Hepatitis B differential diagnosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: João André Alves Silva, M.D. [2], Sara Mehrsefat, M.D. [3]

Overview

Hepatitis B must be differentiated from other diseases that cause fever, nausea, vomiting, jaundice, hepatomegaly, icteric sclera, elevated ALT, and elevated AST, such as other types of viral hepatitis, alcoholic hepatitis, and autoimmune hepatitis.

Differentiating Hepatitis B from other Diseases

The table below summarizes the findings that differentiate hepatitis B from other conditions that cause fever, nausea, vomiting, jaundice, hepatomegaly, and icteric sclera.

Disease	Findings
Viral Hepatitis A	Abrupt onset of prodromal symptoms Detectable serum immunoglobulin M (IgM) anti-HAV antibodies Hepatitis, caused by the hepatitis A virus, produces a self-limited disease
Viral Hepatitis C	Acute hepatitis with possible recent exposure to HCV (needle-stick) Symptoms are similar to the ones of hepatitis B, however, hepatitis C can cause acute and/or chronic hepatitis Serologic testing will help differentiate these two conditions Detectable HCV RNA by PCR and anti-HCV antibody testing by enzyme-linked immunosorbent assay (ELISA)
Viral Hepatitis D	Symptoms are similar to the ones of hepatitis B, however, hepatitis D is a serious liver disease caused by infection with the Hepatitis D virus Only occurs among people who are infected with the hepatitis B virus (HBV) May complicate into cirrhosis and hepatocellular carcinoma. Serologic testing will help differentiate these two conditions Detectable IgM anti-HBc with Serum HDAg (enzyme-linked (EIA) or radioimmunoassays (RIA))
Viral Hepatitis E	Symptoms are similar to the ones of hepatitis B, however, hepatitis E may complicate into chronic hepatitis and liver failure in rare cases Detectable IgM antibodies to HEV or HEV in serum or stool by polymerase chain reaction (PCR)
Alcoholic Hepatitis	Symptoms are similar to the ones of hepatitis B, however, alcoholic hepatitis is related to the excessive use of alcohol Often leads to cirrhosis and liver failure Moderately elevated aminotransferases (typically <300 int. unit/mL) ALT<AST in alcoholic hepatitis (inverse from viral hepatitis, which is ALT>AST) Elevated serum bilirubin (>5 mg/dL), elevated INR, and possible leukocytosis
Autoimmune Hepatitis	Autoimmune hepatitis occurs when the body's immune system attacks the hepatocytes It often affects young females and may present with signs of acute hepatitis or chronic liver disease Autoimmune hepatitis has a fluctuating nature It may be asymptomatic or at the far end of the spectrum, may present with acute liver failure with jaundice, elevated PT, and aminotransferase values >1000 U/L

Hepatitis B must be differentiated from other causes of rash and arthritis

Disease	Findings
Nongonococcal septic arthritis	Presents with an acute onset of joint swelling and pain (usually monoarticular) Culture of joint fluid reveals organisms
Acute rheumatic fever	Presents with polyarthritis and rash (rare presentation) in young adults. Microbiologic or serologic evidence of a recent streptococcal infection confirm the diagnosis. Poststreptococcal arthritis have a rapid response to salicylates or other antiinflammatory drugs.
Syphilis	Presents with acute secondary syphilis usually presents with generalized, pustular lesions at the palms and soles with generalized lymphadenopathy Rapid plasma reagin (RPR), Venereal Disease Research Laboratory (VDRL) and Fluorescent treponemal antibody absorption (FTA-ABS) tests confirm the presence of the causative agent.
Reactive arthritis (Reiter syndrome)	Musculoskeletal manifestation include arthritis, tenosynovitis, dactylitis, and low back pain. Extraarticular manifestation include conjunctivitis, urethritis, and genital and oral lesions. Reactive arthritis is a clinical diagnosis based upon the pattern of findings and there is no definitive diagnostic test
Hepatitis B virus (HBV) infection	Presents with fever, chills, polyarthritis, tenosynovitis, and urticarial rash Synovial fluid analysis usually shows noninflammatory fluid Elevated serum aminotransaminases and evidence of acute HBV infection on serologic testing confirm the presence of the HBV.
Herpes simplex virus (HSV)	Genital and extragenital lesions can mimic the skin lesions that occur in disseminated gonococcal infection Viral culture, polymerase chain reaction (PCR), and direct fluorescence antibody confirm the presence of the causative agent.
HIV infection	Present with generalized rash with mucus membrane involvement, fever, chills, and arthralgia. Joint effusions are uncommon
Gout and other crystal-induced arthritis	Presents with acute monoarthritis with fever and chills Synovial fluid analysis confirm the diagnosis.
Lyme disease	Present with erythema chronicum migrans rash and monoarthritis as a later presentation. Clinical characteristics of the rash and and serologic testing confirm the diagnosis.

Differential diagnosis of jaundice are:

Classification of jaundice based on etiology Disease History and clinical manifestations Diagnosis Lab Findings Other blood tests Other diagnostic Family history Fever RUQ Pain Pruritis AST ALT ALK BLR Indirect BLR Direct Viral serology Jaundice Hepatocellular Jaundice Liver infiltration: Hemochromatosis, amyloidosis + - -/+ - ↑ ↑ ↑/N ↑/N N - Ferritin ↑ in hemochromatosis Liver biopsy Wilson's disease + - -/+ - ↑ ↑ N ↑/N N - Serum cerulloplasmin ↑ Liver biopsy Viral hepatitis - -/+ - - ↑ ↑ N ↑/N N + Specific viral antibody for each type - Alcoholic hepatitis - -/+ -/+ - ↑↑ ↑ N ↑/N N - - - Drug induced hepatitis - -/+ - - ↑ ↑ N ↑/N N - - - Autoimmune hepatitis -/+ - - -/+ ↑ ↑ N ↑/N N - Anti-LKM antibody Liver biopsy Cirrhosis -/+ -/+ -/+ - ↑ ↑ ↑/N ↑/N ↑/N -/+ Low platate Small liver on ultrasond Nonalcoholic steatohepatitis -/+ - - - ↑ ↑ N ↑/N N - High lipids liver biopsy Ischemic hepatopathy -/+ - -/+ - ↑ ↑ N ↑/N N - Cardiovascular risk factors Clinical setting Cholestatic Jaundice Common bile duct stone -/+ - + + N N ↑ N ↑ - Dilated ducts on sono CT/ERCP Hepatitis A cholestatic type - -/+ + + N N ↑ N ↑ + HAV- AB Abdominal ultrasound EBV / CMV hepatitis - -/+ + + N N ↑ N ↑ + Positive serology - Primary biliary cirrhosis -/+ - -/+ + N/↑ N/↑ ↑ N ↑ - AMA positive Liver biopsy Primary sclerosing cholangitis -/+ - -/+ + N/↑ N/↑ ↑ N ↑ - Pos. autoantibodies Beading on MRCP, Liver biopsy Sickle cell disease + - - +/- N/↑ N/↑ ↑ N ↑ - Genetic testing Pancreatic carcinoma + - -/+ -/+ N/↑ N/↑ ↑ N ↑ - - CT scan for diagnosis AIDS cholangiopathy - - -/+ -/+ N/↑ N/↑ ↑ N ↑ - Pos. HIV Sono or ERCP for diagnosis Parasites induces cholestasis - - -/+ -/+ N/↑ N/↑ ↑ N ↑ - Ab or parasite serology Sono or ERCP for diagnosis Intrahepatic cholestasis of pregnancy -/+ - -/+ + ↑ ↑ ↑ N ↑ - Low PLT, Neg viral serology Diagnosed clinically Isolated Jaundice Crigler-Najjar type 2 + - - - N N N ↑ ↑ - Genetic testing Gilbert + - - - N N N ↑ ↑ - Genetic testing Rotor syndrome + - - - N N N N ↑ - Genetic testing Liver biopsy Dubin-Johnson syndrome + - - - N N N N ↑ - Genetic testing Liver biopsy Hereditory spherocytosis + - -/+ - N N N ↑ N - Genetic testing Osmotic fragility G6PD deficiency + - - - N N N ↑ N - Genetic testing Thalassemia + - - - N N N ↑ N - Genetic testing Paroxismal nocturnal hemoglobinoria - - - - N N N ↑ N - Flocytometery Immune hemolysis - -/+ - - N N N ↑ N - Autoantibodies Hematoma - -/+ - - N N N ↑ N - Anemia Truma or surgery in history

References

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