Nav: Home

Scientists identify genes associated with biliary atresia survival

June 19, 2019

CINCINNATI -- Scientists at Cincinnati Children's Hospital Medical Center have identified an expression pattern of 14 genes at the time of diagnosis that predicts two year, transplant-free survival in children with biliary atresia - the most common diagnosis leading to liver transplants in children.

The researchers also found that the antioxidant N-acetyl-cysteine (NAC) reduced liver injury and fibrosis (excess fibrous connective tissue) in mice with biliary atresia and increased survival times.

Biliary atresia is a rare disease of the liver and bile ducts that occurs in infants. Symptoms of the disease appear or develop about two to eight weeks after birth. When a baby has biliary atresia, bile flow from the liver to the gallbladder is blocked. This causes the bile to be trapped inside the liver, eventually causing liver failure.

"The relationship between a 14-gene signature at diagnosis and two-year survival provides insight into staging of liver disease and the development of new therapies," says Jorge Bezerra, MD, director of Gastroenterology, Hepatology and Nutrition at Cincinnati Children's. "A particularly appealing possibility is the design of a clinical trial designed to activate the glutathione pathway - a molecule highly expressed in infants with biliary atresia. The activation of the pathway by the antioxidant NAC has the potential to improve bile flow and block fibrosis development."

The study is published online in the journal Gastroenterology.

The researchers obtained liver biopsies and clinical data from infants with cholestasis - a reduction or stoppage of bile flow. The infants were enrolled in a prospective study of the Childhood Liver Disease Research Network, funded by the National Institutes of Health, and from infants evaluated at Cincinnati Children's. Liver biopsies were obtained at the time of diagnosis of biliary atresia. They performed RNA sequencing and developed a prognostic index.

The scientists administered NAC to neonatal mice with biliary atresia and fibrosis, which decreased bilirubin and liver fibrosis. Bilirubin is an orange-yellow substance made during the normal breakdown of red blood cells. Bilirubin passes through the liver and is eventually excreted out of the body. Higher levels, however, can indicate liver problems.

"We don't yet know if NAC is safe and effective in young babies with biliary atresia. Future clinical trials are needed before use in clinical practice," says Dr. Bezerra.
-end-
The study was supported by grants from the National Institutes of Health (DK-64008, DK-83781) and by the Gene Analysis Cores of the Digestive Health Center (DK-78392). The work also was supported by U01 and UL1 grants from the National Institute of Diabetes, Digestive and Kidney Diseases.

Cincinnati Children's Hospital Medical Center

Related Liver Disease Articles:

Fatty liver disease is underdiagnosed in the US
According to an analysis published in Alimentary Pharmacology & Therapeutics, nonalcoholic fatty liver disease (NAFLD) is grossly underdiagnosed in the United States.
Possible new treatment strategy for fatty liver disease
Researchers at Karolinska Institutet in Sweden have identified a molecular pathway that when silenced could restore the normal function of immune cells in people with fatty liver disease.
Longevity protein SIRT6 also protects against fatty liver and fatty liver disease
SIRT6 regulates fat metabolism by activating another protein called peroxisome proliferator-activated receptor alpha (PPAR-alpha).
Fresh insights could lead to new treatments for liver disease
The fight against liver disease could be helped by the discovery of cells that cause liver scarring.
Better methods needed for predicting risk of liver disease
While blood samples can reliably identify people with a low risk of developing severe liver disease, better methods are needed in primary care for identifying people in most need of care.
Lab-on-a-chip may help identify new treatments for liver disease
Investigators have developed a 'lab on a chip' technology that can simulate different levels of non-alcoholic fatty liver disease progression.
Novel discovery of links between liver dysfunction and Alzheimer's disease
New research from the Alzheimer's Disease Metabolomics Consortium (ADMC) and Alzheimer's Disease Neuroimaging Initiative (ADNI) has uncovered novel connections between liver dysfunction and Alzheimer's disease (AD), paving a new path toward a systems level view of Alzheimer's relevant for early detection and ultimately for prevention.
It's in the weeds: Herbicide linked to human liver disease
Exposure to glyphosate, the primary ingredient in the popular weed killer Roundup, correlates to more severe cases of nonalcoholic fatty liver disease.
How common is alcoholic fatty liver disease?
This study used national survey data from 2001-2016 to examine how common alcoholic fatty liver disease is in the United States.
New insights into how fatty liver disease progresses to cancer
The buildup of fat in the liver known as fatty liver disease sometimes leads to hard-to-treat liver cancer.
More Liver Disease News and Liver Disease Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Listen Again: Meditations on Loneliness
Original broadcast date: April 24, 2020. We're a social species now living in isolation. But loneliness was a problem well before this era of social distancing. This hour, TED speakers explore how we can live and make peace with loneliness. Guests on the show include author and illustrator Jonny Sun, psychologist Susan Pinker, architect Grace Kim, and writer Suleika Jaouad.
Now Playing: Science for the People

#565 The Great Wide Indoors
We're all spending a bit more time indoors this summer than we probably figured. But did you ever stop to think about why the places we live and work as designed the way they are? And how they could be designed better? We're talking with Emily Anthes about her new book "The Great Indoors: The Surprising Science of how Buildings Shape our Behavior, Health and Happiness".
Now Playing: Radiolab

The Third. A TED Talk.
Jad gives a TED talk about his life as a journalist and how Radiolab has evolved over the years. Here's how TED described it:How do you end a story? Host of Radiolab Jad Abumrad tells how his search for an answer led him home to the mountains of Tennessee, where he met an unexpected teacher: Dolly Parton.Jad Nicholas Abumrad is a Lebanese-American radio host, composer and producer. He is the founder of the syndicated public radio program Radiolab, which is broadcast on over 600 radio stations nationwide and is downloaded more than 120 million times a year as a podcast. He also created More Perfect, a podcast that tells the stories behind the Supreme Court's most famous decisions. And most recently, Dolly Parton's America, a nine-episode podcast exploring the life and times of the iconic country music star. Abumrad has received three Peabody Awards and was named a MacArthur Fellow in 2011.