Objections to Liver Biopsy for Diagnosing Hemochromatosis or related condition.

The process is somewhat dangerous. There has been one death in a thousand reported from this procedure.

The needle biopsy has a high error rate. Corwin Edwards MD at our annual symposium in San Diego 1998 presented that there is a 13% error rate for this process. That is that underlying iron might be missed by this operation. If you undergo the liver biopsy and are found clear, you will not be treated for your iron overload. The doctor will instead move to managing ever worsening symptoms while casting about for another diagnosis. Iron overload is fatal if left undetected or untreated.

Liver biopsy can add quite a bit of delay between the diagnosis and treatment. First there is the initial appointment and consultation with the gastroenterologist. Then later you have to undergo the procedure. Then a local lab will read the results. Next a more distant lab may confirm the results. Really all that is necessary is to get right into protocol treatment. The patient needs to outrun lethal jeopardys such as liver cancer, heart attack and stroke.

The invasive process is expensive - approximately $4,000-$6000 - even as an out office procedure. The insurance industry and the medical community need to hold down costs so that more people might be served.

Newer imaging techniques are much improved in recent years and offer more information non invasively. They can see anomalies, surface variations, scaring, shape, size and other areas of concern. A needle biopsy can not see these problems.

The liver will begin repairing and improving itself as soon as treatment starts. The liver has wonderful recuperative properties and will regenerate itself if caught in time. Even cirrhosis can be reversed with protocol treatment. So the liver biopsy will only give you an assessment of how bad the liver was at the start.

In the 20 years since we stopped recommending the liver biopsy The National Institutes of Health in Bethesda and the Centers for Disease Control in Atlanta have followed us in that lead.

If you were told that you could not be treated without a liver biopsy, then you need to find a different doctor.

Open letter to all doctors involved in Hereditary Hemochromatosis
Philip de Sterke

Should we continue to perform liver biopsies in Hereditary Hemochromatosis (HH)?

Introduction
Being involved in writing an evidence based protocol for the diagnosis and treatment of HH in the Netherlands1 I learned that before you can start (invasive) treatment or even measuring ferritin you need to have evidence based proof that this procedure is effective and efficient.
When there is an increased risk of cirrhosis in HH the current protocols^1,2 recommended a liverbiopsy. I argue that a liver biopsy has not been proven to be efficient and/or effective and is thus not evidence based.

Background
Was a liver biopsy the gold standard for the diagnosis of HH, with the DNA-test (since 1996!) and MRI this necessity to confirm a diagnosis has become obsolete.

Proposal
This act should be reevaluated and validated (evidence based). Till this is done the procedure should be discontinued. If there is enough evidence that a liver biopsy is efficient and effective... patients should given a brochure with all the pros and cons in an unbiased way, and the patient should make a decision based on this information and the information given by the physician.
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It is argued that patients with hemochromatosis and a ferritin higher than 1000 痢/l have an increased risk of developing cirrhosis^3,4 Physicians use this as the main argument to perform a liver biopsy in these cases. This argument on itself is not sufficient to warrant the performance of a liver biopsy. Before considering a liver biopsy a series of questions should be answered to proof the efficiency and effectivity of a liver biopsy in HH. A number of these questions have been answered in the literature whereby the answer is most often negative, strengthening the advocators against performing liver biopsies in HH.

Some of these questions might never be answered in large series of patients undergoing a liver biopsy, since in clinical practice already a lot of physicians do not perform liver biopsies anymore (especially non hepatologists⁵). Also the Fibroscan might substitute the liver biopsy altogether in the future⁶.

The accuracy of a liver biopsy is also not always as clear as we would like to⁷. In hepatitis C patients, that sampling error was 35% and 25% in 15-mm and 25-mm liver biopsies specimens with respect to ﬁbrosis grading,⁸ Also in a number of cases the biopsy is too small to correctly diagnose cirrhosis.

Another issue is that not finding cirrhosis does not exclude the possibility of the development of a HepatoCellular Carcinoma (HCC) ^9-13.

Liver fibrosis (and cirrhosis) regresses in many cases after treatment with phlebotomies¹⁴. This regression might also predict the later development of a HCC. If this is the case, it might be a good argument to perform a liver biopsy after de-ironing. Falize et al. showed that in their series of patients with HH, no patient with HCC at the time of the second liver biopsy (after de-ironing) had regression of fibrosis, all patients still had cirrhosis. They conclude that it is likely that a regression of fibrosis lowers the risk of the development of a HCC¹⁴. Performing a liver biopsy after de-ironing might thus be a more accurate predictor for the chance of developing a HCC. Because many patients will recline a liver biopsy after de-ironing it is important that the patient gets unbiased information about the pro's and cons.

There is much more to be said about this topic. But for now I am eagerly awaiting the response of physicians involved in hemochromatosis and hope they will give us, the patients, the right answers.

* How many complications/fatalities develop as a result of a liver biopsy in HH and which factors effect this (guide or not, number of biopsies per year, etc.)?
* How many biopsies are inconclusive (sample size, etc.)?

* Does a (single) biopsy give a good impression of the fibrosis/cirrhosis in the liver?

* Are there any other methods of estimating the chance of developing a HCC (ferritin above 3000, alcohol abuse, fibroscan, AFP, pateletcount, etc.) that could be a surrogate for a liver biopsy?http://www.hemochromatosis.co.uk/liverbiopt/cirr-iron.pdf

* How much is the benefit of knowing that the patient has cirrhosis in case a liver transplantation is necessary? Or do general symptoms eventually give the same results?

* How many patients do you have to follow for how long till you find one HCC?
* How much sooner do you find a HCC using screening? There is anecdotal information that the echo used for follow up is not accurate and when a HCC is found it is too late to treat.

* How effective is the treatment of livercelcarconoma in HH? (see http://www.hemochromatosis.co.uk/liverbiopt/HHC-surgery.pdf)
* How often is a HCC multifocal? And how often will another HCC develop after removing a single HCC?
* How many HCC's are there effectively treated in HH?

* How many years are added to a patient𠏋 life if a liver transplant is performed?

* A full cost/benefit analysis should be made! Including costs of biopsy, follow up, treatment, etc. including quality of life

* Should a liver biopsy be performed after de-ironing?
* Is there a role for the fibroscan diagnosing cirrhosis? http://www.hemochromatosis.co.uk/liverbiopt/fibroscan-hh.pdf
* How often does a HCC develop if only fibrosis is found?

Literature

1 Swinkels DW, Jorna AT, Raymakers RA.; Synopsis of the Dutch multidisciplinary guideline for the diagnosis and treatment of hereditary haemochromatosis.; Neth J Med. 2007 Dec;65(11):452-5;http://hemochromatosis.co.uk/liverbiopt/synopsis.pdf

3. Guyader D, Jacquelinet C, Moirand R, Turlin B, Mendler MH, Chaperon J, David V, Brissot P, Adams P, Deugnier Y.; Noninvasive prediction of fibrosis in C282Y homozygous hemochromatosis.; Gastroenterology. 1998 Oct;115(4):929-36;http://hemochromatosis.co.uk/liverbiopt/guyader-noninvasive.pdf
4. Beaton M, Guyader D, Deugnier Y, Moirand R, Chakrabarti S, Adams P.; Noninvasive prediction of cirrhosis in C282Y-linked hemochromatosis.; Hepatology. 2002 Sep;36(3):673-8; http://hemochromatosis.co.uk/liverbiopt/noninv.pdf

5: Result of talking to many phycisians specialised in hemochromatosis over the last years.

6: Adhoute X, Foucher J, et al.; Diagnosis of liver fibrosis using FibroScan and other noninvasive methods in patients with hemochromatosis: a prospective study; Gastroenterol Clin Biol. 2008 Feb;32(2):180-7;http://www.hemochromatosis.co.uk/liverbiopt/fibroscan-hh.pdf

8: Bedossa P, Dargere D , Paradis V. Sampling variability of liver ﬁbrosis in chronic hepatitis C. HEPATOLOGY2003; 38: 1449-1457.

9: Fellows IW, Stewart M, et al. Hepatocellular carcinoma in primary haemochromatosis in the absence of cirrhosis. Gut 1988; 29:1603-1606.
10: Deugnier YM, Guyader D, et al. Primary liver cancer in genetic hemochromatosis: a clinical, pathological, and pathogenetic study of 54 cases. Gastroenterology 1993; 104:228-234.

11: Goh J, Callagy G, et al. Hepatocellular carcinoma arising in the absence of cirrhosis in genetic haemochromatosis: three case reports and review of literature. Eur J Gastroenterol Hepatol 1999; 11: 915-919.

12: Kohler HH, Hohler T, et al. Hepatocellular carcinoma in a patient with hereditary hemochromatosis and non-cirrhotic liver: a case report. Pathol Res Pract 1999;195: 509-513.

13: Britto MR, ThomasLA,et al. Hepatocellular carcinoma arising in non-cirrhotic liver in genetic haemochromatosis. Scand J Gastroenterol 2000; 35: 889-893.

14: Falize L, Guillygomarc'h A, et al. Reversibility of hepatic fibrosis in treated genetic hemochromatosis: a study of 36 cases; Hepatology. 2006 Aug;44(2):472-7.