Differential production of insulin-like growth factor-binding proteins in liver fibrosis progression.

Noninvasive methods for liver disease diagnoses offer great advantages over biopsy, but they cannot be utilized in all cases. Therefore, specific indicators for chronic liver disease management are necessary. The aim was to assess the production of insulin-like growth factor-binding proteins (IGFBPs) 1-7 and their correlation with the different stages of fibrosis in chronic hepatitis C (CHC). A prospective, cross-sectional, multicenter study was conducted. CHC patients were categorized by FibroTest® and/or FibroScan®. Serum concentrations of IGFBPs 1-7 were determined through multiple suspension arrangement array technology. Significant differences were validated by the Kruskal-Wallis and Mann-Whitney U tests. Logistic regression models were performed to assess the association between the IGFBPs and fibrosis stages. The association was determined utilizing odds ratios (ORs), and receiver operating characteristic (ROC) curves were constructed to distinguish the IGFBPs in relation to the diagnosis of fibrosis. IGFBP-1 and IGFBP-7 concentrations were higher in CHC than in the healthy individuals, whereas IGFBP-3, IGFBP-5, and IGFBP-6 were downregulated in the patients. An apparent increase of all the IGFBPs was found at fibrosis stage F4, but with different regulations. IGFBP-2, -4, -6, and -7 had the best OR, showing the relation to fibrosis progression. The ROC curves showed that IGFBP-7 was the only protein that distinguished F1 from F3 and F2 from F3. IGFBPs participate in liver fibrosis progression and could be employed as circulating novel protein panels for diagnosis and as possible therapeutic targets in liver fibrosis progression.

Xenoimplant of Collagen Matrix Scaffold in Liver Tissue as a Niche for Liver Cells.

Hepatitis C virus-induced liver damage, chronic liver damage due to alcohol, and non-alcoholic liver disease-induced cellular alterations promote fibrosis, cirrhosis, and/or hepatocellular carcinoma. The recommended therapeutic option for advanced liver damage is liver transplantation. Extracellular matrix scaffolds have been evaluated as an alternative for tissue restoration. Studies on the biocompatibility and rejection of synthetic and natural scaffolds as an alternative to organ transplantation have been evaluated. Our group has recently described the xenoimplant of collagen matrix scaffold (CMS) in a rat model. However, no complete macroscopic and histological description of the liver parenchyma at the initial (day 3), intermediate (day 14), and advanced (day 21) stages has been obtained. In this study, we described and compared liver tissue from the CMS zone (CZ, CMS, and liver parenchyma), liver tissue from the normal zone (liver parenchyma close to the CMS), and basal tissue (resected tissue from the CMS implantation site). Our data strongly suggest that the collagen matrix xenoimplant is a good niche for hepatocytes, with no rejection, and does not affect liver function tests. The liver can regenerate after damage, but this capacity is inhibited in a chronic injury. At present, the use of CMS after liver damage has not been reported. This biomaterial could be a novel alternative in the field of regenerative medicine for liver diseases.

Alcoholic Liver Disease.

Content available: Author Interview and Audio Recording.

Three-Dimensional Collagen Matrix Scaffold Implantation as a Liver Regeneration Strategy.

Liver diseases are the leading cause of death worldwide. Excessive alcohol consumption, a high-fat diet, and hepatitis C virus infection promote fibrosis, cirrhosis, and/or hepatocellular carcinoma. Liver transplantation is the clinically recommended procedure to improve and extend the life span of patients in advanced disease stages. However, only 10% of transplants are successful, with organ availability, presurgical and postsurgical procedures, and elevated costs directly correlated with that result. Extracellular matrix (ECM) scaffolds have emerged as an alternative for tissue restoration. Biocompatibility and graft acceptance are the main beneficial characteristics of those biomaterials. Although the capacity to restore the size and correct function of the liver has been evaluated in liver hepatectomy models, the use of scaffolds or some kind of support to replace the volume of the extirpated liver mass has not been assessed. Partial hepatectomy was performed in a rat liver with the xenoimplantation of a collagen matrix scaffold (CMS) from a bovine condyle. Left liver lobe tissue was removed (approximately 40%), and an equal proportion of CMS was surgically implanted. Liver function tests were evaluated before and after the surgical procedure. After days 3, 14, and 21, the animals were euthanized, and macroscopic and histologic evaluations were performed. On days 3 and 14, adipose tissue was observed surrounding the CMS, with no clinical evidence of rejection or infection, as was vessel neoformation and CMS reabsorption at day 21. There was histologic evidence of an insignificant inflammation process and migration of adjacent cells to the CMS, observed with the hematoxylin and eosin (H&E) and Masson's trichrome staining. The CMS was shown to perform well in liver tissue and could be a useful alternative for studying tissue regeneration and repair in chronic liver diseases.

Assessment of urinary TWEAK levels in Mexican patients with untreated lupus nephritis: An exploratory study.

OBJECTIVES: Urinary levels of TWEAK (uTWEAK) may be correlated with the degree of lupus nephritis (LN) activity. Our objective was to determine the sensitivity and specificity of uTWEAK in Mexican patients with untreated active lupus nephritis. METHODS: An exploratory study was performed; four groups of patients were analyzed as follows: 1) patients with systemic lupus erythematosus (SLE) without renal activity (SLE-LN), 2) patients with SLE with renal activity (SLE+LN), 3) patients with other types of glomerulopathy (glomerulonephritis, GMN), 4) and healthy patients (controls). RESULTS: In all, 44 patients, with an average age of 35.9±11.5 years, were evaluated. uTWEAK levels were higher in patients with SLE+LN compared with patients in the other groups: SLE+LN 12.88±8.33, SLE-LN 3.12±2.31, GMN 4.36±2.31 and controls 2.41±1.94pg/mg Cr (p=0.007). A total of 72.7% of the cases had renal activity index scores above 12, and 90.9% of the cases had scores of chronicity below 6 points. Receiver Operating Characteristic (ROC) curve analysis revealed that uTWEAK levels above 4.91pg/mg Cr had a sensitivity of 81% and a specificity of 75% for the diagnosis of renal activity due to lupus, with an area under the curve of 0.876 (95% CI: 0.75-0.99). However, no significant correlation was observed between the levels of uTWEAK and the histological findings specific to the activity and chronicity associated with SLE. CONCLUSIONS: Our study revealed that uTWEAK can adequately distinguish renal activity due to lupus, but cannot predict the degree of histological activity in Mexican patients with active lupus nephropathy.

Behavior of Oxidative Stress Markers in Alcoholic Liver Cirrhosis Patients.

Alcohol is the most socially accepted addictive substance worldwide, and its metabolism is related with oxidative stress generation. The aim of this work was to evaluate the role of oxidative stress in alcoholic liver cirrhosis (ALC). This study included 187 patients divided into two groups: ALC, classified according to Child-Pugh score, and a control group. We determined the levels of reduced and oxidized glutathione (GSH and GSSG) and the GSH/GSSG ratio by an enzymatic method in blood. Also, protein carbonyl and malondialdehyde (MDA) content were estimated in serum. MDA levels increased in proportion to the severity of damage, whereas the GSH and GSSG levels decreased and increased, respectively, at different stages of cirrhosis. There were no differences in the GSH/GSSG ratio and carbonylated protein content between groups. We also evaluated whether the active consumption of or abstinence from alcoholic beverages affected the behavior of these oxidative markers and only found differences in the MDA, GSH, and GSSG determination and the GSH/GSSG ratio. Our results suggest that alcoholic cirrhotic subjects have an increase in oxidative stress in the early stages of disease severity and that abstinence from alcohol consumption favors the major antioxidant endogen: GSH in patients with advanced disease severity.

Assessment of urinary TWEAK levels in Mexican patients with untreated lupus nephritis: An exploratory study / Evaluación de los niveles urinarios de TWEAK en pacientes mexicanos con nefritis lúpica sin tratamiento farmacológico: Estudio exploratorio

Objectives: Urinary levels of TWEAK (uTWEAK) may be correlated with the degree of lupus nephritis (LN) activity. Our objective was to determine the sensitivity and specificity of uTWEAK in Mexican patients with untreated active lupus nephritis. Methods: An exploratory study was performed; four groups of patients were analyzed as follows: 1) patients with systemic lupus erythematosus (SLE) without renal activity (SLE-LN), 2) patients with SLE with renal activity (SLE+LN), 3) patients with other types of glomerulopathy (glomerulonephritis, GMN), 4) and healthy patients (controls). Results: In all, 44 patients, with an average age of 35.9±11.5 years, were evaluated. uTWEAK levels were higher in patients with SLE+LN compared with patients in the other groups: SLE+LN 12.88±8.33, SLE-LN 3.12±2.31, GMN 4.36±2.31 and controls 2.41±1.94pg/mg Cr (p=0.007). A total of 72.7% of the cases had renal activity index scores above 12, and 90.9% of the cases had scores of chronicity below 6 points. Receiver Operating Characteristic (ROC) curve analysis revealed that uTWEAK levels above 4.91pg/mg Cr had a sensitivity of 81% and a specificity of 75% for the diagnosis of renal activity due to lupus, with an area under the curve of 0.876 (95% CI: 0.75-0.99). However, no significant correlation was observed between the levels of uTWEAK and the histological findings specific to the activity and chronicity associated with SLE. Conclusions: Our study revealed that uTWEAK can adequately distinguish renal activity due to lupus, but cannot predict the degree of histological activity in Mexican patients with active lupus nephropathy (AU)

Objetivos: Los niveles urinarios de TWEAK (uTWEAK) pueden correlacionarse con el grado de actividad de nefritis lúpica (NL). Nuestro objetivo fue determinar la sensibilidad y especificidad de los uTWEAK en pacientes mexicanos con NL activa sin tratamiento farmacológico previo. Metodología: Se realizó un estudio exploratorio en el que se incluyeron 4 grupos de pacientes: 1) pacientes con lupus eritematoso sistémico sin actividad renal (LES-NL); 2) pacientes con lupus eritematoso sistémico con actividad renal (LES+NL); 3) pacientes con otras glomerulopatías y 4) controles sanos. Resultados: La edad promedio de los 44 pacientes fue de 35,9±11,5 años. Los uTWEAK fueron más elevados en pacientes con LES+NL comparados con los otros grupos: LES+NL (12,88±8,33), LES-NL (3,12±2,31), otras glomerulopatías (4,36±2,31) y grupo control (2,41±1,94pg/mgCr) (p=0,007). En el 72,7% de los casos se observó un índice de actividad renal mayor a 12 puntos y en el 90,9% de los casos los índices de cronicidad estaban por debajo de 6 puntos. La curva ROC reveló que los niveles urinarios por encima de 4,91pg/mg Cr tienen sensibilidad del 81% y especificidad del 75% para el diagnóstico de actividad renal secundaria a lupus, con área debajo de la curva de 0,876 (IC 95%: 0,75-0,99). Sin embargo, no se observó correlación significativa entre los uTWEAK y los hallazgos histológicos específicos de actividad y cronicidad asociados a LES. Conclusiones: Nuestro estudio revela que los uTWEAK pueden distinguir adecuadamente actividad renal secundaria a lupus, pero no predicen el grado de actividad histológica en pacientes mexicanos con NL activa (AU)