Liver specialist Maurizio Bonacini is spearheading efforts to develop a cure for chronic hepatitis B, a disease that affects millions worldwide and is a leading cause of liver cancer. Based in San Francisco, Bonacini emphasizes the urgency of his mission, stating, “It’s the last frontier.” Over two million individuals in the United States are estimated to live with chronic hepatitis B, a condition that remains largely untreated despite being preventable and manageable.
The World Health Organization reports that approximately one in three people globally has been infected with acute hepatitis B. The risk of developing chronic hepatitis B is particularly high among infants, with a staggering 90 percent likelihood of progression for those infected at birth. Without treatment, the virus leads to liver cancer in 25 percent of cases, resulting in a mortality rate of one in four.
Despite the availability of vaccines and antiviral treatments, the spread of hepatitis B continues to persist six decades after its initial discovery. Bonacini is now part of a clinical trial called B-United, which involves 300 chronic hepatitis B patients across 80 sites in 18 countries. Sponsored by GlaxoSmithKline, this initiative aims to find a viable cure. Bonacini oversees one of the two investigation sites in California, the other being led by Dr. Huy A. Nguyen in San Jose.
The current treatment protocol requires patients with hepatitis B to take antiviral pills for life to prevent the virus from rebounding. These medications inhibit the replication of hepatitis B DNA, effectively halving the risk of liver cancer and other health complications. However, such treatments also come with potential side effects, including upper respiratory infections, fatigue, nausea, and gastrointestinal issues. In some cases, patients may develop resistance to the antivirals, leading to severe kidney or liver complications.
Bonacini aims for a “gold medal” solution—a sterilizing cure that eliminates the virus entirely. In the interim, he is focused on achieving a “functional cure,” which would significantly reduce the risk of cancer by 80 percent and allow patients to discontinue antiviral medications. Currently, he is monitoring ten participants from the Bay Area while overseeing an additional 200 patients who do not qualify for the trial.
Participants in the study receive monthly injections of an investigational drug designed to slow the production of the surface antigen associated with hepatitis B. After 24 weeks, they are given a different research drug for another 24 weeks. If the surface antigens remain absent after an additional 24 weeks, participants will cease treatment but continue to be monitored closely. According to Bonacini, the U.S. Food and Drug Administration may consider the approval of these injections for market use as early as late 2027.
In addition to his research, Bonacini advocates for improved prevention and diagnosis protocols. In June, he approached over 60 primary care physicians in California, urging them to incorporate state-mandated screening for hepatitis B into their electronic health records. He encountered resistance from busy practitioners who felt that implementing such changes would be burdensome.
Many physicians expressed reluctance to subject their patients to additional testing, despite the theoretical coverage by insurance in California. “The consensus seemed to be that implementing this would be very burdensome,” Bonacini noted, reflecting on the challenges faced in pushing for better public health measures.
Current U.S. immigration laws require proof of vaccination against hepatitis B for newcomers but do not mandate screening for the virus itself—a loophole Bonacini describes as a significant oversight. For example, one of Bonacini’s study patients, a San Francisco resident in his 40s, immigrated from Southeast Asia at age nine. Although he received a hepatitis B vaccination later in life, he discovered during a routine check-up that he had already contracted the virus, resulting in fatty liver and mild cirrhosis.
The patient, who prefers to remain anonymous due to the stigma surrounding hepatitis B, enrolled in Bonacini’s research after participating in COVID-19 vaccine trials. Within months of starting oral medication, his hepatitis B DNA became undetectable, and after 26 weeks of trial injections, he is now considered non-contagious.
He expressed frustration over the financial burden associated with his ongoing health monitoring, which costs between $100 and $200 for blood tests and approximately $500 to $700 for imaging every six months. “I will participate in any clinical trial just to find a cure,” he stated, highlighting the need for systemic improvements in managing hepatitis B.
Bonacini believes that enhanced prevention strategies could significantly reduce the number of new cases in the coming generations. Nonetheless, he maintains that a cure is still essential since it is impractical to inoculate the entire population. He collaborates with respected virologists and clinicians from regions like Tanzania and Hong Kong, where up to 7 percent of the population is affected by the disease. “We just have to find the right drugs,” he concluded, optimistic that a breakthrough may soon be within reach.
