Hope for Patients with Hepatitis C

New drug combinations suppress virus

The most common form of the hepatitis C virus in the United States and worldwide — known as genotype 1 — also remains the most difficult to treat. Hepatitis C infects the liver and can lead to cirrhosis and liver cancer; an estimated 170 million people around the globe are infected. Although there is no vaccine to prevent hepatitis C, it is a potentially curable disease. A recent U-M study added to that potential with a new combination of investigational drugs that suppressed hepatitis C genotype 1 in a high percentage of patients who hadn’t responded to previous treatment.

Two antiviral agents, known as PEG-interferon alfa and ribavirin, are typically used to treat this form of hepatitis C. The U-M study, published January 19 in the New England Journal of Medicine, focused on patients with hepatitis C genotype 1 who had not responded to treatment with these drugs.

“The two recently approved hepatitis C drugs — telaprevir and boceprevir — combined with PEG-interferon alfa and ribavirin have limited success in patients who have not responded to previous treatment with PEG-interferon alfa and ribavirin,” says Anna S. Lok, M.D., the Alice Lohrman Andrews Research Professor of Hepatology, director of clinical hepatology, and lead author of the study. A new combination regimen to increase response rates in that population was the goal of the phase 2 clinical trial conducted by Lok and colleagues, including scientists from Bristol-Myers Squibb, which funded the study. Patients were given a combination of two investigational direct-acting antiviral agents (daclatasvir and asunaprevir) alone, or with PEG-interferon alfa-2a and ribavirin. All of the patients saw their hepatitis C viral load drop rapidly, Lok says.

Of the 10 patients who were given the four-drug treatment, all had sustained virologic response at the end of treatment and at 12 weeks after stopping treatment. Sustained virologic response means there is no hepatitis C virus detected in a patient’s blood after treatment is stopped, and research has shown later relapse to be rare. Four of the 11 patents who were given only the two direct-acting antiviral agents also achieved sustained virologic response.

Lok finds the high rate of sustained virologic response in patients who received the four-drug regimen “very exciting,” and although just 36 percent of patients given only the two direct-acting antiviral agents achieved sustained virologic response, Lok is encouraged by those results as well. “This is the first study to show that sustained virologic response can be achieved without the use of interferon or ribavirin,” Lok says. “These data are very encouraging because PEG-interferon alfa and ribavirin are associated with many side effects, and many patients with hepatitis C choose not to receive treatment for fear they cannot tolerate those drugs.”

The results suggest that further research into combinations of direct-acting antiviral agents should be encouraged, Lok says, but she also cautions about selecting the right combination of direct-acting antiviral agents in studies of interferon-free regimens. “In this study, all seven patients who received only two direct-acting antiviral agents and did not achieve sustained virologic response had emergence of drug resistance variants to both drugs,” she says.

Hepatitis C is transmitted through direct contact with infected blood and blood products. Up to 80 percent of those infected with hepatitis C will become chronically infected and, of those, 20 percent will develop cirrhosis. Up to 25 percent of patients with cirrhosis of the liver may progress to liver cancer. —MARY MASSON/RICK KRUPINSKI

An expanded version of the story

Pathology On-Site, Fewer Second Breast Cancer Operations

Nearly one in three women who have breast cancer surgery will need to return to the operating room for additional surgery after the tumor is evaluated by a pathologist. But a service that began two years ago at the University of Michigan Comprehensive Cancer Center cuts that number drastically by having pathologists on-site in the operating suite to assess tumors and lymph nodes immediately after removal. The surgeon and patient remain in the operating room until the results are known, and any additional surgery can be done immediately.

A study evaluating 271 patients treated eight months before the program began and 278 treated eight months after showed that the new process decreased the number of second operations needed by 64 percent, to one of every 10 women. Patients must return to the operating room for two primary reasons: to remove additional tissue when the cancer cells are too close to the margin of tissue removed, and, in some cases, to remove additional lymph nodes if the initial sentinel lymph node biopsy tests positive for cancer.

“The frequent need for second surgeries represents a tremendous burden for patients,” says lead study author Michael S. Sabel, M.D., associate professor of surgery in the Medical School. “Additional surgeries can result in worse cosmetic outcomes and increased complication rates.” Not only is the on-site pathology service beneficial for patients, “but it reduced the costs of caring for patients with breast cancer,” Sabel adds.

The U-M study showed that before the service, 25 percent of patients needed a second operation to remove more tissue, compared to 11 percent after the service began. Among patients with cancerous lymph nodes, 93 percent of them avoided a second operation. —NF

An expanded version of the story

Tinnitus Tied to Touch-Sensing Nerves

U-M researchers have previously demonstrated that after hearing damage from overexposure to noise, touch-sensing “somatosensory” nerves in the face and neck can become overactive, seeming to overcompensate for the loss of auditory input in a way the brain interprets — or “hears” — as noise that isn’t really there: tinnitus, commonly known as “ringing in the ears.”

Now a new study, published in the February 1 issue of The Journal of Neuroscience, has found that somatosensory neurons maintain a high level of activity following exposure to loud noise, even after hearing itself returns to normal.

The findings were made in guinea pigs, but mark an important step toward potential relief for people plagued by tinnitus, says lead investigator Susan E. Shore, Ph.D., of U-M’s Kresge Hearing Research Institute, who also is a professor of otolaryngology and of molecular and integrative physiology at the Medical School.

“The animals that developed tinnitus after a temporary loss in their hearing after loud noise exposure were the ones who had sustained increases in activity in these neural pathways,” Shore says. “In the future it may be possible to treat tinnitus patients by dampening the hyperactivity by reprogramming these auditory-touch circuits in the brain.” —ID

Health Briefs

Most parents report that they typically require their child to use a lifesaving booster seat, but more than 30 percent say they don’t enforce this rule when their child is riding with another driver, according to child health experts at U-M’s C.S. Mott Children’s Hospital. The study also reports that 45 percent of parents don’t require their children to use a booster if other children in the car do not have one.

An expanded version of the story

An updated review of data from the Selenium and Vitamin E Cancer Prevention Trial concluded that men who took 400 international units of vitamin E daily had 17 percent more prostate cancers than men who took a placebo. The NIH-funded study was conducted at more than 400 sites in the U.S. and Canada by the Southwest Oncology Group, headquartered at the U-M. Except for skin cancer, prostate cancer is the most common type of cancer among men in the U.S.

An expanded version of the story

Living in a lower socioeconomic neighborhood was linked with increased pain, pain-related disability and mood disorders for young adults, according to a U-M study — but young black patients faced difficulties with pain management no matter where they lived. The study suggests that physicians may need to be more aware of a patient’s life circumstances and resources when treating their chronic pain. —RK

An expanded version of the story