Published online 2012 October 21. doi:
10.3748/wjg.v18.i39.5514.
Checkmate to liver biopsy in chronic hepatitis C?
Author contributions: Trifan A and Stanciu C equally
participated in the conception, design and drafting of this article; both
authors revised the article critically for important intellectual content and
gave the final approval for the version to be published.
Correspondence to: Carol Stanciu, MD, FRCP, Gastroenterology and
Hepatology Center, “Sf. Spiridon” University Hospital, Independenţei 1, 700111
Iaşi, Romania. stanciucarol@yahoo.com
Telephone: +40-72-2306020 Fax: +40-23-2264411
Received March 13, 2012; Revised July 6, 2012; Accepted
July 18, 2012;
View Full Text Here
In France, a survey of 546 hepatologists revealed that 81% of them used noninvasive methods[102], while in the United States, despite the aforementioned shortcomings of LB, there is still significant resistance to accepting noninvasive methods as an alternative to biopsy. We believe that sooner or later this will change, and the requirement of LB prior to starting antiviral therapy in patients with CHC will be reassessed.
View Full Text Here
Abstract
Liver biopsy (LB) has traditionally been considered
the gold standard for pretreatment evaluation of liver fibrosis in patients with
chronic hepatitis C (CHC). However, LB is an invasive procedure with several
shortcomings (intra- and interobserver variability of histopathological
interpretation, sampling errors, high cost) and the risk of rare but potentially
life-threatening complications. In addition, LB is poorly accepted by patients
and it is not suitable for repeated evaluation. Furthermore, the prevalence of
CHC makes LB unrealistic to be performed in all patients with this disease who
are candidates for antiviral therapy. The above-mentioned drawbacks of LB have
led to the development of noninvasive methods for the assessment of liver
fibrosis. Several noninvasive methods, ranging from serum marker assays to
advanced imaging techniques, have proved to be excellent tools for the
evaluation of liver fibrosis in patients with CHC, whereas the value of LB as a
gold standard for staging fibrosis prior to antiviral therapy has become
questionable for clinicians. Despite significant resistance from those in favor
of LB, noninvasive methods for pretreatment assessment of liver fibrosis in
patients with CHC have become part of routine clinical practice. With protease
inhibitors-based triple therapy already available and substantial improvement in
sustained virological response, the time has come to move forward to
noninvasiveness, with no risks for the patient and, thus, no need for LB in the
assessment of liver fibrosis in the decision making for antiviral therapy in
CHC.
Keywords: Liver
biopsy, Fibrosis, Noninvasive methods
INTRODUCTION
Chronic hepatitis C (CHC) is a major public health concern, with
around 180 million individuals affected worldwide[1]. Liver
fibrosis and its end-point cirrhosis are the main causes of morbidity and
mortality in patients with CHC[2]. Information on the stage of liver fibrosis is
useful in patients with CHC not only for estimation of prognosis, but also for
indication of antiviral therapy. Early international guidelines, consensus
statements and expert panel opinions on the management of CHC unanimously
recommended that decisions on treatment should be made only after performing a
liver biopsy (LB) for pretreatment evaluation of the disease[3-5]. Consequently, antiviral treatment for patients
with CHC has been indicated only for those with moderate to severe stages of
fibrosis (Metavir F2, F3 or F4), while patients with no or minimal fibrosis
(Metavir F0, F1) have not been treated[6]. The rationale of such a strategy was to treat
all patients with advanced fibrosis to halt disease progression and prevent
complications, rather than those with no or minimal fibrosis who may await
better treatments considering the slowly progressing natural history of
CHC[7].
The recommendations mentioned above led to the routine performance of LB in
nearly all patients who were newly diagnosed with CHC and potential candidates
for antiviral therapy. More recent guidelines[8] still
recommend LB in making treatment decisions, although it has been recognized that
it is not necessary in patients with genotype 2 or 3, who can have as high as a
80% sustained virological response (SVR) rate.
For several decades, LB has been widely regarded as the
gold standard for the staging of liver fibrosis[9]. However, LB
is an invasive procedure and it is sometimes associated with rare but severe
complications[10]. In addition, LB has several drawbacks (intra- and
interobserver variability in histopathological interpretation, sampling errors,
variable accessibility, high cost) which raises questions about its value for
pretreatment assessment of liver fibrosis in patients with CHC[11,12]. Nowadays, many clinicians no longer cite LB
as the gold standard but, at best, it can only be considered an imperfect
standard for the staging of liver fibrosis[13]. It was
this context that, in recent years, triggered a huge interest in the noninvasive
assessment of liver fibrosis in patients with CHC. The introduction of a
noninvasive methodology for the assessment of liver fibrosis as an alternative
to LB in patients with CHC represents a major advancement in clinical
hepatology[14]. Many of the noninvasive methods demonstrated accuracy
to a considerable degree in identifying significant fibrosis, particularly
cirrhosis, and consequently, noninvasive assessment of fibrosis is already a
reality in patients with CHC[15]. Obviously, with the recent therapeutic
development in CHC and reliable noninvasive diagnostic procedures available, LB
has lost both its monopoly in the pretreatment assessment of fibrosis and the
influence on decision making for antiviral therapy in patients with
CHC.
CASE AGAINST
LB
For the last 50 years, LB has been considered the gold standard for
the staging of liver fibrosis in spite of its several shortcomings: intra- and
interobserver variability in histopathological interpretation[16,17], sampling errors[18,19], and potentially life-threatening
complications[20,21]. In clinical practice, we frequently
encounter the intra- and interobserver variability in the staging of liver
fibrosis[16,17]. Diagnostic errors made by nonspecialist
pathologists were reported in > 25% of patients undergoing LB in academic
centers[22,23]. According to a recent study[24], community
pathologists understaged liver fibrosis in > 70% of cases with CHC. Several
studies have shown that sampling errors occur when the LB specimen size is too
small for an accurate estimation of fibrosis[18,19]. Both the length and the diameter of the
biopsy core may affect the accuracy of fibrosis stage evaluation in patients
with CHC[25,26]. Obviously, the shorter and thinner the
samples are, the greater is the number of misclassifications of liver fibrosis.
There is some controversy among pathologists in defining an adequate LB sample
for an accurate staging of liver fibrosis. Some investigators[27] suggest
that a sample of at least 15 mm in length and containing more than five portal
tracts is adequate, while others recommend biopsy samples of 20 mm containing at
least 11 portal tracts[26] or even larger samples, up to 25 mm[18]. Bigger is
better[28], but at the price of an increased risk of severe
complications[10,18]. However, it should be noted that, in
clinical practice, few LB specimens reach an adequate length of 20 mm[29].
Furthermore, LB only samples an extremely small part of the whole organ
(1/50 000) and therefore, there is a risk in the evaluation of lesions that are
heterogeneously distributed throughout the entire liver[21]. LB may
underestimate the amount of fibrosis, and cirrhosis could be missed in 10%-30%
of cases[30]. Studies concerning fibrosis staging have also shown
differences in one third of cases with CHC between LB samples obtained from the
right and left lobes of the liver during laparoscopy[19]. Data on
LB complications are heterogenous and contain wide variations in reported rate
from one study to another[10,20,21,31-34]. Major
complications include bleeding and bile peritonitis, with a reported mortality
rate ranging from 0.03% to 0.1%[10,20,31,32,34]. It is worthwhile mentioning that both the
transjugular route and ultrasound guidance approaches to LB do not significantly
reduce the rate of major complications[35,36].
Complication rates are higher when LB is performed by less-experienced
physicians[31,37]. In addition, LB is costly, variably
available, poorly accepted by patients, and not suitable for repeated
evaluation. The cost of an LB in the United States, United Kingdom and Australia
varies between 1000 and 2000 USD, and it could go over 3000 USD if complications
occur[12,38-40]. LB is not
welcomed by patients and it may be refused by more than half of those with
CHC[41]. LB is inappropriate for a dynamic evaluation of liver
fibrosis over time, and recommendation to repeat biopsy every 3-5 years to
follow up disease progression is certainly unrealistic, mainly due to patient
nonadherence[40]. LB is contraindicated in the presence of coagulopathy
and thrombocytopenia. Last but not least, the prevalence of CHC makes LB
impossible in all patients with CHC who are candidates for antiviral therapy. It
is these drawbacks of LB that have led to the development of noninvasive methods
for the assessment of liver fibrosis in patients with CHC and, hopefully, to a
major change in hepatology practice.
Nevertheless, LB has some well-recognized advantages for
assessing fibrosis in CHC, such as direct measuring of liver fibrosis,
well-established staging system, and evaluation of associated lesions
(steatosis, iron deposition, inflammation, alcoholic liver disease, nonalcoholic
fatty liver disease, metabolic syndrome), although these diagnostic advantages
are counterbalanced by the aforementioned disadvantages.
CASE IN FAVOR OF
NONINVASIVE METHODS
Noninvasive methods for detecting liver fibrosis may be divided in
two main groups: serum markers of fibrosis and transient elastography
(Fibroscan).
Serum markers for liver fibrosis are commonly divided into direct
serum markers, which are directly linked to the modifications in extracellular
matrix turnover produced by hepatic stellate cells during the process of
fibrogenesis in the liver, and indirect serum markers which reflect alterations
of the hepatic functions. The direct markers include glycoproteins (hyaluronate,
laminin, YKL-40), collagen family (procollagen III, type IV collagen),
collagenases and their inhibitors (matrix metalloproteases, tissue inhibitory
metalloprotease-1), and they are not routinely available in most clinical
laboratories. The indirect markers are biochemical parameters determined in
routine blood tests [platelet count, prothrombin time, aspartate
aminotransferase (AST)/alanine aminotransferase (ALT) ratio]. Serum markers for
liver fibrosis may be used singly[42-45] or
combining panels of direct or indirect serum markers and demographic
parameters[46-55], with the aim of increasing the accuracy of
single parameters. Some of them are patent-protected and commercially available:
FibroTest® (Biopredictive, Paris, France) licensed under the name of
Fibrosure® in the United States (LabCorp, Burlington, NC, United
States)[51], Fibrometer® (BioLiveScale, Angers,
France)[52], Hepascore (PathWest, University of Western Australia,
Australia)[53], ELF® (Enhanced Liver Fibrosis Test, iQur
Ltd, Southampton, United Kingdom)[54], and FibroSpectII® (Promotheus
Laboratory Inc. San Diego, Ca, United States)[55]. Among
these, Fibrotest [α-2-macroglobulin, γ-glutamyl transpeptidase (GT),
apolipoprotein A1, haptoglobin, total bilirubin, age, sex] is the most widely
used and was validated by several studies on patients with CHC[56-63]. The reported accuracy of Fibrotest for
significant fibrosis/cirrhosis expressed as area under receiving operating
characteristic curve (AUROC) ranges from 0.74% to 0.87%[46,51]. To improve the performance of Fibrotest,
its combination with Fibroscan has been suggested; with such a combination, one
study reported AUROC of 0.88 for at least F2 (stage in the Metavir scoring
system) and 0.95 for F3 or F4[56]. The sensitivity and specificity of
serum-marker-based tests could also be improved by combining them using
sequential algorithms. Thus, Sebastiani et al[64] combined
AST/platelets ratio (APRI) with Fibrotest - a combination known as sequential
algorithm for fibrosis evaluation biopsy - and found it to have an accuracy of
92.5% in the detection of fibrosis in CHC, obviating 81.5% of liver biopsies.
APRI has a slightly lower performance than Fibrotest, with an accuracy between
60% and 82% for significant fibrosis and 60% and 88% for cirrhosis[46,64], but it is a simple cost-free readily
available test in all hospital settings. Both Fibrometer (platelet count,
hyaluronate, AST, α-2-macroglobulin, international normalized ratio, urea, age)
and Hepascore (bilirubin, γGT, α-2-macroglobulin, hyaluronic acid, age, sex)
showed good performance for detection of significant fibrosis[52,53,65].
There are several advantages of serum markers such as high
applicability, with no risk for the patient and no contraindication; they can be
performed and repeated in outpatient clinics; widespread availability; and
interlaboratory reproducibility[66]. However, there are some limitations of
serum markers: none is liver specific; results are unreliable in comorbidities
(hemolysis, Gilbert syndrome, rheumatoid arthritis); and they have poor
performance in the diagnosis of intermediate stages of liver fibrosis[66].
Nevertheless, it is important to note that the performance of each noninvasive
marker is evaluated against LB which is an imperfect gold standard, and the
apparent failure of noninvasive markers to make an accurate distinction between
different stages of intermediate fibrosis could be the consequence of
misclassifications from biopsy[67,68].
Transient elastography (Fibroscan®, Echosens, Paris,
France) measures liver stiffness in a volume at least 100 times greater than a
standard LB sample, and therefore, may be more representative of the entire
liver. Fibroscan is composed of an ultrasound transducer probe mounted on the
axis of a vibrator; vibration is transmitted to induce an elastic shear wave
that propagates through the liver. Pulse-echo ultrasound acquisition is used to
measure the velocity of the shear wave, which is directly related to liver
stiffness: the stiffer the liver, the faster the shear wave propagates. Results
are expressed in kPa, and values range from 2.5 kPa to 75 kPa, with normal
values < 5.5 kPa[69]. According to several studies, a cutoff value of 7.2-8.7
kPa defines significant fibrosis, and cirrhosis is diagnosed by a cutoff value
of 12.5-14.5 kPa[70,71]. Fibroscan seems to be a reliable method for
the diagnosis of significant fibrosis (AUROC 0.84) and cirrhosis (AUROC
0.95)[72,73]. Its combination with serum-based tests
(Fibrotest, Fibrometer) increases the performance (but also the costs) for the
diagnosis of significant fibrosis[56,71,72]. Among noninvasive methods for diagnosis of
cirrhosis, Fibroscan has the highest level of performance[62,72,73], and its
combination with serum markers does not increase accuracy[63,72].
Fibroscan has several advantages: it is painless; quick
(< 5 min); highly reproducible, with results immediately available;
inexpensive; and easy to perform in the outpatient clinic and at the
bedside[66]. In addition, Fibroscan can be repeated for longitudinal
disease monitoring, which is difficult, if not impossible, with LB. In cirrhotic
patients, Fibroscan values correlate with portal pressure (based on the hepatic
venous pressure gradient measurement), which is a reliable predictor of clinical
outcomes[74-77], disease severity[78], and the
risk of hepatocellular carcinoma[79]. Finally, Fibroscan and serum markers are
well accepted by patients, therefore, they could be used as screening methods
for the detection of liver fibrosis/cirrhosis in at-risk groups[80] and even
in general population[81], while LB is unacceptable for screening purposes.
Fibroscan measurement failure and unreliable results are due to limited operator
experience[82], narrowed intercostal spaces[82], and
obesity[82,83], although this last problem seems to be
overcome by a new specially designed probe[84-86]. Results are influenced by ALT
flares[87,88], extrahepatic cholestasis[89,90], and congestive heart failure[91].
DISCUSSION
In the past, expert consensus guidelines on the management of CHC
unanimously recommended routine LB before initiation of antiviral
therapy[3-5,92,93]. Based on LB findings, treatment has often
been advocated only for patients with at least moderate to severe stages of
fibrosis (Metavir F2, F3 or F4), and withheld for those with no or minimal
fibrosis (F0, F1)[6,93]. As a consequence, tens of thousands of
patients were most likely denied proper antiviral therapy. More recent
guidelines[8,94] recommend LB only in patients with CHC
genotype 1 (SVR rate < 50%) in treatment decision making, and consider it
unnecessary in those with genotype 2 or 3 who may have an SVR rate as high as
80%. The primary endpoint of antiviral therapy for CHC is achieving SVR -
defined as undetectable serum HCV RNA at 24 wk after discontinuation of therapy.
Viral eradication prevents disease progression, improves survival, and reduces
health care costs associated with the management of complications. Thus, if
viral clearance is the aim of antiviral therapy in CHC, then to what degree does
an exact histopathological fibrosis stage established through biopsy still
matter? With the new protease inhibitor (PI)-based triple therapy (addition of
telaprevir or boceprevir to pegylated interferon and ribavirin) available and
SVR rates approaching 75% in patients with CHC genotype 1[95,96], it is clear that LB has lost its importance
in the recommendation of antiviral therapy.
During the past 10 years, an intensive debate has taken place
between those in favor of LB and those who promote noninvasive methods for
pretreatment assessment of liver fibrosis in patients with CHC. There is
extensive literature showing the pros and cons of LB or noninvasive methods. As
in chess, winning does not come easy for a supporter of noninvasive methods
against a supporter of LB with a firmly rooted preference. Step by step, those
in favor of non-invasive methods have gained ground, waiting for the final move:
checkmate! Today, several noninvasive methods, ranging from serum marker assays
to advanced imaging techniques, have proved to be excellent tools for the
evaluation of liver fibrosis in patients with CHC. According to the latest
European Association of the Study of the Liver clinical practice
guidelines[97] and United Kingdom consensus guidelines[98]
recommendations, noninvasive methods can be used instead of LB in patients with
CHC to assess liver disease severity prior to antiviral therapy. It is therefore
surprising that many experts in the field of hepatology and the most recent
American Association for the Study of Liver Diseases 2011 practice
guidelines[99] favor LB before therapy initiation, despite substantial
improvement in treatment success rate for genotype 1 patients with PI-based
triple therapy. The main reason against noninvasive methods for evaluation of
liver fibrosis is their apparent failure to make an accurate distinction between
different stages of intermediate fibrosis. It is important to note that the
performance of each noninvasive method was evaluated in all studies by
calculating the AUROC using LB as a reference standard. As LB is an imperfect
standard, a perfect noninvasive method will never reach the maximum value
(1.0)[100], and therefore, noninvasive methods are as inaccurate
as LB for the assessment of fibrosis stage. Thus, the failure of noninvasive
methods to discriminate between different stages of intermediate fibrosis could
be the consequence of classification errors from histopathological findings of
biopsy[67,68]. For clinicians, it is more important to
know if their patients have no/mild or advanced fibrosis/cirrhosis, rather than
the exact pathological scoring system through LB, and this could be easily
achieved by means of noninvasive methods. Taking into account that all recent
international guidelines[97-99] recommend treatment with PI-based triple
therapy in all patients with CHC genotype 1, provided that they have no
contraindications to peg-interferon and ribavirin, the need to stage liver
fibrosis accurately is decreasing in treatment decisions.
The final move - checkmate to LB - is, therefore, possible once the rate of SVR has reached 75% with PI-based triple therapy for patients with CHC genotype 1. Consequently, it is clear that in the era of PI-based triple therapy and other new potent direct-acting agents in the pipeline, the information obtainable from LB has little, if any, influence on treatment decisions. It should be underlined that in this article, checkmate to LB in patients with CHC refers strictly to cases with no need for this invasive and risky procedure in therapeutic decision making. With PI-based triple therapy already available in many countries, and an allocation system probably based mainly on medical need (therapy for those likely to develop complications in the next few years), noninvasive methods with the highest accuracy for detecting severe fibrosis/cirrhosis used as an alternative to LB for pretreatment assessment of liver fibrosis in patients with CHC are now part of routine clinical practice. Fibroscan or any patented biomarkers (Fibrotest, Fibrometer and Hepascore) have recently been recommended for first-line staging of liver fibrosis[101] before deciding on antiviral therapy. However, the adoption rates of noninvasive methods by hepatologists differ from country to country.
The final move - checkmate to LB - is, therefore, possible once the rate of SVR has reached 75% with PI-based triple therapy for patients with CHC genotype 1. Consequently, it is clear that in the era of PI-based triple therapy and other new potent direct-acting agents in the pipeline, the information obtainable from LB has little, if any, influence on treatment decisions. It should be underlined that in this article, checkmate to LB in patients with CHC refers strictly to cases with no need for this invasive and risky procedure in therapeutic decision making. With PI-based triple therapy already available in many countries, and an allocation system probably based mainly on medical need (therapy for those likely to develop complications in the next few years), noninvasive methods with the highest accuracy for detecting severe fibrosis/cirrhosis used as an alternative to LB for pretreatment assessment of liver fibrosis in patients with CHC are now part of routine clinical practice. Fibroscan or any patented biomarkers (Fibrotest, Fibrometer and Hepascore) have recently been recommended for first-line staging of liver fibrosis[101] before deciding on antiviral therapy. However, the adoption rates of noninvasive methods by hepatologists differ from country to country.
In France, a survey of 546 hepatologists revealed that 81% of them used noninvasive methods[102], while in the United States, despite the aforementioned shortcomings of LB, there is still significant resistance to accepting noninvasive methods as an alternative to biopsy. We believe that sooner or later this will change, and the requirement of LB prior to starting antiviral therapy in patients with CHC will be reassessed.
In conclusion, in the era of PI-based triple therapy and
other new potent direct-acting agents on the horizon that can achieve SVR rates
approaching 100%, the time has come to move forward to risk-free noninvasive
methods for the patient, leaving LB behind in the evaluation of liver fibrosis
in decision making for CHC antiviral therapy. In other words, checkmate to
LB?
Footnotes
Peer reviewers: Giuseppe Montalto, Professor, Clinical
Medicine and Emerging Diseases, University of Palermo, via del Vespro, 141,
90100 Palermo, Italy; Masahito Uemura, MD, Associate Professor, Third Department
of Internal Medicine, Nara Medical University, Shijo-cho, 840, Kashihara, Nara
634-8522, Japan; Dr. Bernardo Frider, MD, Professor, Department of Hepatology,
Hospital General de Agudos Cosme Argerich, Alte Brown 240, Buenos Aires 1155,
Argentina
S- Editor Lv S L- Editor Kerr C E- Editor Li
JY
References
2.
EASL International Consensus Conference on Hepatitis
C.Paris, 26-28, February 1999, Consensus Statement. European Association for the
Study of the Liver. J Hepatol. 1999;30:956-961.[PubMed]
4.
NIH Consensus Statement on Management of Hepatitis C:
2002.NIH Consens State Sci Statements. 2002;19:1-46.[PubMed]
5.
6.
7.
10.
McGill DB, Rakela J, Zinsmeister AR, Ott BJ. A 21-year
experience with major hemorrhage after percutaneous liver biopsy. Gastroenterology. 1990;99:1396-1400.[PubMed]
11.
Reiss G, Keeffe EB. Role of liver biopsy in the management
of chronic liver disease: selective rather than routine. Rev Gastroenterol Disord. 2005;5:195-205.[PubMed]
12.
20.
Thampanitchawong P, Piratvisuth T. Liver biopsy:
complications and risk factors. World J Gastroenterol.
1999;5:301-304.[PubMed]
21.
22.
Hahm GK, Niemann TH, Lucas JG, Frankel WL. The value of
second opinion in gastrointestinal and liver pathology. Arch Pathol Lab Med. 2001;125:736-739.[PubMed]
24.
29.
Stone MA, Mayberry JF. An audit of ultrasound guided liver
biopsies: a need for evidence-based practice. Hepatogastroenterology. 1996;43:432-434.[PubMed]
37.
Pokorny CS, Waterland M. Short-stay, out-of-hospital,
radiologically guided liver biopsy. Med J Aust.
2002;176:67-69.[PubMed]
39.
Chalmers RJ, Kirby B, Smith A, Burrows P, Little R, Horan M,
Hextall JM, Smith CH, Klaber M, Rogers S. Replacement of routine liver biopsy by
procollagen III aminopeptide for monitoring patients with psoriasis receiving
long-term methotrexate: a multicentre audit and health economic analysis. Br J Dermatol. 2005;152:444-450.[PubMed] [DOI]
40.
40.
Wong JB, Koff RS. Watchful waiting with periodic liver
biopsy versus immediate empirical therapy for histologically mild chronic
hepatitis C. A cost-effectiveness analysis. Ann Intern
Med. 2000;133:665-675.[PubMed]
41.
Bonny C, Rayssiguier R, Ughetto S, Aublet-Cuvelier B,
Baranger J, Blanchet G, Delteil J, Hautefeuille P, Lapalus F, Montanier P.
Medical practices and expectations of general practitioners in relation to
hepatitis C virus infection in the Auvergne region. Gastroenterol Clin Biol. 2003;27:1021-1025.[PubMed]
42.
Sebastiani G, Alberti A. Non invasive fibrosis biomarkers
reduce but not substitute the need for liver biopsy. World J Gastroenterol. 2006;12:3682-3694.[PubMed]
47.
Castéra L, Vergniol J, Foucher J, Le Bail B, Chanteloup E,
Haaser M, Darriet M, Couzigou P, De Lédinghen V. Prospective comparison of
transient elastography, Fibrotest, APRI, and liver biopsy for the assessment of
fibrosis in chronic hepatitis C. Gastroenterology.
2005;128:343-350.[PubMed] [DOI]
57.
57.
Halfon P, Bourliere M, Deydier R, Botta-Fridlund D, Renou C,
Tran A, Portal I, Allemand I, Bertrand JJ, Rosenthal-Allieri A. Independent
prospective multicenter validation of biochemical markers (fibrotest-actitest)
for the prediction of liver fibrosis and activity in patients with chronic
hepatitis C: the fibropaca study. Am J Gastroenterol.
2006;101:547-555.[PubMed] [DOI]
58.
58.
Boursier J, de Ledinghen V, Zarski JP, Rousselet MC, Sturm
N, Foucher J, Leroy V, Fouchard-Hubert I, Bertrais S, Gallois Y. A new
combination of blood test and fibroscan for accurate non-invasive diagnosis of
liver fibrosis stages in chronic hepatitis C. Am J
Gastroenterol. 2011;106:1255-1263.[PubMed] [DOI]
73.
73.
Castéra L, Le Bail B, Roudot-Thoraval F, Bernard PH, Foucher
J, Merrouche W, Couzigou P, de Lédinghen V. Early detection in routine clinical
practice of cirrhosis and oesophageal varices in chronic hepatitis C: comparison
of transient elastography (FibroScan) with standard laboratory tests and
non-invasive scores. J Hepatol. 2009;50:59-68.[PubMed] [DOI]
74.
74.
Roulot D, Buyck JF, Gambier N, Warzocha U, Czernichow S,
Costes JL, Le Clesiau H, Beaugrand M. Liver stiffness measurement: an
appropriate screening method to detect liver fibrosis in the general population
(abstract). J Hepatol. 2009;50:(Suppl 1):S89. [DOI]
82.
82.
Kemp W, Graham M, Roberts S. Comparison of the M and XL
probe in transient elastography using fibroscan. J
Gastroenterol Hepatol. 2010;25:A29.
86.
Trifan A, Sfarti C, Cojocariu C, Dimache M, Cretu M,
Hutanasu C, Stanciu C. Increased liver stiffness in extrahepatic cholestasis
caused by choledocholithiasis. Hepat Mon.
2011;11:372-375.[PubMed]
91.
Sherman M, Shafran S, Burak K, Doucette K, Wong W, Girgrah
N, Yoshida E, Renner E, Wong P, Deschênes M. Management of chronic hepatitis C:
consensus guidelines. Can J Gastroenterol.
2007;21 Suppl C:25C-34C.[PubMed]
95.
Ramachandran P, Fraser A, Agarwal K, Austin A, Brown A,
Foster GR, Fox R, Hayes PC, Leen C, Mills PR. UK consensus guidelines for the
use of the protease inhibitors boceprevir and telaprevir in genotype 1 chronic
hepatitis C infected patients. Aliment Pharmacol Ther.
2012;35:647-662.[PubMed] [DOI]
99.
99.
de Sant HA. Non invasive methods for the evaluation of
hepatic Fibrosis/cirrhosis: an update. Available from: http: //www.has-sante.fr.
No comments:
Post a Comment