In
an effort to reduce the need for repeated liver biopsies -- which are uncomfortable,
expensive, and associated with a small risk of complications -- researchers have
developed various non-invasive methods for assessing liver
fibrosis using serum biomarkers and imaging techniques.
As
reported in the May 2007 Journal of Hepatology, researchers compared the
diagnostic performance of 6 non-invasive biomarker scores:
•
APRI:
AST-to-platelet ratio index;
•
Fibrotest:
an index combining a2-macroglobulin, haptoglobin, gamma globulin, apolipoprotein,
and bilirubin;
•
Fibrometer:
platelet count, prothrombin time, AST, a2-macroglobulin, age, urea, and hyaluronic
acid;
•
Forns'
index: age, platelet count, gamma-glutamyl transpeptidase (GGT), and cholesterol;
•
Hepascore:
bilirubin, GGT, hyaluronic acid, a2-macroglobulin, age, and sex;
•
MP3:
an index that incorporates procollagen III N-terminal peptide (PIIINP) and matrix
metalloprotease 1 (MMP1), substances involved in production and breakdown of fibrous
tissue.
The
study included 180 patients with chronic hepatitis C patients. Liver fibrosis
was staged according to the METAVIR scoring system.
Results
•
For
distinguishing absent or mild fibrosis (stage F0-F1) versus moderate to sever
fibrosis (F2-F4), the overall diagnostic performance of the indices determined
by areas under the receiver operating characteristic curve (AUROCs) ranged from
0.86 for Fibrometer to 0.78 for the Forns' index, a non-significant difference.
•
For
discriminating between stage F0-F2 fibrosis versus stage F3-F4, AUROCs ranged
from 0.91 for Fibrometer to 0.78 for Forns' index (P < 0.02).
•
Significant
or extensive fibrosis was accurately predicted in 10%-86% of patients, with positive
predictive values ranging from 55% to 94%.
•
Using
logistic regression analysis, statistical independence was demonstrated for MP3,
Fibrotest, and APRI.
•
In
an evaluation of diagnostic performance of paired-combination scores, the best
combinations could accurately select one-third of patients for whom either absence
of significant fibrosis or presence of extensive fibrosis could be predicted with
more than 90% certainty.
Conclusion
In
conclusion, the authors wrote, "Current non-invasive scores give reliable
information on liver fibrosis in one-third of chronic hepatitis C patients, especially
when used in combination."
This
study confirms past research showing that while non-invasive tests perform well
in distinguishing between absent or mild fibrosis versus advanced fibrosis
or cirrhosis, they are not as good
at distinguishing between intermediate stages.
Such
tests are gaining greater acceptance for aiding decisions about when to start
hepatitis C treatment and assessing how well
treatment is working, but some experts believe they are not yet ready for prime
time.
In an accompanying
editorial, Andrew Burroughs and Evangelos Cholongitas wrote that, "Non-invasive
tests for liver fibrosis have the potential to become an important tool in clinical
practice, but better validation is needed before starting to consider [them] as
established tests…It is likely that an initial diagnostic biopsy will still
be needed, but follow up for fibrosis could be based on [non-invasive tests],
providing that encouraging results [are] published in the future."
However,
an international panel of experts that recently issued guidelines
for the management of HIV-HCV coinfection* stated that, "liver biopsy
is not mandatory for considering the treatment of chronic HCV infection,"
given that a combination of non-invasive methods "accurately predicts hepatic
fibrosis in most cases."
06/19/07
References
V
Leroy, M-N Hilleret, N Sturm, and others. Prospective comparison of six non-invasive
scores for the diagnosis of liver fibrosis in chronic hepatitis C. Journal
of Hepatology 46(5): 775-782. May 2007.
AK
Burroughs and E Cholongitas. Non-invasive tests for liver fibrosis: Encouraging
or discouraging results? Journal of Hepatology 46(5): 751-755. May 2007.
*V
Soriano, M Puoti, M Sulkowski, and others. Care of patients coinfected with HIV
and hepatitis C virus: 2007 updated recommendations from the HCV-HIV International
Panel. AIDS 21(9): 1073-1089. May 31, 2007.
