Autoimun Hepatitis

8/12/2019 Autoimun Hepatitis

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Autoimmune hepatitis

An unresolving inflammation of the liver ofunknown cause.

Characterized by the presence of : interface hepatitis on histologic examination

Hypergammaglobulinemia

autoantibodies


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Diagnosis requires the exclusion ofother chronic liver diseases:

Wilson disease chronic viral hepatitis

1-anti-trypsindeficiency

Hemochromatosis

drug-induced liverdisease

nonalcoholicsteatohepatitis

primary biliary cirrhosis(PBC)

primary sclerosingcholangitis (PSC)

autoimmune

cholangitis


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EPIDEMIOLOGY white northern Europeans:

incidence :1.9 cases per 100,000 persons per year prevalence : 16.9 cases per 100,000 persons per year.

United States: AIH affects 100,000 to 200,000 persons 2.6% of the transplantations in the European Liver Transplant

Registry and 5.9% in the National Institutes of Health LiverTransplantation Database.

Alaskan natives : 43 per 100,000 population

white Norwegian: 16.9 per 100,000 population

AIH among patients with chronic liver disease in NorthAmerica: 11% - 23%.

populations are susceptible to AIH : African Americans,Brazilians, Argentinians, Arabs, Japanese, and Indians.


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PATHOGENESIS

The pathogenic mechanisms of AIH are unknown. constellation of interactive factors : triggering agent,

genetic predisposition, and various determinants ofautoantigen display, immunocyte activation, and effectorcell expansion.

Triggering factors : infectious agents, drugs, andtoxins.

The CD4+ helper T cell is the principal effector celland its activation is the initial step in the pathogenic

pathway. Liver cell destruction : cell-mediated cytotoxicity or

antibody-dependent cell-mediated cytotoxicity, or acombination of both mechanisms


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CLINICAL FEATURES


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CLINICAL FEATURES


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CLINICAL FEATURES


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CLINICAL FEATURES


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SCORING

CRITERIAof AIH


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The revised original scoring system performsbetter in patients with few or atypicalfeatures of AIH, and the simplified system is

better at excluding the diagnosis in diseaseswith concurrent immune manifestations

Sensivity : 100% vs 95%

Specifity : 90% vs 73%

excluding the diagnosis in other diseases withconcurrent immune features : 83% vs 64%

Albert J. Czaja, May 2008


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DIAGNOSTIC CRITERIA

The serologic tests essential for diagnosis are assays for

antinuclear antibodies (ANA), smooth muscle antibodies

(SMA), and antibodies to liver-kidney microsome type 1 (anti-

LKM1).

Peri-nuclear anti-neutrophil cytoplasmic antibodies (pANCAs)

are common in type 1 AIH

Antibodies to soluble liver antigen/liver pancreas (anti-

SLA/LP), actin (anti-actin), chromatin (anti-chromatin),asialoglycoprotein receptor (ASGPR), and liver cytosol type 1

(anti-LC1) associated with severe disease, poor treatment

response, and relapse after drug withdrawal


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CLINICAL CRITERIA

The definite diagnosis : exclusion of other similardiseases

laboratory findings that indicate substantial

immunoreactivity histologic features of interface hepatitis

A probable diagnosis : findings are compatible withAIH but insufficient for a definite diagnosis


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CLASSIFICATION

Three types of AIH : on the basis of serologicmarkers, but only two types have distinctiveserologic profiles.

Variant forms : Patients who have atypical featuresof AIH currently lack an official designation andconfident treatment strategy:

manifestations of AIH and another type of chronic liver

disease overlap syndrome

findings that are incompatible with AIH by currentdiagnostic criteria outlier syndrome


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Classification ofAutoimmune

Hepatitis Based onAutoantibodies


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Variant Forms of Autoimmune Hepatitis


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Conventional Repertoire ofAutoantibodies

ANA can be found in primary biliarycirrhosis, primary sclerosing cholangitis,chronic viral, hepatitis, drug-related

hepatitis, nonalcoholic steatohepatitis andalcohol-induced liver disease

ANA are the traditional markers of AIH :

present alone (13%) or with SMA (54%)in 67% of patients with the disease


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SMA are present in 87% of patients withAIH, either as the sole marker of thedisease (33%) or in conjunction with ANA

(54%)

Anti-LKM1 typically occur in the absenceof SMA and ANA.


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LABORATORY INDICES

Serum AST and gamma globulin levels theseverity of disease and immediate prognosis.

Sustained severe derangements poor

outcome unless therapy is started. Less severe laboratory abnormalities better

prognosis

Spontaneous resolution is possible in 13% to20% of patients regardless of disease activity.


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HISTOPATHOLOGIC FINDINGS

The histologic findings : indices of diseaseseverity, pattern of liver cell injury prognostic implication

Inactive cirrhosis develops in 41%.

Hepatocellular carcinoma also can occur inpatients with cirrhosis (small risk)


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Precise histological evaluation of liver biopsy

specimen is indispensable for diagnosis andtreatment of acute-onset autoimmune hepatitisJ Gastroenterol 2008; 43:951958

Histological examination of the liver is necessary forearly diagnosis of acute-onset AIH. Moreover, we shouldevaluate liver biopsy specimens precisely and should beready for a timely initiation of corticosteroid therapy toimprove the prognosis.

KEIICHI FUJIWARA1,2, YOSHIHIRO FUKUDA1,2, and OSAMU YOKOSUKA


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PROGNOSTIC INDICES

the severity of liver inflammation at theinitial medical consultation :

the laboratory indices and the histologicfindings

HLA status and ethnicity influence disease

occurrence, clinical phenotype, and treatmentoutcome


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Treatment Indications inAutoimmune Hepatitis


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Preferred Treatment Regimensin Autoimmune Hepatitis


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TREATMENT END POINTS

Glucocorticoid therapy until remission, treatment failure,incomplete response, or drug toxicity occurs

Liver biopsy examination before drug withdrawal ensures anoptimal end point. Improvement of the liver tissue to normal: relapse only 20% after

cessation of treatment. Improvement to portal hepatitis alone 50% frequency of relapse. Progression to cirrhosis or persistence of interface hepatitis 100%

frequency of relapse.

The presence of plasma cells within the portal tract persistentimmune reactivity and the propensity for relapse


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End Points of Initial Treatment andCourses of Action


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Remission

the absence of symptoms, resolutionof inflammatory indices and histologic

improvement to normal or minimalactivity.


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TREATMENT FAILURE

deterioration during therapy (9%)

It is characterized by worsening of the serumAST or bilirubin levels by at least 67% of

previous values, progressive histologic activity,or onset of ascites or encephalopathy.

Conventional glucocorticoid therapy should bestopped, and a high-dose regimen should beinstituted.


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INCOMPLETE RESPONSE

13% : clinical improvement but the findingsdo not satisfy remission criteria

A low-dose prednisone regimen and theadministration of azathioprine (2 mg/kgdaily) as the sole drug are reasonableapproaches.

The goal of treatment is to reduce andstabilize disease activity


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LIVER TRANSPLANTATION

Liver transplantation is effective in the treatment ofdecompensated AIH

Five-year survival rates for patients and grafts rangefrom 83% to 92%, and the actuarial 10-year survival

rate after transplantation is 75%. Autoimmune hepatitis recurs in at least 17% of patients,

and AIH develops de novo in 3% to 5% of patientsundergoing transplantation for nonautoimmune liverdisease.

Acute rejection, glucocorticoid-resistant rejection, andchronic rejection occur more commonly in patientsundergoing transplantation for AIH


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RELAPSE

Relapse occurs in 50% within 6 months, and most patients(70% to 86%) experience exacerbation within 3 years.

The major consequence of relapse and retreatment is thedevelopment of drug-related complications (70% of thosewho have multiple relapses and retreatments)

Patients who have had at least two relapses should begiven either low-dose prednisone or azathioprine as thesole drug 87% can be managed long term on prednisone at less than 10 mg

per day (median dose, 7.5 mg per day).

Continuous azathioprine therapy (2 mg/kg per day) is analternative strategy that can be used in patients who arenot severely cytopenic. 83% remain in remission for up to 10 years


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Recurrent AIH

typically is mild and develops in patientswho are inadequately immunosuppressed.

Dose adjustments usually are sufficient tosuppress the disease, but progression tocirrhosis and graft failure have beenreported


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Autoimun Hepatitis