No Hit for the Liver

11. November 2008

Up to today, only biopsy provided reliable results for the diagnosis of liver fibrosis. But now physicians bear down the liver with a vibrator – and fire a whole line of test batteries to draw the secrets of fibrosis without puncture.

So close and yet so far away. Even though the liver lays right underneath the costal arch and although it is big, compact and easy to touch: If a physician wants to know exactly whether this organ shows any connective tissue related changes or not, he had to puncture it. Liver biopsy was and still is golden standard for fibrosis diagnosis because it allows the coloring of fibrosepts directly under the microscope – the only way to enable the five-state classification (F0 to F4) allowing an assessment just how close a patient is to an irreversible liver cirrhosis – with all known therapeutic consequences such as recommendation of an invasive variceal screening.

The liver vibrates: Simple, fast and very precise

But biopsy is getting a bit long in the tooth. First of all it is not reliable: “For at least every fifth patient the result is wrong” says Dr. Dominique Thabut vom Hôpital Pitié Salpêtrière in Paris/France. And secondly biopsy is getting some real competition here. Officially the mainly in France tested technique is called “resilience measuring”. De facto the Fibroscan (its trade name) is a vibrator setting the liver tissue in vibrations by a pulse wave. The speed of this wave spreading in the tissue can be defined with ultrasound. And this again allows a classification by stages which – at least according to the protagonists of that method – correlate closely with those cirrhosis stages identified by biopsy. “The method is simple, fast and not very expensive” as Dr. Michel Beaugrand at Hôpital Jean Verdier Bondy/France describes the advantages.

Beaugrand is that convinced about this method that he started testing it as a screening tool. Because such a fibrosis screening is a wonderful thing: For people enjoying to have one over the eight, it is a tool to estimate how much the drinking of alcoholic beverages has gotten to the liver just yet. And in the 21st century the increasing number of heavily obese people adds as a potential target group for this screening. Here steatosis, fat liver hepatitis and worst case – cirrhoses are threatening just as they do with alcohol abuse.

Screening studies: Every twentieth patient has a problem

Beaugrand considers initial data regarding the effectivity of “vibrator screening” of risk populations promising. In an own study he screened 227 patients with liver diseases caused by alcohol. 41 patients reached the prior defined limit value for diagnosis of a cirrhosis of 13 kilopascal. 354 of those patients agreed to a liver biopsy to verify the diagnosis which was done successfully for 33 patients. Which means a very high hit ratio. In a second step, the French now tested the measuring of the resilience in a collective of 1300 people which is representative for the entire population. According to first results, the cirrhosis rate is at about half a percent and another five percent are having considerable fibrotizations. How things will proceed remains to be seen. Perhaps liver vibration might become a treatment benefit reimbursable by health insurance companies like other standard screenings.

The lab physicians are also shuffling their feet

But may be a fibrosis screening will look completely different, because next to the resilience measuring, several laboratory chemical test batteries were checked regarding their suitability as a screening tool. On one hand, unspecific combination tests such as the FibroTest or Hepscore could be a possibility. They analyze common and less common parameter of liver dysfunction to come to conclusions about the extent of a fibrosis. Nonetheless many experts set their hope on fibrospecific tests measuring matrix components and other structure proteins of the liver.

One example is the ELF-test which, among others, measures hyaluron acid and liver specific metal proteinases. It was validated by Professor William Rosenberg at the University College London in a collective of 921 patients with unspecific liver diseases. The accuracy in predicting the stage of fibrosis was at about 80 percent. “For children, the accuracy was a lot higher which might be caused in them developing a liver fibrosis in its pure form not interfered by other factors”, explains Rosenberg. Vibrator or lab test? Which one will make the race? The supporters of the lab tests and the ones of the vibrator method plan to join forces in getting the unpopular liver biopsy – at least for fibrosis staging – to retire.

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