Tests
1st tests to order
liver biochemistries
Test
Request in all patients as part of the initial evaluation:
Alanine aminotransferase (ALT)
Aspartate aminotransferase (AST)
Alkaline phosphatase (ALP)
Total bilirubin (direct and indirect)
Albumin.
Results may be normal but aminotransferases (ALT and AST), ALP, and/or bilirubin levels may be elevated in chronic hepatitis D virus (HDV) infection. Albumin level may be low in patients with decompensated cirrhosis.
Result
normal or elevated aminotransferases (ALT/AST), ALP, and bilirubin; low albumin
complete blood count (CBC)
Test
Request in all patients as part of the initial evaluation:
Hemoglobin/hematocrit
White cell count and differential
Platelet count.
May be decreased in patients with cirrhosis and portal hypertension (particularly platelet count).
Result
low (particularly platelet count)
basic metabolic panel
Test
Request in all patients as part of the initial evaluation:
Electrolytes
BUN
Creatinine.
In patients with cirrhosis and ascites, there may be electrolyte disturbances including hyponatremia. Renal dysfunction is a risk in decompensated cirrhosis due to pre-renal azotemia or hepatorenal syndrome.
Result
normal or hyponatremia and/or high BUN
coagulation profile
Test
Request in all patients as part of the initial evaluation:
Prothrombin time (PT) and international normalized ratio (INR).
May be normal. In patients with cirrhosis, however, levels may be elevated indicative of liver synthetic dysfunction.
Result
normal or elevated
serum antibody to HDV
Test
Request antibody to HDV (anti-HDV) (IgG and IgM) in all patients with confirmed hepatitis B virus (HBV) infection.[45]
The European Association for the Study of the Liver (EASL) recommends that screening for anti-HDV antibody should be performed with a validated assay at least once in all hepatitis B surface antigen (HBsAg)-positive individuals, and that re-testing for anti-HDV antibody should be performed in those who initially test negative whenever clinically indicated (such as in those with aminotransferase flares or acute decompensation of chronic liver disease) and annually in those remaining at risk of infection.[1]
Guidelines from the American Association for the Study of Liver Diseases (AASLD) recommend risk-based screening of HBsAg-positive patients for HDV infection in the following situations:[2]
Elevated alanine aminotransferase (ALT) or aspartate aminotransferase (AST) with low or undetectable HBV DNA
HIV infection
Hepatitis C virus (HCV) infection
History of injection drug use
Men who have sex with men
Those with multiple sexual partners or any history of sexually transmitted disease
Immigrants from areas with high HDV endemicity (western and mid-Africa, parts of the Mediterranean, Pacific Islands, Middle East, Mongolia, eastern Europe, and the Amazonian basin).[1]
Anti-HDV antibodies appear 3-4 weeks after HDV infection.[43] The result will be positive in people with chronic HDV infection, but levels can fluctuate based on the degree of replication.
Result
variable
serum HDV RNA
Test
Request HDV RNA (where available) as part of the initial evaluation in all patients with a positive anti-HDV test result. A standardized and sensitive reverse transcription polymerase chain reaction assay should be used.[1]
Anti-HDV antibodies may persist after the clearance of HDV infection and therefore testing for HDV RNA is required to confirm ongoing HDV infection.[1]
HDV RNA assays are increasingly available, but require greater standardization, particularly with some less common HDV genotypes.
One systematic review and meta-analysis found that the pooled proportion of detectable HDV RNA in 5073 people with a positive anti-HDV test result was 58.5% (95% CI 52.4 to 64.5). The rate of HDV RNA detection was higher in cohorts with higher prevalence of anti-HDV and in hepatology clinic populations than in the general population.[11] Variable performance of HDV RNA with some HDV genotypes indicates that this figure should be interpreted with caution.
Result
positive
serum hepatitis B surface antigen
Test
Request hepatitis B surface antigen (HBsAg) in all patients as part of the initial evaluation.
A positive HBsAg result indicates a current hepatitis B virus (HBV) infection. Persistence for more than 6 months indicates chronic HBV infection.
Result
positive
serum antibody to hepatitis B surface antigen
Test
Request antibody to hepatitis B surface antigen (anti-HBs) in all patients as part of the initial evaluation.
In resolved acute infections, appears several weeks after hepatitis B surface antigen has disappeared, and in most patients indicates lifelong immunity. It is also detectable in those immunized with hepatitis B vaccine.
Result
undetectable
serum antibody to hepatitis B core antigen
Test
Order both IgM and IgG antibody to hepatitis B core antigen (anti-HBc) in all patients as part of the initial evaluation.
IgM anti-HBc appears within weeks of acute infection and remains detectable for 4-8 months. During the window period (several weeks to months) after the disappearance of hepatitis B surface antigen (HBsAg) and before appearance of antibody to HBsAg, detection of anti-HBc IgM may be the only way to make the diagnosis of acute hepatitis B virus (HBV) infection. Some patients with chronic HBV infection become positive for IgM antibody during acute flares or reactivation, making positive anti-HBc IgM not an absolutely reliable marker for acute infection.[46]
Anti-HBc IgM and IgG antibodies are detectable in virtually all patients who have been exposed to HBV (acute or chronic HBV infection). They may be positive in the following settings: 1) acute infection: during the window period (mostly IgM); 2) chronic infection (IgG and occasionally IgM), when HBsAg has decreased to undetectable levels; and 3) resolved infections (IgG): detection of anti-HBc IgG in the absence of HBsAg and with or without anti-HBe and anti-HBs antibodies characterizes HBV infection in the past. The pattern is common in areas with high prevalence of HBV infection and in those patients who are coinfected with HIV or hepatitis C. Patients with HBV infection in the past remain at risk of reactivation if immunosuppressed.
Result
positive
serum hepatitis B e antigen
Test
Request hepatitis B envelope antigen (HBeAg) in all patients as part of the initial evaluation.
This is a soluble viral protein found in serum in the early part of acute hepatitis B virus (HBV) infection, and it usually disappears at or soon after the peak in serum alanine aminotransferase (ALT) levels. Its presence ≥3 months after onset of illness indicates a high likelihood of development of chronic HBV infection. HBeAg can also be present in chronic HBV infection.
Result
undetectable or positive
serum antibody to hepatitis B e antigen
Test
Request antibody to hepatitis B envelope antigen (anti-HBe) in all patients as part of the initial evaluation.
Seroconversion from hepatitis B e antigen (HBeAg)-positive to antibody to hepatitis B e antigen (anti-HBe)-positive is a useful indicator of clearance of virus. Patients with sustained seroconversion typically have improvement of liver histology. However, some patients will become anti-HBe-positive without complete clearance of virus, due to pre-core or core-promoter mutations (HBeAg-negative chronic HBV).
Seroconversion can be a temporary phenomenon and should be analyzed in association with the serum hepatitis B virus DNA level.
Result
undetectable or positive
serum HBV DNA
Test
Request hepatitis B virus (HBV) DNA in all patients as part of the initial evaluation.
HBV DNA levels are generally measured by polymerase chain reaction (PCR) amplification assay. Newer PCR technology has allowed for improved sensitivity. HBV DNA may be positive but is often suppressed in active HDV infection.
Result
undetectable or positive
abdominal ultrasound
Test
Request in all patients as a useful first imaging test to evaluate the liver for advanced fibrosis, cirrhosis, and portal hypertension, and for hepatocellular carcinoma.
Ultrasound may be normal. In patients with cirrhosis, the liver may look coarsened with irregular contours and there may be signs of portal hypertension (which may include increased spleen longitudinal diameter, esophageal varices, or mild ascites).
Continued surveillance imaging every 6 months using ultrasound is recommended in patients with advanced fibrosis or cirrhosis to look for hepatocellular carcinoma.[1]
Result
may reveal coarsened appearance of the liver with irregular contours and signs of portal hypertension, or hepatocellular carcinoma
Tests to consider
testing for coinfections
Test
Check the patient’s HIV, hepatitis A, and hepatitis C status as this affects management options.
Result
variable
liver biopsy
Test
Histology remains the gold standard for the most accurate characterization of liver disease, and enables categorical grading and staging of necro-inflammation and fibrosis. However, liver biopsy should not be obtained routinely unless there is a diagnostic dilemma or if there is some debate over whether treatment is required.[1]
Result
may demonstrate inflammation or fibrosis
transient elastography
Test
Consider transient elastography as a noninvasive alternative to liver biopsy.[1] Evaluates liver injury by measuring liver stiffness.
Transient elastography is used routinely in Europe and may be considered as a noninvasive alternative to liver biopsy. However, specific cutoff values are not well established.[1]
Magnetic resonance elastography has been shown to be more accurate than Fibroscan® in diagnosing liver fibrosis in patients with chronic hepatitis B virus infection.[47]
Result
may demonstrate increased liver stiffness
serum liver fibrosis biomarkers
Test
Noninvasive alternative to liver biopsy or to transient elastography which may be used to assess fibrosis severity.[1]
Result
normal or elevated
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