Yes, for "nearly half" it is "reasonably predictive". For SOME patients,
it can eliminate the need for a biopsy. Which is what I've been saying.

Thomas

Thanks, Kim. I printed it and will show it to the specialist.

You're one of the few that post here that actually post useful information
and I want you to know I appreciate it.

Cody, back to lurking

"The

sensitivity

F2F3F4

tracts

Ok, I'll eat my hat on this one!  Thanks, Kim.
Elmo
//////
Australian study
USE OF FIBROTEST TO PREDICT LIVER FIBROSIS IN HEPATITIS C : A
REPLACEMENT FOR LIVER BIOPSY ?
Leon Adams1, Enrico Rossi2, Bastiaan DeBoer2, David Speers2, Gerry
Macquillan3, George Garas1, Gary Jeffrey1,3.
Department of Gastroenterology and Hepatology, Sir Charles Gairdner
Hospital, Nedlands, WA, Australia The Western Australian Centre for
Pathology and Medical Research, Queen Elizabeth Medical Centre,
Nedlands, WA, Australia Department of Medicine, University of Western
Australia, Nedlands, WA, Australia
Background
Australian patients chronically infected with hepatitis C currently
require a liver biopsy to demonstrate a minimum stage of fibrosis
(METAVIR F2 or greater) to qualify for standard interferon-alpha and
ribavirin combination therapy.
Aims
To examine in patients chronically infected with hepatitis C; The
correlation between five biochemical parameters and liver fibrosis The
accuracy of FibroTest in distinguishing between the METAVIR stages of
hepatic fibrosis The predictive value of FibroTest to accurately
identify patients with sufficient fibrosis to qualify for combination
treatment, therefore avoiding liver biopsy
Methods
Patients with chronic hepatitis C infection and detectable hepatitis C
RNA by RT-PCR, who had undergone liver biopsy between January 1998 and
November 2001 were identified. Biopsies were staged according to the
METAVIR group scoring system. Serum taken at the time of biopsy was
analysed for haptoglobin, gamma glutamyl transferase (GGT), bilirubin,
alpha 2 macroglobulin and apolipoprotein A1. A FibroTest score was
computed by accessing the Experts-MD website (now tranfered to
BioBredictive.com )
Results
Results were obtained for 125 patients, 82 males and 43 females, with a
mean age of 40 years. Seventy-seven patients had METAVIR fibrosis scores
of F0 or F1, and 48 had higher METAVIR fibrosis scores of F2, F3 or F4.
Thirty-three patients had a FibroTest score of 0.1 or less and 24 had
Fibrotest scores greater than 0.6 (see Figure 1). Regression analysis
demonstrated that all biochemical markers were significantly associated
with the FibroTest score (p<0.001) as was METAVIR fibrosis grade
(p<0.001). Similarly all biochemical markers were significantly
correlated with the FibroTest score (p<0.01). There was moderate
correlation between METAVIR fibrosis stage and FibroTest score (r
= 0.59). The sensitivity and specificity of a FibroTest score greater
than 0.1 for the presence of fibrosis grades F2-4, was 92% and 29%
respectively. The sensitivity and specificity of a FibroTest score
greater than 0.6 for fibrosis F2-4, was 42% and 94% respectively with a
likelihood ratio of 6.4. With a prevalence of 37 % for the presence of
fibrosis F2-4, as in our population, the negative predictive value of a
score less than 0.1 was 85 %. The positive predictive value of a score
greater than 0.6 for the presence of significant fibrosis was 79 %.
Conclusion
Nearly half of the patients chronically infected with hepatitis C in our
population had a FibroTest score of less than 0.1 or greater than 0.6.
In these patients the FibroTest is reasonably predictive of the absence
or presence of METAVIR fibrosis grades F2 to F4, respectively. Fibrotest
may allow some patients to receive combination treatment for hepatitis C
infection without the need for liver biopsy.
Reference: Adams L et al. Gastroenterology 2002;122:1615 A.
  Recently the same authors with the same results presented in the
abstract, had a surprisingly opposite conclusion in an article: Rossi E,
Adams L, , Prins A, Bulsara M, DeBoer B, Garas G, Macquillan G, Speers
D, Jeffrey G. Validation of the Fibrotest biochemical markers score in
assessing liver fibrosis in hepatitis C patients. Clinical Biochemistry
2003;49: 450-454.
The following response has been send by: Thierry Poynard, Françoise
Imbert-Bismut, Vlad Ratziu, Rob Myers, Vincent Di Martino, Dominique
Thabut, Joseph Moussalli and Yves Benhamou. Service
d’Hépato-Gastroentérologie, Groupe Hospitalier
Pitié-Salpêtrière, Université Paris VI, CNRS ESA
8067, 47 Boulevard de l’Hôpital 75651 Paris Cedex 13,
France. Paris, France.
  We acknowledge the results observed on this small sample size
study. We disagree with the interpretation and the conclusion.
We were surprised with the opposite conclusion presented in this article
in comparison with that of the same work when presented in abstract
form: “The FibroTest is reasonably predictive of the absence or
presence of METAVIR fibrosis grades F2 to F4, respectively.”
(1).
As far as the statistical analysis, we were unable to recalculate some
indices. In the discussion it is stated that “among 33 patients
with scores <0.1, F2F3F4 was observed in 6”. As there were 48
F2F3F4 patients, the sensitivity should be 88 % (42/88) instead of 92 %
as described in Table 1 and on page 451; the specificity should be 35%
(27/77) and not 29% and the positive predictive value 46% (42/92). It is
also stated that “of the 24 patients with scores
0.6 ...F0F1 was observed in 5 patients”. Therefore 19 patients
were F2F3F4
and the sensitivity should be 19/48, which is 39.5% instead of 42% as
stated in Table 1 and page on 451.
This validation study indeed confirms the excellent specificity (94% for
a Fibrotest cutoff >0.6) for the diagnosis of significant fibrosis
(F2F3F4). This is similar to what we observed in our first study (95%
specificity in the second year population). The specificity of Fibrotest
can be further improved if identified causes of false positives have
been excluded. Our experience in France with 4,000 Fibrotests has shown
two main causes of false positives, hemolysis (mainly due to cardiac
valvular prosthesis) and Gilbert syndrome (2-5). We wonder if these
diagnoses had been ruled out in their 5 false positive cases.
Since the specificity is similar in this and our study, the 13%
difference observed in positive predictive values, (78% in the
validation versus 91% in our study) could be related to differences
between prevalence of significant fibrosis stages and/or sensitivity of
the Fibrotest. There was indeed a difference in the prevalence of
fibrosis stages, 38 % (F2F3F4) in this study versus 45% (F2F3F4) in our
study. However the main difference concerns the sensitivity: this was
92% in the Rossi study vs 100% in ours for the 0.10 cutoff, and was 42%
vs. 72% respectively, for the 0.60 cutoff. One explanation is the
difference in the prevalence of cirrhosis, which was present in only 7%
in the Rossi study versus 16 % in our study. Among F2F3F4 patients, the
sensitivity of Fibrotest is higher for F4 than for F2.
Another reason for discrepancy between the two studies, as discussed by
Rossi et al, is a difference in instrumentation. We recently published a
study documenting significant variability in Fibrotest results obtained
using different kits and automates (5). It is therefore important that
the laboratories apply the quality charter when performing the Fibrotest
(5), which is available at www.biopredictive.com. A true objective
validation of Fibrotest should use this recommended procedure.
Rossi et al do not discuss the important limitations of liver biopsy:
sampling error, intra and inter pathologist errors and risks.
Sampling error is paramount and leads to inaccurate estimates of
sensitivity and specificity in small sample size studies. In hepatitis C
there is a 33% discordance rate in the same patient for fibrosis staging
when assessed in the right and left lobes of the liver (6). This 33%
discordance rate should be weighted against the 27% discordance rate
observed between Fibrotest and one biopsy in the Rossi study.
Therefore discordances between biochemical markers and liver biopsy can
be either due to limitations of the biochemical markers or those of
liver biopsy. As there is no other “gold standard”, we
recently compared the diagnostic values of Fibrotest and Actitest for
significant features (A2A3-F2F3F4 vs A0A1-F0F1) in relation to the size
of liver biopsy (greater or less than 15 mm) (3). The area under the ROC
curve (AUROC) among 200 patients with a biopsy size <15 mm was 0.705
± 0.04 (se) which was lower than 0.879 ± 0.03 in 152 patients
with biopsy size >15 mm (p<0.001). The AUROC was also significantly
lower in 39 patients with less than 6 portal tracts on the histological
sample (0.615 ± 0.09) in comparison with 313 patients with 6 or
more portal tracts (0.803 ± 0.03 p<0.001).
                        In
conclusion we think that a true validation study of Fibrotest must apply
the recommended procedures, include several hundred cases and use
sensitivity analysis according to biopsy size and number of portal
tracts.
Even with the diagnostic value observed in this report, (94 %
specificity for a 0.6 cutoff and 92% sensitivity for a 0.1 cutoff), the
Fibrotest seems to have a much better benefit-risk ratio than liver
biopsy, because of the biopsy sampling error (33% discordance between
left and right lobe stages) and the biopsy risk (3 deaths out of 10,000
procedures and, 3 severe adverse events out of 1,000).
References
Adams L, Rossi E, DeBoer B, Speers D, Macquillan G, Garas G, Jeffrey G.
Use of Fibrotest to predict liver fibrosis in hepatitis C: a replacement
for liver biopsy? Gastroenterology 2002;122: 1615 A.(abstract) Myers RP,
Messous D, Thabut D, Imbert-Bismut F, Ratziu V, Mercadier A, Poynard
T. Life is possible without biopsy in patients with chronic hepatitis C:
validation of biochemical markers of liver fibrosis and activity in 1570
patients and blood donors. Hepatology 2002; 36:351A. (Abstract) Poynard
T, McHutchison J, Manns M, Myers RP, Albreht J. Biochemical markers as
surrogate markers of liver fibrosis and activity in patients infected by
hepatitis C virus: an example in a randomized trial of
pegylated-interferon alfa-2b and ribavirin combination. Hepatology
2002;36:351A. (Abstract) Myers RP, Messous D, Thabut D, Imbert-Bismut F,
Ratziu V, Mercadier A, Poynard
T. The prediction of fibrosis with serum biochemical markers in patients
with chronic hepatitis C: Prospective validation in 534 patients.
Hepatology 2002;36:351A. (Abstract)
Halfon P, Imbert-Bismut F, Messous D, Antoniotti G, Benchetrit D,
Cart-Lamy P, Delaporte G, Doutheau D, Klump T, Sala M, Thibaud D, Trepo
E, Robert P. Myers RP, Poynard T. A prospective assessment of the
inter-laboratory variability of biochemical markers of fibrosis
(FibroTest) and activity (ActiTest) in patients with chronic liver
disease. Comparative Hepatology 2002;30 December; 2:3. Regev A, Berho M,
Jeffers LJ, Milikowski C, Molina EG, Pyrsopoulos NT, Feng ZZ, Reddy KR,
Schiff ER. Sampling error and intraobserver variation in liver biopsy in
patients with chronic HCV infection. Am J Gastroenterol. 2002;97:2614-8.
http://www.biopredictive.com/Information/HealthcareProfessionals/Validatio
nStudies/ExternalValidation

http://community.webtv.net/elmoemerson/DocElmosHepFile

I would be grateful to have something besides a biopsy to check my liver.
With a cat scan, I was dx. as having a hemangioma in my liver.  Nothing much
was said at that time, other than it scared me enough to start treatment.
However, one of my docs told me that I would have to tell anyone that is
going to do a liver biopsy that I have a hemangioma.  She said it is like
one of those bright red spots some people have on their body that is full of
blood.  They don't generally remove them because they bleed a lot.  She said
that with a biopsy, if they punctured it, I could bleed to death.  Not real
reassuring.  Thought about having a tattoo placed over my liver that says
hemangioma.  Well, that might be a little extreme, but I think it is
something I'll have to be careful of.  Another type of test sounds like a
good option.

Susie

"The

sensitivity

F2F3F4

tracts