ACUTE HEPATITIS

DR NJOKU
 Introduction

• The term hepatitis refers to any

inflammatory process causing hepatocellular
injury. (viruses, alcohol, drugs, autoimmune
etc)
• Hepatitis is clinically classified into acute
hepatitis and chronic hepatitis.

2
 DEFINITION
• Diffuse inflammation of liver parenchyma leading
to widespread damage to hepatocytes that
resolves within six months of the onset
• Incidence is quite common; data rely on public
health records or institutional reports. May not
reflect true burden due to underreporting and
asymptomatic cases
• Common causes are viral, alcohol and drugs
especially in certain patient groups e.g. HIV
infected Patients and those on anti-TB Rx
 Causes
• Infective-viral ,bacterial, parasitic
• Alcohol
• Drugs-Anti-TB drugs, Paracetamol overdose,
HAART (nevirapine/efavirenz)
• Chemical- halothane anaesthesia
• Metabolic-NAFLD/NASH
• Toxins/Poisons eg Amanita phalloides
(mushrooms), Aflatoxins
 Causes-viral & bacterial
• Hepatitis A,B,C,D, E(Hepatitis A and E >95% of viral causes)

• Non-hepatotrophic viruses- CMV, Herpes, Varicella, Epstein-Barr virus,

Coxsackie, Measles
• Others- yellow fever virus, Lassa fever, Ebola virus, Corona virus
--Bacterial hepatitis
-- E. coli, Klebsiella pneumionia, N. meningitidis, N, gonorrhoea,
Campylobacter sp, Lyme disease
– Leptospirosis(spirochaete)-Leptospia interrogans
– Q fever-Coxiella burnetti
– Rocky moutain spotted fever-(Rickettsia ricketsii
– Secondary syphilis(Spirochaete)-Treponema pallidum
– Typhoid fever-Salmonella typhi
– Sepsis
 Parasitic causes
• Parasites can also infect the liveR and activate
an immune response
• Examples- Entamoeba histolytica(Liver
abscess), Trypanosoma cruzi, Leishmania sp,
Plasmodium sp
• Dog tapeworm-Echinococcus
granulosus(Hydatid cysts), Liver flukes(Fasciola
hepatica, Clonorchis sinensis.
 PATHOLOGY
• Similar irrespective of cause
• Hepatocyte degeneration (swelling,
cytoplasmic granularity, vacuolation) and
necrosis
• Necrosis in three zones –A, B, C.
• Ranges from focal necrosis to massive, with
fulminant hepatic failure
• Fatty change in toxins and pregnancy
 Viral Viral Viral Viral Viral
Hepatitis A Hepatitis B Hepatitis C Hepatitis D Hepatitis E

Agent Hepatitis A Hepatitis B Hepatitis C Hepatitis D Hepatitis E

virus virus (HBV); virus (HCV); virus (HDV); virus (HEV);
(HAV); dsDNA ssRNA ssRNA ssRNA
ssRNA

Route of Fecal-oral Parenteral, Parenteral Parenteral Fecal-oral

Transmission Vertical,
Sexual.
Age affected Children Any age Adults Any age Young adults

Carrier state Nil Common Present Nil (only Nil

with HBV)

Incubation 10-50 days 50-180 days 40-120 days 2-12 weeks 2-9 weeks
period (avg. 25-30) (avg. 60-90)

Chronic No Yes Yes Yes No

infection
Specific Ig and Ig and Nil HBV vaccine Nil
8
Prophylaxis Vaccine Vaccine
 VIRAL HEPATITIS
A E B C D HGV

Genetic type RNA 27nm ? DNA 42nm RNA 30- RNA 36nm RNA 30-
60nm 60nm
Fecal route Yes Yes No No No No

Blood route Rare No Yes Yes Yes Yes

Vertical No No Yes Yes Probable No

Saliva Yes ? Yes ?Yes Yes No

Sexual Occasional No Yes Yes Yes ?

Incubation P 2-3 wks Short 1-5mts Intermediate Long 30-120?

14-160 days
Age of pts Young Any Any Any Any

Carrier state No No Yes Yes Yes Yes

Liver Ca No No Yes Yes Yes ?

Acute < 0.5% 1-2%, 10% in < 1% < 1% ?

mortality pregnant
Passive Imm Immunoglob - Hyerimmuno - - No
ulins globulins
Active immu Available None Vaccine None HBV vaccine No
 HEPATITIS A
• Commonest form, occurring mainly in childhood
• Excreted in feces for 2 weeks before clinical
jaundice, and one week after
• Other organs involved—heart, pancreas, etc
• Prodromal illness for 2 wks and improves with
appearance of jaundice
• Lasts 2-3 wks but may relapse or be fulminant
• Diagnosis - clinical, HAV IgM, stool electron
microcopy
 Introduction
• Hepatitis A refers to liver inflammation
caused by infection with the hepatitis A
virus(HAV).
• HAV has been known as infectious
jaundice since 1912.
• According to WHO, HAV had many
names in the past:
• Epidemic hepatitis
• Epidemic jaundice 11
 Epidemiology
• Globally, symptomatic HAV infections are believed
to occur in around 1.5 million people a year.
• In 2010, acute hepatitis A resulted in 102,000
deaths, which is slightly up from 99,000 in 1990.
• Hepatitis A is much more common in countries
with underdeveloped sanitation systems and, thus,
is a risk in most of the world.

• HAV is a common infection in developing nations of Africa, Asia, and

Central and South America.
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 HEPATITIS A VIRUS
• Naked RNA virus
• HAV is an enterovirus type 72 of the
Picornaviridae family and genus Hepatovirus
• Previously known as enterovirus(type 72).
• One stable serotype only.
• 7 genotypes exist(four human & three simian)
• Human and vertebrates serve as natural hosts.
• Replication in hepatocytes.

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 Contd…..
• Fairly resistant to low pH, heat and chemicals.
• Survives more than 10 weeks in well water.
• Resistant to heat at 60 degree Celsius for 1 hr.
• Not affected by chlorination.
• Formalin-effective disinfectant.
• Virus inactivated by UV rays, boiling(5
minutes) or autoclaving.

15
 Infective material
• Mainly man’s faeces
• Blood, serum and other fluids(during stage of
viraemia)
• HAV is excreted in faeces for about 2 weeks before
onset of jaundice and for up to 2 weeks thereafter.
• Also excreted in urine.

16
 Period of infectivity
• Risk of transmitting HAV is greatest from 2 weeks
before to 1 week after the onset of jaundice.
• Infectivity falls rapidly with the onset of jaundice.

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CONCENTRATION OF HEPATITIS A VIRUS IN VARIOUS BODY FLUIDS

Feces
Body Fluids

Serum

Saliva

Urine

100 102 104 106 108 1010

Infectious Doses per mL

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Source: Viral Hepatitis and Liver Disease 1984;9-22

J Infect Dis 1989;160:887-890
 Age
Frequent among children than adults.
People from all ages get infected (if Sex
susceptible).
Severity increases with age. Both sex are equally
Anicteric : icteric susceptible.
1:3(adults)
12:1(children)

Pregnancy
Immunity
Acquired after an infection. VHA during pregnancy
Immunity after attack lasts for life. carries a high mortality.
Second attack reported in about 5% No transplacental
patients. transmission
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 Environmental factors
• Can occur throughout the year
• Especially during heavy rainfall
• Poor sanitation and over crowding favours spread of
infection.

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 Transmission

• Faecal oral route

• Direct contact(person to person)
• Indirect- contaminated water, food or milk
• In developed countries, foodborne outbreaks are
frequent.
• Eg. Consumption of salads, vegetables and raw
or inadequately cooked shellfish cultivated in
sewage polluted water.
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22
 • Parenteral route
• Occur during the stage of viremia
• Rare; mode is of minor importance.
• Eg. By blood or blood products or skin penetration
through contaminated needles

• Sexual transmission
• Occurs in homo sexual men
• Oral anal contact
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RISK FACTORS
• Unknown or unidentifiable (65%)
• International travel (15%)
• Contact with hepatitis A patient (12%)
• Sexual or household contact with hepatitis A patient (10%)
• Men who have sex with men (9%)
• Food or waterborne outbreak (7%)
• Child or employee in a daycare center (4%)
• Contact with a daycare child or employee (4%)
• Injection drug use (2%)
Sjogren MH & Cheatham JG, (In: Sleisenger & Fordtran’s Gastrointestinal and Liver Disease,
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9th Edition, 2010; p. 1280)
 HEPATITIS A -PATHOGENESIS &
CLINICAL FEATURES
• HAV has been detected in lymph
nodes, spleen & kidney but it appears
to replicate only in the hepatocytes

• Mode of entry into hepatocytes is

unknown but once in the cell, it starts
to replicate in the cytoplasm

• HAV-associated hepatocyte injury is

immunologically mediated cell damage

• Acute hepatitis A is self-limiting and

does not result in chronic infection

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INCUBATION PERIOD

• 10-50 days( usually 14-28 days).

• Length of incubation period inversely
proportional to dose of virus ingested .

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HEPATITIS A - CLINICAL
PATTERNS
1. Asymptomatic without jaundice
2. Symptomatic with jaundice & self-limited after about 8
weeks
3. Cholestatic, with jaundice lasting ≥ 10 weeks (this is
commonly seen in HBsAg carriers and sicklers)

4. Relapsing with 2 or more episodes occurring over a 6-10

week period
5. Fulminant hepatic failure
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 CLINICAL FEATURES
Icteric stage
Pre-icteric stage • Onset of jaundice
• With onset of jaundice, fever subsides.
• Sudden onset of fever, chills, • Sclera looks yellow and skin looks

fatigue, malaise, head ache and lemon tinged.

• Nausea and vomiting decreases.
body ache
• High coloured urine continues for
• Within a day or two, develops
several days.
gastro intestinal symptoms
• Jaundice usually reaches maximum by
• High coloured urine, light
2 weeks and decreases steadily
coloured stools lasting for about thereafter. 28

of 3 to 5 days. • Stage lasts for 4 to 6 weeks.

 Convalescent stage
• After about 6 to 8 weeks,
inflammatory process comes
down, there is regeneration of
cells.
• Appetite improves
• Icterus disappears
• Urine and stools become
normal
• Stage lasts for 2 to 6 weeks.
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• Resolves in 98% cases but relapse of symptoms noted in
3-20% cases.
Outcome Children Adults
Sub clinical 80-95% 10-25%
infection
Icteric disease 5-20% 75-90%
Complete > 98% > 98%
recovery
Chronic disease None None
Mortality rate 0.1% 0.1% 30
 DIAGNOSIS
• Demonstration of HAV particles in the faeces, bile or blood.
• HAV is detected in the stool from about 2 weeks prior to the onset
of jaundice and 2 weeks thereafter.
• Anti HAV appears in IgM fraction during acute phase.
• Anti HAV IgM usually declines to non detectable level within 3-6
months.
• Anti HAV IgG appears more slowly and persist for decades.

• Acute infection is diagnosed by the detection of HAV-IgM in

serum by (enzyme immunoassay)EIA.
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• Past Infection i.e. immunity is determined by the detection of
HAV-IgG by EIA.
HEPATITIS A TREATMENT

• No treatment/specific therapy
• Supportive therapy—avoid alcohol, herbal medication,
etc.
• May take anything they want if not in liver failure
• Does not progress to chronic liver disease
 HEPATITIS B
• World wide 350-400 million carriers, mostly in Africa
and Far East
• Vertical transmission most important world wide
• Only replicates in liver and may be integrated into host
genome
• HBsAg(surface Ag-chronic) and IgM Anti-HBc (core Ag-
acute)appear early and indicate current infection
• HBeAg(viral protein secreted by infected hepatocytes)
indicates replication& infectivity, Anti-HBs- immunity;
anti-HBe(resolution + recovery)
 HBV—CLINICAL FEATURES
• Most infections asymptomatic
• Serum sickness feeling, like for HAV- urticaria,
polyathritis, fever, arteritis, glomerulonephritis
• 90% of infants become chronic carriers while
10% adults become carriers
• Treatment: Peg-interferon, Tenofovir,
Lamivudine, Adefovir dipivoxil.
 HEPATITIS C
• Most important cause of end-stage liver disease and
transplantation in developed countries
• Becoming important in developed nations also
• Transfusion, I.V drug users and homosexuals mainly at risk
• May cause acute hepatitis but usually less severe than HBV
• Great propensity for long term carrier status and late
chronic liver disease (up to 70%)
• Treatment as for HAV & HBV. Acute antivirals to reduce risk
of chronic infection now available (interferons, DAAs,
Ribavirin)
 HEPATITIS D
• A defective RNA virus that requires the
presence of HBV for propagation
• It causes severe hepatitis in those with
previous HBV infection and less severe in
concurrent infection
• Associated with progressive liver disease
 HEPATITIS E
• Sporadic or epidemic in nature
• Water borne like HAV(faeco-oral)
• Illness like HAV but more severe
• High morbidity and mortality in pregnant
women, especially in the 2nd trimester (>10%)
 Clinical features
• Asymptomatic but may be detected by liver
biochemistry
• Non-specific
• Fever which subsides at the onset of
jaundice(viral hepatitis)
• Jaundice, Malaise, Anorexia
• Aversion to tobacco/alcohol
• Fulminant liver failure
• Persisting inflammation
 Clinical features
• Asymptomatic but may be detected by liver
biochemistry
• Non-specific
• Fever which subsides at the onset of
jaundice(viral hepatitis)
• Jaundice, Malaise, Anorexia
• Aversion to tobacco/alcohol
• Fulminant liver failure
• Persisting inflammation
 Diagnosis
• Liver biochemistry typically ALT>10x upper limit. In
paracetamol toxicity up to 70x.
• Serology for viral causes- IgM HAV, HbsAg, Aniti HCV
• PCR for viral causes
• Imaging-Ultrasound scan- normal liver size with varying
echo pattern. In cases of fulminant failure reduction in size
• Histopathology- spotty necrosis in viral causes. In some
cases, macro vesicular steatosis with displacement of the
nuclei with ballooning degeneration and necrosis +/-
Mallory bodies (alcoholic and NASH).
• Liver biopsy seldom done for acute hepatitis
 Treatment
• Largely supportive- Adequate hydration.
• Bed rest –patient preference
• Diet- patient’s preference but low fat , high caloric meal better tolerated.
• Antiviral therapy for acute HCV using standard interferon or peg Interferon
for 12 to 24 weeks if no clearance after about 12 weeks.
• Withdrawal of offending drug or alcohol
• Use of glucocorticoids in severe alcohol hepatitis as defined by Maddrey
discriminant function(D-F) score (>/=32). D-F identifies patients at risk of
mortality within 30days, and is calculated as follows 4.6(PT-control in
secs. ) + serum bilirubin (in mg/dl). Infection is an issue when using steroid
and should be screened for.
• Pentoxyfylline an inhibitor of TNF-alpha& can be used as an alternative to
steroid.
•Liver support device (artificial and bioartificial device) in situation of
liver failure in addition to routine management of encephalopathy
while waiting spontaneous recovery or as a bridge to transplantation.

• Conventionally medical treatment involves no protein diet, use of

non absorbable disaccharides(Lactulose) and management in an
intensive care unit. Currently Rifaximin is in use.

•Follow-up with liver biochemistry at 6/52 and 6/12

 FULMINANT HEPATIC FAILURE (FHF)

• Severe impairment of hepatic function/hepatocyte necrosis within 8

weeks of onset of liver disease
• Clinical feature of jaundice, encephalopathy, ascites, coagulopathy,
shrunken liver and hypotension progressing rapidly in days
• Causes are Drugs, Alcohol, Viruses, Acute Fatty liver of pregnancy,
Sepsis, etc
• PT(Prothrombin time) very high poor prognosis. Other features-
hypoglycemia and electrolyte abnormalities
• No specific treatment
• Cerebral edema and infection most common cause of death.
• Patient may benefit from IV Mannitol
• No effective treatment other than early transplantation