Mandana Khalili, MD
Chief of Clinical Hepatology at San Francisco General Hospital, University of California–San Francisco
|ADA Research Funding|
Clinical Research Award
Hepatitis C is a virus that infects the liver. Once inside the body, hepatitis C (HCV, for short) can take decades to manifest itself, but once it does, the consequences are severe: The disease leads to scarring of the liver that eventually damages the critical organ beyond repair. Late-stage HCV patients need liver transplants to survive, and even a new liver isn’t enough to rid the body of the tenacious virus.
Public-health experts say HCV is a major problem: More than 4.1 million Americans are estimated to carry it, and 80 percent of them are capable of passing the infection along. That makes it America’s most common bloodborne infection. “You can catch it from anything that allows exposure to blood or blood products,” says University of California–San Francisco researcher Mandana Khalili. That’s a wide spectrum that includes everything from intravenous drug use and unprotected sex to accidental contact with blood or blood transfusions from someone infected with the virus.
In recent years Khalili and others have begun studying the connections between hepatitis C and diabetes. It turns out that people with hepatitis C infections have a much higher prevalence of type 2 diabetes, and people with diabetes are more likely than most to have hepatitis C. The correlation is so strong that type 2 diabetes is often considered a symptom of hepatitis C. “Diabetes is associated with a faster progression of liver disease,” Khalili says. “And HCV could be accelerating diabetes.”
Khalili is a hepatologist, or liver specialist. Her work focuses on high-risk populations. For reasons researchers don’t fully understand, HCV is more common in Latinos and African Americans than whites. Although research has been limited, one study suggested that Mexican Americans are up to six times as likely to have HCV as whites.
For people with a higher likelihood of developing diabetes—whether due to lifestyle or genetics—the liver infection may push things over the cliff. “Probably hepatitis C is going to affect people with a predisposition for diabetes and make it more likely that they’ll develop full-blown diabetes,” Khalili says. For Latinos, already one of the groups most at risk for diabetes, the possibility that an HCV infection might compound their risk is particularly serious.
That’s why Khalili and others are working hard to unravel the complex relationship between diabetes and HCV. “We’re trying to establish the cause-and-effect scenario,” Khalili says. “If we understand the mechanisms by which these two are connected, we could design treatments to deal with both.”
To tease out some of the links between the chronic liver infection and type 2 diabetes, Khalili is working with about 75 Latinos, two thirds with HCV infections and a third without. With a grant from the American Diabetes Association in conjunction with the Abby Mauzé Charitable Trust, she’s using state-of-the-art blood-testing technology to compare the two groups. “We’re using direct physiological tests that measure the presence of insulin resistance and abnormalities in insulin secretion,” Khalili says.
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The goal is to see whether insulin resistance—a key early indicator of type 2 diabetes—is more pronounced in people with HCV. By testing people whose HCV is in its early stages and who don’t have diabetes, she’s trying to eliminate “confounders,” or outside factors that would affect the experiment’s results. “We’re looking at patients where hepatitis C on its own would have an impact on insulin resistance,” she explains. Participants are also given a follow-up exam after 18 months, which offers Khalili and her collaborators a way to see if insulin resistance progresses faster in patients with HCV infections.
Khalili’s early results suggest that HCV does indeed increase the likelihood that people will have trouble both secreting insulin and responding to it. That’s a prediabetic double whammy that puts Latinos with hepatitis C infections in an extremely high-risk group for developing type 2 diabetes.
The good news is that treatments for hepatitis C are getting more and more effective all the time. Using the latest medicines, the infection can now be effectively cured in up to 70 percent of the people who are treated. A better understanding of how HCV leads to diabetes might show a need for treatments that target HCV early, before it can contribute to the onset of diabetes. It might also help doctors tailor diabetes treatment for people infected with HCV.