent. Secretions and blood products should be handled with care gowns, masks,
and gloves are not necessary, but a prominent sign reading "needle and blood precautions" is
appropriate. Labeling of blood specimens from a patient with hepatitis, is a common practice. It
should be stressed, however, that all blood from any patient should be handled as if potentially
infectious.
If the patient with viral hepatitis is at home, the patient should be advised about care in
personal hygiene - careful hand washing. Attention also should be paid to blood and blood
products and the handling of cuts and lacerations.
Recommendations regarding the prevention of acute hepatitis are governed by the type of
viral hepatitis that is being considered. In the case of acute type A hepatitis, all family members,
and close personal contacts should receive immune serum globulin (ISG) at a dosage of 2-5 mL
in as soon as possible after exposure. Office, factory, and school contacts do not need to be
treated. Immune serum globulin can be given for up to 4 weeks after exposure, but it probably
is only effective if given within 7-14 days.
The hepatitis B virus itself does not directly cause damage to the liver. Rather, the body's
immune (protective) response to the virus (a foreign material) paradoxically causes the
damage. Thus, in an hepatitis B viral infection, the body's immune response to the virus is
responsible for both the elimination of the hepatitis B virus from the body and recovery from
the infection. Yet, at the same time, the injury to the liver cells is caused by that same immune
response to the hepatitis B virus in the liver cells. Therefore, there is a balance between the
protective and destructive effects of the immune system's response to the hepatitis B virus.
Accordingly, an acute hepatitis B viral infection can lead to recovery (the usual outcome), to
acute liver failure (rarely), and sometimes to chronic infection. The chronic infection can result
in a healthy carrier state (in which the affected person harbors the virus but remains healthy) or
progress to cirrhosis (sever scarring, or fibrosis, of the liver) and its complications, including
liver cancer.
Hepatitis B virus is spread or acquired through exposure to infected blood or the body's
secretions. The highest concentrations of hepatitis B virus are found in the blood, semen, aginal
discharge, breast milk, and saliva. There are only low concentrations of hepatitis B virus in the
urine and none in the feces. Therefore, hepatitis B is not spread through food or water or by
casual contact. Furthermore, hepatitis B virus is no longer transmitted by blood transfusions
because all blood for transfusion is screened (tested) to exclude contamination with hepatitis B
virus. In the U.S., adolescents and young adults account for the majority of reported cases of
hepatitis B infection. Sexual contact (intercourse) is the most common means of transmission.
The virus also can be spread by hepatitis B virus-contaminated blood or body fluid in several
different ways. These ways include intravenous drug use, skin-popping (injecting under the
skin), tattooing, body piercing, and acupuncture using unsterile instruments. Additionally,
hepatitis B virus can be transmitted through the sharing of toothbrushes and razors. Finally,
blood-sucking insects such as mosquitoes and bed bugs in the tropics have reportedly spread
hepatitis B virus.Last (but not least), hepatitis B virus can be spread from infected mothers to
their babies at the time of birth (so-called vertical transmission). This is the most important
means of transmission in regions where the hepatitis B viral infection is always present
(endemic), such as in Southeast Asia and Sub-Saharan Africa. The rate of transmission of
hepatitis B virus to the newborn of highly infectious mothers is very high, approaching 100%.
Moreover, as indicated earlier, almost all of these infants will develop chronic hepatitis B viral
infection.
Hepatitis C is a blood-borne, infectious, viral disease that is caused by a hepatotropic
virus called Hepatitis C virus (HCV). The infection can cause liver inflammation that is often
asymptomatic, but ensuing chronic hepatitis can result later in cirrhosis (fibrotic scarring of the
liver) and liver cancer. The hepatitis C virus (HCV) is spread by blood-to-blood contact with an
infected person's blood. The symptoms can be medically managed, and a proportion of patients
can be cleared of the virus by a long course of anti-viral medicines. Although early medical
intervention is helpful, people with HCV infection often experience mild symptoms, and
сonsequently do not seek treatment. An estimated 150-200 million people worldwide are
infected with hepatitis C. In the U.S., those with a history of intravenous drug use, inhaled drug
usage, tattoos, or who have been exposed to blood via unsafe sex or social practices are
increased risk for this disease. Hepatitis C is the leading cause of liver transplant in the United
States.Acute hepatitis C refers to the first 6 months after infection with HCV. Between 60% to
70% of people infected develop no symptoms during the acute phase. In the minority of
patients who experience acute phase symptoms, they are generally mild and nonspecific, and
rarely lead to a specific diagnosis of hepatitis C. Symptoms of acute hepatitis C infection
include decreased appetite, fatigue, abdominal pain, jaundice, itching, and flu-like symptoms.
The hepatitis C virus is usually detectable in the blood within one to three weeks after
infection, and antibodies to the virus are generally detectable within 3 to 12 weeks.
Approximately 20-30% of persons infected with HCV clear the virus from their bodies during
the acute phase as shown by normalization in liver function tests (LFTs) such as alanine
transaminase (ALT) & aspartate transaminase (AST) normalization, as well as plasma HCVRNA clearance (this is known as spontaneous viral clearance). The remaining 70-80% of
patients infected with HCV develop chronic hepatitis C, i.e., infection lasting more than 6
months. Previous practice was to not treat acute infections to see if the person would
spontaneously clear; recent studies have shown that treatment during the acute phase of
genotype 1 infections has a greater than 90% success rate with half the treatment time required
for chronic infections, but that the majority of acute hepatitis C is cleared.
The Hepatitis C virus (HCV) is a small (50 nm in size), enveloped, single-stranded,
positive sense RNA virus in the families Flaviviridae.
The diagnosis of "hepatitis C" is rarely made during the acute phase of the disease because
the majority of people infected experience no symptoms during this phase of the disease. Those
who do experience acute phase symptoms are rarely ill enough to seek medical attention. The
diagnosis of chronic phase hepatitis C is also challenging due to the absence or lack of
specificity of symptoms until advanced liver disease develops, which may not occur until
decades into the disease. Chronic hepatitis C may be suspected on the basis of the medical
history (particularly if there is any history of IV drug abuse or inhaled substance usage such as
cocaine), a history of piercings or tattoos, unexplained symptoms, or abnormal liver enzymes
or liver function tests found during routine blood testing. Occasionally, hepatitis C is diagnosed
as a result of targeted screening such as blood donation (blood donors are screened for
numerous blood-borne diseases including hepatitis C) or contact tracing. Hepatitis C testing
begins with serological blood tests used to detect antibodies to HCV. Anti-HCV antibodies can
be detected in 80% of patients within 15 weeks after exposure, in >90% within 5 months after
exposure, and in >97% by 6 months after exposure. Overall, HCV antibody tests have a strong
positive predictive value for exposure to the hepatitis C virus, but may miss patients who have
not yet developed antibodies (seroconversion), or have an insufficient level of antibodies to
detect. While uncommon, a small minority of people infected with HCV never develop
antibodies to the virus and therefore, never test positive using HCV antibody screening. AntiHCV antibodies indicate exposure to the virus, but cannot determine if ongoing infection is
present. All persons with positive anti-HCV antibody tests must undergo additional testing for
the presence of the hepatitis C virus itself to determine whether current infection is present. The
presence of the virus is tested for using molecular nucleic acid testing methods such as
polymerase chain reaction (PCR), transcription mediated amplification (TMA), or branched
DNA (b-DNA). All HCV nucleic acid molecular tests have the capacity to detect not only
whether the virus is present, but also to measure the amount of virus present in the blood (the
HCV viral load). The HCV viral load is an important factor in determining the probability of
response to interferon-based therapy, but does not indicate disease severity nor the likelihood
of disease progression. In people with confirmed HCV infection, genotype testing is generally
recommended. There are six major genotypes of the hepatitis C virus, which are indicated
numerically (e.g., genotype 1, genotype 2, etc.). HCV genotype testing is used to determine the
required length and potential response to interferon-based therapy.
The VHE causes an acute viral hepatitis. Incubation period is between 15 and 50 days,
average 6 weeks. In a typical case the preicteric phase may last 10 days and consists of nausea,
vomiting and epigastric pain. The jaundice will last an average of 10 days. Recovery will occur
within one month.Children below 14 and adults above 55 are prone to develop a subclinical
form without jaundice. The clinical course of hepatitis E is similar to hepatitis A, however, the
fatality rate which is due to fulminant hepatitis is much higher: 1-2/1000 in hepatitis A, 1-2/100
in hepatitis E. In pregnant women fatality rate could be up to 22% occurring exclusively in the
third trimester. These patients develop an unusual form of DIC (diffuse intravascular
coagulation) besides fulminant hepatitis. Chronicization of this infection does not appear to
exist.
Laboratory data:
Bilirubin, up to 8-10 mg/dl. ALT, high up to 1000 deceasing to normal values in 3-4 months.
Virus in blood and feces at the beginning of the jaundice for a brief period of 15-20 days. Large
amounts of IgM antibodies from the pick of the jaundice and for over 25 weeks. IgG antibodies
appear in the jaundice but are of low-titer. They seem to persist for long time, 14 years in a
report from Kashmir, and appear to offer protection against subsequent infections.
The most practical and convenient test is Enzyme Immuno Assay (EIA) which detects
IgM and IgG antibodies to HEV. Other tests, although less convenient and practical are:
-Immuno Electron Microscopy to detect viral particles in stool and serum.
-Immunofluorescence to detect viral antigen in liver tissue. Not practical.
-Polymerase Chain Reaction to detect viral genome in serum, feces, and liver tissue.
The virus is endemic In a broad region of Asia, Nord Africa and only Mexico in the
American continent. The vast Asiatic region involves India, southeast Asia and central Asia
from Turkey to south Russia and China.
5. Test questions.
1. What kind of a virus hepatitis A?
2. How does hepatitis A virus cause liver injury?
3. How is hepatitis A spread (transmitted)?
4. What are the symptoms of acute hepatitis A?
5. How is hepatitis A diagnosed?
6. What medications are used to treat hepatitis A?
7. What can be done to prevent hepatitis A?
8. What is new in the treatment of hepatitis A virus?
9. What kind of a virus hepatitis B?
10. How does hepatitis B virus cause liver injury?
11. How is hepatitis B spread (transmitted)?
12. What are the symptoms of acute hepatitis B?
13. What are the symptoms of chronic hepatitis B viral infection?
14. How is hepatitis B diagnosed?
15. What is the role of a liver biopsy in chronic hepatitis B?
16. What is the natural progression or course of chronic hepatitis B?
17. What are healthy carriers of hepatitis B virus?
18. What medications are used to treat hepatitis B?
19. What are the effects of alcohol on hepatitis B virus?
20. What are the effects of immunosuppressive medications on hepatitis B virus?
21. What is delta hepatitis?
22. What about co-infection of hepatitis B virus with hepatitis C virus?
23. What happens in co-infection of hepatitis B virus with human immunodeficiency virus?
24. What is the role of liver transplantation in hepatitis B viral infection?
25. What can be done to prevent hepatitis B?
26. What is new in the treatment of hepatitis B virus?
6. Literature:
1. Harrison A. Internal Diseases. Part of Infectious Diseases.
2. Nikitin E., Andreychyn M., Servetskyy K., Kachor V., Holovchenko A., Usychenko
E. Infectious Diseases. – Ternopil: Ukrmedknyga, 2004. – P. 149-163.