AUTOIMMUNE HEPATITIS

AUTOIMMUNE HEPATITIS
 Chronic hepatitis of unknown etiology
 Can progress to cirrhosis
 Characteristics include:
– presence of autoimmune antibody
– evidence of hepatitis
– elevation of serum globulins
 OTHER NAMES
 Active chronic hepatitis or chronic active
hepatitis
 Chronic aggressive hepatitis
 Lupoid hepatitis
 Plasma cell hepatitis
 Autoimmune chronic active hepatitis
 BACKGROUND
 First described in 1950’s
 Accounts for 5.6% of liver transplants in
the US
 Affects women more than men (3.6:1)
 If untreated approximately 40% die within
6 months
 40% develop cirrhosis
 CLASSIFICATION
 TYPE 1
 TYPE 2
 OVERLAP SYNDROMES
 TYPE 1
 ANA or Anti-Smooth Muscle antibody positive
 Titer usually > 1:100
 10% will have an antibody to Soluble Liver
antigens (SLA)
 Other Antibodies: anti-DNA, ANCA, Anti-
mitochondrial, Anti-Actin (AAA), cytoskeletal
antibody, nuclear envelope proteins lamin A and
C, plasma membrane sulfatides
 TYPE 1
 Bimodal Age distribution (ages 10-20 and 45-70)
 Female:male (3.6:1)
 Associated with extrahepatic manifestations:
– Autoimmune thyroiditis, graves disease, chronic UC
– Less commonly with RA, pernicious anemia, systemic
sclerosis, ITP, SLE
 40% present with acute onset of symptoms
similar to toxic hepatitis or acute viral hepatitis
 TYPE 2
 Presence of anti-Liver/Kidney Microsome
Antibodies or anti-Liver Cytosol antibody
(ALC-1)
 OVERLAP SYNDROMES
 Primary Biliary Cirrhosis
 Primary Sclerosing Cholangitis

 5% of patients with chronic hepatitis C will

have an ANA titer of >1:100
 A homogeneous pattern of staining is
more common in ANA positive
autoimmune hepatitis compared to that of
ANA positive chronic hepatitis C
 CLINICAL PRESENTATION
 Hepatomegaly
 Jaundice
 Stigmata of chronic liver disease
 Splenomegaly
 Elevated AST and ALT
 Elevated PT
 Non-specific symptoms: malaise, fatigue,
lethargy, nausea, abdominal pain, anorexia
 DIAGNOSIS
 Elevated AST and ALT
 Elevated IgG
 Rule out other causes:
– Wilsons disease
– Alpha 1 antitrypsin deficiency
– Viral hepatitis (A, B, C)
– Drug induced liver disease (alcohol, minocycline, nitrofurantoin,
INH, PTU, methyldopa, etc)
– NASH
– PBC, PSC, autoimmune cholangitis
 Presence of autoimmune antibodies
 Liver biopsy
 HISTOLOGY
 Chronic hepatitis with marked piecemeal
necrosis and lobular involvement
 Numerous plasma cells
 Interface hepatitis: hallmark finding
HISTOLOGY
INTERFACE HEPATITIS
 PATHOGENESIS
 Mechanism is generally unknown
 Genetically predisposed individual with exposure to an
environmental agent that triggers the autoimmune
pathogenic process
 Genetic predisposing factors:
– HLA-DR3: early onset, severe form
– HLA-DR4: white individuals, late onset, better response to
steroids, higher incidence of extrahepatic manifestations
– IgG: part of the IgG molecule (mainly the heavy chain)
– T-Cell receptors
 PATHOGENESIS
 Environmental Triggers: presumed to be
certain viruses, toxins, drugs
 Drugs:
– Oxyphenisatin
– Methyldopa
– Nitrofurantoin
– Diclofenac
– Minocycline
– statins
 TREATMENT
 Should be based on:
– Severity of symptoms
– Degree of elevation in transaminases and IgG
– Histologic findings
– Potential side effects of treatment
American Association for the Study of
Liver Diseases
RECOMMENDATIONS
 Treat if serum aminotransferases are greater
than 10 times normal
 Treat if serum aminotransferases are greater
than 5 times normal and IgG is elevated to
greater than 2 times normal
 In patients with inactive cirrhosis evaluate for
preexisting comorbidities (hep C), pregnancy,
and drug intolerances (increased risk of steroid
side effects in pts with DM, osteoporosis, HTN)
 TREATMENT
 Corticosteroids
 Azathioprine
 Children: azathioprine or 6MP
 PREDNISONE ONLY
 Prednisone 60mg PO daily with a taper
down to 30mg at the 4th week into
treatment and then maintenance of 20mg
daily until reach endpoint
 Reasons for Prednisone only:
– Cytopenia
– TPMT (thiopurine methyltransferase) deficiency
– Malignancy
– Pregnancy
 COMBINATION THERAPY
 Prednisone + Azathioprine
 Prednisone: start at 30mg daily and taper
down to 15mg at week 4, then maintain
on 10mg daily until therapy endpoint
 Azathioprine 50mg daily
 TREATMENT REMISSION

 Disappearance of symptoms
 Normal serum bilirubin and IgG
 Serum aminotransferases normal or less
than twice normal
 Normal hepatic tissue or minimal
inflammation and no interface hepatitis.
 Action: d/c azathioprine and taper
prednisone
 TREATMENT FAILURE
 Worsening clinical, laboratory and
histologic findins despite compliance with
therapy
 Increase in aminotransferases by >60%
 Action: increase prednisone to 60mg daily
and azathioprine to 150mg daily for one
month
 TREATMENT FAILURE
 Treatment failures are frequent in patients
with established cirrhosis, HLA-DR3 or in
patients who present with disease at a
younger age and with a longer duration of
symptoms
 INCOMPLETE RESPONSE
 Some or no improvement in clinical,
laboratory or histologic features
 Failure to achieve remission after 3 years
 Action: indefinite treatment
 LIVER TRANSPLANT
 Patients with ascites and hepatic encephalopathy
(generally will have a poor prognosis, but
consider liver transplant if they have failed
glucocorticoid therapy.
 Considered in patients with multilobar necrosis
and have at least one laboratory parameter
which does not normalize within 2 weeks of
treatment (theses patients have a high
immediate mortality rate)
 LIVER TRANSPLANTATION
 Considered in pts who worsen while on
glucocorticoid therapy.
 Recurrence of disease after transplant is
common in those with AIH but has only
been described in patients who are not
adequately immunosuppressed.
PROGNOSIS
 PROGNOSIS
 40% of all pts with AIH develop cirrhosis
 54% develop esophageal varices within 2 years
 Poor prognosis if has presence of ascites or hepatic
encephalopathy
 13-20% of patients can have spontaneous resolution
 Of patients who survive the most early and active stage
of disease, approximately 41% of them develop inactive
cirrhosis.
 Of patients who have severe initial disease and survive
the first 2 years, typically survive long term.
 Algorithm of treatment CVH B
1. Therapy in a phase of viral replication with the minimum and moderate
activity
Monotherapy:
Interferon - 10-15 million IU 3 times p.w. for 3 months, then – 5-10 million IU
3 times p.w. The course is 6 months
2. Therapy in a phase of viral replication with high and moderate activity.
Combined:
Prednisolone – the first week-0,6 mg/kg p.d.; the second week - 0,6 mg/kg
p.d.; the third week-0,45 mg/kg p.d.; the fourth week – 0,25 mg/kg p.d.; the
fifth and sixth weeks – having interruption in treatment. Interferon – 10
million IU 3 times p.w. for 3 months, then- 1mln. IU 3 times p.w. for 6
months
Essentsiale - 5 ml i.v. on autoblood for 2 weeks, then - two caps. 3 times p.d.
The course is 6 months
3. Therapy in a phase of integration of a virus
Essentsiale - 5 ml i.v. on autoblood for 2 weeks, then 2 caps. 3 times p.d. The
course is 6 months
Cocarboxylase - 0,05 – 0,1 g 1 time p.d. The course of treatment is 15-20 days.
Pyridoxine hydrochloride - 1 %solution i.m. 2 ml 2 times p.d.
Ascorbinic acid-5 ml of 5% solution for 2 weeks.
α-tocopherol acetate-1 ml i.m. of 10 % solution for 15 days.
Unitiol - 5 ml i.v. of 5% solution for 10 days.
 Algorithm of treatment CVH С
1. 1 stage: Interferon - 3 million IU 3 times p.w. for 24 weeks.
Essentiale - 2 caps. 3 times p.d. for 24 weeks.
2- nd stage : a) aminotransferases level are normalized, virus
elimination has taken place: Interferon - 3 million IU 3 times p.w.
for 6-12 months
Essentsiale - 2 caps. 3 times p.d. for 6-12 months
b) aminotranferases level are decreased, but has not reached norm,
partial or unstable virus eradication:
Interferon - 3 million IU 3 times p.w. for 6-12 months
Essentsiale - 5 ml i.v. 2 times p.d. for 4 weeks, then – 2 caps. 3 times
p.d. for 6-12 months
c) aminotranferases level remained at initial level, virus elimination has
not taken place:
Interferon - 3 times p.d. for 6 months
Ribovirin – 1000-1200 mg p.d. for 6 months
Essentsiale - 2 caps. 3 times p.d. for 6-12 months
d) aminotransferases level remained invariable or has decreased, virus
elimination has not taken place:
Symptomatic therapy since treatment by interferon is not perspective
(antioxidants, vitamins, immunomodulators, deintoxication)
2. Pharmacotherapy of complications and systematic manifestations
3. Surgical treatment: liver transplantation
 Algorithm of treatment CVH D
1. Dietary food: with cellulose and vitamins
2. Pharmacotherapy:
Essentsiale – 5 ml i.v. 2 times p.d. for 4 weeks, then 2
caps. 3 times p.d. for 6-12 months.
Symptomatic therapy (hepatoprotectors, antioxidants,
vitamins, immunomodulators, deintoxication drugs).
Therapy of complications and systematic manifestations.
3. Therapy without medications: resort treatment in a
stage of remission.
4. Surgical treatment: liver transplantation.