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Francesco Negro

Publications and source records attributed to Francesco Negro.

36 records · Page 2Linked to original sources
PubMed2004

Alcohol is an important co-factor for both steatosis and fibrosis in Northern Italian patients with chronic hepatitis C.

BACKGROUND/AIMS: Steatosis in patients with chronic hepatitis C (CHC) may be the result of both viral and host factors. To evaluate: (1) the relationship between steatosis and either host or viral factors; (2) the correlation between steatosis and fibrosis in patients with CHC. METHODS: A consecutive series of 349 patients were evaluated for steatosis. At liver biopsy, patients were tested for virological, and laboratory analysis and questioned for alcohol consumption. RESULTS: Logistic regression analysis demonstrated that steatosis was independently associated with genotype 3a (odds ratio, OR 3.5), alcohol intake at the time of biopsy (OR 2.6) and age >35 years (OR 2.7). In multivariate analysis the presence of fibrosis was associated with past alcohol abuse (OR 3.7), and age older than 44 years (OR 2.2). Overall, a weak correlation was found between grade of steatosis and fibrosis score (r=0.861, P=0.05), which disappeared excluding patients without past or current alcohol intake. A direct correlation emerged between grade of steatosis and both 'grading' and 'staging' only in patients with genotypes other than 3a. CONCLUSIONS: Genotype 3a is the main risk factor for steatosis in patients with CHC. The grade of steatosis correlated with both grading and staging only in patients with genotypes other than 3a and this relationship is strictly linked to alcohol consumption.

Adolescent↗
PubMed2003

Hepatocellular adenoma and polycystic ovary syndrome.

Various identified risk factors predispose to hepatocellular adenomas. We present the case of a young woman with liver adenoma in a context of polycystic ovary syndrome, associated with high levels of androgens and following a high dose hormonal therapy. In view of this complication, we recommend a close screening of patients with such hormonal imbalance, especially those who are treated with high doses of hormones, with repeated liver tests and ultrasonographies.

Adenoma, Liver Cell↗
PubMed2003

Impaired hepatic mitochondrial oxidation using the 13C-methionine breath test in patients with macrovesicular steatosis and patients with cirrhosis.

BACKGROUND: In cirrhosis, hepatic mitochondriae exhibit morphological and functional abnormalities. In human steatosis, ultrastructural changes are reported in the absence of ethanol. Routine evaluation of mitochondrial function is difficult. We used a breath test to explore hepatic mitochondrial oxidation in vivo. MATERIAL/METHODS: The 13C-methionine breath test was performed in healthy subjects (n=15), patients with cirrhosis (n=25), and patients with biopsy-proven severe (> 40% involved hepatocytes), non-alcoholic macrovesicular steatosis (n=18). After oral administration of 13C-methionine (200 mg), hepatic mitochondrial decarboxylation was measured by breath [13C]-C02 enrichment, expressed as dose/h and delta over base (DOB), for 1 hour, by isotope ratio infrared spectroscopy. Results were normalized against BMI. RESULTS: At 60 minutes, patients with steatosis had reduced exhalation of 13C02 as compared to healthy subjects (dose/h: -47%, 18.8+/-12 vs 36+/-6.1; DOB: -52%, 40.4+/-32 vs 85+/-20, p<0.05). Cirrhotics had even lower values as compared to patients with steatosis (dose/h: -60%, 7.5+/-3.4 vs 18.8+/-12, p<0.05). In cirrhosis, dose/h correlated (r=0.68) to aminopyrine breath test values, a microsomal function test, and was inversely correlated (r=-0.48) to the Child-Pugh score. CONCLUSIONS: Hepatic mitochondrial oxidation as reflected by the 13C-methionine breath test is impaired both in patients with pure non alcohol-related severe macrovesicular steatosis and in patients with cirrhosis of mixed etiologies. This non- invasive test can be used to monitor hepatic mitochondrial function in vivo.

Adult↗
PubMed2002

Immunological and virological effects of ribavirin in hepatitis C after liver transplantation.

BACKGROUND: Hepatitis C recurring after liver transplant may cause progressive liver dysfunction, and available treatment regimens are unsatisfactory. A better understanding of the mechanisms of action of drugs currently used to manage hepatitis C would be helpful. METHODS: In a pilot, uncontrolled clinical trial, we treated 12 patients with post-liver transplantation hepatitis C with 1000-1200 mg qd of ribavirin, given as a monotherapy. We measured the transaminases levels, the liver disease grading and staging scores, the intrahepatic interferon-gamma, tumor necrosis factor-alpha, interleukin (IL)-4 and IL-10 mRNA levels, the serum and liver hepatitis C virus (HCV) RNA titers, and the intrahepatic HCV envelope 2 protein staining score before and after 12 weeks of ribavirin monotherapy. RESULTS: Ribavirin induced a significant amelioration of the transaminases levels. This biochemical response was not associated with a distinct change in the intrahepatic T helper 1/T helper 2 cytokine mRNA profile. Furthermore, some histological parameters, such as the portal inflammation and the fibrosis scores, worsened significantly even in the short term. A slight, albeit not significant, decrease of serum HCV RNA level and intrahepatic HCV antigen staining score was observed. Intrahepatic genomic-strand (but not negative-strand) HCV RNA titer decreased significantly (P=0.024). CONCLUSIONS: Contrary to what is suggested by experimental data, administration of ribavirin alone to patients with recurrent hepatitis C after liver transplantation is not accompanied by a specific change of the intrahepatic interferon-gamma, tumor necrosis factor-alpha, IL-4, or IL-10 mRNA transcription profile.

Adult↗
PubMed2002

Lack of in vivo blockade of Fas- and TNFR1-mediated hepatocyte apoptosis by the hepatitis C virus.

In vitro data have shown that the hepatitis C virus (HCV) core protein binds to protein members of the tumour necrosis factor receptor (TNFR) superfamily. Since this interaction could be relevant to HCV persistence and oncogenesis, this study assessed whether HCV may interfere with the apoptotic cascade in vivo. Apoptosis (by TUNEL) and Fas and TNFR1 expression (by immunohistochemistry) were scored in the liver of 60 chronic hepatitis C patients. Results were compared with the liver disease grading and staging scores and the HCV replication level in serum and liver. Apoptotic hepatocytes were stained in 29 cases. Fas was expressed in 35 cases and TNFR1 in 21, 15 patients (25%) being negative for both receptors. Overall, the numbers of TUNEL-, Fas- and TNFR-positive hepatocytes did not correlate with the extent of intrahepatic CD8+ T-lymphocyte infiltration, the grading and staging of liver disease, or the serum or liver HCV RNA levels. Furthermore, when patients expressing either Fas or TNFR1 were stratified according to serum HCV RNA levels, cases with detectable hepatocyte apoptosis had higher HCV viraemias. In conclusion, an HCV-mediated, in vivo blockade of hepatocyte apoptosis via the Fas- or TNFR1-dependent pathways seems unlikely.

Antigens, CD↗
PubMed2002

Molecular evidence that the hepatitis C virus replicates in the oral mucosa.

BACKGROUND/AIMS: Patients infected with the hepatitis C virus (HCV) often have extrahepatic manifestations, which significantly contribute to HCV-related morbidity, but whose pathogenesis is largely unknown. Our aim was to evaluate the HCV replication in oral mucosa of chronic hepatitis C patients. METHODS: We collected oral mucosa specimens from 17 anti-HCV-positive and four anti-HCV-negative patients. Fifteen had oral lichen (12 anti-HCV-positive). Total mucosa RNA was extracted and analyzed for presence and titer of genomic and negative-strand HCV RNA. Findings were compared with clinical and pathological features. RESULTS: Genomic and negative-strand HCV RNA were detected, respectively, in 12 of 17 (70.6%) and four of 17 (23.5%) specimens from the chronic hepatitis C patients. No negative-strand HCV RNA was detected in five anti-HCV-positive patients without lichen (including three with normal mucosa). Presence and titer of the negative-strand HCV RNA were independent of HCV genotype, serum viral load, and histological diagnosis of liver lesions. The phylogenetic analysis of the envelope 2 region cloned from a normal mucosa and the corresponding serum further suggested that only lichen tissues appear to harbor replicating HCV. CONCLUSIONS: HCV may occasionally replicate in oral lichen tissue, possibly contributing to the pathogenesis of mucosa damage.

Adult↗
PubMed2002

Oral lichen planus pathogenesis: A role for the HCV-specific cellular immune response.

Hepatitis C virus infection can be associated with different extrahepatic manifestations, including lichen planus; however, no clear role for HCV in their pathogenesis has been established. T cells were isolated from lichen biopsy specimens of 7 HCV positive patients with oral lichen planus. HCV-specific CD4(+) T-cell lines were obtained in 4 patients from lichen lesions but only in 2 of them from the peripheral blood. Different clonal populations were found in oral tissue and peripheral blood of individual patients, as shown by TCR-Vbeta analysis of antigen-specific T cells. Frequency of HCV-specific CD8(+) cells tested with 4 different HCV tetramers was significantly higher in the lichen tissue than in the circulation; moreover, lichen-derived HCV-specific CD8(+) T cells showed the phenotype of recently activated T cells because most of them were CD69(+) and produced interferon gamma (IFN-gamma) but expanded poorly in vitro upon antigen stimulation. The specificity of HCV-reactive T-cell recruitment into the lichen tissue was further confirmed by the absence of HBV-specific T cells within lichen lesions in 3 additional patients with lichen planus associated with HBV infection. Our study shows HCV-specific T-cell responses at the site of the lesions of an HCV-associated dermatologic disease, sustained by HCV-specific T cells with phenotypic and functional characteristics of terminally differentiated effector cells. In conclusion, this finding and the detection of HCV RNA strands in the lichen tissue strongly suggest a role for HCV-specific T-cell responses in the pathogenesis of oral lichen planus associated with HCV infection.

Antibody Specificity↗
PubMed2000

Expression of Hepatocyte Growth Factor (HGF) and its Receptor (MET) in Medullary Carcinoma of the Thyroid.

The tyrosine kinase receptor encoded by the MET oncogene has the unusual property of mediating the invasive growth of epithelial cells upon binding with the hepatocyte growth factor (HGF). The MET/HGF receptor is known to be overexpressed in thyroid carcinomas originated from follicular cells, but has not been reported in C cell tumors. To investigate the role of HGF and of its receptor (encoded by MET oncogene) in medullary carcinoma of the thyroid (MCT), we studied the expression of HGF and MET in 20 cases by means of different techniques. By RT-PCR, HGF mRNA was found in 10/20 cases, while MET mRNA presence was demonstrated in 8/20, of which 7 also expressed HGF. Northern blot analysis and in situ hybridization were performed in selected cases and confirmed RT-PCR data in some cases, although the lower sensitivity of these procedures did not allow the identification of all RT-PCR positive cases. By immunohistochemistry (using specific monoclonal antibodies) HGF was demonstrated in 8/9 RT-PCR positive cases and a monoclonal to MET immunostained 5/6 RT-PCR positive cases. All receptor positive cases also expressed the ligand in the same tumor cell population. These findings demonstrate MET and HGF co-expression in a subset of MCT, in which autocrine/paracrine circuits may be active. No correlation was found between HGF/MET expression and clinico-pathological parameters, except for the more common multifocality of HGF/MET positive MCT. Whether the potential activation of MET in MCT is responsible for local invasion and malignant evolution is to be further investigated, especially in multifocal and aggressive tumors.

Journal Article↗
PubMedDate not supplied

Presacral epidermoid cyst. A case report.

INTRODUCTION: Most of the primitive cystic neoplasms arising in the retrorectal presacral space are congenital. Presacral epidermoid cysts are classified as a type of developmental cysts, resulting from an error during the embryogenesis. They have a slowly-progressive growth that only lately can cause clinically remarkable symptoms. Most patients are middle-aged women. They are often asymptomatic. The discovery is almost always casual. It happens during controls like US, CT MRI, gynecological visit. The surgical treatment must be effected for a correct diagnosis of nature of the lesion and to remove the mass. In fact, infective complications may occur and the increasing volume of the cyst can give clinical symptoms. Posterior approach is indicated for low or mid presacral space tumors; it is the most commonly followed route. The abdominal approach may be adequate for large developmental cysts. CASE REPORT: A case of an incidentally found large presacral epidermoid cyst in a young woman, which was excised through an abdominal approach is reported.

Epidermal Cyst↗