**11.** *Pseudomonas aeruginosa*

biochemical derangements in liver enzymes. Structural disease develops next and manifests as fatty infiltration on ultrasound scan or increased bile content in liver parenchyma. Decom‐ pensated liver disease occurs last, which can involve portal hypertension, ascites, variceal disease, and impaired coagulation. These disease processes occur as a consequence of altered viscous bile due to abnormal CFTR-regulated ion transport across cholangiocytes. Conse‐ quently, biliary flow is reduced and there is obstruction of intrahepatic bile ducts. This causes damage to hepatocytes and cholangiocytes through inflammatory processes, bile duct proliferation, and portal tract fibrosis. The pathogenesis of fatty liver disease in CF is less well understood and has been loosely attributed to fatty acid deficiency, malnutrition, and insulin

Attempts have been made to link the development of CFLD with the presence of certain underlying CFTR mutations, the assumption being that CFLD would be seen with increasing frequency in patients with the classically severe or high-risk phenotypes as described above. However, this relationship has not been demonstrated to date. Non-CFTR modifier genes have been proposed to increase susceptibility to development of CFLD and it is thought that identifying these genetic modifiers may allow early identification of patients at risk. To date only polymorphisms in the SERPINA1 allele, which codes for an alpha-1 antitrypsin, has been

Liver disease is widely cited as the third most common cause of death in CF patients after respiratory failure and transplant complications, with a mortality rate estimated at 2.5% [30] and a higher mortality risk is observed in those with liver disease than in those without [40]. However, there continues to be massive variability in the severity of CFLD without adequate explanation as to why it affects only certain patients, thus it is a complex prognostic index.

Whilst recognising the importance of tailoring care of patients with CF to the individual genotypes and associated co-morbidities is essential, many of these factors are established and

The prognostic value of more dynamic markers of clinical condition offer more practical longterm targets around which to focus treatment and goals in the individual patient. On a day to day basis, these parameters guide practice and stratify patients in terms of expected outcomes.

Spirometric measurement of lung function, specifically FEV1, has been the pre-eminent surrogate marker of disease staging in CF for a long time. As it is reproducible, readily available, and cheap, it provides longitudinal measurement of airflow obstruction over years.

demonstrated to be significantly related to CFLD and portal hypertension [41].

**8. Clinical measurements of disease severity and how they predict**

in many ways less dynamically modifiable than others in clinical practice.

**9. Pulmonary function and how it predicts prognosis**

resistance [40].

10 Cystic Fibrosis in the Light of New Research

**prognosis**

The most prominent pathogen with a specific affinity for the CF lung is *Pseudomonas Aerugi‐ nosa* (PA). Though its prevalence in CF populations varies with age [51], it is the most common airway pathogen in adult CF patients. PA colonisation predicts lower FEV1 at the time of culture [52, 53] and greater rate of decline in pulmonary function over time [54-56] when compared with Methicillin Sensitive *Staphylococcus Aureus* colonised (MSSA) and noncolonised patients. Moreover, evidence suggests that patients in whom PA colonisation is eradicated in a systematic manner have a significant reduction in treatment burden and days spent in hospital. This, in turn, can result in reduced expense on treatment of exacerbations [57].
