RESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: TianJiu (TJ) therapy, one type of cold moxibustion, applies to specific acupuncture points with herbal patches of hot nature, providing a constant irritant to the skin until the presence of hyperemia and blistering. Traditional and clinical reports suggest that TJ is an effective therapy for the treatment of jaundice with fresh Ranunculus sceleratus L. (RS), in which protoanemonin is one of the main irritant constituents. However, the therapeutic effect of TJ treatment with fresh RS against intrahepatic cholestasis has not been studied in animal experiments. AIM OF THE STUDY: Present study was undertaken to investigate the effect of TJ treatment with fresh RS against intrahepatic cholestasis in rats and provide an experimental basis for the underlying mechanism of TJ therapy. MATERIALS AND METHODS: Male intrahepatic cholestatic Sprague-Dawley rats induced by 2% α-naphthylisothiocyanate (ANIT, 80â¯mg/kg B.W.) were treated by TJ therapy with fresh RS. The levels of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), direct bilirubin (DBIL), total bilirubin (TBIL), total bile acid (TBA), hepatic malondialdehyde (MDA) and nitric monoxide (NO), as well as hepatic body ratio, bile flow and hepatic histopathological assay were measured and evaluated to investigate the therapeutic effect of TJ treatment with fresh RS. Phytochemical analysis of fresh and dried RS was performed by gas chromatography-mass spectrometer (GC-MS). RESULTS: After TJ treatment with fresh RS, the abnormally elevated levels of serum AST, ALT, ALP, DBIL, TBIL and TBA, as well as hepatic MDA and NO at 108â¯h were reduced significantly (versus model group, Pâ¯<â¯0.01). The hepatic body ratio, bile flow and hepatic pathological change of cholestatic rats at 108â¯h in TJ group were restored when compared with those of model group. Thirty-one compounds including lactones, flavonoids and phenolic acids were identified and determined by GC-MS analysis. The content of protoanemonin in fresh RS (9.49%) was about 25-fold higher than that in dried RS (0.38%). CONCLUSIONS: TJ treatment with fresh RS exhibited good therapeutic effect on ANIT-induced intrahepatic cholestasis in rats, which may be due to the attenuated oxidative stress in the liver tissue. It is rational for the ancients to choose fresh RS as TJ herbal patches because of its abundant protoanemonin with the character of irritant. The qualitative and quantitative results of GC-MS analysis provided the chemical basis of TJ therapy with fresh RS, which can be regarded as a simple and efficient method for the treatment of cholestasis hepatitis.
Asunto(s)
Colestasis Intrahepática/terapia , Hígado , Moxibustión , Ranunculus , 1-Naftilisotiocianato , Animales , Biomarcadores/sangre , Colestasis Intrahepática/sangre , Colestasis Intrahepática/inducido químicamente , Colestasis Intrahepática/patología , Modelos Animales de Enfermedad , Peroxidación de Lípido , Hígado/metabolismo , Hígado/patología , Masculino , Estrés Oxidativo , Ratas Sprague-DawleyRESUMEN
OBJECTIVES: Byler disease, originally described in Amish kindred, results from mutations in ATPase Class I Type 8b Member 1 (ATP8b1). Specific clinical reports of Amish Byler disease were last published 40 years ago. These investigations were directed at the present detailed clinical understanding of the early course of hepatic manifestations of Byler disease. METHODS: This study analyzed routine clinical practice and outcomes of children with Byler disease (defined by homozygous c.923G>T mutation in ATP8b1), who initially presented to Children's Hospital of Pittsburgh of UPMC between January 2007 and October 2014. Data were analyzed to the earlier of 24 months of age or partial external biliary diversion. RESULTS: Six children presented between 1 and 135 days of life: 2 presented with newborn direct hyperbilirubinemia, 2 had complications of coagulopathy, 1 had failure to thrive and rickets, and 1 sibling was identified by newborn genetic testing. Intensive fat-soluble vitamin supplementation was required to prevent insufficiencies in vitamins D, E, and K. Hyperbilirubinemia was variable both over time and between children. Serum bile acid levels were elevated, whereas γ-glutamyltranspeptidase levels were low normal. Scratching behavior (pruritus) was intractable in 4 of 6 children with onset between 6 and 12 months of age. Features of portal hypertension were not observed. Partial external biliary diversion was used during the second year of life in 4 children. CONCLUSIONS: Detailed analysis of Byler disease revealed varied disease presentation and course. Nutritional issues and pruritus dominated the clinical picture in the first 2 years of life.
Asunto(s)
Adenosina Trifosfatasas/genética , Conductos Biliares/patología , Colestasis Intrahepática/patología , Hígado/patología , Mutación , Avitaminosis/etiología , Ácidos y Sales Biliares/sangre , Conductos Biliares/cirugía , Colestasis Intrahepática/epidemiología , Colestasis Intrahepática/terapia , Insuficiencia de Crecimiento/epidemiología , Insuficiencia de Crecimiento/etiología , Pruebas Genéticas , Hospitales , Humanos , Hiperbilirrubinemia/epidemiología , Hiperbilirrubinemia/etiología , Incidencia , Lactante , Recién Nacido , Pennsylvania/epidemiología , Prevalencia , Prurito/etiología , Raquitismo/epidemiología , Raquitismo/etiología , gamma-Glutamiltransferasa/sangreRESUMEN
We previously reported the beneficial effect of fish oil-based lipid emulsions (FOLEs) as monotherapy in the treatment of parenteral nutrition-associated liver disease (PNALD). In this report, we share our ongoing experience at Texas Children's Hospital, Houston, Texas in the use of FOLE in treatment of PNALD as presented at the 2013 Experimental Biology meeting. We describe the findings of a single center, prospective, observational study of infants <6 mo of age with PNALD who received parenteral FOLE as monotherapy. A total of 97 infants received FOLE under the compassionate-use protocol for the treatment of PNALD. Eighty-three (86%) survived with resolution of cholestasis and 14 (14%) died. The median conjugated bilirubin (CB) concentration at the initiation of FOLE therapy was 4.8 mg/dL (range 2.1-26). The median time to resolution of cholestasis was 40 d (range 3-158). Compared with infants with mild cholestasis (CB of 2.1-5 mg/dL at the initiation of FOLE), nonsurvivors were significantly more premature and took longer to resolve their cholestasis. Gestational age at birth correlated inversely with CB at the beginning of FOLE and peak CB. Infants with an initial CB >10 mg/dL had a higher mortality rate than infants with an initial CB <5 mg/dL (35% vs. 6%; P < 0.05). Our experience with the use of FOLE in PNALD continues to be encouraging. Prematurity continues to be a major determinant in mortality and severity of cholestasis. This calls for further controlled studies designed to optimize dose and timing of intervention in the use of FOLE in neonates.
Asunto(s)
Colestasis Intrahepática/terapia , Emulsiones Grasas Intravenosas/uso terapéutico , Aceites de Pescado/uso terapéutico , Enfermedades del Prematuro/terapia , Nutrición Parenteral Total/efectos adversos , Colestasis Intrahepática/etiología , Colestasis Intrahepática/fisiopatología , Ensayos de Uso Compasivo , Congresos como Asunto , Emulsiones/efectos adversos , Emulsiones Grasas Intravenosas/administración & dosificación , Femenino , Aceites de Pescado/administración & dosificación , Hospitales Pediátricos , Humanos , Lactante , Recien Nacido con Peso al Nacer Extremadamente Bajo , Recien Nacido Extremadamente Prematuro , Recién Nacido , Enfermedades del Prematuro/etiología , Enfermedades del Prematuro/fisiopatología , Masculino , Estudios Observacionales como Asunto , Fosfolípidos/efectos adversos , Índice de Severidad de la Enfermedad , Aceite de Soja/efectos adversos , Texas , TriglicéridosRESUMEN
Parenteral nutrition (PN) is a life-saving nutritional support for a large population of hospitalized infants, and lipids make a substantial contribution to their energy and essential fatty acid (FA) needs. A challenge in the care of these infants is that their metabolic needs require prolonged PN support that increases the risk of PN-associated liver disease (PNALD). In recent years, the emergence of new parenteral lipid emulsions containing different source lipids and FA profiles has created nutritional alternatives to the first-generation, soybean oil-based lipid emulsion Intralipid. The limited U.S. introduction of the new-generation fish-oil emulsion Omegaven has generated promising results in infants with PNALD and spawned a renewed interest in how PN and lipid emulsions, in particular, contribute to this disease. Studies suggest that the lipid load and constituents, such as specific FAs, ratio of n-3 (ω-3) to n-6 (ω-6) long-chain polyunsaturated FAs, phytosterols, and vitamin E content, may be involved. There is an existing literature describing the molecular mechanisms whereby these specific nutrients affect hepatic metabolism and function via lipid and bile acid sensing nuclear receptors, such as peroxisome proliferator-activated receptor α, liver X receptor, and farnesoid X receptor, yet virtually no information as to how they interact and modulate liver function in the context of PN in pediatric patients or animal models. This article will review the recent development of parenteral lipid emulsions and their influence on PNALD and highlight some of the emerging molecular mechanisms that may explain the effects on liver function and disease.
Asunto(s)
Colestasis Intrahepática/prevención & control , Emulsiones Grasas Intravenosas/uso terapéutico , Ácidos Grasos Omega-3/uso terapéutico , Enfermedades del Prematuro/prevención & control , Estrés Oxidativo , Nutrición Parenteral Total/efectos adversos , Colestasis Intrahepática/etiología , Colestasis Intrahepática/metabolismo , Colestasis Intrahepática/terapia , Congresos como Asunto , Combinación de Medicamentos , Emulsiones Grasas Intravenosas/efectos adversos , Emulsiones Grasas Intravenosas/metabolismo , Ácidos Grasos Omega-3/efectos adversos , Ácidos Grasos Omega-3/metabolismo , Factores de Crecimiento de Fibroblastos/metabolismo , Aceites de Pescado/efectos adversos , Aceites de Pescado/metabolismo , Aceites de Pescado/uso terapéutico , Humanos , Recién Nacido de Bajo Peso , Recién Nacido , Recien Nacido Prematuro , Enfermedades del Prematuro/etiología , Enfermedades del Prematuro/metabolismo , Enfermedades del Prematuro/terapia , Hígado/inmunología , Hígado/metabolismo , Fosfolípidos/efectos adversos , Fosfolípidos/metabolismo , Fosfolípidos/uso terapéutico , Aceites de Plantas/efectos adversos , Aceites de Plantas/metabolismo , Aceites de Plantas/uso terapéutico , Receptores Citoplasmáticos y Nucleares/metabolismo , Transducción de Señal , Sorbitol/efectos adversos , Sorbitol/metabolismo , Sorbitol/uso terapéutico , Aceite de Soja/efectos adversos , Aceite de Soja/metabolismo , Aceite de Soja/uso terapéutico , Receptor Toll-Like 4/metabolismo , Triglicéridos , Vitamina E/metabolismoRESUMEN
Intrahepatic Cholestasis of Pregnancy (ICP) constitutes the most common, reversible liver disease closely connected with pregnancy and spontaneously resolving in puerperium. ICP usually reoccurs in consecutive pregnancies (45-90%), often in a more intensified form. Many compounds (hormones, cytokines, medicines, endotoxins) can impair transport in the hepatocyte, disturb the intracellular transport and increase the permeability of the intercellular connections. As a result, the elements of bile may appear in the peripheral blood. Gestational cholestasis constitutes a classic example of intrahepatic cholestasis. The etiology of ICP is multifactorial with hormonal, genetic and environmental factors participating in the process. The diagnosis is based on the presence of pruritus, elevated values of bile acids in the blood serum and of aminotransferases (aspartic, aminopropionic and gamma-glutamylotranspeptydase (AspAt, AlAt, GGTP)), as well as spontaneous remission in the second or third week after childbirth, of lack of other illnesses causing pruritus and icterus. Clinical and biochemical symptoms of ICP include: pruritus without skin rash (usually after 30 weeks of gestation), mild icterus, steatorrhea etc. Abnormalities in the laboratory tests of the LFT (liver function tests) encompass: an increase in the serum concentration of fatty acids (BA) which can be the first and only laboratory abnormality. Concentrations surpassing 10 micromol/l are considered to be abnormal. Concentration of BA higher than 40 micromol/l allows to recognize a case of severe ICP, connected with the risk of premature delivery presence of the meconium liquor, surgical means of delivery and low APGAR score of the newborn (< 7 pt). In about 80% of pregnant women with ICP, the BA concentration ranges between 10-40 micromol/l, but perinatal results are comparable with uncomplicated pregnancies. Some authors are of the opinion that abnormal AlAt value is the most sensitive test, other authors consider the abnormal values of alkaline phosphatase and bilirubin to be the most pathognomonic factors. Other abnormal tests include: higher activity of alpha-hydroxybutyric dehydrogenase correlated with an increase of the alkaline phosphatase and bilirubin; mild metabolic acidosis; dyslipidemia with elevated concentrations of the total lipids, total cholesterol and free LDL cholesterol and apolipoprotein; abnormal glucose tolerance test. ICP constitutes a medical problem that carries a considerable risk for the fetus, resulting from an increased flow of bile acids to the fetal blood circulation (elevated level in the amniotic fluid, in the umbilical blood serum and meconium). The risk of adverse effects for the fetus correlates with the rise of BA concentration in maternal blood serum. Cholestasis increases the risk of premature labor, presence of meconium in the amniotic fluid, fetal bradycardia, intrauterine asphyxia and stillbirth, particularly when the concentration of serum bile acids on an empty stomach is above 40 micromol/l. However, maternal clinical signs and symptoms do not correlate with the fetal outcome. Aspiration of bile acids or their accumulation in the fetal blood circulation are responsible for the increased frequency of RDS appearing in ICP. The aim of the obstetric management of ICP is to reduce maternal symptoms and biochemical disorders and to minimize the risk of premature delivery fetal distress and sudden death. ICP management should include: bed regime, light, low-fat diet, no stress, upper abdomen ultrasound examination, LFT tests and thrombotic tests once a week, monitoring of the fetal well-being with the available biophysical methods, pharmacotherapy and therapeutic termination of pregnancy in case of serious illness and/or the fetal distress. Ursodeoxycholic acid (UDCA) is the basis of the pharmacological treatment of pregnant women and currently constitutes the most promising treatment option of ICP. UDCA is administered orally in the dosage of 10-16 mg/kg/24, what in practice means 250-300 mg/2-3 times a day.
Asunto(s)
Colestasis Intrahepática/diagnóstico , Colestasis Intrahepática/terapia , Complicaciones del Embarazo/diagnóstico , Complicaciones del Embarazo/terapia , Resultado del Embarazo , Salud de la Mujer , Femenino , Ginecología/normas , Humanos , Capacitación en Servicio/normas , Programas Nacionales de Salud/normas , Obstetricia/normas , Polonia , Guías de Práctica Clínica como Asunto , Embarazo , Prevención Primaria/normas , Garantía de la Calidad de Atención de Salud/normas , Sociedades Médicas/normasRESUMEN
PURPOSE: Dependence on total parenteral nutrition in intestinal failure or short bowel syndrome patients can lead to many complications. The most significant complication is progressive liver injury leading to liver failure. This study assesses the potential of hepatocyte growth factor (HGF) in modulating the hepatic response in a rat cholestatic liver injury model. METHODS: Female Sprague-Dawley rats were divided into 3 groups: control (n = 5), chronic liver injury (alpha-naphtylisocyocyanate [ANIT] every 3.5 days at 75 mg/kg; n = 5), and chronic liver injury plus HGF (ANIT + HGF at 250 microg kg(-1) d(-1); n = 5). The rats initially underwent massive (80%) small bowel resections. Seven days later, they were given intraperitoneal injections of saline (control) or ANIT and implantation of an osmotic minipump for continuous intravenous saline or HGF. Intraperitoneal saline or ANIT injections were subsequently administered every 3.5 days to create a chronic cholestatic model. After 14 days, the animals were euthanized, and liver biopsies were obtained. The liver biopsies were evaluated by histology, immunofluorescence staining for interleukin-6 and tumor necrosis factor alpha, and assessment of apoptosis by terminal dUTP-transferase-mediated nick end labeling (TUNEL) technique. RESULTS: In this chronic liver injury model, HGF did not effect the grade of inflammation. However, HGF did induce retention of the ductal structures and avoided ductal proliferation, damage, and evidence of primary sclerosing cholangitis (P < .05). Hepatocyte growth factor induced less interleukin-6 (P < .011) and tumor necrosis factor alpha (P < .01) expression. Apoptotic activity was also significantly less in the HGF group (P < .01). CONCLUSION: Hepatocyte growth factor preserved the hepatic ductal system, modulated the hepatic inflammatory response, and reduced the apoptotic index in this chronic cholestatic liver injury model. It may diminish or prevent liver damage in patients with total parenteral nutrition-induced liver injury.
Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas/terapia , Factor de Crecimiento de Hepatocito/uso terapéutico , Hepatopatías/tratamiento farmacológico , Fallo Hepático/prevención & control , Nutrición Parenteral Total/efectos adversos , 1-Naftilisotiocianato , Animales , Colestasis Intrahepática/etiología , Colestasis Intrahepática/prevención & control , Colestasis Intrahepática/terapia , Modelos Animales de Enfermedad , Femenino , Factor de Crecimiento de Hepatocito/farmacología , Inmunohistoquímica , Etiquetado Corte-Fin in Situ , Interleucina-6/análisis , Interleucina-6/metabolismo , Hígado/química , Hígado/efectos de los fármacos , Hígado/patología , Hepatopatías/etiología , Hepatopatías/patología , Pruebas de Función Hepática , Ratas , Ratas Sprague-Dawley , Síndrome del Intestino Corto/terapia , Factor de Necrosis Tumoral alfa/análisisRESUMEN
AIM: Plurietiological hepatic cholestasis involves an increased risk of protein-caloric malnutrition and specifical nutritional deficiencies. Biological investigations to determine deficiencies in fat-soluble vitamins are essential for specific nutritional therapy . Although malnutrition is not an absolute contraindication for liver transplantation, its gravity has complex consequences in relation to this intervention. MATERIAL AND METHOD: The authors present a study conducted over a period of 5 years following the analysis of 293 children diagnosed with intra- or extrahepatic abnormalities that caused varying degrees of cholestasis. RESULTS: In the study group, the percentage of infants with cholestasis was 45.39% (133 cases) and among them 62.12% had malnutrition (82 children). Clinical evaluation of fat-soluble vitamins deficiency, in particular, but also of the soluble and minerals was performed in all patients. Liver transplantation was successfully performed in three cases. CONCLUSIONS: Most important factors affecting growth after transplantation were age at the time of the liver transplant and primary diagnosis that required transplant. The role of nutritional support prior to liver transplantation is of great importance. Quality nutritional support change impact that malnutrition has on survival after liver transplantation.
Asunto(s)
Colestasis/diagnóstico , Colestasis/terapia , Trasplante de Hígado , Desnutrición/diagnóstico , Desnutrición/terapia , Estado Nutricional , Adolescente , Niño , Preescolar , Colestasis/complicaciones , Colestasis/epidemiología , Colestasis/etiología , Colestasis Extrahepática/diagnóstico , Colestasis Extrahepática/terapia , Colestasis Intrahepática/diagnóstico , Colestasis Intrahepática/terapia , Suplementos Dietéticos , Humanos , Lactante , Recién Nacido , Desnutrición/epidemiología , Desnutrición/etiología , Evaluación Nutricional , Apoyo Nutricional/métodos , Estudios Prospectivos , Estudios Retrospectivos , Factores de Riesgo , Rumanía/epidemiología , Tasa de SupervivenciaRESUMEN
OBJECTIVE: To evaluate the therapeutic effect of compound salvia injection combined with ursodeoxycholic acid (UDCA) in treating pregnant women with intrahepatic cholestasis (ICP) and its influence on perinatal babies. METHODS: One hundred and twenty-eight patients of ICP were assigned to two groups. The 72 patients in the treatment group were treated with salvia injection (20 mL in 10% glucose 500 mL for intravenous dripping once a day) and UDCA (15 mg, thrice daily by oral taken), and the 56 patients in the control group were treated with UDCA alone, all were treated for 14 days. Changes of itching symptom (estimated by scoring) and serum levels of biochemical indexes, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin (TBil) and glycocholic acid (GCA), were determined before and after treatment, and conditions of the newborns were compared after delivery. RESULTS: Compared with before treatment, scores of itching were lowered from 3.6 scores to 1.4 scores in the treatment group, and from 3.4 scores to 1.6 scores in the control group, showing no significant difference between groups (P > 0.05), but the lowering was shown earlier in the former. Levels of biochemical indexes were improved significantly (P < 0.01) in both groups, but the improvements were more significant in the treatment group, the difference between groups was significant (P < 0.05). The difference between groups in the incidence of fetal distress, meconium-stained fluid and neonatal asphyxia were insignificant (P > 0.05). The birth weights of the newborns were higher in the treatment group than in the control group (3,108 +/- 236 g vs 2,681 +/- 269 g, P < 0.05). CONCLUSION: The combined therapy of compound salvia injection and UDCA shows better effect in treating ICP than that of UDCA alone.
Asunto(s)
Colestasis Intrahepática/terapia , Medicina Tradicional China/métodos , Fitoterapia , Complicaciones del Embarazo/terapia , Salvia miltiorrhiza/química , Ácido Ursodesoxicólico/uso terapéutico , Adulto , Terapia Combinada , Femenino , Humanos , Embarazo , Resultado del Embarazo , Adulto JovenRESUMEN
OBJECTIVE: The objective of this report was to describe a case of prolonged intrahepatic cholestasis likely associated with the use of loxoprofen, a phenylpropionate NSAID. METHODS: A 36-year-old female patient was transferred to Gunma University Hospital, Maebashi, Japan, with progressive pruritus and jaundice that developed after 5-day treatment with 120 mg/d of loxoprofen (maximum recommended dose, 180 mg/d) for menstrual pain. Liver function tests found the following concentrations: total bilirubin, 27.5 mg/dL (normal [nl] range, 0.3-1.2 mg/dL); aspartate aminotransferase, 151 IU/L (nl, 13-33 IU/L); alkaine aminotransferase, 470 IU/L (nl, 8-42 IU/L); alkaline phosphatase, 1082 IU/L (n1, 115-359 IUAL); and gamma-glutamyl transpeptidase, 795 IU/L (nl, 10-47 IU/L) indicative of intrahepatic cholestasis. No use of alcohol or other drugs or herbal products was reported. The patient had a history of elevated hepatic enzymes of unknown origin following the use of mefenamic acid. The patient was prescribed ursodeoxycholic acid 3 weeks after the onset of symptoms of intrahepatic cholestasis. Thereafter, due to progressive cholestasis, an IV pulse of methylprednisolone (1000 mg/d) and the herbal product Inchin-ko-to (TJ-135) were administered. Plasma bilirubin adsorption (PA) and plasma exchange (PE) were performed. RESULTS: Following treatment with PA and PE for 3 weeks with administration of methylprednisolone and Inchin-ko-to, signs and symptoms of intrahepatic cholestasis began to resolve (3.5 months after the onset); they were completely resolved 8 months after the initial episode. A Naranjo scale score of 6 suggested that loxoprofen was likely the cause of the prolonged cholestasis in this patient. CONCLUSION: Based on the Naranjo score, this case of prolonged intrahepatic cholestasis in a young woman was likely associated with loxoprofen use.
Asunto(s)
Colestasis Intrahepática/inducido químicamente , Fenilpropionatos/efectos adversos , Adulto , Antiinflamatorios no Esteroideos/efectos adversos , Antiinflamatorios no Esteroideos/uso terapéutico , Bilirrubina/sangre , Colestasis Intrahepática/complicaciones , Colestasis Intrahepática/terapia , Medicamentos Herbarios Chinos/administración & dosificación , Medicamentos Herbarios Chinos/uso terapéutico , Femenino , Humanos , Ictericia/complicaciones , Ictericia/diagnóstico , Metilprednisolona/administración & dosificación , Metilprednisolona/uso terapéutico , Fenilpropionatos/uso terapéutico , Intercambio Plasmático/métodos , Prurito/complicaciones , Prurito/diagnóstico , Factores de TiempoRESUMEN
Taurine deficiency in patients on long-term parenteral nutrition may be involved in cholestasis. We aimed to assess plasma taurine and tauro-conjugated bile acids in adults with short-bowel syndrome and their response to intravenous taurine. Thirty-two adult patients, who had been on taurine-free parenteral nutrition for a mean of 59 (SE 14) months for short-bowel syndrome, were studied retrospectively. In a second study, a subgroup of ten patients with chronic cholestasis received taurine-enriched (6.0 (SE 0.6) mg/kg per d) parenteral nutrition for 55 (SE 13) months. Post-absorptive plasma taurine and bile acid concentrations were measured and liver function tests routinely sampled. At baseline, plasma taurine was lower in patients with a jejunal length of less than 35 cm (group A, n 16) than in those with a jejunal length of 35 cm or more (group B, n 16): 43 (SE 3) v. 58 (SE 4) micromol/l (P=0.01). The groups were no different in terms of chronic cholestasis (12/16 v.13/16 patients), total bile acids (26 (SE 13) v.14 (SE 5) micromol/l) or the ratio of tauro-conjugated:glyco-conjugated bile acids (5 (SE 2) v.8(SE 4)%, usual range 30-60%). After supplementation, there was an increase in plasma taurine level (63 (SE 8) v. 43 (SE 4), P=0.007) but was no change in either total bile acids or the ratio of tauro-conjugated: glyco-conjugated bile acids. There was a significant decrease in aspartate aminotransferase level. Long-term parenteral nutrition for short-bowel syndrome is associated with an impaired tauro-conjugation of bile acids (enterohepatic pool), irrespective of plasma taurine level (systemic pool) and despite long-term taurine intravenous supplementation.
Asunto(s)
Nutrición Parenteral/métodos , Síndrome del Intestino Corto/terapia , Taurina/sangre , Adulto , Aminoácidos/análisis , Ácidos y Sales Biliares/sangre , Colestasis Intrahepática/sangre , Colestasis Intrahepática/etiología , Colestasis Intrahepática/terapia , Enfermedad Crónica , Métodos Epidemiológicos , Femenino , Humanos , Infusiones Intravenosas , Yeyuno/patología , Masculino , Persona de Mediana Edad , Síndrome del Intestino Corto/sangre , Síndrome del Intestino Corto/complicaciones , Síndrome del Intestino Corto/patología , Taurina/administración & dosificación , Taurina/deficienciaRESUMEN
BACKGROUND: A newborn with cholestatic hepatic disease and hemophagocytic lymphohistiocytosis due to rhesus hemolytic disease (RHD) is reported. OBSERVATION: A 34 weeks' gestation baby with RHD, who had received multiple intrauterine transfusions (IUT), developed cholestatic hepatic disease and secondary hemophagocytic lymphohistiocytosis (HLH). Her serum ferritin level increased to 5,527 ng/mL, and liver biopsy showed severe iron overload. Treatment with intravenous desferrioxamine resulted in a marked decrease in serum ferritin levels and normalization of liver function CONCLUSION: We suggest that patients who have undergone IUT be evaluated for hyperferritinemia. If hyperferritinemia is noted, chelation therapy should be considered. As another rare finding, HLH can complicate the course of RHD.
Asunto(s)
Anemia Hemolítica Autoinmune/complicaciones , Sobrecarga de Hierro/etiología , Linfohistiocitosis Hemofagocítica/etiología , Reacción a la Transfusión , Adulto , Anemia Hemolítica Autoinmune/terapia , Colestasis Intrahepática/etiología , Colestasis Intrahepática/terapia , Deferoxamina/uso terapéutico , Femenino , Humanos , Recién Nacido , Sobrecarga de Hierro/terapia , Linfohistiocitosis Hemofagocítica/terapiaRESUMEN
Progressive intrahepatic familial cholestasis (PFIC), previously called Byler's disease, is a syndrome in which children develop severe cholestasis progressing to biliary cirrhosis and chronic liver failure, usually during the first decade of life. Clinical features include jaundice, hepatomegaly, splenomegaly, growth retardation and severe pruritus. Laboratory tests demonstrate elevated bilirubin and bile acids, without an increase in serum gamma-glutamyl-transpeptidase or cholesterol. This study was performed to evaluate our experience with medical therapy as well as two types of surgical treatment used in children with PFIC, particularly partial external biliary diversion (PEBD) as an alternative method of therapy to liver transplantation (OLTx). Between 1979 and 1998 we have treated 46 children with PFIC (27 boys and 19 girls), aged 10 months to 19 yr (at the time of this study). Medical treatment with ursodeoxycholic (UDCA) was used in 39 patients for the period between 6 and 82 months. PEBD (cholecysto-jejuno-cutaneostomy) was performed in 16 patients, OLTx in eight children (including one after unsuccessful PEBD). Retrospective analysis of the clinical course and selected laboratory tests (bilirubin, ASPAT, ALAT, bile acids), and histopathological examinations were performed. Results of treatment were assessed by means of influence of the type of treatment on clinical symptoms, laboratory tests, progress of liver cirrhosis and hepatic failure, as well as physical development and survival. Medical therapy was effective in the long term in four (10%) of the patients resulting in clinical and biochemical normalization. Both surgical methods of therapy of PFIC, PEBD and OLTx, resulted in an 80% success rate and therefore should be used as complementary therapies. In patients before established liver cirrhosis, PEBD should be the first choice of treatment. Patients presenting with cirrhosis or after ineffective PEBD should qualify for OLTx. With this strategy most children with PIFC can be cured.
Asunto(s)
Colestasis Intrahepática/cirugía , Colestasis Intrahepática/terapia , Procedimientos Quirúrgicos Dermatologicos , Vesícula Biliar/cirugía , Yeyuno/cirugía , Trasplante de Hígado , Estomas Quirúrgicos , Adolescente , Adulto , Niño , Preescolar , Colagogos y Coleréticos/uso terapéutico , Colestasis Intrahepática/genética , Interpretación Estadística de Datos , Femenino , Estudios de Seguimiento , Humanos , Lactante , Masculino , Factores de Tiempo , Resultado del Tratamiento , Ácido Ursodesoxicólico/uso terapéuticoRESUMEN
BACKGROUND: Inborn errors of bile acid synthesis are newly recognized disorders that may cause the phenotypic appearance of neonatal hepatitis or neonatal cholestasis. METHODS: This is a clinicopathologic study of two sets of siblings with cholestatic neonatal liver failure. RESULTS: In 3 of the infants, diagnostic evaluation, including analysis of urinary bile salts, revealed a predominance of 7 alpha-hydroxy-3-oxo-4-cholenoic and 7 alpha, 12 alpha-dihydroxy-3-oxo-4-cholenoic acids, a pattern consistent with delta 4-3-oxosteroid 5 beta-reductase deficiency, which could be primary or secondary. The fourth infant died before such testing could be carried out. In addition, all 4 infants had histologically disseminated hemochromatosis and met diagnostic criteria for neonatal hemochromatosis. In the 3 infants studied, histologic examination of the liver disclosed giant cell hepatitis with extensive loss of hepatic parenchyma and rapid progression to cirrhosis. Early treatment with ursodeoxycholic acid and cholic acid, previously reported as effective therapy, was given to 2 siblings; it failed to reverse or halt the liver damage, and both infants died. One infant, with the original diagnosis of neonatal hemochromatosis, was treated with a variety of antioxidants and chelation therapy, as recently reported. No improvement was demonstrated, and he went on to liver transplantation. CONCLUSIONS: The presentation of delta 4-3-oxosteroid 5 beta-reductase deficiency as neonatal hemochromatosis may represent a distinct subset of this disorder with an accelerated course, no response to therapy and poor prognosis.
Asunto(s)
Ácidos y Sales Biliares/metabolismo , Hemocromatosis/metabolismo , Errores Innatos del Metabolismo/metabolismo , Oxidorreductasas/deficiencia , Adulto , Biopsia , Colestasis Intrahepática/etiología , Colestasis Intrahepática/patología , Colestasis Intrahepática/terapia , Ácido Cólico , Ácidos Cólicos/uso terapéutico , Femenino , Cromatografía de Gases y Espectrometría de Masas , Humanos , Recién Nacido , Hígado/patología , Fallo Hepático/etiología , Fallo Hepático/patología , Fallo Hepático/terapia , Masculino , Pronóstico , Espectrometría de Masa Bombardeada por Átomos Veloces , Ácido Ursodesoxicólico/uso terapéuticoRESUMEN
Pruritus associated with hepatic cholestasis may cause significant morbidity and its correlation to retention of bile acids in skin is inconsistent. Available treatment modalities are only partially effective and can have several adverse effects. Phototherapy has recently been reported to improve cholestatic pruritus, but has not been evaluated previously in children, and its mechanism is still unclear. We report the outcome of multiple Daylite phototherapy treatments over two years in a seven-year-old child with chronic hepatic cholestasis that was resistant to other therapeutic modalities. Bile acid levels in urine were used as markers of effectiveness in parallel with clinical response. Night phototherapy alone increased the bile acids/creatinine ratio in urine from 1.54 +/- 0.04 mumol/mg at baseline to 2.07 +/- 0.29 mumol/mg. Continuous phototherapy combined with night diuresis raised the ratio further to 2.28 +/- 0.55 mumol/mg. Night diuresis alone had no effect. Continuous phototherapy combined with night diuresis raised the bile acids/creatinine ratio by 44% on the first day and by 61% on the second day, but declined to baseline on the third day of treatment. A marked clinical improvement was noted for one week following two days of phototherapy. This schedule has been repeatedly effective in improving pruritus for approximately one year and may be due to the ability of phototherapy to enhance excretion of bile acids and other possible pruritogens into urine.
Asunto(s)
Colestasis Intrahepática/terapia , Fototerapia/métodos , Prurito/terapia , Ácidos y Sales Biliares/orina , Bilirrubina/sangre , Niño , Colestasis Intrahepática/metabolismo , Diuresis , Humanos , Pruebas de Función Hepática , Masculino , Prurito/metabolismoRESUMEN
On the basis of experience in the treatment of 1,276 patients who were operated on for various forms of obstructive jaundice and acute hepatic insufficiency, the author recommends including in the therapeutic complex, besides the commonly accepted therapy, hemo- and lymph sorption, combined anesthesia including electroanalgesia, and controlled dosed decrease of pressure in the biliary system during and after the operation. With the use of this complex of treatment in obstructive jaundice complicated by acute hepatic insufficiency, lethality fell from 13.1% to 5.9%.
Asunto(s)
Colestasis Intrahepática/terapia , Encefalopatía Hepática/terapia , Enfermedad Aguda , Colestasis Intrahepática/complicaciones , Terapia Combinada , Encefalopatía Hepática/etiología , Humanos , Desintoxicación por Sorción/métodos , Estimulación Eléctrica Transcutánea del NervioAsunto(s)
Colestasis Intrahepática/terapia , Hepatitis B/terapia , Oxigenoterapia Hiperbárica , Hipoxia/terapia , Enfermedad Aguda , Adolescente , Adulto , Colestasis Intrahepática/complicaciones , Femenino , Hepatitis B/complicaciones , Humanos , Hipoxia/etiología , Masculino , Persona de Mediana EdadRESUMEN
Intrahepatic biliary obstruction was treated in 60 patients (49 with cholangiocarcinoma and 11 with sclerosing cholangitis) who were classified according to the upper limit of their obstruction (Group I, proximal common hepatic duct; Group 2, right and left main hepatic ducts; Group 3, intrahepatic bile ducts). Thirty-six patients underwent percutaneous transhepatic biliary drainage, and 14 underwent catheterization through a T-tube track, Five of this latter group had the T-tube placed to establish a route of access for later interventional radiologic manipulations. Since most diseases that produce intrahepatic biliary obstruction are progressive, the use of any single approach is limited. The advantages of a surgically created route of access combined with the flexibility of interventional radiologic techniques help to maximize the therapy and extend the palliation that many of these patients receive.