IN BRIEF:

Despite the development of an effective vaccine, hepatitis B infection remains a serious health problem worldwide.

Adults exposed to hepatitis B typically fight off the infection; infants and children almost always develop chronic infections.

People can carry hepatitis B virus without having symptoms, even though the infection may be damaging the liver.

Although not everyone infected develops serious complications, hepatitis B can lead to liver disease and cancer.

With seven treatments approved for hepatitis B, doctors can successfully control the infection in most patients.

The decisive scientific battle against hepatitis B has been won. Thanks to a vaccine approved in the 1980s, transmission of this potentially deadly virus can now be stopped. In countries where the vaccine is widely used, the series of three shots has almost completely halted the spread from infected mothers to their infants, one of the most common routes of transmission, and the one most likely to lead to chronic infection and serious liver disease. The vaccine has also significantly reduced transmission between adults.

Still, an estimated 1.3 million Americans and 400 million people worldwide harbor the virus. Chronic infection with hepatitis B can lead to cirrhosis, or scarring of the liver, and liver failure. Those infected with the virus have a 100-fold higher than average risk of liver cancer.

In the United States, most new cases occur in recent immigrants who were exposed as infants or young children in their native countries. Many don’t know they harbor the virus. A 2005 screening program of Asians and Pacific Islanders in New York City, for example, documented a 15 percent infection rate. One in three of those found to carry the virus were unaware they had been infected.

“These are hard populations to reach,” said Dr. Adrian Di Bisceglie, chief of hepatology at Saint Louis University School of Medicine. “Some are illegal immigrants who are afraid to go to the doctor. Others are self-employed first-generation immigrants who don’t want to get involved in the health care system.”

To reach more chronic carriers, the Centers for Disease Control and Prevention issued new guidelines in September recommending testing for everyone born in regions where hepatitis B infects 2 percent or more of the population. That includes large swaths of Asia, the Pacific Islands, Africa, Eastern Europe and the Middle East, where the virus still runs rampant. Others at increased risk are men who have sex with men and intravenous drug users. Patients receiving chemotherapy or immunosuppressive drugs should also be tested; dormant infections can flare up dangerously when the immune system is suppressed.

For those already infected, the prognosis has brightened considerably with the approval of a succession of new and more effective drugs. The first drug used against the virus, interferon, has been supplanted by a longer-lasting version, called pegylated interferon, or peginterferon. In addition, six antiviral drugs, called nucleoside and nucleotide analogs, have been approved.

“Thirty years ago there was nothing we could offer these patients,” said Dr. Emmet B. Keeffe, chief of hepatology at Stanford University School of Medicine. “Today we can control the infection in a majority of patients.”

The most striking evidence comes from waiting lists for liver transplants, long the last-resort treatment for patients infected with hepatitis B who develop severe liver disease. Since 2000, the number of Americans registered for liver transplantation as a result of hepatitis B infection has dropped by 37 percent, according to a study by Dr. W. Ray Kim, a hepatitis expert at the Mayo Clinic College of Medicine.

Encouraging news also emerged from a landmark 2004 study in Taiwan that tested an antiviral drug called lamivudine against a placebo in patients with advanced disease. The trial was halted early because patients receiving the medication improved so much that the investigators felt obliged to switch all the volunteers to the active drug.

“This was the definitive study,” Dr. Di Bisceglie said. “We knew antiviral drugs could suppress virus levels and improve liver function. This showed that treatment also lowered rates of liver cancer and liver failure.”

Even with an arsenal of seven drugs, deciding when to start treatment — and when to stop it — is surprisingly complicated.

“The problem with hepatitis B infection is that the natural history of the disease is so variable,” said Dr. Nancy Reau, assistant professor at the University of Chicago Medical Center. When adults are exposed to the virus, they almost always fight it off successfully on their own. When infants are infected, however, their immature immune systems don’t recognize the invader, which almost always goes on to cause chronic infection. A decades-long period may follow during which the virus continues to replicate but causes little damage.

Then, for reasons not well understood, the immune system becomes triggered and begins to attack the virus. The battle itself accelerates damage to the liver, increasing the risk of cirrhosis, liver failure and liver cancer.

Yet a majority of patients with hepatitis B, again for unknown reasons, carry the virus without ever developing these serious consequences. Unfortunately, doctors cannot reliably predict who is at risk for trouble. “Our crystal ball just isn’t very good yet,” Dr. Reau said.

Physicians wouldn’t need a crystal ball if they had a drug that reliably cured the infection. But in most patients, the available drugs suppress the virus but do not eliminate it. Patients often have to stay on medication for years, even indefinitely.

“Obviously we don’t want to start patients on drugs if they don’t need them,” Dr. Di Bisceglie said. “And because the virus can develop resistance to antiviral drugs we have, we don’t want to start treating patients before they really need it. And the drugs are expensive.”

Deciding when to stop treatment can be equally difficult. In some patients, treatment suppresses the virus to undetectable levels, and once the drug is stopped, the infection remains quiet. But in others, the virus can flare up again after treatment ends, sometimes causing rapid liver damage.

Since some of the drug treatments are so new, and the course of hepatitis B so long, researchers are only beginning to answer questions about optimal long-term treatment. Still, helpful insights have emerged. Patients with hepatitis B who test positive for a protein in the blood called e-antigen appear to have the best shot at going off treatment without a flare-up. Those with e-antigen negative infections, on the other hand, are likely to need to be on therapy indefinitely. Researchers are also gaining insight into which patients will do best on peginterferon versus the newer antiviral drugs.

“Ironically, the more we learn, the more complicated our clinical decisions have become,” Dr. Reau said. “The field is moving so fast that what we did two years ago is already fairly obsolete.”

For people infected with hepatitis B, the rapid progress in research means having to weigh complicated options. But it also means a far greater chance that the virus can be kept at bay for a lifetime.