Spotlight on HBV infection

In the past month, the U.S. Preventive Services Task Force published a draft recommendation statement on screening for hepatitis B virus (HBV) infection, and two systematic reviews and meta-analyses looked at treatments and a novel immunoassay to quantify HBV DNA.

Recent research and recommendations focused on hepatitis B virus (HBV) infection.

On May 5, the U.S. Preventive Services Task Force (USPSTF) published a draft recommendation statement that recommends screening asymptomatic, nonpregnant adolescents and adults at increased risk for HBV infection, including those who were vaccinated before being screened (B recommendation). The draft recommendation statement is consistent with the group's 2014 recommendation and is bolstered by new evidence reporting that antiviral therapy reduces risk of mortality and hepatocellular carcinoma (HCC). The document is available online for public comments until June 1.

The USPSTF said it is reasonable for clinicians to screen adolescents and adults born in countries or regions with a hepatitis B surface antigen (HBsAg) prevalence of 2% or greater (regardless of vaccination history in their country of origin) and those born in the U.S. who did not receive the HBV vaccine as infants and whose parents were born in regions with an HBsAg prevalence of 8% or greater (regardless of their mother's HBsAg status). In addition, clinicians should also offer screening to other groups at increased risk, which include past or current users of injection drugs, men who have sex with men, and people with HIV, as well as sex partners, needle-sharing contacts, and household contacts of those known to be HBsAg positive, the Task Force said.

Next, two systematic reviews and meta-analyses, both published by Clinical Gastroenterology and Hepatology, looked at two first-line treatments for HBV infection and an alternative to nucleic acid testing to quantify HBV DNA.

In the first, published online on May 11, researchers analyzed 15 studies published from 2010 through 2019 to compare the effectiveness of tenofovir disoproxil fumarate and entecavir in preventing HCC. Of 61,787 total patients with chronic HBV infection, 16,101 received tenofovir and 45,686 received entecavir.

Treatment with tenofovir was associated with a 20% lower risk of HCC than treatment with entecavir (hazard ratio, 0.80; 95% CI, 0.69 to 0.93; P=0.003). The lower risk of HCC in patients given tenofovir compared with entecavir persisted in sensitivity and subcohort analyses of patients who were propensity matched or had cirrhosis. Among other limitations, all included studies were nonrandomized prospective or retrospective comparative studies, and the majority of patients were from Asia, the authors noted. “Given that an RCT [randomized controlled trial] cannot be conducted in the near future, this meta-analysis may provide the best approach to resolve conflicts at the moment. … Ideally, future RCTs comparing the efficacy of [tenofovir] and [entecavir] in the prevention of HCC would draw a firm conclusion,” they wrote.

In the second analysis, published online on April 29, researchers assessed the performance of a novel immunoassay, HBV core-related antigen (HBcrAg), as a low-cost (<$15/assay) alternative to nucleic acid testing to indicate clinically important high viremia in patients with chronic HBV infected with different genotypes. They looked at studies measuring HBV DNA and HBcrAg in the same blood samples. Of 74 eligible studies, they obtained individual participant data for 60 (81%). The meta-analysis included 5,591 individuals not on antiviral therapy and 4,806 receiving antivirals.

In untreated patients, the pooled area under the receiver operating characteristic curve and optimal cut-offs (log U/mL) were 0.88 (95% CI, 0.83 to 0.94) and 3.6, respectively, to diagnose HBV DNA level ≥2,000 IU/mL, and 0.96 (95% CI, 0.94 to 0.98) and 5.3, respectively, to diagnose HBV DNA level ≥200,000 IU/mL. In the validation set, the sensitivity and specificity were 85.2% and 84.7%, respectively, for ≥2,000 IU/mL, and 91.8% and 90.5%, respectively, for ≥200,000 IU/mL. The performance of HBcrAg did not vary by HBV genotypes. In patients receiving anti-HBV therapy, the correlation between HBcrAg and HBV DNA was poor.

Most included studies were from high-income countries, mainly in Asia, with an overrepresentation of HBV genotypes B and C, among other limitations, the authors noted. While low- and middle-income countries account for the highest HBV burden, they face enormous challenges in scaling up treatment services with the limited access to nucleic acid testing, they said. “HBcrAg, an attractive alternative to HBV DNA [real-time polymerase chain reaction], has potential to contribute to the global elimination goals,” they concluded, adding that future studies should assess the feasibility and cost-effectiveness of HBcrAg assays in low- and middle-income countries.