biliary tree infection, liver abscess and hepatitis a

Biliary Tree Infection, Liver Biliary Tree Infection, Liver Abscess and Hepatitis AAbscess and Hepatitis A

OCTOBER 2005

Biliary Tree InfectionBiliary Tree Infection

Acute cholecystitis Cholangitis Liver abscess Hepatitis

All cause jaundice

}Viral

Bacterial

Bacterial/Protozoan

Cholecystitis

Hepatitis/Liver abscess Cholangitis

JaundiceJaundice

= 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 Sclera

BilirubinBilirubin

Bilrubin is bound to albumin in blood delivered to liver, conjugated to sugar

residues to make it water solublesecreted in bileOnce in gut bilirubin reduced to

urobilinogen (by bacterial flora) urobilinogen is required (indirectly) to give

stools characteristic colour

BilirubinBilirubin

If this process is blocked:

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 EnzymesLiver Enzymes

Some are a better measure of hepatocellular damage e.g. Alanine aminotransferase (ALT), Aspartate aminotransferase (AST)

This can be due to hepatitis, drugs, alcohol, toxins etc

Others are a better measure of obstruction e.g. Alkaline phosphatase, serum bilirubin

This can be due to cholecystitis, cholangitis, tumours, gall stones

Cholestatic Jaundice Laboratory Evaluation

Lab TestIntrahepatic

(hepatocellular)Extrahepatic(obstructive)

AST, ALT +++ +

Alk. Phos. + +++

Bilirubin ++ +++

Acute CholecystitisAcute Cholecystitis

Acute inflammation of gallbladderAffects 10% of Western populationOf these only 1/5 symptomaticOf these, 1-3% develop cholecystitis,

i.e. ~ 1/2500 of general pop)Does not always involve infection

Acute CholecystitisAcute CholecystitisPathogenesis

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

ClassificationClassificationOEDEMAOEDEMA plus CONGESTIONFOCAL NECROSIS

SUPPURATION

GANGRENE

PERFORATION

INTRAMURAL

INTRALUMINAL

PERI-CHOLECYSTIC

LOCALISED

FREE

Gall StonesGall Stones

Gall stones can consist of bile salt, cholesterol or be mixed

Prostaglandins mediate inflammatory response, vicious circle


Clinical Features

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


Diagnosis Based on Clinical Features and

Investigations

Radiological findings US, PFA,

Lab findings, increased WCC, ESR, CRP

Radiological Investigations

Ultrasound scan – can reveal stones, oedema of gall bladder wall, fluid around gall bladder

Plain film of abdomen (X-ray) shows stones in 10%, may show air level in emphesymatous cholecystitis

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

CT may also be useful

UltrasoundUltrasound

Gallstones seen on X-ray

PFA findings in Emphysematous Cholecystitis

Organsims InvolvedOrgansims Involved

Usually mixed, derived from bowel floraEnterobacteriaceae 68%Enterococci 14%Bacteroides spp. 10%Clostridium sp. 7%


Complications

Perforation, necrosis gangrene, suppuration

Abscess formation Septicaemia Peritonitis


Treatment 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)


Treatment 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

CholangitisCholangitis

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.

Definition

Ascending CholangitisAscending 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 Piperacillin-tazobactam+/-Ciprofloxacin

Decompression by endoscopy(ERCP), radiological stenting or surgical drainage

Delay in treatment can result in septicaemia, liver abscess

Liver AbscessLiver Abscess

Liver is a very vascular organ, receiving blood from systemic and portal circulation

Bile drainage also provides route of bacterial entry especially when obstruction occurs

Usually Kuppfer cells lining hepatic sinusoids clear bacteria to prevent infection


Source FrequencyBiliary 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


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


Clinical Features Fever, chills for several days or weeks Spiking temperatures with ascending

cholangitis Malaise Anorexia Weight loss +/- referred pain to right shoulder


Clinical Findingshepatomegaly+/- tendernessReduced breath sounds on right hand

sideHepatic friction rubJaundice 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 sppStreptococcus milleri from GITBacteroides, Fusobacterium and other anaerobes from GITS. aureus from haematogenous spread Entamoeba histolyticaFungal abscesses e.g. C. albicans in patients with prolonged

antibiotic exposure, transplants, immunocompromised patients


InvestigationsFBC: anaemia, raised WBCsRaised CRP and ESRRaised liver enzymes esp Alk PhosBlood culturesCulture abscess fluidRadiology: CT or ultrasound


TreatmentPercutaneous drainage of abscess

under CT or US guidanceIf this fails – surgical drainageException is Entamoeba histolytica

which responds to metronidazole without surgery

CT/US to monitor Tx


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 HepatitisCauses of HepatitisInfectious Bacterial

Leptospirosis

Syphillis

Tuberculosis

Parasitic

Toxoplasmosis

Amoebiasis

Viral

Hepatitis Viruses A, B,C, D, E, G

Epstein Barr

Cytomegalovirus

Herpes Simplex

Varicella Zoster

Coxsackievirus

Rubella

Yellow Fever

Noninfectious

Alcohol

Drugs

Hepatitis VirusesHepatitis Viruses

Types A to GNo relation to each other, simply

infect same organViral hepatitis can also be caused by

other viruses e.g. EBV, CMV and HSV

Hepatitis AHepatitis A

Hepatitis A - HistoryHepatitis A - History

“Catarrhal jaundice” recognised in ancient China, Greece and Rome Hippocrates

Epidemic in Minorca in 1745

McDonald first to suggest viral cause in 1907

Viral Hepatitis - HistoryViral Hepatitis - History

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

Other causes of jaundice complicated early understanding and were separated into “infectious hepatitis” and “serum hepatitis”

Hepatitis A - ClassificationHepatitis A - Classification

Picornaviridae of which there are 3 genera: – Rhinovirus (Rhinoviruses)– Enteroviruses (Polio, coxsackie, echo and

enteroviruses)– Hepatavirus (Hepatitis A)

RNA virus, ss + RNA (7.5 kb) Only one serotype Non-enveloped 27-28 nm icosahedral structure

Hepatitis A Virus (HAV)Hepatitis A Virus (HAV)

First isolated in 1979Natural host: humanStable: heat and acid-resistantInactivated by high temperature,

formalin, chlorine

Hepatitis A – Life CycleHepatitis A – Life Cycle

Infected material ingestedAbsorbed through stomach or small

intestineReplicates in liverSecreted into bileExcreted into stool or reabsorbedSpread: Faecal-oral route

HAV Life CycleHAV Life Cycle


Robust virus:stable after incubation at 56oCLasts for years at –20oCIn dried form at room temperature

can last for several weeksKilled by boiling for 5 minutes


Therefore steaming shellfish probably insufficient

Survives for days/months in live oysters, waste water, soil

Stable at pH 3Resistant to diethyl ether, chloroform

and 50% trichlorotrifluorethane

Hepatitis AHepatitis A i.e. tough organism which, because of its ability to

survive, is easily transmitted

Therefore meticulous care is needed when handling clinical specimens

Destroyed by: – Boiling– Autoclaving– Chlorine– Iodine– Radiation– formaldehyde

HAV EpidemiologyHAV Epidemiology

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 - EpidemiologyHepatitis A - Epidemiology CDC 10,600 cases in USA/2001, 22% hospitalised, ~

100 deaths/yr

Over last 40 years average age of infection increasing due to improved sanitation, detection and prevention

Approx 10% of children and 40% of adults will have IgG

Highest rate of seropositivity in Africa, Asia and South America

But epidemiology is changing with improved hygiene and increasing travel

Hepatitis A - EpidemiologyHepatitis A - Epidemiology

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

Unknown 44.5% Personal

contact 24%

Day Care 15.1%

Injecting drug use 2.4%

International travel 5.5%

Homosexual men 3.8%

Outbreaks 4.7%

Prevalence of Risk Factors in Patients with HAV

Hepatitis A - EpidemiologyHepatitis A - Epidemiology

Mortality about 2% in elderly, about 0.02% in normal population

Also higher in those with coincidental liver disease

Hepatitis A in Ireland: 112 cases in 2001NO chronic carrier state

Hepatitis A IrelandHepatitis A Ireland

Hepatitis A - TransmissionHepatitis A - Transmission

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 How is HAV different from foodborne bacteria?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 PathogenesisHAV Pathogenesis 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 FeaturesHepatitis A - Clinical Features

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 InfectionClinical Course of HAV Infection Incubation phase: 15-50 days, i.e. can infect others

before symptoms develop

Preicteric phase– Abrupt appearance– Fever, fatigue, nausea, loss of appetite, abdominal pain

leading to Icteric phase (jaundice)

Icteric phase – Symptoms lessen– Jaundice, dark urine

Convalescent phase– Complete recovery 99% of cases

Clinical Diagnosis of HAVClinical Diagnosis of HAV

Discrete onset of symptoms

History

Jaundice

Lab Findings in HAV InfectionLab Findings in HAV Infection

Elevated serum aminotransferase levels (ALT and AST elevated)

Alkaline Phosphatase only mildly elevated (elevation is a sign of cholestasis)

Mild lymphocytosisIncrease in prothrombin time bad signSpecific Ig tests for Diagnosis by ELISA

Hepatitis A - DiagnosisHepatitis 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

Complications of HAVComplications of HAV

Fulminant Hepatitis– 1-3/1000 cases; 80% mortality– Extensive necrosis of the liver– Includes hepatic encephalopathy

Relapsing hepatitis ~ 12%– 4-15 weeks after initial symptoms– Biochemical changes only in some patients

Cholestatic hepatitis– Total blockage/suppression of bile – High bilirubin levels

Complications of HAVComplications of HAV

NO CHRONIC INFECTION

NO CARRIER STATE

VERTICAL TRANSMISSION RARE

Hepatitis A – TreatmentHepatitis A – Treatment

Symptomatic Tx (e.g. rehydration, antiemetics)

Immune serum globulin– Given before or early in incubation phase

(effective within 2 weeks of exposure)

Contact tracing Those with fulminant hepatitis and hepatic

failure occasionally require transplant

Hepatitis A – PreventionHepatitis A – Prevention

Adequate sanitation, disrupt Faecal-oral spread

Good hygieneEffective (inactivated) vaccine availableImmunoglobulins also available for

passive protection

HAV VaccineHAV Vaccine No adverse reactions but not used in those < 2 yrs of

age Recommended for:

– international travelers to endemic areas (effective 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 ImmunityHAV ImmunityInfected > Vaccinated > passive IgG Tx

Infection provides lifelong immunity

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

Passive Immunization with IgG provides protection for about 5 months and straight away

HAV SummaryHAV Summary

biliary tree infection, liver abscess and hepatitis a

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