Reuters Health Information (2011-11-09): Early liver transplantation cuts deaths from severe alcoholic hepatitis
Early liver transplantation cuts deaths from severe alcoholic hepatitis
Last Updated: 2011-11-09 18:41:03 -0400 (Reuters Health)
NEW YORK (Reuters Health) - Early liver transplantation improves survival when alcoholic hepatitis isn't responding to medical therapy, according to a French study released online today in The New England Journal of Medicine.
The report raises new questions about the common practice of setting a six-month abstinence requirement before patients with alcoholic hepatitis can be listed for transplant.
Many patients don't have that much time. About 40% of patients with alcoholic hepatitis don't respond to conventional treatment, and their six-month survival rate is about 30%.
"Your survival rate is three times higher" with a transplant than if you are forced to wait, lead author Dr. Philippe Mathurin of Claude Huriez Hospital in Lille, France, told Reuters Health in a telephone interview.
He and his colleagues note there's no set waiting period for people whose transplant is due to voluntary acetaminophen overdose or hepatitis B related to drug abuse, or other personal choices. It only applies to liver transplants for alcoholic hepatitis, and most doctors now regard alcoholism as a disease.
"It will certainly ignite some debate within the transplant community because there's strong feelings about transplantation for acute alcoholic hepatitis," said Dr. Charles Rosen of the Mayo Clinic in Rochester, Minnesota, who was not connected with the new study.
In the study by Dr. Mathurin's team, all the volunteers needed to promise never to drink alcohol again, and they had to go through a rigorous screening process. Among the medical criteria were nonresponse to medical therapy, severe alcoholic hepatitis as the first liver-decompensating event, and absence of severe coexisting or psychiatric disorders.
In addition, "Only people whose family wanted to support the patient, who deeply wanted the patient to recover from this disease, were considered for this program," said Dr. Mathurin.
Ultimately the study group consisted of 26 patients, who represented less than 2% of patients admitted for an episode of severe alcoholic hepatitis.
The decision to list subjects for transplantation was made at a median of 13 days after nonresponse to medical treatment was confirmed. The median Model for End-Stage Liver Disease (MELD) score at listing was 34; the MELD score range is 6 (less ill) to 40 (gravely ill).
The cumulative six-month survival rate for the 26 patients who received an early transplant was 77%, compared with 23% for 69 matched controls who also had not responded to medical therapy (p<0.001). Ninety percent of deaths in the control group occurred within two months after those patients stopped responding.
After two years of follow-up, the survival rate was 71% with a new liver and 23% without (p<0.001).
On multivariate analyses adjusted for transplant center and MELD score, patients were six times more likely to be alive at two years if they received a new liver.
Dr. Robert Brown of Columbia University in New York, in a Journal editorial, characterized the transplant results as "excellent."
Dr. Brown said it was noteworthy that "the rate of recidivism to alcohol use was low, with only three of 26 patients resuming drinking alcohol; of these three, none had graft dysfunction."
According to Dr. Rosen, "in the literature (the recidivism rate) is 20 to 30% within a couple of years after transplantation," whereas it was 12% in this study.
He added, "Perhaps they selected these patients better than other programs that are treating patients with chronic alcohol-related liver disease."
Dr. Brown, in his editorial, said the argument that alcoholics are less deserving of new livers because theirs is a self-inflicted disease "is not a valid one. When one looks at the causes of liver disease, much of it could be perceived as self-inflicted, such as prior drug use resulting in viral hepatitis or obesity leading to nonalcoholic fatty liver disease. Alcoholism is a disease, and it should not be used to exclude patients from transplantation."
"We will change this rule, but we have to make it step by step," said Dr. Mathurin. "You don't want to lose those grafts."
Another paper in the same issue of the Journal concludes that the combination of corticoids with N-acetylcysteine does not improve survival in acute alcoholic hepatitis.
That study, also done in France, found that, after six months, 27% of the 85 volunteers getting prednisolone plus N-acetylcysteine had died versus 38% of the 89 given prednisolone alone (p=0.07).
The only significant difference in survival was seen one month after treatment, with mortality rates of 8% for the combination compared to 24% with prednisolone alone (p=0.006). But at the three-month mark, the difference had become insignificance.
"These findings may be related to a lack of power," said the research team, led by Eric Nguyen-Khac of Amiens University Hospital, France. "It is also possible that 5 days of N-acetylcysteine was not enough. A longer period of intravenous N-acetylcysteine combined with prednisolone could perhaps be considered, with subsequent oral administration of N-acetylcysteine until 1 month."
SOURCES: http://bit.ly/v60LLY and http://bit.ly/rqqHmY
N Engl J Med 2011.