HEPATITIS В

 Clinical forms of HB are various from

asymptomatic and mild to severe cases.
 In clinical cases HB may be characterized by

intoxication, jaundice, hepato- and

splenomegaly, arthralgias, itching and other
symptoms.
 Fulminant hepatitis with the development of

encephalopathy may occur in severe cases.

 Chronic hepatitis, cirrhosis and hepatocellular

carcinoma (HCC) may develop as well.

 Hepatitis В virus (HBV) is a small,
hepatotropic virus containing DNA molecule
 It contains four antigens:

 hepatitis В core antigen (HB Ag),

c
 hepatitis В е antigen (HBe Ag),
 the viral surface antigen (HBs Ag)
 HBx Ag.
 There are 8 main genotypes of the virus: A, B,

C, D, E, F, G and H.
 HBV retains infectivity for humans
at room temperature for 3
months,
 in refrigerator - for 6 months and
15 years when frozen at -20 °C.
 In 1 - 2% chloraminum infectivity
is destroyed in 2 hours and by
boiling - in 30 minutes.
 The only source of infection is
infected humans contracted
with acute, chronic HB and
carriers.
 The contact mechanism of

transmission is common for

this disease.
 sexual
pathway
vertical

contact
with
fomities
 by heterosexual and
homosexual contacts
 The probability of infection is

very high, up to 98%

 today is the main pathway of

transmission
 It is possible to be transmitted through
the placenta
 5% of affected children are infected in

utero
 95% are infected at the moment of
delivery as the result of contact with
maternal blood
 infants may be infected during the first

few months or years of life having

contacts with their infected mothers.
 blood
through transfusions or
injections other blood
products
a pathway
associated with
invasive medical
procedures
A person can get infected
during tattooing, piercing,
manicure.
 Medical and dental workers

may be infected through the

blood of infected patients.
 viralantigens may be found during
HBV infection in the blood and some
other body fluids,
 only blood, serum and semen play an
important role in transmitting
hepatitis B,
 because concentration of viruses in
other fluids is considerably lower than
that in the blood, serum and semen.
 AsHBV is quite stable in the
external environment, in rare
cases, the disease is possible to
be transferred in the home -
through objects contaminated
with blood (razors, toothbrushes).
 nocases of transmission the
disease to humans from insect
vectors (mosquitoes, bedbugs
and other blood-feeding
insects) have been registered.
 Post-infectious immunity is
long-lasting, probably,
lifelong.
 The repeated cases of HB

occur rarely.
 drug-takers through shared needles
 patients in haemodialysis centres
 patients receiving blood transfusions or other
blood products
 commercial sex workers
 medical personnel frequently contacting blood,
blood-contaminated body fluids, and laboratory
personnel who work with human blood
 household contacts with persons with chronic
HBV infection
 newborns and young infants whose mothers are
infected
 In any routes of transmission HBV reach liver and
attach hepatocytes where extensively multiply.
 But HBV can replicate in polymorphonuclear
leucocytes, lymphocytes, monocytes, bone
marrow cells, pancreatic cells, cells of skin and
kidneys.
 Virus and viral antigens eliminate in blood and
may be found during HBV infection in the liver
cells, in the blood and some other body fluids
(semen, urine, sweat, bile, saliva, tears, breast
milk, vaginal secretion) of acutely ill patients.
 Anatomic and pathophisiological
changes in VHB are similar to
those in hepatitis A
 develops
 cytolytic syndrome
 cholestatic syndrome
 mesenchymal-inflammatory syndrome

 but morphological and metabolic shifts are
usually more severe.
 Dystrophic and necrotic processes in liver

cells may lead to its destruction with

development of severe metabolic shifts.
 In severe cases of the disease extensive

necrosis of hepatocytes may develop.

 In such a case encephalopathy develops –

the most serious complication of HB.

 Immuno-mediated mechanism plays an
important role in the development of
morphological changes.
 Liver damage is caused not so much by the

virus itself as by cellular immune responses.

 Cytotoxic Т-cells recognize and lyse

infected hepatocytes.
 T-lymphocytes produce γ-interferon,

triggering a number of immune reactions.

 virus specific antibodies are formed.
 the immune response may be adequate.
 Then there can be recovery.
 But the immune response may be weak.
 Then there can be development of chronic

hepatitis
 With an adequate immune response, the

jaundice form of hepatitis often develops

 With a weak immune response, an

asymptomatic form of hepatitis often

develops
 In the course of the disease autoimmune
mechanisms are possible with the
production of antibodies to native
hepatocytes.
 Immune complexes with HBV may be

adsorbed to different tissues with

subsequent development of periarteritis,
pancreatitis, glomerulonephritis
 The incubation period of acute
hepatitis В is from 6 weeks to
6 months, but in most cases
this interval is between 2 and
4 months.
 pre-icteric period lasting 7-14 days,
 is characterized by
 dyspeptic symptoms
 astheno-vegetative syndrome with malaise, loss
of appetite, headache

Usually moderate fever (37.5-38.5 °C) is present
only for a few days.
 30-35% of patients have arthralgia.
 But the joints do not change in size and the skin over
them has normal colour.
 Arthralgia usually disappears in 5-7 days, but may
remain for several weeks.
 Urticaria is possible with HBV
 During the last days of the preicteric stage urine
becomes dark and stool is light, clay-coloured.
 symptoms described above, in contrast with
hepatitis A, usually progress in severity with the
onset of jaundice.
 In many patients bradycardia is revealed, the
blood pressure drops and the heart sounds
become dull.
 The enlargement of the liver may be observed
already at the end of the pre-icteric period.
 The liver may continue to enlarge for the first 2
weeks.
 The spleen is palpable in 30 to 40 per cent of
patients.
 the jaundice period extends to several
months,
 the intensity of jaundice is great,
 During preictreric and icteric stages

approximately 20% of patients may have mild

or severe itching of the skin. The itching may
sometimes disturb the patient's sleep and
general state.
 the serum activity of alkaline phosphatase is

significantly increased.
 Most patients with icteric acute hepatitis В recover
and have no residual disease.
 Adults usually recover in 4 to 6 weeks, but this
process may be prolonged because of development
of relapses.
 Relapses occur in a low proportion of cases and are
usually milder than the initial acute illness.
 Relapses may be attributed to consumption of
alcohol, treatment with corticosteroids during the
acute illness, etc.
 If clinical symptoms don't disappear in 6 months
after the onset of the disease and HBV DNA, HBsAg,
HBeAg remain in the blood there is a high risk of
chronic form development.
 Encephalopathy is the most severe complication of
HB, which develops most often when the patient is
infected both with HBV and HDV, and in pregnant
women – with HЕV.
 Encephalopathy manifests itself with progressive
 adynamia,
 vomiting,
 complete loss of appetite,
 impaired mental activity,
 considerable sleepiness during the daytime and
insomnia at night
 Rise in temperature
 These symptoms sometimes go to the extreme
degree leading to
 hyperexcitability,
 delirium,
 hallucinations,
 aggressive actions
 Epileptic seizures,
 involuntary urination and defecation
 Oliguria
 Bleeding from the nose, gums, intestines and
skin petechiae may be present.
 In such cases coma frequently develops
 On physical examination the
patient's liver contracts rapidly
within 2 – 3 days
 The pulse is rapid.
 The pupils are dilated
 edema and ascites may develop
 Extensive hepatic necrosis is associated with
a decrease of serum transaminase activity
 increased levels of bilirubin due to indirect

fraction
 progressive decrease of prothrombin index,
 azotemia may develop
 leucocytosis may occur
 The prognosis in such cases is always bad

and the mortality is exceedingly high.

 Mild, moderate or severe Hepatitis may
develop as in HAV.
 Other forms of hepatitis В include prolonged,

anicteric and subclinical acute hepatitis.

 Prolonged acute hepatitis may persist for

several months and is characterized by mild

symptom and abnormal laboratory and
physical findings.
 The period of convalescence for HBV lasts as

in HAV
 Icteric forms of HBV may be
determined on the basis of clinical
and epidemiological data.
 In any case laboratory investigations

play an important role in diagnosis.

 The diagnosis may be confirmed by

using specific and highly sensitive

tests (ELISA, PCR)
 DNA can be detected in the blood from the first 3-5
weeks of the incubation period and during the acute
stage of the disease
 HBsAg can be detected from the first 3-5 weeks of the

incubation period and may persist for up to some

months (not more than six months)
 HBeAg appears together with HBsAg, but disappears

in the jaundice period

 HBcAg (internal antigen of virion) is detected only in
hepatocytes
 Anti-HBc IgM is detected in the first days of the

disease and disappears in the jaundice period

 anti-HBc Ig G is detected in the jaundice period
 IgM and IgG are detected for some time in the jaundice

period
 anti-HBcIgG can be detected for a long time after acute

infection in most patients, probably during a lifetime.

 Anti-HBs can be detected only in several weeks
after HBsAg disappearance from the blood.
 Anti-HBe appears in most patients after HBeAg
disappearance in 1 – 2 weeks
 Anti-Hbe, Anti-HBs may persist for 1 to 2 years
after recovery from HBV infection.
 Anti-HBs and anti-HBe are associated with
protection against reinfection.
 In case of recovery after 6 months from the onset
of the disease HBsAg and HBеAg should not be
detectable in the blood.
 When chronic viral hepatitis B
HBsAg and DNA continue to be
detected.
 HBeAg, Anti-HBc IgM may

periodically be detected.
 HВsAg – detected
 HВeAg – detected
 Anti HВcorAg IgМ – detected
 Anti HВcorAg IgG – not detected
 Anti HВеAg – not detected
 Anti HВsAg – not detected
 HВsAg – detected
 HВeAg – not detected
 Anti HВcorAg IgМ – not detected
 Anti HВcorAg IgG – detected
 DNA HВV – not detected
 HВsAg – detected
 HВeAg – not detected
 Anti HВcorAg IgМ – not detected
 Anti HВcorAg IgG – detected
 DNA HВV – detected
 HВsAg – not detected
 HВeAg – not detected
 Anti HВcorAg Ig М – not detected
 Anti HВcorAg IgG – detected
 PCR –DNA HВV – not detected
 HВsAg – not detected
 HВeAg – not detected
 Anti HВcorAg Ig М – not detected
 Anti HВcorAg IgG – not detected
 Anti HВeAg – not detected

Anti HВsAg – detected

 PCR – DNA HВV – not detected
 Changes in biochemical analysis
of blood,
 general blood analysis,

 general are much

urine analysis
the same as in HAV.
 Аll patients with VHB are
hospitalized.
 In severe cases complete bed

rest is administered.
 The symptomatic treatment of

acute hepatitis В is identical to

that of hepatitis A.
 Antiviral therapy is used to treat
chronic hepatitis B.
 Synthetical nuceosides (entecavir, etc.)

and recombinant interferons

(interferon-alpha 2a or intron A,
roferon A, realderon, etc.) are used.
 Antiviral therapy stops viral replication

in about one-third of patients.

 For the treatment of chronic hepatitis B, the
recommended dose of telbivudine is 600 mg (1
tablet) once a day, regardless of meal.
 To assess the effectiveness of treatment, the
amount of HBV DNA should be determined every
6 months of therapy.
 The viral response on 24th week of treatment is
shown to be a predictor of a long-term response
to treatment.
 For patients with a defined amount of HBV DNA
(more than 300 copies/ml) on 24th week of
treatment alternative therapy should be used.
 The optimal duration of treatment has not been
established.
 Forpreviously
untreated
patients: 0.5
mg / day
regardless of
meal
Resistance Tactics

To lamivudine - tenofovir
To telbivudine - tenofovir
To entecavir - tenofovir
To tenofovir Not treated with the
lamivudine - entecavir
To several drugs Tenofovir + entecavir
The optimal duration of
treatment has not been
established.
ToCURE chronic HBV is
IMPOSSIBLE

Because the virus DNA is

integrated into the
hepatocytes DNA
HEPATITIS D
 Hepatitis D (HD) is a viral disease, anthroponosis,
caused by simultaneous affection of HDV and
HBV.
 HDV is a defective virus because it cannot
replicate and develop disease alone.
 Epidemiology and pathogenesis of the disease is
much the same as in HB.
 But in contrast to HB, the disease is characterized
by more extensive pathomorphological and
metabolic changes.
 Therefore, severe clinical picture often develops.
A person infected with HDV and
HBV is the source of the disease.
 Human may be infected with HDV

and HBV simultaneously (co-

infection) or HDV may affect
patients with chronic VHB or
chronic HBsAg carriers
(superinfection).
HDV is directly responsible for
cytotoxic lesions of the
hepatocytes.
Extensive hepatic necrosis is

characteristic of this disease.

 The incubation period of acute hepatitis D may
last from 1 to 6 months (in case of co-infection)
or 3-4 weeks (in case of superinfection).
 The clinical picture of the disease resembles

manifestation of HB but is characterized by a

more severe course with frequent development
of fulminant hepatitis, encephalopathy or chronic
course often resulting in cirrhosis.
 Acute co-infection (HBV+HDV)
usually develops as acute HB.
 Co-infection leads to fulminant

hepatitis in approximately 5—25%

of cases with acute HD.
 Chronic forms develop only in 1—

5% of all cases.
 Superinfection with HDV is able to
convert mild, asymptomatic HBV-
infection into severe or even fulminant
course of the disease.
 Only in rare cases convalescence may

occur.
 Chronic forms resulting in cirrhosis

develop in 80% among those who

survive.
 Indicatorof acute HDV infection is the
presence of IgM anti-HDV in the serum.
 Later IgG anti-HDV may be detected.
 PCR allows to reveal HDV RNA in

serum
 Biochemical investigations of

serum, urine and faeces show the

same changes as in other types of
viral hepatitis.
 Treatment and prevention of
HD are the same as those in
HB.
 Hepatitis В vaccination

prevents delta virus infection

as well.
HEPATITIS С
 Hepatitis С (НС) is an anthroponotic,
bloodborne infection caused by hepatitis С virus
(HCV).
 The disease is transmitted primarily through

parenteral mechanism.
 Acute hepatitis С is usually asymptomatic or has

a mild clinical picture but in the majority of

cases it progresses to chronic hepatitis with a
high risk of cirrhosis and hepatocellular
carcinoma (HCC) development.
 Hepatitis C virus is RNA containing virus, a
hepatotropic virus
 HCV genome is extremely changeable.
 This feature allows the virus to avoid immunological

control and hinders the development of vaccines

 there are 6 genotypes of HCV and more than 50

subtypes are described (la, lb, 2a, 2b, 3a are

registered more often).
 In the external environment VHC is unstable.
 Structure of HCV

Metalloprotease
Serine protease
RNA helicase IFN-PKR
repressor
Envelope
Nucleocapsid Transmembrane RNA-dependent
Cofactor
RNA polymerase

5'UTR 3'UTR
C E1 E2 NS2 NS3 NS4A NS4B NS5A NS5B
 hepatitis С is a frequent liver disease among
population.
 The source of infection is a sick human.
 Patients with asymptomatic or mild hepatitis С,
with chronic HC are more often the sources of
infection.
 The period of communicability starts at the
incubation time (1—2 weeks before clinical signs)
and continues during prodromal period and
jaundice.
 patients with chronic viral hepatitis C are
contagious all their lives
 The viral RNA is found in blood,
semen and other biological fluids
(saliva, tears, urine, cerebrospinal
fluid, ascitic fluid).

But only the patient's blood
plays the major epidemiological
role.
 the mechanism of transmission, transmission
pathways, risk groups for infection in viral
hepatitis C are the same as in viral hepatitis
B
 artificial transmission routes are the main

ones
 sexual, vertical routes do not play much role
 It is known that HCV is transmitted by sexual

route 5 - 10 times less frequently than HBV.

 HCV spread from the entry of infection by the
blood and reach the liver where infect only
hepatocytes and multiply there.
 extremely changeable genome HCV leads to
formation of numerous new variants of the
viruses and allows them to escape from a cellular
and a humoral adequate immune response,
which may contribute to viral persistence for a
long time turning into a chronic disease.
 HCV are directly cytopathic to hepatocytes but
they are able to activate the destruction of
infected cells by immune-mediated mechanisms
as well.
 HCV infection leads to hepatic inflammation
with periportal lymphocyte infiltration.
 Subsequently fibrosis develops in portal

triads and bridges between them.

 This process destroys the hepatic architecture

and gradually progresses to cirrhosis.

 there is a great risk in the development of

hepato­cellular carcinoma.
 Cirrhosis, hepato­cellular carcinoma are long-
term complications usually occur in 20 - 30
years or more after the onset of infection.
 Co-infection with HBV, HIV and alcohol taking

may accelerate the progression of HC.

 The infection may develop more rapidly in the

elderly patients as well.

 Infection with genotype lb virus increases the

risk of hepatocellular carcinoma

development.
 Metabolic shifts (ALT, AST, bilirubin in the
blood, urobilin and bile pigments in the
urine, stercobilin in the faeces) are similar to
those of other viral hepatites.
 stable immunity after infection does not

develop because the immune system does

not have enough time to produce adequate
antibodies against new-born types of
antigens.
 Most cases of HC are asymptomatic and are
not recognized.
 Only about 25% of patients after the

incubation period (2 – 26 weeks) develop

clinical signs of acute hepatitis.
 acute hepatitis С may be clinically

indistinguishable from other types of acute

viral hepatitis.
  is characterized by
 dyspepticsymptoms
 astheno-vegetative syndrome


moderate fever (37.5-38.5 °C) which is
usually present only for a few days.
 Arthralgia is possible.
 Some patients complain of itching.
 During the last days of the preicteric stage

urine becomes dark and stool is light or clay-

coloured.
 Clinical picture is frequently characterized only
by a slight fatigue and mild jaundice.
 The patient's liver is frequently slightly enlarged.
 Spleen enlarges in 20% of patients.
 Over 75% of acute hepatitis С infections are
unicteric.
 In acute hepatitis С fulminant forms of the
disease develop very seldom.
 But in about 75 – 95% of patients with acute
hepatitis С the disease progresses to chronic
hepatitis С.
 In the majority of patients this form of the
disease is asymptomatic for a long time, with a
gradual development of hepatocyte damage.
 serum ALT and AST levels increase periodically
 Many patients have minimal elevation in ALT,
AST and bilirubin in serum or even normal level
of these indexes.
 Symptoms of the disease (fatigue, esophageal
varices, ascites, jaundice and in some cases -
encephalopathy) appear when the disease
progresses.
 In 18 - 30% of these patients
cirrhosis develops
 and
 in 1 - 5% - hepatocellular

carcinoma develop within 20—

30 years after initial infection.
 The laboratory diagnosis of HCV infection is
based on the detection of HCV antibodies
(anti-HCV Ig M and Ig G) in plasma and
serum by ELISA.
 antibodies appear 20-150 days after the

onset of the disease

 PCR allows the detection of serum HCV RNA

and to determine the genotype of a viral

strain within the early stage of the disease
before HCV antibodies appear.
Biochemical

investigations of urine
and faeces show the
same changes as in other
types of viral hepatitis.
 Elastometry (liver firoscanning) is an
innovative method of liver research used in
hepatology, which is similar to simple
ultrasound in ease of carrying out, and is
close to biopsy in terms of information.
 Elastometry is an instrumental, but non-

invasive method of research, which allows for

a short period of time (10-15 minutes) to
determine the degree of liver fibrosis in
patients with chronic liver diseases of any
etiology.
 Stage fibrosis by METAVIR
 F0 1,5 – 5,8 kPa
 F1 5,9 – 7,2 kPa
 F2 7,3 – 9,5kPa
 F3 9,6 – 12.5kPa
 F4 more than 12.5kPa
50 mcg 80 mcg
Pegylated interferons in
combination with ribavirin
are not currently used for
the treatment of chronic
hepatitis C
  Interferon
 rise in temperature
 weight loss
 hair loss
 Irritability
 Depression
 Ribavirin
 leukopenia
 thrombocytopenia
 anemia
 Currently, interferon-free treatment regimens
are used
 a direct-acting antiviral agent is used
 The IFN-free combination regimens for each

genotype/subtype are shown (Table 6, 7, 8).

(European recommendations for the treatment of
chronic hepatitis C 2018)
 new drugs are effective, safety, tolerability,
and easy to use
 drug Patients Dose of preparation Duration of therapy,
weeks./ The rate of
sustained virologic
response
Daclatasvir + without cirrhosis Daclatasvir -60 mg 1 24 weeks/
Asunaprevir time per day 91%
(genotype lb) Asunaprevir -2 tablets
of 100 mg once a day
Daclatasvir + with cirrhosis Daclatasvir -60 mg 1 24 weeks/
Asunaprevir time per day 89%
(genotype lb) Asunaprevir -2 tablets
of 100 mg once a day
 drug Patients Dose of preparation Duration of therapy,
weeks./ The rate of
sustained virologic
response
without cirrhosis Ombitasvirum / 12 weeks/
Paritaprevirum
Paritaprevirum / Ritonavir 100%
+ Ombitasvirum
12,5 mg + 75 mg + 50 mg
+ Dasabuvir
2 tablets in the morning
+ Ritonavir
Dasabuvir 250 mg of 1 tab
(genotype lb)
in the morning and evening

Paritaprevir with cirrhosis Ombitasvirum / 12 weeks/

+ Ombitasvirum Paritaprevirum / Ritonavir 100%
+ Dasabuvir 12,5 mg + 75 mg + 50 mg
+ Ritonavir 2 tablets in the morning
(genotype lb) Dasabuvir 250 mg of 1 tab
in the morning and evening
Ribavirin -15 mg / kg / day
 Elbasvir
 grazoprevir
 Treatment-naive patients infected with HCV genotype 1a,
without cirrhosis or with compensated (Child-Pugh A)
cirrhosis, should be treated with the fixed-dose combination
of sofosbuvir and ledipasvir for 12 weeks (A1).
 Treatment-naive patients infected with HCV genotype 1a
without cirrhosis can be treated with the fixed-dose
combination of sofosbuvir and ledipasvir for 8 weeks
 (B2).
 The combination of sofosbuvir and ledipasvir is not
recommended in treatment-experienced patients infected
with genotype 1a (B1).
 duration of treatment - 12 weeks
 The rate of sustained virologic response

without cirrhosis – 98 -100%

 with decompensated cirrhosis duration of

treatment - 16 weeks
 with Ribavirin
 The rate of sustained virologic response with

decompensated cirrhosis – 94%

 Sofosbuvir – 400 mg
 Velpatasvir – 100 mg
 one tablet per day
 duration of treatment - 12 weeks
 for the treatment of patients with any of the six

hepatitis C virus genotypes

 with any degree of fibrosis
 The rate of sustained virologic response – 95 -

100%
 determining the level of RNA - PCR
 HCV RNA should be determined before the

start of therapy,
 through 2 weeks,
 and then through 4, 8, and 12 weeks,
 and through12 and 24 weeks after the end of

treatment.
 is to completely remove the virus
 and prevent liver and extrahepatic

diseases,
 including inflammatory and

degenerative lesions, fibrosis,

cirrhosis, liver cancer, and severe
extrahepatic manifestations.
 Chronic viral hepatitis B is possible in 3-5 % of
cases. In case of intrauterine route of infection
and in the first year of life the possibility is up to
95%.
 Chronic viral hepatitis C develops in 70-95% of

the cases.
 chronic viral hepatitis B, C may develop

subclinically for many years

 Often the disease is detected by accident

(examination before surgery, blood donation,

pregnancy, etc.)
 Enlarged liver and spleen are typical.
 It is clinically characterized by asthenic-
vegetative symptom, less often there are
dyspeptic manifestations.
 “Biochemical" exacerbations often occur.
 Jaundice is possible in patients with

cholestatic component, which is rare.

 In such patients, jaundice is accompanied by

skin itching, sometimes there are

xanthelasmas.
 Exacerbations occur due to intercurrent
diseases, errors in diet, sometimes for no
apparent reason.
 It may develop as a result of metabolic

disorders in the liver of sex hormones, kinins,

prostaglandins, followed by a violation of
microcirculation when «palmar erythema»
and «spider veins» appear.
 basic therapy
 Antiviral drugs. New antiviral drugs
are constantly emerging.
 In the presence of cytolytic syndrome
Hepatoprotectors can be used
 according to the testimony of a liver
transplant
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