Autuimmun Hepatitis

8/12/2019 Autuimmun Hepatitis

1/32

AUTOIMMUNE HEPATITISSima Patel

Morning Report9/10/08


2/32

AUTOIMMUNE HEPATITIS

Chronic hepatitis of unknown etiology

Can progress to cirrhosis

Characteristics include: presence of autoimmune antibody

evidence of hepatitis

elevation of serum globulins


3/32

OTHER NAMES

Active chronic hepatitis or chronic activehepatitis

Chronic aggressive hepatitis

Lupoid hepatitis

Plasma cell hepatitis

Autoimmune chronic active hepatitis


4/32

BACKGROUND

First described in 1950s

Accounts for 5.6% of liver transplants inthe US

Affects women more than men (3.6:1)

If untreated approximately 40% die within

6 months 40% develop cirrhosis


5/32

CLASSIFICATION

TYPE 1

TYPE 2

OVERLAP SYNDROMES


6/32

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 andC, plasma membrane sulfatides


7/32

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, systemicsclerosis, ITP, SLE

40% present with acute onset of symptomssimilar to toxic hepatitis or acute viral hepatitis


8/32

TYPE 2

Presence of anti-Liver/Kidney MicrosomeAntibodies or anti-Liver Cytosol antibody(ALC-1)


9/32

OVERLAP SYNDROMES

Primary Biliary Cirrhosis

Primary Sclerosing Cholangitis

5% of patients with chronic hepatitis C willhave an ANA titer of >1:100

A homogeneous pattern of staining is

more common in ANA positiveautoimmune hepatitis compared to that of

ANA positive chronic hepatitis C


10/32

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


11/32

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


12/32


13/32

HISTOLOGY

Chronic hepatitis with marked piecemealnecrosis and lobular involvement

Numerous plasma cells

Interface hepatitis: hallmark finding


14/32

HISTOLOGY


15/32


16/32

PATHOGENESIS

Unknown mechanism but several proposed mechanisms

Genetically predisposed individual with exposure to anenvironmental agent triggers the autoimmunepathogenic process

Genetic predisposing factors: HLA-DR3: early onset, severe form

HLA-DR4: caucasian, late onset, better response to steroids,higher incidence of extrahepatic manifestations

IgG: part of the IgG molecule (mainly the heavy chain)

T-Cell receptors


17/32

PATHOGENESIS

Environmental Triggers: presumed to becertain viruses, toxins, drugs

Drugs:

Oxyphenisatin Methyldopa

Nitrofurantoin

Diclofenac Minocycline

statins


18/32

TREATMENT

Should be based on:

Severity of symptoms

Degree of elevation in transaminases and IgG

Histologic findings

Potential side effects of treatment


19/32

AASLD RECOMMENDATIONS

Treat if serum aminotransferases are greaterthan 10 times normal

Treat if serum aminotransferases are greater

than 5 times normal and IgG is elevated togreater than 2 times normal

In patients with inactive cirrhosis evaluate forpreexisting comorbidities (hep C), pregnancy,and drug intolerances (increased risk of steroidside effects in pts with DM, osteoporosis, HTN)


20/32


21/32

TREATMENT

Corticosteroids

Azathioprine

Children: azathioprine or 6MP


22/32

PREDNISONE ONLY

Prednisone 60mg PO daily with a taperdown to 30mg at the 4thweek intotreatment and then maintenance of 20mg

daily until reach endpoint Reasons for Prednisone only:

Cytopenia

TPMT deficiency Malignancy

pregnancy


23/32

COMBINATION THERAPY

Prednisone + Azathioprine

Prednisone: start at 30mg daily and taperdown to 15mg at week 4, then maintainon 10mg daily until therapy endpoint

Azathioprine 50mg daily


24/32

TREATMENT REMISSION

Disappearance of symptoms

Normal serum bilirubin and IgG

Serum aminotransferases normal or lessthan twice normal

Normal hepatic tissue or minimal

inflammation and no interface hepatitis.Action: d/c azathioprine and taper

prednisone


25/32

TREATMENT FAILURE

Worsening clinical, laboratory andhistologic findins despite compliance withtherapy

Increase in aminotransferases by >60%

Action: increase prednisone to 60mg dailyand azathioprine to 150mg daily for onemonth


26/32

TREATMENT FAILURE

Treatment failures are frequent in patientswith established cirrhosis, HLA-DR3 or inpatients who present with disease at a

younger age and with a longer duration ofsymptoms


27/32

INCOMPLETE RESPONSE

Some or no improvement in clinical,laboratory or histologic features

Failure to achieve remission after 3 years

Action: indefinite treatment


28/32

LIVER TRANSPLANT

Patients with ascites and hepaticencephalopathy (generally will have a poorprognosis, but consider liver transplant if they

have failed glucocorticoid therapy. Considered in patients with multilobar necrosis

and have at least one laboratory parameterwhich does not normalize within 2 weeks of

treatment (theses patients have a highimmediate mortality rate)


29/32

LIVER TRANSPLANTATION

Considered in pts who worsen while onglucocorticoid therapy.

Recurrence of disease after transplant iscommon in those with AIH but has onlybeen described in patients who are notadequately immunosuppressed.


30/32

PROGNOSIS


31/32

PROGNOSIS

40% of all pts with AIH develop cirrhosis

54% develop esophageal varices within 2 years

Poor prognosis if has presence of ascites or hepaticencephalopathy

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 inactivecirrhosis.

Of patients who have severe initial disease and survivethe first 2 years, typically survive long term.


32/32

REFERENCES

Czaja AJ, Freese DK. Diagnosis and Treatmentof Autoimmune Hepatitis. Hepatology 2002;479-497

Feldman, Mark and Lawrence Friedman.

Sleisenger & Fordtrans Gastrointestinal andLiver Disease: Pathophysiology, Diagnosis, andManagement. Autoimmune Hepatitis. ElsevierHealth Sciences. 1869-1882. July 2006.

Czaja, Albert J. Current Concepts in AutoimmuneHepatitis. Annals of Hepatology 2005. 4(1) Jan-Mar: 6-24.

www.uptodate.com
http://www.uptodate.com/http://www.uptodate.com/

Date post:	03-Jun-2018
Category:	Documents
Upload:	siusiuwidyanto
View:	215 times
Download:	0 times

Autuimmun Hepatitis

Documents