Corrigendum to "Redox Signaling in Diabetic Nephropathy: Hypertrophy versus Death Choices in Mesangial Cells and Podocytes".

[This corrects the article DOI: 10.1155/2015/604208.].

Redox Signaling in Diabetic Nephropathy: Hypertrophy versus Death Choices in Mesangial Cells and Podocytes.

This review emphasizes the role of oxidative stress in diabetic nephropathy, acting as trigger, modulator, and linker within the complex network of pathologic events. It highlights key molecular pathways and new hypothesis in diabetic nephropathy, related to the interferences of metabolic, oxidative, and inflammatory stresses. Main topics this review is addressing are biomarkers of oxidative stress in diabetic nephropathy, the sources of reactive oxygen species (mitochondria, NADPH-oxidases, hyperglycemia, and inflammation), and the redox-sensitive signaling networks (protein kinases, transcription factors, and epigenetic regulators). Molecular switches deciding on the renal cells fate in diabetic nephropathy are presented, such as hypertrophy versus death choices in mesangial cells and podocytes. Finally, the antioxidant response of renal cells in diabetic nephropathy is tackled, with emphasis on targeted therapy. An integrative approach is needed for identifying key molecular networks which control cellular responses triggered by the array of stressors in diabetic nephropathy. This will foster the discovery of reliable biomarkers for early diagnosis and prognosis, and will guide the discovery of new therapeutic approaches for personalized medicine in diabetic nephropathy.

Triple immunohistochemistry for assessing the inflammatory, vascular and progression of adenomyosis.

Adenomyosis is a benign pathology, common to both women at reproductive age as well as later during menopause. This condition is accompanied by a strong symptomatology, which has induced intense research on this topic. From a morphological point of view, it is represented by the existence of endometrial glands and, sometimes, of the periglandular stroma (endometriosis) in the structure of the myometrium, at a significant distance from the normal endometrium. Various inflammatory, vascular and mechanical factors accentuate the symptoms and evolution of this pathology. Our study included a total number of 32 patients, eight cases for each of the following histopathological subtypes: endometrium - proliferative phase, endometrium - secretory phase, myometrium with endometrial glands (adenomyosis), and myometrium with hyperplastic transformation of endometrial glands (hyperplastic adenomyosis), respectively. We have conducted clinical, morphological and morphopathological studies of the structures in question. Using the classical histological technique (Hematoxylin-Eosin), we identified the glandular structures; utilizing immunohistochemistry, we have labeled the endometrial epithelium with the anti-cytokeratin 7 (CK7) antibody and we analyzed the periglandular cell types of the immune system: T-lymphocytes using anti-cluster of differentiation (CD) 3 antibody, macrophages using anti-CD68 antibody, mast cells using anti-tryptase antibody, periglandular vascularization with the reaction using anti-CD34∕anti-CD31 antibodies, thus demonstrating their involvement in the development of adenomyosis. The interesting aspect of this study is the technique of simultaneously labeling of the inflammatory, vascular and epithelial elements.

Mutational status of KRAS and MMR genes in a series of colorectal carcinoma cases.

BACKGROUND: The KRAS gene mutation is the most common somatic change in colorectal carcinoma (CRC) and is predictive of resistance to anti-epidermal growth factor receptor (EGFR) therapy in the metastatic forms. Microsatellite instability (MSI), a mismatch repair (MMR) system defect, accounts for 15-20% of all CRCs, more frequent in early stages. CRCs with MSI present better prognosis, a distinct histopathological aspect and a different response to chemotherapy. Patients with both KRAS wild type and MSI have a reduced risk of dissemination and recurrence. MATERIALS AND METHODS: Our study included formalin-fixed paraffin-embedded tissue samples from 40 patients with metastatic CRCs, aged between 40 and 71 years old, gender (males/females) ratio 2.33:1. The MMR proteins were analyzed using an indirect bistadial immunohistochemical (IHC) technique with monoclonal antibodies. KRAS mutations were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. RESULTS: Of the 40 tumors analyzed, 40% presented KRAS mutations located in codon 12 or codon 13. IHC expression of MMR proteins revealed a microsatellite stable status in 35 cases, including 15 cases with mutated KRAS. MSI status was identified in five cases (four with KRAS wild type). All MSI tumors had a poorer histological differentiation and four cases revealed a mucinous phenotype. Eighty percent of the patients with MSI status were older women. CONCLUSIONS: Our study demonstrates a 20% frequency of mutated KRAS in MSI CRCs, the incidence of KRAS mutations being inversely correlated with MSI status in these tumors. MMR protein deficient CRCs tend to occur in older females, have a poorer differentiation and are frequently associated with KRAS wild type.

A morpho-functional study using PEP/LVET ratio and global longitudinal strain in patients with dilated cardiomyopathy.

AIM: To assess left ventricular (LV) systolic function and morphology in patients with severe dilated cardiomyopathy (DCM), using both conventional and a complex technique, speckle-tracking echocardiography, and evaluate the correlation between pre-ejection period and left ventricular ejection period (PEP/LVET) ratio, global longitudinal strain (GLS), and severity of the condition. PATIENTS, MATERIALS AND METHODS: Seventeen patients were enrolled after rigorous criteria. Echocardiography was performed in conventional and speckle-tracking mode, in all patients with DCM, in sinus rhythm. LV dimensions, volumes and ejection fraction (LVEF) were measured. PEP/LVET ratio was obtained from apical 5-chamber axis and was defined as the time between QRS onset and LV ejection reported to LV ejection period. Speckle-tracking imaging was performed in offline mode and GLS was obtained from parasternal 4-, 3-, 2-chamber apical view, by averaging longitudinal peak systolic strain of all 17 LV-segments. RESULTS: New York Heart Association (NYHA) functional class correlated significantly with LVEF (-0.82; p=0.0006), PEP/LVET (0.86; p=0.001) or GLS (0.85; p=0.0002). Considerable correlations were between mitral regurgitation (MR) severity and LVEF (-0.65; p=0.01) or PEP/LVET (0.69; p=0.0059), but higher were between MR severity and GLS (0.76; p=0.0018). Tricuspid regurgitation (TR) grading correlated statistically with LVEF (-0.62; p=0.01), PEP/LVET and GLS (0.6; p=0.018; and 0.62; p=0.014, respectively). As opposed to the parameters in conventional echocardiography, GLS correlated with DCM etiology (p=0.0046) and with the gender (p=0.048). CONCLUSIONS: This study demonstrates that, in patients with DCM, assessment of cardiac dyssynchrony can be accurately accomplished by combining parameters in conventional and in speckle-tracking echocardiography.

The impact of liver steatosis on early and sustained treatment response in chronic hepatitis C patients.

Steatosis is a frequent feature of hepatitis C virus (HCV) infection. Steatosis may be an important cofactor in both accelerating fibrosis and increasing liver necroinflammatory activity in chronic hepatitis C. The main objective of this study was the evaluation of biological response rates, early viral response, sustained viral response in patients with chronic hepatitis C treated with Interferon-alpha (IFN-α), Pegylated (PEG)-IFN-α2a or -α2b plus Ribavirin and to relate it to the presence of hepatic steatosis. There were selected to take part to the research 210 patients with chronic hepatitis C who have fulfilled all inclusion and exclusion criteria and were treated with PEG-IFN plus Ribavirin. Patients' progress has been monitored by determining next parameters: age, gender; biochemical tests - alanine aminotransferase (ALT), aspartate aminotransferase (AST); serological assays - detect antibody to hepatitis C virus (anti-HCV); molecular assays - detect, quantify and/or characterize HCV-RNA; liver histopathological examination. Steatosis was graded using the Brunt system. These parameters were included in an area under curve (AUC) analysis. Purpose is to estimate their degree of influence on getting early viral response (EVR) and sustained viral response (SVR). Based on the obtained results, it appears that initial value of HCV-RNA, dVL parameter value (low relative percentage of viral load during the first 12 weeks of treatment), histological scores steatosis may be predictive in the viral response in chronic hepatitis C. Our research demonstrates that a high degree of liver steatosis impairs both EVR and SVR in chronic hepatitis C treated with standard PEG-IFN and Ribavirin for 48 weeks and that a steatosis score of ≤3 predicts EVR with a sensibility of 91.03% with specificity of 21.54%.

Non-alcoholic fatty liver disease - clinical and histopathological aspects.

INTRODUCTION: We conducted a retrospective study on patients who were hospitalized in the Emergency County Hospital of Craiova, Romania, between 2009-2014. We selected 75 patients out of 248 cases of fatty liver disease who underwent liver biopsies performed during surgical procedures for various diagnoses. PATIENTS AND METHODS: We analyzed the patients' data recorded in examination charts: anthropometric parameters [height, weight, body mass index (BMI), abdominal circumference], metabolic lab tests (blood glucose, lipid profile), liver destruction enzymes, imaging examinations (abdominal ultrasound). The pathological study was performed on specimens directly after sampling as well as after staining. RESULTS: After analyzing the results of the histological examination, we grouped our studied patients according to the degree of the liver steatosis: 21 (28%) cases with mild steatosis, 46 (61.33%) cases with moderate disease and eight (10.66%) cases with severe steatosis. The necrotic-inflammatory activity was mild in 28 (37.33%) cases, moderate in 36 (48%) cases and severe in 11 (14.66%) cases. Most of the studied patients exhibited septal fibrosis (45 cases - 60%) and porto-portal and porto-central bridging fibrosis (21 cases - 28%). Septal fibrosis and cirrhosis were recorded in four (5.33%) and five (6.66%) cases, respectively. There was a significant correlation between the degree of the hepatic steatosis, the degree of obesity (as expressed by BMI) and the waist circumference (as a measure of central obesity) - p<0.001. CONCLUSIONS: The non-alcoholic fatty liver disease (NAFLD) was found to be significantly associated with waist circumference, BMI, triglycerides. The liver enzymes are not considered to be sensitive or specific for diagnosing NAFLD. Concerning the association between the steatosis and fibrosis, in our study the septal fibrosis was associate with mild steatosis in most of the cases. Moderate steatosis was mostly associated with septal fibrosis as well as porto-portal and porto-central fibrosis. Severe steatosis was correlated with both porto-portal and porto-central fibrosis and cirrhosis in the majority of cases.

Neuro-neoplastic interrelationships in colorectal level - immunohistochemical aspect in three cases and review of the literature.

Colorectal cancer represents a severe public health issue. Recent studies have shown the essential role played by nerves and their neurotransmitters in tumor initiation and progression. The aim of this study is to asses the expression of beta 2-adrenergic receptors (ß2A) for adrenaline and noradrenaline, and the expression of M3 muscarinic receptors (M3R) for acetylcholine (neurotransmitters produced and released by sympathetic and parasympathetic afferents of the digestive tract and also by the enteric nervous system) in different tumor gradings of colorectal adenocarcinoma, and also the tropomyosin receptor kinase A (TrkA) for the nerve growth factor produced by the cells of colorectal adenocarcinoma. Beta 2-adrenergic receptors were expressed both in normal colic tissue and in the tumor tissues, from the three patients included in the study. It was observed that both area and integrated optical density (IOD) are more elevated for this type of receptor in tumor tissues than in normal colic tissue. For the M3 muscarinic receptors, similarly to beta 2-adrenergic receptors, it was observed a growth both of the area and of the IOD with the tumor grading. The presence of TrkA receptors was also observed both in the normal colic mucosa and in the tumor tissues examined, but with a significant reduction of the signal in the poorly differentiated tumor tissue. Understanding the neurobiology of cancer in this context becomes necessary for establishing much more complex and targeted molecular targeted therapies.

Histological factors that predict the liver fibrosis in patients with chronic hepatitis C.

In chronic hepatitis, pathologies reveal a prominent inflammatory infiltrate portal consisting mostly of lymphocytes and plasma cells invading the portal spaces, although one can also identify macrophages, neutrophils or eosinophils. In all the forms of chronic hepatitis, fibrosis starts in the portal area, namely periportally, subsequently extends towards the lobules to the central veins, causing septa, followed by fibrosis. We studied 52 patients with chronic hepatitis C, who underwent a hematological, biochemical, virological and histopathological investigation. We found that the severity degree of the portal inflammation was in direct relation to the hepatitis activity index (HAI) and to the degree of fibrosis. The portal inflammation is dependent to the degree of fibrosis. The degree of inflammation significantly changes the distribution of cases with different degrees of fibrosis (chi-square p=0.00011 <0.001). Periportal inflammation, periportal necrosis and focal necrosis are the morphological aspects of the necroinflammatory process best correlated to the occurrence and development of fibrosis.

The redox biology network in cancer pathophysiology and therapeutics.

The review pinpoints operational concepts related to the redox biology network applied to the pathophysiology and therapeutics of solid tumors. A sophisticated network of intrinsic and extrinsic cues, integrated in the tumor niche, drives tumorigenesis and tumor progression. Critical mutations and distorted redox signaling pathways orchestrate pathologic events inside cancer cells, resulting in resistance to stress and death signals, aberrant proliferation and efficient repair mechanisms. Additionally, the complex inter-cellular crosstalk within the tumor niche, mediated by cytokines, redox-sensitive danger signals (HMGB1) and exosomes, under the pressure of multiple stresses (oxidative, inflammatory, metabolic), greatly contributes to the malignant phenotype. The tumor-associated inflammatory stress and its suppressive action on the anti-tumor immune response are highlighted. We further emphasize that ROS may act either as supporter or enemy of cancer cells, depending on the context. Oxidative stress-based therapies, such as radiotherapy and photodynamic therapy, take advantage of the cytotoxic face of ROS for killing tumor cells by a non-physiologically sudden, localized and intense oxidative burst. The type of tumor cell death elicited by these therapies is discussed. Therapy outcome depends on the differential sensitivity to oxidative stress of particular tumor cells, such as cancer stem cells, and therefore co-therapies that transiently down-regulate their intrinsic antioxidant system hold great promise. We draw attention on the consequences of the damage signals delivered by oxidative stress-injured cells to neighboring and distant cells, and emphasize the benefits of therapeutically triggered immunologic cell death in metastatic cancer. An integrative approach should be applied when designing therapeutic strategies in cancer, taking into consideration the mutational, metabolic, inflammatory and oxidative status of tumor cells, cellular heterogeneity and the hypoxia map in the tumor niche, along with the adjoining and systemic effects of oxidative stress-based therapies.

Sonographic evaluation of fetal cerebral structures correlated with histological aspects.

Prenatal development of the human brain from undifferentiated neuroepithelium, crosses numerous steps towards primordial organization and subsequent cytoarchitectural layering, ascending and progressive from the lower cortical layers to the superior ones. Our study represents a systematic, comparative assessment of imaging studies and the histological evaluation of the prenatal development of the human brain. We evaluated 232 cases using 3D ultrasound. Histological study was performed on 17 cases aged between 8 and 32 weeks pregnancy and compared with imaging results. For the ultrasound study, we chose five anatomical landmarks: the choroid plexus, thalamus, cerebellum, hippocampus and island (Sylvian fissure). The histological study was performed on dissected brain specimens preserved in formaldehyde and was followed by immunohistochemical determination in order to complete the picture of the morphological evolution of the structures evaluated. We analyzed the accuracy of the description of marker elements (choroid plexus, thalamus, cerebellum, hippocampus and Sylvian fissure) in three-dimensional ultrasound evaluation. This showed a good correlation with the morphological evaluation as well as with the dimensional descriptions from the literature. Histological and immunohistochemical assessment helped complete the picture of the central nervous system development. Highlighting fetal cerebral structures by three-dimensional ultrasound, together with morphological examination helped us create a dynamic array of the central nervous system development.

Histopathological aspects described in patients with chronic hepatitis C.

Chronic hepatitis C affects an estimated 170 million people worldwide and causes approximately 350 000 deaths each year. The current antiviral therapy allows the virus eradication or the permanent inhibition of the virus replication (sustained virological response, SVR), the reduction of the inflammation, and the prevention or the reduction of liver fibrogenesis (histological response). We studied the histopathological aspects found during percutaneous liver biopsy in patients with chronic hepatitis C viral infection who were treated and monitored over a period of two years. The assessment of the histological activity index through Ishak score determined the presence of: mild chronic hepatitis in 12 (23.1%) patients, moderate chronic hepatitis in 21 (40.4%) patients, and severe chronic hepatitis in 19 (36.5%) patients. The percutaneous liver biopsy performed on the patients with chronic viral hepatitis C showed a series of histological alterations, the most frequent being: portal inflammation, periportal necrosis, lobular inflammation, focal necrosis, and hepatic fibrosis (scarring). The severity degree of this histopathological aspect was correlated with the hepatitis activity index. The association of piecemeal with bridging necrosis is the deadline at which the antiviral treatment can still be effective. Evidence of early fibrosis represent the important moment for the antiviral treatment start. The specific histopathological aspects, but not pathognomonic, of chronic hepatitis C (hepatic steatosis, portal lymphoid infiltrates and bile duct damage) had a reduced incidence, occurring in only half (hepatic steatosis), a quarter (portal lymphoid infiltrates) and a fifth (destruction of biliary ducts) of all the patients with chronic viral hepatitis C, and these patterns was correlated with advanced degree of necroinflammatory process of the liver, particularly in the portal tracts.

Histochemical and immunohistochemical evidence of tumor heterogeneity in colorectal cancer.

INTRODUCTION: Intratumoral heterogeneity implies the existence of differences between tumor cells, which can best be shown by histochemical and immunohistochemical techniques. The histological study is a mandatory step in any research aimed at characterizing tumor heterogeneity. Immunohistochemistry (IHC) also plays an important role in the differentiation of tumor types, assessing aggressiveness. MATERIALS AND METHODS: Investigated group consisted of 50 patients with colorectal adenocarcinoma, for each were recorded clinicopathological data and harvested samples intraoperatively, which were included in paraffin blocks. We perform Hematoxylin-Eosin staining for histological grade and other indices. IHC study used Avidin-Biotin-Peroxidase (ABC), with the markers: CK7, CK20, MUC1, MUC2, Ki-67, PCNA, p53, KRAS, BCL2, PTEN, EGFR. The resulting data were analyzed by statistical methods. RESULTS: Most of colorectal adenocarcinoma studied had no special histological features and had G2 grade. IHC detected in most cases the CK20+÷CK7- phenotype (78%) and MUC1 (74%) protein expression. The proliferation markers (Ki-67 and PCNA) were present in all tumor mass with a variable index, which shows high intratumoral heterogeneity, but p53 and KRAS were distributed more uniformly, showing low intratumoral heterogeneity. PTEN was expressed nuclearly in 86% of the cases and EGFR in 42%. CONCLUSIONS: The expression profiles of cytokeratins and mucins in the colorectal adenocarcinomas are useful in defining tumor phenotypes with different prognosis and therapy. We found a significant positive correlation between KRAS protein expression and BCL2 and TP53 expression. The study demonstrated the intratumoral and intertumoral heterogeneity, expressed at phenotypic level.

Toxicity of L-DOPA coated iron oxide nanoparticles in intraperitoneal delivery setting - preliminary preclinical study.

Iron oxide nanoparticles are promising candidates for theranostics in cancer, that aims to achieve in one-step precise tumor imaging by magnetic resonance, and targeted therapy through surface attached anti-cancer drugs. The aim of this study was to investigate in preclinical setting the biocompatibility of new iron oxide-based nanoparticles that were coated with L-DOPA for improved dispersion in biological media. These nanostructures (NPs) were designed for biomedical applications as contrast agents and/or drug carriers. We investigated the effect exerted in vitro by NPs and L-DOPA on the viability and proliferation of normal mouse L929 fibroblasts. NPs exhibited good biocompatibility against these cells. Moreover, L-DOPA contained in NPs sustained fibroblasts proliferation and/or limited anti-proliferative effects of naked nanoparticles. In the animal study, C57BL/6 mice were injected intraperitoneally with a single dose of NPs (approximately 125 mg/kg body weight). We followed up hematological and histological parameters for one, three and seven days after NPs administration. Results indicated that NPs possibly induced local inflammation and consequent recruitment of peripheral lymphocytes, whilst the decrease of platelet counts may reflect tissue lesions caused by NPs. The histopathological study showed mild to moderate alterations in the hepatocytes, splenic and renal cells, while the brain parenchyma only presented nonspecific congestive changes. Taken altogether, the preclinical study indicated that the new iron oxide nanoparticles coated with L-DOPA were biocompatible against fibroblasts and had a convenient toxicological profile when administered intraperitoneally in a single dose to C57BL/6 mice. Accordingly, the proposed nanostructure is a promising candidate for imaging and treating dispersed peritoneal tumors.

Different patterns of heterogeneity in ovarian carcinoma.

Ovarian cancer is still the leading cause of death from malignant genital tract lesions. Ovarian carcinomas represent about 90% of cancers that arise in the ovaries and are commonly diagnosed around menopausal age. This study examines different aspects of the heterogeneity of ovarian carcinomas and included 50 cases, 10 cases for each subtype. Our data showed that tumor types have distinct morphological and phenotypic patterns: high- and low-grade serous carcinoma, endometrioid, clear cell and mucinous carcinoma. The different subtypes of ovarian carcinomas have different molecular, pathological and clinical characteristics, the histological diversity of epithelial ovarian carcinoma mirroring thus distinct entities not just one disease.

Non-Hodgkin lymphomas of Waldeyer's ring.

Lymphomas represent malignant lymphoproliferative diseases and they are generally classified as Hodgkin's (HL) or non-Hodgkin malignant lymphomas (NHML). Head and neck lymphomas represent one of the most common sites of extranodal lymphomas, second after the gastrointestinal tract. Waldeyer's ring structures include the palatine tonsils, the nasopharyngeal lymphatic tissue, and the lingual tonsil. We investigated 38 patients with malignant lymphoma with ages ranging from 21 to 95 years, all localized in the Waldeyer's ring. Good knowledge of the clinical characteristics of these lymphomas and the methods to establish the differential diagnosis are essential for a correct therapy of the disease.

Invasive papillary carcinoma of the mammary gland: histopathologic and immunohistochemical aspects.

Papillary lesions of the breast, both being and malignant, can prove to be a very challenging diagnosis in histological preparations. This study emphasizes on the importance of immunohistochemistry and in particular, the identification of myoepithelial cells for the correct evaluation of these lesions.

Retropancreatic cystic lymphangioma - considerations upon a case.

UNLABELLED: Cystic lymphangiomas are benign tumors developing as an anomaly of the lymphatic channels. Most of them are discovered in children and are located mostly in the head and neck with no differences between sexes. Retroperitoneal locations are rare, clinical symptoms not specific and are discovered incidentally. We report the case of a 32-year-old female sex patient with a cystic tumor situated in the retroperitoneum, behind the pancreas, discovered by abdominal ultrasound during a diagnostic work-out for urinary infection and hypertension. Anamnesis, physical examination and CT-scan could not indicate the nature of the cyst. The cystic tumor had a shape of a butterfly, crossing the midline in front of the aorta and vena cava. A laparotomy was indicated and established the diagnosis of a cystic lymphagioma based on its macroscopic appearance. The tumor was approached from its right side by a generous Kocher maneuver and then from the left by disinsertion of the Treitz ligament and elevating the pancreatic body and splenic vessels. It was completely removed. Postoperative course was uneventful. Histopathologic examination confirmed the diagnosis of benign cystic lymphangioma. At 2 years of follow-up the patient was free of recidive. CONCLUSIONS: Retropancreatic cystic lymphangioma are rarely seen in adults. Precise diagnosis is made at laparotomy, imagistic test give details about walls, content, relationship with the surrounding structures and major blood vessels. Complete surgical resection represents the treatment of choice avoiding recurrence.

Immunohistochemical study of stellate cells in patients with chronic viral hepatitis C genotype 1.

INTRODUCTION: Hepatic stellate cells (HSC) are key-players in the pathogenesis of liver fibrosis, inducing collagen deposition and abnormal extracellular matrix remodeling. AIM: The purpose of this study was to identify the stellate cells using immunohistochemical techniques and to establish if there is a correlation between the expression of stellate cells and the clinical and histological parameters in patients with chronic viral hepatitis C. MATERIALS AND METHODS: The studied group included 30 patients with chronic viral hepatitis C genotype 1, in whom a liver biopsy was performed previous to the antiviral treatment. After the histological analyze, the biopsy was stained with an anti-SMA antibody (Dako, Carpinteria, CA). The amount of positive stained area was determined using an arbitrary semiquantitative score from 1 to 4. RESULTS: Our observations suggest that there is a strong correlation between the stellate cells activity, evaluated using a semiquantitative score, and the stage of liver fibrosis (rs=0.76, p<0.001). Also, our study revealed a direct correlation, but less intense, with the necro-inflammatory activity (rs=0.39, p=0.03), the steatosis degree (rs=0.428, p=0.01) and the value of alanine aminotransferase (rs=0.4, p=0.03). The age and the viremia level were not correlated with the activity of the stellate cells. CONCLUSIONS: This study suggests that the transition of stellate cells from inactivated state to the state of highly fibrogenic cell is influenced mainly by the histological liver modifications (necroinflammatory activity and steatosis) and less by clinical parameters (age, sex) or the viremia level.