Hepatitis is inflammation of the liver tissue.[3][5] Some people or animals with hepatitis have no symptoms, whereas others develop yellow discoloration of the skin and whites of the eyes (jaundice), poor appetite, vomiting, tiredness, abdominal pain, and diarrhea.[1][2] Hepatitis is acute if it resolves within six months, and chronic if it lasts longer than six months.[1][6] Acute hepatitis can resolve on its own, progress to chronic hepatitis, or (rarely) result in acute liver failure.[7] Chronic hepatitis may progress to scarring of the liver (cirrhosis), liver failure, and liver cancer.[3] Hepatitis Alcoholic hepatitis.jpg Alcoholic hepatitis as seen with a microscope, showing fatty changes (white circles), remnants of dead liver cells, and Mallory bodies (twisted-rope shaped inclusions within some liver cells). (H&E stain) Specialty Infectious disease, gastroenterology, hepatology Symptoms Yellowish skin, poor appetite, abdominal pain[1][2] Complications Scarring of the liver, liver failure, liver cancer[3] Duration Short term or long term[1] Causes Viruses, alcohol, toxins, autoimmune[2][3] Prevention Vaccination (for viral hepatitis),[2] avoiding excessive alcohol Treatment Medication, liver transplant[1][4] Frequency > 500 million cases[3] Deaths > One million a year[3] Hepatitis is most commonly caused by the virus hepatovirus A, B, C, D, and E.[2][3] Other viruses can also cause liver inflammation, including cytomegalovirus, Epstein–Barr virus, and yellow fever virus. Other common causes of hepatitis include heavy alcohol use, certain medications, toxins, other infections, autoimmune diseases,[2][3] and non-alcoholic steatohepatitis (NASH).[8] Hepatitis A and E are mainly spread by contaminated food and water.[3] Hepatitis B is mainly sexually transmitted, but may also be passed from mother to baby during pregnancy or childbirth and spread through infected blood.[3] Hepatitis C is commonly spread through infected blood such as may occur during needle sharing by intravenous drug users.[3] Hepatitis D can only infect people already infected with hepatitis B.[3] Hepatitis A, B, and D are preventable with immunization.[2] Medications may be used to treat chronic viral hepatitis.[1] Antiviral medications are recommended in all with chronic hepatitis C, except those with conditions that limit their life expectancy.[9] There is no specific treatment for NASH; physical activity, a healthy diet, and weight loss are recommended.[8] Autoimmune hepatitis may be treated with medications to suppress the immune system.[10] A liver transplant may be an option in both acute and chronic liver failure.[4] Worldwide in 2015, hepatitis A occurred in about 114 million people, chronic hepatitis B affected about 343 million people and chronic hepatitis C about 142 million people.[11] In the United States, NASH affects about 11 million people and alcoholic hepatitis affects about 5 million people.[8][12] Hepatitis results in more than a million deaths a year.

1. Hepatitis viruses. HIV. Features
of structure and main biological
properties
Vinnitsa National Pirogov Memorial
Medical University / Department of
microbiology

2.  The term “viral hepatitis” refers to a
primary infection of the liver by any
one of a heterogeneous group of
“hepatitis viruses”. It consists of
types A, B, C, D, E, G.
 Hepatitis viruses are taxonomically
unrelated (DNA and RNA viruses). The
features common to them are:
1. hepatotropism
2. ability to cause a similar icteric illness
3. Infective for human beings

4. Infective or infectious hepatitis:
1. Occurred sporadically or as epidemics;
2. Affecting mainly children and young adults;
3. Transmitted by the fecal-oral route.
Serum hepatitis or transfusion hepatitis:
1. transmitted mainly by parenteral route via
blood and sexual intercourse
2. Affecting professional risk groups, newborns,
drug users, prostitutes etc.
By epidemiological and clinical criteria,
two types of viral hepatitis:

5. Causing infective hepatitis:
*hepatitis virus A (HAV) world-spread
*hepatitis virus E (HEV) tropical spreading
Causing serum hepatitis:
*Hepatitis virus B (HBV) pandemic, world
spread
*Hepatitis virus D (HDV) coinfection with HBV
*Hepatitis virus C (HCV) primary chronic or
latent
*Hepatitis virus G (HGV) post-hemotransfused

6. Picornaviridae family:
HAV
1. HAV is a spherical
naked virus
2. 27-30 nm in diameter
*Genome: ss(+)RNA
Caliciviridae family
HEV
*HEV is a spherical naked
virus
*32-34 nm in diameter
Genome: ss (+) RNA
Morphology of viruses causing infectious
hepatitis

7. HAV

8. * HAV, HEV are inactivated by
1. Heating at 60oC for one hour
2. Acidity at pH 3
3. Boiling for one minute
4. Autoclaving 1210C for 20 minutes
5. Usage of 1:4000 formaldehyde at 370C for
72 hours
* It survives prolonged storage at a
temperature of 40C or below
Resistance

9. Epidemiological points for infectious
hepatitis
*Transmitted by the fecal-oral route
*Hepatitis A and E have been shown to occur in
epidemic, endemic and sporadic forms
*It occurs predominantly in young to middle-aged
adults
*The disease is generally mild and self limited, with
a low case fatality
*Immunity after infection is strong, long-lasting
*A unique feature of HEV is the clinical severity and
high case fatality in pregnant women, especially in
the last trimester of pregnancy

11. Pathogenesis
Virus multiplies in the intestinal
epithelium and GALT and via lymph
reaches blood stream
Viremia (short) corresponds prodromal
(preicteric) period: fever, malaise, anorexia,
nausea, vomiting and liver tenderness
Virus reaches the liver via blood and affects
hepatocytes (icteric stage): jaundice, with
yellowing of the skin and the whites of the
eyes and the dark urine typical of liver
infections

12. Laboratory diagnosis
* Etiological diagnosis of infectious
hepatitis may be done by demonstration
of the virus, viral antigens or
corresponding antibody
1. IEM – the virus can be visualized in fecal
extracts
2. Serology: CFT, immune adherence,
reaction of the passive hemagglutination,
radioimmunoassay and ELISA (for
detection of antibody: Ig M and Ig G)

13. Laboratory diagnosis
*Immunoelectron microscopy – feces is
examined by electron microscopy of
aggregated calicivirus-like particles
using monoclonal antibodies
*ELISA test and western blot assay –
these are used for detection of Ig M and
Ig G antibodies
*Polymerase chain reaction – HEV RNA
can be detected in feces or acute phase
sera of patients

14. Prophylaxis
* General prophylaxis consists of:
1. improved sanitary practices;
2. prevention of fecal contamination of food and
water
* Specific prophylaxis
1. Active– use a live attenuated or inactivated
vaccine (protection begins 4 weeks after
injection and lasts for 10 to 20 years (HAVrix,
Avaccim)
2. Passive – usage of normal human Ig
* Treatment is symptomatic. No specific antiviral
drug is available

15. Type B hepatitis (HBV)
*Morphology
*Enveloped, spherical
*HBV is a 42 nm
*DNA virus with an outer envelope and inner
core, enclosing the viral genome and a DNA
polymerase
*HBV is assigned to a separate family
Hepadnaviridae

17. *Under the electron microscope, sera
from type B hepatitis patients show 3
types of particles:
*The first type of particles are spherical (20 nm in
diameter)
*The second type of particles are tubular (20 nm in
diameter)
These two types of particles represent Australia
antigen
*The third type of particles are double shelled
spherical (42 nm) and also called Danes particles

18. Antigen Structure
*HBsAg – hepatitis B surface antigen
(glycoprotein)
*HBcAg – hepatitis B core antigen
(nucleocapsid)
*HBeAg – hepatitis B core antigen, is
derived from HBcAg (contains viral
DNA polymerase enzyme)
*HBxAg – abnormal Ag arising in the
blood at tumor transformation of the
infected hepatocytes

19. Resistance
*HBV is a relatively heat stable virus
*It survives at room temperature for
long periods and at boiling for 30-40
min
*It is susceptible to chemical agents:
hypochlorite, 2% gluteraldehyde
*It is relatively stable to UVR

20. *There are three important modes of
transmission of HBV infection:
parenteral, perinatal, sexual
*The incubation period is long (about 1-
6 months)
*The clinical picture of hepatitis B is
similar to that of type A, but it tends to
be more severe and protracted

21. Features of pathogenesis
*The pathogenesis of hepatitis appears
to be immune mediated.
*Hepatocytes carry viral antigens and
are subject to antibody-dependent NK
cell and cytotoxic T-cell attack
*In the absence of adequate immune
response HBV infection may not cause
hepatitis, but may lead to carrier state

22. Laboratory diagnosis
* Laboratory diagnosis of HBV infections can be
carried out by detection of hepatitis B antigens
and antibodies (viral markers). These can be
detected by sensitive and specific tests like ELISA
and RIA
1. HBsAg – it is the first marker to appear in blood
after infection. Peak levels of HBsAg are seen in
the preicteric phase of the disease. It remains in
circulation throughout the icteric or
symptomatic course of the disease

24. Laboratory diagnosis
*HBeAg – appears in the serum at the same time
as HBsAg. HBeAg is an indicator of active
intrahepatic viral replication and the presence in
blood of HBV DNA, virions and DNA polymerase.
*HBcAg – is not detectable in the serum but can
be demonstrated in liver cells by
immunofluorescence. Anti-HBc antibody is the
earliest antibody to appears in the blood.
*Viral DNA polymerase – it appears transiently in
serum during preicteric phase (the level DNA can
be detected in serum by PCR)

25. Prophylaxis
* Prophylaxis includes:
* General preventive measures (these include
health education, improvement of personal
hygiene and strict attention to sterility
* Immunisation
1. Passive – usage of anti HB immunoglobulin
(HBIG is prepared from donors with high titre of
anti-HBs)
2. Active. Following vaccine preparation may be
useful:
* Recombinant vaccines including HBsAg
synthesized by recombinant strains of E.coli,
yeasts (HB-VaxII, Engeenerix, HAVrix)

26. Treatment of HBV infection
*Inhibitors of virus DNA-polymerase:
Foscarnet, Lamivudin
*Recombinant interferone : Betaphor,
Rebif, Realderon, Intron, Imukin

27. Type D (Delta) hepatitis (HDV)
*HDV is a defective RNA virus depending on the
helper function of HBV for its replication and
expression. It belongs to genus Deltavirus
Morphology:
*It is spherical,
36-38 nm diameter
*The genome is
a small circular
molecule of ss (-) RNA.
Lipid envelope is HBsAg-including

28. * Two types of infection are recognized
1. Coinfection – delta and HBV are
transmitted together at the same time.
Coinfection clinically presents as acute
hepatitis B, ranging from mild to fulminant
disease
2. Superinfection – in superinfection, delta
infection occurs in a person already
harbouring HBV. Superinfection usually
leads to more serious and chronic illness

29. Laboratory diagnosis
*Delta antigen is primarily expressed in liver
cell nuclei, where it can be demonstrated by
immunofluorescence
*Anti-delta antibodies appear in serum and
can be identified by ELISA test
Prophylaxis
*No specific prophylaxis exists, but
immunisation with the hepatitis B vaccine is
effective because delta virus cannot infect
persons immune to HBV

30. Viral hepatitis C and G (HCV, HGV)
*Hepatitis C virus and hepatitis G virus
belong to family Flaviviridae
*HCV is a 50-60 nm enveloped virus with
a linear single stranded RNA of positive
polarity (ss(+)RNA)
*Enclosed within a core and surrounded
by an envelope, carrying glycoprotein
spikes

33. HGV
*HGV RNA has been found in patients
with acute, chronic and fulminant
hepatitis, haemophillic patients with
multiple transfusions, blood donors and
intravenous drug addicts
*The virus is transmitted parenterally,
sexually and from mother to child
*Infection may occur in patients
coinfected with hepatitis C
*HGV infection can be detected by PCR
and by detection of antibody with ELISA

34. Laboratory diagnosis
*It can be established by
detection of anti-HCV / anti
HGV by ELISA. Antibody
detection becomes positive
only month after the infection
*Viral genome (HCV RNA)
can be detected by PCR
and immunofluorescence
in hepatocytes (biopsy
samples).

35. Prophylaxis
*Only general prophylaxis, such as blood or
blood products screening is possible.
*Avoidance of use of unsterile needles,
syringes and other material is another
important general prophylactic measure

37. Retroviruses
Classification
*Family Retroviridae
*Subfamilies:
*Lentivirinae (It includes the causative
agent of the slow virus diseases)
*Oncovirinae
*Spumavirinae

38. Structure of HIV

39. Morphology
*HIV is a spherical enveloped virus
*Diameter is about 90-120 nm
*It contains two identical copies of ds (+)
RNA genome
*In association with viral RNA is the reverse
transcriptase enzyme
*The virus contains a lipoprotein envelope
*The major virus coded envelop
glycoproteins are the projecting spikes on
the surface (spikes bind to the CD4 receptor
on susceptible host cells)

40. Viral genes and antigens
* The genome of HIV contains the three
structural genes:
1. gag
2. pol
3. env
* The products of these genes act as antigens

41. Major antigens of HIV-1
• Envelope antigens:
1. Spike antigen – gp 120 (principal envelop
antigen)
2. Transmembrane pedicle protein – gp 41
• Shell antigen:
1. Nucleocapsid protein – p 18
• Core antigens:
1. Principal core antigen – p 24 (matrix protein)
2. Other core antigens – p 7; p 9
• Viral enzymes – p11 (integrase); p31 (protease);
p 51 (reverse transcriptase)

42. Antigenic variation
* HIV undergoes frequent antigenic variation of
core and envelope antigens.
* Two distinct antigenic types of HIV have been
identified
1. HIV-1 – represents the original isolate from
America, Europe and other Western countries
2. HIV-2 - represents isolates from West Africa
* The envelope antigens of the two types are
different.
* Their core polypeptides show some cross
reactivity

43. Resistance
*Temperature: HIV is heat-lable, being
inactivated at 560C in 30 min and in seconds at
1000C. At room temperature, it may survive up
to seven days
*Disinfectants: It is inactivated in 10 min by
treatment with 35% isopropyl alcohol, 70%
ethanol, 0.5% Lysol, 0.5% sodium hypochlorite
and 3% hydrogen peroxide, detergents
(because of presence of lipid membrane
envelope)

44. Epidemiology
* There are three modes of transmission:
1. sexual intercourse
2. parenteral – it may occur through blood
after receiving infected blood transfusions,
blood products, sharing contaminated
syringes and needles
3. perinatal - infection may be transmitted from
an infected mother to her child either
transplacentally or perinatally .

45. Pathogenesis
*Infection is transmitted when the virus enters
the blood or tissues of a person and comes into
contact with a suitable host cell, carrying CD4
receptor (T- lymphocytes (helper), B-
lymphocytes, monocytes, macrophages, glial
cells, microglia, follicular dendritic cells from
tonsils)
*Once in the cell, RNA is transcribed by reverse
transcriptase into ss DNA, that is converted into
dsDNA with host enzyme (provirus)

46. *Intraspecies classification
*According to the type of the infected cell (cellular tropism) two
strains of the HIV have been recognized:
1.X4 strain infects the activated T-helpers, carrying the CXCR4
receptor to chemokine on their surface
2.R5 strain infects macrophages and non-activated T-helpers,
carrying the chemokine receptor CCR5
3. Strains with double tropism are signed as R5X4

47. Virus reproduction

48. Releasing of the progeny virions from
infected T-helper by budding

49. Clinical periods of infection
*The clinical course of HIV infection has been
classified into various groups:
*Group 1 – Acute HIV infection. The illness is
characterized by acute onset of fever, malaise,
sore throat, myalgia, arthralgia, skin rash and
lymphadenopathy
*Group 2 – Asymptomatic infection. This
includes all infected persons who are usually
well

50. Clinical periods of infection
*Group 3 - Persistent generalized
lymphadenopathy. This group is characterized
by enlarged nodes (more than 1 cm) at two or
more extragenital sites for at least three
months.
*Group 4 – Syptomatic HIV infections. When
CD4 T-lymphocyte count falls the patient may
develop symptoms like fever, diarrhea, weight
loss, night sweats and opportunistic infections.
In addition to the opportunistic infections,
patient may also develop primary lymphoma,
sarcoma Kaposhi, and progressive multifocal
leukoencephalopathy

51. HIV-associated opportunistic
infections
*Bacterial infections: tuberculosis, shigellosis,
salmonellosis, mycobacteriosis, staphylococcal
and streptococcal purulent infections, etc.
*Fungal infections: generalized candidosis,
cryptococcal infection, histoplasmosis
*Protozoan invasions: pneumocystosis,
toxoplasmosis, amoebaean dysentery,
lambliosis
*Viral infections: generalized herpetic infection,
CMV, VEB, sarcoma Kaposhi

52. Sarcoma Kaposhi

53. Laboratory diagnosis (seronegative
period)
Specific tests for HIV infections (early diagnosis)
1. Antigen detections – following a single massive
infection, the virus antigen (p24) and reverse
transcriptase may be detected in blood after about
two weeks.
2. Virus isolation (It is not used as laboratory
method widely!) - patient‘s lymphocytes are co-
cultivated with uninfected human lymphocytes in
the presence of interleukin
Viral replication can be detected by demonstration
of reverse transcriptase activity and presence of
viral antigen
3. Detection of viral nucleic acid (PCR)

54. Laboratory diagnosis (seroconversion
period)
3. Antibody detection – there are two types of
serological tests:
Screening
*Particle agglutination (latex, gelatin)
*ELISA test
Supplemental (confirming tests)
*Western blot test
*Indirect immunofluorescence test
*Radio immunoprecipitation assay

56. Laboratory diagnosis
Non-specific tests
1. Total and differential leukocyte count
2. T-lymphocyte subset assays
3. Platelet count
4. Ig G and Ig A levels
Tests for opportunistic infections and
tumors

57. Prevention and therapy
Nucleoside inhibitors of
reverse transcriptase
(Zydovudin, Viro-Z,
Didanozin, Lamivudin,
complex medicines –
Virocomb, Duovir, Combivir)
Non-nucleoside inhibitors
of reverse transcriptase
(Nevirapin, Ifavirenz)
Viral protease inhibitors
(Sacvinavir, Ritinovir)
Fusion inhibitor (Zintevir)