Date Published: 24 July 2012

Research into predictors of hepatitis C severity

What are the best predictors of the severity of hepatitis C ?

Recent research indicates that viral evolution and host protein levels may predict rapid disease progression.

Scientists in the USA have recently identified risk factors in people infected with the hepatitis C virus that may predict if rapid progression of hepatitis C from initial infection to severe liver conditions, e.g. cirrhosis, is likely in specific individual cases. Knowing if a particular patient's condition is likely to deteriorate quickly could help physicians choose the most appropriate treatment.

" Treatment for hepatitis C is often expensive and poorly tolerated," said NIAID Director Anthony S. Fauci, M.D, director of the National Institute of Allergy and Infectious Diseases (NIAID) .
" Tools that would enable physicians to better predict the course of disease progression in hepatitis C patients would help guide treatment decisions. This small study is a potentially important step in developing such tools."

Symptoms of acute infection with the hepatitis C virus, one of five viruses that cause acute and chronic hepatitis, include fatigue, jaundice and loss of appetite. Between 70% and 80% of people infected with the hepatitis C virus develop chronic infection, which over a patient's lifetime may lead to severe liver diseases, such as liver cancer and cirrhosis.

After a person is infected with hepatitis C, the virus evolves and circulates in the body in the form of several closely related strains, which allows it to adapt to drug treatments and avoid elimination. Some genetic differences between these strains result in changes to the proteins they encode, while others do not.

" A major mystery in the study of hepatitis C is that the disease course can be highly variable," explained lead researcher Dr. Farci.
" Some patients show no symptoms for decades and eventually die of other causes. Other patients rapidly develop cirrhosis and liver cancer, leading to liver-related death in less than ten years."

Research studies have revealed that having a weakened immune system, e.g. due to HIV infection or organ transplantation, can exacerbate hepatitis C-related diseases. However, this does not fully explain which hepatitis C patients will ultimately experience a more rapid health decline. There has been no reliable way to scientifically predict how the disease will progress in any particular patient.

The recent study involved samples collected from six patients who were infected with hepatitis C via contaminated blood transfusions in the 1970s, before the virus was identified. (Blood donations have been routinely tested for hepatitis C since 1990.) The patients' symptoms and clinical outcomes were closely followed from the day they received the transfusion for up to 30 years, and ranged from mild and stable chronic hepatitis C to rapid disease progression and death.

Dr. Alter and his Clinical Center colleagues periodically collected blood serum samples from each of the six patients. Dr. Farci and her colleagues used up to 17 of these archived samples per patient to obtain and analyze a total of 1,876 genetic sequences of the hepatitis C virus. The researchers used the genetic sequences to reconstruct the evolution of two particular hepatitis C genes, E1 and E2, and the research team analyzed the types of genetic changes that took place in order to understand their relationship with disease progression. They also studied the levels of 39 blood serum proteins during the acute and chronic phases of disease.

" We thoroughly characterized the biological changes that occurred in these patients, and we discovered that patients who developed rapidly progressive disease had specific changes in their blood that were detectable since the early acute phase of infection," said Dr. Farci.

Patients with rapid disease progression had significantly higher levels of a protein known as MCP-1, which is believed to play a major role in the development of liver fibrosis, and, eventually, cirrhosis. Moreover, in these patients, the genetic changes in the virus as it evolved over time were less likely to result in changes to the virus proteins. According to the researchers genetic and blood serum markers might eventually enable physicians to identify hepatitis C patients at risk for rapid progression and to use this information to adjust their treatment. Dr. Farci explained that additional markers might exist and said that the research team is working to increase the sample size by doing similar analyses on the remaining stored samples.

" Now that we know what to look for, we believe it is extremely important to extend our observation to a larger number of patients" Dr. Farci said.

Ref. to Paper:
Farci P et al. Profibrogenic chemokines and viral evolution predict rapid progression of hepatitis C to cirrhosis. Proceedings of the National Academy of Sciences. DOI: 10.1073/pnas.1210592109.

About NIH:
The National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov - statement understood to be correct as of publication date.

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