Broadly effective metabolic and immune recovery with C5 inhibition in CHAPLE disease.

Complement hyperactivation, angiopathic thrombosis and protein-losing enteropathy (CHAPLE disease) is a lethal disease caused by genetic loss of the complement regulatory protein CD55, leading to overactivation of complement and innate immunity together with immunodeficiency due to immunoglobulin wasting in the intestine. We report in vivo human data accumulated using the complement C5 inhibitor eculizumab for the medical treatment of patients with CHAPLE disease. We observed cessation of gastrointestinal pathology together with restoration of normal immunity and metabolism. We found that patients rapidly renormalized immunoglobulin concentrations and other serum proteins as revealed by aptamer profiling, re-established a healthy gut microbiome, discontinued immunoglobulin replacement and other treatments and exhibited catch-up growth. Thus, we show that blockade of C5 by eculizumab effectively re-establishes regulation of the innate immune complement system to substantially reduce the pathophysiological manifestations of CD55 deficiency in humans.

Erratum.

Author's name was mis-typed. The name "Oya B Sezer" in the original article should have been written as "Oya Balci Sezer."

Can platelet count/spleen diameter ratio be used for cirrhotic children to predict esophageal varices?

AIM: To determine the laboratory and radiologic parameters, including the platelet count (PC)-to-spleen diameter (SD) ratio as a non-invasive marker that may predict the presence of esophageal varices (EV) in children with cirrhosis. METHODS: Eighty-nine patients with cirrhosis, but without a history of variceal bleeding were prospectively included. The children were grouped into 6-12 and 12-18 years of age groups. These groups were also divided into 2 sub-groups (presence and absence of EV). All of the patients underwent a complete biochemical and radiologic evaluation. The PC (n/mm3)-to-SD (mm) ratio was calculated for each patient. RESULTS: Sixty-nine of 98 (70.4%) patients had EV. The presence of ascites in all age groups was significantly associated with the presence of EV. There were no differences in serum albumin levels, PC, SD and the PC-to-SD ratio between the presence and absence of EV groups in both age groups (P > 0.05). CONCLUSION: Laboratory and radiologic parameters, including the PC-to-SD ratio as a non-invasive marker (except for the presence of ascites), was inappropriate for detecting EV in children with cirrhosis.

Low 25-hydroxyvitamin D level is not an independent risk factor for hepatosteatosis in obese children.

BACKGROUND: Obesity is an important risk factor for non-alcoholic fatty liver disease. Few studies have evaluated the association between vitamin D and non-alcoholic fatty liver disease in obese children. Therefore, we conducted a study to examine the relationship of vitamin D levels and hepatosteatosis in obese children. METHODS: One hundred and eleven children with obesity participated in this study. Hepatosteatosis was diagnosed and graded using ultrasonography in all patients. Study participants were divided based on the presence of hepatosteatosis into two subgroups (hepatosteatosis and non-hepatosteatosis). Serum levels of 25-hydroxyvitamin D, calcium, phosphate, alkaline phosphatase, parathormone, and lipids were measured and compared. RESULTS: Hepatosteatosis existed in 52% of obese children without chronic diseases. There was no statistically significant difference in the vitamin D level between the hepatosteatosis and non-hepatosteatosis groups. Alanine aminotransferase levels and the triglycerides-to-high density lipoprotein ratio were significantly higher, and the high density lipoprotein levels were significantly lower in the hepatosteatosis group compared to the non-hepatosteatosis group. CONCLUSIONS: Vitamin D deficiency is not directly related with hepatosteatosis. A high ALT level and a high triglycerides-to-HDL ratio and low HDL levels are more significant in hepatic steatosis in obese children.

Is it necessary to re-evaluate diagnostic criteria for Wilson disease in children?

BACKGROUND/AIMS: The differential diagnosis of Wilson Disease (WD) is challenging, especially in children, because liver copper levels may also increase in other chronic liver diseases with bile stasis. The aim of this study is to determine urine and liver copper cut-off values to differentiate WD from other chronic liver diseases (non-WD, NWD) in children. MATERIALS AND METHODS: Seventy-six patients participated in the study, 35 with WD and 41 with NWD. The two groups were divided into two subgroups according to the presence of cholestasis. At the time of diagnosis, age, sex, biochemical test results, serum ceruloplasmin, baseline 24-h urinary copper levels, liver biopsy histological findings, liver copper levels, and Child-Pugh scores were obtained from medical records. Copper content in liver tissue and copper levels in urine were measured by atomic absorption spectrometry. Cut-off values for differentiation of WD from NWD were determined by receiver operating characteristic (ROC) analysis. RESULTS: A liver copper cut-off value of 98 µg/g indicated WD with 91% sensitivity and 65.4% specificity (area under the curve =0.838, 95% CI: 0.749-0.927). A 24-h urinary copper cut-off value of 67.5 µg/24h indicated WD with 85% sensitivity and 71% specificity (area under the curve =0.843, 95% CI: 0.752-0.934). CONCLUSION: In this study of pediatric chronic liver disease patients, copper cut-off values for distinguishing WD differed substantially from those used for diagnosis. A larger scale study is warranted to re-evaluate liver copper and 24-h urinary copper cut-offs for children with suspected WD.