Differentials
Primary biliary cirrhosis
SIGNS / SYMPTOMS
Main complaints are fatigue and pruritus, which are usually more pronounced than in AIH.
INVESTIGATIONS
Alkaline phosphatase and gamma glutamyl transferase elevated more strikingly than aminotransferase levels. Antimitochondrial antibodies (AMAs) present in 95% of cases and antinuclear antibodies (ANAs) in up to 70%.
Liver biopsy shows bile duct lesion or periductal fibrosis.
Primary sclerosing cholangitis
SIGNS / SYMPTOMS
Features often overlap with AIH.
More common in men than in women. Median age at diagnosis is approximately 40 years.
Strongly associated with inflammatory bowel disease.
INVESTIGATIONS
Markedly elevated alkaline phosphatase. Perinuclear antineutrophil cytoplasmic autoantibodies are dominant autoantibodies.
Abnormal cholangiogram.
Liver biopsy shows bile duct abnormalities.
No response to corticosteroids.
Chronic hepatitis B
SIGNS / SYMPTOMS
Clinical presentation sometimes similar with mild elevations of liver function tests.
INVESTIGATIONS
Presence of hepatitis B serologic markers: HBsAg, antibody to hepatitis B surface antigen, antibody to hepatitis B core antigen, hepatitis B e-antigen, and antibody to hepatitis B e-antigen.
Histology: ground-glass hepatocytes; immunoperoxidase staining for hepatitis B virus antigens.
Chronic hepatitis C
SIGNS / SYMPTOMS
Clinical presentation sometimes similar with mild elevations of liver function tests.
INVESTIGATIONS
Presence of hepatitis C serologic markers (hepatitis C antibody, hepatitis C viral RNA). Antinuclear antibody (ANA), smooth muscle antibody (SMA), and anti-liver kidney microsome antibodies (anti-LKM-1) occasionally present.
Histology: ground-glass hepatocytes; nodular-appearing infiltrates; steatosis in hepatitis C virus genotype 3.
Chronic hepatitis D
SIGNS / SYMPTOMS
Clinical presentation may be similar. It occurs only in the presence of hepatitis B infection.
INVESTIGATIONS
Presence of hepatitis B virus and hepatitis D virus serologic markers.
Hepatitis due to other viruses
SIGNS / SYMPTOMS
Clinical presentation sometimes similar, with signs of involvement of other organs.
INVESTIGATIONS
Presence of serologic markers of viral infection (cytomegalovirus, Epstein-Barr virus).
Chronic drug-induced hepatitis
SIGNS / SYMPTOMS
History of precipitating drug, for example, methyldopa, minocycline, nitrofurantoin, diclofenac, phenytoin, propylthiouracil.
Clinical presentation similar to AIH; female preponderance.
INVESTIGATIONS
Patients may have experienced previous episode of hepatotoxicity. Improvement upon withdrawal of the suspected agent.
Autoantibodies (antinuclear antibody [ANA], smooth muscle antibody [SMA], anti-LKM) and hyperglobulinemia may be present.
Histologic features may be consistent with AIH.
Genetic hemochromatosis
SIGNS / SYMPTOMS
Patients may present with hepatomegaly, abdominal pain, and darkened skin pigmentation.
Continued deposition of iron in other tissues (pancreas, heart, and pituitary) may lead to progressive damage and dysfunction, and additional complications may ensue (diabetes, dysrhythmias, cardiomyopathy, and hemolytic anemia).
INVESTIGATIONS
Increased hepatic iron concentrations and elevated serum ferritin levels.
Genotyping: C282Y homozygosity or C282Y/H63D compound heterozygosity.
Histology: qualitative and quantitative hepatic iron determination.
Alpha-1 antitrypsin deficiency
SIGNS / SYMPTOMS
Clinical manifestations related to the lung, the liver, and, much less often, the skin.
INVESTIGATIONS
Diagnosis of severe alpha-1 antitrypsin deficiency is confirmed by a serum level below 50 to 80 mg/dL (11 micromol/L) in combination with a severe deficient genotype, generally determined by isoelectric focusing.
Wilson disease
SIGNS / SYMPTOMS
Symptoms originating from liver or central nervous system (neuropsychiatric disease). Sometimes cardiac manifestations (arrhythmias).
Kayser-Fleischer rings usually present, sometimes skin pigmentation and bluish discoloration at the fingernail base.
INVESTIGATIONS
Reduced serum ceruloplasmin levels (less than 20 mg/dL) in a patient who also has Kayser-Fleischer rings is considered to be diagnostic.
Additional findings: serum copper decreased with excessive urinary copper excretion.
Cholangiopathy related to AIDS
SIGNS / SYMPTOMS
Typical symptoms include right upper quadrant and epigastric pain and diarrhea; fever and jaundice are less common, occurring in 10% to 20% of patients.
INVESTIGATIONS
Liver function tests usually indicative of cholestasis. Serologic evidence of HIV infection. CD4 count below 100/mm³.
Diagnosis is made by endoscopic retrograde cholangiopancreatography or magnetic resonance cholangiopancreatography.[38]
Metabolic dysfunction-associated steatohepatitis (MASH; formerly nonalcoholic steatohepatitis)
SIGNS / SYMPTOMS
Presence of 1 or more components of metabolic syndrome: obesity, diabetes, hyperlipidemia, hypertension.
INVESTIGATIONS
Antinuclear antibodies (ANAs) and smooth muscle antibodies (SMAs) sometimes present at low titer; other autoantibodies absent.
Magnitude of fatty infiltration, presence of polymorphonuclear (PMN) leukocytes, and central fibrosis in the liver biopsy point to steatohepatitis.
Alcoholic liver disease
SIGNS / SYMPTOMS
Similar presentation with chronic elevation of aminotransferases and similar symptoms.
History of excessive alcohol drinking.
INVESTIGATIONS
Autoantibodies absent. Carbohydrate-deficient transferrin present.
Liver histology showing macrovesicular steatosis, infiltration by neutrophils, perivenular distribution of inflammation and fibrosis, Mallory bodies.
Systemic lupus erythematosus
SIGNS / SYMPTOMS
Organ systems affected include: skin (photosensitive rash), joints (arthralgia, arthritis), kidneys (nephritis or nephrotic syndrome), lungs (pneumonitis), nervous system (seizures, psychosis), serous membranes (pleuritis, pericarditis, peritonitis), and/or other.
AIH is sometimes associated with a number of autoimmune extrahepatic disorders similar to lupus.
INVESTIGATIONS
Smooth muscle antibodies (SMAs) and antimitochondrial antibodies (AMAs) are rare in lupus; their presence suggests AIH.
Antinuclear antibodies (ANAs) are present in both conditions.
For systemic lupus erythematosus, the following are typical: antiphospholipid antibodies, anti-dsDNA, and anti-Smith (Sm) antibodies.
Granulomatous hepatitis
SIGNS / SYMPTOMS
Granulomas in the liver are associated with a number of disorders. Infectious disorders are the most important: bacterial (e.g., tuberculosis and other mycobacterial infections, brucellosis, tularemia, actinomycosis); fungal (e.g., histoplasmosis, cryptococcosis, blastomycosis); parasitic (e.g., schistosomiasis, toxoplasmosis, visceral larva migrans); less common viral infections (e.g., infectious mononucleosis, cytomegalovirus); and numerous others (e.g., Q fever, syphilis, cat-scratch fever).
Sarcoidosis is the most important noninfectious cause; liver involvement occurs in about two thirds of patients and occasionally is the dominant clinical manifestation. Hepatic granulomas can also occur in polymyalgia rheumatica and other collagen-vascular diseases, in Hodgkin disease, and some other systemic conditions.
INVESTIGATIONS
Conspicuous and frequent granulomas.
Graft-versus-host disease (GVHD)
SIGNS / SYMPTOMS
The skin, liver, gastrointestinal tract, and hematopoietic system are the principal target organs in patients with acute GVHD. Hepatic involvement is manifested by abnormal liver function tests (LFTs), with the earliest and most common finding being a rise in the serum levels of conjugated bilirubin and alkaline phosphatase.
Although the concurrent presence of the characteristic rash provides suggestive clinical evidence, biopsy is the most definitive method to diagnose GVHD of the liver.
INVESTIGATIONS
LFTs consistent with cholestasis, with elevations in the serum alkaline phosphatase and bilirubin concentrations.
Histology: lymphocytic and granulomatous infiltrates of bile ducts; ductopenia.
Cryptogenic chronic hepatitis or cirrhosis
SIGNS / SYMPTOMS
Similar clinical features.
INVESTIGATIONS
Autoantibodies absent.
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