Diagnostic Approach to Acute Liver Failure in Children: A Position Paper by the SIGENP Liver Disease Working Group.

Acute liver failure (ALF) is a clinical condition characterized by the abrupt onset of coagulopathy and biochemical evidence of hepatocellular injury, leading to rapid deterioration of liver cell function. In children, ALF has been characterized by raised transaminases, coagulopathy, and no known evidence of pre-existing chronic liver disease; unlike in adults, the presence of hepatic encephalopathy is not required to establish the diagnosis. Although rare, ALF has a high mortality rate without liver transplantation (LT). Etiology of ALF varies with age and geographical location, although it may remain indeterminate in a significant proportion of cases. However, identifying its etiology is crucial to undertake disease-specific management and evaluate indication to LT. In this position statement, the Liver Disease Working Group of the Italian Society of Gastroenterology, Hepatology and Nutrition (SIGENP) reviewed the most relevant studies on pediatric ALF to provide recommendations on etiology, clinical features and diagnostic work-up of neonates, infants and children presenting with ALF. Recommendations on medical management and transplant candidacy will be discussed in a following consensus conference.

Is primary meningococcal arthritis in children more frequent than we expect? Two pediatric case reports revealed by molecular test.

BACKGROUND: Primary meningococcal arthritis is a rare infectious disease that occurs in less than 3% of meningococcal infections and is characterized by arthritis without meningitis, fever, rash, or hemodynamic instability Barahona [Case Rep Orthop 4696014:2017 ]. There are no validated clinical criteria that can be used for the diagnosis. We present two pediatric cases of atypical presentation of meningococcal disease revealed by molecular tests. CASE PRESENTATION: The clinical presentation of the two children (6- and 9-years-old) was characterized by signs of arthritis. By Real Time Polymerase Chain Reaction (RT-PCR), we identified N. meningitidis serogroup Y in the joint fluid in both cases. After specific antimicrobial treatment, the clinical conditions of the two patients quickly improved during hospitalization. CONCLUSIONS: We believe that the incidence of meningococcal arthritis could be underestimated in those settings where the use of RT-PCR is limited. Clearer data on the incidence of meningococcal disease would help to design specific treatments and the best possible national vaccine strategies [Fiji Sci Rep 23:39784, 2016, J Infect 67:385-90, 2013].

Increase of natural killer cells in children with liver transplantation-acquired food allergy

BACKGROUND: Transplantation-acquired food allergies (TAFA) are frequently reported and considered to be caused by immunosuppressive therapy. The aim of this study was to investigate the allergic and immunologic responses in children who had liver or kidney transplantations. METHODS: Twelve children receiving liver transplantations and 10 children receiving kidney transplantations were investigated. All children underwent the allergy work-up and in most of them, lymphocyte screening and serum cytokine measurements were also performed. RESULTS: TAFA were found in 7/12 (58%) children with liver transplantations and in none of the 10 children with kidney transplantations. The mean age at transplantation was significantly lower in children who underwent liver transplantations (p < 0.001). The immunosuppressive therapy administered to children with liver transplantation was tacrolimus in 11 patients and cyclosporine in one patient, while all 10 children with kidney transplantation received tacrolimus plus mycophenolate. The most common antigenic food was egg. The natural killer (NK) cell numbers were significantly higher in liver-transplant children than in kidney-transplant children. No significant differences were found in the serum cytokine levels. CONCLUSIONS: This study confirms that liver-transplant children treated with tacrolimus alone have a higher risk of developing TAFA than kidney-transplant children treated with tacrolimus plus mycophenolate. NK cells might be involved in this difference

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Increase of natural killer cells in children with liver transplantation-acquired food allergy.

BACKGROUND: Transplantation-acquired food allergies (TAFA) are frequently reported and considered to be caused by immunosuppressive therapy. The aim of this study was to investigate the allergic and immunologic responses in children who had liver or kidney transplantations. METHODS: Twelve children receiving liver transplantations and 10 children receiving kidney transplantations were investigated. All children underwent the allergy work-up and in most of them, lymphocyte screening and serum cytokine measurements were also performed. RESULTS: TAFA were found in 7/12 (58%) children with liver transplantations and in none of the 10 children with kidney transplantations. The mean age at transplantation was significantly lower in children who underwent liver transplantations (p<0.001). The immunosuppressive therapy administered to children with liver transplantation was tacrolimus in 11 patients and cyclosporine in one patient, while all 10 children with kidney transplantation received tacrolimus plus mycophenolate. The most common antigenic food was egg. The natural killer (NK) cell numbers were significantly higher in liver-transplant children than in kidney-transplant children. No significant differences were found in the serum cytokine levels. CONCLUSIONS: This study confirms that liver-transplant children treated with tacrolimus alone have a higher risk of developing TAFA than kidney-transplant children treated with tacrolimus plus mycophenolate. NK cells might be involved in this difference.

Altered natural killer cells subsets distribution in children with hepatitis C following vertical transmission.

BACKGROUND: Natural killer (NK) cells number, phenotypes and function have been evaluated in many studies in adults with hepatitis C as compared with healthy controls or dynamically during interferon-based and interferon-free treatments. Overall, in adults with chronic infection number of circulating NK cells has been reported to be lower when compared to spontaneous resolvers and healthy subjects. Different studies yielded inconsistent findings due to patient and virus heterogeneity. AIM: To evaluate NK cells in children according to the different outcomes of the infection. METHODS: In this cross-sectional study, we examined numbers and phenotypes of circulating NK cells from a homogenous cohort of Italian children with vertically acquired hepatitis C. RESULTS: We compared 31 children who developed chronic infection with nine who presented spontaneous clearance and 13 controls. CD56(+) CD3(-) NK cell numbers were consistently lower in the persistently infected group (P = 0.03 and 0.04). This decrease was due to depletions of CD56(dim) NK cells (P = 0.03 chronic infection vs. spontaneous clearance), while CD56(bright) NK cells were expanded (P = 0.03). No significant difference was found in the frequencies of CD56(+) CD16(+) and CD56(dim) CD16(-) cells. Perforin expression was higher in children with chronic infection (P = 0.03 vs. spontaneous clearance). CONCLUSIONS: Altered NK cells number and phenotypes could impact the outcome of HCV infection in children following vertical transmission. This study suggests for the first time that NK cells cytolytic function, featured by CD56(dim) cells, contributes to the elimination of HCV in children presenting spontaneous clearance.

Cost of varicella-related hospitalisations in an Italian paediatric hospital: comparison with possible vaccination expenses.

OBJECTIVE: The aims of the study were to evaluate the economic burden of hospitalisations due to varicella in an Italian paediatric hospital during a 1-year period and to compare the data with potential expenses projected for a varicella mass vaccination programme. RESEARCH DESIGN AND METHODS: An observational, retrospective, cohort study was designed to measure hospital admission costs in a cohort of paediatric patients with varicella in a 12-month period. A cost comparison with a vaccination programme planned to prevent varicella in a whole birth cohort was performed. All children 0-16 years referred to the Anna Meyer Children's Hospital (AMCH) were considered. Since AMCH is a tertiary-level hospital and accept patients from other Italian regions, in order to avoid overestimation of hospitalisation expenses, all analyses pertaining to both vaccination and hospitalisation costs were uniquely calculated on the basis of the cohort of residents in the district of Florence. RESULTS: A total of 279 children were examined in the emergency department for varicella; 47/279 (16.8%) were sent to the inpatient clinic. The highest rate of hospitalisation (85.1%) was found in children < 4 years of age, and the largest number of complications (87.2%) occurred in previously healthy children. Mean length of hospitalisation (5.7 +/- 0.6 days) was similar to that reported in other western countries. CONCLUSION: Excluding any indirect cost, permanent sequelae and serious outcomes such as death, hospital expenses (corresponding to euro239 654 in a 1-year period), would account for around 80% of total expenses for vaccinating an entire birth cohort (euro310353).

SEN virus co-infection among HCV-RNA-positive mothers, risk of transmission to the offspring and outcome of child infection during a 1-year follow-up.

SEN is a newly discovered blood-transmissible virus. Among its variants, SENV-D and -H are most often associated with non-A, -E hepatitis. Very little is known about the risk of vertical transmission of the virus. By using polymerase chain reaction with specific primers for SENV-D and -H, we investigated the prevalence of SENV-H and -D infection, the transmission rate of SENV infection and clinical features of SENV-infected children in 89 hepatitis C virus (HCV)-positive human immunodeficiency virus type 1-negative mothers. SENV infection was found in 36 (40%) mothers, and SENV-D was more frequent than SENV-H infection (34/36, 94%vs 5/36, 14%, P < 0.01). No difference in SENV infection rates was found between injection drug user (IDU) mothers (17/51, 33%) and mothers with no risk for bloodborne infection (19/38, 50%, P = ns). SENV-H infection was found only in IDU mothers and mothers with HCV genotype1b. Both SENV-D and -H can be transmitted to the offspring with an overall rate of 47%. Vertical transmission of HCV does not facilitate SENV infection of the offspring. Among 17 SENV-infected children, none was co-infected with HCV. Maternal HCV genotype or viral load does not interfere with mother-to-infant transmission of SENV. Persistence of SENV infection was demonstrated in 100% of infected children after 1-year follow-up, but none had clinical evidence of liver disease.

Vertical hepatitis C virus transmission is not related to mother-child class-1 HLA concordance.

Mother-child human leukocyte antigen (HLA)diversity is protective for vertical transmission of some viruses. The aim of this study is to evaluate the role of mother-child HLA diversity on hepatitis C virus (HCV) vertical transmission. Forty consecutive HCV infected and 46 consecutive control uninfected children born to HCV-RNA positive mothers were evaluated for HLA class-1 type concordance with their mothers. No significant difference in the degree of HLA concordance was found between HCV infected and uninfected children both when A, B, C (p=0.30) and when only A and B alleles were evaluated (p=0.59). Mother-infant HLA concordance does not affect HCV vertical transmission.