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.

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.

Uso de corticosteroides no tratamento da lesão hepática aguda grave decorrente de anabolizante estanazolol / Use of corticosteroids in the treatment of stanazolol-induce severe acute liver injury

A busca pelo corpo perfeito pode gerar graves consequências para a população que faz uso indiscriminado de substâncias visando a resultados rápidos. O caso relatado se refere a um pa- ciente de 21 anos, do sexo masculino, na cidade de São Paulo (SP), que apresentou quadro de síndrome colestática 15 dias após uso do anabolizante estanazolol para fins estéticos na ativi- dade física, evoluindo com hepatite medicamentosa grave, com aumento de transaminases, hiperrubilinemia às custas de bilirrubina direta e fatores de coagulação, sem resposta satis- fatória ao tratamento de suporte convencional, com melhora significativa após introdução de corticoterapia.

Searching for the perfect body image can cause severe conse- quences to the population using substances indiscriminately to reach results fast. The case reported refers to a male patient, 21 years old, from the city of São Paulo (SP), who developed choles- tatic syndrome 15 days after the use of the steroid Stanazol for aesthetic purposes during physical activity, progressing with se- vere drug-induced hepatitis, transaminases, bilirubin, and coagu- lation factors increase with no satisfactory response to the con- ventional support treatment, and significant improvement after the introduction of corticotherapy.

Percutaneous transbiliary biopsy / Biópsia percutânea transbiliar

ABSTRACT Percutaneous drainage of the bile ducts is an established procedure for malignant obstructions, in which a histological diagnosis is often not obtained. We describe the biopsy technique of obstructive lesions through biliary drainage access, using a 7F endoscopic biopsy forceps, widely available; some are even reusable. This technique applies to lesions of the hepatic ducts, of the common hepatic duct and of all extension of the common bile duct.

RESUMO A drenagem percutânea das vias biliares é um procedimento estabelecido para obstruções malignas, nos quais, muitas vezes, não se consegue um diagnóstico histológico. Descrevemos a técnica de biópsia da lesão obstrutiva através do acesso de drenagem biliar, utilizando um fórcipe de biópsia endoscópica 7F, amplamente disponível e alguns reutilizáveis. Esta técnica aplica-se a lesões dos ductos hepáticos, do hepático comum e de toda extensão do colédoco.

Grape seed protects cholestatic rats liver from ischemia/reperfusion injury

ABSTRACT PURPOSE: To determine the effect of grape-seed extract against ischemia/reperfusion injury in cholestatic liver. METHODS: Eighteen Wistar albino rats were divided into three groups. In control and study groups, cholestasis was provided by bile duct ligation. Seven days later, the rats were subjected to 30 min hepatic ischemia, followed by 60 min of reperfusion. Oral administration of 50 mg/kg/day grape-seed extract was started 15 days before bile duct ligation and continued to the second operation in the study group. Serum, plasma and liver samples were taken. Laboratory analysis, tissue gluthation, malondialdehyde, myeloperoxidase levels and histopathological examination were performed. RESULTS: Significant decrease in liver gluthation level and significant increase in malondialdehyde level and myeloperoxidase activity were observed after ischemia/reperfusion in cholestatic rats. Serum and plasma levels for laboratory analysis were also significantly higher in cholestatic I/R group. Hepatic necrosis and fibrosis were detected in histopathological examination. Oral grape-seed extract administiration reversed all these parameters and histopathological findings except serum bilirubin levels. CONCLUSION: Oral grape-seed extract treatment can improve liver functions and attenuate the inflammation and oxidative stress in cholestatic ischemia/reperfusion injury.

Estenosis biliares benignas: experiencia 77 casos / Benign biliary strictures: experience 77 cases

Se presenta la experiencia de los autores con 77 casos de estenosis biliares benignas tratadas en Unidad de Cirugía Hepática, Biliar y trasplante de hígado del Hospital Universitario de Maracaibo. Desde agosto de 1989 hasta diciembre de 2009, fueron registrados 77 casos de estenosis biliares benignas. Se tipificaron según la clasificación de Bismuth. 83,12% (64) de los pacientes habían sido colecistectomizados (estenosis post-iatrogenia durante este procedimiento): 41 (53,25%) abiertas y 23 (29,87%) laparoscópicas. 89,61 (69) de los pacientes consultaron por ictericia, 62,34% fiebre y 58,44% dolor abdominal. 9% (7) presentó estenosis Bismuth I, 22% (17) tipo II, 44,16% (34) tipo III y 24,68% (19) tipo IV. A todos se les realizó exploración biliar quirúrgica y anastomosis mucosa-mucosa con Y-Roux, tipo Hepp-Couinaud en 70 (87,5%) de los pacientes. La mortalidad fue 2,6% (2) paciente en el transoperatorio. Se presentaron en el peri-operatorio 19 (24,39%) complicaciones en 17 (22%) pacientes: 12 (15,6%) mayores y 7 (8,79%) menores. En un seguimiento promedio de 49 meses, 7-79% (6) pacientes presentaron re-estenosis de la derivación bilioentérica. El mayor porcentaje de estenosis biliares benignas son posteriores a procedimientos quirúrgicos, principalmente colecistectomia. La anastomosis bilioentérica tipo Hepp-Couinaud se realizó en el mayor número de pacientes con excelentes resultados.

Present experience of the authors with 77 cases of bening biliary strictures. From August of 1989 to December of 2009, 77 patients were recorded. Classification of Bismuth was used to classificate the strictures 64 (83,12%) patients were cholecistectomizated (stricture by iatrogenia during this procedure): 41 (53,25%) open and 23 (29,87%) laparoscopic. 89,61% (69) consulted by jaundice, 62,34 by fever and 58,44% by abdominal pain. 9%(7) had stricture Bismuth 1,22% (17) type II, 44,16% (34) type III and 24,68% (19) type IV. All patients were summated to surgical biliary exploration and mucous-mucous biliary anastomosis with Y-Roux. Hepp-Couinaud type in 70 (87,7%) of the patients. Perioperative mortality was 2,6% (2). Perioperative complications were 19 (24,39%) in 17 (22%) patients: 12 (15,6%) mayor and 7(8,79%) minors. In medial following of 49 months, 7,79% (6) presented re-stricture of bilio-enteric anastonosis. The majority of the strictures were due to surgical procedures. Hepp-Couinaud anastomosis was performed in almost all the patients with excellent outcome.

Colestasis: enfoque actual / Cholestasis: current approach

La colestasis, tiene incidencia de 1:60-375 ictéricos a las 2 semanas de edad, es potencialmente grave, presentan riesgos inmediatos como coagulopatías por hemorragia severa ante el déficit de la absorción de la vitamina K, y con su diagnóstico precoz, se identifican patologías que tienen tratamiento, incluso, trasplante hepático. Como consecuencia de la colestasis, hay retención de sales biliares, daño celular hepático, y descenso de la bilis a nivel intestinal, que ocasionan mala digestión de grasas y proteínas, con defectos en las vitaminas liposolubles. Existen hepatopatías primariassecundarias a una serie de entidades genéticas y metabólicas, y colestasis secundarias a otros problemas, que en el adulto generan enfermedad hepática. Es necesario establecer protocolos deidentificación del niño con ictericia.

Cholestasis has 1:60-375 incidence of jaundice at 2 weeks of age, are potentially serious, immediateand present risk of severe bleeding coagulopathy to the shortfall in the absorption of vitamin K, andearly diagnosis, identify diseases that are treatable, even liver transplantation.As a result of cholestasis, there is retention of bile salts, liver cell damage and decrease of bile in the intestine, causing poor digestion of fats and protein, with defects in soluble vitamins. There are primaryliver disease secondary to a variety of metabolic and genetic entities, and cholestasis secondary toother problems, generated in the adult liver disease. It is necessary to establish protocols for the identification of children with jaundice.

Oxidized low-density-lipoprotein accumulation is associated with liver fibrosis in experimental cholestasis

OBJECTIVE: The aim of the present study was to examine the probable relationship between the accumulation of oxLDL and hepatic fibrogenesis in cholestatic rats. INTRODUCTION: There is growing evidence to support the current theories on how oxidative stress that results in lipid peroxidation is involved in the pathogenesis of cholestatic liver injury and fibrogenesis. One of the major and early lipid peroxidation products, OxLDL, is thought to play complex roles in various immuno-inflammatory mechanisms. METHODS: A prolonged (21-day) experimental bile duct ligation was performed on Wistar-albino rats. Biochemical analysis of blood, histopathologic evaluation of liver, measurement of the concentration of malondialdehyde (MDA) and superoxide-dismutase (SOD) in liver tissue homogenates, and immunofluorescent staining for oxLDL in liver tissue was conducted in bile-duct ligated (n = 8) and sham-operated rats (n = 8). RESULTS: Significantly higher levels of MDA and lower concentrations of SOD were detected in jaundiced rats than in the sham-operated rats. Positive oxLDL staining was also observed in liver tissue sections of jaundiced rats. Histopathological examination demonstrated that neither fibrosis nor other indications of hepatocellular injury were found in the sham-operated group, while features of severe hepatocellular injury, particularly fibrosis, were found in jaundiced rats. CONCLUSION: Our results support the finding that either oxLDLs are produced as an intermediate agent during exacerbated oxidative stress or they otherwise contribute to the various pathomechanisms underlying the process of liver fibrosis. Whatever the mechanism, it is clear that an association exists between elevated oxLDL levels and hepatocellular injury, particularly with fibrosis. Further studies are needed to evaluate the potential effects of oxLDLs on the progression of secondary biliary cirrhosis.

Immunohistochemical studies of stellate cells in experimental cholestasis in newborn and adult rats

BACKGROUND AND AIMS: Although there is much known about liver diseases, some aspects remain unclear, such as the nature of the differences between the diseases observed in newborn infants and those in adults. For example, how do newborns respond to duct epithelial cell injury? Do the stellate cells in newborns respond similarly to those in adults during biliary obstruction? METHODS: Ninety newborn Wistar rats aged six days, weighing 8.0 - 13.9 g each, and 90 adult rats weighing 199.7 - 357.0 g each, were submitted to bile duct ligation. After surgery, they were randomly divided and sacrificed on the 3rd, 5th, 7th, 14th, 21st or 28th day post-bile duct ligation. Hepatic biopsies were obtained and immunohistochemical semi-quantification of desmin and á-SMA expression was performed in hepatic stellate cells and in myofibroblasts in the portal space, and between the portal space and the liver lobule. RESULTS: Desmin expression in the myofibroblast cells post-bile duct ligation was higher in young rats, reaching its peak level in a shorter time when compared to the adult animals. The differences between the groups for á-SMA expression were less significant than for desmin. CONCLUSIONS: These findings indicate that there is an increase in the number of collagen-producing myofibroblast cells in young animals, suggesting that there is more intense fibrosis in this population. This finding may explain why young animals with bile duct obstruction experience more intense portal fibrosis that is similar to the pathology observed in the livers of newborns with biliary atresia.

Apolipoprotein deficiency and chronic liver disease.

Deficiency of apolipoprotein can be of genetic origin or due to diseases like advanced chronic liver disease. Deficiency of apolipoprotein A causes Tangier disease without any major hepatic involvement being reported. Deficiency of apolipoprotein B causes abetalipoproteinemia or familial hypobetalipoproteinemia; with hepatic involvement in the form of raised transaminases, fatty liver and cirrhosis. Advanced chronic liver disease itself can cause reduction of apolipoprotein A and apolipoprotein B levels and acanthocytosis. In patients with chronic liver disease of undetermined etiology, lipid profile and apolipoprotein levels should be obtained routinely. If it suggests apolipoprotein B deficiency, then liver biopsy can be avoided, as the etiology of chronic liver disease is established. Isolated deficiency of either apolipoprotein A or apolipoprotein B suggests etiology of chronic liver disease, while deficiency of both apolipoprotein A and apolipoprotein B is a manifestation of advanced chronic liver disease.

Renal effects of experimental obstructive jaundice: morphological and functional assessment

Background. The pathophysiology of renal impairments occurring in obstructive jaundice has been extensively studied, but underlying mechanism of these derangements remains unclear. The aim of the present study was to investigate the time-related morphological and functional changes occurring in the kidneys of rats undergoing obstructive jaundice. Methods. Histological examination, renal function assessment and determination of (Na + K)-ATPase activity were performed in the kidneys of rats 7, 14, and 21 days following bile duct ligation (BDL) or sham operation (sham). Results. Glomerular filtration rate was unaffected by BDL throughout the period of the study. Tubular effects occurred at days 7 ant 14, being more marked at day 7, and consisted of an increase of about twice in the fractional excretion of sodium and chloride, paralleled by a decreased proximal and distal tubular reabsorption of sodium of about 50 and 40 percent, respectively. Natriuresis was consistent with augmentation of osmolar clearance but it was not associated with changes in the acivity of renal (Na+ + K+)-ATPase. The ability to dilute urine was imparied at days 14 and 21 after BDL. Additionally, these effects were accompanied by decreased tubulointerstitial fibrosis and vasodilation of inner medullary capillaries. At day 21, the parameters of tubular function in BDL and sham groups were not significantly different. Conclusions. These data support the view that rasied natriuresis taking place in the initial 2 weeks following BDL is due mainly to tubular effects. The contribution of hemodynamic, paracrine and humoral mediators is discussed

Hepatitis neonatal durante los años 1987 a 1991 / Neonatal hepatitis during the years 1987 to 1991

Con la finalidad de conocer la morbi-morbilidad de la Hepatitis Neonatal se realizó un estudio retrospectivo en el Hospital de Niños "J.M. de los Ríos" de Caracas, Venezuela, entre los años 1987-1991. Seleccionándose 47 pacientes de 0 a 3 meses con diagnóstico de Hepatitis Neonatal. Los signos y síntomas que predominaron fueron ictericia, coluria, hipocolia, y hepatomegalia. Se confirmó la etiología de la Hepatitis Neonatal en 7 casos. La edad promedio en que se efectuó la primera biopsia fue de 64,9 días; con un dignóstico de Hepatitis Neonatal en 97,9 por ciento de los casos. Sólo a 8 pacientes se les realizó una segunda biopsia, confirmándose el primer diagnóstico en 4 de ellos. Evolucionando satisfactoriamente el 70,2 por ciento de los casos

Síndrome de alagille en dos hermanos / Alagelle's syndrome in two brothers

Se reportan las características clínicas, bioquímicas y anatomopatológicas de dos hermanos de una misma familia, los cuales presentaron ictericia y otros hallazgos sugestivos del síndrome. Sus estudios demostraron la presencia de hipoplasia de vías biliares intrahepáticas asociadas a anormalidades faciales, vertebrales, pero sin evidencia de otros criterios mayores del síndrome en el área cardíaca y ocular. Estos pacientes podrían englobarse dentro de los síndromes incompletos de Alagille. Es el primer estudio reportado en nuestro país con afectación de miembros de una misma familia

Patologia da icterícia obstrutiva / Pathology of obstructive jaundice

Neste artigo, säo abordados dois aspectos da patologia da icterícia obstrutiva. O primeiro se refere à repercussäo, a nível hepático, sendo analisadas as características morfológicas da colestase e seus principais marcadores, com ênfase no diagnóstico diferencial com causas intra-hepáticas e nas situaçöes em que a biópsia hepática está indicada. O segundo destaca a importância do estudo anatomopatológico das doenças causadoras de obstruçäo extra-hepática, principalmente no diagnóstico diferencial entre colangiopatias inflamatórias e neoplásicas.

Ictericia obstructiva en paciente senil / Obstructive jaundice in senilis patient

El caso de autopsia que se presenta se refiere a paciente masculino de 77 años, vecino de San José, con cuadro de ictericia obstructiva progresiva de poco tiempo de evolución, con dolor abdominal y hepatomegalia, con hiperbilirrubinemia de predominio directo, con colelitiasis y dilatación de vías biliares intrahepáticas detectado por estudio de ultrasonido. Durante su corta estancia intrahospitalaria (4 días) se mantuvo desorientado y con insuficiencia renal aguda. En la autopsia se encontró un carcinoma de vías biliares intrahepáticas (colangiocarcinoma con metástasis a pulmones y cerebro, causando en éste último edema cerebral y herniación bilateral de amígdalas cerebrales que fue la causa inmediata de su deceso. Se agregó además necrosis tubular aguda. Se revisa factores etiológicos relacionados con el tumor que se ha postulado en la literatura, su aspecto macro y microscópico y sus vías de diseminación.

Experimental model of obstructive jaundice in mongrel dog: study of subsequent pathological changes in liver.

BACKGROUND: Attempts at creating an experimental model of obstructive jaundice in large animals have been unsuccessful because of frequent fistulization of the ligated bile duct. OBJECTIVES: To produce a model of obstructive jaundice in mongrel dogs and to study subsequent serial pathological changes in the liver. METHODS: Four techniques were evaluated in four dogs to produce obstructive jaundice. After creation of a successful model, subsequent clinical and biochemical outcome and serial pathological changes in the liver were studied in another 14 dogs. RESULTS: Complete extrahepatic biliary dissection produced a model of persistent obstructive jaundice. Serial histological changes included inflammation and edema in the first 14 days followed by lymphocytic infiltration at 28 days. Fibrosis started by day 7 and resulted in architectural distortion by day 21. CONCLUSION: An acute, complete and irreversible model of obstructive jaundice can be produced by extrahepatic biliary tree excision and ligation. Serial pathological changes showed acute inflammation, followed by fibrosis and architectural distortion.