Cystic fibrosis associated liver disease in children

Cystic fibrosis(CF)is an autosomal recessive disorder caused by mutations in the CF transmembrane conductance regulator gene.CF liver disease develops in 5%-10%of patients with CF and is the third leading cause of death among patients with CF after pulmonary disease or lung transplant complications.We review the pathogenesis,clinical presentations,complications,diagnostic evaluation,effect of medical therapies especially CF transmembrane conductance regulator modulators and liver transplantation in CF associated liver disease.

Cystic fibrosis patients on cystic fibrosis transmembrane conductance regulator modulators have a reduced incidence of cirrhosis

BACKGROUND Cystic fibrosis transmembrane conductance regulator(CFTR)modulators significantly improve pulmonary function in patients with cystic fibrosis(CF)but the effect on hepatobiliary outcomes remains unknown.We hypothesized that CF patients on CFTR modulators would have a decreased incidence of cirrhosis compared to patients not on CFTR modulators or on ursodiol.AIM To investigate the effect of CFTR modulators on the development of cirrhosis in patients with CF.METHODS A retrospective analysis was performed using Truven MarketScan from January 2012 through December 2017 including all patients with a diagnosis of CF.Patients were excluded if they underwent a liver transplantation or if they had other etiologies of liver disease including viral hepatitis or alcohol use.Subjects were grouped by use of CFTR modulators,ursodiol,dual therapy,or no therapy.The primary outcome was development of cirrhosis.Kaplan-Meier curves estimated the incidence of cirrhosis and log-rank tests compared incidence curves between treatment groups.RESULTS A total of 7201 patients were included,of which 955(12.6%)used a CFTR modulator,529(7.0%)used ursodiol,105(1.4%)used combination therapy,and 5612(74.3%)used neither therapy.The incidence of cirrhosis was 0.1%at 1 year and 0.7%at 4 years in untreated patients,5.9%and 10.1%in the Ursodiol group,and 1.0%and 1.0%in patients who received both therapies.No patient treated with CFTR modulators alone developed cirrhosis.Patients on CFTR modulators alone had lower cirrhosis incidence than untreated patients(P=0.05),patients on Ursodiol(P<0.001),and patients on dual therapy(P=0.003).The highest incidence of cirrhosis was found among patients treated with Ursodiol alone,compared to untreated patients(P<0.001)or patients on Ursodiol and CFTR modulators(P=0.01).CONCLUSION CFTR modulators are associated with a reduction in the incidence of cirrhosis compared to other therapies in patients with CF.

Ciliated hepatic foregut cyst:an increasingly diagnosed condition

BACKGROUND:Ciliated foregut cysts of the liver are rare, with only 96 cases diagnosed since the first description in 1857.They are being increasingly diagnosed recently;the majority of the cases have been reported in the last 15 years. Although they bear a close resemblance to the simple cyst of the liver which has essentially a benign course,ciliated hepatic foregut cysts(CHFCs)can progress to malignancy with devastating consequences.It is imperative that this group of conditions be diagnosed and treated adequately. DATA SOURCES:This review includes discussion of the data from all the 96 reported cases from English and non-English literature.Analysis of the incidence rates, embryogenesis,growth,clinical features,risk of malignancy and the prognosis are highlighted systematically.The roles of various diagnostic modalities including ultrasound, CT,MRI,fine needle aspiration cytology(FNAC), immunohistochemistry and surgery are further discussed. RESULTS:The mean age of patients with CHFC was 48± 12 years.The male/female ratio was 1.1∶1.The majority of patients with CHFC(62%)were asymptomatic,and the common mode of presentation was right upper abdominal pain.The cysts occurred in the left lobe in 51 patients, with sole location in segmentⅣin 44,and in the right lobe in 26.The average size of the cysts was 3.6±2.12 cm. The majority of the cysts were unilocular,and only 7 cases were multilocular.Cyst contents were described as viscous or mucinous in 73 patients,whereas bilious fluid was noted in 3.Large cysts having squamous carcinoma were cited in 3 patients,and 2 had extensive squamous metaplasia without malignancy.Others had benign histopathology. CONCLUSIONS:Clinicians have become increasingly aware of CHFC.Imaging alone is not diagnostic per se, but when considered in the context of the global picture does provide important clues to the diagnosis.FNAC is diagnostic by the presence of the ciliated columnar aspirate but lacks sensitivity.Infantile presentation is usually accompanied by biliary communication and mandates a different surgical approach.The demonstration of malignant transformation in 3 cases and its fatal course emphasizes the need for surgical resection in all cases once the diagnosis is made.