Gene Linked to Liver Disease in Cystic Fibrosis

Screening for the variation could help identify risk factors early on, researchers say

Posted September 8, 2009

TUESDAY, Sept. 8 (HealthDay News) -- A variant of a particular gene in people with cystic fibrosis greatly increases their chances of developing severe liver disease, new research shows.

Cystic fibrosis is an inherited disorder that can lead to deadly lung infections and digestive problems.

About 3 percent to 5 percent of the 30,000 people in the United States with the condition will also develop a serious form of liver disease, including cirrhosis and portal hypertension, or high blood pressure caused by obstruction in the liver, according to the Cystic Fibrosis Foundation.

Researchers from University of North Carolina at Chapel Hill analyzed nine variants in five genes previously implicated in cystic fibrosis liver disease. The study included 124 patients with cystic fibrosis liver disease and 843 patients without liver disease. A second study looked at a different group of 136 patients with cystic fibrosis liver disease and 1,088 without liver disease.

The researchers found that people who had the "SERPINA1 Z allele," or gene variation, had a five times greater chance of developing liver disease. The other variants did not increase the risk of liver disease.

About 2.2 percent of people with cystic fibrosis carry the SERPINA1 Z allele, according to the study published in the Sept. 9 issue of the Journal of the American Medical Association

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Screening for the gene variation could help identify those at risk of developing the liver disease, the researchers wrote.

"The identification of the SERPINA1 Z allele as the first marker for the development of severe liver disease in CF [cystic fibrosis] illustrates the possibility of identifying CF risk factors early in life, conceptually as a secondary component of neonatal screening after the diagnosis of CF is confirmed," researchers wrote.

Hepatobiliary Abnormalities and Disease in Cystic Fibrosis: Epidemiology and Outcomes Through Adulthood.

J Clin Gastroenterol. 2009 Jun 11. [Epub ahead of print]

Hepatobiliary Abnormalities and Disease in Cystic Fibrosis: Epidemiology and Outcomes Through Adulthood.

Bhardwaj S, Canlas K, Kahi C, Temkit M, Molleston J, Ober M, Howenstine M, Kwo PY.

*Division of Gastroenterology/Hepatology, Departments of Medicine daggerBiostatistics double daggerDivision of Pediatric Gastroenterology section signDivision of Pulmonary Medicine and Critical Care parallelDivision of Pediatric Pulmonary Medicine, Indiana University Medical Center, Indianapolis, Indiana.

OBJECTIVES: There is limited data regarding the prevalence of hepatobiliary disease in North American patients with cystic fibrosis (CF) through adulthood. Our aim was to determine the prevalence of, and risk factors for, CF-related hepatobiliary abnormalities and determine factors that predict the development of CF-related hepatobiliary disease.

METHODS: We performed a retrospective cohort study of all CF patients who presented to a UnitedStates tertiary care referral academic center over a 32-year period. "CF-related hepatobiliary abnormality" was defined as the presence of abnormal liver chemistries on one or more occasion and "CF-related hepatobiliary disease" was defined as biochemical, physical examination, or ultrasonographic abnormalities on at least 2 consecutive examinations spanning a 1-year period.

RESULTS: Two-hundred eighty-three CF patients who presented between the years 1970 and 2002 were identified, with an age range of 2 months to 63 years. Sixty-five percent had CF-related hepatobiliary abnormalities with a higher prevalence seen in CF patients <18 years of age (84% vs. 16%, P<0.01). Fifteen percent of our cohort had CF-related hepatobiliary disease with 93% of cases occurring in individuals before age 18. One quarter of individuals with CF-related hepatobiliary abnormalities developed hepatobiliary disease.

CONCLUSIONS: Abnormal liver chemistries in CF are common though most of CF patients lack clinical evidence of liver disease and the severe complications of fibrosis/cirrhosis are rare. The risk of liver involvement decreases significantly with age, falling by 10% per annum for those described as having CF-related hepatobiliary disease. CF-related hepatobiliary disease is a rare occurrence after age 18.

PMID: 19525864 [PubMed - as supplied by publisher]

Hepatobiliary disease in patients with cystic fibrosis.

http://www.ncbi.nlm.nih.gov/pubmed/19381084?dopt=Abstract


I don't have access to the full study (it costs money) but I'll do my best to find more info.

Ask your doc if he/she subscribes or has access to Curr Opin Gastroenterol. Or call Cincinnati - I'm sure they'd be happy to help out