The Hepatitis B e-Antigen Negative Disease - Directly Offered Study of Treatment Withdrawal in Patients With e-Antigen Negative Chronic HBV Infection (BeNEG-DO).

Open to people ages 18-67

1. HBeAg-CHB with at least 192 weeks (3.7 years) of complete viral suppression (serum HBV DNA <50 IU/ml) on NA therapy
2. No bridging fibrosis (≥ Metavir stage 3)
3. Normal liver tests and platelet count
4. Age 18-67
5. Otherwise healthy with no serious co-morbidities
6. Patients who are willing, prepared, and able to immediately resume antiviral treatment upon medical instruction and on satisfying study re-treatment criteria.

1. HBeAg-CHB with virologic breakthrough while on NA therapy during the prior 192 weeks (3.7 years)
2. Age <18 or >67 years
3. Significant co-morbidities including co-infection and significant co-existing liver disease or anemia. Mild Non-Alcoholic Fatty Liver Disease (NAFLD) without Non-Alcoholic Steatohepatitis (NASH) or associated liver enzyme elevation will be allowed.
4. Bridging hepatic fibrosis (≥ Metavir stage 3) at the time of potential study entry
   1. Control Group: Determination will be based on historical biopsy data, imaging studies, Platelet count (<150,000), Aspartate aminotransferase to Platelet Ratio Index (APRI) <1.5) and Red Cell Distribution Width-to-Platelet Ratio (RPR) (<0.16) scores, and clinical assessment
5. Alanine Aminotransferase (ALT) above the quoted normal range
6. Clinical, serologic, radiological or biochemical suspicion for cirrhosis
7. Prior liver transplantation
8. A documented history of extrahepatic manifestations of hepatitis B, including renal disease and/or vasculitis
9. Cases: A family history of hepatocellular carcinoma due to hepatitis B virus in a first degree family member
10. On Prednisone or other immunosuppressive or immune-modulating therapy during the 6 months before study entry
11. Pregnancy
12. Patients who are not willing, prepared, and able to immediately resume antiviral treatment upon medical instruction and on satisfying re-treatment criteria

No one will be excluded on the basis of race, gender, religion, sexual orientation, or any cultural factor. An Institutional Review Board (IRB)-approved, translated consent will be used for patients that do not speak English