Ductular reaction and hepatocyte ballooning identify patients with fibrosing cholestatic hepatitits after liver transplantation.

INTRODUCTION: Diagnosis of severe hepatitis C recurrence is based on analytical and histological criteria but there is little information about their correlation. AIM: To assess the accuracy of laboratory criteria for the diagnosis of fibrosing cholestatic hepatitis (FCH). PATIENTS AND METHODS: Retrospective analysis of prospectively collected data form HCV positive patients who underwent liver transplantation (LT) between 2000 and 2014 in two European university hospitals. Patients were classified according to laboratory criteria such as FCH, cholestatic hepatitis (CH) and non-cholestatic acute hepatitis (NCAH). Histological characteristics were also evaluated. RESULTS: Seventy patients with acute HCV recurrence within the first year after LT with an available liver biopsy were included in the study. Most patients were male (70%) with a median age of 58 years (50-64) and infected with genotype 1b (71.4%). Median time from LT to diagnosis of recurrence was 2.96 months (2.1-5.3). Thirty-nine patients were classified as FCH, 21 as CH and 10 as NCAH. Marked hepatocyte ballooning and ductular reaction were associated with the presence of FCH with an OR of 4.66 (p=0.047) and 20.58 (p=0.025), respectively. Considering liver biopsy as the gold standard, the sensitivity, specificity, positive and negative predictive values of the analytical criteria were 0.8, 0.5, 0.3 and 0.9, respectively. However, correlation between histological and analytical criteria was poor (k=0.033). DISCUSSION: Analytical criteria may be used to rule out the presence of FCH, but a biopsy is mandatory to confirm the diagnosis. Ductular reaction and hepatocyte ballooning were independent predictors of FCH.

Advances in drug-induced cholestasis: Clinical perspectives, potential mechanisms and in vitro systems.

Despite growing research, drug-induced liver injury (DILI) remains a serious issue of increasing importance to the medical community that challenges health systems, pharmaceutical industries and drug regulatory agencies. Drug-induced cholestasis (DIC) represents a frequent manifestation of DILI in humans, which is characterised by an impaired canalicular bile flow resulting in a detrimental accumulation of bile constituents in blood and tissues. From a clinical point of view, cholestatic DILI generates a wide spectrum of presentations and can be a diagnostic challenge. The drug classes mostly associated with DIC are anti-infectious, anti-diabetic, anti-inflammatory, psychotropic and cardiovascular agents, steroids, and other miscellaneous drugs. The molecular mechanisms of DIC have been investigated since the 1980s but they remain debatable. It is recognised that altered expression and/or function of hepatobiliary membrane transporters underlies some forms of cholestasis, and this and other concomitant mechanisms are very likely in DIC. Deciphering these processes may pave the ways for diagnosis, prognosis and prevention, for which currently major gaps and caveats exist. In this review, we summarise recent advances in the field of DIC, including clinical aspects, the potential mechanisms postulated so far and the in vitro systems that can be useful to investigate and identify new cholestatic drugs.

Post-transplant cholangiopathy: Classification, pathogenesis, and preventive strategies.

Biliary complications are the most frequent cause of morbidity, re-transplantation, and even mortality after liver transplantation. In general, biliary leakage and anastomotic and non-anastomotic biliary strictures (NAS) can be recognized. There is no consensus on the exact definition of NAS and different names and criteria have been used in literature. We propose to use the term post-transplant cholangiopathy for the spectrum of abnormalities of large donor bile ducts, that includes NAS, but also intraductal casts and intrahepatic biloma formation, in the presence of a patent hepatic artery. Combinations of these manifestations of cholangiopathy are not infrequently found in the same liver and ischemia-reperfusion injury is generally considered the common underlying mechanism. Other factors that contribute to post-transplant cholangiopathy are biliary injury due to bile salt toxicity and immune-mediated injury. This review provides an overview of the various types of post-transplant cholangiopathy, the presumed pathogenesis, clinical implications, and preventive strategies.

Colestasis: un enfoque actualizado / Cholestasis: an updated approach

Mediante una extensa revisión bibliográfica fue posible profundizar en el tema de las ictericias obstructivas o las colestasis, sobre todo en los aspectos más importantes de su definición, semiogénesis, clasificación, etiopatogenia, manifestaciones clínicas, estudios de laboratorio e imagenológicos, además del diagnóstico, la evolución, el pronóstico y tratamiento, con el objetivo de proporcionar los elementos más novedosos de cada uno de ellos, a través de un enfoque didáctico y una base científica, desde la óptica del internista, para así facilitar conocimientos prácticos acerca del síndrome

It was possible to deepen in the topic of the obstructive icterus or cholestasis by means of an extensive literature review, mainly in the most important aspects of its definition, semiogenesis, classification, etiopathogenesis, clinical manifestations, laboratory and imagenological studies, besides diagnosis, clinical course, prognosis and treatment in this respect, with the objective of providing the most original elements of each of them, through a didactic approach and a scientific base, from the internist's optics, and in this way, to facilitate practical knowledge about the syndrome

Improved classification of indeterminate biliary strictures by probe-based confocal laser endomicroscopy using the Paris Criteria following biliary stenting.

BACKGROUND AND AIMS: Probe-based confocal laser endomicroscopy (pCLE) using the Miami Criteria has improved classification of indeterminate biliary strictures. However, previous biliary stenting may result in their misclassification as malignant strictures. Inflammatory criteria were added to form the Paris Classification to prevent this misclassification and reduce false positives. The aim of this study was to assess if the Paris Classification was more accurate than the Miami Classification in classifying indeterminate biliary strictures after biliary stenting. METHODS: This was a retrospective observational study involving 21 patients with indeterminate biliary strictures from whom 27 pCLE video sequences were obtained (20 benign and seven malignant). Patients with and without prior biliary stenting underwent pCLE. Two investigators classified the strictures as malignant or benign using the Miami and Paris Classifications. Diagnostic accuracy, sensitivity (Se), and specificity (Sp) of endoscopic retrograde-guided pCLE were compared with final histopathology. RESULTS: In those without biliary stenting, the Miami Criteria resulted in Se 88%, Sp 75%, positive predictive value (PPV) 64%, negative predictive value (NPV) 92%, and accuracy 79%, while the Paris Classification resulted in Se 63%, Sp 88%, PPV 71%, NPV 82%, and accuracy 79%. In those with prior biliary stenting, the Miami Criteria resulted in Se 88%, Sp 36%, PPV 23%, NPV 93%, and accuracy 45%, while the Paris Classification resulted in Se 63%, Sp 73%, PPV 31%, NPV 91%, and accuracy 71%. The kappa statistic was 0.56. CONCLUSION: The Paris Classification improved specificity and accuracy of biliary stricture classification in those who had been previously stented and decreased the rate of misclassification of benign strictures as malignant.

Clinical Application of Six Current Classification Systems for Iatrogenic Bile Duct Injuries after Cholecystectomy.

BACKGROUND/AIMS: Due to being a severe complication, iatrogenic bile duct injury is still a challenging issue for surgeons in gallbladder surgery. However, a commonly accepted classification describing the type of injury has not been available yet. This study aims to evaluate ability of six current classification systems to discriminate bile duct injury patterns. METHODOLOGY: Twelve patients, who were referred to our clinic because of iatrogenic bile duct injury after laparoscopic cholecystectomy were reviewed retrospectively. We described type of injury for each patient according to current six different classifications. RESULTS: 9 patients underwent definitive biliary reconstruction. Bismuth, Strasberg-Bismuth, Stewart-Way and Neuhaus classifications do not consider vascular involvement, Siewert system does, but only for the tangential lesions without structural loss of duct and lesion with a structural defect of hepatic or common bile duct. Siewert, Neuhaus and Stewart-Way systems do not discriminate between lesions at or above bifurcation of the hepatic duct. CONCLUSION: The Hannover classification may resolve the missing aspects of other systems by describing additional vascular involvement and location of the lesion at or above bifurcation.

Refined probe-based confocal laser endomicroscopy classification for biliary strictures: the Paris Classification.

BACKGROUND: Most modalities for tissue confirmation during endoscopic retrograde cholangiopancreatography (ERCP) suffer from low sensitivity and poor diagnostic accuracy. Probe-based confocal laser endomicroscopy (pCLE) was prospectively evaluated in a multicenter registry including 102 patients with indeterminate strictures and demonstrated excellent sensitivity (98 %). Yet, several false-positive cases were induced by benign inflammatory conditions resulting in a specificity of 67 %. AIMS: To evaluate the diagnostic performance of pCLE for the diagnosis of indeterminate biliary stricture; and to propose interpretation criteria for benign inflammatory conditions to reduce the number of false positives. METHODS: Sixty cases from the prospective registry were reviewed retrospectively (27 malignant, 33 benign) by a panel of three biliary endoscopists. Each case's clinical history, ERCP impression, and corresponding pCLE sequences was used to score image quality, propose presumptive diagnoses, and rate level of diagnostic confidence. RESULTS: Using the Miami Classification (MC), the overall accuracy in retrospectively diagnosing malignancy in those 60 cases was 85 versus 78 % for the prospective analysis, reducing the number of false positives from 12 to 8. A second review of the false-positive cases' pCLE sequences (benign inflammatory) helped refine the existing classification by identifying four descriptive criteria specific to benign inflammatory conditions (Paris Classification): Vascular congestion, dark granular patterns with scales, increased inter-glandular space, and thickened reticular structure. CONCLUSIONS: The Paris Classification is a refinement of the existing Miami Classification to improve the accuracy of pCLE for diagnosing benign inflammatory strictures. Prospective multicenter studies are needed to further validate this refined classification criteria.

Síndrome de Alagille experiencia clínica de catorce casos en Medellín, Colombia / Alagille syndrome, clinical experience of fourteen cases in Medellin, Colombia

Introducción: El Síndrome de Alagille corresponde a una alteración autosómica dominante con expresión variable. Se caracteriza por colestasis crónica con escasez de los conductos biliares interlobulares asociada a alteraciones cardiovasculares, oftálmicas, sistema esquelético, riñones y facies característica. Su distribución es mundial con frecuencia de 1 por cada 100000 nacidos vivos. Objetivo: Describir las características clínicas, la evolución y la sobrevida de catorce pacientes, con diagnóstico de Síndrome de Alagille atendidos en un período de 16 años en Medellín, Colombia. Materiales y métodos: Es un trabajo observacional descriptivo de reporte de casos de los hallazgos morfológicos y la evolución de los pacientes con diagnóstico de Síndrome de Alagille. Resultados: Grupo compuesto por ocho niños y seis niñas, con edades entre los dos meses y los diez años al momento de diagnóstico. El síndrome completo se presentó en 28%. Los hallazgos más frecuentes, estenosis valvular de la arteria pulmonar y la alteración vertebral se presentaron en el 79%. Tres pacientes 21%, fallecieron, uno de ellos después de recibir trasplante hepático. De los once sobrevivientes dos niñas fueron sometidas a trasplante y se encuentran en buenas condiciones. Los nueve restantes padecen hepatopatía colestásica crónica y reciben tratamiento médico. Conclusión: El Síndrome de Alagille se debe tener en cuenta en el diagnóstico de colestasis crónica infantil. Para establecer la distribución y frecuencia de esta enfermedad en nuestro país es necesario desarrollar investigaciones que idealmente incluyan el estudio de la mutación genética en los pacientes y su familia cercana.

Introduction: The Alagille Syndrome is an autosomic dominant disorder with variable expression. Chronic cholestasis, characteristic facial appearance and abnormalities heart, skeleton, eye, kydnes with hypoplasia of the biliary ducts. Initial description in France, with mundial distribution her frecuence is 1/100000. Objective: To describe the clinical characteristic and evolutions of fourteen patients with diagnosis Alagille Syndrome in Medellín Colombia. Materials and methods: Descriptive retrospective study with variables obtained from clinical records of patients with diagnosis Alagille Syndrome. Results: Eight boys and six girls. The age at diagnosis varied two months at nine years. Complete syndrome was present in 28%. The most frecuent alterations were valvular stenosis pulmonary artery and failure of anterior vertebral arch fusion (butterfly vertebrae) 79%. The clinical evolution was variable, death occurred in three patients 21%, one girl post liver transplantation. Nine children had chronic hepatopathy controlled with medical treatment and two girls had liver transplantation with satisfactory evolution. Conclusions: In Colombia, the poblational incidence is not defined it is necessary to know the distribution of syndrome at future study.

[10 years of cholelithiasis classification (Central Scientific Research Institute of Gastroenterology): highlights of scientific and practical applications].

Clinical classification of cholelithiasisis presented, which includes 4 stages: stage without calculi, stage of formed gallstones, chronic calculous cholecystitis and complications. Sonographic description of main versions of biliary sludge, its causes and therapy efficacy are also given.

[Current management of benign and malignant bile duct strictures]. / Manejo de las estenosis benignas y malignas de las vías biliares.

Benign and malignant bile duct strictures require multidisciplinary management. The radiologist, endoscopist and surgeon must assess the general conditions of the patient, as well as the etiology of the stenosis and the therapeutic options (palliative, temporal, or definitive). Stenotic injuries that maintain bilioenteric continuity are susceptible to radiologic and/or endoscopic treatment, specially benign lesions, usually appearing in the postsurgical period. Injuries with loss of continuity require surgical management in almost every case. Iatrogenic bile duct injuries with preserved continuity (Strasberg A and D) may be treated by endoscopy. Types B and C, in which a liver segment loses communication with the remaining bile tree, need surgical repair and/or resection. Complete sections of the bile ducts require surgical intervention, with hepatojejunostomy being the best choice. The use of metallic endoluminal stents is almost prohibited in these types of injuries. Benign, non-iatrogenic injuries (sclerosing cholangitis, autoimmune cholangiopathy) require surgical intervention in rare occasions. Malignant injuries are extremely aggressive and only a small percentage (less than 15%) is candidate for curative resection, which unfortunately does not preclude recurrence.

Portal cholangiopathy: radiological classification and natural history.

BACKGROUND/AIM: Portal cholangiopathy (PC) is identified in over 80% of patients with portal vein thrombosis (PVT), but the true impact of this condition is not well known. This study investigated the relationship between cholangiographic abnormalities and clinical symptoms and their evolution over time. PATIENTS/METHODS: 67 consecutive patients with non-tumoral non-cirrhotic PVT following a standardised diagnostic protocol were studied. Findings at magnetic resonance angiography and cholangiography (MRA/MRC) were classified as no PC, grade I PC (minimal irregularities), grade II PC (stenosis without dilation) and grade III PC (stenosis with dilation). These changes were related to the presence of symptoms. RESULTS: 22 patients were diagnosed with acute PVT and 45 presented with chronic PVT. Overall, 52 patients had PC (6 grade I, 12 grade II and 34 grade III). 14 patients developed symptoms, all of whom had grade III PC. 30% of patients with acute PVT developed grade III PC within 1 year. In those without grade III PC, follow-up MRC showed no progression of the biliary lesions to grade III. The 5-year probability of developing symptoms of PC after acute PVT was 19%. In 45 patients with chronic PVT, MRA/MRC showed grade III PC in 26. In those without grade III PC, no progression of PC was observed at further follow-up MRC. The prevalence of symptoms of PC in these patients was 22%. CONCLUSIONS: PC is a frequent complication that develops and stabilises early after PVT and becomes symptomatic in its more severe form (grade III). These data suggest that follow-up MRA/MRC is not mandatory and strategies to prevent the development of symptoms of PC should be tested in patients with grade III PC.

Application of a new histological staging and grading system for primary biliary cirrhosis to liver biopsy specimens: Interobserver agreement.

Recently the authors proposed a new staging and grading system for primary biliary cirrhosis (PBC) that takes into account necroinflammatory activity and histological heterogeneity. Herein is proposed a convenient version of this system. Scores for fibrosis, bile duct loss, and chronic cholestasis were combined for staging: stage 1, total score of 0; stage 2, score 1-3; stage 3, score 4-6; and stage 4, score 7-9. Cholangitis activity (CA) and hepatitis activity (HA) were graded as CA0-3, and HA0-3, respectively. Analysis of interobserver agreement was then conducted. Digital images of 62 needle liver biopsy specimens of PBC were recorded as virtual slides on DVDs that were sent to 28 pathologists, including five located overseas. All participants were able to apply this version in all 62 cases. For staging, kappa was 0.385 (fair agreement) and the concordance rate was 63.9%. For necroinflammatory activity, the kappa and concordance rate were 0.110 (slight agreement) and 36.9% for CA, and 0.197 (slight agreement) and 47% for HA, respectively. In conclusion, this new staging and grading system for PBC seems to be more convenient and practical than those used at present, but more instruction and guidance are recommended for the grading of necroinflammatory activity in practice.

Differential diagnosis of neonatal cholestasis: clinical and laboratory parameters.

OBJECTIVE: To evaluate if clinical and laboratory parameters could assist in the differential diagnosis of intra and extra-hepatic neonatal cholestasis (NC). METHODS: Retrospective study of NC patients admitted at the Pediatric Hepatology Outpatient Clinic of the teaching hospital of Universidade Estadual de Campinas (UNICAMP), Campinas, Brazil, between December 1980 and March 2005. The approach to the diagnosis of NC was standardized. According to diagnosis, patients were classified into two groups: I (intra-hepatic neonatal cholestasis) and II (extra-hepatic neonatal cholestasis). In order to verify if there was association with the categorical variable, the chi-square and Mann-Whitney tests were used, with corrections for age for the covariance analysis (ANCOVA). The determination of accuracy of the clinical and laboratory variables for differentiation of the groups was made using the analysis of the ROC curve. RESULTS: One hundred and sixty-eight patients were evaluated (group I = 54.8% and group II = 45.2%). In the patients with less than 60 days of life there was predominance of intra-hepatic causes, whereas, in those older than 60 days, there was predominance of extra-hepatic etiology (p < 0.001). Median birth weight was lower in group I (p = 0.003), as well as length at birth (p = 0.007). Median values of direct bilirubin were higher in group II (p = 0.006). Values of gamma-glutamyltransferase (GGT) (10 times higher than the limit of normality) presented sensitivity of 56.3%, specificity of 91.5%, and accuracy of 75.7% for the diagnosis of extra-hepatic cholestasis. CONCLUSION: In the present study, extra-hepatic NC presented greater weight and length at birth, fecal hypocholia/acholia, choluria, hepatomegaly, increase in GGT (10.8 times higher than the limit of normality), and a delay for investigation in the tertiary center.

Diagnóstico diferencial de colestase neonatal: parâmetros clínicos e laboratoriais / Differential diagnosis of neonatal cholestasis: clinical and laboratory parameters

Objetivo: Avaliar se os parâmetros clínicos e laboratoriais poderiam auxiliar no diagnóstico diferencial da colestase neonatal (CN) intra- e extra-hepática. Métodos: Estudo retrospectivo de pacientes com CN hospitalizados na Clínica de Hepatologia Pediátrica do Hospital de Clínicas da Universidade Estadual de Campinas (UNICAMP), Campinas (SP), entre dezembro de 1980 e março de 2005. A abordagem para o diagnóstico da CN foi padronizada. De acordo com o diagnóstico, os pacientes foram classificados em dois grupos: I (colestase neo natal intra-hepática) e II (colestase neonatal extrahepática). Para verificar se havia associação com a variável categórica, os testes de qui-quadrado e Mann-Whitney foram utilizados com correções para idade para a análise de covariância (ANCOVA). A determinação da precisão das variáveis clínicas e laboratoriais para a diferenciação dos grupos foi realizada através da análise da curva ROC. Resultados: Cento e sessenta e oito pacientes foram avaliados (grupo I = 54,8 por cento e grupo II = 45,2 por cento). Nos pacientes com menos de 60 dias de vida, houve predominância de causas intra-hepáticas, enquanto que naqueles com mais de 60 dias, houve predominância de etiologia extrahepática (p < 0,001). A mediana de peso ao nascer foi mais baixa no grupo I (p = 0,003), assim como o comprimento ao nascer (p = 0,007). Os valores da mediana de bilirrubina direta foram mais altos no grupo II (p = 0,006). Os valores de gama glutamil transferase (GGT) (10 vezes mais altos do que o limite de normalidade) apresentaram sensibilidade de 56,3 por cento, especificidade de 91,5 por cento e acurácia de 75,7 por cento para o diagnóstico de colestase extra-hepática. Conclusão: No presente estudo, a CN extra-hepática apresentou maior peso e comprimento ao nascer, hipocolia/acolia fecal, colúria, hepatomegalia, aumento de GGT (10,8 vezes mais alto do que o limite de normalidade) e um atraso no encaminhamento para a investigação no hospital terciário.

Objective: To evaluate if clinical and laboratory parameters could assist in the differential diagnosis of intra and extra-hepatic neonatal cholestasis (NC). Methods: Retrospective study of NC patients admitted at the Pediatric Hepatology Outpatient Clinic of the teaching hospital of Universidade Estadual de Campinas (UNICAMP), Campinas, Brazil, between December 1980 and March 2005. The approach to the diagnosis of NC was standardized. According to diagnosis, patients were classified into two groups: I (intra-hepatic neonatal cholestasis) and II (extra-hepatic neonatal cholestasis). In order to verify if there was association with the categorical variable, the chi-square and Mann-Whitney tests were used, with corrections for age for the covariance analysis (ANCOVA). The determination of accuracy of the clinical and laboratory variables for differentiation of the groups was made using the analysis of the ROC curve. Results: One hundred and sixty-eight patients were evaluated (group I = 54.8 percent and group II = 45.2 percent). In the patients with less than 60 days of life there was predominance of intra-hepatic causes, whereas, in those older than 60 days, there was predominance of extra-hepatic etiology (p < 0.001). Median birth weight was lower in group I (p = 0.003), as well as length at birth (p = 0.007). Median values of direct bilirubin were higher in group II (p = 0.006). Values of gamma-glutamyltransferase (GGT) (10 times higher than the limit of normality) presented sensitivity of 56.3 percent, specificity of 91.5 percent, and accuracy of 75.7 percent for the diagnosis of extra-hepatic cholestasis. Conclusion: In the present study, extra-hepatic NC presented greater weight and length at birth, fecal hypocholia/acholia, choluria, hepatomegaly, increase in GGT (10.8 times higher than the limit of normality), and a delay for investigation in the tertiary center.

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.

Usefulness of a scoring system in the interpretation of histology in neonatal cholestasis.

AIM: To ascertain the usefulness of a histological scoring system devised to assist in the interpretation of liver histology in neonatal cholestasis (NC). METHODS: Liver biopsy specimens obtained from infants with NC referred to a tertiary pediatric unit in Malaysia were prospectively studied. The first author, blinded to the final diagnosis, devised the histological diagnosis based on a 7-feature (portal ductal proliferation, bile plugs in portal ductules, porto-portal bridging, lymphocytic infiltration in portal region, multinucleated hepatocytes, neutrophilic infiltration, hepatocellular swelling), 15-point (0 to 15) scoring system. The author classified the histological diagnosis as either biliary atresia (BA) or neonatal hepatitis (NH, all other diagnoses), and subsequently compared the author's diagnosis with the final diagnosis. RESULTS: Eighty-four biopsy specimens obtained from 78 patients were reviewed. Without the scoring system, BA was correctly diagnosed by the author histologically in 30 cases, labelled as NH in 3. For other diagnoses, BA was excluded correctly in 33 cases and mislabeled as BA in 2 cases. The overall sensitivity for BA was 91%, specificity 86% and accuracy 88%. With the scoring system, a score of >or=7 had the best diagnostic utility to differentiate BA from other intrahepatic cholestasis histologically (sensitivity 88%, specificity 94%, accuracy 92%). Four patients with a score<7 had BA, and 3 patients with a score>or=7 had NH. CONCLUSION: A 7-feature, 15-point histological scoring system had good diagnostic accuracy in the interpretation of liver histology in neonatal cholestasis.

[Genetic cholestasis]. / Colestasis genéticas.

During the last 11 years, advances in molecular genetics have changed our approach to children with intrahepatic cholestasis. Progress in identification of mutated genes now allows genetic diagnosis for several forms of cholestasis previously grouped into PFIC (progressive familial intrahepatic cholestasis). Three distinct forms: PFIC1, PFIC2, and PFIC3 are the result of mutations in the ATP8B1, ABCB11, and ABCB4 genes. The diagnosis is supported on clinical, biochemical and histological features. The therapeutic goals in theses diseases are alleviate symptoms and improve quality of life. Inborn errors of bile acid synthesis represent a subset of familial intrahepatic cholestasis. Replacement therapy with ursodeoxycholic acid and cholic acid avoids progression of the liver injury.