Criteria
American Association for the Study of Liver Diseases (AASLD) phases of chronic HBV infection[2]
The AASLD classifies chronic hepatitis B virus (HBV) infection into phases, reflecting the relationship between viral replication and evolution and host immune response. Phases are not always distinct and patients can move from one phase to another and back again without any clinical change.
Chronic hepatitis B (CHB):
Hepatitis B surface antigen (HBsAg): present for ≥6 months
Serum HBV DNA: varies from undetectable to several billion IU/mL
Hepatitis B e antigen (HBeAg): positive (HBV DNA levels are typically >20,000 IU/mL) or negative (HBV DNA levels are typically lower in the range 2000-20,000 IU/mL)
Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) levels: normal or elevated
Liver biopsy: chronic hepatitis with variable necro-inflammation and/or fibrosis
Immune-tolerant CHB:
HBsAg: present for ≥6 months
Serum HBV DNA: typically very high (>1 million IU/mL)
HBeAg: positive
ALT and/or AST levels: normal or minimally elevated
Liver biopsy or non-invasive tests: no fibrosis and minimal inflammation
Immune-active CHB:
HBsAg: present for ≥6 months
Serum HBV DNA: >20,000 IU/mL (HBeAg positive) and >2000 IU/mL (HBeAg negative)
ALT and/or AST levels: intermittently or persistently elevated
Liver biopsy or non-invasive tests: chronic hepatitis with moderate or severe necro-inflammation with or without fibrosis
Immune-inactive CHB:
HBsAg: present for ≥6 months
Serum HBV DNA: <2000 IU/mL
HBeAg: negative (antibody to HBeAg [anti-HBe]-positive)
ALT and/or AST levels: persistently normal
Liver biopsy or non-invasive tests: confirms absence of significant necro-inflammation and shows variable levels of fibrosis
HBV reactivation is defined as:
Loss of HBV immune control in HBsAg‐positive/antibody to hepatitis B core antigen (anti‐HBc)-positive, or HBsAg‐negative/anti‐HBc-positive patients receiving immunosuppressive therapy for a concomitant medical condition
A rise in HBV DNA compared to baseline (or an absolute level of HBV DNA when a baseline is unavailable); and
Reverse seroconversion (seroreversion) from HBsAg-negative to HBsAg-positive for HBsAg‐negative/anti‐HBc-positive patients.
European Association for the Study of the Liver (EASL) phases of chronic HBV infection[38]
The EASL guidelines classify chronic HBV into five phases, according to serological markers and liver disease. Phases are not always distinct and patients can move from one phase to another and back again without any clinical change.
HBeAg-positive chronic HBV infection: normal ALT levels; elevated HBV DNA; liver biopsy shows minimal inflammation and fibrosis; previously known as ‘immune tolerant’ phase.
HBeAg-positive chronic hepatitis B: elevated ALT levels, elevated HBV DNA; moderate-to-severe liver necro-inflammation and accelerated progression of fibrosis; in most patients, HBeAg seroconversion and HBV DNA suppression occurs and they enter the HBeAg-negative infection phase, while in other patients, HBV control does not occur and they progress to the HBeAg-negative chronic hepatitis B phase, which may remain for many years; previously known as ‘immune-reactive HBeAg-positive’ phase.
HBeAg-negative chronic HBV infection: anti-HBe-positive; normal ALT levels; low or undetectable HBV DNA; liver biopsy shows minimal necro-inflammation and low fibrosis; previously known as ‘inactive carrier’ phase.
HBeAg-negative chronic hepatitis B: detectable anti-HBe; moderate-to-high HBV DNA; elevated ALT (persistent or intermittent); moderate-to-severe necro-inflammation and fibrosis.
HBsAg-negative: patient is HBsAg-negative, anti-HBc-positive, and may have detectable anti-HBe; normal ALT levels; usually undetectable HBV DNA; immunosuppression in these patients may lead to reactivation; phase also known as occult HBV infection.
Centers for Disease Control and Prevention: case definitions[95]
Clinical criteria
In the absence of a more likely, alternative diagnosis, acute onset or new detection of at least one of the following:
Jaundice
Total bilirubin ≥51.3 micromoles/L (≥3 mg/dL)
Elevated serum alanine aminotransferase (ALT) levels >200 IU/L
Acute hepatitis B
Confirmatory laboratory evidence (tier 1):
Detection of hepatitis B surface antigen (HBsAg) and detection of antibody to hepatitis B core antigen (anti-HBc IgM); OR
Detection of hepatitis B e antigen (HBeAg) and detection of anti-HBc IgM; OR
Detection of HBV DNA and detection of anti-HBc IgM; OR
Detection of HBsAg, HBeAg, or HBV DNA within 12 months (365 days) of a negative HBsAg test result (i.e., HBsAg seroconversion)
Confirmatory laboratory evidence (tier 2):
Detection of HBsAg, and anti-HBc IgM test not done or result not available; OR
Detection of HBV DNA, and anti-HBc IgM test not done or result not available
Presumptive laboratory evidence:
Detection of anti-HBc IgM; AND
Negative result or test not done for HBsAg, HBV DNA, or HBeAg
A probable case meets the clinical criteria and presumptive laboratory evidence of acute HBV infection. A confirmed case meets tier 1 confirmatory laboratory evidence of acute HBV infection; OR meets clinical criteria and tier 2 confirmatory laboratory evidence of acute HBV infection.
Chronic hepatitis B
Confirmatory laboratory evidence:
Detection of HBsAg in two clinical specimens taken ≥6 months apart; OR
Detection of HBeAg in two clinical specimens taken ≥6 months apart; OR
Detection of HBsAg or HBeAg and total anti-HBc; OR
Detection of HBsAg and HBeAg; OR
Detection of HBV DNA
Presumptive laboratory evidence:
Detection of HBsAg or HBeAg AND anti-HBc IgM test negative, not done, or result not available.
A probable case meets the presumptive laboratory evidence of chronic HBV infection. A confirmed case meets the confirmatory laboratory evidence of chronic HBV infection.
See the full case definition for more detailed information:
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