Hyaluronic acid levels can predict risk of serious liver events in people living with HIV and hepatitis B or C co-infection

Michael Carter
Published: 17 June 2013

A simple blood test can predict the risk of liver-related death or hepatic encephalopathy for people living with HIV who have hepatitis B or hepatitis C co-infection, investigators from the EuroSIDA cohort report in PLoS One.

Their results showed that baseline elevations in plasma levels of hyaluronic acid (HA) were associated with a significant increase in the risk of serious liver-related events. Levels of this biomarker remained stable in people who remained 'event free', but increased in those experiencing disease progression.

“The present study indicates that HA could be a useful biomarker to estimate the long-term risk of liver disease,” write the authors.

Many people with HIV have viral hepatitis co-infections and liver disease related to hepatitis B virus (HBV) or hepatitis C virus (HCV) is now an important cause of serious illness and death in people with these co-infections.

Traditionally, liver biopsy has been the 'gold standard' for diagnosing and monitoring liver disease. However, it is uncomfortable, can lead to complications and is unpopular with patients. Therefore, non-invasive tests are increasingly being used to monitor liver disease. These investigations can accurately assess the extent of liver fibrosis in people with co-infections, but their ability to predict the risk of disease progression is currently unknown.

A potential biomarker is hyaluronic acid. It can be measured during routine care using a simple and cheap blood test.

The clearance of hyaluronic acid is impaired in people with liver disease. Research in people who have viral hepatitis mono-infection has shown that elevations in hyaluronic acid are associated with an increased risk of serious liver-related events. Investigators wanted to see if this was also the case in people with HIV and viral hepatitis co-infections.

The study sample included 1252 people enrolled in the EuroSIDA cohort.

Normal hyaluronic acid levels are between 0-75ng/ml. The median baseline value for all participants in the study was well within this range at 33.9ng/ml. It was higher in people with chronic HCV (37.7ng/ml), than in people with chronic HBV (31.4ng/dl) and people who had had cleared their HCV infection (27.5ng/ml).

Participants in the study were followed-up for a median of 8.2 years. During this time there were 84 serious liver-related events (7%; 52 liver-related deaths and 32 hepatic encephalopathy).

The median baseline hyaluronic acid level was 221.6ng/ml among people experiencing a liver-related event compared to 31.8ng/ml for people whose disease did not progress.

Participants were divided into three groups according to whether their baseline hyaluronic acid levels were within the normal range, mildly elevated (75-250ng/ml) or markedly elevated (above 250ng/ml).

People with normal levels had a 1% five-year risk of a liver-related event. This compared to a 12% risk for individuals with moderate elevations and a 45% risk for those with markedly elevated hyaluronic acid (p < 0.001).

After controlling for potential confounders, the investigators found that, compared to people with normal hyaluronic acid values, participants with moderate elevations had a five-fold increase in the risk of liver-related events (IRR = 5.22; 95% CI, 2.86-9.26, p = 0.0007), while those with marked elevations had an almost 30-fold increase in the risk of an event (IRR = 28.22; 95% CI, 14.95-46,00, p < 0.0001).

Hyaluronic acid remained stable in people who did not experience an event, increasing by a median of 1ng/ml per year. In contrast, the participants who developed serious liver-related events experienced median annual increases of 111.1ng/ml (p < 0.0001).

“This large cohort study demonstrates that baseline HA was a strong predictor of later hepatic encephalopathy or liver-related death in HIV-1 patients co-infected with HBV and/or HCV. Patients, who during follow-up experienced a liver-related event, had higher annual increases in HA compared to patients without an event,” conclude the researchers. “Plasma HA may be useful, either alone or in combination with other non-invasive markers, to monitor progression of liver disease and risk of complications in patients with chronic viral hepatitis.”


Peters L et al. Hyaluronic acid levels predict risk of hepatic encephalopathy and liver-related death in HIV/viral hepatitis coinfected patients. PLoS One, 8:5. e64283, 2013.