Transcript Biliary-obstruction-autoimmune-diseases-of-the

Biliary obstruction,
autoimmune diseases of the
liver
John J O’Leary
Learning objectives
• Understand bile duct obstruction
[causes and effects]
• Understand what is meant by the term
auto-immune liver disease:
– Primary biliary cirrhosis [PBC]
– Primary sclerosing cholangitis [PSC]
– Autoimmune hepatitis [AIH]
Biliary obstruction
Pathological effects of biliary obstruction
Biliary obstruction
High local concentration of bile salts
Inflammation
Fibrosis & scarring
Biliary fistula
Fibrosis and scarring
Biliary stasis
Repeated cholangitis
Liver atrophy
Biliary cirrhosis
& portal HTN
(very late)
Causes of Benign strictures
Causes of Malignant strictures
Symptoms and history:
 Biliary colic
 Obstructive jaundice
 Cholangitis – Charcot’s triad
 jaundice; fever, usually with rigors; and right upper
quadrant abdominal pain.
– Reynold’s pentad
+ hypotension and an altered mental state
 Past history of cholecystectomy/ other GI
surgery (eventful)
 History s/o pancreatitis, trauma, radiation,
alcohol abuse
Signs:
 Icterus
 s/o hepatocellular failure
 Courvoisier's sign
 e/o biliary fistula, peritonitis, biloma
 Nutritional deficiencies
 pale stools
 dark urine
 itchiness (pruritus)
HISTOPATHOLOGY
Under a microscope, the individual hepatocytes will have a
brownish-green stippled appearance within the cytoplasm,
representing bile that cannot get out of the cell.
Canalicular bile plugs between individual hepatocytes or
within bile ducts may also be seen, representing bile that has
been excreted from the hepatocytes but cannot go any further
due to the obstruction.
When these plugs occur within the bile duct, sufficient
pressure (caused by bile accumulation) can cause them to
rupture, spilling bile into the surrounding tissue, causing
hepatic necrosis. These areas are known as bile lakes, and
are typically seen only with extra-hepatic obstruction.
Strasberg classification of
biliary injury & stricture
Laboratory investigations

Bilirubin
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Alkaline phosphatase &

PT
 Anemia, amylase & lipase,
GGT
ESR, LDH
 Tumor markers: CA 19-9, CEA, AFP
Imaging studies:
 Ultrasound
 CT scan
 MRCP
 HIDA scan
 ERCP
 Endoscopic ultrasound
 PTC
 Fistulography
Ultrasonography:
 Detects intra/extra hepatic ductal dilatation
 Less accuracy in defining etiology
 Sensitivity – 94% if bilirubin > 10mg%
– 47% otherwise
Endoscopic ultrasound:
• Extra hepatic bile
duct readily
visualized
• Detects
choledocholithiasis
(>95%)
• Sensitive in
diagnosis & staging
of malignancy
CT Scan:
• Highly sensitive (esp.
with contrast)
• Detects site & cause of
obstruction
• Better anatomical
delineation
• CT cholangiography
MRI & MRCP:
• Bile – high signal
intensity on T2
weighted images
• Visualises – biliary
dilatation (97100%), site of
obstruction (87%),
hepatic parenchyma
& vasculature
• Only diagnostic
HIDA Scan
[Hepatobiliary Imino-Diacetic Acid scan]
• Helps in diagnosing biliary
leaks
• Provides functional
assessment of incomplete
strictures and surgical
anastomosis
• suggest complete biliary
obstruction if the small
intestine is not visualized in
60 minutes
• insensitive for helping
detect biliary dilatation or
the site and cause of bile
duct obstruction
Cholangiography:
 Gold standard
 Endoscopic/ percutaneous
 Features:
– define the anatomy of the proximal biliary tree
– decompression of the biliary system
– Non-operative dilation of bile duct strictures
– allow for the simultaneous placement of
drainage catheters
– of assistance with regard to surgical
reconstruction
Treatment:
 Options:
Endoscopic or percutaneous balloon dilatation
and insertion of an endoprosthesis
Surgery
 Pre-procedure antibiotic prophylaxis
RX of malignant strictures:
 Depends on:
resectability & stage
general condition
 Resectable (15-20%)
– Radical resection with biliary enteric anastomosis
 Palliative
– endoscopic stenting
– percutaneous transhepatic stenting
– Palliative resection with surgical bypass
(mortality – 33%)
RX of benign strictures:
 Operative management
– to surgically re-establish bile flow within the biliary
tree and into the proximal gastrointestinal tract in a
manner that prevents cholestasis, cholangitis,
sludge and stone formation, restricture, or biliary
cirrhosis
 Non–operative management
– to correct the increased resistance to biliary flow
caused by a reduction in the diameter of the
lumen
Autoimmune diseases of
the liver
Autoimmune liver disease
• Primary biliary cirrhosis
• Primary sclerosing cholangitis
• Autoimmune hepatitis
Primary biliary cirrhosis
PRIMARY BILIARY CIRRHOSIS
Primary biliary cirrhosis is an autoimmune disease of the
liver marked by:
- the slow progressive destruction of the small bile ducts (bile
canaliculi) within the liver.
- when these ducts are damaged, bile builds up in the liver
(cholestasis) and over time damages the tissue.
- this can lead to scarring, fibrosis and cirrhosis.
- it was previously thought to be a rare disease, but more
recent studies have shown that it may affect up to 1 in 3-4,000
people; the sex ratio is at least 9:1 (women to men)
In some areas of the US and UK the prevalence is
estimated to be as high as 1 in 4000. This is much more
common than in South America or Africa, which may be
due to better recognition in the US and UK.
First-degree relatives may have as much as a 500 times
increase in prevalence, but there is debate if this risk is
greater in the same generation relatives or the one that
follows.
After liver transplant, the recurrence rate may be as high
as 18% at 5 years, and up to 30% at 10 years. There is no
consensus on risk factors for recurrence of the disease
The following signs may be present in PBC:
• Fatigue
• Pruritus (itchy skin)
• Jaundice (yellowing of the eyes and skin)
• Xanthelasmata (focal collections of cholesterol in the skin,
especially around the eyes)
• Complications of cirrhosis and portal hypertension:
• Fluid retention in the abdomen (ascites)
• Hypersplenism
• Esophageal varices
• Hepatic encephalopathy, up to coma, in extreme cases.
• Association with extra-hepatic autoimmune disorder[s] such
as Rheumatoid arthritis or Sjögren's syndrome (up to 80%
incidence).
To diagnose PBC, distinctions should be established from other conditions with
similar symptoms, such as autoimmune hepatitis or primary sclerosing
cholangitis (PSC).
Diagnostic blood tests include:
• Abnormal liver function tests (high alkaline phosphatase, elevated AST, ALT)
• Presence of certain antibodies: antimitochondrial antibody, antinuclear antibody
(the M2-IgG antimitochondrial antibody is the most specific test)
• Abdominal ultrasound or a CT scan is usually performed to rule out blockage to
the bile ducts. Previously most suspected sufferers underwent a liver biopsy, and - if
uncertainty remained - endoscopic retrograde cholangiopancreatography (ERCP, an
endoscopic investigation of the bile duct). Now most patients are diagnosed without
invasive investigation since the combination of anti-mitochondrial antibodies (see
below) and typical (cholestatic) liver function tests are considered diagnostic.
However, a liver biopsy is necessary to determine the stage of disease.
Anti-nuclear antibodies appear to be prognostic agents in PBC. Anti-glycoprotein-210
antibodies, and to a lessor degree anti-p62 antibodies correlate with progression toward
end stage liver failure. Anti-centromere antibodies correlate with developing portal
hypertension. Anti-np62 and anti-sp100 are also found in association with PBC.
STAGES OF DISEASE
• Stage 1 - Portal Stage: Normal sized triads; portal
inflammation, subtle bile duct damage.
Granulomas are often detected in this stage.
• Stage 2 - Periportal Stage: Enlarged triads; periportal
fibrosis and/or inflammation. Typically characterized by
the finding of a proliferation of small bile ducts.
• Stage 3 - Septal Stage: Active and/or passive fibrous
septa.
• Stage 4 - Biliary Cirrhosis: Nodules present; garland
or jigsaw pattern.
The cause of the disease is unknown at this time
- an immunological basis for the disease, making it an autoimmune disorder.
- most patients (>90%) have anti-mitochondrial antibodies (AMAs) against
pyruvate dehydrogenase complex (PDC-E2), an enzyme complex that is found
in mitochondria.
- an increase in GGT could indicate presence of Primary Biliary Cirrhosis.
- 57% of patients with acute liver failure have anti-transglutaminase antibodies
suggesting a role of gluten sensitivity in primary biliary cirrhosis, and primary
biliary cirrhosis is considerably more common in gluten sensitive enteropathy
than the normal population.
- in some cases of disease protein expression may cause an immune tolerance
failure, as might be the case with gp210 and p62, nuclear pore proteins. Gp210
has increased expression in the bile duct of anti-gp210 positive patients.
- Both proteins appear to be prognostic of liver failure relative to antimitochondrial antibodies.
Course and cure of the disease:
- no known cure, but medication may slow the progression
- ursodeoxycholic acid (Ursodiol) is the most frequently used
treatment. This helps reduce the cholestasis and improves
blood test results (liver function tests).
- to relieve itching caused by bile acids in circulation, which
would normally be removed by the liver, cholestyramine (a
bile acid sequestrant) may be prescribed to absorb bile
acids in the gut and be eliminated, rather than re-enter the
blood stream.
- alcoholic beverages are contraindicated.
- in advanced cases, a liver transplant, if successful, results
in a favourable prognosis.
- multivitamins (esp. Vitamin D) and calcium are also
recommended as patients with PBC have poor lipiddependent absorption of Vitamins A, D, E, K.
Contrast-enhanced helical CT image obtained through liver during hepatic
arterial phase shows several small, homogeneously enhancing lesions
(arrows). Multiple lesions were seen throughout remainder of liver as well.
Primary sclerosing
cholangitis
Primary sclerosing cholangitis (PSC) is a chronic liver disease
caused by progressive inflammation and scarring of the bile ducts
of the liver.
The inflammation impedes the flow of bile to the gut, which can
ultimately lead to liver cirrhosis and liver failure.
The underlying cause of the inflammation is believed to be
autoimmunity.
The definitive treatment is liver transplantation.
The cause(s) for PSC are unknown.
It is often considered to be an autoimmune disorder.
PSC is associated with inflammatory bowel disease and
particularly ulcerative colitis, which coexists in approximately 70%
of patients.
Conversely, the prevalence of PSC in ulcerative colitis patients is
~4%.
There is a 2:1 male-to-female predilection of PSC.
There is an increased prevalence of HLA alleles A1, B8, and DR3
in PSC.
The disease normally starts from age 30 to 60, though
may begin in childhood.
PSC progresses slowly, so the disease can be active
for a long time before it is noticed or diagnosed.
Signs and symptoms
• Fatigue
• Severe jaundice with intense itching
• Malabsorption (especially of fat) and steatorrhea, leading to
decreased levels of the fat-soluble vitamins, A, D, E and K.
• Signs of cirrhosis
• Ascending cholangitis, or infection of the bile duct.
• Pale stools due to biliary obstruction
• Dark urine due to excess conjugated bilirubin, which is water
soluble, being excreted by the kidneys
Diagnosis:
- imaging of the bile duct [ERCP],
- magnetic resonance cholangio-pancreatography (MRCP),
- approximately 80% of patients have perinuclear antineutrophil
cytoplasmic antibodies, also called p-ANCA, however this finding is not
specific for PSC.
- antinuclear antibodies and anti-smooth muscle antibodies are found in
20%-50% of PSC patients and, likewise, are not specific for the disease.
- full blood count, liver enzymes, bilirubin levels (usually grossly
elevated), renal function, electrolytes.
- faecal fat determination is occasionally ordered when the symptoms of
malabsorption are prominent.
The differential diagnosis can include: primary biliary cirrhosis, drug
induced cholestasis, cholangiocarcinoma, and HIV-associated
cholangiopathy.
Treatment:
- ursodiol, a bile acid naturally produced by the liver, which has been
shown to lower elevated liver enzyme numbers in people with PSC,
but has not yet been proven effective at prolonging the life of the liver.
- medication to relieve itching (antipruritics) and bile acid sequestrants
(cholestyramine), antibiotics to treat infections, and vitamin
supplements, as people with PSC are often deficient in vitamin A,
vitamin D, vitamin E and vitamin K.
- in some cases, ERCP, which may involve stenting of the common
bile duct, may be necessary in order to open major blockages
(dominant strictures).
- Liver transplantation is the only proven long-term treatment of PSC.
Indications for transplantation include recurrent bacterial cholangitis,
jaundice refractory to medical and endoscopic treatment,
decompensated cirrhosis and complications of portal hypertension.
PSC is associated with cholangiocarcinoma
Primary sclerosing cholangitis. Single-shot fast spin-echo MRCP image shows
multifocal strictures and dilatations of the intrahepatic bile ducts
Autoimmune hepatitis
Overview
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Definition
Prevalence
Clinical manifestations
Pathogenesis
Subtypes
Diagnosis
Prognostic indices
Treatment
Autoimmune Hepatitis
• self-perpetuating hepatocellular inflammation
• unknown cause
• characterization:
– histologic features of interface hepatitis
– hypergammaglobulinemia
– serum autoantibodies
• affects all ages, may be asymptomatic, frequently has an acute
onset, and can also present as fulminant hepatitis.
• Autoimmune hepatitis has an incidence of 1-2 per 100,000 per
year, and a prevalence of 10-20/100,000. As with most other
autoimmune diseases, it affects women much more often than
men (70%).
Prevalence
• Mean annual incidence among white northern
Europeans: 1.9 cases per 100,000 per year
• US: 100,000-200,000 people
• W>M 3.6:1, unexplained.
• all ages, ethnic groups.
• Frequency of AIH among pts with chronic liver
disease in North America is 11-23%
• Accounts for 5.9% in the National Institutes of
Health Liver transplantation database.
• Prevalence of AIH is greatest among northern
European white groups who have a high
frequency of HLA-DR3 and HLA-DR4
Clinical manifestations
Pathogenesis
• Unknown mechanism
• Most popular hypotheses:interactive factors:
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Triggering agent
A genetic predisposition
various determinants of autoantigen display
immunocyte activation
effector cell expansion.
Pathogenesis
• Triggering agents
– infectious agents, drugs, toxins.
– Multiple agents suggest that triggering
epitope is a short amino acid sequence
that is common in many antigens.
– Possible long lag time b/w exposure to the
trigger and onset of the disease
– Triggering factor may not be needed for
perpetuation of the disorder.
Pathogenesis
• Loss of self-tolerance –
– molecular mimicry of a foreign antigen
– self antigen
• Only the cytochrome monooxygenase P-450 IID6
(CYP2D6) has been recognized as an autoantigen.
– multiple self-antigens or foreign antigens may
satisfy the minimal structural requirements
and serve as immunogenic peptides
Pathogenesis
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genetic predisposition
Susceptibility HLA allelles encoding MHC class II:
– influences the presentation of these autoantigens to CD4+ helper T cell
thereby initiating an immune response.
– the initiation of the immune response is dependent on the antigen binding
groove of the class II MHC molecule. The sequence of amino acids that
make up this antigen binding groove is encoded by a person’s HLA alleles.
Thus, there are specific alleles that make a person more susceptible to
developing AIH by influencing the immune response, and in turn the clinical
manifestations and behavior of AIH.
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Autoimmune promoters:
– polymorphisms for TNF-α gene and cytotoxic T lymphocyte antigen 4 gene
have been associated with increased immune reactivity and disease
severity of AIH type I
– Other: Vitamin D receptor (VDR) gene, point mutation of the tyrosine
phosphatase CD45 gene, polymorphisms of the Fas gene, MHC class 1
chain-related A gene.
APC
MHC
Class II
CD4
Peptide
Antigen
Cytokines
TCR
CD4 T Cell
Pathogenesis
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Mechanism of Liver cell destruction via
cellular and humoral mechanisms
– Cell-mediated cytotoxicity
• TH1 response (IL-2, IFN-γ, TNF-α)
 clonal expansion of cytotoxic T
lymphocytes that infiltrate and
destroy hepatocytes.
• Genetic polymorphism that
affects TNF- production may
facilitate this pathway.
– Antibody-dependent cell-mediated
cytotoxicity
• TH2 response (IL-4,5,6,8,10,13) 
B cell stimulation  Ab
production immunocyte
complexes on hepatocyte surface
 targeted by NKT cells
• Anti-inflammatory effects that
counters TH1 action
– Combination of mechanisms
• Predominant mechanism depends
on the phenotypic differentiation
of CD4+ helper T cell, which in
turn reflects the cytokine milieu,
which in itself reflects the
polymorphisms of the cytokine
genes that favor excessive
production of some modulators,
such as TNF-, or deficient in
others.
AIH subtypes
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AIH type 1
AIH type 2
AIH type 3
on the basis of immunoserologic markers.
The International Autoimmune Hepatitis
Group has not endorsed this
subclassification.
• Used mainly for descriptive value
AIH type 1
• Most common form worldwide
• characterized by the presence or absence of SMA
and/or ANA in serum
• Surrogate markers: Peri-nuclear anti-neutrophil
cytoplasmic antibodies which occur in PSC and
chronic UC, are found in 90% of patients who
have type 1 AIH.
• Bimodal age distribution (10-20; 45-70)
• Female:male 3.6:1
• Risk factors for type 1 AIH
– in whites of northern European descent [HLA-DR3
(DRB1*0301)] and –DR4 (DRB1*0401)]
AIH type 1
• Associated with concurrent extra-hepatic diseases
– Autoimmune thyroiditis (12%)
– Graves disease (6%)
– Chronic UC (6%) * (cholangiography to exclude PSC)
– <1% RA, pernicious anemia, systemic sclerosis,
Coomb’s test-positive HA, ITP, symptomatic
cryoglobulinemia, leukocytoclastic vasculitis, nephritis,
erythema nodosum, SLE, fibrosing alveolitis.
• 40% of AIH type 1 presents with an acute onset of
symptoms/signs indistinguishable from that of acute viral
or toxic hepatitis and the disease may appear fulminant in
fashion.
• target autoantigen is unknown, but ASGPR
(asialoglycoprotein receptor) found on hepatocyte surface
is a candidate
• Responds well to glucocorticoids
AIH type 2
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Characterized by presence of anti-LKM1 (liver/kidney microsome
type 1) in serum
P-ANCA is not found
Mainly children (2-14 yo) but also seen in adults (in Europe, 20%
of pts are adults; in US, 4% of pts are >18 yrs)
Only AIH with an identified target autoantigen: cytochrome
monooxygenase P-450 IID6 (CYP2D6) found in the cytosol of
hepatocytes.
– Recognized homologies b/w epitopes of CYP2D6 and genome
of HCV.
– <10% of Europeans with chronic Hep C have detectable antiLKM1
– Suggests molecular mimicry and antibody cross-reactivity,
multiple exposures to virus mimicking self may be a way to
break self-tolerance and induce AIH type 2.
– Anti-LKM1 + pts with chronic Hep C in US pts is rare –
differences in indigenous virus or host susceptiblity?
Acute or fulminant presentation is possible
– Thus essential to screen all pts who have an acute
decompensation for type-specific autoantibodies.
Associated with HLQA-B14, -DR3, -C4A-QD
Susceptibility factor in German and Brazilians: DRB1*07
Like AIH type 1, also responds well to glucocorticoids
AIH type 2
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Distinct form of anti-LKM positive AIH
Occurs in association with autoimmune polyendocrinopathy
disorder (APECED) aka Polyglandular autoimmune syndrome type
I (APS1)
rare autosomal recessive disorder
Caused by a signal gene mutation of the APS1 gene which
encodes a transcription factor, autoimmune regulator (AIRE)
which is expressed in epithelial and dendritic cells within the
thymus where it regulates clonal deletion of autoreactive T cells,
thus can affect self tolerance
Features of this disease are ectodermal dystrophy,
mucocutaneous candidiasis, multiple endocrine gland failure
(parathyroids, adrenals, ovaries)
Marked by the presence of numerous organ and non-organ
specific autoantibodies and multiple concurrent autoimmune
diseases.
most common among Finns, Sardinians, and Iranian Jews
Pts with APECED and AIH have an aggressive liver disease that
does not respond well to standard immunosuppressive regimens.
AIH type 3
• Least established form of the disease
• Designation largely abandoned
• Characterized by presence of antibodies to
soluble liver antigen and liver/pancreas (anti-SLA,
anti- LP)
• 30-50 yo
• Target autoantigens: thought to be Glutathione Stransferase, but a transfer ribonucleoprotein
(tRNP) 50-kd protein was described in 2000 as the
more likely target.
• Clinical and laboratory features that are
indistinguishable from AIH type 1
• Also responds well to glucocorticoids
AIH subtypes
Variant forms
Diagnosis
• Determination of serum
aminotransferase and –globulin levels
• Rule out ddx
• Detection of ANA and /or SMA, or in
their absence, anti-LKM1
• Liver tissue examination
Diagnosis
• determination of serum aminotransferase and –globulin
levels
– Predominant serum aminotransferase abnormality
– Hypergammaglobulinemia
• exclusion of other chronic liver diseases that have similar
features
– hereditary causes: (Wilson disease, alpha1-antitrypsin
deficiency, genetic hemochromatosis
– infectious causes: chronic viral hepatitis A, B, C
– drug-induced liver disease (ETOH, minocycline, nitrofurantoin,
INH, propylthiouracil, methyldopa)
– NASH
– immune cholangiopathies of PBC, PSC, autoimmune
cholangitis
Diagnosis
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Detection of ANA and /or SMA, or in their absence, anti-LKM1
– conventional immunoserologic tests for AIH:
• antinuclear antibodies (ANA),
– present alone (13%), along with SMA (54%)
– also be found in PBC, PSC, chronic viral hepatitis, drug-related
hepatitis, NASH, alcohol-induced liver disease
• smooth muscle antibodies (SMA),
– Directed against actin and nonactin components (tubulin, vimentin,
desmin, skeletin)
– present (87%), sole marker (33%), with ANA (54%)
• antibodies to liver/kidney microsome type 1 (anti-LKM1)
– Typically occurs in absence of SMA and ANA
– rare in the US (4% of adults with AIH in US)
• perinuclear anti-neutrophil cytoplasmic antibodies (pANCAs) are
common in type 1 AIH,
– useful in evaluation patients who lack conventional autoantibodies.
– Used to reclassify patients with cryptogenic chronic hepatitis as
AIH, but they have not been formally assimilated into the
diagnostic algorithm
– Do not have diagnostic specificity nor do they have prognostic
implications.
Diagnosis
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Detection of ANA and /or SMA, or in their absence, anti-LKM1
– NEW antibodies:
• investigational in nature, but sufficient promise to support a
probable diagnosis, not generally available, assays are not
standardized
• actin (anti-actin)
– has less sensitivity, but greater specificity than SMA for AIH
type 1
• asialoglycoprotein receptor (anti-ASGPR)
– transmembrane glycoprotein on the hepatocyte surface
which can capture, internalize, display potential antigens
– Seen in AIH type 1
• soluble liver antigen/liver-pancreas (A)
– Seen in AIH type 3
– used to reclassification of patients with cryptogenic chronic
hepatitis as AIH
• liver cytosol type 1 (anti-LC1)
– Have been proposed as an antigenic target.
– Seen in AIH type 2
– Prevalence is higher in pts < 20, Rare in pts >40
Diagnosis
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Liver tissue examination
– Liver bx is essential to establish diagnosis and assess disease
severity to determine need for treatment
– histological features of interface hepatitis (hallmark of the
syndrome)
– portal plasma cell infiltration typifies the disorder
• lack of portal plasma cell infiltration does not preclude dx
– 1999 update: lobular hepatitis is now part of histologic spectrum
– aminotransferase and gamma-globulin levels do not predict
histologic pattern of injury or the presence or absence of cirrhosis.
– Histologic changes, such as ductopenia or destructive cholangitis,
may indicate a variant syndrome of AIH and PSC, AIH an PBC, or
autoimmune cholangitis.
– Findings of steatosis or iron overload may suggest alternative
diagnoses:
• NASH
• Wilson disease
• Chronic Hep C
• Drug toxicity
• genetic hemochromatosis
Interface hepatitis
Here you can see the limiting plate of the portal tract, demarcating the hepatocyte boundary,
is disrupted by a lymphoplasmacytic infiltrate.
This histological pattern is the hallmark of autoimmune hepatitis, but it is not disease specific.
Plasma cell infiltration
Lobular Hepatitis
PBC
Marked mononuclear cell infiltrate surrounding and destroying
a bile duct in primary biliary cirrhosis
PSC
Mononuclear cell infiltration and characteristic concentric fibrosis around a small bile duct in PSC
Diagnostic Criteria
Scoring System
Prognosis
Prognosis
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40% develop with cirrhosis
– 54% develop esophageal varices w/in 2 years
– 20% die from variceal hemorrhage if they don’t receive any treatment
– hepatocellular carcinoma can occur in this pts but risk is small.
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Presence of ascites or hepatic encephalopathy identifies pts with
a poor prognosis.
13-20% of patients can have spontaneous resolution regardless of
disease activity.
A critical determinant of survival in the untreated patient is early
tolerance of the disease.
– Of pts who survive the early, most active stage of the disease, inactive
cirrhosis develops in 41% of pts.
– Untreated patients who have initial severe disease and survive the
first 2 years of illness typically survive long term
Treatment
Indication for liver transplantation
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Pts’ with ascites and hepatic encephalopathy identifies pt’s with
poor prognosis. They can still respond to glucocorticoid therapy
and should be treated before a decision regarding liver
transplantation is made.
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Indicated in decompensated pt with hepatic encephalopathy,
ascites, and/or variceal hemorrhage during therapy for treatment
failure.
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Effective in pts who deteriorate during or after corticosteroid tx.
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After transplantation, the autoantibodies and
hypergammaglobulinemia disappear within 2 years the 5 year
survival rate is 96%. Actuarial 10 year survival 75%.
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Recurrent disease after transplantation is common but has been
described mainly in patients who have inadequate
immunosuppression.
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RARE cases (3-5%) pts can develop AIH de novo after undergoing
transplantation for non-autoimmune liver disease.
Immunosuppression with CyA is a common feature. TX with
prednisone or azathioprine is effective.
AIH Summary
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self-perpetuating hepatocellular inflammation of unknown cause
Genetic predispostion
Diverse clinical features
3 subtypes AIH and variants
Dx:
– interface hepatitis
– hypergammaglobulinemia
– serum autoantibodies
– Rule out other liver diseases
Consider in all pts with acute & chronic liver diseases and those with
allograft dysfunction after transplantation
Prednisone, Azathioprine
• Evolving treatment options