Differentials
Acute hepatitis B
SIGNS / SYMPTOMS
Clinical features of viral hepatitis in a person with a history of injection drug use, nasal snorting of drugs, multiple sexual partners, or transfusion of blood products before donors were routinely screened. Disease incubation period is longer.
INVESTIGATIONS
Anti-hepatitis A virus IgM is negative, whereas hepatitis B surface antigen and/or IgM antibody to hepatitis B core antigen are positive.
Hepatitis E
SIGNS / SYMPTOMS
Clinical features of viral hepatitis in a person with a history of recent travel to endemic areas or exposure to an infected person or contaminated water. Hepatitis E is often more severe in pregnant women.
INVESTIGATIONS
Test for anti-hepatitis E virus IgM in acute-phase sera.
Acute hepatitis C
SIGNS / SYMPTOMS
Clinical features of viral hepatitis in men who have sex with men, or in people with a history of injection drug use, positive HIV status, an occupational exposure in the previous 6 months, or blood transfusion before donors were routinely screened.
INVESTIGATIONS
Anti-hepatitis C virus (HCV) positive by enzyme-linked immunosorbent assay (ELISA) and confirmed by recombinant immunoblot assay (RIBA) or positive HCV RNA.
Anti-HCV may be negative in acute HCV infection; thus, patient is tested for HCV RNA if anti-HCV is negative, the patient has HCV-associated risk factors, and acute HCV infection is suspected.
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.
Coxsackie virus
SIGNS / SYMPTOMS
Classically displays buccal or pharyngeal lesions with Coxsackie virus infection.
INVESTIGATIONS
Hand-foot-and-mouth disease mainly is a clinical diagnosis. Coxsackie serology can be helpful if available. Atypical lymphocytes tend to be present.
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.
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.
Auto-immune hepatitis
SIGNS / SYMPTOMS
Approximately 90% of cases occur in women. Other auto-immune disorders may be present; 25% to 40% of cases can present with acute hepatitis. Hepatitis A virus (HAV) has been described as a possible trigger for auto-immune hepatitis.[41][42]
INVESTIGATIONS
Erythrocyte sedimentation rate elevated.
Serum electrophoresis and serum autoantibodies: patients may have serum gamma-globulin concentrations more than twice normal, and sometimes antinuclear antibodies and/or anti-smooth muscle (anti-actin) antibodies. Patients with another subtype may have normal or only slightly elevated serum gamma-globulin concentrations but will have antibodies against a particular cytochrome p450 isoenzyme that are called anti-LKM (liver kidney microsome).
Liver biopsy is characterised by a periportal lesion or interface hepatitis (a portal mononuclear and plasma cell infiltrate).
Alpha-1 antitrypsin disease
SIGNS / SYMPTOMS
Uncommonly presents as acute hepatitis.
INVESTIGATIONS
Alpha-1 antitrypsin serum level reduced; phenotyping demonstrating characteristic alpha-1 antitrypsin-variant proteins. Liver biopsy stain for periodic acid-Schiff-positive inclusions.
Alcoholic hepatitis
SIGNS / SYMPTOMS
History of excessive alcohol consumption.
Hepatomegaly and jaundice are found in approximately 95% and 55% of persons presenting with alcoholic hepatitis, respectively.
INVESTIGATIONS
AST/ALT ratio of at least 2:1 in up to 80% of cases. Full blood count may show anaemia, leukocytosis, and/or thrombocytopenia.
Ischaemic hepatitis
SIGNS / SYMPTOMS
Also referred to as 'shock liver'. History of injury or hypotension, postoperative patient.
INVESTIGATIONS
Negative viral hepatitis serologies.
Drug-induced hepatitis
SIGNS / SYMPTOMS
History of excessive paracetamol ingestion or therapeutic amounts of paracetamol in a patient with alcoholic liver disease or alcohol ingestion; other therapeutic drugs may cause hepatitis (e.g., isoniazid, non-steroidal anti-inflammatory drugs, beta-lactam antibiotics, sulfa-containing compounds, insulin-sensitising drugs); may affect men and women of all ages but more common in women and the elderly.
INVESTIGATIONS
History of drug consumption; improvement usually occurs with discontinuation.
Wilson's disease
SIGNS / SYMPTOMS
Rarely presents after age 40 years without neuropsychiatric symptoms; rarely presents as acute hepatitis.
Kayser-Fleischer rings upon slit-lamp ophthalmological examination.[Figure caption and citation for the preceding image starts]: Eye demonstrating Kayser-Fleischer ringAdapted from Aggarwal A, Bhatt M. BMJ 2009; 339:b3494; copyright 2009 by the BMJ Publishing Group [Citation ends].
INVESTIGATIONS
24-hour urine for copper >100 micrograms, and serum ceruloplasmin <180 mg/L (18 mg/dL) is positive for Wilson's disease. Liver biopsy and assay of copper >250 micrograms/g dry weight indicates Wilson's disease. A liver copper level of <150 micrograms/g dry weight rules out Wilson's disease.
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