Transcript Biliary Tree infection, Liver Abscess and Hepatitis A

Biliary Tree Infection, Liver
Abscess and Hepatitis A
OCTOBER 2005
Biliary Tree Infection
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Acute cholecystitis
Bacterial
 Cholangitis
Bacterial/Protozoan
 Liver abscess
 Hepatitis
Viral
All cause jaundice
Cholecystitis
Hepatitis/Liver
abscess
Cholangitis
Jaundice
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= hyperbilirubinaemia due to various
causes
Can be due to conjugated or unconjugated
bilrubin
Classically presents with yellow eyes,
skin, pale stools and dark urine
May have a hepatomegaly, pruritus
Can be due to obstructive (tumour,
gallstones) or non obstructive causes
(hepatitis, alcoholic hepatitis, haemolysis)
Sclera
Bilirubin
 Bilrubin
is bound to albumin in blood
 delivered to liver, conjugated to sugar
residues to make it water soluble
 secreted in bile
 Once in gut bilirubin reduced to
urobilinogen (by bacterial flora)
 urobilinogen is required (indirectly) to give
stools characteristic colour
Bilirubin
If this process is blocked:
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less bilirubin ends up in bile
 more in blood and therefore more ends up
in urine
 So stools lose their pigment (pale)
 and excess bilirubin in blood exits
through urine giving it dark colour
Liver Enzymes
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Some are a better measure of hepatocellular
damage e.g. Alanine aminotransferase (ALT),
Aspartate aminotransferase (AST)
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This can be due to hepatitis, drugs, alcohol,
toxins etc
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Others are a better measure of obstruction e.g.
Alkaline phosphatase, serum bilirubin
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This can be due to cholecystitis, cholangitis,
tumours, gall stones
Cholestatic Jaundice Laboratory Evaluation
Lab Test
AST, ALT
Alk. Phos.
Bilirubin
Intrahepatic
(hepatocellular)
+++
Extrahepatic
(obstructive)
+
+
++
+++
+++
Acute Cholecystitis
Acute inflammation of gallbladder
 Affects 10% of Western population
 Of these only 1/5 symptomatic
 Of these, 1-3% develop cholecystitis,
i.e. ~ 1/2500 of general pop)
 Does not always involve infection
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Acute Cholecystitis
Pathogenesis
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Gall stones
90% due to Obstruction of cystic duct e.g. by
stones, biliary sludge, tumour or scarring
Necrosis
20% of cases involve infection with normal
bowel flora (E. coli, Klebsiella, Enterococcus
spp., Bacteroides spp., Clostridia spp.)
In developing countries, ascariasis worm
major cause
Classification
OEDEMA
OEDEMA plus CONGESTION
FOCAL NECROSIS
INTRAMURAL
SUPPURATION
INTRALUMINAL
PERI-CHOLECYSTIC
GANGRENE
LOCALISED
PERFORATION
FREE
Gall Stones
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Gall stones can consist of bile salt, cholesterol or
be mixed
Prostaglandins mediate inflammatory response, vicious circle
Acute Cholecystitis
Clinical Features
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Nausea, vomiting, fever
Constant pain in right upper quadrant of abdomen
Murphy’s sign (pain preventing full inspiration during
subhepatic palpation)
+/- jaundice
+/- palpable gall bladder
Temperature
Said to occur classically in women who are “fair, fat
and forty with four children” but can occur in anybody
If infection occurs, may have signs of septicaemia
(worse prognosis) or peritonitis if perforation occurs
Acute Cholecystitis
Diagnosis
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Based on Clinical Features and
Investigations
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Radiological findings US, PFA,
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Lab findings, increased WCC, ESR, CRP
Acute Cholecystitis
Radiological Investigations
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Ultrasound scan – can reveal stones, oedema of gall
bladder wall, fluid around gall bladder
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Plain film of abdomen (X-ray) shows stones in 10%,
may show air level in emphesymatous cholecystitis
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If US unclear, Scintigraphy used. Inject radiolabelled
HIDA which is secreted in bile. Failure of appearance
in gallbladder within 1-2 hours is a sign of blockage
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CT may also be useful
Ultrasound
Gallstones seen on X-ray
PFA findings in Emphysematous Cholecystitis
Organsims Involved
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Usually mixed, derived from bowel flora
 Enterobacteriaceae 68%
 Enterococci 14%
 Bacteroides spp. 10%
 Clostridium sp. 7%
Acute Cholecystitis
Complications
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Perforation, necrosis gangrene,
suppuration
 Abscess formation
 Septicaemia
 Peritonitis
Acute Cholecystitis
Treatment
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Most respond to conservative management,
gallstones falls back into gall bladder, cystic duct
empties and symptoms resolve
Rest gall bladder – no food, IV fluids, pain relief as
required
Indomethacin to reduce prostaglandin effects
If systemic signs or no improvement after 12-24
hours give Antibiotics, usually:
– Co-Amoxiclav or Ampicillin, Ciprofloxacin or
Gentamicin , and Metronidazole
– Piperacillin/Tazobactam (Tazocin)
Acute Cholecystitis
Treatment
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About 20% require emergency surgery
These are patients with deterioration in
condition,perforation with peritonitis, suspected
pericholecystic abscess or emphysematous
cholecystitis
Many others will require surgery but timing of
surgery is a matter of debate
Cholecystectomy = removal of gallbladder, can be
done as an open or laparoscopic procedure
Cholangitis
Definition
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continuous, varying degrees of inflammation and
/or infection involving hepatic and common bile
duct (mucosa continuous) More severe entities
are ascending cholangitis and acute obstructive
suppurative cholangitis.
Pathogenesis
 Essentially obstruction of the common bile duct
due to stones, parasites, surgery, leading to
increased
pressure,
oedema,
congestion,
necrosis and proliferation of bacteria.
Ascending Cholangitis
Signs and Symptoms
 Previous history of gall bladder disease,
 acute onset of Charcot's triad
– RUQ pain,
– fever & rigors
– Jaundice
Treatment
 Antibiotics e.g.Co-Amoxiclav or Ampicillin ,+Ciprofloxacin
or
Gentamicin
,+
metronidazole
or
Piperacillintazobactam+/-Ciprofloxacin
 Decompression by endoscopy(ERCP), radiological stenting
or surgical drainage
 Delay in treatment can result in septicaemia, liver abscess
Liver Abscess
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Liver is a very vascular organ, receiving
blood from systemic and portal circulation
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Bile drainage also provides route of
bacterial entry especially when
obstruction occurs
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Usually Kuppfer cells lining hepatic
sinusoids clear bacteria to prevent
infection
Liver Abscess
Source
Frequency
Biliary tract disease
60%
Portal venous system from GIT
24%
Arterial seeding from systemic
bacteremia
15%
Contiguous spread e.g. from gall
bladder
4%
Other causes include trauma and secondary infection also
crytogenic
Liver abscess can be pyogenic or amoebic
Liver Abscess
Untreated pyogenic liver abscess is
uniformly fatal
 Appropriate antibiotic Tx and drainage
reduces mortality to 5-30%
 Abscess can be single or multiple
( due to biliary disease)
 Right lobe being bigger is more
commonly involved
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Liver Abscess
Clinical Features
 Fever, chills for several days or weeks
 Spiking temperatures with ascending
cholangitis
 Malaise
 Anorexia
 Weight loss
 +/- referred pain to right shoulder
Liver Abscess
Clinical Findings
 hepatomegaly
 +/- tenderness
 Reduced breath sounds on right hand
side
 Hepatic friction rub
 Jaundice in 25%
Most Common Causative Organisms
Usually mixed aerobes and anaerobes,
type often corresponds to source:
 Gram
negative bacilli from GIT e.g E.coli,
Klebiella spp
 Streptococcus milleri from GIT
 Bacteroides, Fusobacterium and other
anaerobes from GIT
 S. aureus from haematogenous spread
 Entamoeba histolytica
 Fungal abscesses e.g. C. albicans in patients
with prolonged antibiotic exposure, transplants,
immunocompromised patients
Liver Abscess
Investigations
 FBC: anaemia, raised WBCs
 Raised CRP and ESR
 Raised liver enzymes esp Alk Phos
 Blood cultures
 Culture abscess fluid
 Radiology: CT or ultrasound
Liver Abscess
Treatment
 Percutaneous drainage of abscess
under CT or US guidance
 If this fails – surgical drainage
 Exception is Entamoeba histolytica
which responds to metronidazole
without surgery
 CT/US to monitor Tx
Liver Abscess
Antibiotic Treatment
depends on culture results:
 Ampicillin+Gentamicin + metronidazole or
Piperacillin-tazobactam
 Clindamycin, Flucloxacillin for sensitive
Staphylococci
 Amphotericin B for fungi
 Entamoeba histolytica – metronidazole
 Usually for 1-4 months
Causes of Hepatitis
Infectious
Bacterial
Parasitic
Viral
Noninfectious
Leptospirosis
Syphillis
Tuberculosis
Toxoplasmosis
Amoebiasis
Hepatitis Viruses A,
B,C, D, E, G
Epstein Barr
Cytomegalovirus
Herpes Simplex
Varicella Zoster
Coxsackievirus
Rubella
Yellow Fever
Alcohol
Drugs
Hepatitis Viruses
Types A to G
 No relation to each other, simply
infect same organ
 Viral hepatitis can also be caused by
other viruses e.g. EBV, CMV and HSV
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Hepatitis A
Hepatitis A - History
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“Catarrhal jaundice” recognised in
ancient China, Greece and Rome
Hippocrates
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Epidemic in Minorca in 1745
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McDonald first to suggest viral cause
in 1907
Viral Hepatitis - History
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Deliberate transmission to human volunteers
in Germany in 1942
 Jaundice committee 1943, One(serum) has
incubation period 60-160 Hep B and another
feacal oral route , I.P shorter Hep A identified
 Mid 1970`s- new serological test for Hepatitis
B did not explain all cases-nonA-nonB now
Hepatitis C (1989) but sporadic and
community acquired Hep E also described
 Rizzetto 1977 described Hep D while working
on Hep B
Hepatitis A - Classification
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Picornaviridae of which there are 3 genera:
– Rhinovirus (Rhinoviruses)
– Enteroviruses (Polio, coxsackie, echo and
enteroviruses)
– Hepatavirus (Hepatitis A)
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RNA virus, ss + RNA (7.5 kb)
 Only one serotype
 Non-enveloped
 27-28 nm icosahedral structure
Hepatitis A Virus (HAV)
First isolated in 1979
 Natural host: human
 Stable: heat and acid-resistant
 Inactivated by high temperature,
formalin, chlorine
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Hepatitis A – Life Cycle
Infected material ingested
 Absorbed through stomach or small
intestine
 Replicates in liver
 Secreted into bile
 Excreted into stool or reabsorbed
 Spread: Faecal-oral route
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HAV Life Cycle
Hepatitis A
Robust virus:
 stable after incubation at 56oC
 Lasts for years at –20oC
 In dried form at room temperature
can last for several weeks
 Killed by boiling for 5 minutes
Hepatitis A
Therefore steaming shellfish
probably insufficient
 Survives for days/months in live
oysters, waste water, soil
 Stable at pH 3
 Resistant to diethyl ether, chloroform
and 50% trichlorotrifluorethane
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Hepatitis A
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i.e. tough organism which, because of its
ability to survive, is easily transmitted
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Therefore meticulous care is needed when
handling clinical specimens
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Destroyed by:
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Boiling
Autoclaving
Chlorine
Iodine
Radiation
formaldehyde
HAV Epidemiology
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Man is natural host
Worldwide distribution
Late Autumn , early Winter
Virus spread in feces
Virus contaminates
– Water: drinking, bathing; washing food
– Food: shellfish and other filter feeders
– Hands: personal hygiene; contaminated water
Hepatitis A - Epidemiology
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CDC 10,600 cases in USA/2001, 22% hospitalised,
~ 100 deaths/yr
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Over last 40 years average age of infection
increasing due to improved sanitation, detection and
prevention
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Approx 10% of children and 40% of adults will have
IgG
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Highest rate of seropositivity in Africa, Asia and South
America
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But epidemiology is changing with improved hygiene
and increasing travel
Hepatitis A - Epidemiology
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High risk groups include:
– Contacts of recently infected individuals
– Foreign travellers (esp visitors to Third world)
– Military personnel
– Male homo/bisexuals
– IV drug abusers
– Those living in poverty or in institutions
– Childcare and sewage workers
– Recognised Foodborne or water outbreaks
Prevalence of Risk Factors in Patients with HAV
Unknown
44.5%
Outbreaks
4.7%
Personal
contact
24%
Day Care
15.1%
Homosexual men
Injecting drug use
3.8%
2.4%
International travel
5.5%
Hepatitis A - Epidemiology
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Mortality about 2% in elderly, about 0.02%
in normal population
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Also higher in those with coincidental liver
disease
Hepatitis A in Ireland: 112 cases in 2001
 NO chronic carrier state
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Hepatitis A Ireland
Hepatitis A - Transmission
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Faecal-oral spread, shed in faeces 2-3
weeks before jaundice and 1 week after
 Close person-to-person contact
 poor hygiene, foodborne or waterborne
outbreaks e.g. faecal contamination of
food such as Oysters or by food handler
 Via shared needles/blood transfusions
(rare)
How is HAV different from
foodborne bacteria?
 Does
not replicate in infected food
 Virus
remains stable for long periods of
time in a wide range of conditions, e.g. in
one outbreak, the virus survived for > 1 year
in frozen fruit
HAV Pathogenesis
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Incubation period 15-50 days weeks, depends
on infective dose
Replication: liver (hepatocytes and Kuppfer’s
cells); peak viraemia 10-12 days after infection
(appearance of HAV in serum and feces)
Virus released into bile and stool
Virus does not induce cytopathic effects
Damage to liver is immune mediated, thought
to be via cell-mediated immune response
Histology is similar to hepatitis B virus infection,
portal inflammation but less focal necrosis
Hepatitis A - Clinical Features
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In Western world tends to be symptomatic
In Third world, often asymptomatic and
subclinical
Majority of infected children are
asymptomatic(70%), majority of adults have
symptoms(70% jaundice)
symptoms and severity of illness increase
with age
Flu-like illness
Jaundice, hepatomegaly, splenomegaly
Usually uneventful recovery
Symptoms of patients with Hepatitis A
Symptom
Reported Ranges (%)
Jaundice (Yellow Eyes)
40-80
Dark urine
68-94
Fatigue/Lassitude
52-91
Loss of appetite
42-90
Abdominal pain/discomfort
37-65
Light-coloured stools
52-58
Nausea or vomiting
26-87
Fever or chilliness
32-73
Headache
26-73
Arthralgias
11-40
Myalgia
15-52
Clinical Course of HAV Infection
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Incubation phase: 15-50 days, i.e. can infect
others before symptoms develop
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Preicteric phase
– Abrupt appearance
– Fever, fatigue, nausea, loss of appetite, abdominal
pain leading to Icteric phase (jaundice)
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Icteric phase
– Symptoms lessen
– Jaundice, dark urine
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Convalescent phase
– Complete recovery 99% of cases
Clinical Diagnosis of HAV
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Discrete onset of symptoms
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History
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Jaundice
Lab Findings in HAV Infection
Elevated serum aminotransferase levels
(ALT and AST elevated)
 Alkaline Phosphatase only mildly elevated
(elevation is a sign of cholestasis)
 Mild lymphocytosis
 Increase in prothrombin time bad sign
 Specific Ig tests for Diagnosis by ELISA
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Hepatitis A - Diagnosis
Anti HAV IgM appears just before
jaundice and remains elevated for 4/12
up to 6 months(ELISA)
 IgG levels used to determine immune
status
 Virus culture for diagnosis not an option
as it is slow, difficult and expensive
 Positive RT-PCR and/or antigen test
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Complications of HAV
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Fulminant Hepatitis
– 1-3/1000 cases; 80% mortality
– Extensive necrosis of the liver
– Includes hepatic encephalopathy
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Relapsing hepatitis ~ 12%
– 4-15 weeks after initial symptoms
– Biochemical changes only in some patients
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Cholestatic hepatitis
– Total blockage/suppression of bile
– High bilirubin levels
Complications of HAV
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NO CHRONIC INFECTION
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NO CARRIER STATE
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VERTICAL TRANSMISSION
RARE
Hepatitis A – Treatment
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Symptomatic Tx (e.g. rehydration,
antiemetics)
 Immune serum globulin
– Given before or early in incubation phase
(effective within 2 weeks of exposure)
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Contact tracing
 Those with fulminant hepatitis and hepatic
failure occasionally require transplant
Hepatitis A – Prevention
Adequate sanitation, disrupt Faecal-oral
spread
 Good hygiene
 Effective (inactivated) vaccine available
 Immunoglobulins also available for
passive protection
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HAV Vaccine
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No adverse reactions but not used in those <
2 yrs of age
 Recommended for:
– international travelers to endemic areas (effective
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–
–
–
–
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4 weeks after administration)
Homo/bisexual men
I.v. drug users
Persons with coagulopathies, chronic liver disease
(including hepatitis C)
Those who regularly receive blood products
Persons at occupational risk (sewage workers,
those in mental institutions , consider in certain
Health care workers groups)
Contacts of known cases
HAV Immunity
Infected > Vaccinated > passive IgG Tx
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Infection provides lifelong immunity
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Vaccination thought to be largely sufficient
and should provide immunity for at least 10
years, probably longer(2 doses, o and 6-12
months later) e.g Havrix and Vapta
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Passive Immunization with IgG provides
protection for about 5 months and straight away
HAV Summary