AUTOIMMUNE HEPATITIS

Description • Progressive and chronic

o Hepatocellular necroinflammation
o Autoantibodies (IgG)
o Responsive to immunosuppressive therapy
• More commonly affects FEMALES
o Bimodal age distribution – children and adults
• Genetic predisposition based on your HLA
• Types of autoantibodies
o ANA – anti-nuclear antibody
o SMA – smooth muscle antibody
o SLA/LP – Antibodies against soluble liver antigen/liver
pancreas antigen
o LKM-1 – Anti Liver kidney microsomal Ab (KIDS)
• Two types
o Type 1 Autoimmune Hepatitis
§ 80% of all cases
§ + for ANA, ASMA, or both
§ 70% females
§ commonly assoc. with other autoimmune dz.
(thyroid, celiac, ulcerative colitis, etc)
o Type 2 Autoimmune Hepatitis
§ Mostly children
§ Anti-LKM antibody
§ Commonly with vitiligo or Diabetes 1
§ More common to fail with treatment à leads to
liver transplant
Presentation/ o Asymptomatic
Symptoms o Acute hepatitis (25-30%)
o Younger age
o Fatigue, myalgias, athralgias
o Rise in liver enzymes but normal synthetic fxn
o Fulmnant hepatitis less common <5%

Diagnosis o Scoring system

o Autoantibodies (ANA, ASMA)
o Elevated IgG
o Histology
Biopsy/
Pathology

• PLASMA CELLS bc antibodies from B cells in absence of virus

• Interface hepatitis
• Lobar infiltrate

Treatment o Goal: induce remission and prevent progression to cirrhosis

or HCC
o Treat with immunosuppression
§ Start with corticosteroid: PREDNISONE
§ Add Azathioprine (inhibits purine synthesis)
• Then wean off prednisone
o Majority relapse if they stop treatment à life-long
Primary Biliary Cholangitis (PBC)
Description • Autoimmune dz with SLOW destruction of small bile ducts in
liver
• Anti-mitochondrial Antibody (AMA) is hallmark of PBC
• Female predominant
Presentation/ • Fatigue, pruritis, jaundice, RUQ pain, Hyperpigmentation,
Symptoms Xanthomas, Dyslipidemia, vitamin deficiencies
XANTHELASMA bc too much cholesterol

HYPERCHOLESTEROLEMIA
• Accumulation of Lipoprotein X (abnormal)
• Stage 1,2 – high HDL
• Stage 3,4 – High LDL
Diagnosis Positive AMA
High AP and GGT
Biopsy/ Useful for staging – will see enormous inflammatory infiltrate
Pathology surrounding small bile ducts
Treatment Ursodeoxycholic Acid to promote normal bile acid secretion, and reduce
hepatotoxic bile acids
• Also stabilizes biliary epithelial cell membranes by altering HLA-
2 expression
• Inhibits biliary cell apoptosis
• Delays dz progression
• Well tolerated life-long
• Some pts still need liver transplant
PRIMARY SCLEROSING CHOLANGITIS (PSC)
Description Chronic, cholestatatic (affects bile) liver dz
• Inflammation nd fibrosis of BOTH intra and extrahepatic bile ducts
• PSC AFFECTS LARGER BILE DUCTS
• Leads to multifocal bile duct strictures
Male predominant
SCREEN PSC PATIENTS FOR IBD, especially ULCERATIVE
COLITIS
Presentation/ • Fatigue, abdominal discomfort, pruritis, weight loss
Symptoms • 44% asymptomatic
Diagnosis Labs
• high AP and GGT (cholestatic picture)
• increased transaminases
• elevated IgG
• autoantibodies à p-ANCA, ANA, ASMA (NEG FOR AMA)
MRCP à beads on a string appearance

Biopsy/ Liver biopsy used to stage dz but usually doesn’t picture the large bile
Pathology ducts
• may show onion-skin (periductal) fibrosis in ~10% of biopsies

•
Treatment Only treatment is liver transplant
MONITOR FOR
• choloangiocarcinoma
• colon cancer (esp. if pt has UC)
HEREDITARY HEMOCHROMATOSIS
Description Autosomal recessive
• defective HFE gene (on chromosome 6)
• C282Y or H63D missense mutations
increased iron absorption and deposition
Iron accumulates gradually over decades
• Transferrin saturation >45%
• Rise in serum ferritin
• Women somewhat protected bc menses
Untreated à cirrhosis, HCC
Presentation/ • Liver: hepatomegaly elevated enzymes
Symptoms • Cardiac: cardiomyopathy, MI
• Endocrine: amenorrhea/impotence, diabetes
• MSK: arthritis, arthralgia,
• Systemic: chronic fatigue
• Skin bronzing

Diagnosis Charcot triad

1. Cirrhosis – hepatic damage
2. Diabetes mellitus 2 –pancreatic damage
3. Bronzing of skin – hyperpigmentation
Diagnose with iron levels (high transferrin sats, ferritin >1000), confirm
with genetic testing (HFE gene, C282Y mutation)
Biopsy/ Not routine
Pathology
Treatment Frequent phlebotomy
Or chelators if phlebotomy is a no go
Liver transplant for decompensated dz
WILSON’S DISEASE
Description Autosomal recessive
Dz of copper transport
• Cu normally eliminated in bile
Cu accumulates in hepatocytes and can accum in brain and kidneys
• LIVER and CNS/psychiatric damage

Presentation/ Usually youngsters (age 2-40)

Symptoms • Liver: hepatomegaly, acute hepatitis, liver failure, cirrhosis
• Hematologic: hemolysis
• Neuro: hypokinetic speech, tremor, dystonia
• Psych: depression, ADHD, irritability

Two types of liver injury

1. Acute – mainly young young females, acute hep, ALF, AKI (LOW
AP)
2. Chronic – adolescents and adults, indolent progression to cirrhosis,
gradual extrahepatic deposition

Extra-Hepatic Manifestation
• EYES – Kayser Fleisher Rings

•
• CNS – behavioral changes, dystonia
• Renal
• Liver
• Bone
• cariac
Diagnosis KF Rings, low ceruloplasmin <14g/L (suggests Cu overload), elevated
urinary Cu
Biopsy/ nah
Pathology
Treatment Chelation therapy to deplete excess copper
Zinc for maintentenance therapy à prevents dietary abs of Cu
Liver transplant in ALF or decom cirrhosis
ALPHA-1 AntiTRYPSIN DEFICIENCY
Description Alpha Antitrypsin=circulating protease inhibitor made in LIVER
à inhibits neutrophil elastase (protects lung from injury)

Homozygous mutation à accumulate protein product in hepatocytes à

injury

Liver disease genotype: ZZ, SZ, sometimes SS

Presentation/ • neonatal hepatitis (ZZ homozygotes), jaundice

Symptoms • present in adulthood with liver or lung dz

High transaminases (hepatocell injury) à fibrosis à cirrhosis à maybe

HCC
Diagnosis Under-diagnoses
Indicated in those with COPD, Asthma, unexplained liver dz
Biopsy/ Chronic hepatitis with or without cirrhosis
Pathology PAS positive globules on biopsy

Treatment Stop smoking, pneumovax

No specific therapy rly