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Vir al hepatitises (VH) Group of clinical similar vir al diseases of the man with the peroral or parenteral m odes of infection described by a preferred d amage of hepatocytes and by toxic manifestations N ow adays t he following the agents of VH are known : - Hepatitis A virus (HAV) – cause of v iral hepati ti s A (VHA) - Hepatitis E virus (HEV) - cause of v iral hepatitis E (VHE) - Hepatitis B virus ( HBV ) - cause of v iral hepatitis B (VHB) - Hepatitis C virus ( HCV ) - cause of v iral hepatitis C (VHC) - Hepatitis D virus ( HDV) - cause of v iral hepatitis D (VHD)
There are in a stage of stad ing are following hepatitises : Hepatitis F virus (HFV) - cause of v iral hepatitis F ( VHF ) Hepatitis G virus ( HGV) - cause of v iral hepatitis G ( VHG) Hepatitis TT virus ( TTV) - cause of v iral hepatitis TT ( VHTT) Hepatitis SEN virus ( SENV) – cause of v iral hepatitis SEN A ll vir al hepatitises a re divided into 2 groups o n the m odes of transmission 1- st group - with peroral infection - (A, E) 2- nd group-with parenteral infection ( B, C, D, F, G, TT V, SEN) PATHOGENY: at all vir al hepatitises is observed virusemia with the subsequent d amage of hepatocytes and development of the following syndromes:
1. Syndrome of an intoxication (exogen ic and endogenic) 2. Cytolitic s yndrome 3. Syndrome of a cholestasia : 4. Syndrome hepato-cellular of unsufficiency: 5. Syndrome of an inflammation: 1. Syndrome of an intoxication (exogen ic and endogenic) The exogenous intoxication – it is cause d of viremia and a ppears by the following variant s: - influenza-similar variant : - fever, cephalic and м uscular pain by duration 5 - 7 days, but without catarrh and hypersecretion mucous of respiratory tract
- arthralgia variant : - ostealgia or arthralgia often in evening time without limitation th en function, sometimes with the phenomen a of reactive arthritis d yspeptic variant : - nausea, vomiting, anorexia, perverted taste astheno -vegetative variant - weaknees, hypotonia, t achycardia, mental depression m ixed variant (most often) - combined of the several variant s is simultaneous ly ! The endogenic intoxication - occurs as a result of violation of the desintoxication liver function with intensifying in accordance with weighting a state person
2 Cytolitic s yndrome - si g n s of lesion hepatocytes, what are accompanied by rise a ctivity of the following enzymes: Indicator enzymes: - А L Т (а lanine-aminotransferase ) - increase from tenfold to fifteenfold time. - А S Т (asparti ne-aminotransferase ) - LDG ( lactat-dehydrogenase and its isoenzymes) Specific hepatic enzymes: - fructose- 1- phosphataldolase - Sorbitum - dehydrogenase - Ornithine - carbamiltrasferase and o ther aldolases О rganello-specific enzymes: (in mitochondrions of hepatocytes ): - glutamat-dehydrogenase - succinat-dehydrogenase - h yperbilirubinemia - i ncrease of concentration in a blood of cyancobalamine
3. Syndrome of a cholestasia: - i ncrease excretory of enzymes ( alkaline p hospha - tases, leucyn-aminopeptidase, 5 – nucleo-peptidase, gamma – glutamiltranspeptidase ) - i ncrease of phospholipids - i ncrease in a blood of cholic acids 4. Syndrome hepato-cellular of unsufficiency: - l owering activity of a cholinesterase - l owering a thrombinogen - t he decrease of protein s (especial of a lbuminum) - l owering 2,5,7 factors of coagulat ing blood - l owering a cholesterin of blood - i ncrease in blood indirect bilirubin
5. Syndrome of an inflammation : - i ncrease in plasma Ig G, M, A - c hange of albumino -sedimental tests (increase t hymol test) - t he appearance in a blood of antibodies to DNA, s mooth - muscular to fibers, mitochondrions and microsomas - c hange of a leukopenia on neutrophia The expressiveness of these syndromes is individual and depends both on sort of a virus, and from protective responses of an organism:
Viral hepatitis may proceed as: Acute cyclic form of disease arise at sufficient xenogenic of virus and at e xpressed the interferon answer of an organism Carriage or chronic hepatitis form at low paphogenic and antigenic xenogenic of a virus, inefficiency cellular and h umoral immunity, defective of the system interferon of an organism ( low interferon the answer ) F ulminant forms of hepatitises arise at s ufficient xenogenic of a virus, low interferon the answer on a background generically determine hypersesitivity response of an organism
PATHOMORPHOLOGY - a t all hepatitises to change in liver, practically, identical and at r esearch hepatobiopsy ( percutaneus hepatic aspiration or at а utopsy ) reveal the following changes: - dilatat ion of portal pathes and inflammatory infiltrates in them consisting from lymphocytes, macrophages, plasma cells, eosinophiles and neutrophils - d amage of an internal boundary slice - p roliferation of an epitheli um cholic ducts, at caus ing to a stasis bile in them
- fa tty a dystrophia of hepatocytes and their d estruc - tion. Sometimes it so considerable, that in a lesion zone preserves only reticular frame of a liver - i s simultaneously observed regeneration as m itosises, both particular cell and whole groups - also the centers of a fibrosis is reveale d The morphology of a liver after clinical recovery is normalized not earlier than 3 months - histological changes of a liver in this period are conform ed for clinic of a chronic hepatitis
CLASSIFICATION of VIR AL HEPATITIS 1. On an etiology ( A,B,C Д, Е, T T, SEN, G, F etc. ) 2. On duration of current: - Acute - about 3 of months - Lingering - up to 6 of months - Chronic - more 6 of months 3. On an expressiveness of clinical manifestations: - Asymptomatic (carriage of virus and subclinical of the form s of disease) - Demonstrative - (icteric and anicteric ) 4. On current: - Cyclic - Acyclic (with peakings and relapses)
5. On a dominating syndrome: - cytolitic the form s - cholestatic the form s (30 %) - cholestatic the form s (1 %) 6. On a degree of clinical gravity and hyperbilirubinemia: - m ild (up to 80 - 100 mCml / l ) - moderate (up to 160 - 200 mCml / l ) - s e vere (more than 160 - 200 mCml / l ) - fulminant form - (early and late) The e xample of the diagnosis: an acute vir al hepatitis A, anti- НАV Ig M (+), mild icteric form - (common bilirubin is 6 5 mCml / l) cyclic current with predominance а cytolysis (А L Т - 7 mMm / h / l )
VIRAL HEPATITIS A (VHA) ETIOLOGY: Shallow inenvelope a virus by a size 27 - 30 nm. S. Picornaviridae, R.Hepatovirus contains one-filamentous RN A (+) V irus is open ed in 1973 year. V irus has 1 serotype and 7 genotypes. V irus is well survives in the environment: - a t 20 гр. C - 1 month - a t 4 гр. C - some years - рН of a stomach from 3 up to 10 not influence a survival v irus!!! - a t рН is lower 3 - survives till 4 hour s - a t 60 dg. C - maintains 12 hour s - a t 100 гр. C - perishes instantly - desinfectants inactivate it s for 15 minutes - i s steady to alcohol
EPIDEMIOLOGY- it is antroponosis The sourse - the patient with any form Illnesses (obvious or erased) The m ode of transmission - faeco -oral The factors of transmission: - p ersonal contact to the patient or polluted him by subjects (do not have seasonal prevalence!!!) - p olluted nutrition and water (as flashouts) - i s possible percutaneus (seldom) Susceptibility general!! More often children are sick after 1 year of life. By 40 years up to 80 -90 % of the people transfer a hepatitis A ( In their blood is taped anti- НАV Ig G )
CLINIC: Incubation 15 - 50 days (30 days ) Prodromal stage - 1 - 2 weeks Appearance of an icterus for 70 - 80 % hospitalized of the patients The asymptomatic forms - 10 - 25 % of the adults Complications: - f ulminant current - 0,04 - 0,4 % - l ingering current ( 2 - 3 months ) - less than 10 % - relapses - 6 - 10 % The chronic current - is not described!!! Lethality - 0,02 - 1,5 %
FREQUENCY of SIGNS VHA in %: Children adults Nausea, vomiting 65 26 Yellowness of white of the eyes 65 88 Yellowness of a skin 65 88 Diarrhea 58 18 Dark urine 58 68 Decolorized feces 58 58 Pain in epigastriums 48 37 Weakness 48 63 Fever, chill 41 32 Anorexia 41 42 Pain in muscles, joints 6 30 Headache - 17 Pharyngitis 6 -
Diagnosis marks of VHA ( ELISA and PCR) 1 anti -HAV Ig M – sign of acute infection 2 anti - HAV Ig G – sign forming of a immunity or vaccination 3 HAV Ag – sign of presense HAV in feces or blood ( seldom) 4 RNA – HAV - sign of presense HAV in feces or blood and it replication Therapy - pathogenetic and symptomatic : - bed rest, - diet N5, - hepatoprotections, - vitamin therapy, - desintoxication PO or IV ( seldom), - antioxidants - antiviral t herapy does not used
A 53-year-old male presented with jaundice, fatigue,and hepatomegaly. These symptomes developed 3 days after onset of dark urine, fever, and chill. He denid alcohol abuse and exposure to rick factors for viral hepatitis. However, 6 weeks disease onset he visited North Africa. Laboratory investigations: Bilirubin 248 m mol/L ( 1.7 – 17.1 m mol/l), ALT 640 U/L ( 5 – 40 U/L), AST –200 U/L ( 5 – 40 U/L), Prothrombin time 16 seconds, Platelet count 240 x10 in 9dg /L HBs Ag absent, Anti- HCV absent, IgM anti HAV present. The diagnosis ( Acute infection with hepatitis A virus ) rest on detection of serum IgM antibody to hepatitis A virus. IgM antibody is almost invariably found at onset of symptoms or 1 week later, and may persist for months. The clinical picture of hepatitis A differs according to the patient’s age. Jaundice is unusual in infants, whereas symptomatic, icteric hepatitis is common in adults. Fulminant hepatitis A occurs in 1% patients above the age of 50.
VIR AL HEPATITIS Е (VHE) The agent - shallow spherical Calicinoviruses 27 - 34 nm, containing one chain RNA, well sevives at temperature (-) 20 гр. C, but at temperature is higher 0 гр. C are fast inactivated. Are very sensitive to desinfectants Те ratogenic of operation does not render, with milk of the mother do not se crete. Are sensitive to it s- monkeis and pigs, on cellular cultures does not grow. FEATURES of a VIRUS HEPATITIS Е: - t he age is more often than 15-40 years (man more often in 2 times) - i s more often as aqueous explosive character of the flashouts - l ow family case rate ( contrast to VHA )
The seasonal prevalence - is more often in period monsoon of rains Irregular distribution on territory To othen in locales with scanty water supply The m ode of transmission - faeco -oral The carrying on factor of transmission - potable water High lethality among the pregnant woman in 3 rd t rimester ( to 25 %) and children in neonatal period (Up to 77 % ) Incubation interval from 2 about 8 weeks (36 days) The expressed pain syndrome in the right hypochondrium and epigastriums for 70 % of the patients In preicteric period frequently arthralgias and d iarrhea
f ever – sign is nonconstant w ith appearance of an icterus aggravation of symptoms with b y increase of intoxication ( contrast to VHA ) ! i s accompanied micro and macro hematuria typical two-phase rise cytolitical of enzymes (on 6-12 and 14 - 26 days of illness) n ormal or slightly increase t hymol test ( contrast to VHA ) t he test a n t ibody VH E Ig M it raises!!!) c an ha s lingering current, but chronic t he forms are not registered r elation icteric and anicteric of the forms 1:5 duration of icteric period 1 - 2 weeks
Lethality no more than 0,4 % The pregnant women in 3 td trimester - interuption of pregnency (40%) and perish from DIC – syndrome ( disseminated intravascular coagulopathy) and acute hepatic insuffiency (5,6% - 17,6%). Differential d iagnosis VHA and VHE - har d in preicteric p eriod and more often is reg ister ed as ARVD. With appearance of an icterus it is necessary to eliminate all superhepatic, hepatic and subhepatic of its reason Diagnosis marks of VHE ( ELISA and PCR) 1 anti - HEV Ig M – sign of acute infection 2 anti - HEV Ig G – sign forming of a immunity 3 HEV Ag – sign of presense HEV in feces or blood 4 RNA – HEV - sign of presense HEV in feces or blood and it replication
A 39-year-old Chinese businessman travelling to Italy presents fatigue, anorexia, jaundice, and elevated ALT. He denies risk factors for viral hepatitis or heavy alcohol consuption. On admission, the liver is tender with a 14 cm span. The spleen is palpable. Laboratory investigation: ALT –740 U/L, ASI –680 U/L, Bilirubin – 188 m mol/L, ALP -178 U/L, HBsAg- abcent, anti- HBs Ag – present, anti- HBc Ag – present, Total anti-HAV - present, anti-HAV I gM- abcent, anti-HEV lgM – present 1. What is the diagnosis? The diagnosis ( Acute infection with hepatitis E ) rest on detection of serum IgM antibody to hepatitis E virus.
A 27-year-old water engineer returns from working in West Africa and 3 weeks later develops: low grade fever, malaise and jaundice. Laboratory investigation are shown: Hemoglobin – 134 g/L, WBC count – 4.0 x 10 in 9 dg./L with lymphocytosis on a differential count, Albumin – 42 g/L, ALP – 280 U/L, Prothrobin time – 13 seconds. ALT –538 U/L, AST – 220 U/L, Bilirubin – 80 mmol/L, ALP -178 U/L, HBsAg- abcent, Total anti-HAV - present, anti-HAV I gM- abcent, anti-HEV lgM – present What is the diagnosis? The diagnosis ( Acute infection with hepatitis E ) rest on detection of serum IgM antibody to hepatitis E virus.
Therapy - pathogenetic and symptomatic : bed rest, diet N5, hepatoprotections, vitamin therapy, PO desintoxication, antioxidants Prophylaxis: i mprovement of quality of water and nutrition t he isolation contact (brings small effect) p assive (VHА, VHE ) and active immunization ( VHА )
Appearance encephalopathy with an oppression of consciousness, degree e xpressivenesses which is estimated in mark s on Glasgow scale : 1 Opening spontaneous 4 of an eye s in reply to the verbal order 3 In reply to pain stimulation 2 absence 1 2. Active move - spontaneus and reply in the order 6 ments single-minded on pain 5 unsingle-minded on pain 3 p athological tonical flexion to pain 3 p athological tonical extension to pain 2 a bsence of a motion to pain stimulation 1
Последний слайд презентации: Vir al hepatitises (VH) Group of clinical similar vir al diseases of the man
3. Verbal is oriented F ast answers - 5 The answers the confused speech - 4 The inadequate answers - 3 Inarticulate sound - 2 Absence of speech - 1 15 numbers - norm, 13 - 14 numbers - somnolencea 9-12 numbers - sopor, 4-8 numbers - coma, 4 numbers and less - out-of-limit coma.