Retrospective review of cystic fibrosis presenting as infantile liver disease

The mode of presentation, clinical course, and outcome of 12 infants with cystic fibrosis and liver disease referred over an 18 year period were investigated retrospectively. Median age at presentation was 6.5 weeks (range, 5-12). Two thirds were boys. Conjugated hyperbilirubinaemia was the presenting symptom in 11patients, and hypoalbuminaemia in one. Jaundice was cleared over a median period of 7.36 months. Eight patients had bile duct proliferation on liver biopsy and one required cholangiography to exclude biliary atresia. Classic histological features of cystic fibrosis were only present in two children biopsied at 8 and 18 months. Three patients had meconium ileus, including one infant with concomitant α₁ antitrypsin deficiency, who required early liver transplantation. All other patients had no signs of significant chronic liver disease during a median follow up of 42 months (range, 10-205). Children with cystic fibrosis and infantile liver disease have a good short and medium term prognosis.

     

Liver transplantation for cholestasis associated with cystic fibrosis in the pediatric population

The most common hepatic complications of cystic fibrosis (CF) are steatosis, fibrosis, biliary cirrhosis, atretic gallbladder, cholelithiasis, and sclerosing cholangitis. Cholestatic liver disease is a slow progressive disorder, but will stabilize for many patients. CF patients may suffer from the consequences of their liver disease and without liver transplantation, variceal hemorrhage, malnutrition, or end-stage liver disease can lead to death. Prospective data were collected and reviewed on 311 liver transplants performed in 283 patients at the Children's Medical Center of Dallas between October 1984 and November 2000. Ten children received an orthotopic liver transplant (OTLX) for end-stage liver disease associated with cystic fibrosis. Pulmonary function tests were obtained preoperatively in all cases. There were nine boys and one girl. Six are currently alive, and four are dead. Both patient and graft survival was 5.75 yr. Among those currently alive, mean patient and graft survival is 7.71 yr (range 0.10-12.62 yr). Mean patient and graft survival of those who died was 2.35 yr (range 0.78-5.33 yr). No survivor required re-transplantation and currently, all have normal serum aminotransferase values. Chronic sinusitis was not a significant pre- or post-transplant morbidity, although systematic radiographic evaluation of the sinuses did not occur. Pulmonary deaths occurred in three patients from pulmonary hemorrhage, pulmonary infection with Aspergillus and Candida glabrata, and acute bronchopneumonia associated with polymicrobial sepsis because of Pseudomonas, Klebsiella, and Candida albicans 1.44, 0.78, and 1.83 yr, respectively, after transplantation. The fourth death was associated with chronic rejection, and occurred 5.33 yr after transplantation. All non-survivors were below the 5th percentile for height and weight at the time of liver transplantation. Mean age at transplantation was 9.72 yr (range 1.23-19.09, median 9.61). Survivors were transplanted at a younger age than non-survivors (mean of 9.21 yr vs. 10.66 yr), and had shorter waiting times from diagnosis of end-stage liver disease to transplantation (6.87 months vs. 13.83 months). Eighty percentage (n = 8) of patients had pretransplant variceal bleeds (83% of survivors, 75% of non-survivors). While all non-survivors had a history of meconium ileus and preoperative need of pancreatic enzymes, only 67% of those alive experienced these complications. Preoperative forced vital capacity FVC was 103% for survivors and 95% for non-survivors. The corresponding numbers for forced expiratory flow (FEF) 25-75 were 74-84% respectively. Preoperative Aspergillus was identified in 30% of patients (n = 3). Two of these patients are alive. Cystic fibrosis constitutes an indication for 3.5% of pediatric liver transplants. Evaluation and transplantation for end-stage liver disease associated with cystic fibrosis should be undertaken at an early age. Most deaths were associated with pulmonary/septic events, and occurred less than 2 yr after OLTX. Those children who did not survive had poor growth and nutrition, prolonged waiting times prior to transplantation, were transplanted at an older age, and had a higher incidence of pancreatic insufficiency and meconium ileus. The presence of Aspergillus in the sputum does not constitute a contraindication for OLTX.     

Night blindness and conjunctival xerosis caused by vitamin A deficiency in patients with cystic fibrosis.

Forty three patients with cystic fibrosis, aged 8-44 years (median 16 years), were examined for evidence of vitamin A deficiency. Eight patients had abnormal dark adaptation tests and three had conjunctival xerosis. Serum vitamin A and retinol binding protein concentrations were significantly lower in the affected patients who were also more likely to have abnormal liver function tests. Five patients were treated with 100,000-200,000 IU water miscible vitamin A orally and their daily vitamin supplements were increased to maintain normal concentrations. In four patients dark adaptation tests were repeated. Three were normal, but one patient required three further doses of water miscible vitamin A and a daily supplement of 12,000 IU vitamin A before her dark adaptation threshold returned to normal. Adolescents with cystic fibrosis are liable to develop night blindness and conjunctival xerosis, particularly if they have liver disease or fail to take daily vitamin supplements.     

IgG antibodies in early Pseudomonas aeruginosa infection in cystic fibrosis.

The relationship between IgG antibodies to Pseudomonas aeruginosa and its isolation from sputum was determined in 100 patients with cystic fibrosis observed at intervals of two months for a median period of one year. Only one patient had a raised antibody titre (greater than 22.9 ELISA units) before isolation of P aeruginosa. Initially 65 patients were antibody negative, of whom 48 were also culture negative. Of 24 patients with positive sputum culture and negative antibodies, seven became antibody positive at a median (range) 15 (6-25) months later. The remaining 17 patients continued antibody negative until the end of the study at a median range 15 (1-123) months after becoming culture positive. This latter group were younger and had more intermittently positive sputum cultures. In general positive IgG antibody titres do not predate isolation of P aeruginosa, but in some patients are present soon after acquisition of infection. A positive titre indicates significant exposure to P aeruginosa and could be used to detect infection in patients unable to produce sputum and possibly indicate the effect of early antipseudomonal treatment.     

Failure of ursodeoxycholic acid to dissolve radiolucent gallstones in patients with cystic fibrosis

Ursodeoxycholic acid has been used widely to dissolve cholesterol gallstones and more recently was shown to improve clinical symptoms and biochemical indices in different chronic liver diseases, including that associated with cystic fibrosis. We treated 10 cystic fibrosis patients (5 males, 5 females, age range 2–22 years) with pancreatic insufficiency and normal liver function with ursodeoxycholic acid 15–20 mg/kg/day. Seven patients had radiolucent gallstones (in 3 cases associated with biliary sludge) and 3 had sludge; all were asymptomatic. Before treatment, the gallbladder was well opacified in oral cholecystogram. The gallbladder was scanned by ultrasound in similar conditions and by the same operator before administration of ursodeoxycholic acid and after a median period of treatment of 16 months (range 11–32 months). During treatment, all patients remained asymptomatic and the relative proportion of ursodeoxycholic acid in duodenal bile increased from 4.7 ± 3.2% at baseline to 34.7 ± 8.6%. Complete or partial dissolution of gallstones was never observed and the maximum diameter of stones increased from a mean of 6.1 ± 3.4 to 8.0 ± 5.3 mm; in one case the development of biliary sludge occurred during bile acid therapy. Sludge disappeared in 1 of the 6 patients who initially had it, while in 2 cases its volume increased. We conclude that ursadeokycholic acid is not effective in most CF patients with gallstones, probably because cholesterol is not the main component of stone or sludge.     

Clinical and mutation profile of children with cystic fibrosis in Jammu and Kashmir

Objective

To study the clinical and mutation profiles of children with cystic fibrosis in Jammu and Kashmir

Methods

One hundred consecutive patients presenting with one or more phenotypic features suggestive of cystic fibrosis (CF) were screened by quantitative sweat chloride testing. For patients with positive/equivocal test result on two occasions, CFTR gene mutation analysis was done by polymerase chain reaction.

Results

Of the 100 patients, 18 (10 females) were diagnosed to have CF at a median age of 10.5 y (IQR 4.75–15.25 y) while the median age at the onset of symptoms was 12 mo (IQR 4–63 mo) with a delay in diagnosis by 102.4±80.5 months. Clinical features at presentation included failure to thrive (94.4%), chronic cough (78%), recurrent pneumonia (61%), persistent pneumonia (11%), and chronic diarrhea (50%). Positive sweat chloride (>60 meq/L) was seen in 14 (14%) patients and 4 (4%) patients had equivocal (40–60 meq/L) value on two different occasions. Mutational analysis done in 15 patients showed DeltaF508 mutation in 20% (3/15) patients in homozygous form and in 13% (2/15) patients in heterozygous form. Intron 19 mutation 3849+10kb C>T was found in 40% (6/15) in heterozygous form. One (6.6%) patient had DeltaF508 and 3849+10kbC>T mutations in compound heterozygous form. Patients with equivocal sweat chloride and 3849+10kbC>T mutation had delayed onset of pulmonary involvement.

Conclusion

3849 +10kbC>T mutation appears to be common in children with cystic fibrosis in Jammu and Kashmir followed by DeltaF508, although the data are quite limited. Although presentation is delayed and sweat chloride is in the equivocal range, severe lung involvement may occur in these patients.     

13Carbon mixed triglyceride breath test and pancreatic enzyme supplementation in cystic fibrosis

Children with cystic fibrosis have variable degrees of exocrine pancreatic insufficiency which, if untreated, is the main cause of fat malabsorption. The impact of pancreatic enzyme supplementation on fat digestion was measured in 41 children with cystic fibrosis, 11 healthy controls, and five children with mucosal diseases by a non-invasive test of intraluminal lipolysis using 13carbon (13C) labelled mixed triglyceride (1,3-distearyl, 2[13C] octanoyl glycerol). The children with cystic fibrosis without pancreatic supplements had a median (range) 13C cumulative percentage dose recovered over six hours (cPDR) of 3.1% (0-31.7), the controls 31.0% (21.8-41.1), and the subjects with mucosal disease 27.8% (19.7-32.5). In 23 subjects with cystic fibrosis the usual dose of pancreatic enzyme supplements increased the cPDR to a median of 23.9% (0-45.6), and twice the usual dose of enteric coated microspheres increased the cPDR to 31.1% (11.1-47.8). There was no significant difference between the median cPDR of normal controls and children with mucosal disease, but there was a highly significant difference between these groups and children with untreated cystic fibrosis. Thirteen children with cystic fibrosis had no 13C recovery in their breath without enzymes and 10 showed marked increases with regular enzymes. In eight children doubling the dose of enzymes caused no or minimal improvement. The mixed triglyceride breath test offers a simple, non-invasive way of assessing the need for pancreatic enzyme supplementation in children with cystic fibrosis and could be used to optimise treatment.     

13C and H2 breath tests to study extent and site of starch digestion in children with cystic fibrosis.

BACKGROUND: Starch is an important source of energy for children with cystic fibrosis, but little is known about their capacity to digest it. METHODS: A 13C breath test was used to measure starch digestion and oxidation in 16 children with cystic fibrosis (median [range] age, 7.9 [4-15] years; 7 girls, 9 boys) and 5 normal healthy control subjects (median age, 8.3 [7-13] years; 3 girls, 2 boys). A test meal of 13C flour and lactulose was consumed and breath samples were obtained half-hourly thereafter for 6 hours to measure 13C enrichment by isotope ratio mass spectrometry and H2 by electrochemistry. The test was repeated on 10 children with cystic fibrosis when they were taking pancreatic supplements. RESULTS: The median (range) cumulative percentage 13C dose recovery (cPDR), was 35% (18-52%) in control subjects, 18% (9-33%) in children with cystic fibrosis without enzymes, and 29% (22-51%) in those with pancreatic supplements. cPDR differed significantly between healthy control subjects and children with cystic fibrosis without enzymes (p = 0.01) and between children with cystic fibrosis with and without enzymes (p < 0.0001), but there was no difference between control subjects and children with cystic fibrosis taking enzymes (p = 0.5). Eight children with cystic fibrosis had a cPDR within control range, and in six there was a second peak in 13CO2 enrichment coincident with an increase in H2. CONCLUSIONS: Starch digestion and oxidation are diminished in children with cystic fibrosis, but pancreatic enzymes restored them to near normal levels. A second peak in 13CO2 enrichment, suggestive of colonic starch fermentation was absent in healthy children, but present in some children with cystic fibrosis and abolished by pancreatic enzymes.     

Serum hyaluronic acid concentrations are increased in cystic fibrosis patients with liver disease.

AIM: To determine whether serum hyaluronic acid (HA) concentrations are abnormal in patients with cystic fibrosis (CF) liver disease, and if so, whether the abnormality is associated with disease severity. METHODS: A total of 74 patients with CF were assessed for evidence of liver involvement as indicated by clinical, ultrasound, and biochemical findings. Serum hyaluronic acid concentrations were measured and compared with concentrations in 293 normal controls. Lung function in the CF patients was also recorded. RESULTS: Thirty four CF patients had no evidence of liver disease; in these, serum HA concentrations were similar to those in healthy controls (median (range): 16.1 (9.4-75.1) v 15 (1-77) microg/l). Nineteen CF patients had established liver disease detected by clinical and ultrasound examination, with significantly increased HA concentrations (56.1 (26-355) microg/l). Serum HA concentrations were also significantly increased, although to a lesser extent, in 21 CF patients with an abnormal liver ultrasound scan alone (22.4 (9.5-43.4) microg/l). There was no correlation between serum HA concentration and lung function. CONCLUSION: Serum HA concentrations were significantly increased in children with clinical or ultrasound evidence of liver disease, being higher in those with more advanced hepatic damage. Despite the inflammation and fibrosis present in CF lungs there was no correlation between HA concentration and lung function, suggesting that high concentrations were a failure of hepatic clearance rather than overproduction in the lung. Longitudinal measurement of HA concentrations may prove a useful marker for the development of significant liver damage in CF patients.     

Treatment and prognosis of symptomatic gallbladder disease in patients with cystic fibrosis

Twenty-four (3.6%) of 670 patients with cystic fibrosis seen over a 25-year period developed symptomatic gallbladder disease. Only four patients were less than 16 years old. Four patients presented with unusual problems, including one with acute cholangitis and two with atonic gallbladder, one of whom required cholecystectomy. Another patient was found to have cholangiocarcinoma of the gallbladder when an exploratory laparotomy was performed to investigate biliary obstruction. Twenty patients had cholelithiasis, 15 of whom underwent cholecystectomy. Only one patient had substantial pulmonary difficulties postoperatively. Patients who presented with classic biliary colic had no further symptoms after cholecystectomy. One patient developed intrahepatic stones 6 years later and required a choledochoduodenostomy. As the pulmonary status of most cystic fibrosis patients will eventually deteriorate, we recommend that serious consideration be given to performing a cholecystectomy as soon as practical after the diagnosis of symptomatic cholelithiasis. Our experience indicates that surgery can be performed safely unless pulmonary status is already extremely compromised and the patient is in overt respiratory failure.     

Juvenile hyperthyroidism: an experience

OBJECTIVE: To analyze the clinical profile of juvenile hyperthyroidism at presentation, their treatment outcome; predictors of remission and relapse. METHODS: Retrospective analysis of medical records of 56 patients with juvenile hyperthyroidism seen over a period of 16 years. A cohort of 38 females and 18 males with mean (+/-SD) age of 14.9 +/- 3.4 years (range 3 to 18 years) was analyzed. RESULTS: Majority of patients was in the age group of 12-16 years. Common symptoms observed at presentation were weight loss (82.1%), excessive sweating (78.6%), heat intolerance (76.8%), increased appetite (73.2%) and diarrhea in 48.2%. In addition, accelerated linear growth was observed in 7.1% of patients. Goiter was present in 98.2% of children; 94.5% of which was diffuse and 4.8% was multinodular. The mean ((+/-SD) T3 was 4.8 +/- 3.4 ng/mL (N, 0.6-1.6), T4 was 218 +/- 98 ng/mL (N, 60-155) and TSH was 0.44 +/- 0.36 (N, 0.5-5.5 microIU/mL). TMA positivity seen in 36.9% of patients. All patients were treated with carbimazole; subsequently 4 patients required thyroidectomy and one required radioactive iodine ablation. Mean (+/-SD) duration of follow-up in our patients was 4.9 +/- 3 years, ranging between 1.6 to 16 years and mean (+/-SD) duration of treatment was 34.4 +/- 22.6 months (range 12 to 120 months). Mean (+/-SD) duration to achieve euthyroidism was 5.2 +/- 4.7 months, ranging between 1-33 months. On intention to treat analysis, remission with carbimazole was achieved in 47.6%, remaining patients failed to achieve remission with drug treatment. CONCLUSION: Graves disease is the commonest cause of juvenile hyperthyroidism. Carbimazole is safe, effective, cheap, and easily available form of therapy. It is occasionally associated with serious side effects but requires prolonged follow up.     

Early experience of heart-lung transplantation.

We report our experience of heart-lung transplantation for the treatment of children with terminal respiratory disease. Between May 1987 and October 1988 we performed heart-lung transplantation in five children under the age of 16 (age range 11-15). All the patients were severely disabled by dyspnoea and hypoxia. Two had primary pulmonary hypertension, two cystic fibrosis, and one had Eisenmenger''s syndrome. All five children are alive and well five to 17 months after operation and have returned to activities normal for their age. Three of the five patients had episodes of infection after operation. These were staphylococcal pneumonia, herpes simplex pneumonitis and, in one of the patients with cystic fibrosis, persistent purulent sputum. The mean number of episodes of rejection per child was 2.7 per half year. Heart-lung transplantation is a practical treatment for children in these disease groups with terminal respiratory failure.     

Determinants of serum vitamin D levels in preadolescent cystic fibrosis children

The effects of liver disease, fat malabsorption and sunlight exposure on serum vitamin D levels were determined in 21 optimally treated preadolescent cystic fibrosis (CF) children over a 12-month period. Manifest liver disease and fat malabsorption appeared not to affect the vitamin D level. However, the level fell significantly in winter, although not below the normal range, suggesting that sunlight exposure is a more important determinant of vitamin D levels in preadolescent CF children than liver disease and fat malabsorption.     

胆道闭锁术后高胆红素血症并胆管扩张二次手术的探讨

目的 探讨胆道闭锁(BA)术后高胆红素血症者二次手术的条件及必要性、可行性和效果.方法 2001年3月至2007年12月,共对10例BA术后患儿实施了二次手术,男4例,女6例;年龄5个月～6.5岁.距第一次Kasai's手术时间2个月～6年.其中Ⅲ型BA Kasai's手术后9例,Ⅱ型BA囊肿空肠吻合术后1例;所有患儿第一次术后3个月总胆红素(TBIL)直接胆红索(DBIL)曾降至正常,谷草转氨酶(AST)、谷丙转氨酶(ALT)等酶水平下降,后再次出现高胆红素血症、酶水平升高、陶土样便等情况.二次术前经影像学检查证实所有患儿肝门、肝内胆管扩张,1例并发肝门胆管结石;6例伴有肝门部囊肿形成.结果 8例患儿行开腹肝门空肠再吻合术,2例患儿实施囊肿空肠吻合术,手术全部成功,无术中并发症发生.手术时间为2.6～3.2h(平均3.0h),术中出血15～30ml.术后进食中位数时间32h(24～52h);术后2～4d(平均3d)排黄色大便;腹腔引流放置中位时间58 h(38～96 h),黄疸减退至轻度或消退中位时间为术后12 d(7～24 d),6例患儿术后4周 TBIL、DBIL,降至正常水平,4例患儿6周后降至正常水平,转氨酶术后均下降.术后中位住院时间15 d(12～29 d).术后随访4～36个月,3例患儿于术后4周内发牛胆管炎,2例患儿于术后6个月内发作胆管炎2次,均治愈.术后3个月所有患儿 TBIL、DBIL、总蛋白(TP)正常;3例患儿术后3个月AST、ALT、ALP恢复正常,3例术后5～8个月恢复正常.生长发育正常.无吻合口狭窄、粘连肠梗阻等术后并发症.结论 对BA术后高胆红素血症患儿恰当的实施二次肝门肠吻合术能够建立有效的胆汁引流,改善患儿症状,提高生活质量,并长期带自体肝脏生存,避免肝移植或为等待肝源提供时间保障.     

Autoimmune hepatitis as a late complication of liver transplantation

BACKGROUND: The development of de novo autoimmune hepatitis as a long-term complication after liver transplantation has been recently reported. The authors describe five liver allograft recipients who developed chronic hepatitis associated with autoimmune features. METHODS: Five of 155 liver transplant recipients at risk (2.5%) developed this particular form of graft dysfunction. The authors review the clinical records, liver histology, therapy, and outcome of these five patients. RESULTS: Patients included two boys and three girls. Median age at transplantation was 3.5 years (range, 0.5-14 years), median age at presentation was 9 years (range, 2-17 years), and median interval after transplantation was 5.1 years (range, 1.5-9 years). Indications for liver transplant included biliary atresia in four patients and primary sclerosing cholangitis in one patient. At the time of presentation, all patients were receiving cyclosporine as their primary immunosuppressive agent. Only one patient had a history of rejection, which had resolved. All patients presented with increased transaminase levels, and one had a mildly elevated conjugated bilirubin level. Only one patient had constitutional complaints. Acute and chronic rejection, viral hepatitis, vascular insufficiency, and biliary tract obstruction were excluded. Antinuclear antibody levels were elevated in four patients (titer range, 1:160-1:640), one of whom also had positive antismooth muscle antibody (titer 1:80) results. The fifth patient had an elevated serum total protein level. Histologic analysis of liver biopsy samples from the five patients showed findings consistent with chronic autoimmune hepatitis. All patients were treated with standard therapy for autoimmune hepatitis, which included daily steroids and azathioprine. Cyclosporine doses were reduced in three patients and eliminated in two. All patients responded with normalization (n = 2) or improvement (n = 3) of liver transaminases within the first 3 months of therapy. Histologic analysis of the 3-month follow-up liver biopsy was normal (n = 2) or showed improvement in inflammation (n = 2). Two patients developed acute allograft rejection within 6 to 12 months after discontinuation or reduction in cyclosporine. CONCLUSIONS: Autoimmune hepatitis occurs after liver transplantation in patients without a previous history of autoimmune hepatitis. The risk of developing autoimmune hepatitis appears to be greater in children after liver transplantation than in the general pediatric population. Standard therapy for autoimmune hepatitis is effective.     

Adrenal Cortical Tumors in Childhood

In a 41-year period, 18 children with a diagnosis of an adrenal cortical tumor were identified (14 carcinoma : 4 adenoma). The majority of patients had clinical signs of endocrine dysfunction at presentation, with virilization (11 patients) and a cushingoid appearance (8 patients) the commonest findings. Abnormal biochemical activity was identified in 16 tumors (94%). The primary treatment in 17 patients was surgical. In addition, 12 children, all with carcinomas, had radiotherapy. Of those children with a carcinoma, 12 are dead, with a median survival of 52 months (range 1–317 months). The three second primary tumors all developed at sites within the field of previous radiotherapy, and proved fatal at 127, 176, and 317 months (median 207 months). This series confirms the poor prognosis in adrenocortical carcinoma in childhood, but a complete resection is compatible with cure of the primary disease. The frequency of second, fatal, primary tumors is of particular concern and long-term follow-up is mandatory in survivors, especially if radiotherapy was part of the treatment protocol.     

Diminished concentrations of insulin-like growth factor I in cystic fibrosis

Cystic fibrosis is frequently accompanied by a catabolic condition with low body mass index caused by a number of disease complications. Insulin-like growth factor-I (IGF-I) is an anabolic hormone and an important marker of nutritional status, liver function, and linear growth. Available data on IGF-I in cystic fibrosis are sparse and conflicting. From 1990-3, 235 of our 240 patients (114 males, 121 females, median age 16.2 years, ranged 0.1-44.0 years) had IGF-I measured once by radioimmunoassay. IGF-I was significantly reduced compared with a healthy Scandinavian control population: mean (-2 SD to +2 SD) IGF-I SD score was -0.97 (-3.7 to 1.7) in males and -0.67 (-3.2 to 1.9) in females. Height SD score was -0.95 (-3.3 to 1.4) in males and -0.81 (-3.2 to 1.6) in females. In patients who were still in the growth period a significant correlation of IGF-I SD score to height SD score (r = 0.28, p < 0.001) was found. The low IGF-I concentrations may reflect the catabolic state of many patients with cystic fibrosis and play a part in their abnormal growth pattern.     

Diminished concentrations of insulin-like growth factor I in cystic fibrosis.

Cystic fibrosis is frequently accompanied by a catabolic condition with low body mass index caused by a number of disease complications. Insulin-like growth factor-I (IGF-I) is an anabolic hormone and an important marker of nutritional status, liver function, and linear growth. Available data on IGF-I in cystic fibrosis are sparse and conflicting. From 1990-3, 235 of our 240 patients (114 males, 121 females, median age 16.2 years, ranged 0.1-44.0 years) had IGF-I measured once by radioimmunoassay. IGF-I was significantly reduced compared with a healthy Scandinavian control population: mean (-2 SD to +2 SD) IGF-I SD score was -0.97 (-3.7 to 1.7) in males and -0.67 (-3.2 to 1.9) in females. Height SD score was -0.95 (-3.3 to 1.4) in males and -0.81 (-3.2 to 1.6) in females. In patients who were still in the growth period a significant correlation of IGF-I SD score to height SD score (r = 0.28, p < 0.001) was found. The low IGF-I concentrations may reflect the catabolic state of many patients with cystic fibrosis and play a part in their abnormal growth pattern.     

Liver disease as risk factor for cystic fibrosis-related diabetes development

AIM: To evaluate clinical and genetic factors, besides pancreatic insufficiency, associated with increased risk of cystic fibrosis-related diabetes. METHODS: Case-control (1:1) study on 138 cystic fibrosis patients. Data were collected on gender, age at diagnosis, reason for cystic fibrosis diagnosis, family history of type 1 or 2 diabetes mellitus, pre-existing severe liver disease, and class of cystic fibrosis transmembrane regulation mutation. Moreover, information was obtained on lung involvement and degree of exocrine pancreatic insufficiency evaluated 1 year before the diagnosis of cystic fibrosis-related diabetes in patients and age-matched controls. RESULTS: Compared to controls, patients with cystic fibrosis-related diabetes had a higher probability of having already been diagnosed with liver disease (16.7% versus 1.7%, OR = 11.6, 95% CI 1.43-93.0). Moreover, in the year before diabetes onset, cases had slightly worse pulmonary function compared to controls (FEV1 = 58.4 +/- 27% predicted versus 67.4 +/- 21% predicted; p = 0.05). No significant effects related to the other factors considered were found. CONCLUSION: Severe liver disease was found to significantly increase the risk of developing cystic fibrosis-related diabetes. Patients with liver disease should be scheduled for earlier diabetes screening in order to identify and possibly treat glucose intolerance.     

Determinants of Serum Vitamin D Levels in Preadolescent Cystic Fibrosis Children

ABSTRACT. The effects of liver disease, fat malabsorption and sunlight exposure on serum vitamin D levels were determined in 21 optimally treated preadolescent cystic fibrosis (CF) children over a 12-month period. Manifest liver disease and fat malabsorption appeared not to affect the vitamin D level. However, the level fell significantly in winter, although not below the normal range, suggesting that sunlight exposure is a more important determinant of vitamin D levels in preadolescent CF children than liver disease and fat malabsorption.