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Prevalence of liver disease in cystic fibrosis ‘slowly increasing’ in UK

The burden of cystic fibrosis-associated liver disease in the United Kingdom increased from 2008 to 2013, with new estimates showing a rising prevalence and higher mortality than patients with cystic fibrosis and no liver disease.

The overall prevalence of cystic fibrosis-associated liver disease rose from 203.4 per 1,000 patients in 2008 to 228.3 per 1,000 patients in 2013, according to data from a new longitudinal, population-based cohort study recently published in PLOS ONE.

“We have demonstrated that cystic fibrosis-associated liver disease prevalence in the U.K. is slowly increasing and is associated with higher mortality compared to cystic fibrosis patients without liver disease,” researchers wrote in the study.

Using 2008-2013 data from the U.K. Cystic Fibrosis Registry, the researchers identified 3,417 patients with cystic fibrosis-associated liver disease. The mean age of the patients was 21 years and 59% were men. Ninety percent of patients had noncirrhotic liver disease. About half had portal hypertension.

The overall incidence rate of liver disease was 63.5 per 1,000 patients with cystic fibrosis, which the researchers noted is “significantly higher than previous estimates.” The annual incidence of cirrhosis in this population increased from 12.2 per 1,000 patients with cystic fibrosis-associated liver disease in 2009 to 16 cases per 1,000 patients in 2013.

When the researchers looked at the annual prevalence of cirrhosis during the study period, they observed a decrease from 157.6 cases per 1,000 patients with cystic fibrosis-associated liver disease in 2008 to 137.9 per 1,000 patients in 2013. The median age at cirrhosis diagnosis was 19 years, ranging from 5 to 53 years.

Overall, 200 patients with cystic fibrosis-associated liver disease died from 2008 to 2013. The rate of mortality in patients with cystic fibrosis-associated liver disease was more than double the rate in patients without liver disease: 19.3 deaths per 1,000 patients vs. 7.6 deaths per 1,000 patients. Survival was significantly shorter among patients with cirrhosis compared with no cirrhosis (HR = 1.54; 95% CI, 1.09-2.18). The majority of deaths occurred in adults.

Independent risk factors for cirrhosis in adults included male sex, cystic fibrosis-related diabetes and chronic Pseudomonas aeruginosa infection. In children, older age (9-16 years), cystic fibrosis-related diabetes and chronic P. aeruginosa infection were associated with the presence of cirrhosis in cystic fibrosis-associated liver disease, according to the results.

In other results, patients treated with ursodeoxycholic acid had an improved rate of survival, especially patients without cirrhosis. Although the effect of ursodeoxycholic acid was modest, the researchers noted that “such an observation from this large data set warrants further investigation.” Use of this treatment option for the management of cystic fibrosis-associated liver disease “has long been an area of debate,” according to the researchers.

“Our data suggest that progression to cirrhosis remains an ongoing issue in a significant proportion of [cystic fibrosis-associated liver disease] patients, even into adulthood. This contradicts observations from previous longitudinal studies in which clinically relevant [cystic fibrosis-associated liver disease] primarily develops before puberty,” the researchers wrote.

Moreover, “‘Adult-onset’ disease may represent a distinct, less-severe form of [cystic fibrosis-associated liver disease]. ... The ongoing incidence of cirrhosis into adulthood may reflect the impact of other risk factors for liver disease. Such ‘adult-onset’ cirrhosis may commence with fatty change and steatohepatitis through parallel mechanisms with the rest of the adult U.K. population,” the researchers wrote. – by Katie Kalvaitis

Disclosures: One author reports consulting for Chiesi, Gilead, Pulmocide, Roche, Teva and Vertex. Please see the study for all other authors’ relevant financial disclosures.