What is the difference between acute hepatitis B and chronic hepatitis B?

Differences Between Acute Hepatitis B and Chronic Hepatitis B

The key difference between acute and chronic hepatitis B is the duration of infection: acute hepatitis B resolves within 6 months of infection, while chronic hepatitis B persists beyond 6 months with continued viral replication and potential for progressive liver damage.

Diagnostic Criteria

Acute Hepatitis B

• Incubation period of 1-4 months after exposure 1
• Presence of HBsAg and IgM anti-HBc in serum 2
• Symptoms may include influenza-like syndrome, right upper-quadrant pain, jaundice 1
• Higher likelihood of symptomatic infection in adults (30%) compared to children <4 years (10%) 1
• Diagnosed through detection of viral proteins and host anti-HBV antibodies 1
• Usually self-limited with spontaneous clearance of HBsAg within 6 months

Chronic Hepatitis B

• Defined by persistence of HBsAg for >6 months 2
• Serologic markers include positive HBsAg, positive total anti-HBc, negative IgM anti-HBc 2
• May be asymptomatic or present with a spectrum of disease from chronic hepatitis to cirrhosis or liver cancer 1
• Often diagnosed incidentally through screening or evaluation of abnormal liver enzymes

Risk of Progression from Acute to Chronic

The probability of progression from acute to chronic HBV infection is strongly age-dependent:

• 90% of infected infants develop chronic infection 1
• 25-30% of children <5 years develop chronic infection 1
• <5-10% of adults with acute infection progress to chronic infection 1, 3
• Immunosuppressed persons have increased risk for chronic infection 1

Clinical Phases of Chronic HBV Infection

Chronic HBV infection typically progresses through four phases 1:

1. Immune Tolerant Phase

   • High viral replication (high HBV DNA)
   • HBeAg positive
   • Normal or minimal ALT elevation
   • Minimal liver inflammation
   • Can last for decades, especially in perinatally acquired infection

2. Immune Active/Clearance Phase

   • HBeAg positive
   • High or fluctuating HBV DNA levels
   • Elevated ALT levels
   • Active liver inflammation
   • Higher risk for progression to cirrhosis and HCC

3. Inactive Carrier Phase

   • HBeAg negative, anti-HBe positive
   • Low or undetectable HBV DNA levels
   • Normal ALT levels
   • Minimal liver inflammation
   • Better prognosis than other phases

4. HBeAg-Negative Chronic Hepatitis B

   • HBeAg negative (often due to viral mutations)
   • Moderate to high HBV DNA levels (>2,000 IU/ml)
   • Elevated ALT levels
   • Continued liver inflammation
   • Often represents a later stage of chronic infection 1

Differentiating Acute from Chronic Infection

Distinguishing between acute HBV infection and acute exacerbation of chronic HBV can be challenging:

• IgM anti-HBc is traditionally used to diagnose acute infection, but may also appear during exacerbations of chronic infection 4
• Patients with chronic infection typically have higher levels of HBeAg/anti-HBe immune complexes compared to those with acute infection 5
• History of prior HBV testing or risk factors may help differentiate
• Evidence of advanced liver disease or portal hypertension suggests chronic infection

Long-term Outcomes

Acute Hepatitis B

• 90% of adults with acute infection achieve complete recovery 6

• Fulminant hepatic failure occurs in <1% of acute cases 1
• No long-term sequelae after resolution

Chronic Hepatitis B

• Responsible for majority of HBV-related morbidity and mortality 1
• Approximately 25% of persons infected as infants/young children and 15% of those infected at older ages die from cirrhosis or liver cancer 1
• Annual spontaneous clearance rate of only 0.5% 1, 7
• Increased risk for cirrhosis, hepatic decompensation, and hepatocellular carcinoma with active viral replication 7
• May cause extrahepatic complications including polyarteritis nodosa and glomerulonephritis 1

Management Implications

The distinction between acute and chronic HBV infection has important treatment implications:

• Acute HBV rarely requires treatment except in severe/fulminant cases 4
• Chronic HBV often requires antiviral therapy to suppress viral replication, reduce liver inflammation, and prevent complications 6
• Regular monitoring for disease progression and hepatocellular carcinoma is necessary for chronic infection 6

Common Pitfalls

• Mistaking an acute exacerbation of chronic HBV for new acute infection (both may present with jaundice and elevated IgM anti-HBc) 4
• Failing to recognize chronic HBV in asymptomatic patients
• Not considering HBV reactivation in patients with resolved infection who undergo immunosuppression 1
• Overlooking the need for HBV screening in high-risk populations, including those born in regions with HBsAg prevalence >2% 1