Viral hepatitis

Lecturer:Lecturer:

Gorishna Ivanna LubomyrivnaGorishna Ivanna Lubomyrivna

Plan of the lecture

Definition of the acute hepatitisDefinition of the acute hepatitis Classification of hepatitis Clinical manifestation Methods of examinations Treatment of the different kinds of hepatitis

Definition of the acute hepatitis

a continuing hepatic inflammatory process a continuing hepatic inflammatory process manifested by elevated hepatic transaminase manifested by elevated hepatic transaminase level, lasting less than 6 mo and accompanied level, lasting less than 6 mo and accompanied with pain, dyspeptic, intoxication and with pain, dyspeptic, intoxication and cholestatic syndromescholestatic syndromes

Pathogenesis:Hepatitis A, EHepatitis A, E Inoculation of the pathogen (entrance gate – small Inoculation of the pathogen (entrance gate – small

intestine).intestine). Viremia.Viremia. Viral fixation on hepatocytes, intracellular localization.Viral fixation on hepatocytes, intracellular localization. Primary replication of the virus.Primary replication of the virus. Excretion with a goal to intestine.Excretion with a goal to intestine. Part of the viruses caused viremia (prodromal period of Part of the viruses caused viremia (prodromal period of

the disease).the disease). Activation of immune system, that causes cytolysis, Activation of immune system, that causes cytolysis,

mesenchimal inflammation and cholestasis.mesenchimal inflammation and cholestasis. Immune response, elimination of the virus.Immune response, elimination of the virus.

Pathogenesis:

Hepatitis B Inoculation of the pathogen. Viremia. Viral integration and replication in hepatocytes, also

may be in blood cells, bone marrow, lymph nodes, spleen.

Activation of immune system, that causes cytolysis, mesenchimal inflammation and cholestasis.

Immune response, elimination or persistence of the virus.

Pathogenesis:Hepatitis C Inoculation of the pathogen. Viremia. Viral integration and replication in hepatocytes, also

may be in blood cells, bone marrow, lymph nodes, spleen.

Activation of immune system with low immune response.

Mutation changeability of the virus. Persistence of the virus.Hepatitis D Need virus hepatitis B for its replication, develops only

in infected HBV patients

Classification1. 1. Form of disease Form of disease • TypicalTypical• Atypical Atypical

• Anicteric hepatitis Anicteric hepatitis • Subclinical hepatitisSubclinical hepatitis• Cholestatic hepatitisCholestatic hepatitis• Fulminant hepatitisFulminant hepatitis

2. 2. Periods of the diseasePeriods of the disease::• Incubation Incubation • Pre-ictericPre-icteric• IctericIcteric• Post-icteric Post-icteric • Recovery Recovery

Classification

Severity: mild moderate severe

Duration: acute (2-3 months); prolonged (3-6 months); chronic.

Diagnostic criteria of incubation period

absence of clinical signs viral antigens are present in blood alanine aminotranspherase, aspartate

aminotranspherase may be enlarged

Pre-icteric (prodromal, prejaundice) period Caroli’s triad Caroli’s triad

headacheheadache rashes (often in HBV-hepatite)rashes (often in HBV-hepatite) arthralgiasarthralgias

"flu like syndrome“"flu like syndrome“ Loss of appetiteLoss of appetite NauseaNausea VomitingVomiting hepatomegaly, pain in right costochondrial rib, hepatomegaly, pain in right costochondrial rib,

epigastriumepigastrium in the end – appearing of pale-colored stoolsin the end – appearing of pale-colored stools elevationelevation of ALT, AST, special hepatitis markers.of ALT, AST, special hepatitis markers.

pale-colored stools

Icteric period Jaundice of mucous membranes, sclera, and Jaundice of mucous membranes, sclera, and

skin.skin. Urobilinuria, bilirubinuria.Urobilinuria, bilirubinuria. Hepatomegaly, tenderness of liver.Hepatomegaly, tenderness of liver. Hyperbilirubinemia with conjugate bilirubin Hyperbilirubinemia with conjugate bilirubin

prevalence.prevalence. skin rashesskin rashes hemorrhagic syndromehemorrhagic syndrome splenomegalysplenomegaly

Jaundice of the hard palate

Jaundice of the mucous membranes

Sclera and skin jaundice

Dark urine

Hepatomegaly

Hepato-spleno-megaly

Laboratory testsLaboratory testsProdromal periodProdromal period Enlargement of ALAT and ASAT, urobilinuria. Enlargement of ALAT and ASAT, urobilinuria. Anti-HAV Ig M, HAV-RNA Anti-HAV Ig M, HAV-RNA (hepatitis A).(hepatitis A). HBsAg, HBeAg, HBV-DNA and anti-НВс IgM HBsAg, HBeAg, HBV-DNA and anti-НВс IgM

((hepatitis B).hepatitis B). HBsAg, HBeAg, HBV-DNA, anti-НВс IgM HBsAg, HBeAg, HBV-DNA, anti-НВс IgM

and HDVAg, HDV-RNA and HDVAg, HDV-RNA (hepatitis delta (hepatitis delta coinfection).coinfection).

HCV-RNA HCV-RNA (hepatitis C).(hepatitis C). Anti-HEV Ig M, HEV-RNA Anti-HEV Ig M, HEV-RNA (hepatitis E).(hepatitis E).

Jaundice periodNonspecific tests enlargement of ALAT and ASAT , hyperbilirubinemia with conjugate bilirubin

prevalence, marking of bile pigment in urine, increased sediment tymol test decreased sulemic test (severe hepatitis B) decreased prothrombine index, fibrinogen in cholestasis alkaline phosphatase, cholesterol,

GGTP are increased

Jaundice period

Specific tests (markers) Anti-HAV Ig M, HAV-RNA (hepatitis A). HBsAg, HBeAg, HBV-DNA and anti-НВс IgM

(hepatitis B). HBsAg, HBeAg, HBV-DNA, anti-НВс IgM

and HDVAg, anti-HDV IgM, HDV-RNA.(hepatitis delta coinfection)

HCV-RNA, anti-HCVcore IgM and IgG (acute hepatitis C).

Anti-HEV Ig M, HEV-RNA (hepatitis E).

Post-icteric period

Urine becomes lighterUrine becomes lighter Stools darkerStools darker Jaundice fadesJaundice fades Decreasing ALAT, ASATDecreasing ALAT, ASAT Decreasing of the liver sizes Decreasing of the liver sizes

Laboratory tests (Laboratory tests (Posticteric period)Posticteric period) Normalization of bilirubin, ALAT and ASAT, other

indexes, later - sediment tymol test Anti-HAV Ig G, HAV-RNA (hepatitis A). Anti-НВс IgM , anti-Нве IgM, later- anti-НВс (total)

IgM and anti-НВс IgG (hepatitis B). Anti-НВс IgM , anti-Нве IgM, later- anti-НВс (total)

IgM and anti-НВс IgG and anti-HDV IgG (hepatitis D). Anti-HCVcore IgG (past hepatitis C). Anti-HCVcore IgG, anti-HCV NS in hepatitis C latent

phase. Anti-HCVcore IgM and IgG (with IgM predominance),

anti-HCV NS and HCV-RNA in hepatitis C reactivation phase.

Anti-HEV Ig G (hepatitis E).

Severity of the disease MildMild

Mild symptoms of intoxicationMild symptoms of intoxication Mild jaundiceMild jaundice Mild enlargement of the liverMild enlargement of the liver Total bilirubin up to 85 mcmol/l (norm up to 20 Total bilirubin up to 85 mcmol/l (norm up to 20

mcmol/l) unmcmol/l) unconjugatedconjugated up to 25 mcmol/l (norm up to up to 25 mcmol/l (norm up to 15 mcmol/l)15 mcmol/l)

Mild elevation of sediment tymol test (norm up to 5 Mild elevation of sediment tymol test (norm up to 5 U)U)

elevationelevation of ALATof ALAT << 10 10 times times Prothrombine index is normalProthrombine index is normal Duration of icteric phase 7-10 daysDuration of icteric phase 7-10 days Liver sizes normalize in 25-35 days Liver sizes normalize in 25-35 days

Severity of the disease ModerateModerate

Moderate symptoms of intoxicationModerate symptoms of intoxication Moderate or significant jaundice Moderate or significant jaundice Moderate enlargement of liver (+2-5 cm), enlargement of Moderate enlargement of liver (+2-5 cm), enlargement of

spleenspleen Decreasing of diuresisDecreasing of diuresis Total bilirubin is between 85-200 mcmol/l, unTotal bilirubin is between 85-200 mcmol/l, unconjugatedconjugated

up to 50 mcmol/lup to 50 mcmol/l Prothrombin index is decreased (60-90 %)Prothrombin index is decreased (60-90 %) elevation of sediment tymol test elevation of sediment tymol test elevationelevation of ALATof ALAT in 10-15in 10-15 times times Liver sizes normalize in 40-50 days Liver sizes normalize in 40-50 days Duration of icteric phase 7-14 daysDuration of icteric phase 7-14 days

Fulminant hepatitis Acute failure of the liverAcute failure of the liver Confusion and drowsinessConfusion and drowsiness Delirium and convulsions Delirium and convulsions Liver gets smallerLiver gets smaller Coma I-II ESG is abnormalComa I-II ESG is abnormal Hepatic smellHepatic smell Hemorrhagic syndromeHemorrhagic syndrome Encephalopathy Encephalopathy Decreasing of diuresisDecreasing of diuresis Total bilirubin is increased Total bilirubin is increased Prothrombin time is prolongedProthrombin time is prolonged Decreasing Decreasing of ALAT, ASATof ALAT, ASAT Decreasing of proteinsDecreasing of proteins

Severity of the disease SevereSevere

severe symptoms of intoxicationsevere symptoms of intoxication significant jaundice significant jaundice Moderate enlargement of the liver (+2-5 cm), enlargement Moderate enlargement of the liver (+2-5 cm), enlargement

of the spleenof the spleen Hemorrhagic rashHemorrhagic rash Decreasing of diuresisDecreasing of diuresis Total bilirubin is more 200 mcmol/l, unTotal bilirubin is more 200 mcmol/l, unconjugatedconjugated more more

50 mcmol/l50 mcmol/l Prothrombin index is decreased (50-60 %)Prothrombin index is decreased (50-60 %) elevation of sediment tymol test (norm up to 5 U)elevation of sediment tymol test (norm up to 5 U) elevationelevation of ALATof ALAT in 15-30in 15-30 times times Duration of icteric phase 2-3 weeksDuration of icteric phase 2-3 weeks Liver sizes normalize in 40-60 daysLiver sizes normalize in 40-60 days

Outcome of diseaseFor HAV, HEVFor HAV, HEV Recovering Recovering Residual fibrosis of liver (posthepatitis hepatomegaly)Residual fibrosis of liver (posthepatitis hepatomegaly) Biliary dyskinesiaBiliary dyskinesia Chronic cholecystitis and cholecystocholangitisChronic cholecystitis and cholecystocholangitis

For HBV, HCVFor HBV, HCV Recovering Recovering Residual fibrosis of liver (posthepatitis hepatomegaly)Residual fibrosis of liver (posthepatitis hepatomegaly) Biliary dyskinesiaBiliary dyskinesia Chronic cholecystitis and cholecystocholangitisChronic cholecystitis and cholecystocholangitis transition in chronic hepatitis;transition in chronic hepatitis; cirrhosiscirrhosis hepatic carcinomahepatic carcinoma death.death.

Palm erythema

Spider-angiomas in chronic liver diseases

Biliary cirrhosis, collateral circulation

Cholestasis

Ascyte, laparocentesis

Differential diagnosis

Prejaundice period: viral upper respiratory tract infections, bowel infection, acute appendicitis, diseases caused by parasites, acute pancreatitis.

Differential diagnosis

Jaundice period: suprahepatic icterus (hemolytic anemia), hepatic icterus (Gilbert, Krigler-Nadjar

syndrome, infectious mononucleosis, leptospirosis, pseudotuberculosis, congenital liver diseases),

subhepatic icterus (mechanical jaundice).

Hepatitis A Patients age Incubation period beginning Intoxication in preicteric

period Intoxication in icteric

period Allergic rashes Severity Duration of the icteric

period transition in chronic

hepatitis Tymol test

Elder than 1 yr. 14-45 days acute Moderate

Mild

Absent Mild and moderate 1-1.5 wks –– Elevated

elevated

Hepatitis E Patients age Incubation period beginning Intoxication in preicteric

period Intoxication in icteric

period Allergic rashes Severity Duration of the icteric

period transition in chronic

hepatitis Tymol test

Elder than 1 yr. 15-45 days Acute moderate

Absent or mild

Absent Mild 1-2 wks

–– high

Signs Hepatitis B

Patients age All age groups

Incubation period 2-6 mo.

beginning subacute

Intoxication in preicteric period

mild

Intoxication in icteric period severe

Allergic rashes May be present

Severity Often moderate and severe

Duration of the icteric period 3-5 wks

transition in chronic hepatitis

Often normal

Hepatitis C Patients age Incubation period beginning Intoxication in preicteric

period Intoxication in icteric

period Allergic rashes Severity Duration of the icteric

period transition in chronic

hepatitis Tymol test

All age groups 2 wks. - 3 mo. Subacute Mild

Absent or mild

May be present Mild and moderate 2 wks

in 50 % Moderately elevated

Hepatitis D Patients age Incubation period beginning Intoxication in preicteric

period Intoxication in icteric

period Allergic rashes Severity Duration of the icteric

period transition in chronic

hepatitis Tymol test

All age groups 2 wks. - 6 mo. Acute Often moderate

severe

May be present Severe and fulminant 2-8 wks

Often Moderately elevated

Basic treatment (for mild form): bed regimen up to intoxication disappear,bed regimen up to intoxication disappear, half-bed regimen (up to icterus disappear, half-bed regimen (up to icterus disappear,

normalization of ALAT, ASAT)normalization of ALAT, ASAT) special diet (diet N 5): special diet (diet N 5):

Exclude heavy fats (like pork), spices, fried foods, "fast Exclude heavy fats (like pork), spices, fried foods, "fast food"”; avoid stimulators of gastrointestinal secretions, the food"”; avoid stimulators of gastrointestinal secretions, the diet must be rich by metionine, lecithin, and choline to diet must be rich by metionine, lecithin, and choline to stimulate synthesis of proteins and enzymes in the liver. stimulate synthesis of proteins and enzymes in the liver. Diet with normal value of proteins and vitamins, with Diet with normal value of proteins and vitamins, with restriction of fats and carbohydrates is administered, also restriction of fats and carbohydrates is administered, also restrict salt. restrict salt.

Foods boiled, steamed and baked are recommended; food Foods boiled, steamed and baked are recommended; food taking 5 times dailytaking 5 times daily

Treatment of moderate hepatitis

basic therapy peroral detoxication 40-50 ml/kg with water balance

control enterosorption 1-2 wks (in case of cholestatic variant) choleretics from the 3-d week of disease

cholagon allocholum cholenzym galstena hepabene

Choleretics Choleretics

Treatment of severe hepatitis Basic therapy intravenously detoxication therapy (total amount – 50-

100 ml/kg/day); 0.9% NaCl, Ringer’s solution 5% glucose, albumin 5 ml/kg

enterosorption 2-3 wks lactulose for 10-14 days desoxycholic acid (ursophalk) in case of cholestasis 10

mg/kg prednizone (in possibility of fulminant form

development and for infants before 1 year with unfavorable premorbid background):

2 - 3 mg/kg/day divided in 4 equal doses 7-10 days

Hepatoprotectors in severe cases in posticteric period

Heptral (tabl. - 0.4 g, amp. - 0.4 g) 1-2 tabl. 3 times a day (20-25 mg/kg/day)

Essentiale (caps., amp.) 1-2 cap. 3 times a day Carsil (dragee) 1-2 dragee 3 times a day Hepabene 1-2 dragee 3 times a day Thiotriazolinum 1 tabl. 3 times a day Chophytol 1-2 tabl. 3 times a day

Treatment of fulminant form Straight bed regimen Diet N 5a with protein restriction up to 40% Intravenously:

prednizone 10-15 mg/kg/day divided in 4 equal doses

detoxication therapy (total – 50-100 ml/kg/day) with diuresis control;

extracorporeal detoxication in case of ineffective previous therapy plasmapheresis

hyperbaric oxygenation

Treatment of fulminant form in case of edema, ascytis – water-electrolyte balance

correction K-serving diuretics (verospiron, triampur) Fresh frozen plasma 10 ml/kg as coagulation factors

donator Heparin 100-300 IU/kg in possibility of DIC-

syndrome development Protease-inhibitors (trasilol, contrical, gordox) in

case of DIC-syndrome development Antibacterial therapy for bacterial complication

prevention (less hepatotoxic medicine) Enema and stomach-washing lactulose for 10-14 days

Discharge from the hospital, supervision, control

patients with mild and moderate forms can be treated at home;

discharge on 15-20 day of illness with the remaining phenomena (hepatomegaly, slight increased ALAT, ASAT, dysproteinemia);

Finish treatment in dispensary cabinet: first examination - in 7 days, then - in 1, 3, 6 months. In absence of the remaining phenomena - stop dispensarization;

can visit school on 40-50 day, release from physical education on 3-6 months, sport - 12 months

Prophylaxis of A hepatitis

Early isolation of ill person.Early isolation of ill person. Looking after contacts, laboratory test every Looking after contacts, laboratory test every

10 – 15 days.10 – 15 days. Personal hygiene.Personal hygiene. Disinfection in the epidemic focus.Disinfection in the epidemic focus. Passive prophylaxis by human immune Passive prophylaxis by human immune

globulin.globulin.

Prophylaxis of parenteral hepatitis

Early isolation of ill person.Early isolation of ill person. Sterilization of instrument.Sterilization of instrument. Passive prophylaxis by human immune Passive prophylaxis by human immune

globulin.globulin. For hepatite B For hepatite B active prophylaxisactive prophylaxis: after the : after the

birth, in 1, 6 months. When mother is birth, in 1, 6 months. When mother is HBs Ag HBs Ag positivepositive – after the birth, in 1,2, 12 months. – after the birth, in 1,2, 12 months.