Risks of Untreated Hepatitis B Infection
Untreated chronic Hepatitis B infection carries substantial mortality risk, with approximately 25% of persons infected during childhood and 15% of those infected as adults dying prematurely from cirrhosis or hepatocellular carcinoma. 1
Immediate Risks in Acute Infection
- Fulminant hepatitis occurs in <1% of acute HBV infections but often results in death or necessitates liver transplantation 1
- The case-fatality rate among reported acute HBV cases is <1.5%, with highest rates in adults aged ≥55 years 1
- Most acute infections (60-70% in adults) are asymptomatic, delaying recognition and increasing transmission risk 2
Progression to Chronic Infection
The risk of chronicity is inversely related to age at infection and represents the gateway to long-term complications:
- 80-90% of infants infected perinatally develop chronic infection 1
- 30% of children infected before age 6 years become chronically infected 1
- <5-12% of immunocompetent adults progress to chronic infection 1
- Immunosuppressed persons (hemodialysis patients, HIV-infected individuals, diabetics) face substantially higher chronicity rates 1
Long-Term Morbidity and Mortality in Chronic Infection
Cirrhosis Development
The 5-year cumulative incidence of cirrhosis in untreated chronic hepatitis B patients ranges from 8% to 20% 1
- Once compensated cirrhosis develops, the 5-year cumulative risk of hepatic decompensation is 20% 1
- Untreated patients with decompensated cirrhosis have only 14-35% probability of survival at 5 years 1
Hepatocellular Carcinoma (HCC)
The annual risk of HCC in patients with established cirrhosis is 2-5% 1
- HCC can develop even in non-cirrhotic patients with chronic active hepatitis 1
- Even if HBsAg loss occurs after cirrhosis has developed, patients remain at risk for HCC and require continued surveillance 1
Risk Factors Amplifying Disease Progression
Host-related factors increasing HCC and cirrhosis risk include 1:
- Cirrhosis presence
- Chronic hepatic necroinflammation
- Older age
- Male sex
- African origin
- Alcohol abuse
- Co-infections (HCV, HDV, HIV)
- Diabetes or metabolic syndrome
- Active smoking
- Positive family history of HCC
Viral factors increasing risk include 1:
- High HBV DNA levels
- High HBsAg levels
- HBV genotype C > B
- Specific viral mutations
Phase-Specific Risks
Immune Active Phase (HBeAg-Positive or HBeAg-Negative Chronic Hepatitis)
Persons remaining in the immune active phase for prolonged periods face the highest risk of developing cirrhosis and hepatocellular carcinoma 1
- This phase is characterized by active hepatic inflammation with or without fibrosis 1
- HBeAg-negative chronic hepatitis is associated with low rates of spontaneous disease remission 1
Inactive Carrier Phase
- Patients with persistently normal ALT and HBV DNA <2,000 IU/mL have low risk of progression to cirrhosis or HCC if they remain in this phase 1
- However, progression to active chronic hepatitis can occur unpredictably 1
- Spontaneous HBsAg loss occurs in only 1-3% of cases per year 1
Extrahepatic Manifestations
Beyond liver disease, untreated HBV infection can cause 1:
- Polyarteritis nodosa
- Membranous glomerulonephritis
- Membranoproliferative glomerulonephritis
- Skin rash, arthralgias, and arthritis
Reactivation Risk
Patients who achieve HBsAg loss or have occult infection (HBsAg-negative, anti-HBc positive) remain at risk for HBV reactivation with immunosuppression 1
- Reactivation can occur with chemotherapy, immunosuppressive medications, or treatment for HCV 1
- HBV DNA (cccDNA) persists in the liver even after serologic clearance 1
Critical Clinical Pitfall
The majority of chronically infected persons remain asymptomatic until onset of cirrhosis or end-stage liver disease, making early identification through screening essential rather than waiting for symptoms 1. This asymptomatic progression explains why approximately 25% of childhood-acquired infections result in premature death despite patients feeling well for decades 1.