INFO: Fibrosis May Develop Quickly After Liver Transplant

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http://www.hepatitisneighborhood.com/content/in_the_news/archive_2123.aspx

Fibrosis May Develop Quickly After Liver Transplant

by C.

Article Date: 11-03-04

Fibrosis, the distorting scarring of healthy liver tissue that can often result as a consequence of hepatitis C, can insidiously develop again following an otherwise normal liver transplant operation.1 But how rapidly it re-develops in hepatitis patients after surgery varies, and depends on several factors. That was the focus of research by doctors at Mount Sinai School of Medicine in New York whose findings were unveiled at the annual conference of the American Association for the Study of Liver Diseases (AASLD) this week.2

Defining Fibrosis Recurrence"There is variability in HCV post-liver transplantation patients with some developing rapid progression of fibrosis to cirrhosis, and others a low rate of fibrosis," wrote M. Isabel Fiel, MD, an associate professor of Pathology at Mount Sinai, and the study's lead investigator, and her colleagues. "It is important to identify which factors influence post-liver transplantation recurrence and rapid fibrosis so appropriate treatment and

donor allocation may be instituted."

Fiel and her colleagues determined that improved survival of transplanted liver is more likely to occur when fibrosis re-development after surgery is either mild or moderate.

In an interview with Priority Healthcare, Fiel explained that there have been theories that fibrosis recurrence may be more rapid in suboptimal donor livers due to a range of factors like hepatitis C infection in the donor, or the level of necrosis (liver cell death) or steatosis (fatty liver) that had occurred. "However, in our study, we didn’t find it to be so," she said.

Liver fibrosis, which often leads to cirrhosis in those with hepatitis C, is the formation of scar tissue, which replaces healthy liver tissue and can negatively impact normal liver function. Outside of liver transplant operations, the risk factors for fibrosis development include a longer duration of hepatitis C infection, older age of the patient, being male, alcohol consumption, co-infection with the AIDS virus, and a low amount of immune system cells that are produced in reaction to the HCV infection.3

What Factors Speed Up Fibrosis Recurrence?Fiel and her team evaluated the rate of fibrosis recurrence after liver transplant procedures by examining the medical records of more than 200 patients who underwent the operation at the hospital. Only those patients who underwent a post-perfusion biopsy; that is, a biopsy performed on the transplanted liver, were included in the study.

The researchers looked at several potential factors that could theoretically boost the rate of fibrosis re-development after surgery: the amount of injury to the transplanted liver; the amount of inflammation in the organ; whether the new organ had steatosis or not; the age of the donor; and gender mismatch, a situation in which men receive livers from women, and vice-versa, that has been found in some cases to increase the risk of organ rejection.4

When looking specifically at donor age, the information was divided into three groups: those older than 50 years of age, those between 30 and 50 years old, and those younger than age 30.

Only Donor Age Had a Direct ImpactIn the end, the study team determined that gender mismatch, steatosis, and the condition of the transplanted liver had no effect on how quickly or slowly fibrosis re-developed after surgery. But they did find significant differences in the rate of fibrosis progression that were directly related to the age of the donor. In cases in which the donor was older than 50, rapid fibrosis re-development occurred nearly half the time. By comparison, mild or moderate fibrosis re-developed in only about one-third of older donor livers, they said.

"Previous studies have shown that older donor age has a significant negative impact on [organ] and patient survival in patients with HCV undergoing liver transplantation," Fiel explained. "Fibrosis appears to be accelerated in older livers initially acquiring HCV when compared to younger donor livers, a conclusion supported by our data."

Why is Age a Factor?What's the reason? Simple aging. Fiel theorizes that livers from older donors age like the rest of the body, meaning their function has deteriorated compared to that of livers taken from younger donors. "I think the liver also incurs damage over the years," she said, due to the accumulation of free radicals, harmful molecules in the body that cause damage to cells.

She says patients who receive livers from older donors and in whom hepatitis C cannot be destroyed following surgery "may be an ideal population for early trials of several antifibrotic medications that are currently under development."

Theoretically, these medications could be prescribed in conjunction with standard hepatitis treatment that includes interferon and the antiviral drug, ribavirin, said Fiel, for patients who initially failed HCV therapy. The goal would be to maintain liver function as best as possible, and to prevent fibrosis from advancing to a stage in which the patient would need yet another liver transplant.

One drawback to the study, Fiel pointed out, is the fact that the researchers were unable to obtain information on which transplant patients were prescribed interferon for their hepatitis, and whether or not immune suppression after surgery had any impact on the rate of fibrosis re-development.

Filling in the Information GapsBut there are theories as to how to prevent such rapid fibrosis progression postoperatively. One way might be targeting "marginal" donor livers for transplant procedures in which the recipient has a liver disease other than hepatitis, such as alcoholic liver disease (ALD) or primary biliary cirrhosis. "These kinds of liver diseases do not necessarily recur as fast as hepatitis C," Fiel said. "Perhaps this may have some use in the future."

Meanwhile, the researchers are making plans to initiate a more detailed study of fibrosis progression after liver transplantation. "We don't have a complete data set on these patients," Fiel pointed out, adding that it may be possible that she and her team may launch "a more consistent study" soon.

1. GL. Chronic hepatitis C and liver transplantation. Rev Gastroenterol Disor 2004 Winter;4(1):7-17.2. Blank A, Schiano T, Guierrez JA, Gan D, Thung SN, Fiel MI. The influence of donor age, gender mismatch and harvesting injury on fibrosis progression rate in recurrent hepatitis C (HCV) post-liver transplantation. 55th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD). 2004 Oct 29-Nov 2. Boston, MA.3. de M, Poynard T. Risk factors for liver fibrosis progression in patients with chronic hepatitis C. Ann Hepatol 2003 Jan-Mar;2(1):5-11.4. BK, Levy MF, Jennings LW et al. Influence of donor and recipient gender on the outcome of liver transplantation. Transplantation 1996 Dec 27;62(12):1784-7.

[Guest guest]

"The researchers looked at several potential factors that could theoretically boost the rate of fibrosis re-development after surgery: the amount of injury to the transplanted liver; the amount of inflammation in the organ; whether the new organ had steatosis or not; the age of the donor; and gender mismatch, a situation in which men receive livers from women, and vice-versa, that has been found in some cases to increase the risk of organ rejection.4"

A lot more attention research and studies are being conducted in reference to the gender mismatch and possible complications after transplant.

Deb

[Guest guest]

"The researchers looked at several potential factors that could theoretically boost the rate of fibrosis re-development after surgery: the amount of injury to the transplanted liver; the amount of inflammation in the organ; whether the new organ had steatosis or not; the age of the donor; and gender mismatch, a situation in which men receive livers from women, and vice-versa, that has been found in some cases to increase the risk of organ rejection.4"

A lot more attention research and studies are being conducted in reference to the gender mismatch and possible complications after transplant.

Deb

[Guest guest]

Egad, I hope I have a chance to enjoy my pretty new, pink liver for a while...Bummmer.Hey Deb, I got this in my mail box, I am so glad I send up for this news letter also ALF>>>.Kathy B.Deb <posttransplant@...> wrote:

"The researchers looked at several potential factors that could theoretically boost the rate of fibrosis re-development after surgery: the amount of injury to the transplanted liver; the amount of inflammation in the organ; whether the new organ had steatosis or not; the age of the donor; and gender mismatch, a situation in which men receive livers from women, and vice-versa, that has been found in some cases to increase the risk of organ rejection.4"

A lot more attention research and studies are being conducted in reference to the gender mismatch and possible complications after transplant.

Deb

Kathy Brunow

[Guest guest]

Egad, I hope I have a chance to enjoy my pretty new, pink liver for a while...Bummmer.Hey Deb, I got this in my mail box, I am so glad I send up for this news letter also ALF>>>.Kathy B.Deb <posttransplant@...> wrote:

"The researchers looked at several potential factors that could theoretically boost the rate of fibrosis re-development after surgery: the amount of injury to the transplanted liver; the amount of inflammation in the organ; whether the new organ had steatosis or not; the age of the donor; and gender mismatch, a situation in which men receive livers from women, and vice-versa, that has been found in some cases to increase the risk of organ rejection.4"

A lot more attention research and studies are being conducted in reference to the gender mismatch and possible complications after transplant.

Deb

Kathy Brunow