Initiating treatment

Given the dynamic nature of chronic hepatitis B infection, ongoing monitoring of HBV DNA and ALT levels is important to characterize the phase of infection and to ensure that treatment is initiated when necessary.1

Although antiviral therapy is generally effective in suppressing HBV DNA, it does not eradicate hepatitis B. Lifelong treatment may potentially be required for some patients.2

Across the following chronic hepatitis B guidelines, treatment initiation is guided by HBV DNA and ALT levels and/or the presence of cirrhosis.1-3

Overview of chronic hepatitis B treatment guidelines and algorithms

Overview of chronic hepatitis B treatment guidelines
  • a ULN for ALT is defined by AASLD as 35 U/L for men and 25 U/L for women, and defined by EASL as approximately 40 U/L for both men and women. ULN is defined by AATA based the physician's local laboratory.1-3
  • b Concurrently consider liver transplantation for eligible patients with decompensated cirrhosis.1
  • c If HBV DNA level is less than specified, consider therapy in patients with known significant histologic disease, even if low-level viral replication occurs.3

For eligible HBV patients, treatment may be associated with benefits.4

However, when discussing treatment with appropriate patients, it is important to explain the risks associated with treatment.

Quotes from key recommendations and guidelines
ACP and CDC recommendations5

Although not all patients with chronic HBV infection require treatment, they all should be routinely evaluated for hepatocellular carcinoma and treatment eligibility through history and physical examination.

  • Hepatitis B Vaccination, Screening, and Linkage to Care: Best Practice Advice from the ACP and CDC
WHO guidelines6

Antiviral agents active against HBV are available, and have been shown to suppress HBV replication, prevent progression to cirrhosis, and reduce the risk of HCC and liver-related deaths.

  • WHO, Guidelines for the Prevention, Care and Treatment of Persons with Chronic Hepatitis B Infection

Due to the persistence of cccDNA, the term “cure” has historically been avoided in the treatment of chronic hepatitis B because there is a lifelong risk of reactivation of infection, even in persons with serologic markers of resolved infection.1

There are currently two definitions of “cure” in chronic hepatitis B1,2,7:

Sterilizing cure
Sterilizing cure

Defined by undetectable HBsAg in serum and eradication of HBV DNA including intrahepatic cccDNA and integrated HBV DNA7

Functional cure
Functional cure

Defined by HBsAg loss and sustained HBV DNA suppression

Currently, only functional cure is considered to be an achievable goal.1

The goals of chronic hepatitis B treatment are to decrease patient morbidity and mortality.1,2

  • Chronic hepatitis B treatment should aim to achieve sustained suppression of the virus and prevent the progression of liver disease and HCC
  • Sustained suppression of hepatitis B replication has been associated with:
    • Loss of HBeAg, with or without detection of anti-HBe
    • Normalization of serum ALT
    • Improvement in liver histology


AASLD=American Association for the Study of Liver Diseases; AATA=Asian American Treatment Algorithm; ACP=American College of Physicians; ALT=alanine aminotransferase; cccDNA=covalently closed circular deoxyribonucleic acid; CDC=Centers for Disease Control and Prevention; EASL=European Association for the Study of the Liver; HBeAg=hepatitis B e-antigen; HBsAg=hepatitis B surface antigen; HBV=hepatitis B virus; HBV DNA=hepatitis B virus deoxyribonucleic acid; HCC=hepatocellular carcinoma; ULN=upper limit of normal; WHO=World Health Organization.