Differentials
Acute viral hepatitis A
SIGNS / SYMPTOMS
There may be no differences in signs and symptoms.
INVESTIGATIONS
Serum hepatitis A virus-IgM antibody will be positive.
Acute viral hepatitis B
SIGNS / SYMPTOMS
There may be no differences in signs and symptoms.
INVESTIGATIONS
Serum hepatitis B surface antigen and serum antibody to hepatitis B surface antigen and/or IgM antibody to hepatitis B core antigen will be positive.
Serum hepatitis B virus (HBV) DNA detected by polymerase chain reaction may be positive for HBV.
Acute viral hepatitis C
SIGNS / SYMPTOMS
There may be no differences in signs and symptoms.
INVESTIGATIONS
Serum hepatitis C virus (HCV) antibody and HCV RNA detected by polymerase chain reaction may be positive. Typically, symptomatic acute HCV patients will show very high alanine aminotransferase, aspartate aminotransferase, and bilirubin.
Acute viral hepatitis E
SIGNS / SYMPTOMS
Symptoms and signs can be identical to those of other acute viral hepatitis. Acute hepatitis E is most commonly found in pregnant women in developing countries with a hot climate.
INVESTIGATIONS
Serum hepatitis E virus (HEV) antibody (IgM) and serum HEV RNA detected by polymerase chain reaction may be positive.
Alcohol-related liver disease
SIGNS / SYMPTOMS
History of moderate/heavy alcohol consumption.
Hepatomegaly and jaundice are found in around 95% and 55% of people presenting with alcoholic hepatitis, respectively.
INVESTIGATIONS
AST:ALT ratio >2:1 in up to 70% of cases.
Complete blood count may show anemia, leukocytosis, and/or thrombocytopenia.
Negative viral hepatitis serology.
Liver biopsy may show steatosis, ballooning hepatocytes, Mallory hyaline, lobular neutrophilic infiltration, with or without pericellular fibrosis.
Autoimmune hepatitis
SIGNS / SYMPTOMS
May be more likely to have constitutional symptoms, such as fever, myalgias, and lymphadenopathy. There may be a history of other autoimmune diseases, such as thyroiditis, type 1 diabetes, celiac disease, and ulcerative colitis.[48][49]
INVESTIGATIONS
There may be increased levels of serum globulin, antinuclear antibody, antismooth muscle antibody, liver/kidney microsomal antibodies, and/or antibodies against soluble liver antigen/liver pancreas antigen. Liver histology may show interface hepatitis with plasma cell infiltrates.
Negative viral hepatitis serology.
Drug- or toxin-induced hepatitis
SIGNS / SYMPTOMS
May have a history of exposure to drugs or toxins. Evidence of hypotension.
INVESTIGATIONS
Liver biopsy may show the features of hepatocellular, cholestatic, or mixed pattern of injury, including cholestasis.
Budd-Chiari syndrome
SIGNS / SYMPTOMS
There may be no differences in signs and symptoms.
INVESTIGATIONS
Doppler ultrasound may show hepatic vein thrombosis or inferior vena caval thrombosis.
Acute ischemic hepatitis
SIGNS / SYMPTOMS
Typically occurs in patients at risk for hypotension or ischemia, including shock, heart failure, or vascular insufficiency. Patients may have symptoms of ischemia such as acute heart failure, shock, or sepsis.
INVESTIGATIONS
ECG may show features of myocardial ischemia or infarction. Chest x-ray and echocardiogram may show features of congestive heart failure. Doppler ultrasound of liver may show portal vein thrombosis or acute occlusion of hepatic artery.
Acute fatty liver of pregnancy
SIGNS / SYMPTOMS
Pregnant patient may present with jaundice.
INVESTIGATIONS
Diagnosis of exclusion of other diseases with characteristic symptoms and signs in pregnant patients.
Hemochromatosis
SIGNS / SYMPTOMS
May have a family history of hemochromatosis. May also have signs and symptoms such as chronic asthenia, arthropathy, impotence, hyperpigmentation and skin bronzing, diabetes mellitus, cardiomyopathy, and porphyria cutanea tarda.
INVESTIGATIONS
Serum transferrin saturation >45%, raised serum ferritin.
HFE genetic testing will be positive for hemochromatosis gene mutations.
Liver biopsy shows iron deposition in hepatocytes.
Biliary disease
SIGNS / SYMPTOMS
May have fever, pruritus, dark urine, pale stool, weight loss.
INVESTIGATIONS
Elevated alkaline phosphatase and bilirubin levels.
Abdominal imaging may show biliary dilation, stricture, or obstruction.
Anti-mitochondrial antibody will be positive in primary biliary cholangitis.
Liver biopsy may show biliary or cholestatic disease.
Alpha-1 antitrypsin deficiency
SIGNS / SYMPTOMS
May have chronic lung disease such as emphysema occurring earlier than expected (in the 40- to 50-year-old age group) as well as liver disease. Some 50% of patients with severe deficiency of alpha-1 antitrypsin have a productive cough.[50] Patients with respiratory disease may present with shortness of breath on exertion.
INVESTIGATIONS
Reduced plasma alpha-1 antitrypsin level <20 micromoles/L confirms the diagnosis.
Lung function tests may reveal reduced FEV₁, FVC, and FEV₁/FVC.
Chest x-ray may reveal emphysema and large lung volumes.
Wilson disease
SIGNS / SYMPTOMS
There may be associated behavioral abnormalities (such as loss of memory, anxiety, disinhibition), dysarthria, and presence of Kayser-Fleischer rings (gold-brown corneal pigments representing copper deposition) on eye exam.
INVESTIGATIONS
Increased 24-hour urinary copper, decreased serum ceruloplasmin, and Kayser-Fleischer rings on slit lamp eye exam.
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