03-19 Autoimmune Hepatitis Flashcards
After this lecture you should have knowledge in the following principles. 1. General insights with respect to the role of the liver as part of the body’s immune system a. i.e. “Discuss the condition of the immune system in a patient with liver disease” 2. The immune system and liver disease 3. Describe autoimmunity with respect to the liver a. Knowledge of key features of the 2 most important autoimmune liver diseases: (1) Classic AIH: hepatocyte = target (2) PBC: small bile d
<p>OBJECTIVE: General insights with respect to the role of the liver as part of the body’s immune system</p>
<p>20% of all liver cells have immune function:</p>
<ul>
<li>NK cells</li>
<li>T lymphocytes</li>
<li>Macrophages (Kupffer cells)</li>
<li>Sinusoidal cells</li>
<li>Dendritic cells</li>
</ul>
<p>OBJECTIVE: Discuss the immune system and liver disease</p>
<p>.</p>
<p>OBJECTIVE: Distinguishing and Dx features of AIH</p>
<ul>
<li>Who get it?</li>
<li>S/Sx</li>
<li>Labs</li>
<li>Bx</li>
<li>Clinical Course</li>
<li>Associated With?</li>
<li>Tx</li>
</ul>
<p><strong>Who gets it?</strong></p>
<ul>
<li>♀ >♂</li>
<li>Autoimmune background (patient/family), HLA DR3 (classic) / DR4 (late onset)</li>
</ul>
<p><strong>S/Sx</strong></p>
<ul>
<li>"Kaleidoscopic" presentation:
<ul>
<li>Range from asx to fulminant liver failure</li>
<li>Symptoms can include
<ul>
<li>77%Dark urine / light colored stools</li>
<li>48%RUQ discomfort/pain</li>
<li>30%Generalized myalgias</li>
<li>30% Anorexia</li>
<li>28% Diarrhea</li>
<li>amenorrhea,itching,arthralgias</li>
</ul>
</li>
</ul>
</li>
<li>Exam can be <u>normal</u> or show:
<ul>
<li>78% Hepatomegaly</li>
<li>58% spider nevi</li>
<li>32-56% palpable spleen</li>
<li>46%Sceral icterus</li>
<li>20%Ascites</li>
<li>14%Encephalopathy</li>
</ul>
</li>
</ul>
<p><strong>Labs: Two Types of Dz</strong></p>
<p><u>Both</u></p>
<ul>
<li><strong>↑Transaminases</strong>(often 500–1000 IU/L)</li>
<li>disproportionately ↓ albumin and prolonged PT/INR</li>
<li>hypergammaglobulinemia</li>
<li>Ig (IgG)/gamma-globulin elevation [TP –MINUSALBUMIN]</li>
</ul>
<p><u>Type 1</u></p>
<ul>
<li>ANA* (+) and/or SMA* (+) ,</li>
</ul>
<p><u>Type 2</u></p>
<ul>
<li>Anti-LKM* (young, ♀, more prevalent in Europe and Japan)</li>
</ul>
<p><em>Pour autant que nous sachions, ces ne sont pas responsables pour la pathologie; ils sont juste des marqueursbiochimiques.</em></p>
<p><strong>Bx</strong></p>
<ul>
<li>Liver biopsy with piecemeal necrosis (interface hepatitis)</li>
<li>often lymphoplasmacytic inflammatory response</li>
<li>plasma cells</li>
<li>sometimes rosettes, bridging necrosis, cirrhosis</li>
</ul>
<p><strong>Clinical Course</strong></p>
<ul>
<li>Responsive to immunosuppression (65% in remission after 18 mos tx)</li>
<li>Flare-up after discontinuation of therapy or undulant course if not treated</li>
<li>10-yr life expect. 93% (similar to age-/sex-matched controls)</li>
</ul>
<p><strong>Associated With</strong></p>
<ul>
<li>most common = thyroiditis</li>
<li>Sjögren’s, ITP, hemolytic anemia, RTA, RA,Fibrosing alveolitis,Peripheral neuropathy, GN, UC, Crohn's)</li>
</ul>
<p><strong>Tx</strong></p>
<ul>
<li>Start high dose pred and azathioprine</li>
<li>Gradual taper off pred</li>
<li>Maintenance azathioprine for years</li>
</ul>
<p>OBJECTIVE: Distinguishing and Dx features of PBC</p>
<ul>
<li>Who get it?</li>
<li>S/Sx</li>
<li>Exam</li>
<li>Labs</li>
<li>Bx</li>
<li>Tx</li>
<li>Clinical Course</li>
<li>Associated Conditions</li>
</ul>
<p><u><strong>Primary Biliary Cirrhosis (PBC)</strong></u></p>
<p><em>Targets Smaller Bile Ducts</em></p>
<p><strong>Who Gets It?</strong></p>
<ul>
<li>♀>>♂;Typically middle-aged folks</li>
</ul>
<p><strong>S/Sx</strong></p>
<ul>
<li>Most asx</li>
<li>May present as itching, though nl bili</li>
<li>Hyperpigmented</li>
<li>Rheum problems
<ul>
<li>Arthritis</li>
<li>Sjogren’s syndrome</li>
<li>Limited scleroderma (CREST)</li>
</ul>
</li>
</ul>
<p><strong>Exam</strong></p>
<ul>
<li>Usu. nl in asx pts</li>
<li>Hyperpigmentation</li>
<li>Excoriations from scratching due to pruritis</li>
<li>Jaundice (late manifestaion)</li>
<li>Xanthomas from hyperlipidemia</li>
<li>Xanthelasmas</li>
<li>Hepatosplenomegaly</li>
</ul>
<p><strong>Labs</strong></p>
<ul>
<li><strong>Cholestatic liver tests</strong>, often found during routine screening</li>
<li><strong>Positive AMA</strong> (anti-mito Abs)</li>
<li>elevated IgM</li>
<li>hyperlipidemia</li>
</ul>
<p><strong>Bx</strong></p>
<ul>
<li>FLORID DUCT LESION (seen here)</li>
<li>vanishing bile ducts</li>
<li>granulomas</li>
</ul>
<p><strong>Tx</strong></p>
<ul>
<li>Ursodeoxycholic acid (UDCA)</li>
<li>Immunosuppressants <u>DON'T</u> help</li>
</ul>
<p><strong>Clinical Course</strong></p>
<ul>
<li>Slowly progressive disease</li>
<li>Long-term risk of hepatic osteodystrophy</li>
</ul>
<p><strong>Associated Conditions</strong></p>
<ul>
<li>Metab bone dz- severe osteoporosis</li>
<li>Hypercholesterolemia
<ul>
<li>But w/o incr risk of CVD for some reason</li>
</ul>
</li>
<li>Fat soluble vitamin malabsorption (w/ advanced PBC)</li>
<li>UTIs</li>
<li>Other autoimmune conditions:
<ul>
<li>thyroid dysfunction</li>
<li>CREST syndrome</li>
<li>Raynaud’s syndrome</li>
<li>Celiac</li>
<li>RA</li>
</ul>
</li>
</ul>
<p>OBJECTIVE: Distinguishing and Dx features of PSC</p>
<ul>
<li>Who get it?</li>
<li>S/Sx</li>
<li>Labs</li>
<li>Bx</li>
<li>Clinical Course</li>
</ul>
<p><u><strong>Primary Sclerosing Cholangitis (PSC)</strong></u></p>
<p><em>Targets Larger Bile Ducts</em></p>
<p><strong>Who Gets It?</strong></p>
<ul>
<li>♂ >>♀ (opposite of PBC)</li>
<li>30-40 y/o (younger than PBC)</li>
<li>~90% PSC pts have UC or Crohn's</li>
</ul>
<p><strong>S/Sx</strong></p>
<ul>
<li>
<p>Cholestatic liver tests</p>
</li>
</ul>
<p><strong>Labs</strong></p>
<ul>
<li>
<p>Cholestatic liver tests</p>
</li>
</ul>
<p><strong>Bx</strong></p>
<ul>
<li>Concentric fibrosis around bile ducts
<ul>
<li>i.e. "onion skinning" (seen here)</li>
</ul>
</li>
</ul>
<p><strong>Clinical Course</strong></p>
<ul>
<li>Slowly progressive disease</li>
<li>Risk for cholangiocarcinoma (often CoD)</li>
<li>higher risk of colon cancer esp in the 90% who also have colitis (even higher than those w/ UC only)</li>
</ul>
<p>OBJECTIVE: Immune features secondary to other liver disease (drugs, alcohol, viral hepatitis etc.)</p>
<p>Hepatitis B</p>
<ul>
<li>Immune system targets infected hepatocytes</li>
<li>The damage is really done by the immune system's reaction to the virus rather than the virus itself.</li>
<li>Those w/ less potent immune system (e.g. neonates) more likely to have subclinical disease but chronic disease (i.e. immune tolerance)</li>
<li>Three degrees of immune response
<ol>
<li>Immune tolerance</li>
<li>Acute hepatitis then clearance</li>
<li>Fulminant hepatitis then death or transplant</li>
</ol>
</li>
</ul>
<p>OBJECTIVE: Liver disease in the immune-compromised host</p>
<p>.</p>
<p>OBJECTIVE: List the general principles of treatment of autoimmune diseases.</p>
<p>Two goals</p>
<ol>
<li>Induction of remission (more aggressive therapy)
<ul>
<li>Example meds include:
<ul>
<li>prednisone (osteoporosis, etc.)</li>
<li>azathioprine (liver failure, etc.)</li>
<li>cyclosporine (HTN, tremors)</li>
</ul>
</li>
</ul>
</li>
<li>Maintenance of remission
<ul>
<li>Try to get off prednisone</li>
<li>Newer options include TNFα antagnoists like infliximab</li>
</ul>
</li>
</ol>
<p> </p>
<p>DDx for Marked Elevated Transaminases (i.e. > 1000)</p>
<ul>
<li>Acute viral hepatitis</li>
<li>Autoimmune hepatitis</li>
<li>Shock liver (ischemic hepatitis)</li>
<li>Acute drug or toxin liver injury</li>
<li>Occasionally bile duct stone</li>
</ul>
<p>If wicked high (i.e. > 10,000) think:</p>
<ul>
<li>Acetaminophen toxicity</li>
<li>Severe shock liver (ischemic liver injury)</li>
</ul>
<p>Describe the significance of different AST: ALT patterns</p>
<p>DDx for cholestatic liver enzyme elevations (i.e. Alk Phos & GGT)</p>
<p><strong>Due to Biliary Obstruction</strong></p>
<ul>
<li>Stones</li>
<li>Tumors</li>
<li>PSC (bigger ducts)</li>
<li>AIDS cholangiopathy
<ul>
<li>Rare now w/ HAART</li>
</ul>
</li>
<li>Biliary strictures</li>
</ul>
<p><strong>Due to Hepatic Cholestasis</strong></p>
<ul>
<li>PBC</li>
<li>Sepsis</li>
<li>TPN</li>
<li>Viral hepatitis</li>
<li>Meds (sometimes)</li>
<li>Alcoholic hepatitis</li>
<li>NASH (sometimes)</li>
</ul>
<p><em>To determine biliary obstruction vs. hepatic cholestasis you need to image the liver/biliary tree with U/S or cross sectional imaging and look for biliary ductal dilation.</em></p>
<p>DDx for chronic (moderately) elevated transaminases (i.e. > 3 mos, elevation < 1000)</p>
<p><strong>Common Causes</strong></p>
<ul>
<li>NAFLD</li>
<li>Alcoholic liver disease</li>
<li>Chronic viral hepatitis (esp Hep C)</li>
<li>Drug-induced liver injury</li>
<li>Hemochromatosis </li>
</ul>
<p><strong>Uncommon Causes</strong></p>
<ul>
<li>AIH</li>
<li>A1AT</li>
<li>Wilson's</li>
<li>Sarcoidosis</li>
<li>Crohn's Dz</li>
</ul>
