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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

IntroductionElevated 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.MethodsThis 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.ResultsOverall, 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

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. [ABSTRACT FROM AUTHOR]

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.

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Cyclin-dependent kinase inhibitors (CDKIs) and endocrine therapy (ET) are the corner-stone of systemic therapy for patients with hormone-positive (HR+) HER2-negative metastatic breast cancer (MBC). However, limited data exist regarding rechallenge treatment strategies with CDKIs after limiting toxicity. In this report, we provide evidence of the safety and efficacy of sequential treatment with palbociclib or abemaciclib in 6 HR+/HER- MBC patients who experienced grade ≥3 ribociclib-induced hypertransaminasemia. Until results from large observational or randomized studies are communicated, empirical evidence may help make individualized decisions on CDKI rechallenge beyond ribociclib-induced unacceptable liver toxicity.

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Diagnosis of pediatric steatohepatitis is a challenging issue due to a vast number of established and novel causes. Here, we report a child with Multiple Acyl-CoA Dehydrogenase Deficiency (MADD) presenting with an underrated muscle weakness, exercise intolerance and an atypically severe steatotic liver involvement. A systematic literature review of liver involvement in MADD was performed as well. Our patient is a 11-year-old otherwise healthy, non-obese, male child admitted for some weakness/asthenia, vomiting and recurrent severe hypertransaminasemia (aspartate and alanine aminotransferases up to ×20 times upper limit of normal). Hepatic ultrasound showed a bright liver. MRI detected mild lipid storage of thighs muscles. A liver biopsy showed a micro-macrovacuolar steatohepatitis with minimal fibrosis. Main causes of hypertransaminasemia were ruled out. Serum aminoacids (increased proline), acylcarnitines (increased C4-C18) and a large excretion of urinary glutaric acid, ethylmalonic, butyric, isobutyric, 2-methyl-butyric and isovaleric acids suggested a diagnosis of MADD. Serum acylcarnitines and urinary organic acids fluctuated overtime paralleling serum transaminases during periods of illness/catabolic stress, confirming their recurrent nature. Genetic testing confirmed the diagnosis [homozygous c.1658A > G (p.Tyr553Cys) in exon 12 of the ETFDH gene]. Lipid-restricted diet and riboflavin treatment rapidly ameliorated symptoms, hepatic ultrasonography/enzymes, and metabolic profiles. Literature review (37 retrieved eligible studies, 283 patients) showed that liver is an extramuscular organ rarely involved in late-onset MADD (70 patients), and that amongst 45 patients who had fatty liver only nine had severe presentation.Conclusion: MADD is a disorder with a clinically heterogeneous phenotype. Our study suggests that MADD warrants consideration in the work-up of obesity-unrelated severe steatohepatitis.

Hepatitis-associated aplastic anemia is a well-recognized clinical syndrome in which marrow failure follows the development of hepatitis. Although aplastic anemia is intimately related to paroxysmal nocturnal hemoglobinuria, until now, no cases of PNH-associated hepatitis have been described. We report a case of recurrent acute hepatitis preceding the clinical onset of PNH. Treatment of PNH with the complement inhibitor eculizumab (Soliris®) prevented both recurrences of episodes of intravascular hemolysis and liver enzyme alteration. This is the first known published case of PNH-associated hepatitis. [ABSTRACT FROM AUTHOR]

Duchenne musculer dystrophy (DMD) is a X linked disorder caused by a deficient or abnormal synthesis of dystrophine protein. Children with DMD are rarely symptomatic at birth or in early infancy, and the diagnosis is extremely difficult and even depends on happenstances. In this article a 5.5-month-old infant in whom increases in liver function tests were detected in routine tests performed for general anesthesia and later diagnosed to have DMD is presented. DMD, as a rare disease should be considered in etiological investigations in infants with elevations in liver function tests of any origin and with normal physical examination findings, and the utility of simple biochemical markers such as creatinin kinase in establishing diagnosis before performing further detailed investigations should be remembered.

Introduction: The clinical spectrum of gluten-sensitive enteropathy is remarkably varied and the disease can affect many extraintestinal organs and systems, including the liver. Liver involvement, which is observed in patients with gluten-sensitive enteropathy, varies from an asymptomatic increase of hepatic enzymes or non-specific reactive hepatitis (cryptogenic hepatic disorders) to chronic liver disease. The histological changes and the dynamics of enzymes are notably different after a gluten-free diet (GFD) treatment. Patients and Methods: A clinical observation included 112 patients with gluten-sensitive enteropathy and 22 patients with gluten sensitivity, who passed through the Clinic of Gastroenterology, Hepatology and Nutrition at St. Marina University Hospital, Varna for the period from January, 2005 to June, 2015. Thirty-four men and 78 women between the ages of 18 and 76 were included. The control group consisted of 22 patients of whom 6 were men and 16 – women. Results and Discussion: Patients with proven hepatic diseases with autoimmune or viral genesis were excluded from the group participating in the current study. The observation and study were conducted on 8 patients – 3 men and 5 women put on a GFD for a period of 6 months. All 8 patients were with abnormal hepatic enzyme levels. The median levels (±SD) of ASAT and ALAT were 62.6 ±16.5 IU/mL with a range of 31-186 IU/mL, and 69.3 ± 9.3 IU/mL and a range of 63-432 IU/mL, respectively. The median concentrations of alkaline phosphatase were ± 280.3±118.7 mmol/L (range -160-428 mmol/L). Six months after GFD, the hepatic enzyme levels decreased to a level of 24.5±5.1 IU/mL in all patients. Hepatic abnormalities varying from mild changes of hepatic enzyme levels to liver failure at the time of diagnosis could be treated with GFD. Its effect on the severity of other hepatic diseases, for example autoimmune hepatitis, is not clear yet. Regardless of the effect on the concomitant hepatic diseases, GFD is needed for the improvement of the symptoms of gluten-sensitive enteropathy and all long-term consequences. The lack of sufficient amount of proof does not undermine the fact that clinicians should consider the diagnosis – gluten-sensitive enteropathy – when hypertransaminasemia is observed without the presence of other causes of liver dysfunction.

Cyclin-dependent kinase inhibitors (CDKIs) and endocrine therapy (ET) are the corner-stone of systemic therapy for patients with hormone-positive (HR+) HER2-negative metastatic breast cancer (MBC). However, limited data exist regarding rechallenge treatment strategies with CDKIs after limiting toxicity. In this report, we provide evidence of the safety and efficacy of sequential treatment with palbociclib or abemaciclib in 6 HR+/HER- MBC patients who experienced grade ≥3 ribociclib-induced hypertransaminasemia. Until results from large observational or randomized studies are communicated, empirical evidence may help make individualized decisions on CDKI rechallenge beyond ribociclib-induced unacceptable liver toxicity. [ABSTRACT FROM AUTHOR]

Objective: We aimed to determine the etiology of hypertransaminasemia in children, demonstrate the differences according to the age and evaluate course of transaminases. Method: We retrospectively analyzed the medical records of children who presented with elevated transaminase levels for at least 2 months, aged between 3 months and 18 years, for demographic features, laboratory, radiologic and histopathological findings. Results: Among total 292 children, 194 (66.4%) were male and 98 (33.6%) were female. The mean age was 6.5±5.4 years. The 45.9% of the children had no complaints at presentation. Majority of the patients had mildly elevated transaminases (81.6%). The most common etiology was nonalcoholic fatty liver disease (NAFLD) (25.7%). The NAFLD was more prevelant in patients older than 5 years-old (p<0.001). The second cause was infectious diseases (97.8% were viral infections) and more prevelant in patients younger than 2 years-old (p=0.043). In 34.1% of the children, no overt cause of hypertransaminasemia was identified. The patients with unidentified etiology were significantly younger, but had higher mean aspartate aminotransferase (AST) levels than the patients in whom the etiology was identified (p= <0.0001, p=0.008 respectively). The normalization of transaminases was seen in 40.4% of the patients at mean 5.4±4.4 months. The shortest normalization time was observed in drug related liver injury (DILI) among all other etiologies (p=0.015). Conclusions: The most common cause of hypertransaminasemia in childhood were NAFLD and viral infections, which varies by age. A stepwise approachment to hypertransaminasemia leads to early diagnosis. [ABSTRACT FROM AUTHOR]

Abstract Background Short stature (SS) is a relatively early sign of poor health. Only in 5% of cases we can explain it through the presence of endocrinological pathologies. Therefore, if SS is present since the first months of life, it is necessary to investigate all systemic disorders with secondary effects on growth. Case presentation We report the case of a 16-months-old male infant with severe SS apparently not associated with other clinical signs or symptoms. The patient arrived to our attention after he was hospitalized for an Echovirus enteritis, associated to moderate neutropenia (800/mm3) and hypertransaminasemia (AST 116 U/L, ALT 88 U/L) at the age of 13 months. SS was detected in that occasion. Since SS persisted even after the complete resolution of enteritis symptoms, he was taken care by our unit. Conclusions SS appeared in the first months of life and associated with moderate neutropenia and hypertransaminasemia led us to the diagnosis of Shwachmann-Diamond syndrome. We recommend paying further attention to this condition during the differential diagnosis of children with severe SS.

Abstract Background Crimean-Congo hemorrhagic fever is a tick-borne disease described in more than 30 countries in Europe, Asia, and Africa. Albania is located in the southwestern part of the Balkan Peninsula. In 1986, the first case of Crimean-Congo hemorrhagic fever was registered, and cases of patients with hemorrhagic fever are rising, and most of them present in a serious condition, when the mortality rate is very high. In districts like Mirdite, Lezhe, Gjirokaster, Skrapar, Erseke, and Kukes, there is delineated human-to-human transmission. Case presentation We report the case of a 32 year-old Albanian woman from a rural area of Albania. She was hospitalized at the Infectious Diseases Service, for a severe influenza-like illness of 4 days duration. Our patient had been bitten by a tick while working in her garden. She presented with nausea, vomiting, headache and muscle pain. A physical examination found a high fever of 40 °C, an enlarged liver, petechia, and vaginal bleeding; flapping tremor and fetor hepaticus were found as a sign for hepatic encephalopathy; and confusion and disorientation were observed in her neurological examination. Her platelet and white blood cell counts were very low, while her aspartate aminotransferase and alanine aminotransferase levels were very high. She was transferred to the intensive care unit because of her worsening condition. Serological and C-reactive protein test results for Crimean-Congo hemorrhagic fever were positive. She was treated with oral ribavirin and discharged with normal parameters. Conclusions People in high-risk professions in the endemic areas should be informed and trained on the risk of Crimean-Congo hemorrhagic fever as a matter of urgency. Vaginal bleeding is not always a gynecological problem. In Albania, these places are the mountainous areas, so people who have traveled to these areas and who have symptoms after a tick bite are advised to contact their doctors.

Alagille syndrome is an autosomal dominant multisystem disorder with variable phenotypic penetrance, caused by heterozygous mutations in JAG1 or NOTCH2, encoding for the components of the Notch signaling pathway. In this paper, we described a novel mutation not yet reported in literature. This 3-years old male child was referred to our Clinical Genetics Unit because of delayed psychomotor development, systolic murmur, dysmorphic facial features, and hypertransaminasemia. The novel JAG1 heterozygous c.2026delT variant in exon 16 was found. JAG1 mutations are classified as protein truncating and non-protein truncating, without any genotype-phenotype correlation. The detected mutation determines a stop codon (p.Cys676AlafsTer67) in the gene sequence, encoding a truncated protein. Our report broadens the spectrum of JAG1 gene mutations.

Aim of the study: To evaluate the prevalence and the type of liver pathology in children at the time of diagnosis of celiac disease (CD). Material and methods: Data from newly diagnosed children with CD hospitalized in the university hospital were retrospectively reviewed. Liver pathology was defined as elevated alanine transaminase (ALT) and/or gamma-glutamyl transpeptidase (GGT) serum activity and/or pathological changes of the organ in ultrasound. Results: Liver pathology was detected in 17 of 149 children (11.4%). Ten patients (6.7%) had an elevated ALT serum activity, whereas no child had an elevated GGT activity. Pathological changes of liver in ultrasound (mainly enlargement or steatosis of the organ) were found in 12 patients (8.1%), of whom 5 children (3.4%) had simultaneously elevated ALT serum activity. Children with liver pathology had lower iron (Fe) (p = 0.02) and folic acid (p = 0.01) concentrations compared to the rest of the patients. There were no statistically significant differences between liver pathology existence and age, sex, serum immunoglobulin A anti-tissue transglutaminase type 2 antibodies (IgA anti-TG2), ferritin, vitamin B12, or vitamin D concentrations. Moreover, a positive correlation between IgA anti-TG2 concentration and ALT serum activity was found (p < 0.01, R = 0.29). Conclusions: Liver pathology is present at diagnosis in a significant proportion of children with CD in the form of hypertransaminasemia and pathological changes of the organ in ultrasound. There is a correlation between IgA anti-TG2 concentration and ALT serum activity. [ABSTRACT FROM AUTHOR]

The paper presents the case of a 12-year-old boy hospitalised due to persistent hypertransaminasemia of unknown origin, in whom rare metabolic disease - Pompe disease, was finally diagnosed. We discuss the possible symptoms and the diagnostic criteria for Pompe disease, as well as modern genetic methods of diagnosing. The importance of including this metabolic disease in differential diagnosis of hypertransaminasemia was underlined. The recombinant human a-glucosidase as the enzyme replacement therapy makes nowadays the early diagnosis of Pompe disease especially important. [ABSTRACT FROM AUTHOR]

Ming-Chang Ku,1,2 Victor C Kok,3,4 Ming-Yung Lee,5 Soa-Min Hsu,1 Pei-Yu Lee,1 Che-Wei Chang,1 Yeu-Sheng Tyan,6 Chi-Wen Juan7,8 1Department of Radiology, Kuang Tien General Hospital, Taichung, 2Department of Nursing, Jen-Teh Junior College of Medicine, Nursing and Management, Miaoli, 3Department of Internal Medicine, Division of Medical Oncology, Kuang Tien General Hospital, 4Department of Bioinformatics and Medical Engineering, Asia University, 5Department of Statistics and Informatics Science, Providence University, 6Department of Medical Imaging, Chung Shan Medical University Hospital, 7Department of Emergency Medicine, Kuang Tien General Hospital, 8Department of Nursing, HungKuang University, Taichung, Taiwan Objectives: Gallbladder opacification (GBO) on computed tomography (CT) imaging may obscure certain pathological or emergent conditions in the gallbladder, such as neoplasms, stones, and hemorrhagic cholecystitis. This study aimed to investigate the clinical contributing factors that could predict the presence of delayed GBO determined by CT.Methods: This study retrospectively evaluated 243 consecutive patients who received enhanced CT or intravenous pyelography imaging and then underwent abdominal CT imaging within 5 days. According to the interval between imaging, the patients were divided into group A (1 day), group B (2 or 3 days), and group C (4 or 5 days). Three radiologists evaluated CT images to determine GBO. Fisher’s exact test and multivariate backward stepwise elimination logistic regression were performed.Results: Positive GBO was significantly associated with the interval between imaging studies, contrast type, contrast volume, renal function, and hypertransaminasemia (P

Background: Short stature (SS) is a relatively early sign of poor health. Only in 5% of cases we can explain it through the presence of endocrinological pathologies. Therefore, if SS is present since the first months of life, it is necessary to investigate all systemic disorders with secondary effects on growth. Case presentation: We report the case of a 16-months-old male infant with severe SS apparently not associated with other clinical signs or symptoms. The patient arrived to our attention after he was hospitalized for an Echovirus enteritis, associated to moderate neutropenia (800/mm³) and hypertransaminasemia (AST 116 U/L, ALT 88 U/L) at the age of 13 months. SS was detected in that occasion. Since SS persisted even after the complete resolution of enteritis symptoms, he was taken care by our unit. Conclusions: SS appeared in the first months of life and associated with moderate neutropenia and hypertransaminasemia led us to the diagnosis of Shwachmann-Diamond syndrome. We recommend paying further attention to this condition during the differential diagnosis of children with severe SS. [ABSTRACT FROM AUTHOR]

The evaluation of serum liver enzyme levels is the most used surrogate marker of liver injury in clinical practice. The prevalence and association of abnormal enzyme values with hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, and with other major causes of liver damage (obesity, diabetes, dyslipidemia, and alcohol abuse) were evaluated in individuals attending the surgeries of 14 general practitioners (GPs) working in Messina. Alanine-amino-transferase, aspartate-amino-transferase, and gamma-glutamyl-transpeptidase measurements were measured in 7816 individuals consecutively attending the GP surgeries between January 1, 2011 and June 30, 2012. Five-thousand-eight-hundred-six subjects (74.3 %) had the tests performed, and 1189 of them (20.5 %) showed increased liver enzyme levels. Sixty-nine of these 1189 individuals (5.8 %) were HCV positive and 12 HBV positive (1 %), 755 (63.5 %) were overweight or obese, 288 (24.2 %) had diabetes, and 351 (29.5 %) had dyslipidemia; 262 (22 %) drank >2 alcoholic units/day. Overall, 57 % of individuals with abnormal liver enzymes had multiple possible causes of liver disease, 28 % one cause, and 15 % no apparent cause. In conclusion, this study shows that 1/5 of individuals attending GP surgeries have altered liver biochemistry and that overweight and metabolic disorders have become the major causes of liver damage even in South Italy, where HBV and HCV were endemic in the past century. Notably, many HCV and HBV patients are still unaware of their infected status, and GPs are essential for their timely identification. [ABSTRACT FROM AUTHOR]

Background: Celiac disease (CD) is an immune mediated condition that leads to small bowel atrophy and improve with a gluten free diet (GFD). Extra-intestinal manifestations of CD include hypertransaminasemia. In this study, the effects of a GFD on hypertransaminasemia in patients with newly diagnosed CD were studied. Methods: Ninety eight new diagnosed consecutive patients with CD 40 males and 58 females) with mean age of 32 ± 17.1 were studied. All patients with CD were treated with a GFD. Patients with hypertransaminasemia, at diagnosis, had a cirrhosis screen performed. Patients with a negative cirrhosis screen were reviewed, 6 months after the introduction of a GFD, and serum levels of liver transaminases were measured again. Results: Nine patients had hypertransaminasemia. One patient was Hepatitis B surface antigen positive and was excluded from this study. The 8 remaining patients had no obvious cause for the hypertransaminasemia. Mean (± SD) of baseline aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were 42.6 ± 16.5 IU/L (range: 16-66 IU/L) and 69.3 ± 9.3 IU/L (range: 52-81 IU/L). Six months after treatment with a GFD, mean AST and ALT levels decreased to 24.5 ± 5.1 IU/L (range: 18-31 IU/L) (P: 0.04) and 24.6 ± 6 IU/L (range: 17-32 IU/L) (P: 0.01), respectively. In 7 patients the hypertransaminasemia, at diagnosis had resolved. Conclusions: This study provides further evidence that some patients with CD have a reversible hypertransaminasemia that resolves with a GFD.

Background: Celiac disease (CD) has been found in up to 10% of the patients presenting with unexplained abnormal liver function tests (LFT). As there is no precise data from our country in this regard, we investigated the prevalence of CD in patients presenting with abnormal LFT. Methods: From 2003 to 2008, we measured IgA anti-tissue transglutaminase (t-TG) antibody (with ELISA technique) within the first-level screening steps for all patients presenting with abnormal LFT to three outpatient gastroenterology clinics in Isfahan, IRAN. All subjects with an IgA anti-tTG antibody value of >10 μ/ml (seropositive) were undergone upper gastrointestinal endoscopy and duodenal biopsy. Histopathological changes were assessed according to the Marsh classification. CD was defined as being seropositive with Marsh I or above in histopathology and having a good response to gluten free diet (GFD). Results: During the study, 224 patients were evaluated, out of which, 10 patients (4.4%) were seropositive for CD. Duodenal biopsies were performed in eight patients and revealed six (2.7%) cases of Marsh I or above (four Marsh IIIA, two Marsh I), all of them had good response to GFD. The overall prevalence of CD among patients with hypertransaminasemia, autoimmune hepatitis, and cryptogenic cirrhosis was determined as 10.7% (3/28), 3.4% (2/59), and 5.3% (1/19), respectively. Conclusion: Serological screening with IgA anti-tTG antibody test should be routinely performed in patients presenting with abnormal LFT and especially those with chronic liver diseases including hypertransaminasemia, autoimmune hepatitis, and cryptogenic cirrhosis.

Celiac disease is an autoimmune disorder primarily targeting the small bowel, although extraintestinal extensions have been reported. The autoimmune processes can affect the liver with manifestations such as primary biliary cirrhosis and autoimmune hepatitis. We describe a 61-year-old woman with celiac disease and an increased levels of aminotransferases. The persistence of increased levels of aminotransferases after 1 year of gluten-free diet and the positivity for an anti-nuclear and anti-double-strand DNA antibodies led to a misdiagnosis of systemic lupus erythematosus-related hepatitis. Based on these findings the patient was placed on steroids, which after a few months were stopped because of the onset of diabetes mellitus. Soon after steroid withdrawal, the patient had a marked increase in aminotransferases and γ-globulins, and a liver biopsy revealed chronic active hepatitis. A course of three months of steroids and azathioprine normalized both biochemical and clinical parameters. Currently the patient is symptom-free and doing well. In conclusion, a hypertransaminasemia persisting after a gluten-free diet should be interpreted as a sign of coexisting autoimmune liver disease. Any autoantibody positivity (in this case to ANA and anti-dsDNA) should be carefully considered in order to avoid misdiagnosis delaying appropriate clinical management.

Objectives: Gallbladder opacification (GBO) on computed tomography (CT) imaging may obscure certain pathological or emergent conditions in the gallbladder, such as neoplasms, stones, and hemorrhagic cholecystitis. This study aimed to investigate the clinical contributing factors that could predict the presence of delayed GBO determined by CT.Methods: This study retrospectively evaluated 243 consecutive patients who received enhanced CT or intravenous pyelography imaging and then underwent abdominal CT imaging within 5 days. According to the interval between imaging, the patients were divided into group A (1 day), group B (2 or 3 days), and group C (4 or 5 days). Three radiologists evaluated CT images to determine GBO. Fisher's exact test and multivariate backward stepwise elimination logistic regression were performed.Results: Positive GBO was significantly associated with the interval between imaging studies, contrast type, contrast volume, renal function, and hypertransaminasemia (P<0.05). Multivariate backward stepwise elimination logistic regression analysis of the three groups identified contrast type and hypertransaminasemia as independent predictors of GBO in group B patients (odds ratio [OR], 13.52, 95% confidence interval [CI], 1.72-106.38 and OR, 3.43, 95% CI, 1.31-8.98, respectively; P<0.05). Hypertransaminasemia was the only independent predictor of GBO in group C patients with an OR of 7.2 (95% CI, 1.62-31.73). Hypertransaminasemia was noted in three patients (100%) who initially underwent imaging 5 days prior to GBO.Conclusion: Delayed GBO on CT imaging may be associated with laboratory hypertransaminasemia, particularly in patients receiving contrast medium over a period of ≥4 days. A detailed clinical history, physical examination, and further workup are of paramount importance for investigating the underlying cause behind the hypertransaminasemia. [ABSTRACT FROM AUTHOR]

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., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2022 by S. Karger AG, Basel.)

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.

Nonalcoholic fatty liver disease (NAFLD) is a medical condition that may progress to end-stage liver disease. The spectrum of NAFLD is wide and ranges from simple fat accumulation in hepatocytes (steatosis), to fat accumulation plus necroinflammatory activity with or without fibrosis (steatohepatitis). In addition, NAFLD is the most common cause of abnormal liver-test results among adults with a prevalence of 13%-23%. This case report is an example of a patient with asymptomatic hypertransaminasemia and severe hepatic steatosis without inflammation in which the diagnosis was made by liver biopsy.

We report a case of a 4-months infant with fever in the absence of other specific symptoms that has rapidly and unexpectedly developed acute liver failure (ALF) with coagulopathy and complicated with bone marrow failure without encephalopathy. The main viral infection agents (hepatitis virus A, B, C, Citomegalovirus, Ebstain Barr virus, Parvovirus B19, Adenovirus), drug-induced hepatotoxicity and metabolic disorders associated to ALF were excluded. Quantitative determination of Human Herpesvirus 6 (HHV6) genome was positive with a significant number of copies for mL. A favorable evolution of the clinical symptoms and a progressive hematochemical resolution were obtained. Plasma and Vitamin K were administrated as a support therapy for treating coagulopathy. The present case report and the cases’ review from the literature, evidence the importance of always including screening for HHV6 infection in the diagnostic approach to acute onset of liver failure. HHV6 is a common virus in the pediatric population with a greater number of cases of fulminant viral non-A, non-B, non-C hepatitis in immunocompetent patients due to this virus: these forms have often a high mortality rate and maybe necessitate liver transplantation; for this reason correct etiological agent identification is mandatory for the prognosis and it has to be based on the quantitative search of the virus’s genome. Pathogenesis of liver-induced damage associated to HHV6 remains unclear; however in vitro studies demonstrate the potential hepatotoxicity effects of this virus.

Background: Celiac disease (CD) is an immune mediated condition that leads to small bowel atrophy that resolves with a gluten free diet (GFD). Extra intestinal manifestations of CD include hypertransaminasemia. In this study, the effects of a GFD on hypertransaminasemia in patients with newly diagnosed CD were studied. Methods: Ninety eight new diagnosed consecutive patients with CD 40 males and 58 females) with mean age of 32 ± 17.1 were studied. All patients with CD were treated with a GFD. Patients with hypertransaminasemia, at diagnosis, had a cirrhosis screen performed. Patients with a negative cirrhosis screen were reviewed, 6 months after the introduction of a GFD, and serum levels of liver transaminases were measured again. Results: Nine patients had hypertransaminasemia. One patient was Hepatitis B surface antigen positive and was excluded from this study. The 8 remaining patients had no obvious cause for the hypertransaminasemia. Mean (± SD) of baseline aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were 42.6 ± 16.5 IU/L (range: 16 66 IU/L) and 69.3 ± 9.3 IU/L (range: 52 81 IU/L). Six months after treatment with a GFD, mean AST and ALT levels decreased to 24.5 ± 5.1 IU/L (range: 18 31 IU/L) (P: 0.04) and 24.6 ± 6 IU/L (range: 17 32 IU/L) (P: 0.01), respectively. In 7 patients the hypertransaminasemia, at diagnosis had resolved. Conclusions: This study provides further evidence that some patients with CD have a reversible hypertransaminasemia that resolves with a GFD. [ABSTRACT FROM AUTHOR]

Summary: Background & aims: Aminotransferase abnormalities have been reported in malnourished patients with anorexia nervosa (AN). The aim of this study was to identify prevalence and risk factors of hyperaminotransferasemia in an adult cohort of AN patients and to describe evolution during nutritional rehabilitation with enteral nutrition for a period of 4 weeks. Methods: Retrospective study of all consecutive malnourished (BMI <16) AN adult patients, without previous liver diseases or hepatotoxic drugs or alcohol consumption, hospitalized for enteral nutrition in a single center between 1998 and 2008. Hypertransaminasemia was defined by an increase in AST and (or) ALT >2N. Results: In all, 126 AN patients (117 W, 9 M), age 30 ± 10.8 years, were included. At admission, 54 (43%) patients presented hypertransaminasemia. In univariate analysis, risk factors for hypertransaminasemia were: lower BMI (11.2 ± 2 vs. 13 ± 2, p < 0.0001) and age (28 ± 9 vs. 32 ± 12, p < 0.05), male sex (p < 0.05) and the pure restrictive form (p = 0.07). In multivariate analysis only BMI, at a threshold of 12, remained significant [OR 3.7, CI: 95% 2.24–5.2]. Normalization of aminotransferases at the end of week 4 of enteral nutrition was obtained in 96%. Only 2/54 patients (4%) presented a worsening of aminotransferases during the refeeding period, including one that died of liver failure. None of the patients without hypertransaminasemia admission presented a subsequent elevation. At the end of the 4-week refeeding period, the increase in BMI was greater in patients without hypertransaminasemia than in those with it (2.0 ± 0.8 vs. 1.5 ± 1.0, p < 0.0001). Conclusion: Elevated transaminases is common in severe malnourished AN patients. Four risk factors were identified: young age, low BMI (the only independent factor in multivariate analysis), the pure restrictive form of the disease and male sex. After 4 weeks of enteral nutrition the evolution is in most cases favourable, albeit with a lower increase in BMI, but can be severe. The long-term evolution remains to be determined. [Copyright &y& Elsevier]

BACKGROUND: Turner syndrome is the most common genetic disorder in females. In most subjects, with a normal physical appearance at birth, the diagnosis is suspected long after birth because of short stature, delayed puberty, primary or secondary amenorrhea or infertility. Abnormalities of liver function tests are reported in literature, with a prevalence ranging from 20% to 80%. In most subjects liver diseases are self-limiting, associated with obesity, hormonal therapy and autoimmune diseases. An association between Turner syndrome and cryptogenic liver disease has been reported. Abnormalities of liver function tests could be the unique sign of Turner syndrome in subjects with normal phenotypes. The histological picture of "fetal liver-like architecture" and "ductopenia" is of fundamental importance for the diagnosis of chromosomopathy. AIM: Review the causes of hypertransaminasemia by focusing on more rare as metabolic and genetic diseases. MATERIALS AND METHODS: We evaluated a 10 year old girl with a normal phenotype affected by chronic hypertransaminasemia and cholestasis, in whom a needle liver biopsy was performed after the most common causes of hypertransaminasemia were excluded. RESULTS: Liver histological evaluation revealed a smoldering colangiopathy with mild ductopenia and a fetal liver-like architecture. Turner syndrome, suspected on the basis of this histological picture, was confirmed by a pelvic ultrasound and a chromosome analysis. CONCLUSIONS: The histological features of "fetal liver-like architecture" and "ductopenia" represent an evocative sign that could indicate the diagnostic suspicion of Turner syndrome in a subject lacking in signs or symptoms of this disease. It is important to perform a pelvic ultrasound and an endocrinological evaluation in all females with chronic asymptomatic hypertransaminasemia even though they have normal phenotypes. [ABSTRACT FROM AUTHOR]

The aim of this study was to call the attention to the often disregarded message that hypertransaminasemia may be a marker of both liver and muscle diseases by presenting personal case reports and a systematic literature review. Three male children (mean age 5.7 years) were inappropriately addressed, during the last 12 months, to our paediatric liver unit for diagnostic work-up of a chronic hypertransaminasemia of unknown origin. In one of them, a liver biopsy had already been performed. On admission, physical examination, evaluation of serum levels of creatine kinase, and dystrophin genetic testing finally led to a diagnosis of muscular dystrophy. One hundred fourteen similar cases, 21 with unnecessary liver biopsy, were found by Medline search. Expensive and invasive tests planned to investigate liver diseases should be postponed until alternative sources of increased serum aminotransferases, primarily myopathic injury, have been excluded. [ABSTRACT FROM AUTHOR]

Background: Celiac disease (CD) has been found in up to 10% of the patients presenting with unexplained abnormal liver function tests (LFT). As there is no precise data from our country in this regard, we investigated the prevalence of CD in patients presenting with abnormal LFT. Methods: From 2003 to 2008, we measured IgA anti-tissue transglutaminase (t-TG) antibody (with ELISA technique) within the first-level screening steps for all patients presenting with abnormal LFT to three outpatient gastroenterology clinics in Isfahan, IRAN. All subjects with an IgA anti-tTG antibody value of >10 μ/ml (seropositive) were undergone upper gastrointestinal endoscopy and duodenal biopsy. Histopathological changes were assessed according to the Marsh classification. CD was defined as being seropositive with Marsh I or above in histopathology and having a good response to gluten free diet (GFD). Results: During the study, 224 patients were evaluated, out of which, 10 patients (4.4%) were seropositive for CD. Duodenal biopsies were performed in eight patients and revealed six (2.7%) cases of Marsh I or above (four Marsh lIlA, two Marsh I), all of them had good response to GFD. The overall prevalence of CD among patients with hypertransaminasemia, autoimmune hepatitis, and cryptogenic cirrhosis was determined as 10.7% (3/28), 3.4% (2/59), and 5.3% (1/19), respectively. Conclusion: Serological screening with IgA anti-tTG antibody test should be routinely performed in patients presenting with abnormal LFT and especially those with chronic liver diseases including hypertransaminasemia, autoimmune hepatitis, and cryptogenic cirrhosis. [ABSTRACT FROM AUTHOR]

Abstract: Background: Despite chronic liver diseases represent an important cause of illness in Italy, data from family practice are poor. Aim: To assess the management of chronic liver diseases by general practitioners in a large area of Southern Italy. Methods: This was a 5-year retrospective analysis from 104 physicians in charge of a population of 143,159 adult subjects. Results: Amongst 6550 patients with chronic liver disease (4.7%, 3400 M, median age 57 years), 1330 (20.3%) had HCV infection, 226 (3.4%) HBV infection, and 293 (4.5%) liver cirrhosis (25 alcohol-related). The prevalence of alcohol consumption, recorded by 90% of physicians, was 20.4%. Hypertransaminasemia and liver steatosis had a prevalence of 6.7% and 2.4%, respectively. Although transaminases were checked 3 times over 5 years in 80% of cases, few patients were investigated for viral infection, and less than 50% underwent ultrasonography and consultation, leaving undefined a consistent number of cases. Alcohol consumption, body mass index and ultrasonography were poorly checked even in hypertransaminasemic patients. Conclusions: This study shows that data recording by general practitioners in chronic liver disease patients lacks homogeneity and can miss important information. One unmet need is therefore the integration between theoretical knowledge and practice to share similar behaviours and improve the management of these patients. [Copyright &y& Elsevier]

Abstract: Background: Non-alcoholic fatty liver disease, ranging from hepatic steatosis to necro-inflammation with or without fibrosis (non-alcoholic steatohepatitis), is a growing clinical liver disorder in children. Aim: The goals of this study were to characterize liver disorders associated with elevated aminotransferases and establish the non-alcoholic fatty liver disease/non-alcoholic steatohepatitis prevalence in hypertransaminasemic children admitted to the emergency room. Methods: The medical records of 3280 children (2–17 years of age) admitted to the emergency room of Bambino Gesù Children''s Hospital of Rome, and presenting with hypertransaminasemia were analysed retrospectively. Results: Elevation of serum alanine aminotransferases was present in 897 patients. Of these, 520 (58%) spontaneously normalized alanine aminotransferases, and 179/897 (20%) maintained persistently elevated alanine aminotransferases levels. Twenty-one patients were excluded because of medication or alcohol use. In the remaining 157 patients with elevated alanine aminotransferases, obesity was found in 87 (55%), viral infections in 52 (33%) and genetic diseases in 14 (9%). Obesity-related alanine aminotransferases elevation was associated with a histological diagnosis of non-alcoholic fatty liver disease in 85% of patients. In particular, steatosis was histologically confirmed in 74 patients; 43/74 (58%) had steatohepatitis, and 12/74 (16%) had fibrosis. Conclusions: Twenty percent of children with elevated aminotransferases on routine testing may hide non-alcoholic fatty liver disease/non-alcoholic steatohepatitis. A careful diagnostic workup of persistent hypertransaminasemia in all obese subjects is warranted in the paediatric setting. [Copyright &y& Elsevier]

Endocrine diseases, such as diabetes mellitus and thyroid dysfunction, have been rarely associated with increased serum transaminase activity. The association of Addison's disease with abnormal liver function tests has received less attention. Addison's disease as a part of autoimmune polyglandular syndrome-1 may be associated with autoimmune hepatitis. Addison's disease may also coexist with celiac disease, an autoimmune disorder commonly associated with hypertransaminasemia. On the other hand, a number of case reports have suggested hypertransaminasemia to be one of the few diagnostic clues to the underlying adrenal insufficiency, allowing the introduction of steroid replacement and obviation of a potential adrenal crisis. We performed a thorough literature review on the prevalence and pathogenesis of hypertransaminasemia as a feature of Addison's disease in an attempt to highlight an as yet under-recognized association. [ABSTRACT FROM AUTHOR]

A new group of genetic diseases characterized by defective glycoprotein biosynthesis was recently described. Transferrin isoelectric focusing enabled identification of several types of patients with congenital disorders of glycosylation (CDG). The authors report on the liver involvement in two siblings with CDG type Ix presenting with failure to thrive and hypertransaminasemia who developed cardiomyopathy. In the initially affected infant, liver biopsy at 13 months of age showed increased periportal cellularity, steatosis, and mild fibrosis. Ultrastructurally, the hepatocytes displayed numerous myelinosomes, mostly with a pericanalicular polarization. No myelinosomes were seen in the bile canaliculi, Kupffer cells, and sinusoidal lining cells. Focal large droplet steatosis was also noticed. These ultrastructural findings represent another diagnostic element in this heterogenic group of conditions. Electron microscopy can contribute to the elucidation of hypertransaminasemia and differentiate some types of CDG from other lysosomal diseases. [ABSTRACT FROM AUTHOR]