Cystic fibrosis related chronic liver disease: a study of its influence upon prognosis and possible mechanisms for this; with specific reference to pulmonary and systemic haemodynamics

MDTo assess the influence of chronic liver disease on survival a time dependent multivariate Cox regression analysis was It performed. The results confirmed that patients with evidence of chronic liver disease have a worse prognosis. The effect of liver disease upon survival was not related to hepatic decompensation, as only 2.2% of deaths were liver-related, suggesting an occult adverse effect. To establish a non-invasive means for the diagnosis of chronic liver disease an ultrasound scoring system was developed, and validated for reproducibility by two independent radiologists. This scoring system correlated well with the capacity of the liver to metabolise lignocaine to monoethylglycine xylidide, with fasting serum bile acids and with the PGA index. While the measurement of the N-terminal propeptide of procollagen III revealed significant differences between subjects with and without liver disease, the results correlated less well with the ultrasound score. Abnormalities documented by quantitative hepatobiliary scintigraphy also correlated well with the ultrasound based scoring system. Having established suitable criteria for diagnosing chronic liver disease in cystic fibrosis the systemic and pulmonary 2 circulations of patients with and without liver disease were evaluated non-invasively. The results confirm the presence of a hyperdynamic circulatory state in patients with chronic liver disease with significant elevations of cardiac output and left ventricular stroke work index and reductions of mean arterial pressure and systemic vascular resistance index. There were no differences in the peripheral circulatory status of the two cohorts. Evaluation of the pulmonary circulation was made using shuntperfusion scans and the 100% oxygen re-breathing technique. Significant pulmonary arterio-venous shunting, consistent with a diagnosis of the 'hepato-pulmonary' syndrome, was only detected in the cohort with liver disease (36% of those studied). The results of studies presented within this thesis suggest that chronic liver disease can be confidently detected using ultrasound criteria, is important in the prognosis of patients with cystic fibrosis due to its covert adverse effect on survival, and may exert some of these effects through systemic and pulmonary circulatory changes