RESUMEN
AIM: Liver fibrosis results in a disproportion of the hepatic composition and architecture, characterized by a progressive accumulation of fibrillar proteins at the liver parenchyma. Modulated-differential scanning calorimetry (mDSC) is an experimental methodology able to determine the specific thermal signature from any biological substance, based on the variation in heat flow and heat capacity. As these physicochemical properties are directly influenced by compositional and structural changes, we decided to study the thermal behavior of the liver during fibrosis using mDSC. METHODS: Liver fibrosis was induced in rats by bile duct ligation or carbon tetrachloride administration. Degree of liver fibrosis was determined by histological examination using the Masson-trichrome stain, accompanied by hepatic expression of α-smooth muscle actin. The thermal analysis was performed in a modulated-differential scanning calorimeter using 20 mg of fresh liver mass. RESULTS: The liver showed a characteristic thermal signature in control animals, which progressively differed among mild (F1), moderate (F2) and advanced (F3-F4) liver fibrosis. For heat flow, the hepatic thermal signature from F3-F4 rats exhibited significant differences when compared with F1, F2 and controls. In terms of heat capacity, liver specimens provided a specific thermal signature for each stage of disease, characterized by a transition temperature onset at 95°C for controls, whereas in F1, F2 and F3-F4 animals this temperature significantly decreased to 93°C, 84°C and 75°C, respectively. CONCLUSION: Because the liver shows a differential thermal signature according to the degree of fibrosis, mDSC could be a novel tool in the study of liver fibrosis progression.
RESUMEN
A case of a 21-year-old single woman with an acute abdomen, vaginal bleeding and an anemic syndrome is presented. Physical examination and ultrasonography showed an enlarged uterus and a little mass in the right ovary, which was thought to be a fibroma versus pregnancy. Serum levels of chorionic gonadotropin were increased. Abundant black blood loose was found in the peritoneal cavity in the surgery performed. Through a wedge resection, a small hemorrhagic nodule was removed from the surface of the right ovary. Microscopic examination showed ovarian stroma, immature chorionic villi and intermediate extravillous trophoblast, which supported the diagnosis of ectopic ovarian pregnancy. This complication requires an opportune diagnosis, because it continues to be one of the leading risk factors in surgical gynecological emergencies and the first cause of maternal death during the first trimester of pregnancy. A brief review on the subject is presented.
Asunto(s)
Embarazo Ectópico/diagnóstico , Femenino , Humanos , Embarazo , Adulto JovenRESUMEN
OBJECTIVE: The aim was to evaluate the concordance in the diagnosis of precursor lesions of intestinal-type gastric carcinoma among observers with different levels of experience. MATERIAL AND METHODS: Gastric biopsies from 1 056 cases were studied: 341 from Colombia, 382 from Mexico, and 333 from Paraguay. Pathologists without experience (A) and with experience (B) in gastrointestinal pathology, as well as experts working in an international reference center (C) participated in the diagnosis of each case. RESULTS: The concordance (k) between pathologists with experience and those without was poor for the diagnosis of atrophic gastritis (k=0.04 to 0.12) and dysplasia (k=0.11 to 0.05), and good for the diagnosis of intestinal metaplasia (k=0.52 to 0.58). Supervision of pathologists without experience by those with experience remarkably improved the concordance in the diagnosis of atrophic gastritis (k=0.65) and intestinal metaplasia (k=0.91), and to a lesser degree, of dysplasia (k=0.28). The concordance among experts before and after the consensus meeting showed no variation in the diagnosis of atrophic gastritis (k=0.57); the concordance varied from good to excellent in the diagnosis of intestinal metaplasia (k=0.67 to 0.81) and from poor to good in that of dysplasia (k=0.18 to 0.66). CONCLUSION: The greatest differences arose in the diagnosis of chronic atrophic gastritis and dysplasia. The interobserver concordance depended on the experience of the observer and the consensus reading.
Asunto(s)
Carcinoma/prevención & control , Gastritis Atrófica/diagnóstico , Lesiones Precancerosas/diagnóstico , Neoplasias Gástricas/prevención & control , Estómago/patología , Adulto , Biopsia , Carcinoma/epidemiología , Competencia Clínica , Colombia/epidemiología , Consenso , Gastritis Atrófica/patología , Gastroscopía , Humanos , Hiperplasia , Intestinos/patología , Metaplasia , México/epidemiología , Variaciones Dependientes del Observador , Paraguay/epidemiología , Patología Clínica , Lesiones Precancerosas/patología , Reproducibilidad de los Resultados , Neoplasias Gástricas/epidemiologíaRESUMEN
OBJECTIVE: The course of Helicobacter pylori infection and antibody response to CagA in patients with preneoplastic lesions and gastric cancer has not been thoroughly studied. We aimed to study H. pylori infection and antibody response to CagA in patients with non-atrophic gastritis, preneoplastic lesions, and gastric cancer. METHODS: We studied patients attending one Oncology Hospital and one General Hospital in Mexico City. Diagnosis was based on endoscopy and histopathology in biopsies from six stomach regions. H. pylori infection was assessed by histology and serology, and antibodies against CagA were measured with immunoassay. RESULTS: We included 618 patients, 368 with non-atrophic gastritis, 126 with precancerous lesions, and 65 with gastric cancer; in addition, 59 patients with duodenal ulcer were studied. Detection of infection and IgG against CagA had a significant increase from non-atrophic gastritis to mild and up to advanced stages of metaplasia (P < 0.05), followed by decreased infection and IgG to CagA in patients with gastric cancer (P < 0.05). However, infection and CagA antibodies were associated with young gastric cancer cases. Duodenal ulcer showed a significant association with infection detected by histology and serology, particularly among women, and a trend to associate with IgG to CagA. CONCLUSIONS: This study shows that H. pylori infection and CagA are risk markers for intestinal metaplasia. The prevalence of these risk markers decreases in gastric cancer, probably reflecting that infection decreases after advanced atrophy and metaplasia in the gastric mucosa. State of the disease, age, and sex influence the association of H. pylori infection and IgG response to CagA with gastroduodenal diseases.
Asunto(s)
Antígenos Bacterianos/sangre , Proteínas Bacterianas/sangre , Gastritis/sangre , Infecciones por Helicobacter/sangre , Helicobacter pylori , Lesiones Precancerosas/sangre , Neoplasias Gástricas/sangre , Adulto , Factores de Edad , Anciano , Biomarcadores/sangre , Distribución de Chi-Cuadrado , Ensayo de Inmunoadsorción Enzimática , Femenino , Gastritis/inmunología , Gastritis/microbiología , Gastritis/patología , Infecciones por Helicobacter/complicaciones , Infecciones por Helicobacter/inmunología , Infecciones por Helicobacter/patología , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Lesiones Precancerosas/inmunología , Lesiones Precancerosas/microbiología , Lesiones Precancerosas/patología , Índice de Severidad de la Enfermedad , Neoplasias Gástricas/inmunología , Neoplasias Gástricas/microbiología , Neoplasias Gástricas/patología , Encuestas y CuestionariosRESUMEN
BACKGROUND: Celecoxib, a cyclooxygenase-2 (COX-2) inhibitor, may reduce the risk and mortality of certain types of human cancer. The chemopreventive effect of celecoxib on preneoplastic lesions induced by chemical hepatocarcinogenesis was investigated. MATERIALS AND METHODS: Male Sprague Dawley rats were fed a celecoxib-supplemented diet between days 18 and 26 post-initiation (1500 ppm) and sacrificed on day 26. The effects of celecoxib on proliferation, apoptosis, COX-2 activity and liver function were evaluated by immunohistochemistry, TUNEL assay, enzyme-immunoassay and spectrophotometry, respectively. RESULTS: Celecoxib decreased, in area and number, gamma-glutamyltranspeptidase and glutathione S-transferase placental-positive lesions, below levels found after 18 days, by 55.2% and 62.2%, and by 50.5% and 71.1%, respectively, (p < 0.05). Celecoxib neither induced apoptosis nor altered the levels of prostaglandin E2, bilirubin or alanine aminotransferase in the plasma; however, proliferating cell nuclear antigen and cyclin D1 decreased by 77.7% and 94.9%, respectively, (p < 0.05). CONCLUSION: Celecoxib regresses existing preneoplastic liver lesions through antiproliferative processes, without altering liver function.
Asunto(s)
Neoplasias Hepáticas Experimentales/prevención & control , Lesiones Precancerosas/tratamiento farmacológico , Pirazoles/farmacología , Sulfonamidas/farmacología , Animales , Celecoxib , Procesos de Crecimiento Celular/efectos de los fármacos , Ciclooxigenasa 2/metabolismo , Inhibidores de la Ciclooxigenasa 2/farmacología , Dinoprostona/sangre , Hígado/anatomía & histología , Hígado/efectos de los fármacos , Neoplasias Hepáticas Experimentales/sangre , Neoplasias Hepáticas Experimentales/enzimología , Masculino , Tamaño de los Órganos/efectos de los fármacos , Lesiones Precancerosas/sangre , Lesiones Precancerosas/enzimología , Ratas , Ratas Sprague-DawleyRESUMEN
At the present time liver biopsy is the most reliable method to determine the grade of necroinflammatory lesion and the amount of fibrosis in chronic hepatitis C. Therefore the liver biopsy should always be performed before initiating therapy. It is suggested to use the METAVIR histological activity to grade chronic hepatitis because it is simple, the reproducibility has been validated, the criteria used to define different lesions has been clearly stated, and there is a significant association between ALT levels and this index. The use of semi-quantitative systems in routine reports of liver biopsies is unnecessary. In these cases the schematic diagrams from Batts and Ludwig can be used, as visual analogue scales, in order to grade and stage chronic hepatitis.
Asunto(s)
Hepatitis C Crónica/patología , Hígado/patología , Biopsia , HumanosRESUMEN
The clinicopathologic conference (CPC) was introduced by Dr. Richard C. Cabot at the Massachusetts General Hospital in the U.S. early in the past century. In a short time, it became one of the most popular medical teaching tools in the world. Despite certain differences between beside diagnosis and CPC diagnosis, the latter is a valuable teaching exercise. During the past few decades, interest in CPCs has declined due to several issues: excessive concern with anatomic diagnosis at the expense of molecular pathogenesis and pathophysiology; emphasis on uncommon diseases; the pathologist being considered an adversary who enjoys demonstrating clinical discussion errors; autopsies failing to reveal abnormalities in physiopathologic disorders and it is not rare to fail to reveal cause of death, and the fact that very few cases are true diagnostic problems, due to advances in diagnostic techniques. In addition, with the decline of interest in autopsies during the past years, in several CPCs, many final diagnosis is performed by biopsy, laboratory tests, or imaging studies. The ideal CPC case to conserve the educational role of this exercise is an autopsy case with adequated clinical, laboratory and/or imaging studies.
Asunto(s)
Educación Médica Continua/métodos , Registros Médicos/normas , Humanos , Patología ClínicaRESUMEN
Objective. To examine the frequency and patterns of association of cardiovascular risk factors with atherosclerosis in five different arterial territories at post-mortem in Mexico City. Methods. We obtained five arterial territories arteries (circle of Willis, coronary, carotid, renal, and aorta) of 185 men and women 0 to 90 years of age who underwent autopsy at the Medical Forensic Service of Mexico City. We determined the prevalence and extent of atherosclerotic lesions by histopathology according to the classification of the American Heart Association as early (types I-III) and advanced (types IV-VI), and according to the degree of stenosis and correlated with cardiovascular risk factors. Results. Atherosclerotic lesions were identified in at least one arterial territory in 181 subjects (97.8%), with involvement of two ore more territories in 178 subjects (92.2%). Advanced lesions were observed in 36% and 67% of subjects under 15 and between 16 and 35 years, respectively. Any degree of atherosclerosis was associated with the presence of diabetes mellitus, hypertension, overweight, obesity, and smoking, and to a greater extent with the presence of two or more risk factors (P < 0.001). However, emerging and advanced athersoclerosis was observed in 53% and 20% people with no risk factors. Conclusions. The study shows a high prevalence of atherosclerosis in all age groups and both sexes. There is considerable development of atherosclerotic disease in subjects without known risk factors.
Asunto(s)
Carcinoma Hepatocelular/patología , Colangiocarcinoma/patología , Neoplasias Hepáticas/patología , Anciano de 80 o más Años , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/metabolismo , Colangiocarcinoma/diagnóstico , Colangiocarcinoma/metabolismo , Colágeno/metabolismo , Femenino , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/metabolismoRESUMEN
BACKGROUND: There is uneven association between obesity, traditional risk factors, and cardiovascular events. We aimed to analyze the relation between cardiovascular risk factors, including obesity, with the severity of atherosclerosis in different arterial territories. METHODS: Arteries from five territories (circle of Willis, carotids, coronaries, aorta, and renal) were taken from 185 persons, newborn to 90 years undergoing autopsy in the Forensic Medical Service in Mexico City, to determine atherosclerotic lesions by histopathological study. Lesions were classified according to the American Heart Association grading system as early (types I-III) and advanced (types IV-VI). The degree of atherosclerosis was correlated with arterial territories and risk factors. RESULTS: Frequencies of advanced lesions according to arterial territories were as follows: circle of Willis, 28%; right carotid, 36%; left carotid, 25%; right coronary, 71%; left coronary, 85%; right renal, 26%; left renal, 29%; and aorta, 52%; P=.0001, for all analyses. There was a higher risk for advanced lesions with increasing body mass index (BMI) (P=.004). However, after adjusting for age, gender, smoking status, hypertension, and diabetes mellitus, BMI was not independently associated with advanced lesions. CONCLUSIONS: Coronary arteries are significantly more affected than other arterial territories regardless of risk factors, showing the effect of local and systemic factors in the severity of atherosclerosis. We did not find an independent association between advanced atherosclerotic lesions and obesity.
Asunto(s)
Aterosclerosis/epidemiología , Aterosclerosis/patología , Obesidad/complicaciones , Obesidad/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Aorta/patología , Aterosclerosis/complicaciones , Índice de Masa Corporal , Arterias Carótidas/patología , Niño , Preescolar , Círculo Arterial Cerebral/patología , Vasos Coronarios/patología , Femenino , Humanos , Lactante , Recién Nacido , Masculino , México/epidemiología , Persona de Mediana Edad , Prevalencia , Arteria Renal/patología , Factores de Riesgo , Adulto JovenRESUMEN
A novel application of diffuse reflectance and fluorescence spectroscopy in the assessment of liver fibrosis is here reported. To induce different stages of liver fibrosis, a sufficient number of male Wistar rats were differentially exposed to chronic administration with carbon tetrachloride. Then, diffuse reflectance and fluorescence spectra were in vivo measured from the liver surface of each animal by a minimal invasive laparoscopic procedure. The liver fibrosis degree was conventionally determined by means of histological examination using the Mason's Trichrome stain, accompanied by hepatic expression of α-sma, and evaluation of the ALT/AST serum levels. The liver from rats exhibiting higher grades of fibrosis showed a significant increase in diffuse reflectance and fluorescence intensity when compared with control animals. At 365 nm, the diffuse reflectance spectrum exhibited an increase of 4 and 3-fold in mild and advanced fibrotic rats, respectively, when compared to the control group. Similarly, the fluorescence emission at 493 nm was 2-fold higher in fibrotic animals than in controls. By using fluorescence intensity, discrimination algorithms indicated 73% sensitivity and 94% specificity for recognition of hepatic fibrosis, while for diffuse reflectance, these values increased up to 85% and 100%, respectively. Taking into consideration there is a special need for developing new diagnostic approaches focused on detecting different stages of liver fibrosis with minimal invasiveness, these results suggest that diffuse reflectance and fluorescence spectroscopy could be worthy of further exploration in patients with liver disease.
Asunto(s)
Cirrosis Hepática/patología , Hígado/patología , Espectrometría de Fluorescencia/métodos , Actinas/biosíntesis , Animales , Tetracloruro de Carbono/toxicidad , Laparoscopía/métodos , Cirrosis Hepática/inducido químicamente , Pruebas de Función Hepática , Masculino , Ratas , Ratas WistarRESUMEN
Cirrhosis is the final outcome of liver fibrosis. Kupffer cell-mediated hepatic inflammation is considered to aggravate liver injury and fibrosis. Alternatively-activated macrophages are able to control chronic inflammatory events and trigger wound healing processes. Nevertheless, the role of alternative Kupffer cell activation in liver harm is largely unclear. Thus, we evaluated the participation of alternatively-activated Kupffer cells during liver inflammation and fibrosis in the murine model of carbon tetrachloride-induced hepatic damage. To stimulate alternative activation in Kupffer cells, 20 Taenia crassiceps (Tc) larvae were inoculated into BALBc/AnN female mice. Six weeks post-inoculation, carbon tetrachloride or olive oil were orally administered to Tc-inoculated and non-inoculated mice twice per week during other six weeks. The initial exposure of animals to T. crassiceps resulted in high serum concentrations of IL-4 accompanied by a significant increase in the hepatic mRNA levels of Ym-1, with no alteration in iNOS expression. In response to carbon tetrachloride, recruitment of inflammatory cell populations into the hepatic parenchyma was 5-fold higher in non-inoculated animals than Tc-inoculated mice. In contrast, carbon tetrachloride-induced liver fibrosis was significantly less in non-inoculated animals than in the Tc-inoculated group. The latter showed elevated IL-4 serum levels and low IFN-γ concentrations during the whole experiment, associated with hepatic expression of IL-4, TGF-ß, desmin and α-sma, as well as increased mRNA levels of Arg-1, Ym-1, FIZZ-1 and MMR in Kupffer cells. These results suggest that alternative Kupffer cell activation is favored in a Th2 microenvironment, whereby such liver resident macrophages could exhibit a dichotomic role during chronic hepatic damage, being involved in attenuation of the inflammatory response but at the same time exacerbation of liver fibrosis.
Asunto(s)
Fibrosis/inmunología , Macrófagos del Hígado/inmunología , Cirrosis Hepática/inmunología , Células Th2/inmunología , Actinas/genética , Animales , Ensayo de Inmunoadsorción Enzimática , Femenino , Péptidos y Proteínas de Señalización Intercelular/genética , Interferón gamma/metabolismo , Interleucina-10/genética , Interleucina-13/genética , Interleucina-4/metabolismo , Ratones , Óxido Nítrico Sintasa de Tipo II/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factor de Crecimiento Transformador beta/genética , Factor de Crecimiento Transformador beta1/genética , Factor de Necrosis Tumoral alfa/genéticaAsunto(s)
Carcinoma Hepatocelular/epidemiología , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/patología , Carcinoma Hepatocelular/etiología , Femenino , Humanos , Cirrosis Hepática/complicaciones , Cirrosis Hepática/patología , Neoplasias Hepáticas/etiología , Masculino , México , Factores de Riesgo , Distribución por SexoAsunto(s)
Granuloma de Células Plasmáticas/patología , Hepatopatías/patología , Niño , Humanos , MasculinoRESUMEN
Objetivo. Evaluar la concordancia en el diagnóstico de lesiones precursoras del carcinoma gástrico de tipo intestinal entre observadores con diferente experiencia. Material y métodos. Se estudiaron 1 056 casos de biopsias gástricas: 341 de Colombia, 382 de México y 333 de Paraguay. En el diagnóstico de cada caso participaron patólogos sin experiencia en patología gastrointestinal (A), patólogos con experiencia en patología gastrointestinal (B) y expertos que trabajan en un centro de referencia internacional (C). Resultados. La concordancia (k) entre patólogos inexpertos y expertos fue pobre en el diagnóstico de gastritis atrófica (k=0.04 a 0.12) y displasia (k=0.11 a 0.05) y buena en el diagnóstico de metaplasia intestinal (k=0.52 a 0.58); la supervisión de un patólogo inexperto por un experto mejoró notablemente la concordancia en el diagnóstico de gastritis atrófica (k=0.65) y metaplasia intestinal (k=0.91) y, en un menor grado, de displasia (k=0.28). Al comparar la concordancia entre expertos antes y después de la reunión de consenso no hubo variación en el diagnóstico de gastritis atrófica (k=0.57); la concordancia varió de buena a excelente en el de metaplasia intestinal (k=0.67 a 0.81) y de pobre a buena en el de displasia (k=0.18 a 0.66). Conclusión. Los principales problemas se presentan en el diagnóstico de la gastritis crónica atrófica y la displasia. La concordancia interobservador depende de la experiencia del observador y la lectura de consenso.
Objective. The aim was to evaluate the concordance in the diagnosis of precursor lesions of intestinal-type gastric carcinoma among observers with different levels of experience. Material and Methods. Gastric biopsies from 1 056 cases were studied: 341 from Colombia, 382 from Mexico, and 333 from Paraguay. Pathologists without experience (A) and with experience (B) in gastrointestinal pathology, as well as experts working in an international reference center (C) participated in the diagnosis of each case. Results. The concordance (k) between pathologists with experience and those without was poor for the diagnosis of atrophic gastritis (k=0.04 to 0.12) and dysplasia (k=0.11 to 0.05), and good for the diagnosis of intestinal metaplasia (k=0.52 to 0.58). Supervision of pathologists without experience by those with experience remarkably improved the concordance in the diagnosis of atrophic gastritis (k=0.65) and intestinal metaplasia (k=0.91), and to a lesser degree, of dysplasia (k=0.28). The concordance among experts before and after the consensus meeting showed no variation in the diagnosis of atrophic gastritis (k=0.57); the concordance varied from good to excellent in the diagnosis of intestinal metaplasia (k=0.67 to 0.81) and from poor to good in that of dysplasia (k=0.18 to 0.66). Conclusion. The greatest differences arose in the diagnosis of chronic atrophic gastritis and dysplasia. The interobserver concordance depended on the experience of the observer and the consensus reading.
Asunto(s)
Adulto , Humanos , Carcinoma/prevención & control , Gastritis Atrófica/diagnóstico , Lesiones Precancerosas/diagnóstico , Neoplasias Gástricas/prevención & control , Estómago/patología , Biopsia , Carcinoma/epidemiología , Competencia Clínica , Colombia/epidemiología , Consenso , Gastritis Atrófica/patología , Gastroscopía , Hiperplasia , Intestinos/patología , Metaplasia , México/epidemiología , Variaciones Dependientes del Observador , Paraguay/epidemiología , Patología Clínica , Lesiones Precancerosas/patología , Reproducibilidad de los Resultados , Neoplasias Gástricas/epidemiologíaRESUMEN
To study the role of neutrophils in the innate resistance to Entamoeba histolytica intestinal infection in mice, animals were treated with anti-neutrophil monoclonal antibodies prior to intracecal parasite inoculation and the resulting lesions were compared with normal mice that had been equally infected. In contrast to our previous finding that neutrophils are critical in eliminating E. histolytica infection in the liver, we show here that neutrophils are not absolutely required to eliminate E. histolytica infection from the intestine. Although the neutrophils are not critical for resolution of the E. histolytica infection, neutrophils do appear to provide some measure of protection as the intestinal amoeba burden was higher at early timepoints after infection in the neutropenic animals. In addition, we found that while both the normal and the neutrophil-depleted mice developed ulcerative lesions in the colon, the neutropenic mice had an increased frequency of granulomas that formed around the amoeba. Thus, our findings appear to be the first evidence showing that granulomatous inflammation can occur after intestinal infection in mice using axenically cultured amoeba.
Asunto(s)
Disentería Amebiana/inmunología , Entamoeba histolytica/inmunología , Granuloma/inmunología , Intestinos/patología , Neutrófilos/inmunología , Animales , Anticuerpos Monoclonales/inmunología , Ciego/parasitología , Disentería Amebiana/patología , Entamoeba histolytica/fisiología , Femenino , Granuloma/parasitología , Granuloma/patología , Inmunoglobulina G/inmunología , Intestinos/inmunología , Intestinos/parasitología , Masculino , Ratones , Ratones Endogámicos BALB C , Neutropenia/inmunología , Neutropenia/parasitología , Neutropenia/patología , Úlcera/inmunología , Úlcera/parasitología , Úlcera/patologíaRESUMEN
La fibrosis hepática congénita es una enfermedad autosómica recesiva caracterizada histológicamente por la presencia de tejido fibroconectivo en los espacios porta con numerosos conductos biliares de mediano calibre. Éste es un estudio inmunofenotípico de la placa ductal y su participación en la génesis de la fibrosis hepática congénita . Se estudiaron cuatro casos postmortem con diagnóstico histopatológico de fibrosis hepática congénita y cortes histológicos de hígados de embriones de ocho, nueve y 10 semanas de gestación. Se obtuvieron cortes histológicos y se utilizaron reacciones de inmunohistoquímica (citoqueratina 7, 8, 18, 19 y laminina). Los hepatocitos primitivos que rodean las ramas de la vena porta, muestran reactividad para citoqueratinas 7, 8, 18, 19 y laminina. La falta de remodelación de la placa ductal resulta en persistencia de conductos biliares embrionarios; estas anormalidades de la placa ductal pueden ser responsables de enfermedades congénitas de los conductos biliares intrahepáticos donde se incluye la fibrosis hepática congénita. Los resultados obtenidos demuestran que las células que forman placas ductales son positivas para citoqueratinas 8, 18, 19 y laminina a partir de la semana ocho de gestación y persiste su positividad en conductos biliares en la fibrosis hepática congénita. Estos hallazgos apoyan la hipótesis del desarrollo de la fibrosis hepática congénita por persistencia de la placa ductal.