In a hepatitis C human challenge study, volunteers would be infected with the virus for several months before receiving free treatment. That’s much shorter than most people live with it. But that doesn’t mean there can’t be risks of harm. So what does the research say? A 2023 scientific paper concluded the risk of liver cancer as a result of a hepatitis C human challenge study was “very low or negligible” — but how did they determine that?
From 1978 to 1979 in East Germany, thousands of women contracted hepatitis C receiving blood products tainted unknowingly tainted with the hepatitis C virus. Many went on to live with the chronic liver disease for decades. Some, however, fought off the virus on their own without treatment, mostly within a year. This provides a natural experiment the ones who fought off the virus quickly were analyzed to see if their health was negatively affected in the long run. This information is useful as scientists consider using human challenge studies for hepatitis C vaccine development, where volunteers would be infected with the virus and treated in under a year.
Hepatitis C infection and the risk of cancer
The hepatitis C virus lives in the liver cells of people it has infected. Some people’s bodies fight off the virus on their own, usually within the first six months of infection. For most people, though, it becomes a life-long (chronic) condition unless they receive treatment. Over time, the virus harms the liver. This can lead to serious liver damage, called cirrhosis, and even liver failure or cancer, usually after several decades.
Scientists and related experts increasingly believe human challenge studies for hepatitis C will be critical for developing an eventual hepatitis C vaccine. But many questions must be answered before this can be done is, including “will giving someone a short-term hepatitis C infection cause serious, long-term harm?” If so, then a hepatitis C challenge study would very likely be unethical.
A group of researchers took up this question in a recent systematic review, focusing specifically on the risk of developing liver cancer. One piece of evidence the researchers analyzed was the “German anti-D cohort,” a group of thousands of German women who were given a product containing an antibody, called anti-D, in the late 1970s. This was done to prevent their immune systems from harming their fetuses if they became pregnant again.
The anti-D product is derived from donated blood. Some of the blood used to make the product in East Germany was unknowingly tainted with the virus and given to the women, infecting them (the hepatitis C virus wasn’t identified until 1989, so it was impossible to screen for at the time these women were given the anti-D). After the virus was discovered, researchers eventually conducted a study observing the health of over 718 of these women over 35 years.
189 of the 718 women had self-limiting infections: their bodies fought off the hepatitis C virus without treatment. (For people who do fight it off naturally, they usually do so within one year.) After 35 years, 180 of these women were still alive. Eight had died of unrelated causes, and one died from cirrhosis caused by alcohol use disorder (alcoholism).
Of the living 180, none had liver cancer. Four had some form of serious liver damage, one of which was directly traced to alcohol use disorder. Liver disease/damage is common among aging populations in the US and Europe, so the remaining 3 cases out of 180 were not considered statistically significant evidence that short-term infection caused lasting liver problems. High body-mass index (BMI) was associated with liver damage and cancer, but not short-term the hepatitis C infection.
Since they were otherwise healthy and relatively young when they were infected, findings from this research are likely very relevant to volunteers in a human challenge study, who will also be screened to make sure they’re under a certain age and don’t have other risk factors or health conditions that could lead to serious problems.
There are other risks due to hepatitis C infection besides just cancer and liver damage, but the German anti-D cohort is one of the reasons researchers (and we) believe short-term infection of healthy adult volunteers with the virus can be done ethically.