Persistence of the virus. Hepatitis D

Need virus hepatitis B for its replication, develops only in infected HBV patients.

Classification

Type: -

• typical (jaundice);

• atypical:

- without jaundice (unicteric hepatitis);

- effaced;

- subclinical hepatitis;

- cholestatic hepatitis;

- fulminant hepatitis.

Severity: •mild

• moderate

• severe Course:

• acute (2-3 months);

• prolonged (3-6 months);

• chronic. Periods:

• incubation

• pre-icteric (prejaundice)

• icteric (jaundice)

• post-icteric (postjaundice)

• recovery

Diagnostic criteria of incubation period

• absence of clinical signs

• viral antigens are present in blood

• alanine aminotranspherase, aspartate aminotranspherase may be enlarged. Prodromal (prejaundice, preicteric) period

• headache

• rashes (often in HBV-hepatitis)

• arthralgias ' Carole's triad

• "flu like syndrome"

• dyspepsia

• hepatomegaly, pain in right hypochondrium, epigastrium

• in the end - appearing of clay-colored stools

• enlargement of ALAT and AS AT, urobilinuria, special hepatitis markers.

Laboratory tests Prodromal period

• Enlargement ofALAT and AS AT, urobilinuria.

• Anti-HAV Ig M, HAV-RNA (hepatitis A).

• HBsAg, HBeAg, HBV-DNA and anti-HBc IgM (hepatitis B).

• HBsAg, HBeAg, HBV-DNA, anti-HBc IgM and HDVAg, HDV-RNA (hepatitis

delta coinfection).

• HCV-RNA (hepatitis C).

• Anti-HEV Ig M, HEV-RNA (hepatitis E). Jaundice (icteric) period

• jaundice of mucous membranes, sclera, and skin (photo 93,94)

• urobilinuria, bilirubinuria

• hepatomegaly (photo 95), tenderness of liver

• ALAT and ASAT are maximally enlarged

• hyperbilirubinemia with conjugate bilirubin prevalence

• skin rashes

• hemorrhagic syndrome

• splenomegaly Nonspecific tests

• enlargement of ALAT and ASAT,

• hyperbilirubinemia with conjugate bilirubin prevalence,

• presence 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

Specific tests (markers)

• Anti-HAV Ig M, HAV-RNA (hepatitis A).

• HBsAg, HBeAg, HBV-DNA and anti-HBc IgM (hepatitis B).

• HBsAg, HBeAg, HBV-DNA, anti-HBc 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).

Aminotranspherases level	5-10 times more than norm	10-15 times more than norm	15-30 times more than norm
Protrombin index	70-80 %	60-70 %	<60%
Tymol test	Mild increased	Moderately increased	Very increased
Normalization of the liver sizes	On 25-35 day from the beginning	On 40-50 day	On 50-60 day
When the jaundice appears the toxic sign	Decreased	Continue for 2-3 days	Continue, sometimes increases
Splenomegaly	—	In 1.5%	Is typical
Diuresis	Normal	Decreased	Severe decreased
Sulemic test	Normal	Normal	Decreased
Duration of icteric phase	7-10 days	1-2 wks	2-3 wks

Posticteric period

• Urine becomes lighter

• Stools-darker

• Jaundice fades

• Decreasing of the liver sizes

• Normalization of bilirubin, ALAT and ASAT, other indexes, later - sediment tymol test.

• Anti-HAV Ig G, HAV-RNA (hepatitis A).

• Anti-HBc IgM, anti-HBe IgM, later- anti-HBc (total) IgM and anti-HBc IgG

(hepatitis B).

• Anti-HBc IgM, anti-HBe IgM, later- anti-HBc (total) IgM and anti-HBc 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). Fulminant form criteria:

- Acute failure of the liver

- Confusion and drowsiness

- Delirium and convulsions

- Liver sizes are reduced

- Coma I-IIECG is abnormal

- Hepatic smell from the mouth

- Hemorrhagic syndrome

- Encephalopathy

- Decreasing of diuresis

- Total bilirubin is increased

- Protrombin time is prolonged

- Decreasing of ALAT, ASAT

- Decreasing of proteins

Atypical (unicteric, effaced, subclinical) forms criteria:

- Contact with patient who had hepatitis

- Hepatomegaly

- Increasing of ALAT, ASAT, tymol test

- Absence of other clinical signs (or they are minimal)

Outcome of the disease

For HAV,HEV

- Recovery

- Residual fibrosis of liver (posthepatitis hepatomegaly)

- Biliary dyskinesia

- Chronic cholecystitis and cholecystocholangitis

For HBV, HCV, HDV

- Recovery

- Residual fibrosis of liver (posthepatitis hepatomegaly)

- Biliary dyskinesia

- Chronic cholecystitis and cholecystocholangitis

- Transition in chronic hepatitis;

- Cirrhosis

- Hepatic carcinoma

- Death

Diagnosis example: Hepatitis A, typical form, icteric period, mild severity, acute course.

Differential diagnosis

Prejaundice period:

- viral upper respiratory tract infections,

- bowel infection,

- acute appendicitis,

- helmintic diseases,

- acute pancreatitis. Jaundice period:

- suprahepatic icterus (hemolytic anemia),

- hepatic icterus (Gilbert, Crigler-Najjar syndrome, infectious mononucleosis,

leptospirosis, pseudotuberculosis, congenital liver diseases),

- subhepatic icterus (mechanical jaundice).

Intoxication in preicteric period	Mild	Moderate	Mild	Moderate	Often moderate
Intoxication in icteric period	Severe	Mild	Absent or mild	Absent or mild	Severe
Allergic rashes	Maybe present	Absent	May be present	Absent	May be present
Severity	Often moderate and severe	Mild and moderate	Mild and moderate	Mild	Severe and fulminant
Duration of the icteric period	3-5 wks	1-1.5 wks	2 wks	1-2 wks	2-8 wks
transition in chronic hepatitis	Often - primary chronic	-	In 50 %	-	Often
Tymoltest	Often normal	Elevated	High	High	Moderately elevated
Specific markers	HBsAg HBeAg anti HBc IgM	Anti HAV IgM	Anti HCV Ig HCV RNA	Anti HEV IgM	HBsAg, anti HBc, anti HDV IgM

Treatment: Basic treatment:

- bed rest up to intoxication disappear,

- semi-bed rest (up to icterus disappear, normalization of ALAT, ASAT),

- special diet (diet N 5):

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

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

daily.

Treatment of mild hepatitis - only basic therapy 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^rd week of disease:

• cholagon,

• allocholum,

• cholenzym,

• galstena,

• hepabene.

Treatment of severe hepatitis

• basic therapy,

• intravenous detoxication therapy (total - 50-100 ml/kg/day):

- 0.9 % NaCl, Ringer's solution,

- Ringer's lactate solution,

- 5 % glucose,

- albumin 5 ml/kg;

• enterosorption 2-3 wks,

• lactulose for 10-14 days,

• deoxycholic 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): in daily dose 2-3 mg/kg 4 times per day divided in equal doses during 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

• Strict bed rest,

• 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:

• 0.9 % NaCl, Ringer's solution,

• Ringer's lactate solution,

• 5 % glucose,

• albumin 5 ml/kg;

• Extracorporeal detoxication in case of ineffective previous therapy (plasmapheresis),

• Hyperbaric oxygenation,

• In case of edema, ascite - water-electrolyte balance correction,

• Potassium-saving 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.

Discbarge from the hospital, observation, 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 increasedALAT, ASAT, dysproteinemia);

• observation 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, Ј hepatitis

• Early isolation of ill person.

• Observation of contacts, laboratory test every 10-15 days.

• Personal hygiene.

• Disinfection in the epidemic focus.

• Passive prophylaxis by human immune globulin. Prophylaxis of parenteral hepatitis

• Early isolation of ill person.

• Sterilization of instrument.

• Passive prophylaxis by human immune globulin.

• For hepatitis B active prophylaxis: after the birth, in 1, 6 months. When mother is

HBs Ag positive - after the birth, in 1,2, 12 months.

Kev words and phrases: Viral hepatitis, hepatitis A virus, hepatitis B virus, viral antigens, alanine aminotranspherase, aspartate aminotranspherase, Carole's triad, "flu like syndrome", clay-colored stools, special hepatitis markers, prodromal period, jaundice period, conjugate bilirubin, bile pigments.

Test and assignments for self assessment

Multiple choices, choose the correct answer / statement:

1. Incubation period at viral hepatitis A lasts:

A. 3-7 days

B. 8-10 days

C. 7-14 days

D.7-21 days

E.10-45 days

2. The pre-jaundice period of viral hepatitis A is characterized by the increase of:

A. Indirect bilirubin, tymol test

B. Cholesterol,ALAT

C. Tymol test, alkaline phosphatase

D. Cholesterol, beta-lipoproteins, indirect bilirubin

E. ALAT, ASAT, direct bilirubin

3. Level ofbilirubin at the viral hepatitis A mild form is:

A. 10-15mcmol/l

B. Not higher than 82 mcmol/1

C. 100-120mcmol/l

D. 150-200mcmol/l

E. More than 200 mcmol/1

4. Atypical viral hepatitis A forms are:

A. Unicteric, effaced, subclinical

B. Fulminant, hypertoxic, effaced

C. Asymptomatic, hemorrhagic, unicteric

D. Generalized, effaced, asymptomatic

E. There is no right answer

5. Name hepatitis C markers:

A. Anti HAV IgM and anti HAV IgG B.AntiHCVIgM, viral RN A C.AntiHEVIgM, viral RN A

D. Anti HBV IgM and HBV IgG

E. HBsAg, HbeAg, HbcAg, anti HBV IgM, IgG

6. In case of hepatitis C infection chronic form develops in:

A. 2-5%

B. 10-20%

C. 20-50%

D. 50-70%

E. 50-100%

7. What diseases does it follow to differentiate the inborn hepatitis C from?

A. Hepatitis A, E, biliary dyskinesia

B. Sepsis, biliary atresia, TORCH-infections, massive hemorrhages

C. Sepsis, pseudotuberculosis, infectious mononucleosis

D. Gilbert syndrome, leptospirosis, hemolytic anemia

E. Hemolytic disease of new-born, hepatitis Delta, cholecystitis.

8. When does it follow to give choleretics at hepatitis B, moderate degree?

A. From the 1st day of jaundice period

B. From the 2nd week of jaundice period

C. From the 3rd week of jaundice period

D. From the 4th week of jaundice period

E. Does not need to give

9. Indicate a dose, number and duration of glucocorticoids administration at severe hepatitis B.

A. Prednisolone 10-15 mg/kg daily in 4 equal doses

B. Prednisolone 2-3 mg/kg daily in 2 equal doses for 3-5 days with sharp abolition

C. Prednisolone 1 mg/kg daily during a month, according to organism's rhythm, with gradual abolition

3. To inspect a patient:

Physical methods of examination of newborns and infants

1. Friendly facial expression and smile.

2. Gentle tone of speech.

3. Greeting and introducing.

4. Explain to the parents what examination should be performed and obtain there informed consent.

5. Prepare for examination(clean and warm hands, warm phonendoscope, etc.).
Physical methods of examination of toddlers and preschoolers

1. Friendly facial expression and smile.

2. Gentle tone of speech.

3. Greeting and introducing.

4. Explain to the parents what examination should be performed and obtain there informed consent.

5. Find a contact with a child; try to gain his/her confidence.

6. Prepare for examination(clean and warm hands, warm phonendoscope, etc.).
Physical methods of examination of school age children

1. Friendly facial expression and smile.

2. Gentle tone of speech.

3. Greeting and introducing.

4. Explain to the parents what examination should be performed and obtain there informed consent.

5. Find a contact with a child; try to gain his/her confidence.

6. Prepare for examination (clean and warm hands, warm phonendoscope, use the screen if necessary etc.).

A. Examination: icterus of skin, sclera, visible mucus membranes, rashes, excoriations,. hemorrhages, bleeding from mucosa, hemorrhage in the place of injections, "hepatic" palms.

B. Palpation: pain in right subcostal area, a liver is enlarged, dense, smooth, with acute or rounded border, shortening of liver sizes on a background of icterus increase; splenomegaly.

C. Percussion: positive Orthner's sign. Conversation accomplishment.

Informing about the results of examination

1. Friendly facial expression and smile.

2. Gentle tone of speech.

3. Greeting and introducing.

4. Explain to a child and his/her parents what examinations should be performed and obtain their informed consent.

5. Involve adolescent and his/her relatives in to the conversation (compare present examination results with previous ones, clarify whether your expectations are clear for them or not).

6. Conversation accomplishment.

4. To estimate the results of additional researches

• Complete blood analysis: leucopenia, lymphocytosis, the ESR acceleration, anemia.

• Analysis of urine: urobilinuria, bilirubinuria.

• Biochemical blood test: enlargement ofALAT andASAT, hyperbilirubinemia with conjugate bilirubin prevalence, marking of bile pigment in urine, enlargement of sediment tymol test, depression of sulemic test, decrease of protrombin index.

• Exposure of specific markers:

• For hepatitis A - anti HAV Ig M, anti HAV Ig G in serum.

• For hepatitis B - HBs Ag, HBe Ag, HBc Ag, anti HBe, anti HBe Ig M and Ig G, viral

DNA, DNA polymerase.

• For hepatitis C - anti HCV, viral RNA.

• For hepatitis D - HBsAg, anti HBS, anti HDV IgM.

• Explaining the results of examination to child's parents.

• Conversation accomplishment.

5. To substantiate the diagnosis

Planning and prediction of conservative treatment results

1. Friendly facial expression and smile.

2. Gentle tone of speech.

3. Greeting and introducing.

4. Explain to child's parents the necessity of further treatment directions correctly and accessibly.

5. Discuss with parents and their child the peculiarities of drug intake, duration of usage, side effects and find out whether they understand your explanations.

6. Conversation accomplishment.

6. To prescribe the treatment:

Basic therapy: regime, diet, vitamins, choleretics (from the 3^th week of illness), oral detoxication; parenteral detoxication, corticosteroids, hepatoprotectors, protease inhibitors, heparin, diuretics, probiotics.

Intensification: enterosorption, interferon.

Informing about treatment prognosis

1. Friendly facial expression and smile.

2. Gentle tone of speech.

3. Greeting and introducing.

4. Correct and clear explanation of expected results of treatment.

5. Discuss with the parents and their child the importance of continuous treatment, following the treatment scheme; make sure that your explanations are properly understood.

6. Conversation accomplishment.

Step

1. The child, 8 years old, was treated because of the hepatitis B. He was discharged from the hospital on 35* day. Objectively: jaundice is absent; liver emerges from the rib arc on 1.5 cm, with normal elasticity. In biochemical blood test: total bilirubin is 18.39 mcmol/1, AST - 0.68, ALT- 0.72. What is the duration of dispensary observation?

A. 3 months

B. 6 months

C. 9 months

D. 12 months

E. 18 months

2. The boy, 14 years old, was treated because of the hepatitis A, moderate degree. He was discharged from the hospital in satisfactory condition. In biochemical blood test: total bilirubin is 15.39 mcmol/1; AST- 0.72; ALT- 0.78. In what time it is necessary to repeate biochemical blood test?

A. In 1,3,6 months

B. In 1,2,4 months

C. In 1,3,6,9 months

D.In2,4,6,8 months

E. In 1,3,6,12 months

3. The child, 8 years old, complains of pain in knee joints, weakness, jaundice of the skin and visible mucous membranes, appearing of the rash on limbs, around joints. The spleen is enlarged to +2 cm and liver - to +3 cm, moderately compacted. 4 months ago the child had operation. In biochemical blood test: total bilirubin is 98.26 mcmol/l; direct- 66.2; AST- 2.12; ALT-2.65. Hepatitis B was suspected. What disease must be differentiated at the first place?

A. Hepatitis A

B. Infectious mononucleosis

C. Pseudotuberculosis

D. Mechanical jaundice

E. Hemolytic anemia

Real situation to be solved:

1. The child, 9 years old, is ill for 6 days. The disease has begun with increasing of the temperature to 37.6 °C, weakness, and poor appetite. On the third day was noted the abdominal pain (in epigastrium and right subcostal region). On the 5^th day have appeared clay-colored stools, dark urine (like beer). Today has appeared jaundice of sclera and skin. During objective examination: liver +2.5 cm, compacted, painful. Orthner's symptom is positive.

1. Name the initial diagnosis.

2. What diseases it must be differentiated from?

2. The child, 5 years old, is treated because of hepatitisA. The intensity of the jaundice, pain and dyspeptic syndrome is moderate. The liver emerges from the rib arc on 4 cm, compacted, painful. In biochemical blood test: total bilirubin is 126.34 mcmol/l, direct - 98.30, indirect - 28.04, AST-1.72, ALT-2.06.

1. Put clinical diagnosis.

2. Child visits kindergarten. What prophylaxis should be performed there?

Answer for the self-control

Test: 1.E; 2.E; 3. B; 4.A; 5. B; 6. C; 7. B; 8. C; 9. E; 10. B. Step: l.B:2.A:3.C.

Real - life situation 1:

1. Acute viral hepatitis

2. Mechanic (infrahepatic jaundice of different etiology) Real - life situation 2:

1. HepatitisA, typical jaundice form, moderate severity

2. Quarantine for 35 days:

• Everyday examination, thermometry, inspection of stools and urine color

• Investigation of ASAT and ALAT every 10 days for 35 days

• Disinfection

Aids and material tools: charts "Viral hepatitis", photo, video.

Result level

Students must know:

1. Etiology, epidemiology, pathogenesis of viral hepatitis.

2. Clinical diagnostic features of viral hepatitis.

3. Laboratory examination of patients with viral hepatitis.

4. Differential diagnosis of viral hepatitis.

5. Main treatment of viral hepatitis.

6. Prophylaxis of viral hepatitis. Students should be able to do:

1. Separate anamnesis data, which told us about viral hepatitis.

2. Find diagnostic criteria of viral hepatitis, while examining the patient.

3. To perform differential diagnosis among diseases, which have the similar clinical features.

4. To learn main tendentions of viral hepatitis treatment.

5. To perform prophylaxis of viral hepatitis.

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