NIAID Research to Address Viral Hepatitis Risk Worldwide

The Year of Hepatitis continues as World Hepatitis Day

Viral hepatitis affects the lives of about one in twenty people worldwide, resulting in more than a million deaths each year. NIAID is working on many ways to prevent and treat different types of hepatitis, including the development of vaccines and improved therapy and diagnosis. July 28 is observed annually as World Hepatitis Day, providing an opportunity to reflect on the impact of hepatitis on global health and focus on strategies to reduce its burden. To mark World Hepatitis Day, NIAID highlights recent advances researchers have made in these areas.

Hepatitis is an inflammation of the liver, which can cause liver damage that is fatal in some cases. Most hepatitis cases are caused by a virus, although other infections, heavy alcohol use, exposure to toxins or certain drugs, or autoimmune disease can also cause hepatitis. There are five main viruses that cause hepatitis, types A, B, C, D and E. Different hepatitis viruses are spread in different ways and each has a unique impact on health. Hepatitis A and E are usually spread through contaminated food and water, while hepatitis B, C and D are spread through body fluids. People with HIV are at increased risk of serious disease when hepatitis A, B, or C is present in the body. In addition, the presence of hepatitis B and C can affect the treatment of HIV. Because of these interactions, people with HIV are disproportionately affected by viral hepatitis.

Progress toward effective hepatitis B vaccines for people with HIV

Conventional vaccines against hepatitis B are sometimes unable to provide sufficient immunity to people with HIV. An ongoing clinical trial is evaluating the effectiveness of a vaccine against hepatitis B called HepB-CPG (also known as Heplisav-B) in people with HIV. HepB-CPG confers high levels of immunity against hepatitis B in people with HIV. The researchers looked specifically at the effects of the HepB-CpG vaccine in people with HIV who had not previously responded to conventional hepatitis B vaccines. The HepB-CPG vaccine uses an adjuvant—or immune booster—called CPG-1018. In the study, they compared HepB-CPG with a hepatitis vaccine that used alum, a more traditional adjuvant, instead of CPG-1018. The researchers found that the vaccine containing CPG-1018 was superior to the conventional hepatitis B vaccine. The vaccines were safe and well tolerated. This work provides important evidence supporting further development of a vaccine to prevent hepatitis B in people with HIV. The study is being led by ACTG, a clinical trials network led by NIAID.

Discovery of new pathways of immunity against hepatitis C

Hepatitis C can be cured with antivirals, but there is currently no vaccine against this type of hepatitis, partly because of the large number of variations and rapid evolution of the virus. Even people who have recovered from hepatitis C can become infected again. The number of people diagnosed with hepatitis C is increasing, and the vaccine will be an important tool to prevent the spread of this dangerous virus, which can cause liver failure and cancer. Some people clear hepatitis C from their bodies naturally and have protective immunity against developing the disease when re-exposed to the virus. NIAID-funded researchers are testing immune responses in these individuals compared to those who develop persistent infection. The researchers found that neutralizing antibodies helped clear the hepatitis C virus from people's bodies and directed these antibodies to specific sites on the surface of the virus. Investigating how these antibodies are produced and how they target the virus could help researchers develop a vaccine against hepatitis C.

Advancing the development of vaccines against hepatitis E

Hepatitis E is the leading cause of acute hepatitis worldwide, causing an estimated 20 million infections and 70,000 deaths each year, with a greater impact in regions with limited access to resources. There is no treatment for acute hepatitis E or approved vaccines against the virus. One vaccine under development, HEV-239, was recently shown in an NIAID-supported trial to elicit a safe and durable immune response in adults in the United States. These promising results support the evaluation of the vaccine in further clinical trials.

Understanding hepatitis B-associated liver cancer

NIAID researchers are studying diseases caused by viral hepatitis-related liver damage, including a liver cancer called hepatitis B-related hepatocellular carcinoma (HCC), which causes malignant tumors in the liver. Although immunotherapy can be effective for treating various forms of solid tumors, HCC-related tumors often do not respond to this treatment. To understand why, researchers carefully studied the tumor microenvironment—the specific molecular and cellular conditions that exist in tumors—in 12 people with HCC. They found that two distinct subtypes of tumors existed in people with HCC. In about half of the people, the tumor microenvironment had high levels of immune activity, while the other half had low levels in the tumor. The discovery may help scientists understand how people with this type of HCC respond to treatment and may allow the development of treatments tailored to individuals with different subtypes.

New animal models for hepatitis B and C

NIAID is funding several new projects focused on developing small animal models to understand and combat hepatitis B and C. This work is important because research on this virus has been hampered by the lack of available animal models to study promising preventive and therapeutic concepts. Recipients of the new awards include:

Wake Forest University for a project titled "Novel Mouse Models of Hepatitis B Virus Infection and Replication." Guangxian Luo is the principal investigator. (Grant number: R01 AI183855-01.)

Research Institute at Nationwide Children's Hospital for a project titled "Animal Models to Study Heterogeneous Consequences of HCV Infection and Pathogenesis." Amit Kapoor is the principal investigator. (Grant number: R01 AI183877-01.)

Rockefeller University for a project entitled "Breaching the Species Barrier: Toward an Immunized HBV-Sensitized Mouse Model." Charles Rice is the principal investigator. (Grant number: R01 AI183884-01.)

Georgetown University for a project entitled "Development of Woodchucks Susceptible to Hepatitis B Virus Infection by Modifying the Virus or Host". Stefan Mayne and Jianming Hu (at Penn State College of Medicine) are the principal investigators. (Grant number: R01 AI183788-01.)

These advances and proactive projects underscore the important work being done by NIAID to prevent and treat viral hepatitis with the goal of reducing the global burden of this disease.