Role of apical sodium-dependent bile acid transporter in hepatobiliary diseases / 临床肝胆病杂志

Apical sodium-dependent bile acid transporter （ASBT） is a key transporter responsible for intestinal reabsorption of bile acid and plays an important role in maintaining bile acid and cholesterol homeostasis， and its expression is regulated by various factors including transcription factors， nuclear receptors， and intestinal microflora. The abnormal expression and function of ASBT can lead to disorders in the metabolism of bile acid and cholesterol， causing a variety of hepatobiliary diseases. At present， ASBT has attracted wide attention as a therapeutic target. This article elaborates on the biological characteristics and expression regulation mechanism of ASBT and reviews the role of ASBT in hepatobiliary diseases， in order to provide a new direction for the treatment of related diseases.

Antioxidant effect of Rosa pimpinellifolia L. fruit extract on cholestatic liver injury: an experimental study

SUMMARY BACKGROUND: Antioxidants have been considered a rational curative strategy to prevent and cure liver diseases involving oxidative stress. An acute obstructive jaundice rat model was established to investigate the in vivo hepatoprotective efficacy of Rosa pimpinellifolia L. METHODS: The experimental jaundice model was performed by binding the main bile duct in 25 male Sprague-Dawley rats. All rats were randomly divided into five groups: first group: laparotomy-sham-only, second group: biliary tract binding (control), and third, fourth, and fifth groups: treatment groups with 250, 500, and 750 mg/kg fruit extracts daily, respectively. RESULTS: Considering dosage, although there was no significant therapeutic effect in the 250 mg/kg of Rosa pimpinellifolia L. group, the best results were found in the 500 mg/kg dose group, while results in the 750 mg/kg dose group showed consistent correlation with proinflammatory response. With regard to biochemical parameters, lipid hydroperoxide level in the rat serum and liver tissue was significantly decreased in all treatment groups. Amadori products, which are one of the early markers of glycol-oxidative stress, showed statistical significance in the treatment. CONCLUSION: It was revealed that the antioxidant effect of Rosa pimpinellifolia L. was more prominent in the early stages of hepatic injury secondary to oxidative stress.

Aspectos clínicos, laboratoriais e evolutivos de pacientes pediátricos com doença hepática por deficiência de alfa 1-antitripsina / Clinical, laboratorial and evolutionary aspects of pediatric patients with liver disease due to alpha 1-antitrypsin deficiency

ABSTRACT Background: Alpha 1-antitrypsin deficiency (AATD) is a hereditary codominant autosomal disease. This liver disease ranges from asymptomatic cases to terminal illness, which makes early recognition and diagnosis challenging. It is the main cause of pediatric liver transplantation after biliary atresia. Objective: To describe the clinical characteristics, as well as those of histologic and laboratory tests, phenotypic and/or genetic evaluation and evolution of a cohort of pediatric patients with AATD. Methods: This is a retrospective observational study of 39 patients with confirmed or probable AATD (without phenotyping or genotyping, but with suggestive clinical features, low serum alpha 1-antitrypsin (AAT) level and liver biopsy with PAS granules, resistant diastasis). Clinical, laboratory and histological varia­bles, presence of portal hypertension (PH) and survival with native liver have been analyzed. Results: A total of 66.7% of 39 patients were male (26/39). The initial manifestation was cholestatic jaundice in 79.5% (31/39). Liver transplantation was performed in 28.2% (11/39) of patients. Diagnosis occurred at an average of 3.1 years old and liver transplantation at 4.1 years of age. 89.2% (25/28) of the patients with confirmed AATD were PI*ZZ or ZZ. The average AAT value on admission for PI*ZZ or ZZ patients was 41.6 mg/dL. All transplanted patients with phenotyping or genotyping were PI*ZZ (or ZZ). Those who were jaundiced on admission were earlier referred to the specialized service and had higher levels of GGT and platelets on admission. There was no significant difference in the survival curve when comparing cholestatic jaundiced to non-cholestatic jaundiced patients on admission. Comparing patients who did or did not progress to PH, higher levels of AST and APRI score at diagnosis (P=0.011 and P=0.026, respectively) were observed and in the survival curves patients with PH showed impairment, with 20.2% survival with native liver in 15 years. Conclusion: Jaundice is an important clinical sign that motivates referral to a specialist, but it does not seem to compromise survival with native liver. Patients progressing to PH had higher AST, APRi score on admission and significantly impaired survival with native liver. It is important to pay attention to these signs in the follow-up of patients with AATD.

RESUMO Contexto: Deficiência de alfa 1-antitripsina (DAAT) é uma doença hereditária, de caráter autossômico codominante. A apresentação da doença hepática varia desde casos assintomáticos até doença terminal, o que dificulta reconhecimento e diagnóstico precoces. É a principal causa de transplante hepático pediátrico após atresia de vias biliares. Objetivo: Descrever as características clínicas, de exames laboratoriais, histológicos, avaliação fenotípica e/ou genética e sobrevida de uma coorte de pacientes pediátricos com DAAT. Métodos: Estudo observacional retrospectivo de 39 pacientes com diagnóstico de DAAT confirmada ou provável (sem fenotipagem ou genotipagem, mas com clínica sugestiva, baixo nível sérico de alfa 1-antitripsina (A1AT) e biópsia hepática com grânulos PAS, diástase resistentes). Variáveis clínicas, laboratoriais, histológicas, presença de hipertensão portal (HP) e sobrevida com fígado nativo foram analisadas. Resultados: Dos 39 pacientes, 66,7% eram do sexo masculino (26/39). A manifestação inicial foi icterícia colestática em 79,5% (31/39). Em 28,2% (11/39) houve necessidade de transplante hepático. O diagnóstico ocorreu com uma idade média de 3,1 anos e, o transplante hepático, 4,1 anos. Dos pacientes com DAAT confirmada, 89,2% (25/28) eram PI*ZZ ou ZZ. O valor médio de A1AT na admissão de pacientes PI*ZZ ou ZZ foi 41,6 mg/dL. Todos os transplantados com fenotipagem ou genotipagem eram PI*ZZ (ou ZZ). Os ictéricos à admissão foram referenciados mais cedo ao serviço especializado e apresentaram níveis mais elevados de GGT e plaquetas à admissão. Não houve diferença significativa na curva de sobrevida ao compararmos icterícia colestática ou não à admissão. Ao comparar os pacientes que progrediram ou não para HP, observou-se níveis mais elevados de AST e APRI escore ao diagnóstico (P=0,011 e P=0,026, respectivamente) e, nas curvas de sobrevida, pacientes com HP apresentaram comprometimento, com 20,2% de sobrevida com fígado nativo em 15 anos. Conclusão: Icterícia é um sinal clínico importante que motiva o encaminhamento ao especialista, mas parece não comprometer a sobrevida com fígado nativo. Pacientes com evolução para HP tiveram AST e escore APRi mais elevados à admissão e comprometimento significativo da sobrevida com fígado nativo. Importante atentar a esses sinais no seguimento de pacientes com DAAT.

Colangiopatía hipertensiva portal por transformación portal cavernomatosa de origen no cirrótica: a propósito de un caso

La colangiopatía portal hace referencia a anomalías colangiográficas que se producen en pacientes con cavernomatosis portal, siendo progresiva, cursando con enfermedad biliar sintomática y anomalías graves de las vías biliares. Y, representa una complicación infrecuente de la hipertensión portal. Se describe el caso de un hombre de 53 años, con historia de larga data de hipertensión portal nocirrótica y cavernomatosis portal, quien presentó un episodio de enfermedad biliar obstructiva sintomática, y en estudios se documentó tejido fibrótico de extensión periportal ascendente con compresión extrínseca del colédoco distal y dilatación de la vía biliar extra e intrahepática. Por lo que se procedió a colangiopancreatografía retrógrada endoscópica, realizándose tratamiento paliativo, con papilotomía pequeña y colocación de endoprótesis biliar plástica, siendo exitoso por ausencia de complicaciones procedimentales, y mejoría clínica y parámetros bioquímicos. Finalmente, recibiendo de alta con indicación de seguimiento prioritario para recambios periódicos de endoprótesis biliares, y valoración por hepatología. La colangiopatía portal es una entidad rara que debe sospecharse en sujetos con hipertensión portal de origen no-cirrótico, con hallazgos imagenológicos de estenosis, angulaciones o dilataciones segmentarias, su tratamiento debe ser individualizado, y la terapia endoscópica es de elección en enfermedad biliar sintomática.

Portal cholangiopathy refers to cholangiographic abnormalities occurring in patients with portal cavernomatosis, being progressive, presenting with symptomatic biliary disease and severe biliary tract abnormalities. And, it represents an infrequent complication of portal hypertension. We describe the case of a 53-year-old man with a long history of non-cirrhotic portal hypertension and portal cavernomatosis, who presented an episode of symptomatic obstructive biliary disease, and studies documented fibrotic tissue of ascending periportal extension with extrinsic compression of the distal common bile duct and dilatation of the extra and intrahepatic biliary tract. Therefore, endoscopic retrograde cholangiopancreatography was performed, and palliative treatment with small papillotomy and placement of a plastic biliary endoprosthesis was successful due to the absence of procedural complications, and clinical improvement and biochemical parameters. Finally, the patient was discharged with indication of priority follow-up for periodic replacement of biliary stents, and evaluation by hepatology. Portal cholangiopathy is a rare entity that should be suspected in subjects with portal hypertension of non-cirrhotic origin, with imaging findings of stenosis, angulations or segmental dilatations, its treatment should be individualized, and endoscopic therapy is of choice in symptomatic biliary disease.

Colestasis intrahepática drepanocítica a propósito de un casoy revisión de la literatura / Sickle cell intrahepatic cholestasis regarding a case and reviewof the literature

La enfermedad de células falciformes (ECF) o anemia drepanocítica, es el trastorno hereditario más frecuente en los glóbulos rojos, y la enfermedad con más complicaciones en diferentes órganos, lo que provoca múltiples presentaciones de una misma enfermedad., se hace revisión literatura sobre ECF y colestasis intrahepática drepanocítica, y se describe un caso presentado en el Hospital General y de Especialidades Nuestra Señora de la Altagracia de Higüey Republica Dominicana en el año 2022. Es un varón de 24 años, con diagnóstico de ECF, que se complicó con una colestasis intrahepática drepanocítica muy severa que se manejó con hemodiálisis. El objetivo de publicar este caso es revisar la información respecto a la incidencia y la morbimortalidad de esta complicación, teniendo en cuenta que fue tratado por un equipo multidisciplinario usando la hemodiálisis como alternativa terapéutica(AU)

Sickle cell disease (SCD) or sickle cell anemia is the most common hereditary disorder in red blood cells, and the disease with the most complications in different organs, which causes multiple presentations of the same disease. Literature review on SCD is made and sickle cell intrahepatic cholestasis,and a case presented at the Hospital General y de Especialidades Nuestra Señora de la Altagracia de Higüey in the Dominican Republic in 2022 is described. Very severe sickle cell intrahepatic disease that was managed with hemodialysis. The purpose of publishing this case is to review the information regarding the incidence and morbidity and mortality of this complication,taking into account that it was treated by a multidisciplinary team using hemodialysis as a therapeutic alternative(AU)

Colestasis intrahepática por Treponema pallidum en paciente inmunocompetente / Intrahepatic cholestasis due to Treponema pallidum in an immunocompetent patient

La hepatitis por Treponema pallidum es una entidad poco frecuente y su diagnóstico representa un reto clínico. Treponema pallidum debe considerarse como etiología presuntiva en todo paciente con enfermedad hepática aguda, en el cual se hayan descartado otras causas más frecuentes. Se presenta el caso de un paciente joven, inmunocompetente, quien presentó elevación de los valores de las pruebas hepáticas con patrón colestásico y lesiones maculopapulares en palmas y plantas. Dado su cuadro clínico, las pruebas diagnósticas y la respuesta a la terapia antimicrobiana instaurada, se estableció el diagnóstico de colestasis por una sífilis secundario sifilítiao. Es importante incluir la sífilis secundaria entre las posibles causas de enfermedad hepática aguda.

Hepatitis due to Treponema pallidum is a rare entity and its diagnosis represents a clinical challenge. Treponema pallidum should be considered as a presumptive etiology in all patients with acute liver disease, when other frequent causes have been ruled out. We present the case of a young, immunocompetent patient with elevated values in his liver tests, a cholestatic pattern, and maculopapular lesions on his palms and soles. Given his clinical picture, diagnostic tests, and response to the antimicrobial therapy, a diagnosis of cholestasis due to secondary syphilis has been established. It is important to include secondary syphilis within the possible causes of acute liver disease.

Neoplasia quística mucinosa en la vía biliar intrahepática. Presentación de dos casos / Mucinous cystic neoplasm in the intrahepatic bile duct. Presentation of two cases

Introducción. Las neoplasias quísticas mucinosas del hígado son tumores poco frecuentes, equivalen a menos del 5 % de todas las lesiones quísticas hepáticas y se originan generalmente en la vía biliar intrahepática, con poco compromiso extrahepático. En la mayoría de los casos su diagnóstico es incidental dado que es una entidad generalmente asintomática con un curso benigno; sin embargo, hasta en el 30 % pueden ser malignas. En todos los casos se debe hacer una resección quirúrgica completa de la lesión. Caso clínico. Se presentan dos pacientes con diagnóstico de neoplasia quística mucinosa en la vía biliar intrahepática, así como sus manifestaciones clínicas, hallazgos imagenológicos y tratamiento. Discusión. Debido a su baja incidencia, esta patología constituye un reto diagnóstico, que se puede confundir con otro tipo de entidades más comunes. El diagnóstico definitivo se hace de forma histopatológica, pero en todos los casos, ante la sospecha clínica, se recomienda la resección completa. Conclusión. Se presentan dos pacientes con diagnóstico de neoplasias quísticas mucinosas del hígado, una entidad poco frecuente y de difícil diagnóstico

Introduction. Mucinous cystic neoplasms of the liver are rare tumors, accounting for less than 5% of all liver cystic lesions, and generally originate from the intrahepatic bile duct with little extrahepatic involvement. In most cases its diagnosis is incidental since it is a generally asymptomatic entity with a benign course; however, up to 30% can have a malignant course. In all cases, complete surgical resection of the lesion must be performed. Clinical case. Two patients with a diagnosis of mucinous cystic neoplasm in the intrahepatic bile duct are presented, as well as their clinical manifestations, imaging findings, and treatment. Discussion. Due to its low incidence, this pathology constitutes a diagnostic challenge, which can be confused with other types of more common entities. The definitive diagnosis is made histopathologically, but in all cases, given clinical suspicion, complete resection is recommended. Conclusion. Two patients with a diagnosis of mucinous cystic neoplasms of the liver are presented, a rare entity that is difficult to diagnose

A Retrospective Analysis of Fetal and Maternal Outcome in Patients with Intrahepatic Cholestasis of Pregnancy

Background: Introduction: Intrahepatic cholestasis of pregnancy (ICP), is the most common liver disease specific to pregnancy. Previous studies of fetal effects have suggested that ICP is associated with a higher rate of adverse neonatal outcomes including preterm birth, neonatal respiratory distress syndrome (RDS), meconium-stained amniotic fluid, neonatal intensive care unit admission, and stillbirth. Material & Methods: This was a 4 year retrospective observational study including 43,344 female who delivered in our hospital out of which 1126 cases of ICP were identified, who were compared with 1136 age and parity matched controls. Results: : Previous history and family history of ICP was significant in the ICP group. Gestational diabetes and preterm labour were more frequent in the ICP group. Mean birth weight was lower in the ICP group, rate of small for gestational age foetuses was not significantly different. Cesearean section and post-partum haemorrhage was more frequent in the ICP group. Adverse neonatal outcomes i.e. respiratory distress syndrome (RDS) and need for NICU admission were more in the ICP group. Conclusion: ICP is associated with increased rate of preterm delivery, post-partum hemorrhage and increased neonatal morbidity. Management of patients with ICP should be individualized based on the severity of symptoms and associated medical complications.

Shunt portosistémico, una causa poco frecuente de hepatitis colestásica en neonatología. A propósito de un caso / Portosystemic shunt, a rare cause of neonatal cholestatic hepatitis. A case report

El shunt portosistémico congénito es una anomalía vascular venosa que comunica circulación portal y sistémica, por la que se deriva el flujo sanguíneo, salteando el paso hepático. Es una entidad poco frecuente, cuya incidencia varía entre 1/30 000 y 1/50 000 recién nacidos. Puede cursar de forma asintomática o presentarse con complicaciones en la edad pediátrica o, menos frecuente, en la edad neonatal. Ante el diagnóstico, se deberá definir la necesidad de intervención quirúrgica o intravascular para el cierre. Esta decisión depende de las características anatómicas de la malformación, de las manifestaciones clínicas y complicaciones presentes. Se presenta el caso de un paciente de un mes de vida derivado a nuestro centro para estudio de hepatitis colestásica neonatal, con diagnóstico de shunt portosistémico extrahepático. Se realizó cierre intravascular de la lesión con mejoría significativa posterior.

Congenital portosystemic shunt is a venous vascular abnormality that connects portal and systemic circulation, resulting in diversion of the blood flow, bypassing the hepatic passage. It is a rare malformation; its incidence varies from 1:30 000 to 1:50 000 newborns. It may be asymptomatic or present with complications in the pediatric age or, less frequently, in the neonatal age. Upon diagnosis, the need for a surgical or an intravascular intervention for closure should be defined. This decision depends on the malformation anatomical characteristics, clinical manifestations, and complications. We present the case of a 1-month-old patient referred to our center for the study of neonatal cholestatic hepatitis, with a diagnosis of extrahepatic portosystemic shunt. Intravascular closure of the defect was performed with significant subsequent improvement.

Cholestatic Jaundice Secondary to Portal Hypertensive Biliopathy Regarding a Case of Cavernous Transformation of the Portal Vein

Portal hypertensive biliopathy comprises the anatomical and functional abnormalities of the intra- and extrahepatic biliary tract, cystic duct, and gallbladder in patients with portal hypertension. The compromise of the bile duct usually occurs in portal obstruction due to the cavernous transformation of the portal vein (CTPV). We present a case of a young patient with a recent history of portal hypertension and CTPV who presented with an episode of cholestatic hepatitis. Studies documented an image of nodular appearance with extrinsic compression of the distal bile duct compatible with a tumor-like cavernoma. Effective endoscopic treatment was performed using endoscopic retrograde cholangiopancreatography (ERCP), sphincterotomy, and biliary stenting.

La biliopatía hipertensiva portal comprende las anomalías anatómicas y funcionales del tracto biliar intra- y extrahepático, el conducto cístico y la vesícula biliar en pacientes con hipertensión portal. El compromiso de la vía biliar suele presentarse en obstrucción portal debido a transformación cavernomatosa de la porta. Presentamos un caso de un paciente joven, con historia reciente de hipertensión portal y cavernomatosis de la porta, que presentó un episodio de hepatitis colestásica y en estudios se le documentó una imagen de apariencia nodular con compresión extrínseca de la vía biliar distal compatible con tumor-like cavernoma. En este caso se realizó un tratamiento endoscópico efectivo mediante colangiopancreatografía retrógrada endoscópica (CPRE), esfinterotomía y stent biliar.

Effect of 28-day administration of Psoraleae Fructus water extract on early liver injury in rats / 中国中药杂志

This study aims to investigate the hepatotoxicity of Psoraleae Fructus water extract and the underlying mechanism in rats. Forty-eight rats were randomly assigned into four groups: a blank group and low-(BZGL, 6.25 g·kg~(-1)), medium-(BGZM, 12.5 g·kg~(-1)), and high-dose(BGZH, 25 g·kg~(-1)) Psoraleae Fructus water extract groups. The rats were treated for 28 days, and toxicity and mortality were observed daily. After 28 days, the rats were sacrificed, and the body weight, liver index, and liver-to-brain ratio were calculated. The morphological changes in the liver tissue were observed, and the serum levels of related biochemical indicators were measured. The results showed that compared with the blank group, Psoraleae Fructus water extracts of different doses decreased the body weight, increased the liver index and liver-to-brain ratio, and caused liver hypertrophy and pathological changes. Pathological examination revealed that the rats in Psoraleae Fructus water extract groups had bile duct hyperplasia, inflammatory cell infiltration, and liver cell fibrosis. Compared with the blank group, BGZL elevated the levels of alanine transaminase(ALT), α-glutathione S-transferase(α-GST), and total bile acid(TBA)(P<0.05), and BGZM and BGZH elevated the levels of ALT, TBA, α-GST, γ-glutamyl transferase(γ-GT), purine nucleoside phosphorylase(PNP), ornithine carbamoyltransferase(OCT), and arginase(ArgI)(P<0.05). Compared with the blank group, Psoraleae Fructus water extracts of different doses down-regulated the mRNA and protein levels of bile salt export pump(BSEP) and farnesoid X receptor(FXR) and up-regulated the mRNA and protein levels of tumor necrosis factor-α(TNF-α), nuclear factor kappaB(NF-κB), and cholesterol 7 alpha-hydroxylase(CYP7A1)(P<0.05). The results suggested that Psoraleae Fructus water extract caused toxicity in rats, showing a dose-toxicity relationship. Psoraleae Fructus water extract may cause liver damage, which may be due to its effect on liver bile acid secretion and induction of inflammation.

The mechanism research of Xiaoyan Lidan formula for the intervention of chronic intrahepatic cholestasis based on metabolomics combined with molecular docking analysis / 药学学报

In this study, the mechanism of Xiaoyan Lidan formula (XYLDF) against 3,5-diethoxycarbonyl-1,4-dihydro-2,4,6-collidine (DDC)-induced chronic intrahepatic cholestasis (CIHC) in mice was investigated based on metabolomics, molecular docking and pharmacological methods. In the pharmacodynamics study, a dosage of 5 g·kg-1 (clinical equivalent) XYLDF was administered in DDC-induced mice, then the effect of XYLDF against CIHC was evaluated by measuring the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AKP) as well as total bilirubin (TBIL) in serum and observing liver histopathological changes. All experiments were approved by the Ethical Committee Experimental Animal Center of Guangzhou University of Chinese Medicine (ZYD-2021-001). The serum metabolites of mice in each group were detected and identified based on ultra-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry, and the relevant biological pathways and molecular key targets were further enriched. Molecular docking technology was used to further evaluate the binding activity of the main active ingredients of XYLDF with potential targets. Subsequently, the in vitro experiment was conducted for the validation of the vital target. The results showed that compared with the model group, XYLDF significantly decreased the levels of ALT, AST, AKP and TBIL in the serum of CIHC mice, as well as alleviated inflammatory infiltration and hepatocyte necrosis in liver tissue. According to the metabonomic study, a total of 35 differential metabolites was identified as biomarkers associated with cholestasis, 12 of which were significantly recovered by XYLDF treatment. These biomarkers were involved in the pathways of primary bile acid biosynthesis and linoleic metabolism, which are closely related to the mechanism of XYLDF against CIHC. Protein-protein interaction network indicated that cytochrome P450 3A4 (CYP3A4) and cytochrome P450 1A1 (CYP1A1) are significant potential targets with good binding properties with six major active ingredients of XYLDF. Furthermore, it was found that 4-methoxy-5-hydroxycanthin-6-one, dehydroandrographolide and isodocarpin, three of the main active components in XYLDF, markedly induced the expression of CYP3A4 mRNA in vitro. This study revealed that XYLDF mainly mediates the biosynthesis of bile acids in CIHC mice to improve liver tissue lesions and bile efflux disorders, among which, CYP3A4 is the key target in the protection of XYLDF against CIHC. This research provides a reference for further elucidation of the pharmacological mechanism of XYLDF.

Phenotype and genotype analysis of progressive familial intrahepatic cholestasis type 4 / 中华实用儿科临床杂志

Objective:To improve the understanding of progressive familial intrahepatic cholestasis type 4 (PFIC4).Methods:Clinical characteristics in a 10-year-old boy with PFIC4 at the Second Hospital of Hebei Medical University in February 2020 were retrospectively analyzed, and the TJP2 gene mutations were analyzed. Results:The proband was a 10-year-old boy with a slow onset of intrahepatic cholestasis[normal γ-glutamyl transpeptidase(GGT)], hepatosplenomegaly and hepatic fibrosis.Laboratory tests showed elevated levels of total bilirubin, especially the direct bilirubin increased.Alanine aminotransferase, aspartate transaminase acid and total bile acid were elevated, while GGT remained in a normal range.Oral medication of ursodeoxycholic acid initially improved liver biochemical parameters, but later fluctuated.Adenosine dehydrogenase, coagulation indicators and hepatic fibrosis indexes were persistently abnormal.The average shear wave velocity of liver was 1.9 times of the upper limit of normal value.Compound heterozygous mutations c. 334G>A(p.A112T)/c.580_639delGACCGGAGCCGTGGCCGGAGCCTGGAGCGGGG-CCTGGACCAAGACCATGCGCGCACCCGA (p.194_213delDRSRGRSLERGLDQDHARTR) were found in the TJP2 gene.The deletion mutation of the TJP2 gene was reported for the first time throughout the world.Both of his parents carried a heterozygous mutation. Conclusions:PFIC should be considered in intrahepatic cholestasis patients with a normal range of GGT.The detection of TJP2 gene mutation is of great value in the clinical diagnosis of PFIC4.The presence of TJP2 gene mutation may be a risk factor for patient developing cirrhosis of liver and primary liver cancer in early childhood.It is necessary for children with PFIC4 to be closely followed up.

Multidisciplinary management and follow-up study of Alagille syndrome / 国际儿科学杂志

Objective:To explore the multidisciplinary management that centred on gastroenterology department, and follow-up study of children with Alagille syndrome(ALGS).Methods:The clinical data of 19 children diagnosed with ALGS in Pediatric Gastroenterology Department, Shengjing Hospital of China Medical University since June 2013 to December 2022 was retrospectively analyzed, and the clinical manifestations of various systems of the body were followed up and evaluated, and then developed the personalised management strategies.Results:Among the 19 confirmed patients, 18 cases were confirmed by genetic testing.Eighteen cases(94.7%) had characteristic facial features.To follow-up node, 8 cases(42.1%) had cholestasis, with alanine aminotransferase(210.20±110.50)U/L, aspartate aminotransferase(187.86±96.70)U/L, and direct bilirubin(110.93±108.15)μmol/L.Eighteen cases(94.7%) had pruritus.Eighteen cases(94.7%) of the patients had a high risk of malnutrition, and the level of total bilirubin[(76.17±107.34)μmol/L] and total bile acid[(100.18±83.78)μmol/L] were significantly increased in the children with obvious growth retardation.Thirteen cases(68.42%) had diffuse liver injury.The clinical opinions on genetic counseling, application of new drugs, liver transplantation, cardiac medicine and surgery follow-up, spine and oral surgery orthodontics were given by multiple disciplines.Conclusion:ALGS children have a high risk of long-term malnutrition and are associated with the severity of liver injury, and pruritus and jaundice are the main clinical manifestations.The management of ALGS patients should be centered around liver disease doctors, combined with multiple disciplines, paying attention to changes in various related organs of ALGS patients, and improving their quality of life.

Evaluation of cholestatic liver disease animal model based on clinical syndrome characteristics of integrated traditional Chinese and Western medicine / 临床肝胆病杂志

Cholestatic liver disease is a common disease of the hepatobiliary system. Its etiology and pathogenesis are complex. The establishment of an appropriate animal model of cholestatic liver disease is the basis for further study of its pathogenesis and prevention. This study summarized the existing modeling methods， mechanisms， and characteristics of this model， and analyzed its alignment with the clinical disease and syndrome characteristics of integrated traditional Chinese and Western medicine based on the modern clinical diagnostic criteria and traditional Chinese medicine syndrome characteristics of cholestatic liver disease， so as to provide a reference for establishing standard animal models and evaluation methods for cholestatic liver disease that accord better with the clinical practice of integrated traditional Chinese and Western medicine.

Research advances in the impact of phthalates on cholestatic liver disease / 临床肝胆病杂志

Cholestatic liver disease is a common hepatobiliary disease caused by bile deposition in the liver due to the disorders of bile production, excretion, and metabolism. At present, the pathogenic factors for cholestatic liver disease have not been fully elucidated, but some researchers believe that environmental factors may play an important role in it. As environmental pollutants, phthalic acid esters (PAE) have been confirmed to interfere with human endocrine system, exert a potential toxic effect on the human body, endanger liver and kidney function, and increase the risk of intrahepatic cholestasis. On this basis, this article reviews the association between PAE and cholestatic liver disease and summarizes related clinical studies, animal experimental studies, in vitro experimental studies, and potential mechanisms, so as to provide ideas and references for the prevention and clinical treatment of cholestatic liver disease.

Value of the combined use of aminotransferase-to-platelet ratio index and total bile acid for predicting parenteral nutrition-associated cholestasis in preterm infants with gestational age <34 weeks / 中国当代儿科杂志

OBJECTIVES@#To explore the value of the combined use of aspartate aminotransferase-to-platelet ratio index (APRI) and total bile acid (TBA) for predicting parenteral nutrition-associated cholestasis (PNAC) in preterm infants with gestational age <34 weeks.@*METHODS@#A retrospective analysis was performed on medical data of 270 preterm infants born at <34 weeks of gestation who received parenteral nutrition (PN) during hospitalization in the First Affiliated Hospital of Wannan Medical College from January 2019 to September 2022, including 128 infants with PNAC and 142 infants without PNAC. The medical data between the two groups were compared, and predictive factors for the development of PNAC were explored through multivariate logistic regression analysis. The receiver operating characteristic (ROC) curve was used to evaluate the value of APRI alone, TBA alone, and the combination of both for predicting PNAC.@*RESULTS@#TBA levels in the PNAC group after 1, 2, and 3 weeks of PN were higher than those in the non-PNAC group (P<0.05). APRI in the PNAC group after 2 and 3 weeks of PN was higher than that in the non-PNAC group (P<0.05). Multivariate logistic regression analysis showed that elevated APRI and TBA after 2 weeks of PN were predictive factors for PNAC in preterm infants (P<0.05). ROC curve analysis showed that the sensitivity, specificity, and area under the curve (AUC) for predicting PNAC by combining APRI and TBA after 2 weeks of PN were 0.703, 0.803, and 0.806, respectively. The AUC for predicting PNAC by combining APRI and TBA was higher than that of APRI or TBA alone (P<0.05).@*CONCLUSIONS@#After 2 weeks of PN, the value of combining APRI and TBA for predicting PNAC is high in preterm infants with gestational age <34 weeks.

Alagille syndrome misdiagnosed as biliary atresia a case report and literature review / 中国热带医学

@#Abstract: By report a case in which the main symptom was cholestasis in an infant and the diagnosis of Alagille syndrome (ALGS) was made after a tortuous treatment process, so as to provide clinicians with experience in diagnosing this type of patient. The patient was a 1-year and 11-month-old male who was admitted to the hospital with "abnormal liver function found for more than 1 year". Physical examination showed a wide forehead, sunken eye sockets, wide eye spacing, a sharp chin, and a grade II systolic murmur in the pulmonary valve region. Biochemical findings showed abnormal liver function accompanied by significant elevation of total bile acids and γ-glutamyl transpeptidase. CT scan of the thoracic vertebrae showed sagittal vertebral fractures in the thoracic 3-7 vertebrae, and pulmonary arteriography showed pulmonary stenosis and genetic testing indicated a JAG1 mutation. Combining the patient's specific facial features, heart defects, spinal deformities, and bile stasis clinical symptoms, along with the genetic analysis results, the final diagnosis was confirmed as Alagille syndrome. Alagille syndrome is the most common cause of chronic cholestasis with phenotypic features and is a dominant inherited disease involving multiple systems. Most patients present with bile stasis as the main symptom within the first three months after birth. Alagille syndrome needs to be distinguished from various forms of cholestasis in infancy, and since biliary atresia requires early surgical treatment, most children with cholestasis as the main clinical manifestation are considered to have biliary atresia at an early stage and undergo a caesarean section. If Alagille syndrome is misdiagnosed as biliary atresia, and surgery may worsen the prognosis. Therefore, the biggest challenge in the early diagnosis of Alagille syndrome is how to distinguish it from biliary atresia. Therefore, physicians need to improve their knowledge of rare cholestatic liver disease in clinical practice to accurately identify rare cholestatic liver disease in the early stages of the disease, and improve improve their diagnosis and treatment levels.

Research advances in animal models of cholestatic liver disease / 临床肝胆病杂志

Cholestatic liver diseases (CLD) are a series of diseases due to impaired bile flow and accumulation of bile acid in the liver and/or systemic circulation caused by immune, genetic, and environmental factors. The pathogenesis of CLD remains unclear and CLD is difficult to treat. As a substitute for human diseases, animal models can provide a platform for exploring the etiology and pathogenesis of the disease and finding appropriate therapeutic targets. This article reviews the current research advances in the animal models of CLD.

Clinical and pathological features of drug-induced liver injury with different types of bile duct injury: An analysis of four cases / 临床肝胆病杂志

Objective To investigate the clinical, biochemical, pathological, disease course, and prognostic features of drug-induced liver injury (DILI) patients with different types of bile duct injury. Methods Four patients who were diagnosed with bile duct injury-type DILI by liver biopsy in Shijiazhuang Fifth Hospital, from March 2015 to October 2010 were selected, and related data were collected, including clinical data, laboratory examinations, radiological examination, and prognosis.The semi-quantitative score was determined for liver pathological morphology, and each indicator was compared between the four patients. Results Bile duct injury-type DILI was more common in female patients, and most patients tended to have a good prognosis.Clinical symptoms, liver biochemical parameters, and prognosis varied with the site, grade, scope, regeneration, and repair of bile duct injury. Conclusion Liver biopsy is still the gold standard for making a definite diagnosis of bile duct injury-type DILI, understanding the condition of lesions, and judging the prognosis of this disease.