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
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
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.”