Saturday, October 12, 2013

Article Review (2003) - Orthotopic liver transplantation for hereditary fibrinogen amyloidosis

Today's article under review is another article that was previously reviewed but only recently acquired. It is from 2003 and I first reviewed it on May 18, 2013. There is not a lot to add to the previous review since it is a relatively short article anyway, so I think I will just start with a copy of the previous review and modify that as necessary.

Title: Orthotopic liver transplantation for hereditary fibrinogen amyloidosis (1)

Authors: Zeldenrust, S.; Gertz, M.; Uemichi, T.; Björnsson, J.; Wiesner, R.; Schwab, T.; Benson, M. (Mayo Graduate School of Medicine, Rochester, MN; Indiana University School of Medicine, Indianapolis, IN)

Journal: Transplantation (2003)


Systemic amyloidosis results from the deposition of insoluble protein fibrils in various organs and tissues. To date, several different proteins have been associated with amyloid fibril formation, including immunoglobulin light chain, serum amyloid A protein, and transthyretin. Recent reports have shown that variant fibrinogen chains can form amyloid in certain kindreds. Hepatic transplantation has previously been reported in the treatment of hereditary amyloidosis associated with variant transthyretin proteins, which are mainly synthesized in the liver. This article reports the first use and long-term follow-up of combined hepatic and renal transplantation in the successful treatment of two patients with hereditary fibrinogen amyloidosis. Both patients experienced sustained improvement in renal function and nutritional status at 6 1/2 years and 28 months of follow-up, respectively. Orthotopic liver transplantation is effective and potentially curative treatment of hereditary fibrinogen amyloidosis.

I want to explain the first word in the title of this article so you don't have to look it up. "Orthotopic" simply means something is occurring in the normal place in the body. In the case of organ transplants, a liver transplant is typically orthotopic because the old liver is removed and the new one is put in its place. Kidney transplants are typically not orthotopic because the old kidneys are left in place and the new kidney is placed below them.

The article begins with a brief overview of systemic amyloidosis and some of the hereditary types that were known at the time. Then while discussing fibrinogen amyloidosis the article has this sentence: "Synthesis of fibrinogen is exclusively hepatic, making liver transplant theoretically curative in hereditary fibrinogen amyloidosis." So the authors are suggesting that since the liver is the sole source of fibrinogen, a liver transplant could be considered a cure. That will be a recurring topic of discussion as we review articles published after this one.

Case 1 in this article was a 62-year-old male who presented with high blood pressure in his thirties. He is a member of an Irish-American kindred with the Glu526Val mutation. His serum creatinine was 2.7 mg/dL and he had proteinuria. A kidney biopsy showed extensive amyloid deposits in the glomeruli. His renal failure progressed and his serum creatinine rose to 4.5 mg/dL. It was known that both his father and brother had been diagnosed with renal amyloidosis, and DNA analysis revealed that he also had the Glu526Val mutation. He underwent a combined liver and kidney transplant in September of 1995.

Six and a half years after the transplant he has stable kidney function (serum creatinine = 1.8 mg/dL) and most of his prior health issues have been resolved. Kidney biopsies of the transplanted kidney have not shown amyloid deposits. He did have his spleen removed due to a type of anemia, and there were extensive amyloid deposits in his spleen.

Case 2 is the older brother of Case 1, and he developed proteinuria at age 47. He had an orthotopic kidney transplant in 1994, which means a native kidney was removed and a transplanted kidney put in its place. The native kidney did have amyloid deposits. The transplanted kidney had to be removed in April of 1997 due to recurring amyloidosis. His spleen was also removed due to anemia and found to have extensive amyloid deposits. In November of 1999 he underwent a combined liver and kidney transplant. His kidney function has improved (serum creatinine = 1.2 mg/dL), and a kidney biopsy of the transplanted kidney does not show amyloid deposits.


Both of these cases follow a clinical path similar to previous published cases of fibrinogen amyloidosis, in which the patient initially presents with some combination of high blood pressure, proteinuria and elevated serum creatinine which steadily progresses toward kidney failure. It is interesting that both of these patients also had their spleens removed, with both spleens showing extensive amyloid deposits.

With this article we now have a total of three published reports of patients with fibrinogen amyloidosis undergoing combined liver-kidney transplants. You may recall the first article to document such a case was published in 2000, and I reviewed that article on April 30, 2013. That patient underwent a combined liver and kidney transplant in October of 1996. Since the Case 1 patient in this 2003 article underwent a liver and kidney transplant in September of 1995, he was actually the first patient to receive a liver-kidney transplant for fibrinogen amyloidosis.

It is worth noting that all three of these patients were doing well at the time these articles were published, with follow-ups ranging from 2.0 to 6.5 years. Both articles say the results suggest that a liver transplant may be curative for fibrinogen amyloidosis. I believe some upcoming articles will have a few more cases of kidney or liver-kidney transplants, but we will have to wait until a 2009 article before a large number of transplant outcomes are documented.


(1) Zeldenrust S, Gertz M, Uemichi T, et al. Orthotopic liver transplantation for hereditary fibrinogen amyloidosis. Transplantation 2003; 75: 560-561.

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