The non-invasive transient elastometry method of
estimating liver damage may be a better way to predict which people co-infected
with HIV and hepatitis C will progress to decompensated liver cirrhosis and
death, researchers reported last week at the 7th International AIDS Society Conference on HIV
Pathogenesis, Treatment and Prevention (IAS 2013) in Kuala Lumpur.
Over years or
decades, hepatitis C can lead to advanced liver disease including cirrhosis and
liver cancer. People with HIV who have hepatitis C virus (HCV) co-infection
experience more rapid liver disease progression, on average, than people with
A variety of
methods are used to determine the extent of liver damage, which is an important
factor in deciding who should be treated for hepatitis C. Liver biopsy is
considered the 'gold standard', but is expensive, variable across testers, inconvenient
and sometimes painful, making it poorly suited for repeat testing to monitor
changes over time.
An accumulation of fluid in the abdomen; may be caused by liver damage, especially cirrhosis.
A disease or infection affecting the brain.
A non-invasive test, used instead of a biopsy, to measure the stiffness
or elasticity of the liver using an ultrasound probe.
non-invasive biomarker indices are used, but they are not as accurate as
biopsy. The transient elastometry – or Fibroscan – technique uses sound waves to measure liver stiffness,
with higher scores (expressed in kiloPascals or kPa) indicating more extensive
fibrosis. Fibroscan has been widely adopted in Europe but remains controversial
in the US.
Juan Macías of Hospital Universitario de Valme in
Seville, Spain, and colleagues compared the performance of liver biopsy versus
liver stiffness measurement as a way to predict survival and liver
decompensation – or loss of essential function – among people with HIV/HCV co-infection, a group that could benefit from
more frequent monitoring using a non-invasive method.
This retrospective cohort study
included 297 people with co-infection who had liver biopsies and liver stiffness
measurements separated by no more than 12 months; the baseline date was considered
to be the halfway point between biopsy and LSM. A majority of participants
(77%) were men, the median age was 42 years and most had a history of injecting
More than 90% were on antiretroviral
therapy at baseline, most with undetectable HIV viral load, and the median CD4
count was high, at 514 cells/mm3. Most had HCV genotypes 1 or 4 and
60% had undergone interferon-based hepatitis C treatment. At baseline, 14% had
no evidence of fibrosis (stage F0), 33% had mild fibrosis (F1), 27% had
moderate fibrosis (F2), 13% had advanced fibrosis (F3) and 14% had cirrhosis
(F4). The median liver stiffness measurement was 7.6 kPa.
Participants were followed from 2005
to 2011, with a median follow-up period of five years. The researchers looked
at rates of first decompensation events and all-cause mortality. Macías explained that they looked at all-cause rather than
liver-related mortality because some deaths that appear
non-liver-related may actually be related – hepatic encephalopathy, or brain impairment,
could lead to a traffic accident, for example.
There were 21 total deaths during the
study period, for an overall mortality rate of 7.1% or 1.6 per 100 person-years.
Twelve deaths were liver-related but none were AIDS-related.
After adjusting for potential
confounding factors, worse fibrosis according to biopsy (adjusted hazard ratio 1.52
per fibrosis stage) and a higher liver stiffness score (1.28 per 5 KPa) both
predicted greater risk of death. Calculating a measure known as integrated
discrimination improvement, the researchers determined that transient
elastometry performed 3.9% better than liver biopsies at predicting death,
which fell just short of statistical significance.
Turning to liver decompensation, there
were again 21 total events – including 12 cases of abdominal fluid accumulation (ascites), four
cases of gastrointestinal bleeding and two cases of hepatic encephalopathy – for a rate of 7.1% or 1.59 events
per 100 person-years.
After adjustment, biopsy and liver
stiffness score again both predicted higher risk (adjusted hazard ratios of
1.67 per fibrosis stage and 1.36 per 5 KPa increase). Most decompensation events
occurred among people with liver biopsies showing cirrhosis. Here, transient
elastometry performed 8.4% better than biopsies, and this was statistically significant.
multivariate analysis, factors that significantly predicted mortality included
older age, higher biopsy stage and higher liver stiffness score. Higher biopsy
stage and liver stiffness score were also significant predictors for
decompensation. Achieving sustained virological response to hepatitis C
treatment reduced the risk of both death and decompensation, but differences
did not reach statistical significance.
"The performance of models based on [transient
elastometry] to predict overall survival among HIV/HCV co-infected patients was
similar to that of [liver biopsy]-based models," while "[transient
elastometry] predicts decompensations better than [liver biopsy]-based
models," the researchers concluded.
"The non-invasive nature of [transient
elastometry] should favour its use instead of [liver biopsy] when the only
issue is predicting the clinical outcome of liver disease in HIV/HCV co-infection,"
In response to an audience question about
when to use transient elastometry versus biopsy, Macías replied that
clinicians are already phasing out biopsy in Spain. "It essentially has
disappeared as a way
of diagnosing patients, and is not used to stage fibrosis anymore," he