Challenges in pediatric inherited/metabolic liver disease: Focus on the disease spectrum, diagnosis and management of relatively common disorders.

The clinical scenario of pediatric liver disease is becoming more intricate due to changes in the disease spectrum, in which an increasing number of inherited/ metabolic liver diseases are reported, while infectious diseases show a decreasing trend. The similar clinical manifestations caused by inherited/metabolic diseases might be under-recognized or misdiagnosed due to nonspecific characteristics. A delayed visit to a doctor due to a lack of symptoms or mild symptoms at an early stage will result in late diagnosis and treatment. Moreover, limited diagnostic approaches, especially liver biopsy, are not easily accepted by pediatric patients, leading to challenges in etiological diagnosis. Liver dysfunction due to inherited/metabolic diseases is often caused by a variety of metabolites, so precision treatment is difficult; symptomatic treatment is a compelling option for inherited disorders.

Gastrointestinal cytomegalovirus disease secondary to measles in an immunocompetent infant: A case report.

BACKGROUND: Gastrointestinal cytomegalovirus (CMV) disease occurs commonly in immunocompromised/immunodeficient patients with advanced human immunodeficiency virus infection, neoplasm, solid organ transplantation, hematopoietic stem cell transplantation, or treatment with immunosuppressants, but is rarely reported in association with measles infection. CASE SUMMARY: We describe a case of extensive gastrointestinal CMV disease secondary to measles infection in a 9-mo-old boy who presented with persistent fever and bloody diarrhea. His condition was improved after ganciclovir treatment. Serological analysis of CMV showed negative immunoglobulin (Ig) M and positive IgG. Blood CMV-DNA was 9.26 × 103 copies/mL. The diagnosis of gastrointestinal CMV disease was confirmed by histopathological findings of intranuclear and intracytoplasmic inclusions and Owl's eye inclusion. This case highlights the differential diagnosis and histopathological characteristics of gastrointestinal CMV infection and laboratory tests. CONCLUSION: Extensive gastrointestinal CMV lesions can be induced by the immune suppression secondary to measles infection. Rational, fast, and effective laboratory examinations are essential for suspected patients.

Predictors of outcomes of endoscopic balloon dilatation in strictures after esophageal atresia repair: A retrospective study.

BACKGROUND: Endoscopic balloon dilatation (EBD) has become the first line of therapy for benign esophageal strictures (ESs); however, there are few publications about the predictive factors for the outcomes of this treatment. AIM: To assess the predictive factors for the outcomes of EBD treatment for strictures after esophageal atresia (EA) repair. METHODS: Children with anastomotic ES after thoracoscopic esophageal atresia repair treated by EBD from January 2012 to December 2016 were included. All procedures were performed under tracheal intubation and intravenous anesthesia using a three-grade controlled radial expansion balloon with gastroscopy. Outcomes were recorded and predictors of the outcomes were analyzed. RESULTS: A total of 64 patients were included in this analysis. The rates of response, complications, and recurrence were 96.77%, 8.06%, and 2.33%, respectively. The number of dilatation sessions and complications were significantly higher in patients with a smaller stricture diameter (P = 0.013 and 0.023, respectively) and with more than one stricture (P = 0.014 and 0.004, respectively). The length of the stricture was significantly associated with complications of EBD (P = 0.001). A longer interval between surgery and the first dilatation was related to more sessions and a poorer response (P = 0.017 and 0.024, respectively). CONCLUSION: The diameter, length, and number of strictures are the most important predictive factors for the clinical outcomes of endoscopic balloon dilatation in pediatric ES. The interval between surgery and the first EBD is another factor affecting response and the number of sessions of dilatation.

Infant cholestasis patient with a novel missense mutation in the AKR1D1 gene successfully treated by early adequate supplementation with chenodeoxycholic acid: A case report and review of the literature.

Steroid 5ß-reductase [aldo-keto reductase family 1 member D1 (AKR1D1)] is essential for bile acid biosynthesis. Bile acid deficiency caused by genetic defects in AKR1D1 leads to life-threatening neonatal hepatitis and cholestasis. There is still limited experience regarding the treatment of this disease. We describe an infant who presented with hyperbilirubinemia and coagulopathy but normal bile acid and γ-glutamyltransferase. Gene analysis was performed using genomic DNA from peripheral lymphocytes from the patient, his parents, and his elder brother. The patient was compound heterozygous for c.919C>T in exon 8 and exhibited a loss of heterozygosity of the AKR1D1 gene, which led to an amino acid substitution of arginine by cysteine at amino acid position 307 (p.R307C). Based on these mutations, the patient was confirmed to have primary 5ß-reductase deficiency. Ursodeoxycholic acid (UDCA) treatment did not have any effect on the patient. However, when we changed to chenodeoxycholic acid (CDCA) treatment, his symptoms and laboratory tests gradually improved. It is therefore crucial to supplement with an adequate dose of CDCA early to improve clinical symptoms and to normalize laboratory tests.

Saturated fatty acid induction of endoplasmic reticulum stress and apoptosis in human liver cells via the PERK/ATF4/CHOP signaling pathway.

Accumulation of saturated fatty acids in the liver can cause nonalcoholic fatty liver disease (NAFLD). This study investigated saturated fatty acid induction of endoplasmic reticulum (ER) stress and apoptosis in human liver cells and the underlying causal mechanism. Human liver L02 and HepG2 cell lines were exposed to the saturated fatty acid sodium palmitate. MTT assay was used for cell viability, flow cytometry and Hoechst 33258 staining for apoptosis, RT-PCR for mRNA expression, and Western blot for protein expression. Silence of PRK-like ER kinase (PERK) expression in liver cells was through transient transfection of PERK shRNA. Treatment of L02 and HepG2 cells with sodium palmitate reduced cell viability through induction of apoptosis. Sodium palmitate also induced ER stress in the cells, indicated by upregulation of PERK phosphorylation and expression of BiP, ATF4, and CHOP proteins. Sodium palmitate had little effect on activating XBP-1, a common target of the other two canonical sensors of ER stress, ATF6, and IRE1. Knockdown of PERK gene expression suppressed the PERK/ATF4/CHOP signaling pathway during sodium palmitate-induced ER stress and significantly inhibited sodium palmitate-induced apoptosis in L02 and HepG2 cells. Saturated fatty acid-induced ER stress and apoptosis in these human liver cells were enacted through the PERK/ATF4/CHOP signaling pathway. Future study is warranted to investigate the role of these proteins in mediating saturated fatty acid-induced NAFLD in animal models.

Therapeutic effect of transcatheter arterial chemoembolization and percutaneous injection of acetic acids on primary liver cancer.

BACKGROUND: The resection rate of primary liver tumor in China is only about 20%. A lot of patients with moderate and advanced liver tumor may lose the chance of operation. The objective of present research was to study the efficacy of transcatheter arterial chemoembolization (TACE) combined with percutaneous injection of chemical agents and acetic acids in the treatment of patients with primary liver cancer (PLC). METHODS: Thirty-three patients with middle and advanced stage of PLC were divided into two groups: percutaneous injection of chemical agents and acetic acids (15 patients, group A) and TACE (18 patients, group B). RESULTS: Tumor diameter and serum AFP level reduced to 86.6% and 83.3% in group A, and 55.5% and 40% in group B, respectively. There was significant difference between the two groups (P<0.01). The 1, 2, 3, 4-year survival rates of group A were 96.7%, 86.6%, 51.3%, 33.3%, respectively and in group B were 66.7%, 44.4%, 16.7%, 0%, respectively (P<0.01). CONCLUSION: TACE combined with percutaneous injection of chemical agents and acetic acids is efficacious to increase the survival rate of patients with PLC.