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 hepatitis B core IgM will be positive.
Serum hepatitis B virus DNA may be positive.
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 may be positive.
Acute viral hepatitis D
SIGNS / SYMPTOMS
Symptoms and signs can be identical to those of other acute viral hepatitis. Note that Hepatitis D infection can only occur in the presence of hepatitis B infection.
INVESTIGATIONS
Serum hepatitis D virus (HDV) RNA and antibodies to hepatitis D (anti-HDV) IgM and IgG may be positive.
Drug- or toxin- induced hepatitis/drug-induced liver injury (DILI)
SIGNS / SYMPTOMS
May have a history of exposure to drugs or toxins.
Should be considered as a differential, especially in older patients who may be on multiple drug treatments. In a cohort study of UK patients with "criterion-referenced" DILI, it was found that in 13% the diagnosis of DILI was erroneous, as the patients had acute hepatitis E.[59]
INVESTIGATIONS
Liver biopsy may show the features of hepatocellular, cholestatic, or mixed pattern of injury, including cholestasis.
Acute alcoholic hepatitis
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
Aspartate aminotransferase to alanine aminotransferase (AST:ALT) ratio >2:1 in up to 70% of cases.
Elevated gamma-glutamyl transferase (GGT).
Positive ethyl glucuronide (ETG).
Positive phosphatidylethanol (PETH).
CBC 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 have an associated lymphadenopathy. There may be a history of other autoimmune diseases, such as thyroiditis, type 1 diabetes, celiac disease, and ulcerative colitis.[60][61]
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.
Cytomegalovirus (CMV) infection
SIGNS / SYMPTOMS
Clinical features of viral hepatitis with no history of exposure to other organisms that can cause hepatitis.
INVESTIGATIONS
Negative serology results for all types of viral hepatitis. Atypical lymphocytes tend to be present. CMV IgM and IgG positive. CMV polymerase chain reaction in blood positive.
Epstein-Barr virus (EBV) infection
SIGNS / SYMPTOMS
Clinical features of viral hepatitis with no history of exposure to other organisms that can cause hepatitis; classically display lymphadenopathy and splenomegaly in EBV infection.
INVESTIGATIONS
Negative serology results for all types of viral hepatitis. Atypical lymphocytes tend to be present.
EBV IgM and IgG positive.
Herpes simplex virus infection
SIGNS / SYMPTOMS
Clinical features of viral hepatitis with no history of exposure to other organisms that can cause hepatitis; may display characteristic cutaneous ulceration.
INVESTIGATIONS
Negative serology results for all types of viral hepatitis. Mainly a clinical diagnosis (aided by presence of typical muco-cutaneous lesions). A liver biopsy confirms diagnosis.
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.
Metabolic dysfunction-associated steatotic liver disease (MASLD)
SIGNS / SYMPTOMS
Often associated with features of the metabolic syndrome (obesity, hypertension, hyperlipidemia, type 2 diabetes mellitus).
INVESTIGATIONS
Abdominal ultrasound may show an echogenic liver.
Ferritin may be elevated with a normal transferrin saturation.
Liver biopsy demonstrates features of nonalcoholic fatty liver disease with or without excess iron.
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.
Biliary disease
SIGNS / SYMPTOMS
May have fever, right upper quadrant pain, pruritus, dark urine, pale stool, weight loss.
INVESTIGATIONS
Elevated alkaline phosphatase and bilirubin levels.
Abdominal imaging may show biliary dilation, stricture, or obstruction.
Antimitochondrial antibody will be positive in primary biliary cholangitis.
Liver biopsy may show biliary or cholestatic disease.
Acute fatty liver of pregnancy (AFLP)
SIGNS / SYMPTOMS
Pregnant patient may present with jaundice.
INVESTIGATIONS
Diagnosis of exclusion of other diseases with characteristic symptoms and signs in pregnant patients.
Hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome
SIGNS / SYMPTOMS
Severe form of preeclampsia characterized by hemolysis, also expressed as microangiopathic hemolytic anemia, elevated liver enzymes, and low platelets.
INVESTIGATIONS
Reduced hemoglobin, low or normal hematocrit, thrombocytopenia.
Peripheral blood smear may show schistocytes, burr cells; polychromasia may be seen secondary to hemolysis and are diagnostic.
Coagulopathy (hypofibrinogenemia, prolonged prothrombin time, low antithrombin) is usually present in later stages of disease.
Hypoglycemia, leukocytosis, and elevated LDH levels may be present. There may also be hemoconcentration, metabolic acidosis, increased ammonia, and elevated serum creatinine.
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