Liver Disease in Cystic Fibrosis

Abstract

Liver involvement in Cystic Fibrosis (CF) is much less frequent than both pulmonary and pancreatic diseases that are present in 80-90% of CF patients; liver disease (LD) affects only one third of CF patients, however, because of the decreasing mortality from extrahepatic causes, its recognition and management is becoming a relevant clinical issue. Recent observations suggest that clinical expression of LD in CF may be influenced by genetic modifiers; their identification is an important issue because it may allow recognition of patients at risk for the development of LD at the time of diagnosis of CF and early institution of prophylactic strategies. Oral bile acid therapy, aimed at improving biliary secretion in terms of bile viscosity and bile acid composition, is currently the only available therapeutic approach for CF-associated LD. However, the impact of this therapy on the natural history of LD remains to be defined and long-term effectiveness on clinically relevant outcomes should be further investigated. Liver transplantation should be offered to CF patients with progressive liver failure and/or with life-threatening sequelae of portal hypertension, who also have mild pulmonary involvement that is expected to support long-term survival. The 1-year survival rate after transplantation in CF patients is approximately 80%, with beneficial effects on lung function, nutritional status, body composition and quality of life in most cases.

Cystic Fibrosis Liver Disease

“…Other studies have also found increasing prevalence with age through childhood to midadolescence with no significant increase thereafter (Colombo, 2007).…”

“…There is a broad spectrum of hepatic manifestations in cystic fibrosis as described in Table 1 (Colombo, 2007). Of those described the most clinically relevant in CF is focal biliary cirrhosis which may extend into multilobular biliary cirrhosis.…”

“…Modifier genes have shown to play a role by increasing susceptibility to the development of CFLD by up-regulating inflammation, fibrosis or oxidative stress. Identifying these genetic modifiers may allow identification of CF patients at risk of developing CFLD and thus allow early use of prophylactic measures (Colombo, 2007). ACE, SERPINA, CSTP1, MBL2, TGF-1 have all been identified as potential gene modifiers but only the SERPINA 1 Z allele has been found to be strongly associated with CFLD and portal hypertension (Bartlett et al, 2009).…”

“…This favours well when compared to the general cirrhotic population where 1 year survival is only 34%. Hence in the absence of other markers of decompensated liver disease, bleeding may not necessarily be a marker of poor prognosis (Colombo, 2007).…”

Liver Disease in Cystic Fibrosis - Presentation in Early Childhood: Report of Two Cases

“…The main factors involved in the pathogenesis of the liver disease are severe genotypes, nutritional status, malabsorption syndrome, antioxidants deficiency, additional hepatic lesion by a hepatotropic virus, sclerosing cholangitis, autoimmune hepatitis, parenteral nutrition, druginduced liver toxicity, surgery and the presence of modifying genes. (6) The new medications and better comprehension of Cystic Fibrosis increased survival of the patients and the occurrence of other complications such as hepatobiliary manifestations, which became more frequent. (4) The liver disease affects one third of the patients (7) and it is the third cause of death in cystic fibrosis (8) despite the lack of association with severity of the pulmonary disease.…”