Acute Viral

Hepatitis
FAKULTAS KEDOKTERAN
UNIVERSITAS ISLAM SUMATERA UTARA
2013
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.
 Etiology
Major agents:
 HAV
 HGV
 HBV

 HCV
 TTV

 HDV  HFV ?
 HEV
Minor agents:
 EBV,CMV

 HSV,VZV

 Rubella,Measles

 CoxsackieB
 Adenovirus
 Transmission
HAV HBV HCV HDV HEV

Fecal-oral
+ - - - +
Percutan.
+ + + + -
Perinatal
- + + + -
Sexual
+ + + + -
 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
 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 % )
 Sexual transmission of HCV

 Multiple sexual partner

 HIV and STD

 Anal sex

 Open sore

 Sex during menstruation

 Pathology
 Infiltrationof mononuclear cells
 Hepatic cells necrosis

 Kupfer cells hyperplasia

 Variable degrees of cholestasis

 In more severe cases;

Bridging necrosis
 Clinical Stages
 Incubation period
 Prodromal (preicteric) phase

 Icteric phase

 Convalescence
Variation in staging
Asymptomatic

Anicteric

Fulminant

Chronic
 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)

 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

 Icteric Phase
 Clinical jaundice
 Dark urine : 1-5 days before jaundice

 Patient may feel better

 Resolution of fever

 Pruritus
Icterus
Icterus
Jaundice
 Icteric Phase
 Liveris enlarged,tender
 Cervical adenopathy(10-20%)

 Splenomegaly(10-20%)

 Fever is absent

 Encephalopathy :Irritability, lethargy,

confusion
 Convalescence
 Resolution of symptoms
 Liver is enlarged

 Pruritus

 Complete recovery:

1-2 months A,E

3-4 months B,C (3/4)
 Laboratory Findings
 CBC :leukopenia, lymphocytosis
 Normal Hb; except haemorrhage

 Normal platelet; except DIC

 ESR is normal
 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
 Serologic Diagnosis
 IgM anti-HAV
 HBs Ag and Ig M anti-HBc

 HCV Ab, HCV RNA PCR

 anti-HDV

 anti-HEV
 Complications
 HepatitisA : Relapsing hepatitis
 Cholestatic hepatitis

 Chronicity : HBV,HCV,HDV

 Fulminancy : HAV, HBV, HDV, HEV

 Diferential Diagnosis
 Viralhepatitis by minor agent
 Gram negative Sepsis

 Cholangitis, cholecystitis

 Acute on chronic hepatitis

 Drug-related hepatitis

 Ischemic hepatitis
 Management
Indication of admission:
 Bilirubin>20 mg/dl

 Hypoglycemia

 Abnormal PT

 Hypoalbuminemia
 Poor oral intake
 Mental change,letargy

 Low compliance

 Other chronic disease

 Management
 Restriction activity
 Drug &Alcohol avoidance

 Isolation is not necessary, unless

special cases
 Symptomatic
 Monitoring
 Regular physical examination
 Liver size, mental state, icterus

 Check of LFT, PT, Bilirubin

 Serial check of HBsAg and

HCVAb
 Prevention
 Hand washing, hygiene
 Universal percaution
 No sharing of personal items
(razor, toothbrush, nail clipper)
 Sexual barrier
Chronic Viral
Hepatitis
 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)
 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)
 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
 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.
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. α1-AT Histology

 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
 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
Natural history of HCV infection
Acute hepatitis

85% 15%

Persistent infection Recovery and clearance

of HCV-RNA

60-70%

Chronic hepatitis

20-30%
~5%

Liver cirrhosis HCC

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
 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 %
 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.
Natural history of HBV infection
1%
Acute hepatitis Fulminant hepatitis

10% 90%

Persistent infection Recovery and clearance

of HBV-DNA

2-3%

Chronic active hepatitis Carrier state

1% 100-fold risk

Liver cirrhosis HCC

Natural History of Chronic HBV
Infection
Compensated
Resolution Cirrhosis
Stabilisation

Acute Chronic Liver

Cirrhosis Cancer
Death
Infection Hepatitis

Chronic Progression Decompensated

Carrier Cirrhosis
(Death)
30–50 Years

Adapted from Feitelson, Lab Invest 1994

Healthy Liver Liver Fibrosis

Cirrhosis Liver Cancer

 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)
 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)
Serological markers in hepatitis B
 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
 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
 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
 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
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