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Early Treatment of HBV
Getting Out of the Gray Zone: Earlier Treatment for HBV Infection

Released: April 04, 2024

Expiration: April 03, 2025

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Key Takeaways
  • Patients who do not meet criteria for treatment initiation according to current guidelines for hepatitis B virus (HBV) infection can still be at increased risk for hepatocellular carcinoma; earlier treatment improves clinical outcomes and is cost-effective.
  • Clinicians must use their judgement in collaboration with patients to expand HBV treatment criteria, which may be considered in all individuals with HBV DNA ≥2000 IU/mL.

Limitations of Current Guideline Recommendations

Chronic hepatitis B virus (HBV) infection increases the risk of cirrhosis, hepatocellular carcinoma (HCC), and liver-related mortality if left untreated. Societal treatment guidelines differ, but most recommend treatment for patients with elevated HBV DNA and alanine aminotransferase (ALT) levels. However, people in the indeterminate phase or “gray zone” who do not meet treatment criteria can still be at risk for HCC.

Despite these risks, HBV treatment uptake, even among those who meet guidelines treatment recommendations, is suboptimal.

Emerging data demonstrate that treatment for HBV reduces viral load, viral integration, and associated hepatocyte clonal expansion, thereby lowering the risk for HCC even in individuals who do not meet treatment criteria.

We need to reframe the way we treat HBV. Current guidelines from the American Association for the Study of Liver Diseases recommend treatment for the inflammatory component of liver disease based on elevated ALT and fibrosis; European Association for the Study of the Liver guidelines recommend treatment as a viral infection independent of these indices. The latter approach allows for more streamlined treatment to increase uptake and avert downstream adverse outcomes.

Considerations for More Expansive HBV Treatment

Simplifying the HBV treatment algorithm is a major step towards ensuring expanded access to treatment. As we await liver society guideline updates, we must use the available data to inform treatment candidacy for patients who may benefit from treatment now. Newer studies have emerged showing that by eliminating ALT restrictions and HBeAg status and using an HBV DNA threshold of at least 2000 IU/mL, treatment would significantly reduce annual liver-related mortality, incidence of decompensated cirrhosis, and HCC. For example, in a study of people with HIV and HBV coinfection, where universal HBV treatment is inherent, sustained HBV suppression was necessary to gain maximal benefit from antiretroviral therapy for HCC prevention. In addition, treating all HBV-positive individuals in the US is cost-effective, and perhaps even cost-saving.

A few proposed treatment algorithms suggest treating every patient with a viral load greater than 2000 IU/mL, regardless of ALT levels. Updates to the World Health Organization (WHO) treatment criteria were just released, and now include all adults and adolescents (≥12 years of age) with a lower APRI score greater than 0.5 and HBV DNA threshold greater than 2000 IU/mL with elevated ALT. These changes are expected to capture at least 50% of all HBsAg-positive people vs about 20% previously. The updated recommendations are a step forward in that they prioritize who to treat rather than who not to treat.

Current HBV antiviral treatment options including tenofovir and entecavir are often given for lifelong durations and are unlikely to be curative. Therefore, they may not be appealing to all patients. However, I counsel my patients that these therapies are typically well tolerated and can be used to protect the liver until novel treatments emerge with the goal of finite durations to achieve functional cure.

On that note, we should consider patient preferences and health-related quality of life when deciding whether to treat an individual with HBV. Chronic hepatitis B can impact psychological well-being, social functioning, and physical well-being. Shared decision-making with patients for earlier treatment can help to address concerns about stigma and transmissibility. If a patient is willing to commit to the treatment, if there are no major risks of treatment-related adverse effects, and if he or she is fit to be treated, then they should be treated.

Conclusions

Expanding access to HBV treatment is sorely needed to improve patient outcomes. Some guidelines’ treatment criteria are limited and leave a large portion of patients who may benefit from treatment on the sidelines. We are unlikely to see long-term randomized trials to settle the question of whether to treat patients in the gray zone. Healthcare professionals must use their judgement in collaboration with patients to optimize treatment for each individual. Updated guidance, such as the WHO guidance, are moving to expanding treatment criteria in order to benefit more individuals living with HBV.  

Your Thoughts?

What is your biggest concern regarding earlier or more expansive treatment for patients with HBV infection? Leave a comment to join the discussion.