Accumulating data on the prevention, surveillance, and treatment of chronic hepatitis B (CHB) has resulted in an updated practice guideline, jointly issued by the American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America in Hepatology.

Thanks to recent immigration trends, the current disease burden of hepatitis B in the US is estimated to be as high as 1.8 million people. Hepatitis B virus (HBV) infection is the leading cause of hepatocellular cancer (HCC) worldwide.

The 23-member guideline panel developed six Population, Intervention, Comparison, Outcomes questions to provide evidence-based recommendations, with background information and implementation advice.

“This update is timely since concerns about the safety and high tolerability of NAs [nucleos(t)ide analogs] — coupled with concerns that existing guidelines are too complex and lead to missed opportunities to intervene for preventing liver-related complications — led to a call globally for broader treatment indications,” co-lead author Norah Terrault, MD, MPH, professor of medicine and chief of gastroenterology and liver diseases in the Keck School of Medicine at the University of Southern California in Los Angeles, told Medscape Medical News. Several other health and medical organizations have published new guidelines or are expected to do so soon, she said.

Nancy Reau, MD, associate director of solid organ transplantation and chief of hepatology at Rush University Medical Center in Chicago, noted that much of the updated focus addresses expanding treatment to subsets of chronically infected individuals who do not meet the traditional 2018 treatment indications. “This is important, as data continue to show that these individuals have ongoing risk for liver disease and HCC, and treatment may decrease this risk,” Reau, who was not a panel member, told Medscape Medical News. Other important areas she referenced are mother-to-child transmission (MTCT), discontinuing treatment in suppressed patients who have not lost hepatitis B surface antigen (HBsAg), and liver cancer surveillance.

“This document works hard to expand treatment, not restrict it,” she noted. “Most people with CHB are potential treatment candidates in a model that places significant weight on patient preferences. Treatment decisions are not always black and white, so “involving the patient in this conversation is imperative.”

Irrespective of treatment decisions, careful monitoring is important both to identify progression or a change in phase and to allow effective surveillance. “While shared decision-making is vital, it requires discussion of the pros and cons of treatment in a very personalized manner compared with a simple decision tree,” Reau said.

Method

The panel conducted four systematic literature reviews and tapped into two existing systematic reviews to develop the new recommendations, of which five relate to treatment and one relates to liver cancer surveillance. The authors conceded that the strength of evidence was largely of low or very low certainty, and most of the new suggestions are conditional, with only one strong suggestion based on moderate certainty (first item below). Most recommendations of the 2018 guidance remain applicable.

Among the update’s specific recommendations:

• For pregnant individuals, the guidelines have been expanded to include antiviral therapy with tenofovir disoproxil fumarate and/or tenofovir alafenamide to prevent MTCT. They also update advice on when to start and stop antiviral therapy solely to prevent MTCT.
• For viremic persons with high HBV DNA levels but without a disease-specific reason for antiviral therapy, the guidelines address when to consider treatment solely for the purpose of preventing transmission to others — for example, in a person engaged in sexual activity and not using barrier protection. Individuals requesting treatment for transmission prevention can be prescribed antiviral medication, Reau said.
• The recommendations provide a stricter definition of the immune-tolerant phase (in which HBV DNA levels are high, but liver enzymes are normal) and expand considerations for treatment based on age and noninvasive assessment.

“This is a significant change from 2018, when guidelines recommended against treatment in this phase,” Terrault said.

Treatment in this gray zone continues to evolve. “Although this guidance leaves much to shared decision-making, it does focus on both age and histology, including noninvasive tools as a surrogate for a biopsy, in defining groups that should be considered for antiviral therapy,” Reau said. The paper also stresses regular monitoring since hepatitis B is dynamic. “Recognizing fibrosis progression or transition to the HBeAg [hepatitis B e-antigen]-negative immune-active phase is important, as both should prompt antiviral treatment.”

• For HBeAg-negative patients with indeterminate phase in whom alanine aminotransferase and/or HBV DNA levels do not meet usual thresholds for treatment, the AASLD suggests considering antiviral therapy. This is another change from the 2018 guideline, which recommended monitoring only.
• For persons on NA therapy with sustained suppression of HBV DNA, the guidelines recommend against stopping NA therapy until patients achieve HBsAg loss. In contrast, the 2018 guidance stated that NA therapy discontinuation could be considered with close monitoring.
• Finally, the guidance on when to start HCC surveillance in persons with CHB and coinfections HIV, hepatitis D virus, or hepatitis C virus — and what to do after HBsAg clearance — has been updated. For example, surveillance in children should be individualized owing to the unknown risk for HCC in this population.

Going forward, said Terrault, “The recent HHS/ACIP [US Department of Health and Human Services/Advisory Committee on Immunization Practices] decision to remove HBV vaccination as a universal neonatal requirement is a major concern since neonates exposed to HBV at birth have the highest likelihood of developing CHB and then must endure a lifetime of monitoring, interventions, and surveillance to prevent liver cirrhosis and cancer.”

Added Reau: “We’ve seen the care cascade improve for multiple diseases when universal rules are in place. The new changes to the HBV schedule must be followed by assessment of its impact to ensure that this vaccine-preventable disease is not given an opportunity to lead to chronic infection.”

Another major concern, said Terrault, is the proportion of infected persons who remain undiagnosed. “But once a person is diagnosed, the new guideline expands indications for treatment and stresses the importance of rediscussing treatment at each clinic visit if a person isn’t on treatment.”

The guidelines will be updated as new data become available and HBV therapeutics evolve.

This guidance was supported by the AASLD. Terrault and fellow lead author Marc G. Ghany had no competing interests to disclose. Several co-authors reported ties to the private sector such as consulting, data monitoring, and speaking for, among others, GlaxoSmithKline, Abbott, Gilead Sciences, AbbVie, Roche, and Novo Nordisk. Reau reported having no competing interests relevant to her comments on the guideline.