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Hospital Healthcare Europe
Hospital Healthcare Europe

Liver fibrosis: minimally invasive measurement

Victor de Ledinghen
31 July, 2012  
Victor de Ledinghen
Hôpital Haut Lévêque
Pessac, France

What is liver fibrosis?
It’s a consequence of chronic liver disease. When you have, for example, hepatitis C or hepatitis B virus (HCV or HBV), you will have inflammation in your liver, which can develop into liver fibrosis, then cirrhosis and then at the end, liver cancer. It’s a step of the disease. 
What causes it?
Causes of liver fibrosis are all causes of chronic liver diseases, so that is viral hepatitis, alcohol use, metabolic syndrome and diseases such as autoimmune hepatitis.
How does FibroScan work?
With FibroScan you can evaluate liver stiffness. We know that there is a relationship between liver stiffness and portal fibrosis, which means it gives a measure of liver fibrosis. When you have cirrhosis, the value of liver fibrosis is elevated over 15kpa. When you don’t have any cirrhosis, it’s lower than 15kpa. 
What diseases is FibroScan useful for?
Hepatitis C. At the beginning, HCV was the disease that we evaluated with FibroScan, but now we know that we can use FibroScan for more conditions, for example for patients with alcoholic disease, hepatitis B and metabolic syndrome. 
What are the cost benefits?
There is no study of the cost effectiveness of FibroScan in chronic liver diseases. However, you can repeat FibroScan every year whereas liver biopsy cannot be repeated as often as it carries risks of morbidities and mortality. By using FibroScan, you can follow up your patients every year or every two years. If there is an increase in liver stiffness, then there is an increase in the disease and you can treat the patients. 
How does the accuracy of FibroScan compare with other invasive methods?
It’s very good at diagnosing cirrhosis; it’s quite comparable to liver biopsy, which is the standard for the evaluation of liver fibrosis. For other stages of fibrosis, its accuracy is slightly lower than biopsy but it’s better at diagnosing fibrosis in HCV patients than in other chronic liver diseases. In HCV patients, it is now the same as liver biopsy. We don’t perform any liver biopsy now in HCV patients. 
What are the time benefits, compared with invasive treatments?
FibroScan takes just five minutes. It’s nothing. Liver biopsy is performed on inpatients, and in France, the patient has to stay in hospital for eight hours. Liver biopsy is very expensive, in comparison.

Is there any rationing of treatment? 
In France, we can use FibroScan to evaluate liver stiffness in all patients, even for screening. In some countries, such as the UK, it’s very difficult to use FibroScan in patients without HCV. In Asia, Hong Kong and China, they use FibroScan in all their HBV patients. 

Who is qualified to use it?
You don’t need to be a medical doctor to use FibroScan. In France, for example, nurses perform FibroScan in different centres. In our centre, we don’t perform FibroScan ourselves. We have nurses who perform all FibroScan examinations (see Fig. 1). I know how to use FibroScan but I don’t have enough time to use it myself.
Are there any other non-invasive methods used widely to image liver disease?
You have blood samples and you can evaluate stiffness using a new device called ARFI, which stands for acoustic radiation force impulse. This is the evaluation of liver stiffness using sonography. We don’t currently have many studies using this new technique. 
Do you know how ARFI compares to FibroScan in accuracy?
The accuracy of ARFI is quite similar to that of FibroScan but there are many fewer studies of ARFI, and so therefore it’s not used a lot over the world at this time in early 2012. But it could be useful in the future.
Box 1: Key evidence

FibroScan and liver biopsy
Laurent Castera and colleagues compared transient elastrography using FibroScan (Echosens) with available biochemical markers and liver biopsy, as reference, in 183 consecutive patients with chronic hepatitis C. 
Combining FibroScan with FibroTest gave areas under the receiver operating characteristic (ROC) curve of 0.88 for F≥2, 0.95 for F≥3 and 0.95 for F≥4. When the findings of FibroScan and FibroTest were combined, they agreed with liver biopsy results in 86% of cases when F≥2, 95% for F≥3 and 94% for F=4. Castera et al concluded that FibroScan is a “simple and effective” method for assessing liver fibrosis, with comparable accuracy to FibroTest and the aspartate transaminase to platelets ratio index. They add that the combination of Fibroscan and Fibrotest  “could avoid a biopsy procedure in most patients with hepatitis C”.
Gastroenterology 2005;128:343–50
Progression: non-invasive methods
Cosimo Colletta and colleagues studied the course of hepatitis C infection in 40 untreated, HCV-RNA-positive individuals who had normal or close-to-normal levels of aminotransferases (NALT). The participants had undergone liver biopsy twice – a median of 78.5 months apart – while aminotransferase levels had never exceeded 1.2 times the upper limit of normal. The focus of the trial was testing using FibroScan and the artificial intelligence algorithm FibroTest within nine months of the second biopsy. Significant fibrosis, F≥2, was detected in one patient at the first biopsy and 14 (35%) at the second biopsy. Inter-rater agreement between the non-invasive method and biopsy, assessed by weighted kappa analysis, was “excellent for FibroScan (weighted kappa – 1.9) and poor for FibroTest (weighted kappa = -0.041)”, Colletta et al report. They conclude that FibroScan is “superior” to FibroTest in non-invasive identification of fibrosis. 
Hepatology 2005;42:838-45
Early prediction of prognosis
Julien Vergniol and team demonstrated in 2011 that non-invasive assessment of liver fibrosis, using FibroTest or liver stiffness assessed by FibroScan, can predict 5-year survival of patients with chronic HCV. They assessed 1457 patients with chronic HCV using clinical and biological parameters, FibroScan or biopsy, and followed them up for five years. Each method predicted shorter survival in patients with severe fibrosis, but FibroScan and FibroTest were most predictive. After adjustment for confounding factors, they both had significant prognostic values with p<0.0001. Vergniol et al suggest that FibroScan might help predict prognosis early and allow discussion of treatments such as transplantation.