Transcript GRANULOMATOUS HEPATITIS

GRANULOMATOUS HEPATITIS
Dr. Shiyas Mohammed
JR Pulmonary Medicine
INTRODUCTION
• Granulomas represent the inflammatory
response of the mononuclear phagocytic
system to the presence of a foreign antigen.
• Granulomas in the liver may be found
incidentally, but more often reflect an
underlying clinically relevant disease.
• However, inspite of an extensive work up and
evaluation, the aetiology remains obscure in
10-25% pts with hepatic granulomas and
these patients have been labelled as having
“granulomatous hepatitis”.
AETIOLOGY
INFECTIONS
Bacterial: Brucella, Salmonella
Mycobacterial: TB, Leprosy, NTM
Ricketssiae: Q fever
Spirochaetal: Syphilis
Fungal: Histoplasma, coccidiodomycosis,
cryptococcosis
Parasitic: Schistosomias
Viral: Hepatitis C, Hepatitis B, Cytomegalovirus
AETIOLOGY
SARCOIDOSIS
PRIMARY BILIARY CIRRHOSIS
HODGKINS DISEASE
AIDS RELATED OPPURTUNISTIC INFECTIONS
DRUGS: Carbamazepine, chlorpromazine,chlorpropamide,
phenylbutazone, procainamide
TB and Sarcoidosis are the most common causes of hepatic
granulomas in various studies.
With the advent of AIDS , hepatic granulomas due to rare causes
such as NTM, Cryptococcosis, etc are being increasingly encountered.
PATHOLOGY
• Hepatic granulomas are the result of a cell mediated immune response by
hepatic reticulo endothelial system to antigen or foreign substances.
• Histopathological features of hepatic granulomas depend on the aetiology.
• Generally hepatic granulomas consists of pale staining epitheloid cells
with sorrounding lymphocytes.
• Sometimes, the foreign body or infecting organism can be identified
within the granuloma.
• Central areas of caseation necrosis, foreign body and langhans giant cells
can also be seen.
• Fibrous capsule and hyaline change representing healing may also be
found.
MORPHOLOGICAL TYPES
• Epitheloid cell granulomas
– Caseating(necrotizing) granulomas
– Non caseating granulomas
• Fibrin ring granulomas
• Granulomatoid reactions with poorly formed
granulomas.
• Bile granulomas
• Lipogranulomas
• Microgranulomas
MORPHOLOGICAL TYPES
• Caseating granulomas have been classically associated
with TB.
• Fibrin ring granulomas with a charecteristic doughnut
appearance occur in Q fever.
• Granulomatoid reactions with poorly formed granulomas
occurs in pts with hematological malignancy and AIDS.
• Bile granulomas has been described in areas of
cholestasis.
• Lipo granulomas can be seen in fatty liver.
• Micro granulomas can occur in pts with AIDS, CMV
hepatitis and can occur along with other type of
granulomas
CLINICAL PRESENTATION
• Depends on aetiology.
• Patients often presents with PUO.
• Mild to moderate hepatomegaly which is
usually non-tender , is common.
• When the disease is due to TB/Sarcoidosis,
associated perepheral mediastinal
lymphadenopathy,erythema nodosum,
jaundice may be found.
LABORATORY ABNORMALITIES
• In a patient with PUO, marked elevation of serum
alkaline phosphatase (3-6 times) with mild elevation of
serum transaminases (2-6 times), well preserved
hepatic synthetic function, normal pro-thrombin time,
serum albumin and a normal to slightly raised bilirubin
should arouse a suspicion regarding the presence of
hepatic granulomas.
• Perepheral blood eosinophilia may suggest Hodgkins
disease, parasitic infestation and drug sensitivity.
HEPATO BILIARY TUBERCULOSIS
• CLINICAL SYNDROMES OF HEPATOBILIARY TB
– Congenital TB
– Primary hepatic TB
– Disseminated/miliary TB
– Tuberculoma
– TB of biliary tract
– Drug induced hepatic failure
– Granulomatous hepatitis
– TB Pylephlebitis
CONGENITAL TB
• Hepatic involvement is very common in congenital TB
and has been recently incorporated to the diagnostic
criteria.
• When an infant born to a mother with active TB
manifests hepatomegaly, jaundice and failure to thrive,
congenital TB should be considered as a DD.
• Porta hepatis area is commonly involved.
PRIMARY HEPATIC TB
• Is said to occur when there is involvement of the hepato biliary tract by TB
without apparent involvement elsewhere or only with local lymphnode or
splenic involvement.
• TB bacilli reach liver via portal vein as opposed to miliary TB where
organism reach liver by hepatic artery.
Two major forms of clinical presentation are there.
1)
A hard nodular liver with fever and weight loss mimicking cancer in
65% pts.
2)
chronic recurrent jaundice mimicking extra hepatic obstruction.
PRIMARY HEPATIC TB
DIAGNOSIS
• The charecteristic serum profile included hyponatremia,
raised ALP, transaminases,GGT, Hypo albuminemia and hyper
gamma globulinemia.
• Per cutaneous liver biopsy and laproscopy are the main
methods of confirmation of diagnosis.
• Histopathologically, AFB, caseation and granulomas are seen
in 9%,80% and 96& of cases respectively.
PRIMARY HEPATIC TB
CT Findings:
1. multiple nodular lesions in the subcapsule of liver
2. multiple, miliary micronodular and low density lesions with
miliary calcfcns
3. singular, low density mass with multiple flecked
calcifications.
4. multiple cystic lesions and
5. multiple micro nodular and low density lesions fusing into
multi loculated cystic mass or cluster sign.
MRI Findings
1) Diffuse nodular involvement was visualized in all pts.
2) Nodules were consistent with granulomas and 0.5-4.5 cm in
diameter.
3) Caseating granulomas were of intermediate and high signal intensity
on T2 weighted images and low-signal on T1 weighted images
4) Non caseating granulomas revealed intermediate signal on T1 and
T2 weighted images and increased enhancement in arterial phase
images with persisting enhancement in late phase findings.
TREATMENT
• Most patients respond to ATT.
• For pts with obstructive jaundice, in addition to
ATT, biliary decompression should be performed
either by stent insertion during ERCP, by
percutaneous trans hepatic biliary drainage or by
surgical decompression whenever feasible.
TUBERCULOMA LIVER
• Sometimes, hepatic TB lesions can present as masses larger
than 2mm in diameter and can mimic the appearance of a
SOL liver on liver scan and arteriography.
• They may also be confused with pyogenic or amoebic liver
abscess.
• Blind percutaneous needle biopsy wasn’t very helpful in the
diagnosis,aspiration cytology at the time of laparoscopy
was more useful in confirming the diagnosis
• Most often these lesions resolve with effective ATT.
SARCOIDOSIS
Sarcoidosis is a multi system granulomatous disorder of
unknown etiology.
PATHOLOGY
• The granulomas are made of epitheloid cells and giant cells,
some of them containing stellate(asteroid) bodies.
• The granulomas may show charecteristic clustering which is
also seen in the lymph nodes.
• As the granuloma ages, there may be deposition of collagen in
a lamellar manner at the periphery of granuloma.
SARCOIDOSIS
CENTRAL NECROSIS/CASEATION IS RARE as compared to TB.
• Granulomas are widely distributed in the liver, very often in
the portal and peri portal regions.
• Granulomas are numerous enough to make it unlikely that
could be missed in a liver biopsy sample of even moderate
size.
SARCOIDOSIS
CLINICAL PRESENTATIONS
• Often, hepatic involvement seems incidental, but a few pts
may present with signs and symptoms of hepatic dysfunction.
• In some patients, the clinical presentation may resemble
primary biliary cirrhosis.
• Sarcoidosis can also present with signs of chronic cholestasis.
PRIMARY BILIARY CIRRHOSIS
• In early stages , the hepatic granulomas in primary biliary
cirrhosis may be in distinguishasble from sarcoidosis.
• But in these multi nucleated giant cells are not common and
necrosis is not present.
SYSTEMIC MYCOSES
• Histoplasma capsulatum and Coccidiodes immitis usually
infects humans by inhalation of organism with primary
infection in the lungs.
• Rarely there is a wide spread dissemination involving liver.
• Hepatic reaction to this fungi is usually by granuloma
formation.
• Histoplasma usually colonises immuno compromised pts but
occasionally immuno competent individuals may also be
affected.
• Usually manifest as fever with hepatosplenomegaly and oral
ulcers.
• Liver granulomas sometimes has central caseation necrosis
resembling TB.
• So use of spl stains like methenamine silver, HotchkissMcManus stain makes identifcation easier and diagnosis
certain.
• Diagnosis is best confirmed by culture of organisms from
blood, bone marrow, sputum and oral ulcer scrappings.
SCHISTOSOMIASIS
• Hepatic amoebiasis are caused by S.mansoni and
S.japonicum.
• Presence of eosinophils and the ova of parasite in the centre
of granuloma clinches the diagnosis.
HODGKINS LYMPHOMA
• Hepatic granulomas are seen in 8-17% of pts.
• Presence of hepatic granulomas doesn’t change the disease
outcome or prognosis.
CAUSES OF HEPATIC GRANULOMAS IN PATIENTS WITH AIDS
• Mycobacterium tuberculosis.
• Mycobacterium avium-intracellulare complex
• Cytomegalo virus
• Histoplasmosis
• Toxoplasmosis
• Cryptococcosis
• Neoplasms
• hodgkins lymphoma
• NHL
• Drugs.
IDIOPATHIC GRANULOMATOUS HEPATITIS
• Despite extensive investigations, 10-25% of pts are
labelled as idiopathic hepatic granulomas.
• It’s a condition characterised by recurrent fever and
granulomas in the liver and other organs where
other causes of hepatic granulomas have been
carefully excluded.
CLINICAL FEATURES
• Prominent feature is fever which is often relapsing in
character, although continuous and remittent fever pattern
has also been described.
• Other symtoms include malaise, chills, weightloss, abd.pain,
anorexia, night sweats, nausea, jaundice, diorrhoea and abd
distension.
• The natural history of disease is marked by multiple
remissions and exacerbations.
• Response to corticosteroids is usually dramatic.
DIAGNOSIS
• Patients with hepatic granulomas should be thoroughly
investigated for a possible aetiological cause.
• Detailed history must be obtained specifically focusing on
exposure to an infectious source, and occupational or
environmental agents including drugs.
• Cultures of blood, body fluids and biopsy material must be
done keeping in mind the common infectious causes of
hepatic granulomas.
• Anti-mitochondrial antibodies may be raised in primary
biliary cirrhosis.
• Elevated serum ACE levels suggest sarcoidosis.
• LIVER BIOPSY IS ESSENTIAL FOR THE DIAGNOSIS
• Biopsy material must be subjected to microbiological and
histopathological examination.
• Special stains may be required to identify infectious agents.
• Examn under polarized light may help in visualizing foreign
bodies.
TREATMENT
• When the investigations are conclusive, treatment
should be directed towards the aetiological agent.
• In a country like India, when aetiology is unclear, a
therapeutic trial with ATT is often given.
• If this fails then cortico-steroid treatment may be tried.
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