Faculty Bibliography

The interleukin-1 (IL-1) family consists of 11 cytokines that play key regulatory roles in many immune and inflammatory processes. Anakinra (Kineret, Amgen, Inc.) is an IL-1 receptor antagonist (IL-1ra). Increased levels of IL-1 are found in several disease states suggesting that anakinra may be beneficial in disorders associated with elevated IL-1 levels. Anakinra has been effectively used in the treatment of systemic juvenile idiopathic arthritis and adult-onset Still's disease (AOSD). Despite its therapeutic benefits, anakinra also has potential side effects, including hepatotoxicity. We present a case of AOSD in an adolescent male that was treated with anakinra. During treatment, the patient developed acute liver failure that resolved upon withdrawal of anakinra. Although anakinra-induced liver injury has been reported in adults, including one case of subacute liver failure, we believe our case is the first to show severe acute liver failure in an adolescent treated with anakinra. This case provides significant insight into a potentially serious complication associated with anakinra. It is important to further delineate these complications as the treatment indications for this drug expand.

BACKGROUND:Serial transverse enteroplasty (STEP) was designed to lengthen and taper the small intestine in patients with short bowel syndrome (SBS) and dilated small bowel. We hypothesized that tolerance for enteral nutrition (EN) improves after STEP. METHODS:Patients who underwent STEP between March 2004 and January 2011 were identified. Candidates for STEP had radiographic evidence of dilated small bowel and either failed to advance EN or demonstrated deterioration in tolerance for EN. Clinical and nutritional data were analyzed pre- and post-STEP. EN was defined as the percentage of calories administered enterally. Statistical analysis employed the signed rank test with significance assumed when p<0.05. RESULTS:Twenty STEPs were performed at a median age of 13.7 months. Median pre-STEP bowel length was 30 cm with a median increase in bowel length of 42%. Five patients achieved enteral autonomy at a median of 6.5 months post-STEP. EN increased in 75%, while 25% exhibited unchanged or decreased EN post-STEP. In aggregate, median EN tolerance increased from 22% at one month pre-STEP to 61% at six months post-STEP (p=0.003). CONCLUSIONS:The STEP is an effective adjunct in the treatment of patients with intestinal failure. While enteral autonomy is eventually possible in some patients, improved enteral tolerance can be achieved in a majority of cases.

Intestinal transplantation is a well-accepted treatment for SBS. However, patients with SBS often have decreased abdominal capacity, which makes size-matching of donor organs more difficult, thus decreasing organ availability. Reported approaches for addressing this problem include surgically reducing the graft size, leaving an open abdomen for a prolonged period, and cotransplanting rectus fascia as a non-vascularized allograft. Each approach has significant disadvantages. There has been one previous report of tissue expanders used intra-abdominally and two reports of subcutaneous use to increase intra-abdominal capacity prior to transplantation. We report the first use of bi-planar expander placement for this purpose. In our case, a two-yr-old male child with SBS due to malrotation was treated with tissue expanders 10 months prior to intestinal transplantation, thus allowing transplantation of a larger graft with the ability to close the abdomen safely. There were no complications, and the patient is now doing well and tolerating diet off PN. The use of tissue expanders prior to intestinal transplantation is a promising approach for such patients and avoids the morbidity associated with other approaches. This approach requires a multidisciplinary effort by gastroenterology, transplant surgery, and plastic surgery teams.

OBJECTIVE:To investigate the histological spectrum of nonalcoholic fatty liver disease (NAFLD) in children with normal, mildly elevated (26-50 U/L boys, 23-44 U/L girls), or elevated (>50 U/L in boys, >44 U/L in girls) serum alanine aminotransferase (ALT) levels. STUDY DESIGN/METHODS:The Nonalcoholic Steatohepatitis Clinical Research Network enrolls children aged 5-18 years with NAFLD. We analyzed baseline clinical and histological data from 91 children with suspected NAFLD and normal or mildly elevated ALT and liver biopsy analysis within 180 days of ALT measurement, and compared them with data from 392 children with elevated ALT. RESULTS:Seventeen of the 91 children with suspected NAFLD (19%) had a normal ALT level, and 74 (81%) had a mildly elevated ALT level. Overall, 45% of the biopsy specimens analyzed had steatosis ≥33%, 22% had grade ≥2 lobular inflammation, 81% had portal inflammation, 29% had ballooned hepatocytes, 35% had "suspicious/borderline" steatohepatitis, 8% had definite nonalcoholic steatohepatitis, 34% had an NAFLD activity score ≥4, and 46% had fibrosis (38% mild/moderate and 8% bridging/cirrhosis). Marked steatosis (50% vs 24%) and fibrosis (54% vs 12%) were significantly more common in the patients with mildly elevated ALT compared with those with normal ALT, with no difference in ballooning, inflammation, or NAFLD activity score ≥4 between the 2 groups. Fibrosis stage 3/4 was seen in none of the children with normal ALT, in 9% of those with mildly elevated ALT, and in 15% of those with elevated ALT. CONCLUSION/CONCLUSIONS:Liver biopsy specimens from children with NAFLD with normal or mildly elevated ALT levels show significant histological abnormalities, including advanced fibrosis in children with mildly elevated ALT. Thus, measurement of ALT may underestimate liver injury in NAFLD. The use of appropriate ALT cutoff levels can help identify children at risk for more severe disease.

OBJECTIVE:Nonalcoholic fatty liver disease (NAFLD) affects 9.6% of children and may put these children at elevated risk of high blood pressure and subsequent cardiovascular morbidity and mortality. Therefore, we sought to determine the prevalence of and risk factors for high blood pressure in children with NAFLD. METHODS:Cohort study performed by the NIDDK NASH Clinical Research Network. There were 484 children with NAFLD ages 2 to 17 at enrollment; 382 children were assessed both at enrollment and 48 weeks afterwards. The main outcomes were high blood pressure at baseline and persistent high blood pressure at both baseline and 48 weeks. RESULTS:Prevalence of high blood pressure at baseline was 35.8% and prevalence of persistent high blood pressure was 21.4%. Children with high blood pressure were significantly more likely to have worse steatosis than children without high blood pressure (mild 19.8% vs. 34.2%, moderate 35.0% vs. 30.7%, severe 45.2% vs. 35.1%; P = 0.003). Higher body mass index, low-density lipoprotein, and uric acid were independent risk factors for high blood pressure (Odds Ratios: 1.10 per kg/m2, 1.09 per 10 mg/dL, 1.25 per mg/dL, respectively). Compared to boys, girls with NAFLD were significantly more likely to have persistent high blood pressure (28.4% vs.18.9%; P = 0.05). CONCLUSIONS:In conclusion, NAFLD is a common clinical problem that places children at substantial risk for high blood pressure, which may often go undiagnosed. Thus blood pressure evaluation, control, and monitoring should be an integral component of the clinical management of children with NAFLD.