In The News
May 2012
New Tests Predict Clinical Outcomes in Chronic Hepatitis C Virus

Ultrasound Dx of HCV Effective in Liver Transplant

Blood Test Instead of Biopsy Identifies Liver Damage
Siemens is marketing the first rapid, automated biomarker  test for diagnosing and assessing liver fibrosis. The ELF
test (Enhanced Liver  Fibrosis test) takes approximately one hour to complete  and requires only a  blood sample
The ELF test (Enhanced Liver Fibrosis test)  takes  approximately one hour to complete and requires only a blood sample. The
process  is therefore less invasive but just as reliable as the previously  required  biopsy, and it usually takes about a week to deliver a biopsy  result.

Jan 2012
How far is noninvasive assessment of liver fibrosis from replacing liver biopsy in hepatitis C?


Liver Biopsy and Noninvasive Tests For Fibrosis
There are several unapproved noninvasive tests that may be used to estimate the amount of fibrosis in the liver. These tests may replace the need for liver biopsy in some patients, although liver biopsy is still the “gold standard” for measuring the amount of liver damage. The goal today is to understand the available noninvasive tests for detecting fibrosis in HCV.
 
Some of the tests used today are biomarker tests or (blood tests) , one such test is better known as the (FibroTest) . These biochemical and hematological tests, such as ALT, AST, prothrombin time, platelets (APRI, AST/ALT ratio, Forns Index; those that include specific indirect markers of liver fibrosis, such as a-2 macroglobulin; those that incorporate only direct markers of liver fibrosis (MP3), or combinations of direct and indirect markers (Hepascore, Fibrometer). Sufficient evidence exists to support the view that algorithms perform well in the detection of significant fibrosis (METAVIR score F2-F4). Thus, their use in patients with chronic hepatitis C can be recommended for this purpose.

 Other noninvasive tests for fibrosis are TE= transient elastography which is an (ultrasound-based scan), we know it as (FibroScan). The FibroScan is for evaluating liver fibrosis by measurement of liver stiffness

*See Below "Physical Non-invasive methods for the assessment of liver fibrosis"

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Noninvasive Blood Tests (Biomarker Test)

What Are These BiomarkerTests Called?
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FibroSure is a safe, convenient and inexpensive (about $300.00) blood test

The FibroTest is also known as the FibroSure in the US and is a biomarker test that uses six blood serum markers to create a score that correlates with the degree of liver damage in those with liver disease. It has the same prognostic value as having a liver biopsy. It has been used on patients with hepatitis C, hepatitis B, non-alcoholic fatty liver disease and alcoholic liver disease. It is used to diagnose and manage the degree of cirrhosis in patients suffering from the disease.
FibroSure requires only a small sample of blood to be drawn, which is then analyzed in six biochemical tests: Alpha 2-macroglobulin, haptoglobulin, apolipoprotein A, bilirubin, Gamma Glutamyl Transpeptidase (GGT), and alanine aminotransferase (ALT).
Gender, age, and the results of these tests are then computed to provide a score.
HCV FibroSure may be used for:
Assessment of liver status following a diagnosis of HCV
Baseline determination of liver status before initiating HCV therapy
Post-treatment assessment of liver status six months after completion of therapy
Noninvasive assessment of liver status in patients who are at increased risk of complications from a liver biopsy.

The FibroTest has a 95 percent degree of accuracy in determining the presence of fibrosis and liver disease. False positives run around 5 percent.


APRI AST: platelet ratio index (APRI),Abbreviation: (APRI), Definition: AST to platelet ratio index

APRI Score is an easy, low cost and practice alternative method which was described as an alternative for assessing structural changes in chronic hepatitis C .The APRI was designed to be a convenient marker of fibrosis because it incorporates laboratory data that are routinely obtained as the standard of care.Initial studies showed that it performed well in predicting fibrosis and cirrhosis in both a training and validation set of adults with chronic HCV infection. APRI, calculates only the AST to platelet ratio .

Fibrotest and APRI

Forns: A non-invasive method for monitoring liver disease . The Forns' score combines age, gGT, cholesterol, and platelet count.platelet count. .

Fib-4 A non-invasive method for monitoring liver disease. FIB-4 score, is based on a calculation of a person’s age, alanine transaminase (ALT) levels and the ratio of aspartate transaminase (AST) levels to platelet count.

SHASTA A non-invasive method for monitoring liver disease. The SHASTA index developed consists of serum hyaluronic acid, AST, and albumin

Fibrometer-FibroMeters are non-invasive blood tests for liver fibrosis . The score combines hyaluronate, prothrombin time, platelets, AST, a2 macroglobulin, urea, and age, and the formula is adjusted based on the cause of the liver disease. EASL 2011- FibroMeter This study, performed in several populations with C hepatitis, shows that the detailed classification in fibrosis stages of FibroMeter3G (1) is as performant as that of an expert pathologist and significantly superior to that of a first line pathologist or that of other non-invasive tests.
See the poster

CirrhoMeter is the first validated and marketed test for cirrhosis diagnosis EASL 2011-CirrhoMeter This study, performed in 1710 C hepatitis, shows that the CirrhoMeter (5) offers an excellent cirrhosis diagnosis: accuracy superior to that of Fibroscan, on an intention to diagnose basis, with a higher precision
See the poster

EASL 2011-During the last EASL meeting (Berlin), 5 communications on CirrhoMeter and FibroMeters were presented. FibroMeters / CirrhoMeter

Hepascore- Hepascore is an Australian blood test combining the following clinical and laboratory variables: age, gender, bilirubin, GGT, hyaluronic acid, alpha 2 macroglobin to create a score.

Hepascore(TM) liver fibrosis blood-serum test

http://www.questdiagnostics.com/hcp/intguide/jsp/showintguidepage.jsp?fn=InfectDis/Hepatitis/TS_LiverFibrosisPnl_HepaScore.htm

Study Finds Noninvasive Blood Test For Liver Fibrosis May Alleviate Need For Liver Biopsies For Some Patients With Chronic Hepatitis C

"Hepatologists have long sought a noninvasive technique for assessing fibrosis without conducting a liver biopsy, a painful procedure that can miss cirrhosis in some patients," said Nezam H. Afdhal, M.D., study investigator and director, Hepatology, Beth Israel Deaconess Medical Center and associate professor, Medicine, Harvard Medical School.

"While Hepascore is unlikely to entirely replace liver biopsy as a staging test for liver fibrosis, one can envision an algorithm using Hepascore in the management of chronic HCV. In fact, the present study suggests that a unique Hepascore-based algorithm we developed that incorporates results of FIB-4 and APRI assessments would have spared 103 of the 391 study participants with chronic HCV the need for liver biopsy, with advanced fibrosis missed in one patient. We look forward to longitudinal studies that may prospectively assess the usefulness of Hepascore in clinical strategy for monitoring, treating and possibly alleviating the need for biopsy in a subset of chronic HCV patients."
Previous studies of Hepascore in populations in France and Australia have showed it is reliable at predicting different degrees of fibrosis in chronic HCV patients. The objective of the present study was to validate the Hepascore test in a U.S. population with chronic HCV infection, and to compare it with two indices that employ nonspecific biomarkers, aspartate aminotranaminase(AST)-platelet ratio index (APRI) and Fibrosis-4 (FIB-4).
Three hundred and ninety one patients with chronic HCV infection undergoing liver biopsy were enrolled from the Liver Center at Beth Israel Deaconess Medical Center in Boston. A reference range for a negative Hepascore was also determined from a study of 214 healthy volunteers. The diagnostic performance score for Hepascore by AUROC(1) was 0.81 for significant fibrosis, 0.83 for advanced fibrosis, and 0.88 for cirrhosis..
Read Complete Article

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Physical Non-invasive methods for the assessment of liver fibrosis

TE= transient elastography  is an (ultrasound-based scan)

What is elastography?

Elastography, is a twist on the traditional ultrasound technique of using sound waves to create a picture of what's going on inside the body.

What Are These Noninvasive Tests Called ?

Fibroscan : The Fibroscan involves what’s known as ultrasound elastography. It uses a modified ultrasound probe to measure the velocity of a shear wave created by a vibratory source. It can predict stiffness of the liver to a 95 percent accuracy. It can be harder to assess the liver in patients who are older and in patients who are obese. The Fibroscan is the most consistently used test for evaluation of liver elasticity. Only 6 percent of people had false positives for liver disease.

Transient elastography (TE)

Transient elastography that uses ultrasound and low frequency elastic waves to measure liver elasticity has improved the ability to define the extent of fibrosis without a liver biopsy, particularly when combined with other noninvasive markers (blood tests) . However, it is not yet ready to replace the liver biopsy since it is not FDA approved, the failure rate is higher in obese patients, and there is now evidence that the transient elastography score can be unexpectedly increased in persons with acute hepatitis who have high necroinflammatory activity but no or minimal fibrosis.

Take Home Message on Elastography

What Is the Role of FibroScan in Diagnosing Liver Fibrosis?
In summary, ultrasound elastography will separate patients with minimal or no fibrosis from those with advanced fibrosis or cirrhosis, although it may occasionally underestimate fibrosis in some patients with advanced fibrosis or macronodular cirrhosis. Additional studies will establish the role of this technique in evaluating hepatic fibrosis in patients with chronic liver disease.

However, it is not yet ready to replace the liver biopsy since it is not FDA approved, the failure rate is higher in obese patients, and there is now evidence that the transient elastography score can be unexpectedly increased in persons with acute hepatitis who have high necroinflammatory activity but no or minimal fibrosis.

Source 2009 : Diagnosis, Management, and Treatment of Hepatitis C: An Update
..

For Acute Liver :
 "Liver stiffness measurement by elastography-Fibroscan (FS) liver damage overestimate the real stage of fibrosis and may erroneously suggest the presence of liver cirrhosis"

FibroScan FibroScan in Patients With Hepatitis B and C Presenting for Liver Biopsy
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 Take Home Message on Noninvasive Blood Test

FibroTest is also known as the FibroSure appears relatively good at gauging both
1) very early or minimal
2) relatively advanced liver disease.
The test doesn't perform as well for people in the middle of the spectrum.

One independent evaluation comparing FibroTest to biopsy results concluded that "the FibroTest score " could not accurately predict the presence or absence of significant liver fibrosis.

The noninvasive tests look promising, but can’t substitute for liver biopsy at the present time. We need to get the quirks out first so that we can differentiate middle stages of disease, rather than just the ends,” says Melissa Palmer, MD, a hepatologist in private practice, Plainview, NY, and author of Dr. Melissa Palmer’s Guide to Hepatitis and Liver Disease.
“These tests give the physician an alternative before going straight to a liver biopsy, and are sensitive to changes associated with disease progression and/or response to therapy. They provide a means for more frequent monitoring as compared to a biopsy,” Faruki says.

Some of these new tests incorporate blood serum markers. LabCorp’s HCV FibroSure combines six biomarkers to determine fibrotic and necroinflammatory damage: alpha2-macroglobulin, haptoglobin, apolipoprotein A1, bilirubin, gamma glutamyl transpeptidase, and ALT.

LabCorp licenses the FibroSure test from BioPredictive, SAS, a company based in Paris that focuses on the development of noninvasive liver diagnostics. FibroSure is not approved by the FDA but is available as a LabCorp offering. Turnaround is roughly 7 days, Faruki says.

“The correlations between a test like FibroSure and biopsy are somewhere between 70% and 80%. But studies have shown that the correlation between two biopsies on the same patient is also between 70% and 80%,” Faruki says.
She suggests that the tests’ flaws may not be solely a reflection of the biomarkers but rather of the imprecision in a liver biopsy. “[A liver biopsy] actually samples only about one fifty-thousandth of the liver. A combination of biochemical markers may give a more comprehensive view.”

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