1. Acute Viral
Hepatitis
FAKULTAS KEDOKTERAN
UNIVERSITAS ISLAM SUMATERA UTARA
2013

2. WHAT IS VIRAL HEPATITIS ?

A serious disease caused by virus that
attacks the liver . There are various strains
of viral hepatitis which can cause lifelong
infection, cirrhosis ( scarring) of the liver
, liver cancer , liver failure, and death.

3. Etiology
Major agents:
 HAV
 HBV
 HGV
 HCV
 TTV
 HDV
 HFV
 HEV
?

4. Minor agents:
 EBV,CMV
 HSV,VZV
 Rubella,Measles
 Coxsackie
B
 Adenovirus

7. Transmission
HAV
HBV
HCV
HDV
HEV
Fecal-oral
+
-
-
-
+
Percutan.
+
+
+
+
-
Perinatal
-
+
+
+
-
Sexual
+
+
+
+
-

8. Epidemiology
HAV:fecal-oral
HEV:fecal-oral
Rarely bloodborne
 HBV:percutaneous contact
Mucous membrane contact
Sexual contact
Perinatal:third trimester and
2 months postpartum
HDV : like HBV


9. Epidemiology

HCV:
Percutaneous transmission
Transfusion(0.1 %),needle stick(1.8 %)
Mucousal transmission (rare)
Sexual transmission is rare(monogamy)
Perinatal transmission is uncommon
(HIV coinfection,less than 5 % )

10. Sexual transmission of HCV
 Multiple
sexual partner
 HIV and STD
 Anal sex
 Open sore
 Sex during menstruation

11. Pathology
 Infiltration
of mononuclear cells
 Hepatic cells necrosis
 Kupfer cells hyperplasia
 Variable degrees of cholestasis
 In more severe cases;
Bridging necrosis

13. Clinical Stages
 Incubation
period
 Prodromal (preicteric) phase
 Icteric phase
 Convalescence

14. Variation in staging
Asymptomatic
Anicteric
Fulminant
Chronic

15. Incubation Period
 HAV:15-45
days(30)
 HBV: 30-180 days(60-90)
 HCV: 15-160 days(50)
 HDV: 30-180 days(60-90)
 HEV: 14-60 days(40)

16. Preicteric Phase
Systemic & nonspecific symptoms
 Flu-like syndrome & dyspepsia
 Fever, sore throat, cough, headache
 Fever, anorexia, malaise, nausea, vomiting,
abdominal pain

Duration : 1-2 weeks

17. Icteric Phase
 Clinical
jaundice
 Dark urine : 1-5 days before jaundice
 Patient may feel better
 Resolution of fever
 Pruritus

18. Icterus

19. Icterus

20. Jaundice

21. Icteric Phase
 Liver
is enlarged,tender
 Cervical adenopathy(10-20%)
 Splenomegaly(10-20%)
 Fever is absent
 Encephalopathy
:Irritability, lethargy, confusion

22. Convalescence
 Resolution
of symptoms
 Liver is enlarged
 Pruritus
 Complete recovery:
1-2 months A,E
3-4 months B,C (3/4)

23. Laboratory Findings
 CBC
:leukopenia, lymphocytosis
 Normal Hb; except haemorrhage
 Normal platelet; except DIC
 ESR is normal

24.  Serum
bilirubin : 5-20 mg/dl
 Direct bil ≥ indirect bil
 SGOT/SGPT = 400-4000 IU
 ALP : mild elevation
 PT is usually normal :
Severe hepatitis  prolonged PT
 Hypoglycemia

27. Serologic Diagnosis
 Ig
M anti-HAV
 HBs Ag and Ig M anti-HBc
 HCV Ab, HCV RNA PCR
 anti-HDV
 anti-HEV

28. Complications
 Hepatitis
A : Relapsing hepatitis
 Cholestatic hepatitis
 Chronicity : HBV,HCV,HDV
 Fulminancy : HAV, HBV, HDV, HEV

29. Diferential Diagnosis
 Viral
hepatitis by minor agent
 Gram negative Sepsis
 Cholangitis, cholecystitis
 Acute on chronic hepatitis
 Drug-related hepatitis
 Ischemic hepatitis

30. Management
Indication of admission:
 Bilirubin>20 mg/dl
 Hypoglycemia
 Abnormal PT
 Hypoalbuminemia

31.  Poor
oral intake
 Mental change,letargy
 Low compliance
 Other chronic disease

32. Management
 Restriction
activity
 Drug &Alcohol avoidance
 Isolation is not necessary, unless
special cases
 Symptomatic

33. Monitoring
 Regular
physical examination
 Liver size, mental state, icterus
 Check of LFT, PT, Bilirubin
 Serial check of HBsAg and
HCVAb

34. Prevention
 Hand
washing, hygiene
 Universal percaution
 No sharing of personal items
(razor, toothbrush, nail clipper)
 Sexual barrier

35. Chronic Viral
Hepatitis

36. Chronic hepatitis (CH)

Definition: chronic necroinflammatory injury
characterized
by
liver
cell
necrosis
and
inflammation lasting more than 6 months that
can lead insidiously to liver cirrhosis, end-stage
liver disease and hepatocellular carcinoma.

Prevalence: ~ 2-3% of the population
(Hungary)

37. Major causes of chronic
hepatitis


Chronic hepatitis C (70-80%)
Chronic hepatitis B (10-20%)

Chronic hepatitis D
Chronic autoimmune hepatitis (<10%)
Wilson’s disease
Haemochromatosis

α1-Antitrypsin deficiency

Drug-induced chronic hepatitis
Cryptogenic hepatitis (non-A-E hepatitis)





38. Clinical appearance of CH

mostly asymptomatic
~20%: mild fatique; rarely: mild RUQ pain

discovered by screening lab tests:
- mildly elevated ALT and AST (<10x ULN);
- ALT>AST
- AP and γ-GT: normal or minimally elevated

progression to cirrhosis is slow: years, decades

39. Late symptoms of CH

Marked symptoms only in the stage of
cirrhosis:
marked fatique, muscle weakness and wasting,
poor appetite, nausea, weight loss;
dark urine, jaundice, itching;
abdominal swelling, ascites, edema,
UGI bleeding,
hepatic encephalopathy, etc.

40. Diagnostic tests for chr. hepatitis
Type of CH
Screening test
Confirm. test
CHC
Anti-HCV
HCV RNA
CHB
HBsAg, anti-HBc
HBV DNA,
CHD
Anti-HDV
HDV RNA
Autoimmune
ANA, SMA, anti-LKM Excl. of others,, histology
Wilson’s dis.
Coeruloplasmin
Urine and hep. copper
Haemochromatosis Se iron, TFS
histology, genetic testing
α1-AT def.
Histology
α1-AT

42. Chronic hepatitis C (CHC)

Hepatitis C is a common infection with variable course

170 million infected pts worldwide

CHC can led to liver cirrhosis and hepatocellular
carcinoma (HCC)

2nd or 3rd most common cause of liver cirrhosis and
HCC

No effective vaccine at present

Prevention: avoidandance of high-risk behaviors

43. Risk Factors Associated with
Transmission of HCV
• Illegal injection drug use
• Transfusion or transplant from infected donor
• Occupational exposure to blood
– Mostly needle sticks
• Iatrogenic (unsafe injections)
• Birth to HCV-infected mother
• Sexual/household exposure to anti-HCV
positive contact
• Multiple sex partners

44. Natural history of HCV infection
Acute hepatitis
85%
15%
Recovery and clearance
of HCV-RNA
Persistent infection
60-70%
Chronic hepatitis
20-30%
Liver cirrhosis
~5%
HCC

45. Factors promoting the progression of
CHC

High viral dose, genotype 1, quasispecies

Older age, male sex

Immunodeficiency

Alcohol abuse

Co-infection with HBV, HIV

Iron overload

Environmental contaminants, geography

47. Epidemiology of HBV

HBV is a common cause of viral hepatitis

400 million carriers worldwide

Prevalence in the population of developed countries:
carriers: 1%, anti-HBsAg +: 10 %;
incidence: 35 per 100 000 in a year;
in the 3rd world (Far/Middle East):
carriers: 8%; anti-HBsAg +: 50 %

48. Transmission of HBV
HBV is present in all body fluids and secretions!

Highly contagious! Blood cc. may be as high as 1013/ml

Vertical transmission: in the perinatal period; > 90%

Horizontal transmission:
by blood, blood products, surgery
injection-drug abuse, needle-stick injury
sexual activity,
occupational exposure
household contact
tattooing, shaving, etc.

49. Natural history of HBV infection
1%
Acute hepatitis
10%
Persistent infection
Fulminant hepatitis
90%
Recovery and clearance
of HBV-DNA
2-3%
Chronic active hepatitis
1%
Liver cirrhosis
Carrier state
100-fold risk
HCC

50. Natural History of Chronic HBV
Infection
Resolution
Acute
Infection
Stabilisation
Chronic
Hepatitis
Chronic
Carrier
Compensated
Cirrhosis
Cirrhosis
Liver
Cancer
Progression Decompensated
Cirrhosis
(Death)
30–50 Years
Adapted from Feitelson, Lab Invest 1994
Death

51. Healthy Liver
Cirrhosis
Liver Fibrosis
Liver Cancer

52. Diagnosis of CHC

Screening for liver disease
elevated se ALT (<10x UNL)

Screening for HCV infection
se anti-HCV (enzyme immunoassay)

Confirmation: detection of viremia
se HCV RNA (rtPCR)

53. Diagnosis of CHB

Follow-up of patients with acute HBV infection

Screening for liver disease (elevated se ALT)

Screening for HBV infection
se HBsAg (enzyme immunoassay)

Confirmation: detailed serology;
detection of viremia se HBV-DNA (PCR)

54. Serological markers in hepatitis B

55. Evaluation of patients with CHB
and C

Clinical: signs and symptoms of chronic hepatitis;
evaluation of coexisting diseases

Laboratory: se
ALT, bilirubin, albumin, prothrombin
(se AP, GGT , Fe, transferrin
saturation, ferritin, renal function tests, autoimmune
markers)

Virological:
HBV: serology, se HBV-DNA; anti-HDV
HCV: se HCV-RNA, viral titer, genotype

Histological: liver biopsy histology

56. CHC: current therapies



Interferon-α: may eradicate HCV infection;
antiviral, immunoregulator, anti-inflammatory;
may inhibit fibro- and carcinogenesis;
costly, unpleasant (injection!); 5-20% efficacy
Interferon-α + ribavirin
doubled efficacy in HCV clearance
Iron reduction (venesections)
biochemical but not virological improvement;
improved responsiveness to IFNα

57. CHB: current therapies

Interferon-α: may eradicate HBV infection;
antiviral, immunoregulator, anti-inflammatory;
may inhibit fibro- and carcinogenesis;
costly, unpleasant, 20-30% efficacy

Lamivudine, adefovir, entecavir (virostatic drugs):
advantages: oral administration; well tolerable;
less contraindications
disadv.: relapse after discontinuation; escape;
long-term (>12 mo) treatment

58. Side effects of therapy
Interferon-alpha:


Early: flu-like illnes, fatique, cytopenias
Late: depression with suicidal
risk, psychosis, anorexia, weight loss, sepsis, thyroid
dysfunction, deteoriation of liver disease, hair-loss
Ribavirin:
• Dose-dependent, mild, reversible hemolytic anemia

59. Therapy of end-stage CHB and C:
liver transplantation




CHC is the leading indication for OLT
Antiviral pretreatment is advised
Recurrence of the infection is universal;
a great problem in hepatitis B infection;
survival rate is less affected by HCV
Therapy with IFN, ribavirin or lamivudine is
possible