Presentation on the topic "viral hepatitis". Viral hepatitis Preventing transmission of the virus

Completed by students gr. L-608 V:

Semyonova S.I. Fazylova S.T. Imankulova A.R. Sagitova Z.Z.

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Viral hepatitis is a group of diseases caused by hepatotropic viruses,

characterized by predominant liver damage with the development of general toxic syndrome, hepatosplenomegaly, dysfunction and the appearance of jaundice.

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Structure of the liver

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Etiotropic classification of hepatitis

1. Infectious (viral) hepatitis:

Enteral hepatitis:

Hepatitis A
Hepatitis E

Parenteral hepatitis:

Hepatitis B
Hepatitis C
Hepatitis D
Hepatitis F
Hepatitis G

Hepatitis as a component of: yellow fever, cytomegalovirus infection, rubella, mumps, Epstein-Barr virus infection, various herpes infections, Lassa fever, AIDS.

Bacterial hepatitis: with leptospirosis, syphilis.

2. Toxic hepatitis

3. Radiation hepatitis (component of radiation sickness)

4. Hepatitis as a consequence of autoimmune diseases

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Viral hepatitis A, E (enteric hepatitis)

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Rice. 1 Hepatitis A virus particles

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Rice. 2 Hepatitis E virus

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Chronic viral hepatitis (parenteral hepatitis)

Chronic viral hepatitis (CVH) is a chronic inflammation of the liver caused by hepatotropic viruses, lasting without a tendency to improve for at least 6 months. The vast majority of cases of chronic hepatitis are caused by hepatitis viruses B, C and D. The role of other hepatotropic viruses (F, G, TTV, SEN, etc.) is questionable.

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Classification of chronic hepatitis (adopted at the International Congress of Gastroenterologists

in Los Angeles in 1994)

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Viral hepatitis B

Hepatitis B is one of the most common infections. There are approximately 300-500 million patients with chronic hepatitis B (CHB) in the world. Regions with high prevalence (10-20%) include South Asia, China, Indonesia, countries of tropical Africa, the Pacific Islands, and Alaska.

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Etiology

The causative agent of HBV infection is a DNA virus from the Hepadnaviridae family. The HBV genome is an incomplete double-stranded circular DNA molecule. There are 9 genotypes of the virus (from A to H). The virus is stable in the external environment.

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Rice. 3 Hepatitis B virus

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Epidemiology

The main route of transmission is parenteral (injection, blood transfusion), as well as through damaged mucous membranes and skin. Hepatitis B is characterized by high contagiousness - infection is possible when a negligible amount of infected material (0.0001 ml of blood) comes into contact with damaged skin or mucous membranes.

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Pathogenesis

In the pathogenesis of chronic viral hepatitis B, the biological cycle of HBV development (its persistence, replication and integration into the DNA of the hepatocyte) and the immune response of the macroorganism are important. (Fig. 6)

The hepatitis B virus does not have a cytopathogenic effect on hepatocytes; their damage is associated with immunopathological reactions that occur to viral antigens and autoantigens. When infected with HBV, HBV DNA replication and synthesis of HBsAg, HBeAg, and HBcorAg occur in hepatocytes. Virus replication is also possible outside the liver. HBsAg and HBcorAg were detected in macrophages, cells of the gonads, salivary glands, thyroid gland, pancreas, and bone marrow. The progression of chronic hepatitis is associated with viral replication, which supports the immunoinflammatory process.

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The main targets of immune aggression are HBcorAg, HBeAg, as well as liver autoantigens. T-cell and antibody-dependent cellular cytolysis is of leading importance. During the replication phase, the immune response to circulating and tissue HBV antigens increases, which leads to massive damage to the liver parenchyma. When the virus enters the integration phase, the activity of the inflammatory process in the liver parenchyma decreases, and in some cases a “virus carrier” is formed when cellular inflammatory infiltration and necrosis are not detected in the liver tissue.

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Rice. 4 Biological development cycle of HBV

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Clinic of acute viral hepatitis B (AVHB)

The duration of the incubation period is from 30 to 180 days (usually 2-3 months).

Pre-icteric period: lasts 3-15 days and is characterized by symptoms of intoxication (fever, general weakness, lethargy, apathy, irritability, sleep disturbance, loss of appetite), arthralgia, pain in the right hypochondrium. In some cases, a skin rash is observed. In the last 1-2 days of the period, stool becomes discolored and urine darkens.

The icteric period lasts from 10-14 to 30-40 days. Jaundice coloration first appears

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on the mucous membranes, then on the skin. Symptoms of intoxication usually intensify after the appearance of jaundice. The liver and spleen (in 30-50% of cases) are enlarged. Bradycardia appears, blood pressure decreases, and heart sounds weaken. In severe forms, central nervous system depression of varying severity, dyspeptic and hemorrhagic syndromes develop. A separate malignant fulminant form is distinguished, caused by massive necrosis of hepatocytes with the development of acute renal failure.

The period of convalescence begins after the disappearance of jaundice and ends after complete clinical and laboratory resolution of the disease, which usually occurs 3 months after its onset.

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Viral hepatitis C

Hepatitis C is the most common form of chronic liver disease in most European countries and North America. According to WHO, there are at least 170 million people infected with HCV in the world.

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Etiology

The causative agent of HCV infection is an RNA virus from the Flaviviridae family. The genome of the virus is formed by single-stranded RNA. HCV is genetically heterogeneous: there are 6 main genotopes (1-6) and at least 50 subtypes.

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Rice. 5 Hepatitis C virus

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Epidemiology

According to WHO, there are at least 170 million people infected with HCV in the world. The prevalence of HCV infection also varies significantly in different regions, averaging 0.5 - 2% (up to 6.5% in tropical African countries). HCV infection causes approximately 40% of cases of chronic liver pathology. The total number of HCV-infected people in Russia is

1 million 700 thousand people.

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Pathogenesis

The virus enters the body in the same way as the hepatitis B virus, although it can also enter through intact skin. Having a tropism for hepatocytes, the virus has a direct cytopathic effect on them. Due to the genetic heterogeneity of the hepatitis C virus, it has many antigenic variants, which makes it difficult to implement an adequate immune response. Viral particles enter the cells of the macrophage system of the body and cause a certain reaction on their part, aimed at eliminating the virus.

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Due to the fact that the antigenic composition of the viral particle is similar to the antigenic composition of hepatocytes, and on the surface of hepatocytes there are also fragments of viral particles synthesized on viral RNA for subsequent assembly into the virus, there is an autoimmune mechanism of damage to hepatocytes. In addition, a direct mutagenic effect of the hepatitis C virus on macrophages cannot be ruled out, changing their properties so that they become capable of reacting with histocompatibility antigens of the HLA system and thereby giving an autoimmune reaction.

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Rice. 6 Life cycle of the hepatitis C virus

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Clinic of acute viral hepatitis C (AVHC)

The duration of the incubation period is 20-90 days. AVGS usually occurs mildly, predominantly in anicteric or subclinical form. It is diagnosed relatively rarely.

The most common symptoms are anorexia, nausea, vomiting, discomfort in the right hypochondrium, and sometimes jaundice.

The risk of chronicity is in more than 80% of patients.

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Viral hepatitis D

Hepatitis D (hepatitis delta) is a viral anthroponotic infection with a parenteral mechanism of infection, which is characterized by inflammatory liver damage.

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Etiology

The disease is caused by a partial RNA virus (HDV, δ virus), the expression of which requires HBV with a genome size of 19 nm. Belongs to the Deltavirus family.

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Rice. 7 Hepatitis D virus

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Epidemiology

The route of transmission is similar to that of HBV infection. HDV infection is most common in Southern Europe, North Africa, the Middle East, and Central and South America. There are about 15 million people with hepatitis D in the world.

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Pathogenesis

The mechanisms of liver tissue damage caused by HDV (hepatitis D virus) and underlying hepatitis D are unclear. It is believed that liver damage is largely associated with the immune response to HDV (hepatitis D virus) infection. Most likely, it is due to the interaction of factors such as the HDV (hepatitis D virus) genotype, the patient's immune system and the characteristics of HBV (hepatitis B virus) (genotype and replication activity).

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Clinic of acute viral hepatitis D (AVHD)

Clinical manifestations of co-infection (simultaneous infection with HBV and HDV) are generally identical to those with HBV. Features include a shorter incubation period, the presence of prolonged high fever, frequent appearance of skin rashes and migrating pain in large joints. The course is relatively favorable, the risk of chronicity is not exceeded, as with HBV.

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Chronic viral hepatitis

Clinical manifestations of chronic hepatitis are quite polymorphic and include a wide range of symptoms.

Dyspeptic syndrome is associated with a violation of the detoxification function of the liver, concomitant pathology of the duodenum and pancreas.

Asthenic syndrome (weakness, fatigue, decreased performance, irritability) is expressed to a greater or lesser extent in patients with chronic hepatitis.

Signs of liver damage:

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With an active process, enlargement, hardening and tenderness of the liver are usually detected;

Jaundice (parenchymal) is observed relatively rarely;

Telangiectasia and palmar erythema are caused by an increase in estrogen concentrations and changes in the sensitivity of vascular receptors. Their severity correlates with the activity of the process and does not always indicate cirrhosis of the liver.

Portal hypertension (ascites, splenomegaly, esophageal varices) signs of liver failure appear and progress.

Amenorrhea, gynecomastia, and decreased libido are associated with impaired metabolism of sex hormones in the liver (usually in the cirrhosis stage).

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Extrahepatic manifestations of CHB develop quite rarely and are usually represented by kidney damage, polyarteritis nodosa or cryoglobulinemia. Somewhat more often, extrahepatic manifestations develop with CHC. Possible cryoglobulinemia, membranous glomerulonephritis, porphyria cutanea tarda, autoimmune thyroiditis, less commonly - Sjögren's syndrome, lichen planus, seronegative arthritis, aplastic anemia, B-cell lymphoma.

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Laboratory research

Clinical blood test: possible increase in ESR, leukopenia, lymphocytosis, and in the fulminant form of AVH - leukocytosis.

General urine analysis: with CVH and exacerbation of CVH, the appearance of bile pigments (mainly direct bilirubin) and urobilin is possible.

Blood chemistry:

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Cytolysis syndrome: increased levels of ALT, AST;

Cholestasis syndrome: increased levels of total bilirubin, cholesterol, alkaline phosphatase, γ-glutamyl transpeptidase, usually observed with jaundice;

Mesenchymal inflammation syndrome: increased content of immunoglobulins, increased thymol test, decreased sublimate test;

Hepatocellular failure syndrome: decreased prothrombin index, serum albumin concentration, cholesterol, total bilirubin: detected in severe forms of chronic hepatitis.

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Hepatitis virus markers:

Hepatitis B virus:

HBsAg is detected 1-10 weeks after infection, its appearance precedes the development of clinical symptoms and an increase in ALT/AST activity. With an adequate immune response, it disappears 4-6 months after infection
HBeAg indicates viral replication in hepatocytes; found in serum almost simultaneously with HBsAg;
Anti-HBe (Ab to e-Ag) in combination with anti-HBc IgG and anti-HBs indicates the complete completion of the infectious process.

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Anti-HBc (Ab to nuclear Ag) is an important diagnostic marker of infection. Anti-HBc IgM is one of the earliest serum markers of CHBV and a sensitive marker of HBV infection. Indicates the replication of the virus and the activity of the process in the liver; its disappearance serves as an indicator of either the sanitization of the body from the pathogen, or the development of the integrative phase of HBV infection.

Anti-HBc IgG persists for many years; indicate an existing or previous infection.

HBV DNA and DNA polymerase are diagnostic markers of virus replication.

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Hepatitis C virus:

HCV RNA is the earliest biochemical marker of infection and occurs from several days to 8 weeks after infection. In cases of recovery from ARCVD, viral RNA disappears from the blood within 12 weeks after the first symptoms appear.

Anti-HCV is determined in the blood no earlier than 8 weeks after infection. It is present in the blood of approximately half of patients with clinically manifest ARVHS at the onset of the disease. In subclinical infections, ATs usually appear much later.

Hepatitis D virus: anti-HDV IgM, HDV RNA (HDV replication marker).

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Stool analysis: decreased content or absence of stercobilin due to cessation of bile flow into the intestines; the appearance of stercobilin in feces during the icteric period of AVH is evidence of resolution of jaundice.
Blood concentration of α-fetoprotein (screening for hepatocellular carcinoma). This study must be carried out over time.

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Instrumental studies

Mandatory examination methods:

Ultrasound of the liver and spleen: characterized by increased echogenicity of the parenchyma, compaction along the liver vessels;
A liver biopsy is necessary to assess the extent of liver damage.
Additional examination methods:
CT scan of the abdominal cavity;
FEGDS.

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Treatment

Non-drug treatment:

In case of CVH and exacerbations of CVH, it is necessary to adhere to bed or semi-bed rest.
A balanced diet is necessary. The consumption of proteins, sodium and liquid is limited only in case of decompensated cirrhosis of the liver.
It is recommended to avoid alcohol intake.

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Drug therapy:

Acute viral hepatitis: treatment is predominantly symptomatic - detoxification infusion therapy, enterosorbents, ursodeoxycholic acid for severe cholestasis, in severe cases - corticosteroids.

Specific antiviral therapy is indicated for ARVHS. Interferon alpha is usually used at a dose of 3 million IU subcutaneously for 12-24 weeks in combination with ribavirin, which can significantly reduce the risk of developing CHC.

Chronic viral hepatitis B:

Interferon alpha at a dose of 5 million IU/day subcutaneously or 10 million IU 3 times a week for 4-6 months.

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Peginterferon alfa-2a (PEGASIS) dose 180 mcg, subcutaneously once a week. Duration of treatment – 1 year.

Lamivudine is prescribed 100 mg/day orally. The duration of treatment is 1 year.

Chronic viral hepatitis C:

Combination therapy is usually carried out:

Peginterferon alfa-2a 180 mcg/kg subcutaneously once a week with ribavirin or peginterferon alfa-2b 1.5 mcg/kg subcutaneously once a week with ribavirin, the dosage of which depends on body weight.

Monotherapy with peginterferon alfa-2a or alfa-2b is carried out if there are contraindications to taking ribavirin.

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Chronic viral hepatitis D: treatment of chronic hepatitis D remains an unresolved problem to date. It is recommended to use interferon alfa in high doses (9-10 million IU subcutaneously every other day for at least 48 weeks), but the effectiveness of such therapy is quite low.

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Prevention

Specific prevention has been developed only for hepatitis B and includes:

measures to prevent drug addiction and promiscuity;
mandatory testing of blood products and organs for transplantation for markers of viral hepatitis.
the need for healthcare workers to exercise extreme caution when

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handling infectious materials (blood and other medical fluids) or medical instruments that have come into contact with them.

Vaccination against hepatitis B is recommended for all newborns and children under 12 years of age, as well as adolescents and adults at risk. In the Russian Federation, genetically engineered recombinant vaccines are used for this purpose.

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Medical labor examination

Temporary disability in patients with chronic hepatitis occurs during the period of exacerbation and lasts 2-3 weeks for the I degree of process activity, and 3-4 weeks for the II degree. Rational employment of patients working in contraindicated working conditions is carried out according to the conclusion and recommendations of the EEC.

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Clinical examination

Regular examinations of patients are carried out with mandatory determination of the main biochemical indicators in the blood: bilirubin, protein and its fractions, aminotransferase activity, prothrombin. Basic or other treatment options are prescribed. The frequency of examination depends on the form of chronic hepatitis.

Presentation on the discipline
“Infectious diseases with a course on HIV infection and epidemiology”
on the topic: “Viral hepatitis B, C, D.”
2013

VIRAL HEPATITIS

A group of anthroponotic viral diseases,
united predominantly by hepatotropy
pathogens and leading clinical manifestations:
1) liver damage with the development of general toxicity
syndrome,
2) hepatosplenomegaly,
3) impaired liver function and the appearance of jaundice.

Structure of the liver

Liver functions

Chronic viral hepatitis (parenteral hepatitis)

Chronic viral hepatitis
(CVH) is a chronic inflammation
liver caused by hepatotropic
viruses, continuing without trend
to improvement for at least 6 months.
The vast majority of cases of chronic hepatitis
caused by hepatitis B, C and D viruses.

Viral hepatitis B

Hepatitis B is one of the most
common infections. In the world
number approximately 300-500 million.
patients with chronic hepatitis B.
To regions with high
prevalence (10-20%) include
South Asia, China, Indonesia, countries
tropical Africa, Pacific Islands
ocean, Alaska.

Etiology

The causative agent of HBV infection is a DNA virus
from the family Hepadnaviridae.
The HBV genome is incomplete
double-stranded circular DNA molecule.
There are 9 genotypes of the virus (from A to H).
The virus is stable in the external environment.

Epidemiology

Source: sick person.
Mechanism of infection:
1) parenteral
2) sexual
3) vertical
4) straight
The main route of transmission is parenteral
(injection, blood transfusion), as well as through
damaged mucous membranes and skin.
Natural receptivity is high. For hepatitis
Characterized by high contagiousness, infection
possible upon contact with damaged skin or
negligible mucous membranes
infected material (0.0001 ml of blood).

Risk group

People who have multiple sexual partners
(prostitutes).
Men who practice homosexual acts.
Sexual partners of infected persons.
Persons who use injection drugs.
Family members of a patient with chronic hepatitis B.
Children born from infected mothers.
Honey. workers.
Patients on hemodialysis ("artificial kidney") or
receiving frequent blood transfusions.

Pathogenesis

The virus enters the human body, then
hematogenously disseminates to the liver, where
fixed on hepatocytes due to
surface receptors containing HBsAg.
In this case, the pathogen does not have a direct
cytopathic effect on liver cells.
Virions multiply and
antigens. Dystrophic and
necrobiotic changes in hepatocytes,
focal necrosis occurs, and in severe cases
massive necrosis in the liver parenchyma.

Hepatitis B Clinic

The duration of the incubation period is from 30 to 180 days (usually 2-3 months).
The following variants of the clinical course of viral hepatitis B are distinguished:
A. According to the cyclicity of the flow:
I. Cyclic forms:
1. Acute hepatitis B - asymptomatic (inapparent and subclinical), anicteric, icteric
(with a predominance of cytolysis or cholestasis);
2. Acute hepatitis with cholestatic syndrome.
II. Persistent forms:
1. Carriage of HBV - chronic asymptomatic form (carriage of HBsAg and other
virus antigens);
2. Chronic viral hepatitis B, integrative phase.
III. Progressive forms:
1. Fulminant (fulminant) hepatitis;
2. Subacute hepatitis;
3. Chronic viral hepatitis B, replicative phase (including with cirrhosis of the liver).
IV. Viral hepatitis B, acute or chronic mixed, in combination with viral hepatitis
A, C, D, E, G.
B. According to the severity of the disease: mild, moderate, severe.

Hepatitis B Clinic

Pre-icteric period (prodromal):
lasts 3-15 days. and is characterized by symptoms
intoxication (fever, general weakness, lethargy,
apathy, irritability, sleep disturbance, decreased
appetite), arthralgia, pain in the right hypochondrium.
In some cases, a skin rash is observed. IN
the last 1-2 days of the period occur
discoloration of stool and dark urine.

Hepatitis B Clinic

The icteric period lasts from 10-14 to 3040 days. Jaundice staining at first
appears on the mucous membranes, then on the skin.
Symptoms of intoxication after the appearance of jaundice
usually intensify. Liver and spleen (in 30-50%
cases) are increasing. Bradycardia appears
decreased blood pressure, weakened heart sounds. At
in severe forms, CNS depression develops
varying degrees of severity, dyspeptic,
hemorrhagic syndromes.

Hepatitis B Clinic

The convalescence period begins
after the jaundice disappears and
ends after complete clinical and laboratory resolution of the disease, which
usually occurs 3 months after
started it.

Viral hepatitis C

Hepatitis C is the most common form
chronic liver diseases in
most European countries and
North America.

Etiology

The causative agent of HCV infection is an RNA virus from the family
Flaviviridae. The genome of the virus is formed
single-stranded RNA. HCV is genetic
heterogeneous: there are 6 main
genotypes (1-6) and at least 50 subtypes.

Epidemiology

According to WHO, there are no
less than 170 million are infected with HCV.
The prevalence of HCV infection is also
varies significantly in different regions,
averaging 0.5 – 2% (up to 6.5% in
countries of tropical Africa). HCV-
infection causes approximately 40
% of cases of chronic liver pathology.
The total number of HCV-infected people in
Russia – 1 million 700 thousand people.

Epidemiology

The source of infection is a sick person or a virus carrier.
Mechanism of infection:
1) parenteral
2) sexual
3) vertical
4) straight
Transmission routes:
1) when transfusing contaminated blood and blood products and when
organ transplantation;
2) with injections with contaminated syringes and injuries from an injection
needle in medical institutions;
3) when using injecting drugs;
4) a newborn child from a person infected with hepatitis C
mother.

Pathogenesis

The virus enters the body in the same way as the virus
hepatitis B. Having tropism for hepatocytes,
the virus has a direct impact on them
cytopathic effect. Due to
genetic heterogeneity of the hepatitis virus
It has many antigenic variants,
which makes it difficult to implement adequate
immune response. Virus particles
enter the cells of the macrophage system
body and cause a certain reaction
on their part, aimed at eliminating
virus.

Pathogenesis

Due to the fact that the antigenic composition of the viral
particles are similar to the antigenic composition of hepatocytes,
and on the surface of hepatocytes there are also
fragments of viral particles synthesized on
viral RNA for subsequent assembly into a virus, then
there is an autoimmune mechanism
hepatocyte damage. Moreover, don't
direct mutagenic effect of the virus is also excluded
hepatitis C on macrophages, changing their properties
so that they become able to react with
histocompatibility antigens of the HLA system and
thereby causing an autoimmune reaction.

Hepatitis C Clinic

From the moment of infection to clinical manifestations
lasts from 2-3 weeks to 6-12 months.
In case of acute onset of the disease, the initial period
lasts 2-3 weeks, accompanied by joint pain,
fatigue, weakness, indigestion.
A rise in temperature is rarely observed. Jaundice as well
little characteristic. Acute hepatitis C is diagnosed very
rarely and more often by accident.
After the acute phase of the disease, a person may
recover, the disease may become chronic
form or into virus carriage. In most patients
(in 70–80% of cases) a chronic course develops.
The transition from acute to chronic hepatitis C occurs
gradually: increases over several years
damage to liver cells, fibrosis develops. Function
the liver may persist for a long time. A
first symptoms (jaundice, abdominal enlargement,
spider veins on the skin of the abdomen, growth
weaknesses) can appear already with cirrhosis of the liver.

Viral hepatitis D

Hepatitis D (hepatitis delta) - viral
anthroponotic infection with parenteral
mechanism of infection for which
characterized by an inflammatory lesion
liver.

Etiology

The disease is caused by an incomplete RNA virus (HDV, δ-virus), for the expression
which requires HBV with genome size
19 nm. Belongs to the Deltavirus family.

Epidemiology

The reservoir and source of the pathogen is man,
sick or virus carrier. In distribution
virus, the main concern is for persons with
chronic forms of viral hepatitis B,
simultaneously infected with a viral
hepatitis D. Period of infectiousness of sources
infection indefinitely long, but sick
most dangerous during the acute period of the disease.
Mechanism of infection:
1) parenteral
2) sexual
3) vertical

Epidemiology

The risk of infection is especially high for permanent recipients
donated blood or its preparations, for persons exposed to frequent
parenteral interventions, as well as for drug addicts injecting
intravenous drugs.
Transplacental transmission of viral hepatitis D is possible from
pregnant fetus.
High incidence of infection among people involved in
promiscuity (especially among homosexual men), gives reason to believe that sexual intercourse is also possible
route of infection.
Natural receptivity is high. To viral hepatitis D
All persons with viral hepatitis D or
are carriers of viral hepatitis B. Most likely
development of viral hepatitis D in chronic carriers of HBsAg.
Populations in hyperendemic areas are especially susceptible
for viral hepatitis B. Severe forms of the disease can occur
even in children.

Pathogenesis

The pathogen is integrated into the genome of the hepatitis B virus, affecting
on its synthesis and enhancing the replication of the latter. The disease may
manifest as co-infection when simultaneously infected with viruses
viral hepatitis B and viral hepatitis D and superinfection in cases
when the hepatitis D virus enters the human body, previously
infected with the hepatitis B virus. Replication of the viral hepatitis B virus
hepatitis D occurs in liver cells.
Pathomorphologically, viral hepatitis D has no specific
signs that distinguish it from viral hepatitis B, and is characterized by
a pronounced picture of necrosis, which prevails over the inflammatory
reaction. Massive necrosis and small droplets are observed in hepatocytes
obesity. Interaction between hepatitis B viruses and viral
hepatitis D aggravates the pathological process and leads to the development of acute
liver failure or chronicity.

Viral hepatitis D clinic

Incubation period. Similar to that for
viral hepatitis B. In cases of coinfection
the clinical course of the disease is similar
clinical manifestations of viral hepatitis B, but with
the predominance of a severe course. In case of superinfection
observed a sharp worsening of the course of the viral
hepatitis B with severe insufficiency of function
liver and the development of a large number of chronic forms,
leading to the rapid formation of liver cirrhosis.

1. Dyspeptic syndrome is associated with
violation of detoxification function
liver, concomitant pathology of the duodenum and pancreas.
2. Asthenic syndrome (weakness,
fatigue, decreased performance,
irritability) is expressed in greater or
to a lesser extent in patients with chronic hepatitis.

Clinical manifestations of chronic viral hepatitis

Signs of liver damage:
enlargement, hardening and tenderness of the liver;
jaundice;
telangiectasia and palmar erythema (due to
an increase in estrogen concentration and a change in
sensitivity of vascular receptors
portal hypertension (ascites, splenomegaly,
varicose veins of the esophagus) appear and
signs of liver failure progress.
amenorrhea, gynecomastia, decreased libido
associated with disturbances in the metabolism of sex hormones in
liver (usually in the stage of cirrhosis).

Diagnostics

1. Epidemiological history data
(indications for parenteral
interventions, contact with the patient,
intravenous drug administration
periods corresponding to incubation
period).
2. Clinical examination (detection
characteristic cyclicality of the disease and
clinical and biochemical syndromes).

Laboratory research

Mandatory examination methods:
UAC: possible ESR, leukopenia,
lymphocytosis, with the fulminant form of AVH
– leukocytosis.
OAM: with OVH and exacerbation of CVH
possible appearance of bile pigments
(mainly direct bilirubin),
urobilin.

Laboratory research

Blood chemistry:
- cytolysis syndrome: increased levels of ALT, AST;
- cholestasis syndrome: increased content of total
bilirubin, cholesterol, alkaline phosphatase, γglutamyl transpeptidase, usually observed with
jaundice;
- mesenchymal inflammation syndrome: increased
immunoglobulin content, increased thymol
samples, decrease in sublimate test;
- liver cell failure syndrome:
decrease in prothrombin index, concentration
serum albumin, cholesterol, total
bilirubin: detected in severe forms of chronic hepatitis.

Markers:
Hepatitis B virus:
HBsAg is detected 1-10 weeks after
infection, its appearance precedes
development of clinical symptoms and
increased ALT/AST activity. At
If there is an adequate immune response, it disappears
4-6 months after infection
HBeAg indicates viral replication in
hepatocytes; found in serum
almost simultaneously with HBsAg;
Anti-HBe (AT to e-Ag) in combination with anti-HBc
IgG and anti-HBs indicate complete
completion of the infectious process.

Anti-HBc (Ab to nuclear Ag) – important
diagnostic marker of infection. AntiHBc IgM is one of the earliest serum
markers of CHBV and a sensitive marker of HBV infection. Indicates virus replication and
activity of the process in the liver; his disappearance
serves as an indicator of either the sanitation of the body from
pathogen, or the development of the integrative phase
HBV infections.
Anti-HBc IgG persists for many years;
indicate existing or previously
past infection.
HBV DNA and DNA polymerase – diagnostic
markers of virus replication.

Hepatitis C virus:
HCV RNA is the earliest biochemical marker
infection occurs within a period of several days to 8
weeks after infection. In cases
recovery from CVHS, viral RNA disappears from
blood within 12 weeks after the first appearance
symptoms.
Anti-HCV is determined in the blood no earlier than after 8
weeks after infection. It is present in the blood
approximately half of patients with clinical
manifest OVHS at the onset of the disease. At
subclinical infections AT usually appear
much later.
Hepatitis D virus: anti-HDV IgM, HDV RNA (marker
HDV replication).

Additional examination methods:

Stool analysis: decreased content or
lack of stercobilin due to discontinuation
the flow of bile into the intestines; appearance
stercobilin in feces during the icteric period
WHG is evidence of resolution of jaundice.
Blood concentration of α-fetoprotein
(screening for hepatocellular carcinoma).
This research needs to be carried out in
dynamics.

Instrumental studies

Required Methods
examinations:
Ultrasound of the liver and spleen:
characterized by increased echogenicity
parenchyma, compactions along the
liver vessels;
Liver biopsy is necessary for
assessing the degree of liver damage.
Additional Methods
examinations:
CT scan of the abdominal cavity;
FEGDS.

Treatment

1. Patients with viral hepatitis are subject to mandatory
hospitalization in an infectious diseases hospital (department,
hospital).
2. Long-term, possibly lifelong dietary
mode (table No. 5).
Acute viral hepatitis: treatment preferentially
symptomatic – detoxification infusion
therapy, enterosorbents, ursodeoxycholic acid for
severe cholestasis, in severe cases - GCS.
Specific antiviral therapy is indicated for
OVGS. Interferon alpha is usually used at 3 million
IU subcutaneously for 12-24 weeks in combination with
ribavirin, which can significantly reduce the risk
development of CHC.

Treatment

Chronic viral hepatitis B:
-Interferon alpha at a dose of 5 million IU/day subcutaneously or 10 million IU
3 times a week for 4-6 months.
- Peginterferon alfa-2a (PEGASIS) dose 180 mcg, subcutaneously 1
once a week. Duration of treatment – 1 year.
-Lamivudine is prescribed 100 mg/day orally.
The duration of treatment is 1 year.
Chronic viral hepatitis C:
Combination therapy is usually carried out:
- peginterferon alfa-2a 180 mcg/kg subcutaneously once a week with
ribavirin or peginterferon alfa-2b 1.5 mcg/kg subcutaneously
Once a week with ribavirin, the dosage of which depends on
body weight.
Monotherapy with peginterferon alfa-2a or alfa-2b is carried out
if there are contraindications to taking ribavirin.

Treatment

Chronic viral hepatitis D:
treatment of chronic hepatitis D before
currently remains unresolved
problem. Recommended to use
interferon-alpha in high doses (9-10
million IU subcutaneously every other day for no
less than 48 weeks), but the effectiveness is the same
therapy is quite low.

Prevention

1. Nonspecific prevention:
a) maintaining hygiene, personal and public;
b) if there is a threat of infection, use individual means
protection, disinfection and sterilization
medical instruments;
c) hospitalization and treatment of chronic patients,
infected with hepatitis B C D viruses or their combinations,
separately from other patients;
d) cultural and educational work with the population;
d) because the likelihood of infection and development of the virus is significant
depends to a large extent on the initial state of the organism, then as
prevention measures can be considered to improve health and
strengthening one’s own immune defense, including
phytohealth (immunomodulatory preparations and
adaptogens).

Prevention

2. Specific prevention:
Specific prevention of viral hepatitis
divided into pre-infection prevention and prevention
after possible infection.
Specific prevention before infection today
carried out only for hepatitis B. Method
immunization with hepatitis B vaccine (med.
all employees).
A vaccine against the hepatitis C virus is being developed.
Specific prevention after possible
infection is an urgent appointment
antiviral drugs in combination with
interferon.

Clinical examination

At least 1 year.
Regular examinations of patients with
mandatory determination in blood
main biochemical indicators:
bilirubin, protein and its fractions,
activity of aminotransferases, prothrombin,
HBsAg markers. Assigned basic or
other treatment options.

2 Introduction Self-help through knowledge! The information presented here is intended only to help you understand and keep hepatitis C under control. It does not replace consultation with a specialist. Every patient with hepatitis C should consult a doctor for all questions of diagnosis and treatment.

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8 Antibody test Elisa II or III tests Most common tests for HCV RIBA test Usually only done when there are no risk factors A positive test result indicates that the body has been exposed to the virus Does NOT indicate the presence of an active infection A viral test is performed to detect an active infection HCV load

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13 Virus transmission Shared needles Drug paraphernalia Blood transfusions before 1992 – donated blood, blood products, transfusion procedure Through sexual contact (1-3%) Health care workers – accidental pricks with contaminated needles Shared household items – razors and toothbrushes From mother to child

14 Tips for preventing infection Injectable and non-injectable drugs Do not use other people's syringes, autoclaves, straws, tubes, cotton wool - any items that may have been in contact with blood Bleach for disinfection Stable monogamous sexual relationships There is no need to change existing sexual habits, but Be aware of the risk! (US Center for Disease Prevention)

17 Tips for preventing infection Tattoos and piercings In specialized salons, the risk is low Make sure that disposable needles are used, separate bottles of mascara are used, and general safety rules are followed The risk of infection is much higher if the piercing is done in non-specialized conditions For example, in a prison or on the street

18 Personal Care Products At home Cover cuts or sores Do not share personal care products (toothbrushes, razors, etc.) In health care facilities or places that provide hygiene services Follow standard precautions Disposable equipment Bring your own personal care products

21 Development of the disease In 10-25% of carriers of the virus, infection will develop into a serious disease within years Fibrosis Minor scarring Cirrhosis Compensated - uncompensated Steatosis Fatty deposits in the liver

22 Treatment General principles of treatment General health Presence of active infection Elevated ALT levels Compensated liver disease More often positive in: young women Low body mass index (BMI) and weight Less steatosis Low viral load Minimal liver damage With genotypes 2 and 3

23 Treatment – clinical data Prospective – well-conducted clinical trials with measurable outcomes Gold standard Retrospective – review of data from previous clinical trials Important for identifying directions and planning future research

26 Treatment - standard regimens Schering - PEG-Intron + Rebetol (800 mg) For genotype 1 - sustained virological response (SVR) in 41% (after 48 weeks of treatment) For genotypes - in 75% (after 48 weeks of treatment) Roche – Pegasys + Copegus (mg) Genotype 1 – SVR in 44-51% (48 weeks of treatment) Genotype 2 and 3 – SVR in 82% (24 weeks of treatment) Genotype – SVR in 70% (48 weeks of treatment) * See insert US Federal Food and Drug Administration

27 Side effects Interferon Chronic fatigue Muscle and joint pain Nausea Headaches Anxiety Depression Skin irritations And others... Ribavirin Increases the side effects of interferon, especially chronic fatigue and anemia ** (both men and women should use contraceptives)

28 Dealing with side effects Injections before bed Drinking as much as possible (water) Ibuprofen or acetaminophen in small doses Painkillers Light exercise Moisturizing the skin Varying injection sites Antidepressants Adequate rest Eating small amounts of food frequently The main thing: full support - doctors, family, friends, colleagues

32 Your own lawyer! Try to learn as much as you can about hepatitis C Build a trusting relationship with your doctor Bring an advocate to your doctor's appointments Ask questions Keep copies of all medical tests Keep a diary Don't limit yourself to the usual limits

33 Resources – HCV Advocate Fact Sheet Educational materials in English, Spanish, Russian, French, German, Chinese, Vietnamese and Tagalog Articles by Medical Writers Circle Factual information pages in English, Spanish, French and Russian List of support groups Recommended links Information about hepatitis C and B, and HIV/HCV co-infection

Slide 1

Department of Polyclinic Therapy Faculty of Medicine VIRAL HEPATITIS Completed by students gr. L-608 B: Semyonova S.I. Fazylova S.T. Imankulova A.R. Sagitova Z.Z.

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Viral hepatitis is a group of diseases caused by hepatotropic viruses, characterized by predominant liver damage with the development of a general toxic syndrome, hepatosplenomegaly, dysfunction and the appearance of jaundice.

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1. Infectious (viral) hepatitis: - Enteral hepatitis: Hepatitis A Hepatitis E - Parenteral hepatitis: Hepatitis B Hepatitis C Hepatitis D Hepatitis F Hepatitis G - Hepatitis as a component of: yellow fever, cytomegalovirus infection, rubella, mumps, Epstein virus infection - Barr, various herpes infections, Lassa fever, AIDS. - Bacterial hepatitis: with leptospirosis, syphilis. 2. Toxic hepatitis 3. Radiation hepatitis (a component of radiation sickness) 4. Hepatitis as a consequence of autoimmune diseases Etiotropic classification of hepatitis

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Viral hepatitis A, E (enteral hepatitis) Hepatitis A Hepatitis E Definition An infectious disease with a fecal-oral transmission mechanism, clinically and morphologically characterized by liver damage with the development of a symptom complex of acute hepatitis. Acute infectious liver injury, manifested by symptoms of intoxication and, less commonly, jaundice

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Etiology Hepatitis A virus (HAV) genus Hepatovirus family Picornaviridae single-stranded RNA-containing virus resistant to acids, alkalis, ether and chloroform destructive boiling for 3-5 minutes (Fig. 1) Hepatitis E virus (HEV) - genus Calicivirus family Caliciviridae single-stranded RNA - containing the virus is resistant to disinfectant solutions, low temperatures, less virulent than HAV (Fig. 2) Epidemiology Source of infection: subclinical patients anicteric patients icteric patients Source of infection: subclinical patients anicteric patients icteric patients

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Mechanism of transmission: fecal-oral contact household water alimentary Incidence: mainly children and adolescents (about 80%) seasonality summer-autumn immunity stable, lifelong. Mechanism of transmission: fecal-oral contact-domestic water route alimentary Incidence: sharply expressed unevenness mainly in persons 15-25 years old, high mortality. Pathogenesis - direct cytopathic effect of the virus, cytolysis syndrome, cholestasis syndrome ___

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- mesenchymal - inflammatory syndrome ___ Clinic Incubation period - 7-50 days I. Pre-icteric period (1 week): - dyspeptic syndrome (abdominal pain, nausea, vomiting, anorexia, diarrhea) - influenza-like variant (fever, cough, runny nose) - asthenovegetative syndrome (sudden weakness) Incubation period – 20-65 days I. Pre-icteric period (gradual onset, duration 3-5 days): - dyspeptic syndrome (abdominal pain, nausea, vomiting, anorexia, diarrhea) - influenza-like variant (cough, runny nose, fever may be absent) - latent

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II. Jaundice period: - rapid increase in jaundice (during the first week); disappearance of symptoms of intoxication after the appearance of jaundice; duration of the jaundice period is on average 2-3 weeks; predominantly mild and moderate course of the disease (97-98%); recovery period 1-3 months. II. Jaundice period: symptoms of intoxication persist for up to a week and a more severe course in pregnant women in the second half of pregnancy; cholestatic forms may develop in 20-30%. Diagnostics Complaints (see clinic) History taking Physical data: - hepatomegaly ___

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splenomegaly flatulence bradycardia visual assessment of urine (dark) Laboratory data: CBC: leukopenia lymphocytosis thrombocytopenia OAM: holiuria HD: bilirubinemia (direct fraction) hypertransaminasemia ___

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(ALT and AST increased 20-100 times) dysproteinemia increased markers of cholestasis (alkaline phosphatase, GGT, cholesterol, 5-NK) increased thymol test decreased mercuric test Serological tests: - anti-HAV IgM in blood serum by ELISA - indicator of infection activity - anti-HAV IgG is an indicator of past infection. - RNA-HAV by PCR in the blood ___ Serological tests: - anti-HEV IgM in the blood serum by ELISA - indicator of infection activity - RNA-HEV by PCR in the blood

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Treatment Non-drug treatment: adequate rehydration is necessary (increasing the amount of fluid taken to 1.5-2 liters per day), bed rest is indicated, complete abstinence from alcohol consumption is required Drug therapy: Cholestyramine (4 g orally 2 times a day) is a symptomatic remedy for skin itching Prednisolone (30 mg/day with gradual dose reduction) Ursodeoxycholic acid (10-15 mg/kg/day for 4-6 weeks) ___

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Prevention 1. Compliance with personal hygiene rules. 2. Control over the quality of drinking water and food. 3. Immunoprophylaxis of hepatitis A includes the administration of a vaccine or immunoglobulin. 1. Compliance with personal hygiene rules. 2. Control over the quality of drinking water and food. 3. There is no specific immunoprophylaxis.

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Chronic viral hepatitis (parenteral hepatitis) Chronic viral hepatitis (CVH) is a chronic inflammation of the liver caused by hepatotropic viruses, lasting without a tendency to improve for at least 6 months. The vast majority of cases of chronic hepatitis are caused by hepatitis viruses B, C and D. The role of other hepatotropic viruses (F, G, TTV, SEN, etc.) is questionable.

Slide 17

Classification of chronic hepatitis (adopted at the International Congress of Gastroenterologists in Los Angeles in 1994)

Slide 18

Viral hepatitis B Hepatitis B is one of the most common infections. There are approximately 300-500 million patients with chronic hepatitis B (CHB) in the world. Regions with high prevalence (10-20%) include South Asia, China, Indonesia, countries of tropical Africa, the Pacific Islands, and Alaska.

Slide 19

Etiology The causative agent of HBV infection is a DNA virus from the Hepadnaviridae family. The HBV genome is an incomplete double-stranded circular DNA molecule. There are 9 genotypes of the virus (from A to H). The virus is stable in the external environment.

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Epidemiology The main route of transmission is parenteral (injection, blood transfusion), as well as through damaged mucous membranes and skin. Hepatitis B is characterized by high contagiousness - infection is possible when a negligible amount of infected material (0.0001 ml of blood) comes into contact with damaged skin or mucous membranes.

Slide 22

Pathogenesis In the pathogenesis of chronic viral hepatitis B, the biological cycle of HBV development (its persistence, replication and integration into the DNA of the hepatocyte) and the immune response of the macroorganism are important. (Fig. 6) The hepatitis B virus does not have a cytopathogenic effect on hepatocytes; their damage is associated with immunopathological reactions that occur to viral antigens and autoantigens. When infected with HBV, HBV DNA replication and synthesis of HBsAg, HBeAg, and HBcorAg occur in hepatocytes. Virus replication is also possible outside the liver. HBsAg and HBcorAg were detected in macrophages, cells of the gonads, salivary glands, thyroid gland, pancreas, and bone marrow. The progression of chronic hepatitis is associated with viral replication, which supports the immunoinflammatory process.

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Clinic of acute viral hepatitis B (AVHB) The duration of the incubation period is from 30 to 180 days (usually 2-3 months). Pre-icteric period: lasts 3-15 days and is characterized by symptoms of intoxication (fever, general weakness, lethargy, apathy, irritability, sleep disturbance, loss of appetite), arthralgia, pain in the right hypochondrium. In some cases, a skin rash is observed. In the last 1-2 days of the period, stool becomes discolored and urine darkens. The icteric period lasts from 10-14 to 30-40 days. Jaundice coloration first appears

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Viral hepatitis C Hepatitis C is the most common form of chronic liver disease in most European countries and North America. According to WHO, there are at least 170 million people infected with HCV in the world.

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Etiology The causative agent of HCV infection is an RNA virus from the Flaviviridae family. The genome of the virus is formed by single-stranded RNA. HCV is genetically heterogeneous: there are 6 main genotopes (1-6) and at least 50 subtypes.

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Epidemiology According to WHO, there are at least 170 million people infected with HCV in the world. The prevalence of HCV infection also varies significantly in different regions, averaging 0.5 - 2% (up to 6.5% in tropical African countries). HCV infection causes approximately 40% of cases of chronic liver pathology. The total number of HCV-infected people in Russia is 1 million 700 thousand people.

Slide 31

Pathogenesis The virus enters the body in the same way as the hepatitis B virus, although it can also penetrate through intact skin. Having a tropism for hepatocytes, the virus has a direct cytopathic effect on them. Due to the genetic heterogeneity of the hepatitis C virus, it has many antigenic variants, which makes it difficult to implement an adequate immune response. Viral particles enter the cells of the macrophage system of the body and cause a certain reaction on their part, aimed at eliminating the virus.

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Clinic of acute viral hepatitis C (AVHC) The duration of the incubation period is 20-90 days. AVGS usually occurs mildly, predominantly in anicteric or subclinical form. It is diagnosed relatively rarely. The most common symptoms are anorexia, nausea, vomiting, discomfort in the right hypochondrium, and sometimes jaundice. The risk of chronicity is in more than 80% of patients.

Slide 35

Viral hepatitis D Hepatitis D (hepatitis delta) is a viral anthroponotic infection with a parenteral mechanism of infection, which is characterized by inflammatory liver damage.

Slide 36

Etiology The disease is caused by a partial RNA virus (HDV, δ-virus), the expression of which requires HBV with a genome size of 19 nm. Belongs to the Deltavirus family.

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Epidemiology The route of transmission is similar to that of HBV infection. HDV infection is most common in Southern Europe, North Africa, the Middle East, and Central and South America. There are about 15 million people with hepatitis D in the world.

Slide 39

Pathogenesis The mechanisms of liver tissue damage caused by HDV (hepatitis D virus) and underlying hepatitis D are unclear. It is believed that liver damage is largely associated with the immune response to HDV (hepatitis D virus) infection. Most likely, it is due to the interaction of factors such as the HDV (hepatitis D virus) genotype, the patient's immune system and the characteristics of HBV (hepatitis B virus) (genotype and replication activity).

Slide 40

Clinic of acute viral hepatitis D (AVHD) Clinical manifestations of coinfection (simultaneous infection with HBV and HDV) are generally identical to those with ARVHV. Features include a shorter incubation period, the presence of prolonged high fever, frequent appearance of skin rashes and migrating pain in large joints. The course is relatively favorable, the risk of chronicity is not exceeded, as with HBV.

Slide 41

Chronic viral hepatitis Clinical manifestations of chronic hepatitis are quite polymorphic and include a wide range of symptoms. Dyspeptic syndrome is associated with a violation of the detoxification function of the liver, concomitant pathology of the duodenum and pancreas. Asthenic syndrome (weakness, fatigue, decreased performance, irritability) is expressed to a greater or lesser extent in patients with chronic hepatitis. Signs of liver damage:

Slide 42

- with an active process, enlargement, thickening and tenderness of the liver are usually detected; - jaundice (parenchymal) is observed relatively rarely; - telangiectasia and palmar erythema are caused by an increase in the concentration of estrogen and a change in the sensitivity of vascular receptors. Their severity correlates with the activity of the process and does not always indicate cirrhosis of the liver. - portal hypertension (ascites, splenomegaly, esophageal varices) signs of liver failure appear and progress. - amenorrhea, gynecomastia, decreased libido are associated with impaired metabolism of sex hormones in the liver (usually in the stage of cirrhosis).

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Laboratory tests Mandatory examination methods: Clinical blood test: possible increase in ESR, leukopenia, lymphocytosis, in the fulminant form of OVH - leukocytosis. General urine analysis: with CVH and exacerbation of CVH, the appearance of bile pigments (mainly direct bilirubin) and urobilin is possible. Blood chemistry:

Slide 45

- cytolysis syndrome: increased levels of ALT, AST; - cholestasis syndrome: increased levels of total bilirubin, cholesterol, alkaline phosphatase, γ-glutamyl transpeptidase, usually observed with jaundice; - mesenchymal inflammation syndrome: increased content of immunoglobulins, increased thymol test, decreased sublimate test; - hepatocellular failure syndrome: decreased prothrombin index, serum albumin concentration, cholesterol, total bilirubin: detected in severe forms of chronic hepatitis.

Slide 46

Markers of hepatitis viruses: Hepatitis B virus: HBsAg is detected 1-10 weeks after infection, its appearance precedes the development of clinical symptoms and an increase in ALT/AST activity. With an adequate immune response, it disappears 4-6 months after infection with HBeAg, indicating virus replication in hepatocytes; found in serum almost simultaneously with HBsAg; Anti-HBe (Ab to e-Ag) in combination with anti-HBc IgG and anti-HBs indicates the complete completion of the infectious process.

Slide 47

Hundreds of suppliers bring hepatitis C medications from India to Russia, but only M-PHARMA will help you buy sofosbuvir and daclatasvir, and professional consultants will answer any of your questions throughout the entire treatment.

Hepatitis is the name given to acute and chronic inflammatory diseases of the liver that are not focal, but widespread. Different hepatitises have different methods of infection; they also differ in the rate of disease progression, clinical manifestations, methods and prognosis of therapy. Even the symptoms of different types of hepatitis are different. Moreover, some symptoms are stronger than others, which is determined by the type of hepatitis.

Main symptoms

Jaundice. The symptom occurs frequently and is due to the fact that bilirubin enters the patient’s blood when the liver is damaged. Blood, circulating throughout the body, carries it to organs and tissues, coloring them yellow.
The appearance of pain in the area of the right hypochondrium. It occurs due to an increase in the size of the liver, leading to pain that can be dull and prolonged or of a paroxysmal nature.
Deterioration of health, accompanied by fever, headaches, dizziness, indigestion, drowsiness and lethargy. All this is a consequence of the effect of bilirubin on the body.

Hepatitis acute and chronic

Hepatitis in patients has acute and chronic forms. In acute form, they appear in the case of viral liver damage, as well as if there has been poisoning with various types of poisons. In acute forms of the disease, the condition of patients quickly deteriorates, which contributes to the accelerated development of symptoms.

With this form of the disease, favorable prognosis is quite possible. Except for its transformation into chronic. In its acute form, the disease is easily diagnosed and easier to treat. Untreated acute hepatitis easily develops into a chronic form. Sometimes, with severe poisoning (for example, alcohol), the chronic form occurs independently. In the chronic form of hepatitis, the process of replacement of liver cells with connective tissue occurs. It is weakly expressed, progresses slowly, and therefore sometimes remains undiagnosed until cirrhosis of the liver occurs. Chronic hepatitis is less treatable, and the prognosis for its cure is less favorable. In the acute course of the disease, health deteriorates significantly, jaundice develops, intoxication appears, the functional functioning of the liver decreases, and the bilirubin content in the blood increases. With timely detection and effective treatment of acute hepatitis, the patient most often recovers. When the disease lasts more than six months, hepatitis becomes chronic. The chronic form of the disease leads to serious disorders in the body - the spleen and liver enlarge, metabolism is disrupted, complications arise in the form of cirrhosis of the liver and cancer. If the patient has reduced immunity, the treatment regimen is chosen incorrectly, or there is alcohol dependence, then the transition of hepatitis to a chronic form threatens the patient’s life.

Types of hepatitis

Hepatitis has several types: A, B, C, D, E, F, G, they are also called viral hepatitis, since they are caused by a virus.

Hepatitis A

This type of hepatitis is also called Botkin's disease. It has an incubation period lasting from 7 days to 2 months. Its causative agent, an RNA virus, can be transmitted from a sick person to a healthy person through poor-quality food and water, or contact with household items used by the sick person. Hepatitis A is possible in three forms, they are divided according to the severity of the disease:

in the acute form with jaundice, the liver is seriously damaged;
with subacute without jaundice, we can talk about a milder version of the disease;
in the subclinical form, you may not even notice symptoms, although the infected person is the source of the virus and is capable of infecting others.

Hepatitis B

This disease is also called serum hepatitis. Accompanied by an enlarged liver and spleen, joint pain, vomiting, fever, and liver damage. It occurs either in acute or chronic forms, which is determined by the state of the patient’s immunity. Routes of infection: during injections in violation of sanitary rules, sexual contact, during blood transfusions, and the use of poorly disinfected medical instruments. The duration of the incubation period is 50 ÷ 180 days. The incidence of hepatitis B decreases with vaccination.

Hepatitis C

This type of disease is one of the most serious diseases, as it is often accompanied by cirrhosis or liver cancer, which subsequently leads to death. The disease is difficult to treat, and moreover, having had hepatitis C once, a person can be infected with the same disease again. It is not easy to cure HCV: after contracting hepatitis C in an acute form, 20% of patients recover, but in 70% of patients the body is not able to recover from the virus on its own, and the disease becomes chronic. It has not yet been possible to establish the reason why some heal on their own and others do not. The chronic form of hepatitis C will not disappear on its own and therefore requires therapy. Diagnosis and treatment of the acute form of HCV is carried out by an infectious disease specialist, and the chronic form of the disease is carried out by a hepatologist or gastroenterologist. You can become infected during a plasma or blood transfusion from an infected donor, through the use of poorly processed medical instruments, through sexual contact, and a sick mother transmits the infection to her child. The hepatitis C virus (HCV) is rapidly spreading throughout the world; the number of patients has long exceeded one and a half hundred million people. Previously, HCV was difficult to treat, but now the disease can be cured using modern direct-acting antivirals. But this therapy is quite expensive, and therefore not everyone can afford it.

Hepatitis D

This type of hepatitis D is possible only with coinfection with the hepatitis B virus (coinfection is the case of infection of one cell with viruses of different types). It is accompanied by massive liver damage and an acute course of the disease. The route of infection is the entry of the disease virus into the blood of a healthy person from a virus carrier or a sick person. The incubation period lasts 20 ÷ 50 days. Externally, the course of the disease resembles hepatitis B, but its form is more severe. It can become chronic, later turning into cirrhosis. It is possible to carry out vaccination similar to that used for hepatitis B.

Hepatitis E

It is slightly reminiscent of hepatitis A in its course and transmission mechanism, since it is also transmitted through the blood. Its peculiarity is the occurrence of lightning-fast forms that cause death in a period not exceeding 10 days. In other cases, it can be effectively cured, and the prognosis for recovery is most often favorable. An exception may be pregnancy, since the risk of losing a child is close to 100%.

Hepatitis F

This type of hepatitis has not yet been studied enough. It is only known that the disease is caused by two different viruses: one was isolated from the blood of donors, the second was found in the feces of a patient who received hepatitis after a blood transfusion. Signs: the appearance of jaundice, fever, ascites (fluid accumulation in the abdominal cavity), an increase in the size of the liver and spleen, an increase in the levels of bilirubin and liver enzymes, the occurrence of changes in urine and feces, as well as general intoxication of the body. Effective methods of treating hepatitis F have not yet been developed.

Hepatitis G

This type of hepatitis is similar to hepatitis C, but is not as dangerous because it does not contribute to the development of cirrhosis and liver cancer. Cirrhosis can only appear in cases of co-infection with hepatitis G and C.

Diagnostics

Viral hepatitis is similar in its symptoms to one another, just like some other viral infections. For this reason, it can be difficult to accurately diagnose a sick person. Accordingly, to clarify the type of hepatitis and the correct prescription of therapy, laboratory blood tests are required to identify markers - indicators individual for each type of virus. By identifying the presence of such markers and their ratio, it is possible to determine the stage of the disease, its activity and possible outcome. In order to track the dynamics of the process, the examinations are repeated after a period of time.

How is hepatitis C treated?

Modern treatment regimens for chronic forms of HCV are reduced to combination antiviral therapy, including direct-acting antivirals such as sofosbuvir, velpatasvir, daclatasvir, ledipasvir in various combinations. Sometimes ribavirin and interferons are added to enhance effectiveness. This combination of active ingredients stops the replication of viruses, saving the liver from their destructive effects. This type of therapy has a number of disadvantages:

The cost of drugs to combat the hepatitis virus is high; not everyone can buy them.
Taking certain medications is accompanied by unpleasant side effects, including fever, nausea, and diarrhea.

The duration of treatment for chronic forms of hepatitis takes from several months to a year, depending on the genotype of the virus, the degree of damage to the body and the drugs used. Because hepatitis C primarily attacks the liver, patients are required to follow a strict diet.

Features of HCV genotypes

Hepatitis C is one of the most dangerous viral hepatitis. The disease is caused by an RNA virus called Flaviviridae. The hepatitis C virus is also called the “gentle killer.” He received such an unflattering epithet due to the fact that at the initial stage the disease is not accompanied by any symptoms at all. There are no signs of classic jaundice, and there is no pain in the area of the right hypochondrium. The presence of the virus can be detected no earlier than a couple of months after infection. Before this, the reaction of the immune system is completely absent and markers cannot be detected in the blood, and therefore genotyping is not possible. Another feature of HCV is that after entering the bloodstream during the process of reproduction, the virus begins to rapidly mutate. Such mutations prevent the infected person’s immune system from adapting and fighting the disease. As a result, the disease can proceed for several years without any symptoms, after which cirrhosis or a malignant tumor appears almost immediately. Moreover, in 85% of cases, the disease goes from an acute form to a chronic one. The hepatitis C virus has an important feature - a variety of genetic structure. In fact, hepatitis C is a collection of viruses, classified depending on their structural variants and divided into genotypes and subtypes. The genotype is the sum of genes encoding hereditary traits. So far, medicine knows 11 genotypes of the hepatitis C virus, which have their own subtypes. The genotype is designated by numbers from 1 to 11 (although genotypes 1 ÷ 6 are mainly used in clinical studies), and subtypes are designated by letters of the Latin alphabet:

1a, 1b and 1c;
2a, 2b, 2c and 2d;
3a, 3b, 3c, 3d, 3e and 3f;
4a, 4b, 4c, 4d, 4e, 4f, 4h, 4i and 4j;

In different countries, HCV genotypes are distributed differently; for example, in Russia, the most common genotypes are the first to the third. The severity of the disease depends on the type of genotype; they determine the treatment regimen, its duration and the result of treatment.

How are HCV strains distributed across the planet?

Hepatitis C genotypes are distributed heterogeneously across the globe, and genotypes 1, 2, 3 can most often be found, and in certain areas it looks like this:

in Western Europe and its eastern regions, genotypes 1 and 2 are most common;
in the USA - subtypes 1a and 1b;
in northern Africa, genotype 4 is the most common.

People with blood diseases (tumors of the hematopoietic system, hemophilia, etc.), as well as patients undergoing treatment in dialysis units, are at risk of possible HCV infection. Genotype 1 is considered the most common across the world - it accounts for ~50% of the total number of cases. In second place in prevalence is genotype 3 with an indicator of slightly more than 30%. The spread of HCV throughout Russia has significant differences from the global or European variants:

genotype 1b accounts for ~50% of cases;
for genotype 3a ~20%,
~10% of patients are infected with hepatitis 1a;
hepatitis with genotype 2 was found in ~5% of infected people.

But the difficulties of HCV therapy depend not only on the genotype. The effectiveness of treatment is also influenced by the following factors:

age of patients. The chance of cure is much higher in young people;
It is easier for women to recover than for men;
the degree of liver damage is important - the favorable outcome is higher with less damage;
the magnitude of the viral load - the fewer viruses in the body at the time of treatment, the more effective the therapy;
the patient’s weight: the higher it is, the more complicated the treatment becomes.

Therefore, the treatment regimen is chosen by the attending physician, based on the above factors, genotyping and recommendations of the EASL (European Association for Liver Diseases). EASL constantly keeps its recommendations up to date and, as new effective drugs for the treatment of hepatitis C become available, it adjusts the recommended treatment regimens.

Who is at risk for HCV infection?

As you know, the hepatitis C virus is transmitted through blood, and therefore the following are most likely to become infected:

patients receiving blood transfusions;
patients and clients in dental offices and medical institutions where medical instruments are improperly sterilized;
visiting nail and beauty salons can be dangerous due to unsterile instruments;
piercing and tattoo enthusiasts can also suffer from poorly processed tools,
there is a high risk of infection for those who use drugs due to repeated use of unsterile needles;
the fetus can become infected from a mother infected with hepatitis C;
During sexual intercourse, the infection can also enter the body of a healthy person.

How is hepatitis C treated?

It was not for nothing that the hepatitis C virus was considered a “gentle” killer virus. It can remain silent for years, and then suddenly appear in the form of complications accompanied by cirrhosis or liver cancer. But more than 177 million people in the world have been diagnosed with HCV. The treatment that was used until 2013, combining injections of interferon and ribavirin, gave patients a chance of healing that did not exceed 40-50%. Moreover, it was accompanied by serious and painful side effects. The situation changed in the summer of 2013 after the US pharmaceutical giant Gilead Sciences patented the substance sofosbuvir, produced in the form of a drug under the Sovaldi brand, which included 400 mg of the drug. It was the first direct-acting antiviral drug (DAA) to combat HCV. The results of clinical trials of sofosbuvir pleased doctors with the effectiveness, which reached 85 ÷ 95% depending on the genotype, while the duration of the course of therapy was more than halved compared to treatment with interferons and ribavirin. And, although the pharmaceutical company Gilead patented sofosbuvir, it was synthesized in 2007 by Michael Sophia, an employee of Pharmasett, which was later acquired by Gilead Sciences. From Michael’s last name, the substance he synthesized was named sofosbuvir. Michael Sofia himself, together with a group of scientists who made a number of discoveries that revealed the nature of HCV, which made it possible to create an effective drug for its treatment, received the Lasker-DeBakey Award for Clinical Medical Research. Well, almost all of the profit from the sale of the new effective product went to Gilead, which set monopoly high prices for Sovaldi. Moreover, the company protected its development with a special patent, according to which Gilead and some of its partner companies became the owners of the exclusive right to manufacture the original DPP. As a result, Gilead's profits in just the first two years of sales of the drug many times covered all the costs that the company incurred to acquire Pharmasett, obtain a patent and subsequent clinical trials.

What is Sofosbuvir?

The effectiveness of this drug in the fight against HCV has proven to be so high that now almost no treatment regimen can do without its use. Sofosbuvir is not recommended for use as monotherapy, but when used in combination it shows exceptionally good results. Initially, the drug was used in combination with ribavirin and interferon, which made it possible to achieve a cure in just 12 weeks in uncomplicated cases. And this despite the fact that therapy with interferon and ribavirin alone was half as effective, and its duration sometimes exceeded 40 weeks. After 2013, each subsequent year brought news of the emergence of more and more new drugs that successfully fight the hepatitis C virus:

daclatasvir appeared in 2014;
2015 was the year of birth of ledipasvir;
2016 pleased with the creation of velpatasvir.

Daclatasvir was released by Bristol-Myers Squibb in the form of Daklinza, containing 60 mg of the active substance. The next two substances were created by Gilead scientists, and since neither of them was suitable for monotherapy, the drugs were used only in combination with sofosbuvir. To facilitate therapy, Gilead prudently released the newly created drugs immediately in combination with sofosbuvir. This is how the drugs appeared:

Harvoni, combining sofosbuvir 400 mg and ledipasvir 90 mg;
Epclusa, which included sofosbuvir 400 mg and velpatasvir 100 mg.

During therapy with daclatasvir, two different drugs, Sovaldi and Daklinza, had to be taken. Each paired combination of active ingredients was used to treat specific HCV genotypes according to treatment regimens recommended by EASL. And only the combination of sofosbuvir with velpatasvir turned out to be a pangenotypic (universal) drug. Epclusa cured all genotypes of hepatitis C with almost equally high effectiveness of approximately 97 ÷ 100%.

The emergence of generics

Clinical trials confirmed the effectiveness of the treatment, but all these highly effective drugs had one significant drawback - too high prices, which prevented the majority of patients from purchasing them. Monopoly high prices for products set by Gilead caused outrage and scandals, which forced patent holders to make certain concessions, granting some companies from India, Egypt and Pakistan licenses to produce analogues (generics) of such effective and popular drugs. Moreover, the fight against patent holders offering drugs for treatment at biasedly inflated prices was led by India, as a country where millions of chronic hepatitis C patients live. As a result of this struggle, Gilead issued licenses and patent developments to 11 Indian companies to independently produce first sofosbuvir, and then its other new drugs. Having received licenses, Indian manufacturers quickly began producing generics, assigning their own trade names to the drugs they produced. This is how generics Sovaldi first appeared, then Daklinza, Harvoni, Epclusa, and India became the world leader in their production. Indian manufacturers, under a licensing agreement, pay 7% of earnings to patent holders. But even with these payments, the cost of generics produced in India turned out to be tens of times less than the originals.

Mechanisms of action

As already reported above, the new HCV therapy products that have emerged are classified as DAAs and act directly on the virus. Whereas interferon with ribavirin, previously used for treatment, strengthened the human immune system, helping the body resist the disease. Each substance acts on the virus in its own way:

Sofosbuvir blocks RNA polymerase, thereby inhibiting viral replication.

Daclatasvir, ledipasvir and velpatasvir are NS5A inhibitors that interfere with the spread of viruses and their entry into healthy cells.

This targeted effect makes it possible to successfully combat HCV using sofosbuvir for therapy in combination with daklatasvir, ledipasvir, velpatasvir. Sometimes, to enhance the effect on the virus, a third component is added to the pair, which most often is ribavirin.

Manufacturers of generics from India

Pharmaceutical companies in the country have taken advantage of the licenses granted to them, and now India produces the following generic Sovaldi:

Hepcvir - manufactured by Cipla Ltd.;
Hepcinat - Natco Pharma Ltd.;
Cimivir - Biocon ltd. & Hetero Drugs Ltd.;
MyHep is manufactured by Mylan Pharmaceuticals Private Ltd.;
SoviHep - Zydus Heptiza Ltd.;
Sofovir - manufactured by Hetero Drugs Ltd.;
Resof - produced by Dr Reddy's Laboratories;
Virso - produced by Strides Arcolab.

Analogs of Daklinza are also made in India:

Natdac from Natco Pharma;
Dacihep by Zydus Heptiza;
Daclahep from Hetero Drugs;
Dactovin by Strides Arcolab;
Daclawin from Biocon ltd. & Hetero Drugs Ltd.;
Mydacla from Mylan Pharmaceuticals.

Following Gilead, Indian drug manufacturers also mastered the production of Harvoni, resulting in the following generics:

Ledifos - released by Hetero;
Hepcinat LP - Natco;
Myhep LVIR - Mylan;
Hepcvir L - Cipla Ltd.;
Cimivir L - Biocon ltd. & Hetero Drugs Ltd.;
LadyHep - Zydus.

And already in 2017, the production of the following Indian generics of Epclusa was mastered:

Velpanat was released by the pharmaceutical company Natco Pharma;
the release of Velasof was mastered by Hetero Drugs;
SoviHep V was launched by Zydus Heptiza.

As you can see, Indian pharmaceutical companies do not lag behind American manufacturers, quickly mastering their newly developed drugs, while observing all qualitative, quantitative and medicinal characteristics. Maintaining, among other things, pharmacokinetic bioequivalence in relation to the originals.

Requirements for generics

A generic is a drug that, based on its basic pharmacological properties, can replace treatment with expensive original drugs with a patent. They can be produced either with or without a license; only its presence makes the produced analogue licensed. In the case of issuing a license to Indian pharmaceutical companies, Gilead also provided the production technology for them, giving the license holders the right to an independent pricing policy. In order for a drug analogue to be considered a generic, it must meet a number of parameters:

It is necessary to observe the ratio of the most important pharmaceutical components in the drug according to qualitative as well as quantitative standards.

Compliance with relevant international standards should be adhered to.

Proper production conditions are required.

The preparations should maintain the appropriate equivalent absorption parameters.

It is worth noting that the WHO is guarding the availability of medicines, seeking to replace expensive branded medicines with the help of budget generics.

Egyptian generics of sofosbuvir

Unlike India, Egyptian pharmaceutical companies have not become world leaders in the production of generic drugs for hepatitis C, although they have also mastered the production of sofosbuvir analogues. True, the bulk of the analogues they produce are unlicensed:

MPI Viropack, produces the drug Marcyrl Pharmaceutical Industries - one of the very first Egyptian generics;

Heterosofir, produced by Pharmed Healthcare. Is the only licensed generic in Egypt. There is a code hidden on the packaging under the hologram that allows you to check the originality of the drug on the manufacturer’s website, thereby eliminating its counterfeit;

Grateziano, manufactured by Pharco Pharmaceuticals;

Sofolanork produced by Vimeo;

Sofocivir, manufactured by ZetaPhar.

Generics to fight hepatitis from Bangladesh

Another country producing large volumes of generic anti-HCV drugs is Bangladesh. Moreover, this country does not even require licenses for the production of analogues of branded medicines, since until 2030 its pharmaceutical companies are allowed to produce such medications without having the appropriate licensing documents. The most famous and equipped with the latest technology is the pharmaceutical company Beacon Pharmaceuticals Ltd. The design of its production capacity was created by European specialists and meets international standards. Beacon produces the following generics for the treatment of hepatitis C virus:

Soforal is a generic version of sofosbuvir, containing 400 mg of active substance. Unlike traditional packaging in bottles of 28 pieces, Soforal is produced in the form of blisters of 8 tablets in one plate;
Daclavir is a generic version of daclatasvir, one tablet of the drug contains 60 mg of the active substance. It is also produced in the form of blisters, but each plate contains 10 tablets;
Sofosvel is a generic version of Epclusa, containing sofosbuvir 400 mg and velpatasvir 100 mg. A pangenotypic (universal) drug, effective in the treatment of HCV genotypes 1 ÷ 6. And in this case, there is no usual packaging in bottles, the tablets are packaged in blisters of 6 pieces in each plate.
Darvoni is a complex drug that combines sofosbuvir 400 mg and daclatasvir 60 mg. If it is necessary to combine sofosbuvir therapy with daklatasvir, using drugs from other manufacturers, you must take a tablet of each type. And Beacon combined them into one pill. Darvoni is packaged in blisters of 6 tablets in one plate and sent for export only.

When purchasing medications from Beacon for a course of therapy, you should take into account the originality of their packaging in order to purchase the quantity required for treatment. The most famous Indian pharmaceutical companies As mentioned above, after the country's pharmaceutical companies received licenses to produce generics for HCV therapy, India has become a world leader in their production. But among the many companies, it is worth noting a few whose products are the most famous in Russia.

Natco Pharma Ltd.

The most popular pharmaceutical company is Natco Pharma Ltd., whose drugs have saved the lives of several tens of thousands of people with chronic hepatitis C. It has mastered the production of almost the entire line of direct-acting antiviral drugs, including sofosbuvir with daclatasvir and ledipasvir with velpatasvir. Natco Pharma appeared in 1981 in Hyderabad with an initial capital of 3.3 million rupees, then the number of employees was 20 people. Now in India, 3.5 thousand people work at five Natco enterprises, and there are also branches in other countries. In addition to production units, the company has well-equipped laboratories that allow it to develop modern medications. Among her own developments, it is worth noting drugs to combat cancer. One of the most well-known drugs in this area is Veenat, produced since 2003 and used for leukemia. And the production of generics for the treatment of hepatitis C virus is a priority area of activity for Natco.

Hetero Drugs Ltd.

This company has set its goal to produce generics, subordinating its own network of production facilities, including factories with branches and offices with laboratories. Hetero's production network is designed to produce medicines under licenses received by the company. One of its areas of activity is medications that help fight serious viral diseases, the treatment of which has become impossible for many patients due to the high cost of original drugs. The acquired license allows Hetero to quickly begin producing generics, which are then sold at a price affordable for patients. The creation of Hetero Drugs dates back to 1993. Over the past 24 years, a dozen factories and several dozen production units have appeared in India. The presence of its own laboratories allows the company to carry out experimental work on the synthesis of substances, which contributed to the expansion of the production base and the active export of drugs to foreign countries.

Zydus Heptiza

Zydus is an Indian company that has set as its goal the creation of a healthy society, which, according to its owners, will be followed by a positive change in the quality of life of people. The goal is noble, and therefore, to achieve it, the company conducts active educational activities that affect the poorest segments of the country's population. Including through free vaccination of the population against hepatitis B. Zidus is in fourth place in terms of production volumes on the Indian pharmaceutical market. In addition, 16 of its drugs were included in the list of 300 most important drugs of the Indian pharmaceutical industry. Zydus products are in demand not only on the domestic market; they can be found in pharmacies in 43 countries on our planet. And the range of drugs produced at 7 enterprises exceeds 850 drugs. One of its most powerful production facilities is located in the state of Gujarat and is one of the largest not only in India, but also in Asia.

HCV therapy 2017

Hepatitis C treatment regimens for each patient are selected by the doctor individually. To correctly, effectively and safely select a regimen, the doctor needs to know:

virus genotype;
duration of illness;
degree of liver damage;
presence/absence of cirrhosis, concomitant infection (for example, HIV or other hepatitis), negative experience of previous treatment.

Having received this data after a series of tests, the doctor, based on EASL recommendations, selects the optimal treatment option. EASL recommendations are adjusted from year to year, with newly introduced drugs being added to them. Before new treatment options are recommended, they are submitted to Congress or a special session. In 2017, a special EASL meeting in Paris considered updates to the recommended schemes. The decision was made to completely stop using interferon therapy in the treatment of HCV in Europe. In addition, there is not a single recommended regimen left that uses one single direct-acting drug. Here are several recommended treatment options. All of them are given for informational purposes only and cannot become a guide to action, since the prescription of therapy can only be given by a doctor, under whose supervision it will then be carried out.

Possible treatment regimens proposed by EASL in case of hepatitis C monoinfection or concomitant HIV+HCV infection in patients who do not have cirrhosis and have not previously been treated:

for treatment genotypes 1a and 1b can be used:

- sofosbuvir + ledipasvir, without ribavirin, duration 12 weeks; - sofosbuvir + daclatasvir, also without ribavirin, treatment period is 12 weeks; - or sofosbuvir + velpatasvir without ribavirin, course duration 12 weeks.

during therapy genotype 2 used without ribavirin for 12 weeks:

- sofosbuvir + dklatasvir; - or sofosbuvir + velpatasvir.

during treatment genotype 3 without the use of ribavirin for a period of therapy of 12 weeks, use:

- sofosbuvir + daclatasvir; - or sofosbuvir + velpatasvir.

during therapy genotype 4 You can use without ribavirin for 12 weeks:

- sofosbuvir + ledipasvir; - sofosbuvir + daclatasvir; - or sofosbuvir + velpatasvir.

EASL recommended treatment regimens for hepatitis C monoinfection or concomitant HIV/HCV infection in patients with compensated cirrhosis who have not previously been treated:

for treatment genotypes 1a and 1b can be used:

- sofosbuvir + ledipasvir with ribavirin, duration 12 weeks; - or 24 weeks without ribavirin; - and one more option - 24 weeks with ribavirin if the response prognosis is unfavorable; - sofosbuvir + daclatasvir, if without ribavirin, then 24 weeks, and with ribavirin, the treatment period is 12 weeks; - or sofosbuvir + velpatasvir without ribavirin, 12 weeks.

during therapy genotype 2 apply:

- sofosbuvir + dklatasvir without ribavirin the duration is 12 weeks, and with ribavirin in case of poor prognosis - 24 weeks; - or sofosbuvir + velpatasvir without combination with ribavirin for 12 weeks.

during treatment genotype 3 use:

- sofosbuvir + daclatasvir for 24 weeks with ribavirin; - or sofosbuvir + velpatasvir, again with ribavirin, treatment period is 12 weeks; - as an option, sofosbuvir + velpatasvir is possible for 24 weeks, but without ribavirin.

during therapy genotype 4 apply the same schemes as for genotypes 1a and 1b.

As you can see, the result of therapy is influenced, in addition to the patient’s condition and the characteristics of his body, by the combination of prescribed medications chosen by the doctor. In addition, the duration of treatment depends on the combination chosen by the physician.

Treatment with modern drugs for HCV

Take tablets of direct antiviral drugs as prescribed by a doctor orally once a day. They are not divided into parts, not chewed, but washed down with plain water. It is best to do this at the same time, this way a constant concentration of active substances in the body is maintained. There is no need to be tied to the timing of meals, the main thing is not to do it on an empty stomach. When you start taking medications, pay attention to how you feel, since during this period it is easiest to notice possible side effects. DAAs themselves do not have very many of them, but drugs prescribed in combination have much less. Most often, side effects appear as:

headaches;
vomiting and dizziness;
general weakness;
loss of appetite;
joint pain;
changes in biochemical blood parameters, expressed in low hemoglobin levels, a decrease in platelets and lymphocytes.

Side effects are possible in a small number of patients. But still, all noticed ailments should be reported to the attending physician so that he can take the necessary measures. To avoid increased side effects, alcohol and nicotine should be avoided, as they have a harmful effect on the liver.

Contraindications

In some cases, taking DAAs is excluded, this applies to:

individual hypersensitivity of patients to certain drug ingredients;

patients under 18 years of age, since there is no accurate data on their effect on the body;

women carrying a fetus and breastfeeding babies;

Women should use reliable methods of contraception to avoid conception during therapy. Moreover, this requirement also applies to women whose partners are also undergoing DAA therapy.

Storage

Store direct-acting antiviral drugs in places inaccessible to children and out of direct sunlight. Storage temperature should be in the range of 15 ÷ 30ºС. When starting to take medications, check their production and storage dates indicated on the packaging. Expired medications should not be taken. How to purchase DAAs for residents of Russia Unfortunately, it will not be possible to find Indian generics in Russian pharmacies. The pharmaceutical company Gilead, having granted licenses to produce drugs, prudently banned their export to many countries. Including all European countries. Those wishing to purchase budget Indian generics to combat hepatitis C can use several options:

order them through Russian online pharmacies and receive the goods in a few hours (or days) depending on the delivery location. Moreover, in most cases, even an advance payment is not required;
order them through Indian online stores with home delivery. Here you will need an advance payment in foreign currency, and the waiting time will last from three weeks to a month. Plus there will be the need to communicate with the seller in English;
go to India and bring the drug yourself. This will also take time, plus the language barrier, plus the difficulty of checking the originality of the product purchased at the pharmacy. Added to this is the problem of self-export, which requires a thermal container, a doctor’s report and a prescription in English, as well as a copy of the receipt.

People interested in purchasing medicines decide for themselves which of the possible delivery options to choose. Just do not forget that in the case of HCV, a favorable outcome of therapy depends on the speed of its initiation. Here, in the literal sense, delay is like death, and therefore you should not delay the start of the procedure.