engleski

Liver disease in pediatric patients treated at the Cystic Fibrosis Centre of the University Hospital Centre Zagreb

Objective To describe the characteristics of patients with cystic fibrosis-associated liver disease (CFLD), a complication of cystic fibrosis (CF) that is often asymptomatic until an advanced stage. Methods Retrospective analysis included patients aged 0-20 years followed in 2018. at the Cystic Fibrosis Centre of the University Hospital Centre Zagreb. CFLD1 was diagnosed if ≥2 of the following were present: hepatomegaly and/or splenomegaly, elevated transaminases or gamma- glutamyl transferase (GGT) 3 times during 12 months, ultrasound signs of liver involvement or portal hypertension (PTH), suggestive pathohistological findings. Severe CFLD was defined as a disease with signs of PTH. Results 61 patients with a mean age of 10.9 years (9 months- 19 years, male: female = 34:27) were included. 9/61 (14.8%) of them had CFLD, 6 girls and 3 boys, aged 2-19 years (average age 10.7 years). They all had at least one F508del mutation, and 7/9 were homozygous. Regarding the severity of the disease, 4 patients (3 boys and 1 girl, 6-19 years) had a severe form of CFLD with PTH and presumed cirrhosis, which was confirmed by liver biopsy in one patient. Two patients also had impaired synthetic liver function, two had hypersplenism with platelet count <80x109/L, and one had esophageal varices without bleeding. The remaining 5/9 patients had mild CFLD with ultrasound changes (hyperechoic or nodular liver parenchyma, periportal fibrosis) and/or elevated liver enzymes. We observed a trend of poor nutritional status in patients with severe CFLD (mean BMI z- value -0.66, range -0.26 to 0.62) compared to those with mild form of CFLD (mean BMI z-value -0.41, range – 2.76 to 1.49), but the difference wasn’t significant, and the most severely malnourished patient had mild CFLD. We also assessed some noninvasive biomarkers of fibrosis: the APRI index was elevated (≥0.5) in all patients with severe CFLD and in one with mild CFLD, and Fibrosis-4 score was pathological in only one patient with PTH. Elastography was performed in 5 patients: it was normal in one patient with mild CFLD, whereas in four increased liver stiffness was found (significantly increased in two patients with severe CFLD, and mildly in two patients with mild CFLD). 4/9 patients with CFLD had meconium ileus, which is approximately twice the frequency compared to all included CF patients. Conclusion The diversity of clinical expression and findings in our patients is consistent with the literature data on the spectrum of CFLD manifestations. We confirmed a higher incidence of meconium ileus and severe mutations, and male dominance in CFLD with PTH. In all CF patients, liver disease should be actively sought from an early age (clinical examination once a year + abdominal ultrasound + AST, ALT, GGT).

cystic fibrosis ; children ; liver disorder

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