Download Department of Infectious Diseases

Ministry of Healthcare of Ukraine
N.I. Pirogov National Medical University
Department of Infectious Diseases
Approved at the methodical meeting
«___» _____________ 20 y.
Head of the Department, prof.
Moroz L.V.
WORKBOOK
for practical training on infectious diseases for V-year students of medical departments (1X - X term)
Topic 11.1:
Laboratory Diagnosis of Acute Viral Hepatitises. Specific
and biochemical markers. Differential diagnosis of
viral hepatitises. Therapeutic approach, medical aid
for patients in prehospital phase.
Prepared by : Candidate of Medical Sciences Popovich А.А.
2009
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1. Relevance of the topic.
Among human infectious diseases viral hepatitis takes up special place. In recent years, in
addition to the well-known hepatitis viruses A, B, C, D, E , F and G, other viruses were added - TT
and SEN(non-A, non-G) which can cause hepatitis and possibly many extrahepatic disease processes.
Acute viral hepatitis is an acute viral disease affecting the liver, characterized by necrosis and
inflammatory changes in the hepatic portal system and intralobular parenchyma.
Among parenteral acute viral hepatitises the most dangerous and studied are viral hepatitis B and
C. Every year 50 million people get infected by hepatitis B virus and 1.5 to 2 million people die from
it. In Ukraine, the incidence rate of hepatitis B is about 14.5 per 100,000 of the population and those
who carry the virus are about 1 million people. Hepatitis D as well as hepatitis B is practically
widespread.
The causative agent of hepatitis C was discovered and became the most common at the beginning
of the XXI century. The number of people infected with hepatitis C virus has reached one billion
people, almost 20% of the world's population.
Hepatitis B and C have certain characteristics of the specific laboratory diagnosis and treatment.
The common features of parenteral hepatitises are extremely dangerous consequences of the disease:
cirrhosis and primary liver cancer.
Therefore, early diagnosis is the main factor that allows to carry out the timely treatment of the
patient and thus prevent death from these diseases.
Laboratory diagnostic techniques used in the examination of patients with viral hepatitis provide
a conduction and assessment of clinical, biochemical and specific researches.
Among specific methods of diagnosis of viral hepatitises, the ones that deserve special attention
are molecular biological methods including the polymerase chain reaction (PCR).
Therapeutic approach for viral hepatitises consists of principles of etiotropic and pathogenetic
therapy. In order to use etiotropic treatment, narrow and broad-spectrum antiviral chemotherapies are
carried out. The most commonly used are anomalous nucleosides and interferons. Unfortunately, the
current combination antiviral therapy has a number of adverse events which complicate and limit the
use of appropriate medications, and also significantly worsen the life quality of patients. This factor
applies most to the treatment of patients with chronic hepatitises.
Pathogenetic principles of treatment that eliminate symptoms of intoxication, jaundice, diarrheal
diseases and other syndromes are mainly used for patients with acute hepatitises. In cases of acute
hepatitis A and E, the natural factors of the patient's own immune system act as the means of etiotropic
therapy.
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2. The aim of the course (with an indicating level of adoption of the program):
2.1. A Student must understand (learn):
а-1
- have a general understanding of the place of acute viral hepatitis in the structure of infectious
diseases, prevalence in different regions of the world and age groups, learn the statistical data on the
sickness rate, lethality, complication rates, remote consequences of infections;
- have a general understanding of the laboratory diagnostic methods of acute viral hepatitises
- have a general understanding of the main methods of treatment of acute viral hepatitises
- learn the history of the scientific study of acute viral hepatitises, have an understanding of the
scientific contribution of Russian scientists in the history of scientific research in this field.
а-2
2.2. A student must know:
1. etiology of acute viral hepatitises
2. basic processes of pathogenesis that lead to changes in the general analysis of blood, urine, and
feces of patients with acute viral hepatitises
3. basic processes of pathogenesis that lead to changes in biochemical analysis of blood of
patients with acute viral hepatitises
4. clinical methods
5. biochemical methods
6. specific laboratory methods of research
7. principles of differential diagnosis of acute viral hepatitises among themselves and other
diseases based on laboratory methods for diagnosis
8. treatment principles of acute viral hepatitises
9. characterization of the main antiviral drugs
10. the order for prescribing antiviral drugs to patients with acute viral hepatitises
11. characterization of pathogenic therapy for patients with acute viral hepatitises
12. the order for prescribing pathogenetic therapy drugs to patients with acute viral hepatitises
13. therapeutic approach for helping a patient in the events of emergency conditions
14. medical aid for patients in prehospital phase
2.3. A student must know how to:
а–3
1.
2.
3.
4.
5.
Make a plan for the laboratory examination of the patient.
Interpret the results of clinical and biochemical researches.
Evaluate the results of the specific diagnostic methods
Carry out a differential diagnosis of acute viral hepatitises.
Make an individual treatment plan considering the epidemiological data, stage of disease,
complications, condition severity, allergic history, concomitant pathology and laboratory methods
of examination.
6. Provide emergency care to patients with acute hepatic failure, hemorrhagic syndrome, cerebral
edema.
7. Give an advise on the treatment and the diet.
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2.4. Creative level (for most capable and trained students):
а–4
Develop creative abilities of students in the process of conducting clinical researches and during
analysis of scientific sources: get involved in a scientific study group of the faculty; suggest topics for
essays about the most pressing issues, for example: « Prevention of viral hepatitises with different
mechanisms of transmission», «Population consequences of conducting a mass vaccination against
hepatitis B», «The possibility of using modern antiviral drugs for the treatment of acute viral
hepatitises with different mechanisms of transmission», «Difficulties in the differential diagnosis of
acute viral hepatitises with subclinical course» etc.
3. Educational aims (personality development):
1. Develop a deontological view. Know and be able to follow the principles of medical deontology.
Master the ability to establish psychological contact with the patient and his family.
2. Develop understanding of the impact of antiepidemic measures on the prevalence of acute viral
hepatitises.
3. Develop a sense of responsibility for the timeliness and accuracy of professional activities.
4. Intersubject integration:
Discipline
Microbiology
Internal diseases
propedeutics
Epidemiology
Immunology and
allergology
Physiology
Know
Properties of agents of acute viral
hepatitis, serological response according
to the period of disease, rules and terms of
sample collection for specific diagnosis.
Main stages and methods of clinical
examination of the patient.
An epidemic process (source, infecting
mechanism,way of transmission) of acute
viral hepatitises; prevalence of the disease
in Ukraine and in the world. World Health
Organization (WHO) strategy for
eliminating these infections.
The basic concepts of the subject, Role of
the immune system in the infectious
process, an effect on the period of
elimination of the causative agent from
the human body. Immunological aspects
of the disease complications.
The characteristics of physiological norms
of human organs and systems; norms of
the laboratory examination( blood
sampling, urine, biochemistry of blood,
characteristics of RIH, electrolytes, etc.).
Know how to
Collect specimens fot virological
(feces and blood sample) and
serological researches, interpret the
results of the findings
obtain the medical history, carry out a
clinical examination of the patient's
oragans, identify clinical signs of the
disease. Analyze the results.
Collect an epidemiologic evidence,
conduct an antiepidemic and
preventive measures in the nidus of
infection
Evaluate the results of the
immunological research.
Evaluate the results of the laboratory
examination.
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Neurology
Clinical and laboratory signs of hepatic
encephalopathy
Carry out the clinical examination of
the patient with affection of CNS.
Clinical
pharmacology
Pharmacokinetics and pharmacodynamics
, side effects of etiotropic and
pathogenetic therapy.
Prescribe the treatment based on age,
individual characteristics of the
patient, select a dose regimen, write a
prescription.
Reanimation and
intensive care
Emergency:
 Hepatic encephalopathy
 Brain edema
Diagnose and provide first aid in case
of emergecy:
 Hepatic encephalopathy
 Brain edema
5. The content of the course and its structure.
LABORATORY DIAGNOSIS OF ACUTE VIRAL HEPATITISES
Biochemical markers
1.
Cytolytic syndrome:
Elevated levels of ALT, AST (starting from the end of the incubation period), high iron levels in
blood, reduced PI and other coagulation factors, reduced albumin, cholesteryl ester.
2.
Mesenchymal-inflammatory syndrome:
Increased levels of α2 - β - γ - globulins, all classes of immunoglobulins, modified colloidal
probes (reduced sublimate titer and increased thymol test)
3.
Cholestatic syndrome:
Increased levels of conjugated bilirubin, bile acids, cholesterol, copper, ALP, 5'-nucleotidase,
GGT, bilirubinuria.
Specific markers
VIRAL HEPATITIS A
1.
2.
3.
4.
Virological research (immunoelectron microscopy of fecal filtrate)
Detection of HAVAg by ELISA
Serological methods: detection of anti-НАV IgM by RIA, ELISA (four weeks after exposure)
Positive PCR on RNA in blood and feces
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ACUTE VIRAL HEPATITIS В
1. Serological methods: detection of НВsAg, HBeAg, anti-HBcorIgМ, negative antiHBcorIgМ by ELISA, Counterimmunoelectrophoresis, RIA (eight weeks after
exposure)
2. Positive PCR НВV DNA in blood
ACUTE VIRAL HEPATITIS D (Acute co-infection)
 Detection of acute hepatitis B markers
 Serological methods: detection of HDVAg by ELISA, anti-HDVIgМ (sixteen weeks
after exposure) by ELISA
 Positive PCR НDV RNA in blood
ACUTE VIRAL HEPATITIS С
1. Serological methods: detection of anti-HCVcorIgМ, negative - anti-HCVcorIgG, antiHCVNS4IgG by ELISA (twelve weeks after exposure)
2. Positive PCR НCV RNA in blood
VIRAL HEPATITIS Е
1. Virological research (immune electron microscopy of fecal filtrate)
2. Serological methods: detection of anti-HЕV IgM
3. Positive PCR HEV RNA in blood
Differential diagnosis of viral hepatitises
Characteristics:
HAV
-
Seasonality (summer- fall)
The possibility of group outbreaks
Acute onset (Pseudo-influenza, mixed type)
Short fever (1-3 days)
Improvement of health on the onset of jaundice
Mainly mild course
The presence of specific markers
НВV
-
An indication of the different parenteral manipulations 3-6 months before the development
of symptoms
More common in older people, drug addicts, homosexuals
Sporadic cases
Gradual onset
Preicteric period: arthralgis, dyspepsia, mixed type (fever is not typical)
The condition does not improve since the appearance of jaundice
Mainly moderate course
The presence of specific markers
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НDV
-
Risk group - people with Australia antigen
Preicteric period fever - 60% of the patients
Constant pain in right upper quadrant
Mainly fluctuating course
GC worsen the corse of the disease
The presence of specific markers
-
Risk group - people who received blood transfusions
Gradual onset
Mainly mild course
Chronization in most cases
The presence of specific markers
-
Prevalence mainly in Asia, Africa, South America
An explosive epidemic, mainly water transferred
Age of patients: 15-18 years, 28-40 years
Acute onset
The condition does not improve since the appearance of jaundice
Preicteric period - acute epigastric pain
Phase 2 enzyme activity increase
Severe course with pregnant patients, high mortality rate
GC worsen the corse of the disease
The presence of specific markers
НCV
HEV
Hepatocellular jaundice:
Causes:
-
Transfusion of incompatible blood
Effect of parasites on red blood cells (malaria)
Toxic effect on red blood cells: alcohol, chemicals, medicaments
Toxic effect of pathogenicity factors of different microorganism
Symptoms:
- Yellow discoloration of the skin
- Different degrees of severity of Anemia (high reticulocyte count)
- Dark urine colour
- Pale stool
- Unconjugated hyperbilirubinemia due to increased bilirubin production
- Normal levels of ALT, AST
- Normal levels of ALP
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Post-hepatic Jaundice
Causes:
-
Bile duct obstruction
Liver abscess of the caudate lobule
Severe sepsis
Peptic ulcer, duodenal ulcer, common bile duct tumor
Pancreatic head lesion
Enlarged lymph nodes during hematologic diseases
Symptoms:
- Clinical patterns of the disease
- Yellow discoloration of the skin
- Pale stool
- Dark urine colour
- Conjugated hyperbilirubinemia
- Normal levels of ALT, AST / insignificantlyelevated levels
- Elevated levels of ALP
Pre-hepatic Jaundice
Causes:
-
Crigler-Najjar syndrome
Gilbert's syndrome
Toxic hepatitis
Cholestasis of pregnancy
Hepatic steatosis
Infectious diseases (brucellosis, tularemia, legionellosis, Q fever, leptospirosis,
herpesviridae, yellow fever, etc.)
Viral Hepatitises
Symptoms:
- Crigler-Najjar syndrome: appears in the first days of life , apparent jaundice, affection
of CNS, autosomal recessive inheritance
- Gilbert's syndrome: unconjugated hyperbilirubinemia due to insignificantly increased
bilirubin production, normal activity of transaminases and other hematologic signs, the
dominant-recessive pattern of inheritance, efficacy of phenobarbital
- Toxic hepatitis: anamnesis of aspirin dosage, sulfanilamides, tuberculostatic drugs
and others, mushroom poisoning, increased levels of bilirubin and transaminases
- Cholestasis of pregnancy: mostly during third trimester pregnancy, itch (sometimes
unbearable), jaundice, dark urine, fatigue, nausea, liver is not increased, slightly
increased transaminases , symptoms disappear after pregnancy in a few days.
- Hepatic steatosis (acute fatty liver of pregnancy): mostly during third trimester
pregnancy (late gestosis), acute onset (much like fulminant hepatitis) with rapid
development of kidney and liver failure, possibility of massive bleeding, liver is not
increased, increased levels of conjugated bilirubin, insignificantlyelevated /normal
levels of ALT, AST , high ammonia levels in blood, uric acid, at the beginning of the
first/second week patients usually die.
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Therapeutic approach for acute viral hepatitises (HAV)
Regimen – bed rest in any severity of the disease up to dehydration
Diet - №5, 5а (protein – 1,5-2 g/kg, fat – 0,8-1,8 g/kg, carbohydrates – 4-5 g/kg)
Etiotropic therapy:
- treatment of acute viral hepatitis С
Schemes:
1. Interferon 3-6 m IU х 3 times a week or daily, for 3-6 months
2. Interferon 3-6 m IU х 3 times a week or daily + Ribavirin 1000-1200 mg/day (15mg/kg)
daily, for 3-6 months
3. Peginterferon 180 mcg subcutaneously once a week for 3-6 months
- treatment of acute viral hepatitis B with lingering course
1. Peginterferon 180 mcg subcutaneously once a week for 6 months
Pathogenetic therapy (detoxification therapy, metabolic therapy, decongestant therapy for
improving microcirculation and reducing the itching).
MILD CLINICAL COURSE – diet (with drinking enough water) + bed rest + Ascorutin х 3
times a day (for 7 days) + Lactulose 15-20 mL х 3 times a day (for 7 days).
MODERATE CLINICAL COURSE - diet + bed rest (with drinking enough water)
 microclysters with 2-3% solution of sodium bicarbonate
 rectal infusion of 2-4% sodium bicarbonate solution 150-200 mL per day
 glucose-insulin-potassium mixture 50-70 mL of potassium chloride + 300-500 mL 5% of
glucose + insulin
 «Acesol», «Trisolum» i.v. drip-feed 200-400 mL daily for 5-7 days (especially if the
vomiting occurs)
 Reamberin, Reosorbilact 200-400 mL i.v. drip-feed daily for 7-10 days
 Enterosgel 1 tbsp. 3 times a day, orally, daily for 5-7 days
 Lactulose 15-30 mL х 3 times a day, daily
 Vitamin С 1000 mg i.v. with saline solution or 5% glucose solution
 Hepasol A 500 mL, Aminosteril N-Hера 8% - 500 mL, Hepa-Merz 40 mL with saline
solution, Aminosol 500 mL i.v. drip-feed
 Citrarginine 10 mL х 3 times a day, orally for 5-7 days
 Trental 200 mg х 3 times a day after meals for 7-10 days
 Osetron 8-mg per day for 5-7 days
SEVERE CLINICAL COURSE - diet + bed rest (with drinking enough water)
 microclysters with Lactulose
 rectal infusion of 2-4% sodium bicarbonate solution 150-200 mL per day
 glucose-insulin-potassium mixture 50-70 mL of potassium chloride + 300-500 mL 5% of
glucose + insulin
 «Acesol», «Trisolum» i.v. drip-feed 200-400 mL daily for 5-7 days (especially if the
vomiting occurs)
 Reamberin, Reosorbilact 200-400 mL i.v. drip-feed daily for 7-10 days
 Furosemide 1%-1-2 mL, Mannitol 30% - 200 mL per day
 Vitamin С 1000 mg i.v. with saline solution or 5% glucose solution
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





Amino acids with high levels of branched-chain amino acids and low levels of aromatic
amino acids: Hepasol A 500 mL, Aminosteril N-Hера 8% - 500 mL, Hepa-Merz 40 mL
with saline solution, Aminosol 500 mL i.v. drip-feed
Citrarginine 10 mL х 3 times a day, orally for 5-7 days
Lactulose 30-50 mL х 3 times a day, orally for 7-10 days
Bifiform 2 capsules х 2-3 times a day , orally for 5-7 days
Enterosgel 1 tbsp. 3 times a day, orally, daily for 5-7 days
Trental 200 mg х 3 times a day after meals for 7-10 days
TREATMENT OF HEPATIC ENCEPHALOPATHY
 Diet (protein deprivation up to 50mg per day) + strict bed rest
 For reduction of ammonia formation in the intestine:
- Lactulose 30-120 mL per day orally or rectally 1-3 mL 20% solution.
 The use of oral non-absorbable antibiotics:
- Ciprofloxacin 500 mg х 2 times per day – for 7 days
- Metronidazole 800-1000 mg per day — for 7 days
- Neomycin (in severe cases) 4-6g per day for7 days
 Increase of neutralization of ammonia in the liver:
- L-ornithine - L-Aspartate (Hepa-Merz ) 9-18 g per day, orally or 20-40 g/daily i.v. drip-feed
- Ornicetil - 3-6 g х 3 times a day
Ammonia neutralization in blood:
- Glutamic acid 1% - 150 mL i.v. drip-feed
- L-Arginine -L- glutamate (Glutargin) 40% - 5mL with saline solution
Drugs that reduce inhibitory processes in the CNS:
- Flumazenil
- Levodopa
- Bromocriptine
Combined action drugs:
- Hepasol A 500 mL х 2 times a day, i.v. drip-feed
Siphonage bowel
ATC: Mannitol 30% - 400mL per day, Sorbitol 15% - 400mL в сутки, Furosemide 1% 4-8mL per day
Medical aid for patient in prehospital phase provides oral detoxification (drinking
plenty of fluids, lactulose, sorbents (enterosgel, white coal)), in case of nausea and vomiting use
prokinetics (motilium, ondansetron).
6. Organizational structure and planning of the course:
Main stages of the
course, functions and
content
1
Learning
Methods of
objectives
control and
in levels of
training
adoption
2
3
Methodology
resources (control,
instructions)
4
Time
(min.)
5
1
0
1. Preparatory stage:
1. Planning a course
2. Goal-setting and
motivation
3. Control of the initial
knowledge
II
Interview.
Individual survey.
Test control.
См. п.1 ”Relevance”;
См. п.2 ”Learning
Objectives”;
Personal interview
questions.
2nd level tests.
15 min.
Table of contents - see
P.2.1; P.2.2 ”Learning
Objectives”
2. Main stage:
Shaping a system of
III
professional skills
Table of contents - see
P.2.2; P.2.3 ”Learning
Objectives”
3. Final stage:
1. Control and
improvement of
professional skills
2. Summarizing the
course
3. Homework with the
academic book list
(basic,
complementary)
III
Practical
professional
training in dealing
with different
(typical and
atypical) clinical
tasks.
Patient care
supervision.
Anamnesis.
Discharge abstract.
2nd - 3rd level
situational problems.
Individual control
of practical skills
and professional
activities of the
students. Analysis
of common
mistakes.
Test control.
3rd level tests.
3rd level situational
problems.
60 min.
15 min.
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