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)

Síndrome colestásico como forma de presentación de linfoma no Hodgkin. Reporte de un caso pediátrico / Cholestatic syndrome as a presentation of non-Hodgkin lymphoma. A pediatric case report

La ictericia colestásica se debe a la alteración de la secreción de bilirrubina conjugada; es una de las posibles causas la alteración del flujo biliar por obstrucción de la vía biliar extrahepática. El linfoma es la tercera neoplasia más frecuente en pediatría, mientras que los tumores pancreáticos son poco frecuentes y, en su mayoría, lesiones benignas. Las manifestaciones clínicas de los tumores de localización retroperitoneal son poco específicas y suelen ser tardías, por lo que la sospecha clínica debe ser alta. El objetivo del siguiente trabajo es presentar el caso de un niño de 7 años con síndrome colestásico en el que se halló un tumor en la cabeza del páncreas que comprimía la vía biliar extrahepática. El diagnóstico del tumor fue linfoma no Hodgkin (LNH). Se destaca la infrecuencia de este tumor en esta localización en la edad pediátrica

Cholestatic jaundice is due to an alteration in conjugated bilirubin secretion; a possible cause is an altered bile flow resulting from an obstruction of the extrahepatic bile duct. A lymphoma is the third most common neoplasm in pediatrics, while pancreatic tumors are rare and mostly benign. The clinical manifestations of retroperitoneal tumors are not very specific and are usually late, so a high level of clinical suspicion is required. The objective of this study is to describe the case of a 7-year-old boy with cholestatic syndrome with a tumor in the head of the pancreas compressing the extrahepatic bile duct. The tumor diagnosis was non-Hodgkin lymphoma (NHL). It is worth noting that the presence of a tumor in this location in pediatric age is uncommon

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

Síndrome de Alagille, reporte de un caso y revisión de la literatura / Alagille Syndrome, case study and literature review / Sindrome de Alagille, relato de caso e revisão de literatura

El síndrome de Alagille es una patología poco frecuente, de herencia autosómica dominante. Se caracteriza por la presencia de colestasis crónica progresiva ocasionada por hipoplasia de las vías biliares; anomalías vertebrales, oculares y cardíacas, y fenotipo facial particular. Entre sus diagnósticos diferenciales se incluyen las infecciones, enfermedades endocrinometabólicas, atresia biliar y causas idiopáticas. El pronóstico de este síndrome es variable y depende de la entidad de la afectación hepática y los defectos cardiovasculares. El abordaje terapéutico suele ser interdisciplinario e individualizado, enfocado en el control sintomático, prevención de la malnutrición y el déficit de vitaminas liposolubles. Se presenta el caso de un lactante de 2 meses en el que se estudiaron las causas más frecuentes de colestasis y se llegó al diagnóstico de síndrome de Alagille. Se describe su abordaje terapéutico y seguimiento.

Alagille syndrome is an inherited autosomal dominant rare disease. It is characterized by the presence of progressive chronic cholestasis caused by hypoplasia of the bile ducts; vertebral, ocular and cardiac anomalies, and particular facial phenotype. Its differential diagnoses include infections, endocrine-metabolic diseases, biliary atresia and idiopathic causes. The prognosis of this syndrome is variable and depends on the degree of liver involvement and cardiovascular defects. The therapeutic approach is usually interdisciplinary and customized, focused on symptomatic control, prevention of malnutrition and fat-soluble vitamin deficiency. We present the case of a 2-month-old infant in whom the most frequent causes of cholestasis were studied and to whom Alagille Syndrome was diagnosed. We hereby describe its therapeutic approach and follow-up.

A síndrome de Alagille é uma doença rara, hereditária, autossômica e dominante. Caracteriza-se pela presença de colestase crônica progressiva causada por hipoplasia das vias biliares; anomalias vertebrais, oculares e cardíacas e fenótipo facial particular. Seus diagnósticos diferenciais incluem infecções, doenças endócrino-metabólicas, atresia biliar e causas idiopáticas. O prognóstico desta síndrome é variável e depende do grau de envolvimento hepático e defeitos cardiovasculares. A abordagem terapêutica geralmente é interdisciplinar e personalizada, focada no controle sintomático, prevenção da desnutrição e deficiência de vitaminas lipossolúveis. Apresentamos o caso de uma criança de 2 meses de idade em que foram estudadas as causas mais frequentes de colestase e a quem foi diagnosticada Síndrome de Alagille. Descrevemos a sua abordagem terapêutica e seguimento.

Drug-induced bile duct injury: progress and challenges / 中华肝脏病杂志

Drug-induced bile duct injury is a specific kind of drug-induced liver injury that has two main pathological types, namely ductopenia, or vanishing bile duct syndrome, and secondary sclerosing cholangitis. However, in recent years, the reports of new drugs that cause bile duct injury have been constantly increasing, and these drugs have different clinicopathological features and a novel pathogenesis. Therefore, this paper summarizes and analyzes the progress and challenges in the etiology, pathogenesis, diagnosis and treatment, and other aspects of drug-induced bile duct injury.

Excerpt from the 2022 American Association for the Study of Liver Diseases clinical practice guideline: management of primary sclerosing cholangitis and cholangiocarcinoma / 中华肝脏病杂志

What are the new contents of the guideline since 2010?A.Patients with primary and non-primary sclerosing cholangitis (PSC) are included in these guidelines for the diagnosis and management of cholangiocarcinoma.B.Define "related stricture" as any biliary or hepatic duct stricture accompanied by the signs or symptoms of obstructive cholestasis and/or bacterial cholangitis.C.Patients who have had an inconclusive report from MRI and cholangiopancreatography should be reexamined by high-quality MRI/cholangiopancreatography for diagnostic purposes. Endoscopic retrograde cholangiopancreatography should be avoided for the diagnosis of PSC.D. Patients with PSC and unknown inflammatory bowel disease (IBD) should undergo diagnostic colonoscopic histological sampling, with follow-up examination every five years until IBD is detected.E. PSC patients with IBD should begin colon cancer monitoring at 15 years of age.F. Individual incidence rates should be interpreted with caution when using the new clinical risk tool for PSC for risk stratification.G. All patients with PSC should be considered for clinical trials; however, if ursodeoxycholic acid (13-23 mg/kg/day) is well tolerated and after 12 months of treatment, alkaline phosphatase (γ- Glutamyltransferase in children) and/or symptoms are significantly improved, it can be considered to continue to be used.H. Endoscopic retrograde cholangiopancreatography with cholangiocytology brushing and fluorescence in situ hybridization analysis should be performed on all patients suspected of having hilar or distal cholangiocarcinoma.I.Patients with PSC and recurrent cholangitis are now included in the new unified network organ sharing policy for the end-stage liver disease model standard.J. Liver transplantation is recommended after neoadjuvant therapy for patients with unresectable hilar cholangiocarcinoma with diameter < 3 cm or combined with PSC and no intrahepatic (extrahepatic) metastases.

Effects of Li-Dan-He-Ji on regulating oxidative stress and antagonising infantile cholestatic hepatic fibrosis / 中华危重病急救医学

OBJECTIVE@#To explore the clinical effect of Li-Dan-He-Ji in the treatment of infantile cholestatic hepatic fibrosis.@*METHODS@#Patients who met the diagnostic criteria of infantile cholestatic hepatic fibrosis in the department of integrated traditional Chinese and Western medicine and the department of gastroenterology of Wuhan Children's Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology from January to December 2021 were included in the study by prospective randomized controlled trial. They were divided into the conventional treatment group and Li-Dan-He-Ji group according to the random number table. The patients in the conventional treatment group were given conventional treatment according to the guidelines. In the Li-Dan-He-Ji group, the self-made Chinese medicinal compound Li-Dan-He-Ji (prescription: Herba Artemisiae Scopariae, Fructus Forsythiae, Radix et Rhizoma Rhei preparata, Radix Polygoni Multiflori Preparata, Radix Paeoniae Rubra, Ramulus Cinnamomi, Fructus Aurantii, Rhizoma Atractylodis Macrocephalae, Fructus Schisandrae Chinensis, Carapax Trionycis, and Radix Glycyrrhizae) was given on the basis of the routine treatment, by oral, enema or nasal feeding, 60 mL each day, divided into 2 or 3 times, for 28 days. Outpatient follow-up was maintained for 4 weeks. Before and after treatment, serum liver fibrosis 4 items [type IV collagen (IV-C), hyaluronidase (HA), type III procollagen (PC III), laminin (LN)], liver function and cholestasis-related markers [total bilirubin (TBil), direct bilirubin (DBil), total bile acid (TBA), alkaline phosphatase (ALP), γ-glutamyl transpeptidase (γ-GGT), alanine aminotransferase (ALT), aspartate aminotransferase (AST)], oxidative stress markers [superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione (GSH)], liver stiffness measurement (LSM) detected by transient elastography (TE), aspartate aminotransferase-to-platelet ratio index (APRI), and liver and spleen retraction time were recorded in the two groups.@*RESULTS@#During the observation period, a total of 40 cases of cholestatic hepatic fibrosis were treated, including 21 cases in the conventional treatment group and 19 cases in the Li-Dan-He-Ji group. Before treatment, the differences in serum liver fibrosis 4 items, serum liver function and cholestasis-related markers, oxidative stress indexes, LSM and APRI of the two groups were not statistically significant. After treatment, the liver fibrosis 4 items, liver function and cholestasis-related markers, LSM, and APRI were all significantly decreased in both groups, and the indexes in the Li-Dan-He-Ji group were significantly lower than those in the conventional treatment group [HA (ng/L): 165.81±21.57 vs. 203.87±25.88, PC III (μg/L): 69.86±9.32 vs. 81.82±7.39, IV-C (μg/L): 204.14±38.97 vs. 239.08±24.93, LN (μg/L): 162.40±17.39 vs. 190.86±15.97, TBil (μmol/L): 37.58±27.63 vs. 53.06±45.09, DBil (μmol/L): 20.55±19.34 vs. 30.08±27.39, ALP (U/L): 436.50±217.58 vs. 469.60±291.69, γ-GGT (U/L): 66.78±35.84 vs. 87.00±32.82, ALT (U/L): 64.75±50.53 vs. 75.20±50.19, AST (U/L): 77.25±54.23 vs. 96.80±59.77, TBA (μmol/L): 74.35±44.44 vs. 85.45±39.50, LSM (kPa): 5.24±0.39 vs. 7.53±3.16, APRI: 0.52±0.39 vs. 0.98±0.29, all P < 0.05]. After treatment, MDA in the two groups were significantly lower than those before treatment, and SOD and GSH were significantly higher than those before treatment. The level of SOD in the Li-Dan-He-Ji group was significantly higher than that in the conventional treatment group (kU/L: 64.56±6.69 vs. 51.58±5.98, P < 0.05). In addition, the liver retraction time (day: 20.13±10.97 vs. 24.33±13.46) and spleen retraction time (day: 25.93±13.01 vs. 29.14±14.52) in the Li-Dan-He-Ji group were significantly shorter than those in the conventional treatment group (both P < 0.05).@*CONCLUSIONS@#The use of Li-Dan-He-Ji in the treatment of cholestatic hepatic fibrosis can effectively improve the indicators of cholestasis, hepatic fibrosis, oxidative stress and clinical symptoms in children.

Hidatidosis quística simulando una neoplasia hepática invasiva / Cystic hydatidosis simulating an invasive hepatic neoplasia

La hidatidosis/equinococosis quística es una infección zoonótica, endémica en muchos países de América del Sur, caracterizada por lesiones hepáticas que radiológicamente pueden simular neo-plasias malignas de aspecto quístico y que, dependiendo del tiempo de evolución y del grado de obstrucción de la vía biliar, pueden cursar con insuficiencia hepática, por lo cual es importante un diagnóstico oportuno. Presentamos el caso de un paciente masculino de 35 años, sin antecedentes patológicos de importancia, perteneciente a una comunidad indígena y residente de una zona rural de Colombia, quien presentó un cuadro clínico y pruebas de laboratorio sugestivos de obstrucción de la vía biliar, la cual fue confirmada con el hallazgo de una masa hepática quística infiltrante en los estudios imagenológicos, sospechándose inicialmente una etiología neoplásica maligna. El paciente finalmente falleció tras procedimiento quirúrgico, y su estudio histopatológico reveló una hidatidosis quística como diagnóstico definitivo.

Cystic echinococcosis/hydatidosis is a zoonotic infection, endemic in many South American coun-tries, characterized by liver lesions that radiologically can simulate malignant neoplasms with a cystic appearance, and depending on the time of progression and degree of obstruction of the bile duct, can present with liver failure, so a prompt diagnosis is important. We present the case of a 35-year-old male patient, with no significant pathological history, from an indigenous community and resident of a rural area in Colombia, who presented clinical symptoms and laboratory tests suggestive of bile duct obstruction, which was confirmed with the finding of an infiltrating cystic liver mass in imaging studies, initially suspecting a malignant neoplastic etiology. The patient developed a fulminant course after surgery, and the histopathological study revealed cystic hydatidosis as the definitive diagnosis.

Síndrome biliar obstructivo no litiásico o de Lemmel. ¿Es tan infrecuente como parece? / Non-lithiasic obstructive biliary syndrome or Lemmel's syndrome. Is it as rare as it seems?

Introducción. Aproximadamente el 5 % de los divertículos duodenales pueden causar síntomas y el 1 % presentar complicaciones, siendo la colangitis la más frecuente. El síndrome de Lemmel corresponde a un tipo de ictericia obstructiva intermitente, asociado a la presencia de divertículos periampulares y disfunción del esfínter de Oddi, sin presencia de coledocolitiasis. Método. Se realizó una revisión sistemática de la literatura en Pubmed, Google Académico y ProQuest, con los términos: síndrome de Lemmel, divertículo duodenal sintomático e ictericia obstructiva intermitente. Resultados. Se encontraron 38 casos, siendo España el país con mayor número, seguido de México, Japón y Colombia. No hay diferencias de distribución con respecto al género. El tratamiento más frecuentemente empleado fue la colangio pancreatografia retrógrada endoscópica. Conclusión. El síndrome de Lemmel es poco frecuente, sin un cuadro clínico especifico, con un incremento en los casos informados en los últimos años, posiblemente debido a la mejor disponibilidad de métodos diagnósticos. Es más frecuente en pacientes en la octava década de la vida y su tratamiento generalmente es endoscópico

Introduction. Approximately 5% of duodenal diverticula can cause symptoms and 1% have complications, cholangitis being the most common. Lemmel syndrome corresponds to a type of intermittent obstructive jaundice, associated with the presence of peri-ampullary diverticula and sphincter of Oddi dysfunction, without choledocholithiasis. Method. A systematic review of the literature was carried out in Pubmed, Google Scholar, ProQuest, with the terms: Lemmel syndrome, symptomatic duodenal diverticulum, and intermittent obstructive jaundice.Results. 38 cases were found, Spain being the country with the highest number, followed by Mexico, Japan and Colombia. There are no differences in distribution with respect to gender. The most frequently used treatment was endoscopic retrograde cholangiopancreatography.Conclusion. Lemmel syndrome is a rare disease, without a specific clinical presentation, with an increase in reported cases in recent years possibly due to the better availability of diagnostic methods. It is more frequent in patients in the eighth decade of life and its treatment is generally endoscopic

Colangitis biliar primaria: experiencia de cinco años en el Hospital Clínico de la Universidad de Chile / Primary biliary cholangitis. Experience in 179 patients

BACKGROUND: Primary biliary cholangitis (PBC) is a chronic autoimmune cholestatic disease, which can progress to cirrhosis. It mainly affects middle-aged women. Its most frequent form of presentation is asymptomatic with biochemical cholestasis and the presence of antimitochondrial antibodies (AMA). AIM: To describe the epidemiological characteristics, clinical presentation and treatment for patients with PBC at a clinical hospital. MATERIAL AND METHODS: Descriptive, observational, retrospective study, carried out between January 2015 and December 2020. Results: 179 patients (158 women) were cared in the study period. At the time of diagnosis, the median age was 54 years (range 24-76), 55% of them were asymptomatic, 45% had fatigue and 28% had pruritus. Positive AMA were present in 65% of patients, antinuclear antibodies (ANA) in 51%, and anti-smooth muscle antibodies (ASMA) in 9%. Immunoglobulin M (IgM) was elevated in 30% of the patients and 50% of patients were biopsied. Splenomegaly and esophageal varices were present in 24 and 22% of patients, respectively. PBC was associated with Sjogren's syndrome in 15%, hypothyroidism in 14%, osteoporosis in 13%, and scleroderma in 8%. CONCLUSIONS: The epidemiological characteristics of our patients agree with those published abroad. Laboratory cholestasis associated with the presence of AMA, currently allows diagnosis without the need for histological study. Ursodeoxycholic acid (UDCA) is the first-line treatment for patients with PBC. The use of biochemical response criteria is essential to identify patients who require other UDCA alternatives for isolated or combined treatment.

Liver involvement in endocrine diseases / 中华肝脏病杂志

As a secondary endocrine organ, the liver is closely related to the endocrine system. Liver involvement is not uncommon in endocrine diseases, such as hyper/hypothyroidism, diabetes, dysfunction of adrenal and gonadal. It can be manifested in a variety of forms, including hepatocyte injury (elevated transaminase), bile duct injury (cholestasis), hepatocyte steatosis, vascular injury and liver tumor. Direct and indirect liver injury caused by abnormal hormone levels and side effects of drugs for the treatment of endocrine diseases are common pathogenesis. In addition, endocrine diseases can be concomitant with liver diseases, such as autoimmune thyroiditis and autoimmune hepatitis. Systemic diseases can also involve the endocrine system and liver at the same time, such as systemic lupus erythematosus and IgG4 related diseases. For patients with unexplained liver injury, endocrine system diseases should be considered as the differential diagnosis.

Guidelines on the management of cholestasis liver diseases (2021) / 中华肝脏病杂志

In 2015, the Chinese Society of Hepatology and Chinese Society of Gastroenterology issued the consensus on the diagnosis and management of cholestatic liver diseases. In the past years, more data have emerged from clinical practice. Herein, the Autoimmune Liver Disease Group of the Chinese Society of Hepatology organized an expert group to review the evidence and updated the recommendations to formulate the guidelines. There are 22 recommendations on clinical practice of cholestatic liver diseases. The guidelines aim to provide a working reference for the management of cholestatic liver diseases.

Expert consensus on the diagnosis and treatment of intrahepatic cholestasis (2021 edition) / 中华肝脏病杂志

Intrahepatic cholestasis is a clinical syndrome due to the defect of bile acid synthesis, abnormal bile excretion, and mechanical or functional disturbance of intrahepatic bile flows caused by hepatic parenchymal cell and/or intrahepatic bile duct diseases. It commonly occurs as cholestatic liver diseases, intrahepatic cholestasis of pregnancy, and genetic/metabolic-related cholestatic diseases. In recent years, new information and progress in diagnosis and treatment of intrahepatic cholestatic diseases have been achieved. In order to provide updated clinical reference and guidance for clinicians, we organized experts to compile the Expert Consensus on the Diagnosis and Treatment of Intrahepatic Cholestasis (2021), on the basis of the 2015 edition.

Serum metabolomics of Tibetan medicine Ershiwuwei Songshi Pills against chronic cholestasis in mice / 中国中药杂志

A chronic cholestasis model was induced in mice by feeding a diet containing 3,5-diethoxycarbonyl-1,4-dihydro-2,4,6-trimethylpyridine(DDC). The effects of Ershiwuwei Songshi Pills(ESP) on endogenous metabolites in mice with chronic cholestasis were investigated by metabolomics analysis based on liquid chromatography-mass spectrometry(LC-MS). The results showed that ESP was effective in improving pathological injury and reducing serum levels of alanine aminotransferase(ALT), aspartate aminotransferase(AST), alkaline phosphatase(ALP), and total bile acid in the model mice. Meanwhile, 13 common differential metabolites were revealed in metabolomic screening between the model/control group and the model/ESP group, including uric acid, glycolaldehyde, kynurenine, flavin adenine dinucleotide, L-3-phenyllactic acid, I-urobilin, leukotriene D4(LTD4), taurocholic acid, trioxilin A3, D-inositol-1,4-diphosphate, PC [16:0/20:2(11Z,14Z)], PC[14:0/22:2(13Z,16Z)], and PC[20:4(5Z,8Z,11Z,14Z)/20:4(5Z,8Z,11Z,14Z)]. After ESP intervention, the levels of all 13 differential metabolites were significantly retraced, and pathway analysis showed that ESP achieved its therapeutic effect mainly by affecting arachidonic acid metabolism, glycerophospholipid metabolism, tryptophan metabolism, and primary bile acid biosynthesis. This study elucidated the mechanism of action of ESP against chronic cholestasis based on metabolites.

Analysis of 6 cases with hepatocerebral mitochondrial DNA depletion syndrome and literature review / 中华儿科杂志

Objective: To explore the clinical features of hepatocerebral mitochondrial DNA depletion syndrome (MDS). Methods: The clinical data of 6 hepatocerebral MDS patients diagnosed in the Jinshan Hospital of Fudan University from January 2012 to December 2019 were retrospectively collected and analyzed. Related literature published before January 2020 were searched with the key words of "DGUOK""MPV17""POLG""C10orf2" in PubMed, China national knowledge infrastructure (CNKI) and Wanfang database. Results: All the 6 hepatocerebral MDS cases were male. The age of onset ranged from 3 days to 8 months. The most common initial symptoms were cholestasis and developmental retrogression. The main clinical manifestations included hepatomegaly (4 cases), hypotonia (3 cases), growth retardation (4 cases), cholestasis (5 cases), coagulopathy (5 cases), hypoalbuminemia (3 cases), hypoglycemia (4 cases), hyperlactacidemia (5 cases), and abnormal blood metabolism screening (6 cases). The isotope hepatobiliary imaging revealed no gallbladder and intestinal tract development within 24 hours in 2 patients. Regarding the cranial imaging examination, the head CT found widening of the extracranial space in 1 case, the brain magnetic resonance imaging (MRI) found ventricular enlargement in 2 cases, and the brain ultrasound found peripheral white matter injury in 1 case. Two cases were lost to follow-up, one died of liver failure, and three died of multiple organ failure due to aggravated infection. Among the 6 cases, there were 3 with MPV17 variation (c.182T>C and c.279G>C were novel), 1 with POLG variation (c.2993G>A was novel), 1 with DGUOK variation (c.679G>A homozygous mutation, parthenogenetic diploid of chromosome 2) and 1 with C10orf2 variation (c.1186C>T and c.1504C>T were novel). The literature review found that 129, 100, 51 and 12 cases of hepatocerebral MDS were caused by DGUOK, MPV17, POLG and C10orf2 gene variations, respectively. And the most common clinical manifestations were liver dysfunction presented with cholestasis and elevated transaminase, metabolic disorders including hypoglycemia and hyperlactacidemia, and diverse neurologic symptoms including developmental retardation, hypotonia, epilepsy and peripheral neuropathy. Besides, 1/3 of the patients with C10orf2 variation developed renal tubular injury. Conclusions: Hepatocerebral MDS mainly present with liver dysfunction, metabolic disorder and neuromuscular impairment. Different genotypes show specific clinical manifestations.

Terapias usuales y emergentes en colangitis biliar primaria / Conventional and emerging therapies in primary biliary cholangitis

La colangitis biliar primaria (CBP) es una enfermedad autoinmune caracterizada por daño de los conductos biliares intrahepáticos, que hasta ahora tiene mecanismos poco claros de respuesta celular inflamatoria, con la mitocondria como orgánulo blanco. Durante varias décadas han sido el control de los ácidos biliares y el tratamiento de la colestasis lo que ha permitido el manejo médico de los pacientes, logrando un impacto parcial en el curso y la progresión de la enfermedad, mejorando además la sobrevida de los individuos. Con el hallazgo de nuevos mecanismos fisiopatológicos se han iniciado estudios con terapias inmunomoduladoras, que podrían ser prometedoras en el mejoramiento de la calidad de vida de los pacientes que padecen la enfermedad. Aún los resultados son inciertos, y se hacen necesarios más estudios para aclarar el papel de los nuevos tratamientos en el arsenal terapéutico disponible para la CBP.

Primary biliary cholangitis (PBC) is an autoimmune disease characterized by damage of intrahepatic bile ducts, so far with unclear mechanisms of inflammatory cellular response with the mitochondria as the target organelle. For several decades it has been the control of bile acids and the treatment of cholestasis what has allowed the management of patients, achieving a partial impact on the course and progression of the disease, also improving the survival of individuals. With the discovery of new pathophysiological mechanisms, studies have been initiated with new immunomodulatory therapies that could be promising in improving the quality of life of patients suffering from the disease. The results are still uncertain and further studies are needed to clarify the role of the new treatments in the therapeutic arsenal available for PBC.

Hiperbilirrubinemia: visión del patólogo / Hyperbilirubinemia: pathologist's view

Los niveles de bilirrubina sérica normal en el adulto varían entre 0,3 mg/dL y 1,2 mg/dL, y su valor está determinado por la tasa de captación hepática, conjugación y excreción. La ictericia se hace evidente cuando los niveles de bilirrubina sérica se elevan por encima de 2,5 mg/dL a 3 mg/dL, siendo un indicador de enfermedad subyacente. La bilis es producida por los hepatocitos y fluye desde los canalículos, canales de Hering, conductos biliares intrahepáticos, conductos hepáticos derechos e izquierdos hasta llegar al duodeno. A nivel histopatológico, cualquier entidad que lleve a la acumulación intrahepática de bilis por disfunción hepatocelular u obstrucción biliar genera colestasis, que se observa en la biopsia hepática como la acumulación de tapones de color marrón verdoso de pigmento biliar en los hepatocitos, y secundariamente se observan los canalículos dilatados. Las causas de colestasis intrahepática son diversas e incluyen enfermedades como colangitis biliar primaria, colangitis esclerosante primaria, hepatitis autoinmune, hepatitis virales y toxicidad medicamentosa. Esta revisión tiene como objetivo analizar algunos tipos de hiperbilirrubinemia, resaltando sus características histopatológicas.

Normal serum bilirubin levels in adults range from 0.3 mg/dL to 1.2 mg/dL, and its value is determined by the rate of hepatic uptake, conjugation, and excretion. Jaundice becomes apparent when serum bilirubin levels rise above 2.5 mg/dL to 3.5 mg/dL and is an indicator of underlying disease. Bile is produced by hepatocytes and flows from the canaliculi, Hering's canals, intrahepatic bile ducts, and right and left hepatic ducts to the duodenum. Pathologically, any condition that leadsto intrahepatic accumulation of bile due to hepatocellular dysfunction or biliary obstruction, generates cholestasis, which is observed in liver biopsy as the accumulation of greenish-brown deposits of bile pigment in hepatocytes, with dilated canaliculi. The causes of intrahepatic cholestasis are diverse and include diseases such as primary biliary cholangitis and primary sclerosing cholangitis, autoimmune hepatitis, viral hepatitis, and drug toxicity. This review aims to analyze some types of hyperbilirubinemia, highlighting their histopathological characteristics.