Characteristics of Respiratory Syncytial Virus Infections in Children in the Post-COVID Seasons: A Northern Italy Hospital Experience.

BACKGROUND: Public health measures for COVID-19 mitigation influenced the circulation of Respiratory Syncytial Virus (RSV) during the 2020-2021 winter season. In the following autumn, an unprecedented resurgence of RSV occurred. Our study monitored RSV pediatric infections one and two years after the relaxation of containment measures for the COVID-19 pandemic. METHODS: We analyzed diagnostic molecular data for SARS-CoV-2, flu, and RSV infections and clinical data from children with respiratory symptoms referring to our hospital during the 2021-2022 and 2022-2023 seasons. RESULTS: In the 2021-2022 season, the number of RSV-affected children was very high, especially for babies <1 year. The outbreak appeared in a shorter interval of time, with a high clinical severity. In the 2022-23 season, a reduced number of infected pediatric patients were detected, with a similar hospitalization rate (46% vs. 40%), and RSV accounted for 12% of the infections. Coinfections were observed in age <2 years. In RSV patients, symptoms were similar across the two seasons. CONCLUSIONS: The clinical presentation of RSV in the two post-COVID seasons suggests that the pathophysiology of the virus did not change across these two years. Further studies are needed to continuously monitor RSV to support an effective prevention strategy.

Macro-AST as a cause of hypertransaminasemia: an uncommon entity but it exists

Macroenzymes are complexes formed by the binding of enzyme molecules to each other or to other plasma components. We report the clinical case of a woman with abnormal liver enzymes secondary to macro-AST. Macro-AST should be considered in the differential diagnosis as a cause of isolated AST elevation, thus avoiding unnecessary additional tests. (AU)

The frequency of Duchenne muscular dystrophy/Becker muscular dystrophy and Pompe disease in children with isolated transaminase elevation: results from the observational VICTORIA study.

Introduction: Elevated transaminases and/or creatine phosphokinase can indicate underlying muscle disease. Therefore, this study aims to determine the frequency of Duchenne muscular dystrophy/Becker muscular dystrophy (DMD/BMD) in male children and Pompe disease (PD) in male and female children with isolated hypertransaminasemia. Methods: This multi-center, prospective study enrolled patients aged 3-216 months with serum alanine transaminase (ALT) and/or aspartate transaminase (AST) levels >2× the upper limit of normal (ULN) for ≥3 months. Patients with a known history of liver or muscle disease or physical examination findings suggestive of liver disease were excluded. Patients were screened for creatinine phosphokinase (CPK) levels, and molecular genetic tests for DMD/BMD in male patients and enzyme analysis for PD in male and female patients with elevated CPK levels were performed. Genetic analyses confirmed PD. Demographic, clinical, and laboratory characteristics of the patients were analyzed. Results: Overall, 589 patients [66.8% male, mean age of 63.4 months (standard deviation: 60.5)] were included. In total, 251 patients (188 male and 63 female) had CPK levels above the ULN. Of the patients assessed, 47% (85/182) of male patients were diagnosed with DMD/BMD and 1% (3/228) of male and female patients were diagnosed with PD. The median ALT, AST, and CPK levels were statistically significantly higher, and the questioned neurological symptoms and previously unnoticed examination findings were more common in DMD/BMD patients than those without DMD/BMD or PD (p < 0.001). Discussion: Questioning neurological symptoms, conducting a complete physical examination, and testing for CPK levels in patients with isolated hypertransaminasemia will prevent costly and time-consuming investigations for liver diseases and will lead to the diagnosis of occult neuromuscular diseases. Trial Registration: Clinicaltrials.gov NCT04120168.

[Liver damage in children and adolescents with newly diagnosed celiac disease: clinical and anamnestic, serological and morphological patterns].

Hypertransaminasemia is a common extra-intestinal manifestation of celiac disease. AIM: To analyze the frequency of hypertransaminasemia, clinical and anamnestic, serological and morphological picture in children in the active period of celiac disease. MATERIALS AND METHODS: The study included 272 children with celiac disease aged from 8 months to 17 years. The patients were divided into two groups: the first - children with hypertransaminasemia, the second - without hypertransaminasemia. RESULTS: Hypertransaminasemia was detected in 55.9% of children with celiac disease. The age of manifestation of the disease in the first group was 1.0 [0.5; 2.0] years, in the second group - 1.9 [0.5; 4.0] years (p=0.0004). Children of the first group were diagnosed at 2.5 [1.7; 4.9] years, the second group - at 4.9 [3.0; 10.8] years (p<0.001). The duration of the latency period in children of the first and second groups was 1.4 [0.6; 3.1] years and 2.4 [0.9; 4.3] years, respectively (p=0.002). The average values of IgA anti-tTG antibodies in children of the analyzed groups did not differ, and the indicators of IgG anti-tTG antibodies in the first group were 1.6 (p=0.04) times higher. The level of EMA in children with hypertransaminasemia was 2 times higher than in children without hypertransaminasemia. CONCLUSION: Hypertransaminasemia is more often detected in young children with early manifestation of the disease, increases with the deepening of atrophy in the mucous membrane of the small intestine. Higher titers of celiac-specific antibodies were detected in children with hypertransaminasemia.

A Rare Contiguous Gene Deletion Leading to Trichothiodystrophy Type 4 and Glutaric Aciduria Type 3.

Introduction: Trichothiodystrophy type 4 and glutaric aciduria type 3 are rare autosomal recessive disorders caused by biallelic variants in the MPLKIP and SUGCT genes on chromosome 7p14, respectively. Trichothiodystrophy type 4 is characterized by neurologic and cutaneous abnormalities. Glutaric aciduria type 3 is a rare metabolic disorder with inconsistent phenotype and elevated urinary excretion of glutaric acid. Case Presentation: Here, we report on an infant presenting with hypotonia, failure to thrive, microcephaly, dysmorphic features, brittle hair, hypertransaminasemia, and recurrent lower respiratory tract infections. Microarray analysis revealed a homozygous microdeletion involving the MPLKIP and SUGCT genes, which are located close to each other. Conclusion: Copy number variations should be considered in patients with coexisting clinical expression of different genetic alterations. To the best of our knowledge, our patient is the second case with co-occurrence of trichothiodystrophy type 4 and glutaric aciduria type 3, resulting from a contiguous gene deletion.

Incidental hypertransaminasemia in children-a stepwise approach in primary care.

Children with elevated liver enzymes are occasionally discovered through laboratory work-up from different clinical scenarios. Although the majority will have transient and/or benign conditions, a subgroup will have underlying liver disorders. The differential diagnosis is broad and therefore, a systematic approach is of utmost importance. In this article, we reviewed the most recent and relevant literature to provide a comprehensive overview of the main disease processes that cause hypertransaminasemia in children. Ultimately, we propose a practical stepwise approach to guide primary care physicians in the evaluation of abnormal liver enzymes in asymptomatic children. The first step is to obtain a complete history along with a thorough physical examination to exclude red flags, which should dictate urgent consultation with a paediatric gastroenterologist or hepatologist.  Conclusion: Hypertransaminasemia is a challenging scenario in the primary care setting. The aetiology can be broad, ranging from hepatic and extrahepatic to transient versus chronic liver disease. Timely referral to a specialised centre is of paramount importance for conducting targeted research and to not miss the chance of identifying a progressive, but still asymptomatic, treatable liver disease. What is Known: • Elevated liver enzyme is a challenging scenario in the primary care setting. • There are few studies guiding the evaluation of asymptomatic hypertransaminasemia in the paediatric population and a standardised approach is lacking. What is New: • We propose a practical stepwise approach to guide primary care physicians in the evaluation of abnormal liver enzymes.

Hypertransaminasemia in metastatic renal cell carcinoma patients receiving immune-based combinations: a meta-analysis.

Aims: We performed a meta-analysis to assess the relative risk (RR) of all-grade and grade 3-4 hypertransaminasemia in studies comparing immune-based combinations with sunitinib in treatment-naive patients with advanced renal cell carcinoma. Materials & methods: Outcomes of interest included all-grade and grade 3-4 hypertransaminasemia measured as RRs and 95% confidence intervals (CIs). Results: RRs for all-grade hypertransaminasemia were 1.73 (95% CI: 1.25-2.4) and 1.63 (95% CI: 1.25-2.12) in patients receiving immunocombinations and sunitinib, respectively. The pooled RRs for grade 3-4 hypertransaminasemia were 3.24 and 3.04 in patients treated with immunocombinations or sunitinib. Conclusion: Immune-based combinations were associated with higher hypertransaminasemia risk. Physicians should pay attention to these common but overlooked events. Careful monitoring of tolerability remains a crucial need.

In our study, we aimed to determine the risk for developing alterations in liver function in treatment-naive patients with metastatic renal cell carcinoma, receiving an immunotherapic compound plus a tyrosine-kinase inhibitor or sunitinib alone. We found that combination treatment, compared with sunitinib, is associated with an increased risk to present this type of liver's toxicity, even a high-grade one.

Hypertransaminasemia in cancer patients receiving immunotherapy and immune-based combinations: the MOUSEION-05 study.

BACKGROUND: The antitumor efficacy of immune checkpoint inhibitors (ICIs) has increasingly emerged during the last few years. However, there is a need to identify the safety profile of these agents more comprehensively, including liver toxicity. MATERIALS AND METHODS: Herein, we performed a meta-analysis to assess the risk of all-grade and grade 3-4 hypertransaminasemia in cancer patients receiving ICIs-as monotherapy or in combination with other anticancer agents. All the relevant trials were retrieved through EMBASE, Cochrane Library, and PubMed/Medline databases; eligible studies were selected according to PRISMA statement. The pooled relative risk (RR) and 95% confidence interval (CI) were extracted. RESULTS: Fifty-nine studies were included. The pooled RRs for all-grade AST and ALT increase were 1.45 (95% CI 1.26-1.67) (Supplementary Fig. 3) and 1.51 (95% CI 1.29-1.77) in patients receiving ICIs monotherapy and immune-based combinations compared to control treatment, respectively. The pooled RRs for grade 3-4 AST and ALT increase were 2.16 (95% CI 1.77-2.64) and 2.3 (95% CI 1.91-2.77). CONCLUSIONS: According to our results, ICIs monotherapy and immune-based combinations were associated with higher risk of all-grade and grade 3-4 hypertransaminasemia. Monitoring liver function should be recommended in cancer patients treated with ICIs monotherapy or immune-based combination, and in case of underlying liver disease, a careful risk-benefit assessment appears as a mandatory need.

Mystery(n) Phenotypic Presentation in Europeans: Report of Three Further Novel Missense RNF213 Variants Leading to Severe Syndromic Forms of Moyamoya Angiopathy and Literature Review.

Moyamoya angiopathy (MMA) is a rare cerebral vasculopathy in some cases occurring in children. Incidence is higher in East Asia, where the heterozygous p.Arg4810Lys variant in RNF213 (Mysterin) represents the major susceptibility factor. Rare variants in RNF213 have also been found in European MMA patients with incomplete penetrance and are today a recognized susceptibility factor for other cardiovascular disorders, from extracerebral artery stenosis to hypertension. By whole exome sequencing, we identified three rare and previously unreported missense variants of RNF213 in three children with early onset of bilateral MMA, and subsequently extended clinical and radiological investigations to their carrier relatives. Substitutions all involved highly conserved residues clustered in the C-terminal region of RNF213, mainly in the E3 ligase domain. Probands showed a de novo occurring variant, p.Phe4120Leu (family A), a maternally inherited heterozygous variant, p.Ser4118Cys (family B), and a novel heterozygous variant, p.Glu4867Lys, inherited from the mother, in whom it occurred de novo (family C). Patients from families A and C experienced transient hypertransaminasemia and stenosis of extracerebral arteries. Bilateral MMA was present in the proband's carrier grandfather from family B. The proband from family C and her carrier mother both exhibited annular figurate erythema. Our data confirm that rare heterozygous variants in RNF213 cause MMA in Europeans as well as in East Asian populations, suggesting that substitutions close to positions 4118-4122 and 4867 of RNF213 could lead to a syndromic form of MMA showing elevated aminotransferases and extracerebral vascular involvement, with the possible association of peculiar skin manifestations.

Hepatitis aguda per virus de l’hepatitis E / Hepatitis aguda por virus de la hepatitis E / Acute hepatitis by Hepatitis E virus

Introducció. L’hepatitis aguda és un procés necroinflamatoridel fetge causat per una noxa puntual. Analíticament esmanifesta per un augment de les transaminases i la presentació clínica pot ser variable (de formes subclíniques a insuficiència hepàtica aguda). L’estudi d’hepatitis inclouproves per valorar el grau d’alteració fisiològica i per identificar-ne l’etiologia. La causa més freqüent són les infeccions víriques.Cas clínic. Pacient de 8 anys amb família originària delPakistan, d’on retorna poc abans d’iniciar la clínica. Presenta abdominàlgia, diarrea, febre, colúria i acòlia. En l’exploració física destaca icterícia mucocutània, esplenomegàlia i hepatomegàlia lleus. L’analítica presenta augmentde transaminases i bilirubina directa. S’ingressa per a estudi i tractament simptomàtic. En les serologies s’obté unresultat positiu a virus d’hepatitis E.Comentaris. El virus de l’hepatitis E (VHE) és un virus RNAque pertany a la família Herpesviridae. La caracteritzaciómolecular ha permès identificar-ne quatre genotips: HVE1i HVE2 infecten únicament humans i són predominants enpaïsos en vies de desenvolupament. HVE3 i HVE4 infectentambé altres mamífers. Són responsables dels casos esporàdics a escala mundial. La majoria d’infeccions sónasimptomàtiques en pacients immunocompetents, però demés risc en pacients immunodeprimits pel risc més alt de cronificació. (AU)

Introducción. La hepatitis aguda es un proceso necroinflamatoriodel hígado causado por una noxa puntual. Analíticamente se manifiesta por un aumento de las transaminasas y la presentaciónclínica puede ser variable (de formas subclínicas a insuficienciahepática aguda). El estudio de hepatitis incluye pruebas para valorar el grado de alteración fisiológica y para identificar su etiología. La causa más frecuente son las infecciones víricas.Caso clínico. Paciente de 8 años con familia originaria de Pakistán,de donde vuelve poco antes de iniciar la clínica. Presenta abdominalgia, diarrea, fiebre, coluria y acolia. En la exploración físicadestaca ictericia cutánea-mucosa, esplenomegalia y hepatomegalia leves. En la analítica presenta aumento de transaminasas y bilirrubina directa. Se ingresa para estudio y tratamiento sintomático. En las serologías se obtiene un resultado positivo a virus dela hepatitis E.Comentarios. El virus de la hepatitis E (VHE) es un virus RNA quepertenece a la familia Herpesviridae. La caracterización molecularha permitido identificar cuatro genotipos: HVE1 y HVE2 infectanúnicamente a humanos y son predominantes en países en vías dedesarrollo. HVE3 y HVE4 infectan también a otros mamíferos. Sonresponsables de los casos esporádicos a nivel mundial. La mayoríade infecciones son asintomáticas en pacientes inmunocompetentes, pero de mayor riesgo en pacientes inmunodeprimidos por elmayor riesgo de cronificación. (AU)

Introduction. Acute hepatitis is a necroinflammatory process of theliver caused by isolated noxa. Its laboratory findings are characterized by an increase in liver transaminases, and the clinical presentation may be variable (from subclinical forms to acute liverfailure). The study of hepatitis includes tests to assess the degreeof physiological alteration and to identify its etiology. The mostcommon cause is viral infections.Clinical case. An 8-year-old patient who recently returned from atrip to Pakistan presented with abdominal pain, diarrhea, fever,choluria and acholia. Physical examination revealed mild mucocutaneous jaundice, splenomegaly, and hepatomegaly. Laboratoryevaluation showed an increase in liver transaminases and directbilirubin. He was admitted for diagnostic evaluation and symptomatic treatment. Serology for hepatitis E virus resulted positive.Comments. Hepatitis E virus (HEV) is an RNA virus of the Herpesviridae family. Molecular characterization has identified four genotypes, HVE 1-4. HVE1 and HVE2 infect only humans and are predominant in developing countries, whereas HVE3 and HVE4 alsoinfect other mammals. HVE is responsible for sporadic casesworldwide. Most infections are asymptomatic in immunocompetent patients but risk is higher in immunocompromised patientsdue to increased risk of chronicity. (AU)

Diagnostic action against hypertransaminasemia in paediatrics: Consensus document of Sociedad Española de Gastroenterología, Hepatología y Nutrición Pediátrica (SEGHNP), Asociación Española de Pediatría de Atención Primaria (AEPap) and Sociedad Española de Pediatría de Atención Primaria (SEPEAP).

Hypertransaminasemia is a frequent finding in pediatrics, which could reflect potentially treatable serious disease. The aim of this document is to establish, by reviewing the available evidence, a consensus for an adequate management of hypertransaminasemia, from its detection until the study is complete. To this end, a working group was formed with the participation of members of the Society of Pediatric Gastroenterology, Hepatology and Nutrition (SEGHNP), the Spanish Association of Primary Care Pediatrics (AEPap) and the Spanish Society of Primary Care Pediatrics (SEPEAP). Twenty-one recommendations are established with a marked practical component that will be useful in hospital clinical practice and primary care.

A case of ceftriaxone-induced liver injury and literature review.

Background: Liver injury evoked by drugs spans various clinical manifestations ranging from mild biochemical abnormalities to acute liver failure. Ceftriaxone is a third-generation cephalosporin often used in clinical practice for its long half-life, high tissue penetration rate, wide spectrum and good safety profile. Ceftriaxone, as other cephalosporins have little hepatotoxicity; however, few cases of toxic hepatitis induced by this antibiotic have been reported. Case Presentation: We describe a case of acute, drug-induced liver injury ('hepatitis') in a 77 years-old female patient treated with ceftriaxone for pneumonia. After 48 hours from antibiotic administration, clinical condition worsened with a clinical and laboratory profile compatible with an acute non cholestatic liver injury. Ceftriaxone administration was immediately stopped and the patient was treated with hydro-electrolyte replacement, high-flow oxygen, vitamin K infusion, steroids and proton-pump inhibitors with a progressive clinical improvement. Conclusions: Even if rare, a ceftriaxone-induced hepatotoxicity (confirmed by RUCAM score), should be considered when all other possible causes have been excluded.

Actuación diagnóstica ante hipertransaminasemia en pediatría: documento de consenso de Sociedad Española de Gastroenterología, Hepatología y Nutrición Pediátrica (SEGHNP), Asociación Española de Pediatría de Atención Primaria (AEPap) y Sociedad Española de Pediatría de Atención Primaria (SEPEAP) / Diagnostic action against hypertransaminasemia in paediatrics: Consensus document of Sociedad Española de Gastroenterología, Hepatología y Nutrición Pediátrica (SEGHNP), Asociación Española de Pediatría de Atención Primaria (AEPap) and Sociedad Española de Pediatría de Atención Primaria (SEPEAP)

La hipertransaminasemia es un hallazgo frecuente en pediatría, puede ser banal o reflejar enfermedad grave potencialmente tratable. El objetivo de este documento es establecer, mediante la revisión de la evidencia disponible, un consenso para un adecuado enfoque práctico desde la detección de la hipertransaminasemia hasta completar su estudio en la edad pediátrica. Para ello, se constituyó un grupo de trabajo con participación de miembros de la Sociedad de Gastroenterología, Hepatología y Nutrición Pediátrica (SEGHNP), Asociación Española de Pediatría de Atención Primaria (AEPap) y Sociedad Española de Pediatría de Atención Primaria (SEPEAP). Se establecieron 21 recomendaciones con el objetivo de que sirvan de utilidad en la práctica clínica habitual tanto en atención primaria como hospitalaria. (AU)

Hypertransaminasemia is a frequent finding in pediatrics, which could reflect potentially treatable serious disease. The aim of this document is to establish, by reviewing the available evidence, a consensus for an adequate management of hypertransaminasemia, from its detection until the study is complete. To this end, a working group was formed with the participation of members of the Society of Pediatric Gastroenterology, Hepatology and Nutrition (SEGHNP), the Spanish Association of Primary Care Pediatrics (AEPap) and the Spanish Society of Primary Care Pediatrics (SEPEAP). Twenty-one recommendations are established with a marked practical component that will be useful in hospital clinical practice and primary care. (AU)

Coeliac disease hidden by cryptogenic hypertransaminasaemia in children: a case report.

Celiac disease is a chronic immune-mediated multisystem disorder that may affect several organs. Isolated hypertransaminasemia, with mild or nonspecific histologic changes in the liver biopsy, also known as "celiac hepatitis", is the most frequent presentation of liver injury in celiac disease. Both, histologic changes and liver enzymes reverse to normal after treatment with a gluten-free diet in most patients. Here we report the case of a young boy presenting with asymptomatic and persistent hypertransaminasemia whose etiologic investigation led to the diagnosis of celiac disease that resolved with dietary treatment alone. This case emphasizes the need to screen Celiac disease in patients with cryptogenic hypertransaminasemia, irrespective of the existence of gastrointestinal symptoms. It also exemplifies a particular situation in which a liver biopsy is useful to establish the diagnosis of celiac hepatitis.

Elevated liver enzymes of newly diagnosed pediatric celiac patients-a prospective-observational study.

Celiac disease clinical presentation is constantly changing. We set to determine the prevalence of elevated transaminases in newly diagnosed celiac patients and to evaluate this sub-group of patients for associated clinical and laboratory findings and assess their natural course of disease following therapeutic diet initiation. We conducted a prospective-observational study of all newly diagnosed pediatric celiac patients, between August 2016 and April 2018, in a pediatric gastroenterology clinic. Clinical data, anthropometrics, and blood test results were recorded at diagnosis and at 3, 6, and 12 months, respectively, of follow-up. We compared patients with normal and elevated transaminases at diagnosis. ALT threshold was set at 24 U/l. Of 125 newly diagnosed celiac patients, 31 (24.8%) had elevated ALT at diagnosis; two (1.6%) with over 3 × ULN. Patients with elevated ALT at diagnosis were significantly younger (mean age 5.5 (SD 3.4) vs. 7.3 (SD 3.7) years, p < 0.01) and more commonly presented with diarrhea (32.3% vs. 14.9%, p = 0.03). Eighty percent of patients with elevated ALT levels normalized their ALT within 3 months and all within 1 year. Following gluten-free diet initiation, patients with elevated ALT had similar clinical course, growth, serology normalization rate, and laboratory results, compared to patients with normal ALT over a 1-year follow-up. A single patient was simultaneously co-diagnosed with celiac disease and autoimmune hepatitis.Conclusion: Clinically significant ALT abnormalities are rare among newly diagnosed pediatric celiac patients. Significant elevations failing to normalize on a gluten-free diet should raise concern of a concomitant primary liver disease and warrant further investigations. What is Known: • Elevated liver enzymes may be an extra-intestinal manifestation of celiac disease. • Reported prevalences of ALT elevations among children with a new diagnosis of celiac disease ranges between 5 and 40%. What is New: • ALT elevations are present in 25% of children with a new diagnosis of celiac disease. • Significant elevations (>3 × ULN) are rare (1.6%). • Elevated liver enzymes are associated with earlier age at diagnosis. • The natural history of patients with elevated liver enzymes at diagnosis is comparable to those without.

Early Hypertransaminasemia after Kidney Transplantation: Significance and Evolution According to Donor Type.

Early hypertransaminasemia after kidney transplantation (KT) is frequent. It has been associated with the crosstalk produced between the liver and the kidney in ischemia-reperfusion situations. However, the influence of the donor type has not been evaluated. We present a retrospective study analyzing the increase in serum aspartate aminotransferase/alanine aminotransferase (AST/ALT) during the first three months post-KT in 151 recipients who received thymoglobulin as induction therapy, either from brain-death donors (DBD, n = 75), controlled circulatory death donors (cDCD, n = 33), or uncontrolled DCD (uDCD, n = 43). Eighty-five KT recipients from DBD who received basiliximab were included as controls. From KT recipients who received thymoglobulin, 33.6/43.4% presented with an increase in AST/ALT at 72 h post-KT, respectively. Regarding donor type, the percentage of recipients who experienced 72 h post-KT hypertransaminasemia was higher in uDCD group (65.1/83.7% vs. 20.3/26% in DBD and 20.7/27.6% in cDCD, p < 0.001). Within the control group, 9.4/12.9% of patients presented with AST/ALT elevation. One month after transplant, AST/ALT values returned to baseline in all groups. The multivariate analysis showed that uDCD recipients had 6- to 12-fold higher risk of developing early post-KT hypertransaminasemia. Early post-KT hypertransaminasemia is a frequent and transient event related to the kidney donor type, being more frequent in uDCD recipients.

Celiac Disease in Conjunction with Hereditary Fructose Intolerance as a Rare Cause of Liver Steatosis with Mild Hypertransaminasemia-A Case Report.

Celiac disease (CD) has been associated with several genetic and autoimmune disorders, but its association with hereditary fructose intolerance (HFI) is very rare. The possibility of an association between CD and HFI should be considered, especially in patients with a lack of improvement after a gluten-free diet. Children with HFI often present with a wide range of symptoms, however, data about a strong aversion to fruits and sweets may be helpful to establish the diagnosis. The diagnosis of HFI should be confirmed in genetic testing. Both CD and HFI may present with liver steatosis with hypertransaminasemia. In patients with these two disorders, the dietary restrictions of gluten and fructose improve clinical symptoms and protect them from secondary complications. We report the case of a child with the concurrence of these two disorders.

Atypically Protracted Course of Liver Involvement in Kawasaki Disease. Case Report and Literature Review.

Hypertransaminasemia in patients with Kawasaki disease (KD) is reported to be transient. Here, we describe a child with an atypically protracted course of liver tests abnormalities and review the inherent literature. The patient was hospitalized at age 7-months for isolated hypertransaminasemia detected during a classical KD diagnosed 3 months before, and persistent since then. KD clinical evolution had been favorable, with rapid response to acetylsalicylic acid and intravenous immunoglobulins. Liver enzymes however remained persistently elevated with a fluctuating pattern (ALT > AST levels; peak of AST 186 IU/L and ALT 240 IU/L). During follow-up, the main causes of liver dysfunction had to be excluded through appropriate and extensive laboratory investigations. Transaminases values become steadily normal only 7 months after the acute presentation of KD. Conclusions: Our report shows that an atypically protracted courses of KD-related hypertransaminasemia above the previously reported temporal limits should be taken into account during the stepwise diagnostic approach to the patient's liver dysfunction. Insidious acetylsalycilic acid-hepatotoxicity warrants consideration in the differential diagnosis.