Optical analysis of computed tomography images of the liver predicts fibrosis stage and distribution in chronic hepatitis C.

UNLABELLED: This study was undertaken to evaluate an image processing method for assessing liver fibrosis in conventional computed tomography (CT) scans in patients with chronic hepatitis C. Two cohorts (designated "estimation," n = 34; and "validation," n = 107) of chronic hepatitis C patients were assessed using digitized conventional helical CT. Weighted CT mean fibrosis (Fibro-CT) was calculated as a nonlinear weighted mean F-score for each sample. Fibrosis was defined according to Scheuer on the F0 to F4 scale by 2 pathologists blinded regarding the Fibro-CT data. Fibrosis according to Fibro-CT correlated with histology-determined fibrosis (r = 0.69; P < 0.001) and with increasing F-stage: F0 = 0.23 +/- 0.39; F1 = 0.90 +/- 0.99; F2 = 1.41 +/- 0.94; F3 = 2.79 +/- 0.55; F4 = 3.15 +/- 0.35 [analysis of variance: P < 0.0001). The receiver operating characteristics curve to diagnose significant fibrosis (>/=F2) was 0.83; 95% confidence interval (95%CI), 0.75 to 0.91; and, to diagnose advanced fibrosis (>/=F3), was 0.86, 95%CI: 0.80 to 0.93. The correlation between Fibro-CT and fibrosis was higher in patients with homogeneous distribution of fibrosis than in patients with heterogeneous distribution (r = 0.77 versus r = 0.43; P < 0.05). CONCLUSION: Optical digital analysis of CT images of the liver is effective in determining the stage and distribution of liver fibrosis in chronic hepatitis C. In patients with homogeneous fibrosis distribution, the correlation between Fibro-CT and histology was better than in patients with heterogeneous distribution. Fibro-CT is a simple to use, readily available, and useful method for the diagnosis of fibrosis in patients with chronic hepatitis C.

[Comparative study of two models that use biochemical parameters for the non-invasive diagnosis of fibrosis in patients with hepatitis C]. / Estudio comparativo de dos modelos que utilizan parámetros bioquímicos en el diagnóstico no invasivo de la fibrosis hepática en pacientes con hepatitis C.

BACKGROUND AND OBJECTIVE: Several models for the prediction of liver fibrosis have been developed which consist of the measurement of routine laboratory data: a) a model combining platelets, gamma-glutamil-transpeptidase, cholesterol and age (Forns model), and b) a model using an aspartate-aminotransferase to platelet ratio index (APRI). Our study was aimed to compare both non-invasive methods to predict mild fibrosis (F0-F1) or to confirm advanced fibrosis (F3, F4) in patients with chronic hepatitis C. PATIENTS AND METHOD: We included 199 patients with chronic hepatitis. The average age (standard deviation) was 41 (11) years (16-66), and there were 117 men and 82 women. We found a genotype 1 in 108 patients (54.2%), 45 had a non-1 genotype (22.6%), and 46 (23.1%) had an unknown genotype. Mild fibrosis stage (F0-F1) was found in 96 patients, F2 in 52 and advanced fibrosis (F3-F4) in 51 patients. We calculated the APRI and the Forns's index. RESULTS: Patients infected with genotype 1 were older (44 [11] vs 36 [4.3] years; p = 0.001), presented higher levels of cholesterol (179 [40] vs 160 [42] mg/dl; p = 0.05) and lower levels of alanine-aminotransferase (112 [86] vs 169 [87] IU/l; p = 0.03). The Forns's model predicted mild fibrosis (F0-F1) in 71.4% while the APRI model did it in 72.7%. The Forns's model confirmed advanced fibrosis in 78.6% against 54.2% from the APRI one. The predictive capacity in both models increased when analyzing patients with the genotype 1. Moreover, the predictive capacity of advanced fibrosis or exclusion of significant fibrosis reached more than 90% when both models were used together in patients with a genotype 1. CONCLUSIONS: Non-invasive methods for the prediction of liver fibrosis can be very useful in clinical practice, mainly in patients with genotype 1 when the two methods are used together.

Tumour necrosis factor alpha polymorphisms are not involved in the development of steatosis in chronic hepatitis C.

AIM: To determine whether the different tumour necrosis factor alpha (TNF-alpha) promoter gene polymorphisms are involved in the development of steatosis in chronic hepatitis C. PATIENTS AND METHODS: One hundred and thirty patients (89 men and 41 women; mean age 42.5 +/- 12.3 years) with chronic hepatitis C were included. Insulin resistance was measured according to the Homeostasis model assessment (HOMA IR). Serum leptin levels were also obtained and the body mass index and fat mass were calculated. Liver biopsy was carried out in all the patients, and steatosis was measured as one of four stages (0 to 3): stage 0, no steatosis; stage 1, < 25% of hepatocytes with steatosis; stage 2, 25-50%; and stage 3, > 50%. DNA samples were obtained in order to describe the polymorphisms at the TNF-alpha promoter gene position. RESULTS: Fifty-nine of the 130 (45.38%) patients had different degrees of steatosis, while 71/130 (54.62%) were not steatosic. Six of the 59 (10.2%) patients with steatosis presented mutations at the -238 position of the TNF-alpha promoter region, while 5/71 (7.0%) patients without steatosis also showed mutations at this position (P=NS). Seventeen of the 59 (28.8%) steatosic patients showed a mutation at the -308 position, while 16/71 (22.5%) without steatosis also had this mutation (P=NS). Insulin resistance, beta cells reserve, insulin and leptin levels showed no differences between patients with or without mutations at the promoter region of the TNF-alpha gene. CONCLUSIONS: TNF-alpha mutations do not seem to play any role in the development of steatosis in chronic hepatitis C.

Pathological features and diagnosis of intraductal papillary mucinous neoplasm of the pancreas.

Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is a noninvasive epithelial neoplasm of mucin-producing cells arising in the main duct (MD) and/or branch ducts (BD) of the pancreas. Involved ducts are dilated and filled with neoplastic papillae and mucus in variable intensity. IPMN lacks ovarian-type stroma, unlike mucinous cystic neoplasm, and is defined as a grossly visible entity (≥ 5 mm), unlike pancreatic intraepithelial neoplasm. With the use of high-resolution imaging techniques, very small IPMNs are increasingly being identified. Most IPMNs are solitary and located in the pancreatic head, although 20%-40% are multifocal. Macroscopic classification in MD type, BD type and mixed or combined type reflects biological differences with important prognostic and preoperative clinical management implications. Based on cytoarchitectural atypia, IPMN is classified into low-grade, intermediate-grade and high-grade dysplasia. Based on histological features and mucin (MUC) immunophenotype, IPMNs are classified into gastric, intestinal, pancreatobiliary and oncocytic types. These different phenotypes can be observed together, with the IPMN classified according to the predominant type. Two pathways have been suggested: gastric phenotype corresponds to less aggressive uncommitted cells (MUC1 -, MUC2 -, MUC5AC +, MUC6 +) with the capacity to evolve to intestinal phenotype (intestinal pathway) (MUC1 -, MUC2 +, MUC5AC +, MUC6 - or weak +) or pancreatobiliary /oncocytic phenotypes (pyloropancreatic pathway) (MUC1 +, MUC 2-, MUC5AC +, MUC 6 +) becoming more aggressive. Prognosis of IPMN is excellent but critically worsens when invasive carcinoma arises (about 40% of IPMNs), except in some cases of minimal invasion. The clinical challenge is to establish which IPMNs should be removed because of their higher risk of developing invasive cancer. Once resected, they must be extensively sampled or, much better, submitted in its entirety for microscopic study to completely rule out associated invasive carcinoma.

Pathological aspects of so called "hilar cholangiocarcinoma".

Cholangiocarcinoma (CC) arising from the large intrahepatic bile ducts and extrahepatic hilar bile ducts share clinicopathological features and have been called hilar and perihilar CC as a group. However, "hilar and perihilar CC" are also used to refer exclusively to the intrahepatic hilar type CC or, more commonly, the extrahepatic hilar CC. Grossly, a major distinction can be made between papillary and non-papillary tumors. Histologically, most hilar CCs are well to moderately differentiated conventional type (biliary) carcinomas. Immunohistochemically, CK7, CK20, CEA and MUC1 are normally expressed, being MUC2 positive in less than 50% of cases. Two main premalignant lesions are known: biliary intraepithelial neoplasia (BilIN) and intraductal papillary neoplasm of the biliary tract (IPNB). IPNB includes the lesions previously named biliary papillomatosis and papillary carcinoma. A series of 29 resected hilar CC from our archives is reviewed. Most (82.8%) were conventional type adenocarcinomas, mostly well to moderately differentiated, although with a broad morphological spectrum; three cases exhibited a poorly differentiated cell component resembling signet ring cells. IPNB was observed in 5 (17.2%), four of them with an associated invasive carcinoma. A clear cell type carcinoma, an adenosquamous carcinoma and two gastric foveolar type carcinomas were observed.

Serum leptin levels correlate with hepatic steatosis in chronic hepatitis C.

OBJECTIVES: Hepatic steatosis (HS) has been related to obesity and fibrosis in chronic hepatitis C (CHC). The aim of this study was to determine the role of leptin system in HS development. METHODS: Patients (n = 131) with biopsy-proven CHC, positive HCV RNA, and raised ALT were enrolled. Body mass index, percentage of body fat by skin fold measurement, and bioelectrical impedance analysis was calculated and serum leptin concentration measured. Intrahepatic HCV RNA, HS, necroinflammatory activity, and fibrosis were determined in liver biopsy tissue. RESULTS: HS was present in 63 patients (48.1%). Steatosis was evident in 32 of 91 patients (35.2%) infected with genotype 1 and in 22 of 27 patients (81.5%) with genotype 3a (p < 0.001). In patients infected by genotype 3a, HS correlated significantly with intrahepatic HCV RNA load (r = 0.78; p < 0.001). However, in genotype 1, HS was associated with host factors such as leptin, body mass index, percentage of body fat, and visceral obesity. Multivariate analysis showed genotype (OR = 11.54, 95% CI = 1.13-117.14, p = 0.038), leptin levels (OR = 1.09, 95% CI = 1.03-1.17, p = 0.008) and fibrosis (OR = 9.86, 95% CI = 2.11-5.86, p = 0.03) as independent variables of HS development. CONCLUSIONS: Hepatic steatosis was related to genotype, fibrosis degree, and serum leptin levels. Genotype 3 seems to have a viral specific steatogenic effect. Leptin seems to be a link between obesity and steatosis development in CHC genotype 1-infected patients.

Estudio comparativo de dos modelos que utilizan parámetros bioquímicos en el diagnóstico no invasivo de la fibrosis hepática en pacientes con hepatitis C / Comparative study of two models that use biochemical parameters for the non-invasive diagnosis of fibrosis in patients with hepatitis C

FUNDAMENTO Y OBJETIVO: Recientemente se han desarrollado 2 modelos de cálculo de fibrosis utilizando parámetros bioquímicos analizados en la práctica habitual: a) las plaquetas, la gammaglutamiltranspeptidasa, el colesterol y la edad (índice Forns) y b) el cociente aspartato ahh aminotransferasa/plaquetas (APRI). El objetivo de nuestro estudio ha sido comparar la utilidad de ambos métodos no invasivos para detectar fibrosis leve (F0-F1) o fibrosis avanzada (F3-F4) en pacientes con hepatitis C crónica. PACIENTES Y MÉTODO: Incluimos a 199 pacientes (117 varones y 82 mujeres) con hepatitis crónica C, con una edad media (desviación estándar) de 41 (11) años (extremos, 16-66). Un totalde 108 pacientes (54,2%) eran de genotipo 1, 45 de genotipo no 1 (22,6%), y en 46 (23,1%)se desconocía el genotipo. La distribución de los pacientes según el estadio de fibrosis fue:leve (F0-F1) en 96 pacientes, F2 en 52 y avanzado (F3-F4) en 51. Calculamos el resultado delíndice APRI y del índice de Forns. RESULTADOS: Los pacientes infectados por el genotipo 1 eran mayores (media de 44 [11] frente a 36 [4,3] años; p = 0,001), presentaban valores más altos de colesterol (media de 179 [40]frente a 160 [42] mg/dl; p = 0,05) e inferiores de alaninaminotransferasa (media de 112 [86]frente a 169 [87] UI/l; p = 0,03). El modelo de Forns predijo fibrosis leve (F0-F1) en el 71,4%mientras que el modelo APRI lo consigue en un 72,7%. El modelo de Forns predice fibrosis avanzada en el 78,6% frente al 54,2% del modelo APRI. La capacidad predictiva de ambos modelos aumentó al analizar de forma separada el grupo de pacientes con hepatitis C de genotipo1, sobre todo cuando se utilizaron de forma conjunta, demostrando una capacidad de predecir fibrosis leve (F0-F1) del 95,2% y de detectar fibrosis avanzada del 91,7%.CONCLUSIONES: Los métodos bioquímicos no invasivos para la predicción de la fibrosis pueden ser muy útiles en la práctica clínica, sobre todo en el grupo de pacientes con hepatitis C genotipo1, cuando se utilizan ambos modelos de forma conjunta

BACKGROUND AND OBJECTIVE: Several models for the prediction of liver fibrosis have been developed which consist of the measurement of routine laboratory data: a) a model combining platelets,gamma-glutamil-transpeptidase, cholesterol and age (Forns model), and b) a model using an aspartate-aminotransferase to platelet ratio index (APRI). Our study was aimed to compareboth non- invasive methods to predict mild fibrosis (F0-F1) or to confirm advanced fibrosis (F3,F4) in patients with chronic hepatitis C.PATIENTS AND METHOD: We included 199 patients with chronic hepatitis. The average age (standard deviation) was 41 (11) years (16-66), and there were 117 men and 82 women. We founda genotype 1 in 108 patients (54.2%), 45 had a non-1 genotype (22.6%), and 46 (23.1%)had an unknown genotype. Mild fibrosis stage (F0-F1) was found in 96 patients, F2 in 52 and advanced fibrosis (F3-F4) in 51 patients. We calculated the APRI and the Forns’s index. RESULTS: Patients infected with genotype 1 were older (44 [11] vs 36 [4.3] years; p = 0.001),presented higher levels of cholesterol (179 [40] vs 160 [42] mg/dl; p = 0.05) and lower levels of alanine-aminotransferase (112 [86] vs 169 [87] IU/l; p = 0.03). The Forns’s model predicted mild fibrosis (F0-F1) in 71.4% while the APRI model did it in 72.7%. The Forns’s model confirmed advanced fibrosis in 78.6% against 54.2% from the APRI one. The predictive capacity in both models increased when analyzing patients with the genotype 1. Moreover, the predictive capacity of advanced fibrosis or exclusion of significant fibrosis reached more than 90%when both models were used together in patients with a genotype 1.CONCLUSIONS: Non-invasive methods for the prediction of liver fibrosis can be very useful in clinical practice, mainly in patients with genotype 1 when the two methods are used together