People at high risk for hepatitis B (HBV) should be screened for the virus, according to a new recommendation from the U.S. Preventive Services Task Force (USPSTF).

The recommendation, appearing in Annals of Internal Medicine, is a change from the task force’s 2004 position that the potential harms of screening outweighed any benefits.

But evidence accumulated since then suggests that — at least for people at high risk — the net benefit of screening is moderate, according to task force chair Michael LeFevre, MD, of the University of Missouri School of Medicine in Columbia, and colleagues.

The recommendation brings the USPSTF into line with several other groups, including the CDC, the American Association for the Study of Liver Diseases, and the Institute of Medicine, LeFevre and colleagues noted.

The changed recommendation is “a dramatic and welcome upgrade,” commented Raymond Chung, MD, and Ruma Rajbhandari, MD, both of Massachusetts General Hospital in Boston.

In an accompanying editorial, they argued that the change is “long overdue,” mainly because of increasing evidence that suppressing HBV — after screening has revealed its presence — has important clinical benefits.

Indeed, a separate report in the journal shows that prenatal screening of pregnant women, followed by immunoprophylaxis if HBV is present, prevents vertical (mother-to-child) transmission.

The USPSTF gave such screening the nod in 2009, and the current recommendations don’t address the issue. Instead the focus is on asymptomatic, nonpregnant adolescents and adults at high-risk for HBV infection:

• Those born in countries where the prevalence of HBV infection is 2% or greater
• Those born in the U.S., not vaccinated in infancy, and whose parents were from a country with a high HBV prevalence
• HIV-positive people
• Injection drug users
• Household contacts of people with HBV
• Men who have sex with men

The task force panel noted that between 700,000 and 2.2 million people in the U.S. have chronic HBV, a disease whose natural history can include cirrhosis, hepatic decompensation, and hepatocellular carcinoma. Indeed, estimates are that between 15% and 25% of people with chronic HBV eventually die of cirrhosis or liver cancer.

People with chronic HBV can also transmit the infection to others, the task force noted, and screening could identify people who might benefit from treatment or other interventions.

Evidence for Benefit Versus Risk

The task force found no randomized, controlled trials that demonstrate direct evidence of reduction in morbidity, mortality, and disease transmission after screening.

But there is adequate evidence that vaccination decreases HBV acquisition and convincing evidence that antiviral treatment leads to virologic or histologic improvement or clearance of the HBV e antigen [HBeAg].

Finally, there is adequate evidence that antiviral therapy improves health outcomes, such as reducing the risk of hepatocellular carcinoma.

The task force also found that the harms of screening and of antiviral therapy were “small to none.”

Currently, the U.S strategy to contain HBV is based on infant vaccination, as well as vaccination of adolescents and adults at high risk for infection. Seven drugs are approved to treat infection — interferon-alfa2b, pegylated interferon-alfa2a, lamivudine (3TC), adefovir (Hepsera), entecavir (Baraclude), telbivudine (Tyzeka), and tenofovir (Viread).

The list is evidence of “continued progress in treatment of HBV infection,” Chung and Rajbhandari argued, adding that the “case for suppression of HBV replication is compelling.”

Research has shown that serum HBV DNA levels, a marker of viral replication, are associated with the incidence of hepatocellular carcinoma, cirrhosis, and liver-related deaths, they noted.

And the “preponderance of evidence” shows that virologic suppression cuts the incidence of hepatic decompensation and cancer, reverses cirrhosis, and stabilizes hepatic failure, they wrote.

The task force recommendation, they argued, would be “more useful” with a table listing all the factors that make a patient high risk. “We worry that busy generalist clinicians do not have the time to estimate their patients’ risks for HBV infection,” Chung and Rajbhandari wrote.

Preventing Vertical Transmission

Meanwhile, in a separate article, researchers in California reported that the combination of prenatal HBV screening and postnatal prophylaxis is “highly effective” in preventing mother-to-child transmission.

Investigators led by Ai Kubo, PhD, of the Kaiser Permanente Division of Research in Oakland, studied records of HBV-positive mothers to judge the effectiveness of immunoprophylaxis of the newborns, as well as risk factors for failure.

About 24,000 HBV-positive women give birth every year in the U.S., Kubo and colleagues noted, putting their offspring at risk of the virus.

They added that about one in four children infected with HBV will eventually die of complications from chronic liver disease or cancer. From 35% to 50% of those children are thought to have been infected by perinatal exposure to blood or blood-contaminated fluids.

For those reasons, they argued, “the prevention of vertical transmission from mother to child plays a vital role in decreasing disease prevalence.”

Vertical transmission can be cut by testing for the HBV surface antigen (HBsAg) to identify HBV-positive infected pregnant women and then giving providing HBV immunoglobulin and vaccine to their infants soon after birth.

Both the USPSTF and the CDC strongly recommend the practice, which works well in controlled settings, Kubo and colleagues noted, but effectiveness in clinical practice has been less well studied.

To help fill the gap, they turned to data from Kaiser Permanente Northern California, an integrated health services delivery organization with about 3.3 million members.

The system sees more than 36,000 infants delivered yearly. Kubo and colleagues looked at births from 1997 through 2010, focusing on women who were tested and found to be HBV-positive.

All told, they reported, 4,446 infants were born to 3,253 HBV-positive mothers over the study period.

Analysis of the data showed:

• Overall, the infant infection rate was 0.75 per 100 births.
• If mothers were positive for the HBV e antigen, indicating active HBV replication, the rate per 100 births was 3.37.
• For mothers negative for the e antigen, the rate per 100 births was 0.04.

Viral Load and Transmission Risk

Aside from active HBV replication, viral load also played a role, they reported, with the lowest level associated with transmission being 6.32×10⁷ IU/mL among women whose virus level had been tested.

Among the 83 children born to mothers with a viral load of 5×10⁷ IU/mL or greater, the rate of infection per 100 births was 3.61. On the other hand, if the viral load was lower than that cutoff, no children were infected, regardless of e antigen status.

The researchers cautioned that testing for HBV immunity and infection was “less complete and timely” in the earlier years of the study than it was later. Also, they noted, DNA testing has only recently been widely used, so that only a subset of mothers had DNA viral load levels available.

On the other hand, most women in the study were not given antiviral therapy, allowing the researchers to evaluate the effectiveness of immunoprophylaxis alone.

Kubo and colleagues concluded that using the CDC-recommended protocol when pregnant women with HBV give birth prevents mother to child transmission in most cases, especially if the maternal viral load is low or the mother is e antigen-negative.

“Such women are unlikely to benefit from additional interventions to decrease vertical transmission,” they argued.

Mothers who were e antigen–positive or had a higher viral load had “low but detectable transmission rates,” they noted, and studies are warranted to see the effect of such interventions as late-pregnancy antiviral therapy in high-risk women.