Incidence of biliary atresia associated congenital malformations: A retrospective multicenter study in China

SummaryBackgroundSome patients with biliary atresia (BA) have associated anomalies. Our study aimed to investigate the incidence of BA-associated malformations in mainland China, and compare the results with those reported in the Western literature.MethodsClinical data were collected retrospectively from five medical centers in mainland China. BA patients were diagnosed and confirmed by laparotomy with intraoperative cholangiography and liver biopsy. Cases were divided into isolated type BA and BA with associated anomalies, including polysplenia, situs inversus, intestinal malrotation, and cardiovascular anomalies.ResultsA total of 851 BA patients were recruited from Tianjin, Beijing, Wuhan, Guangzhou, and Shenzhen. Patients were grouped as follows: Type I, 13 cases (1.5%); Type II, five cases (0.6%); Type III, 833 cases (97.9%). Forty-two (4.94%) patients had 54 associated congenital abnormalities. The intra-abdominal anomalies included polysplenia (n = 4, 1 fusion between liver and spleen), situs inversus (n = 2), and intestinal malrotation (n = 3). The cardiovascular anomalies included atrial septal defect and ventricular septal defect (n = 29), patent foramen ovale (n = 1), patent ductus arteriosus (n = 4), and other cardiac malformations (n = 3, including coronary sinus dilation, left superior vena cava, Tetralogy of Fallot).ConclusionOur data showed that spleen anomaly is not as common as reported in the Western literature. The difference may suggests different genetic and environmental risk factors for BA

Silencing of the Rotavirus NSP4 Protein Decreases the Incidence of Biliary Atresia in Murine Model

Biliary atresia is a common disease in neonates which causes obstructive jaundice and progressive hepatic fibrosis. Our previous studies indicate that rotavirus infection is an initiator in the pathogenesis of experimental biliary atresia (BA) through the induction of increased nuclear factor-kappaB and abnormal activation of the osteopontin inflammation pathway. In the setting of rotavirus infection, rotavirus nonstructural protein 4 (NSP4) serves as an important immunogen, viral protein 7 (VP7) is necessary in rotavirus maturity and viral protein 4 (VP4) is a virulence determiner. The purpose of the current study is to clarify the roles of NSP4, VP7 and VP4 in the pathogenesis of experimental BA. Primary cultured extrahepatic biliary epithelia were infected with Rotavirus (mmu18006). Small interfering RNA targeting NSP4, VP7 or VP4 was transfected before rotavirus infection both in vitro and in vivo. We analyzed the incidence of BA, morphological change, morphogenesis of viral particles and viral mRNA and protein expression. The in vitro experiments showed NSP4 silencing decreased the levels of VP7 and VP4, reduced viral particles and decreased cytopathic effect. NSP4-positive cells had strongly positive expression of integrin subunit α2. Silencing of VP7 or VP4 partially decreased epithelial injury. Animal experiments indicated after NSP4 silencing, mouse pups had lower incidence of BA than after VP7 or VP4 silencing. However, 33.3% of VP4-silenced pups (N = 6) suffered BA and 50% of pups (N = 6) suffered biliary injury after VP7 silencing. Hepatic injury was decreased after NSP4 or VP4 silencing. Neither VP4 nor VP7 were detected in the biliary ducts after NSP4. All together, NSP4 silencing down-regulates VP7 and VP4, resulting in decreased incidence of BA

The first case of pediatric bile duct adenoma

Intrahepatic bile duct adenoma (BDA) is a rare benign epithelial liver tumor derived from bile duct cells. We report the first case of pediatric bile duct adenoma in the world. Furthermore, we review the diagnosis, pathology, treatment and prognosis of bile duct adenoma

The Prognostic Role of Glasgow Prognostic Score and C-reactive Protein to Albumin Ratio for Sarcoma: A System Review and Meta-Analysis

Backgrounds. Both pretreatment serum CRP (C-reactive protein) level and ALB (albumin) level have been found to be predictive of survival for multiple malignancies including sarcoma. Since both of the GPS (Glasgow prognostic score) and CAR (C-reactive protein to albumin ratio) are based on the combination of CRP and ALB, we conducted a meta-analysis to evaluate the prognostic role of these two parameters for sarcoma patients. Methods. A detailed literature search was conducted in MEDLINE, Embase, and Cochrane Library for relevant research publications written in English. Patients’ clinical characteristics, outcomes of overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS) were extracted. Pooled hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) were combined to evaluate the prognostic role of GPS or CAR. Results. Twelve articles containing 2695 patients were identified as eligible studies. The results showed that an elevated GPS was significantly correlated with poor OS (HR=2.42; 95% CI: 1.98-2.94; p<0.001; fixed-effects model), DSS (HR=2.28; 95% CI: 1.75-2.97; p<0.001; fixed-effects model), and DFS (HR=2.05; 95% CI: 1.62-2.60; p<0.001; fixed-effects model). A higher CAR also was shown to be significantly correlated with poor OS (HR=2.23; 95% CI: 1.70-2.92; p<0.001; fixed-effects model) and DFS (HR=1.81; 95% CI: 1.7-2.58; p=0.001; fixed-effects model). Conclusion. An elevated GPS is predictive of poor survival in patients with sarcomas and is promising to be used as a factor for risk stratification. A higher CAR value is also predictive of poor survival; however, the optimal CAR cut-off value is still to be determined

Characterization of polyclonal antibodies against nonstructural protein 9 from the porcine reproductive and respiratory syndrome virus

Porcine reproductive and respiratory syndrome (PRRS) is considered to be one of the most important infectious diseases impacting the swine industry and is characterized by reproductive failure in late term gestation in sows and respiratory disease in pigs of all ages. The nonstructural protein 9 gene, Nsp9, encoding the RNA-dependent RNA polymerase, is generally regarded as fairly conserved when compared to other viral proteins. Antibodies against Nsp9 will be of great importance for the diagnosis and treatment of the causal agent, PRRS virus. A study was undertaken to generate polyclonal antibodies against the immunodominant Nsp9. For this purpose, the Nsp9 was expressed in Escherichia coli and subsequently used as an antigen to immunize New Zealand rabbits. Antiserum was identified via an indirect ELISA, and then verified based on the ability to react with both naturally and artificially expressed Nsp9. Results of virus neutralization test showed that this antiserum could not neutralize the PRRSV. Nevertheless, this antiserum as a diagnostic core reagent should prove invaluable for further investigations into the mechanism of PRRS pathogenesis

Rotavirus replication, maturity and cytopathic effect of cultured extrahepatic biliary epithelia (EHBE).

<p>(A) Cytopathic effect (CPE) grading of cultured EHBE. The severity of EHBE injury was graded from 0 to 4 with 4 being the most severe. (B) Ultrastructural CPE. siNSP4 transfected EHBE had normal structure. The other 2 siRNAs also protected the shape of EHBE, but nuclear degeneration was noted (pointed by black arrows). (C) Rotavirus particles. Significantly less double-layered particles (DLPs, pointed by black arrows) and triple-layered particles (TLPs, pointed by black arrow heads with dash lines) existed in siNSP4 protected EHBE. siVP7 caused more synthesis of DLPs. (D) Viral particle quantification. TLPs in EHBE significantly reduced in all siRNA trasfected groups (^*•♦<i>P</i><0.05, compared to NC). DLPs in siVP7 group was increased significantly (^▴<i>P</i><0.05, compared to NC). (E) Representative gel images of reverse transcription polymerase chain reaction (RT-PCR). RT-PCR revealed the presence of 3 viral messenger RNAs (mRNAs) in NC group, but siNSP4 transfection reduced the level of NSP4 mRNA and completely inhibited the transcription of VP7 and VP4 mRNA. siVP7 caused absence of VP4 and VP7 mRNA. siVP4 reduced mRNA transcription. (F) Quantitative analysis using Gel Pro Analyzer. siNSP4 decreased the relative level of all viral mRNAs (^*▴•<i>P</i><0.05, compared to NC). siVP7 inhibited the transcription of VP7 and VP4 mRNAs (^♦★<i>P</i><0.05, compared to NC). siVP4 only inhibited the mRNA expression of VP4 (^▪<i>P</i><0.05, compared to NC).</p

Hepatobiliary injury, incidence of biliary atresia and intraluminal rotavirus replication in the bile ducts.

<p>(A) Hematoxylin and eosin staining of livers. Ballooning degeneration and mononuclear cell infiltration were the basic pathologic changes in the liver of rotavirus infected mice in the NC group, but none suffered from hepatic cirrhosis. siNSP4 and siVP4 transfection decreased hepatic injury, but siVP7 transfected mice still suffered from significant hepatic injury. (B) Grading of extrahepatic bile duct injury. Grade 0: No obstruction, stenosis, necrotic epithelia or inflammatory cell infiltration. Grade 1: Mild stenosis and several inflammatory cells. Grade 2: Stenosis or obstruction caused by necrotic cells or inflammatory cells in bile duct lumens. Grade 3: Complete lumen obstruction. Black arrow pointed at the site of injury. (C) Summary of distribution of biliary injury grading. Biliary injury was significantly inhibited by siNSP4 (0/5), (<i>P</i><0.05) compared to NC (5/5). Three of siVP7 transfected mice suffered mild biliary injury. Half of siVP4 transfected mice suffered BA. (D) Measurement of inner and outer diameters of bile ducts. The dashed line and black line respectively indicated the inner and outer diameters. (E) Summary of distribution of inner/outer diameter index (I/O DI). siRNA transfected mice had relatively higher index value (all <i>P</i><0.05, compared to NC). siNSP4 had the highest I/O DI which was not significantly different from the blank controls (<i>P</i>>0.05). (F) Quantitative analysis of viral messenger RNA (mRNA) in bile ducts on 7 dpi using real-time reverse transcription polymerase chain reaction. siNSP4 decreased the level of all viral mRNAs (^*▴•<i>P</i><0.05, compared to NC). siVP7 inhibited the transcription of VP7 and VP4 mRNAs (^♦★<i>P</i><0.05, compared to NC). siVP4 only inhibited the mRNA expression of VP4 (^▪<i>P</i><0.05, compared to NC).</p