Clinical

IV fish oil helps avoid liver transplant in cirrhotic infants on parenteral nutrition

Last Updated: 2013-02-13 17:00:44 -0400 (Reuters Health)

By Fran Lowry

NEW YORK (Reuters Health) - In infants with liver disease from parenteral nutrition, IV fish oil can normalize bilirubin levels, and a new follow-up study shows that these babies won't need liver transplants, researchers said in Phoenix, Arizona at Clinical Nutrition Week 2013.

Moreover, they can be expected to maintain normal liver function and experience growth, senior author Dr. Mark Puder from Boston Children's Hospital told Reuters Health.

"This is true even in children who remain dependent on intravenous nutrition and regardless of liver biopsy results," Dr. Puder said.

Parenteral nutrition can be life saving for infants and children with intestinal diseases that prevent them from taking nutrition orally. Unfortunately, many children who require long-term IV nutrition develop severe progressive liver disease.

Dr. Puder and his team had previously reported on a new treatment for that liver disease, in which the fat source was switched from soybean oil to fish oil. After they did this, serum lipid profiles improved. Also, jaundice resolved in nearly three quarters of cases, even though some of the children already had cirrhosis when the new treatment was started.

"The impact of this cirrhosis on the children in the long-term is currently unknown. Many of these children have since returned to their home institution where, despite having normal liver function, they have been listed for liver transplantation due to concerns about their cirrhosis," Dr. Puder said.

"In this study, we wanted to investigate the impact of cirrhosis after resolution of jaundice in these children and determine if their disease progresses," he said.

At the meeting this week, he and his colleagues reported on 48 children with parenteral nutrition-associated liver disease (PNALD) and documented cirrhosis who were treated with an IV fish oil-based lipid emulsion from 2005 to 2012.

PNALD was defined as the presence of at least two conjugated bilirubin levels >2 mg/dL one week apart, and cirrhosis was confirmed on biopsy or reversal of portal flow on abdominal ultrasound.

Thirty-four children (71%) showed biochemical reversal of cholestasis, defined as normalization of conjugated bilirubin levels to below 2 mg/dL. Their mean gestational age was 29.4 weeks, their mean age at initiation of fish oil lipid emulsion monotherapy was 148.8 days, and the time to reversal was 88.2 days.

Not only did these babies with normalized bilirubin not need a transplant, but they also had stable normal lab values and evidence of normal growth, Dr. Puder said. Two patients with reversed cholestasis died from non-PNALD associated causes, however.

Of the 14 patients who did not have reversal of cholestasis, seven died and seven progressed towards transplantation.

Speaking of the responders, Dr. Puder said, "In fact, once their bilirubin normalized, their liver function remained normal and they even experienced improvement in growth."

Why fish oil emulsion helps save these children from having to undergo liver transplantation is not entirely clear, Dr. Puder said.

"We still have much to learn about chronic liver disease in children, especially when associated with intravenous nutrition. We don't know if the damage is reversible. We know fish oil is less harmful to the liver than soybean oil, based on animal and clinical studies," he said.

"There is no consensus on the mechanisms by which fish oil may protect the liver," Dr. Puder continued. "Research suggests that the absence of harmful plant byproducts called phytosterols and the presence of anti-inflammatory and anti-oxidant mediators found in fish oil may play important roles in the treatment of this disease. If we can keep the cirrhosis from progressing, liver transplantation will not be necessary."

Reflex recommendations for transplant evaluations for these patients based on biopsy results alone should be avoided, he added.

"If the patient was treated with fish oil lipid emulsion and achieved normalization of their bilirubin, our data suggest that their liver disease may not progress to the need for liver transplantation. As long as the children require no medical treatment for cirrhosis, maintain normal lab values, and continue to grow, transplantation should be avoided," Dr. Puder said.

Dr. Daniel Teitelbaum, who directs the intestinal failure program at the University of Michigan in Ann Arbor, commented on this study for Reuters Health.

"This is a very important study because infants and children who have parenteral nutrition associated liver disease are at high risk for dying and this fish oil therapy may be very important," he said.

At the present time, however, this fish oil is not approved by the U.S. Food and Drug Administration, and neither are other lipids that might be beneficial to these children, Dr. Teitelbaum noted.

He added, "The fish emulsion can be used only with FDA approval by a particular patient or hospital. It's expensive for a hospital because some insurance companies won't pay for it. The challenge will be to try to bring newer lipids into the United States. This study shows that fish oil is an option and something that we should readily have available as opposed to having hospitals, patients and physicians go through hoops to try to get it."