VIRAL HEPATITIS

Dr.Abiy f.
Nov 2019
Arsi University
OUTLINE OF PRESENTATION
 Hepatitis definitions
 Discussion of each types of viral hepatitis
HEPATITIS

 • General term: inflammation of liver

 • Diseases of the liver
 – Infections (viral)
 – Toxins (alcohol, food, chemical)
 – Genetic (hemochromatosis)
 – Immune (autoimmune hepatitis (AIH),PBC)
 – Neoplasm (hepatocellular carcinoma (HCC)
 CLINICAL TERMS
 Hepatitis: inflammation of liver; presence of inflammatory
cells in organ tissue
 Acute Viral Hepatitis: symptoms last less than 6 months
 Acute Hepatic Failure:  Acute liver failure refers to the
development of severe acute liver injury with encephalopathy
and impaired synthetic function (international normalized
ratio [INR] of ≥1.5) in a patient without cirrhosis or
preexisting liver disease in <26weeks.
 Chronic Hepatitis: Inflammation of liver for at least 6
months
 Cirrhosis: Replacement of liver tissue fibrosis, scar tissue
 Fulminant Hepatitis: severe impairment of hepatic
functions or severe necrosis of hepatocytes in the absence
of preexisting liver disease
ACUTE VIRAL HEPATITIS
 Acute viral hepatitis is a systemic infection
affecting the liver predominantly.
 Almost all cases of acute viral hepatitis are
caused by one of five viral agents:
 Hepatitis A virus (HAV)
 Hepatitis B virus (HBV)
 Hepatitis C virus (HCV)
 HBV-associated delta agent or hepatitis D virus
(HDV), and
 Hepatitis E virus (HEV).
ACUTE VIRAL HEPATITIS
 All types of viral hepatitis produce clinically
similar illnesses.
 These range from asymptomatic and
inapparent to fulminant and fatal acute
infections common to all types,
 on the one hand, and from subclinical
persistent infections to rapidly progressive
chronic liver disease with cirrhosis and even
hepatocellular carcinoma, common to the
blood borne types (HBV, HCV,and HDV), on
the other.
CHRONIC HEPATITIS
 Chronic hepatitis represents a series of liver
disorders of varying causes and severity in
which hepatic inflammation and necrosis
continue for at least 6 months.
 Milder forms are non progressive or only
slowly progressive, while more severe forms
may be associated with scarring and
architectural reorganization, which, when
advanced, lead ultimately to cirrhosis.
CHRONIC HEPATITIS-ETIOLOGIES

 chronic viral hepatitis

 drug-induced chronic hepatitis
 autoimmune chronic hepatitis
 Idiopathic
CHRONIC VIRAL HEPATITIS
 Both the enterically transmitted forms of
viral hepatitis, hepatitis A and E, are self-
limited and do not cause chronic hepatitis .
 In contrast, the entire clinicopathologic
spectrum of chronic hepatitis occurs in
patients with chronic viral hepatitis B and C
as well as in patients with chronic hepatitis D
superimposed on chronic hepatitis B.
 VIRAL HEPATITIS-TYPES
Virus Source Transmission Chronicity Prevention

A Stool Feco-oral No Immunoglobulin

Vaccination

B Parentral Percutanous Yes Immunoglobulin

Vaccination
per mucosal
Immunoglobulin
Vaccination

C Parentral Percutanous Yes Blood donor screening

Risk behavior
per mucosal
modification

D Parentral Percutanous Yes HBV Prevention

per mucosal

E Stool Feco-oral No Safe water cleaning

HEPATITIS A VIRUS: HAV

 27nm RNA picornavirus

 4 capsid proteins; 1 serotype
 Virus not cytopathic to hepatocytes; causes
liver injury by stimulating both cellular and
humoral immune responses
HEPATITIS A VIRUS: HAV
 Epidemiology: fecal-oral viral transmission
 • Associated with
– Poor hand washing
– Poor personal hygiene habits
– Inadequate sanitation
– Day-care centers
– Institutionalized populations
– Endemic areas of world
HEPATITIS A VIRUS: HAV
 Symptoms
 – Onset usually abrupt, lasting 1-2 weeks
 – Acute disease, self-limiting, most recover
fully
 More commonly seen in children and
adolescents
 More virulent in middle age and older
 – Diagnosis may be missed: under-reporting
 Rarely complications (0.4%)
 Symptoms
 Vague: flu-like complaints, onset abrupt
 Abdominal pain, diarrhea, fatigue, fever,
headache,
 malaise, anorexia, myalgia, arthralgia,
 nausea/vomiting, sore throat, hepatomegaly,
 hepatic tenderness
 Jaundice: adults ~50-80%; rare in children so
usually not clinically detected
 Urine: amber color, ‘dark’
SEROLOGICAL MARKERS:HAV

 – Virus present in blood briefly (shed in stool)

 – By the time symptoms appear, antibody in
serum HAVAB – present 4 weeks after
infection
 IgM - acute disease (1-8 weeks after onset of
symptoms)
 IgG – immunity after 2 months, continuing for
years
LABORATORY:FOR HAV

 – Test for presence of HAV antibody = HAVAB

• HAVAB-IgM (acute infection)
 • HAVAB-total (IgM and IgG: past infection)
 – Monitor disease with liver enzymes and
bilirubin
• AST, ALT >3XULN (~500-1000 U/L)
• Total bilirubin: increased (~1.1-9.0 mg/dl)
• Urine bilirubin: positive
COMPLICATIONS OF HAV
 Relapsing hepatitis
 cholestatic hepatitis
HEPATITIS B VIRUS: HBV

 42 nm DNA enveloped hepadnavirus virus

 with several surface markers

HEPATITIS B VIRUS: HBV
 >400 million in the world (most are
asymptomatic)
 5-20% carriage in developing countries
 HCC can occur in situ
 Infected patients manifest hepatitis B in
virtually all body fluids; concentration of
virus and infectivity of fluids vary
 Different surface protein determinants and
genotypes (useful for epidemiology and
prognosis)
HEPATITIS B VIRUS: HBV
 Epidemiology: blood-borne pathogen
 – Percutaneous, permucosal, parenteral
 • Associated with
 – Contaminated needles
 – Accidental needle stick
 – Body piercing, tattooing
 – Hemodialysis
 – Sexual contact
 • Rarely associated with blood transfusion
 – Blood/blood products screened for HBsAg
HBV;PREVENTION

 – Standard precautions
 – Passive immunity with HBIG (Hepatitis B
 Immune Globulin)
 – Active immunization with hepatitis B
 recombinant vaccine (3 dose regimen)
HEPATITIS B VIRUS: HBV
 Symptoms
 Onset insidious, sometimes lasting 1.5 – 6
months (avg ~ 60-90 days)
 Clinical course variable: ~66% asymptomatic
or mild flu-like illness
HEPATITIS B VIRUS: HBV
 Symptoms:
 Not all recover from acute disease:
 Fatal (fulminant course): 0.5-1.0% of HB cases
 Chronic (never recover): 10-15% of all HB
cases
 2-10% adults
 80-90% of infants infected during first year of life
 30-50% children infected at 1-4 yrs old
HEPATITIS B VIRUS:HBV
 Symptoms
 – More severe symptoms compared to HAV:
 Abdominal discomfort, diarrhea, fatigue,
 hepatomegaly, hepatic tenderness, malaise,
anorexia, fever, nausea, vomiting
 Jaundice: ~30-50% adults
 Urine: amber color, ‘dark’
HBV:SEROLOGICAL MARKERS

 Virus and antibodies are found in serum

 Hepatitis B has the largest number of
diagnostic tests of any of the hepatitis
viruses
 more complicated interpretation of results
 HBsAg HBsAB
 HBcoreAB-IgM HBeAg
 HBcoreAB-total HBeAB
 HBV DNA
HBV:LABORATORY

 Test for presence of antigens and antibodies

 Monitor disease with liver enzymes, bilirubin
 AST, ALT >3xULN (~1000-4000 U/L)
 Total bilirubin: rarely >10.0 mg/dl
 Urine bilirubin: positive
HBSAG: SURFACE ANTIGEN
 Most widely used marker for detection of
current hepatitis B infection
 First serological marker to appear during
prodrome of acute infection with HBV
 Appears at 14 days, disappears by 4 months
 Presence for more than 6 months indicates
chronic infection and/or the carrier state
HBCOREAG: CORE ANTIGEN
 Found in the core of the intact virus
 Not found in serum: lab does not test for this
 May be found in infected liver cells
 Identified by liver biopsy
HBCOREAB: CORE ANTIBODY
 Most commonly detected AB against HBV
 Does not confer immunity to HBV
 Usually develops before HBsAB is detectable
HBCOREAB: TWO TESTS
AVAILABLE
 1. HBcoreAB-IgM:
 Acute marker, becomes undetectable within ~1-2
months
 – Indicates the level of infectivity has decreased,
but the disease is still active
 – Persistence for 6 months indicative of
progression to chronic HBV infection
HBCOREAB: TWO TESTS
AVAILABLE
2. HBcoreAB-total:
– Detects IgG (and IgM if present)
– Indicates previous infection: detectable in 97%
– Not a protective antibody
CORE WINDOW
 May be only marker to indicate acute HBV
infection
 Period of time when:
 HBsAg is negative or not detectable and
HBsAB not present and HBcoreAB-IgM is
positive
 Present in acute and chronic infections
HBSAB: SURFACE ANTIBODY
 Last antibody to appear: IgG
 Indicates clinical recovery from HBV
infection
 Confers lifelong immunity to HBV infection
 Only marker found in people receiving HB
vaccine
HBEAG: ENVELOPE ANTIGEN
 Rarely used as a marker of acute HBV
infection
 Typically used in patients with chronic HBV
and in HBV carriers
 Persistence for 6-8 weeks suggests chronic
carrier state and/or chronic liver disease
 In chronic HBV and HBV carriers:positive
HBeAg indicates active viral replication and
high infectivity state
HBEAB: ENVELOPE ANTIBODY
 Typically used in patients with chronic HBV
and in HBV carriers
 Indicates clearance of HBeAg
 Indicates decreasing viral replication
(conversion to nonreplicating viral state)
 decreased infectivity (goal of antiviral
treatment)
HBV DNA
 Often measured using amplified PCR
technique

 – Clinically significant viremia: ~100,000

copies/ml
 – Levels used to determine likelihood of
response to treatment
HEPATITIS D VIRUS: HDV

 Incomplete 35-40 nm RNA particle

 Hepatitis B-associated delta virus
 HDV is coated with HBsAg and is dependent
on HBV virus for its activation (satellite virus)
HEPATITIS D VIRUS: HDV
 Requires a co-infection with HBV for viral
replication: found only with concurrent HBV
infection
 Serologic markers not routinely measured
 HDVAg : Present only a few days
 Detected in acute infection
 HDVAB: Excellent marker of exposure to HDV
 Patient may still transmit HDV infection(antibody
not protective)
HEPATITIS D VIRUS: HDV
 Highly infectious: no vaccine, no immunity
 Associated with IV drug abuse
 Same route of transmission as HBV
 More serious disease as compared to HBV
alone: poor prognosis (no carrier state)
 If survive, are at high risk of cirrhosis and
HCC
 – Fulminant hepatic failure
HEPATITIS D VIRUS: HDV
 “Superinfection” – person already had
chronic Hepatitis B at the time of exposure
to HDV
 “Co-infection” – patient becomes infected
with both viruses at the same time
 Suspect in patient with chronic HepB but
condition worsens
HEPATITIS C VIRUS: HCV
 Single stranded enveloped RNA flavivirus
 Cause of majority of cases previously known
as non-A, non-B hepatitis
 First recognized in 1989
HEPATITIS C VIRUS: HCV
 Most common cause of chronic hepatitis in
North America, Europe and Japan
 High prevalence in general population:
 ~ 200 million worldwide
 ~ 4.5 million infected in US
 ~ 230,000 new cases per year in US
 ~ 8,000-10,000 deaths per year in US
HEPATITIS C VIRUS: HCV
 Expected to be major burden to US health
 care system in next 20-30 years
 • >85% develop chronic hepatitis C
 Hepatic fibrosis 􀃆 cirrhosis within 20 yrs,
 HCC in +30 yrs
HEPATITIS C VIRUS: HCV
 80-90% of HCV infections related to blood
 – Hemodialysis from years ago
 – Tattoo parlors
 – Health care workers
 – IV drug users make up the largest
percentage
 – Blood transfusions prior to 1990 when ARC
began screening for HCV antibody
 Vertical and sexual transmission inefficient
HEPATITIS C VIRUS: HCV
 No vaccine available
 • No completely effective treatment
 • Liver transplant
HEPATITIS C VIRUS: HCV
 Symptoms
 – Majority of infected patients are
asymptomatic
 – Vague flu-like symptoms often go unnoticed
 – Jaundice ~25%
HEPATITIS C VIRUS: HCV
 Serological marker:
 HCV antibody detected in
 – 50-70% patients at onset of symptoms
 – 80% patients at 5-6 weeks post initial
infection
 – 90% patients at 3 months post initial
infection
 – Not protective: no immunity
HEPATITIS C VIRUS: HCV
 Laboratory:
 HCV antibody Used to diagnose
 – Indicates active infection with HCV
 – Patient considered to be infective
 Present in acute and chronic infection
 – Current assays can detect AB 9 weeks post
exposure (method dependent)
HEPATITIS C VIRUS: HCV
 HCV RNA: tests for the RNA genomic
fingerprint(1,2,3 & 4)
 AST and ALT
 Levelsfluctuate widely after infection
 – Normal in ~33% of chronic HCV patients
 HCV-antibody is not protective: patients are
considered to be infective
EXTRAHEPATIC
MANIFESTATIONS OF HBV &HCV
 a serum sickness–like syndrome in 5-10% of
HBV
 Glomerulonephritis with the nephrotic
syndrome
 Generalized vasculitis (polyarteritis nodosa)
 mixed cryoglobulinemia(EMC)
 HCV infection may be complicated by hepatic
steatosis,hypercholesterolemia, insulin
resistance (and other manifestations of the
metabolic syndrome), and type 2 diabetes
mellitus.
HEPATITIS E
 enterically transmitted virus
 causes clinically apparent hepatitis primarily
in India, Asia, Africa, and Central America; in
those geographic areas, HEV is the most
common cause of acute hepatitis
 one-third of the global population appears to
have been infected.
 a 27- to 34-nm, nonenveloped, HAV-like virus
 with a 7200-nucleotide, single-strand,
positive-sense RNA genome.
HEPATITIS E
 Hepatitis E virus (HEV) RNA virus of the genus
Hepevirus
 Enterically transmitted infection; fecal-oral
route, typically self-limited
 Most outbreaks occur in developing countries.
 Symptoms of acute hepatitis
 Incubation period of hepatitis E virus is 2-9
weeks
 Case fatality rate is 4%
 Currently, availability and reliability of
serologic/virologic testing for HEV infection
is limited but can be done in specialized
laboratories.
HEPATITIS E: DIAGNOSIS
 Serum, liver, and stool samples can be tested for
HEV RNA
 Anti-HEV antibodies:
 IgM (acute)
 IgG (chronic)

AST & ALT are elevated several days before the onset
of symptoms; return to normal within 1-2 months
after the peak severity of disease.
Treatment: supportive
FULMINANT HEPATITIS
 Severe hepatic necrosis is Rare condition
 Fulminant hepatitis is seen primarily in
hepatitis B(>50%), D, and E(1-2% in pregnant
20%), but rare fulminant cases of hepatitis A
& C.
 Patients usually present with signs and
symptoms of encephalopathy that may
evolve to deep coma. The liver is usually
small and the PT excessively prolonged.
CONT…
 The combination of rapidly shrinking liver
size, rapidly rising bilirubin level, and
marked prolongation of the PT, even as
aminotransferase levels fall, together with
clinical signs of confusion, disorientation,
ascites, and edema, indicates that the
patient has hepatic failure with
encephalopathy.
 Mortality rate is > 80%
 Treatment-liver transplantation
THANK YOU!!!