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Biomedical subjects

F Negro

Publications and source records attributed to F Negro.

At least 19 recordsLinked to original sources
PubMed2007

Impact of hepatic steatosis on viral kinetics and treatment outcome during antiviral treatment of chronic HCV infection.

Liver steatosis is highly prevalent in chronic hepatitis C virus (HCV) infection, especially in patients infected with genotype 3 virus, but its significance for the outcome of antiviral treatment is not fully understood. We have monitored steatosis in liver biopsies from 231 patients with chronic HCV infection who received pegylated recombinant interferon-alpha and ribavirin in a phase III study (DITTO trial). The degree of steatosis, along with relevant metabolic parameters, was correlated with the early disappearance of virus and with the final outcome of treatment. Our data suggest that the presence of steatosis impairs the early reduction of viral load during treatment in patients infected with HCV genotype 3 and non-3. Steatosis negatively affected the final outcome of treatment mainly in patients infected with HCV genotype non-3 virus. Based on these findings, we propose that interventions aiming at reducing hepatic steatosis prior to the onset of antiviral therapy may be of benefit to patients infected with HCV of the non-3 genotypes. Patients infected with genotype 3, on the other hand, should be offered early antiviral treatment.

Adult↗
PubMed2006

Review article: management of patients with chronic hepatitis C virus infection and "normal" alanine aminotransferase activity.

BACKGROUND: Hepatitis C virus infection, a major cause of chronic liver disease, occurs with normal serum alanine aminotransferase activity in approximately 25% of patients. These patients have historically remained untreated but substantial evidence indicates liver damage, progression of disease and impaired quality of life in some individuals. AIM: To review the current management of patients with chronic hepatitis C and normal alanine aminotransferase activity. METHODS: This review represents the summary of discussions at a Clinical Workshop with a comprehensive literature searching of available databases (PubMed and Embase). RESULTS: Current limits defining normal serum alanine aminotransferase activity are not representative of a "healthy" status. Most patients with hepatitis C and normal alanine aminotransferase levels have histologically proven liver damage that, although generally mild, may be significant (> or =F2) in up to 20% of patients and progresses at approximately 50% of the rate in patients with elevated alanine aminotransferase levels. Some patients have persistently normal alanine aminotransferase activity and may have a more benign outcome, but a significant proportion (> or =20%) experience periods of increased serum alanine aminotransferase activity which may be associated with enhanced disease progression. CONCLUSIONS: A treatment approach that considers host and virus-related variables and optimizes patient and cost benefits may therefore provide more effective management of patients with chronic hepatitis C and normal alanine aminotransferase activity.

Alanine Transaminase↗
PubMed2006

[Therapy of chronic hepatitis B].

The aim of chronic hepatitis B therapy is to suppress hepatitis B virus replication, to control disease activity and progression towards cirrhosis. The first-line drug is the pegylated interferon a, which suppresses HBV replication in 40% of cases, albeit burdened with several contraindications and side effects. Lamivudine, a nucleoside analog inhibiting HBV reverse transcriptase, is indicated in case of failure or contraindication to interferon, may however lead to the selection of resistant mutant HBV strains (20% yearly). In that case, adefovir is indicated and has a lower risk of selection of resistant strains (5% yearly). More effective drugs (telbivudine and entecavir) will soon be available in Switzerland. Two inhibitors of HIV (tenofovir and emtricitabine) may also be used to treat hepatitis B in selected cases. Drug combinations, although supported by theoretical considerations, bring no known clinical benefit and are not reimbursed.

Antiviral Agents↗
PubMed2006

Peroxisome proliferator-activated receptor-alpha and -gamma mRNA levels are reduced in chronic hepatitis C with steatosis and genotype 3 infection.

BACKGROUND: Steatosis in chronic hepatitis C is associated with inflammation and accelerated fibrogenesis. AIM: To assess the contribution of peroxisome proliferator-activated receptor-alpha and -gamma to the pathogenesis of hepatitis C virus associated steatosis is unknown. METHODS: We measured peroxisome proliferator-activated receptor (PPAR)-alpha and -gamma mRNA by quantitative polymerase chain reaction in liver biopsies of 35 genotype 1 and 22 genotype 3 infected patients and in Huh7 cells expressing hepatitis C virus 1b or 3a core protein. RESULTS: PPAR-alpha mRNA was significantly reduced in livers of patients with genotype 3 compared with genotype 1. Steatosis was associated to a decreased expression of PPAR-alpha in genotype 1, but not in genotype 3. PPAR-gamma expression was significantly lower in genotype 3 compared with genotype 1 and steatosis was associated to decreased levels of PPAR-gamma, but only in genotype 1. There was no significant relationship between PPARs mRNA levels and liver activity or fibrosis. Expression of the hepatitis C virus 3a core protein was associated with an increase in triglyceride accumulation and with a significant reduction of PPAR-gamma mRNA compared with hepatitis C virus 1b. CONCLUSIONS: The presence of steatosis and hepatitis C virus genotype 3 are both associated with a significant down-regulation of PPARs. These receptors, and also additional factors, seem to play a role in the pathogenesis of hepatitis C virus-associated steatosis.

Adult↗
PubMed2006

Steatosis in chronic hepatitis C: why does it really matter?

Hepatic steatosis is a common histological feature of chronic hepatitis C. Various factors are associated with hepatic steatosis, including obesity, high alcohol consumption, diabetes type II, and hyperlipidaemia. These factors may contribute to steatosis in patients with chronic hepatitis C. In humans, hepatitis C virus (HCV) genotype 3 is more commonly associated with steatosis. In vitro studies and the transgenic mouse model have suggested that the HCV core protein (genotype 1) can induce lipid accumulation within hepatocytes. However, what is the relevance of steatosis in chronic hepatitis C? It seems that in certain populations, steatosis may be associated with fibrosis progression and this may be genotype specific. The mechanisms underlying this association are unknown; neither is it clear whether this holds true for all patients or only a subgroup. Indeed, after antiviral treatment, virus related steatosis disappears whereas the host associated steatosis remains unaffected. This review describes and discusses the basic and clinical aspects of the relationship between steatosis and progression of fibrosis, and response to treatment in patients with chronic hepatitis C.

Animals↗
PubMed2005

[New aspect in the treatment of chronic hepatis B].

The pegylated interferon is now the first choice of treatment for patients without a counter-indication. The association of this treatment with lamivudine does not increase the effectiveness. For patients non-responders to the PEG-IFN or presenting counter-indications, the long-term administration of lamivudine is limited by the frequent appearance of mutations, so that escape from the treatment requires the use of other antivirals. Adefovir is currently the treatment of choice in the event of resistance to lamivudine. Its effectiveness is confirmed by many studies and the risk of emergence of resistance is very low. Entecavir is a selective inhibitor of polymerase HBV and shows a better efficacy than lamivudine. It is well tolerated and is associated only with a weak risk of resistance, even after a prolonged treatment.

Antiviral Agents↗
PubMed2005

Impact of liver steatosis on virological response in [corrected] Italian patients with chronic hepatitis C treated with peg-interferon alpha-2b plus ribavarin.

BACKGROUND: Whether liver steatosis affects sustained virological response in patients with chronic hepatitis C is still under discussion. AIM: To evaluate the impact of liver steatosis in patients treated (for chronic hepatitis C) with combination therapy. METHODS: We evaluated 97 (male/female 82/15, mean age 41.1 years) consecutive naive patients treated with pegylated interferon alpha-2b plus ribavirin. RESULTS: Prevalence and severity of liver steatosis were significantly associated with genotype 3a [grade 3-4 in 14 of 32 patients (44%) vs. 8 of 65 patients (12%) with other genotypes; P = 0.001], while steatosis grade 1 (<10% of hepatocytes affected) was more frequently associated with genotype 1a/1b [9/39 (23%) vs. 4/57 (7%); P = 0.02]. Overall, sustained virological response was 62.8%, and was statistically uninfluenced by the presence/absence of liver steatosis. On the contrary, the following variables were independently associated with sustained virological response at logistic regression analysis: genotype other than 1a/1b, positive association, (odds ratio 3.4, P < 0.04), and low-grade liver steatosis, negative association, (odds ratio 9.0, P = 0.009), whereas sustained virological response was unaffected by severe liver steatosis, which was mainly associated with genotypes 2 and 3 [steatosis grade 2, 18/29 (62%); grade 3, 10/12 (83%); grade 4, 7/10 (70%)]. CONCLUSIONS: Only low-grade liver steatosis negatively affects the outcome of combination therapy, with peginterferon alpha-2b plus ribavirin, while severe steatosis (which is virus-related in most cases) has no impact on virological response.

Adult↗
PubMed2004

[Management of hepatitis B].

Treatment of chronic hepatitis B needs to consider two aspects. First, a certain proportion of patients will spontaneously undergo a stable remission of the underlying liver disease, i.e. without therapeutic intervention, on occasion of the HBeAg --> anti-HBe seroconversion. Second, all drugs that have been used so far in the treatment of HBV have rarely resulted in the definitive eradication of the viral infection, i.e. a permanent disappearance of HBsAg with development of anti-HBs. Thus, the most reasonable, albeit surrogate endpoint of treatment is the acceleration towards HBeAg --> anti-HBe seroconversion and/or the stable suppression of HBV replication at levels below 500000 copies/ml, which is associated with disappearance of intrahepatic necrosis and inflammation and slowing down of the fibrosis progression. Two drugs are currently available--interferon-alpha and lamivudine--and a third antiviral compound (adefovir dipivoxil) will soon appear in the market. Advantages and disadvantages of different therapeutic options are discussed below.

Adenine↗
PubMed2004

Neurosurgical intervention in a haemophilic child with a subdural and intracerebral haematoma.

A case of a 3-year-old boy with severe haemophilia A who had a successful neurosurgical drainage of a combined spontaneous left temporal subdural and intra-parenchimal haematoma is reported. Surgical intervention was required because of clinical worsening during conservative treatment with dexamethasone and factor VIII (FVIII) replacement therapy. Continuous FVIII infusion was given before, during and after the procedure. There were no surgical complications and neurological examination remains intact. Neurosurgical interventions may be reserved for special, high-risk cases, as the one presented.

Child, Preschool↗
PubMed2004

Steatosis affects chronic hepatitis C progression in a genotype specific way.

BACKGROUND AND AIMS: Liver steatosis is frequent in chronic hepatitis C, particularly in patients infected with hepatitis C virus (HCV) genotype 3. The aim of this study was to determine the relationship between steatosis and fibrosis in chronic hepatitis C as a function of viral genotype. METHODS: A multivariable logistic regression analysis was carried out in 755 chronic hepatitis C patients (mean body mass index (BMI) 24.11 kg/m(2); 178 with genotype 3), consecutively admitted to three referral hospitals. Liver histology showed steatosis in 315 and fibrosis in 605 patients, of whom 187 had cirrhosis (78 compensated and 109 decompensated). RESULTS: Steatosis was independently associated with fibrosis (p<0.001), genotype 3 (p<0.001), BMI (p<0.001), ongoing alcohol abuse (p<0.001), and age (p = 0.001). Fibrosis was associated with the Metavir activity score (p<0.001), age (p<0.001), steatosis (p = 0.001), past alcohol abuse for >5 years (p = 0.015), and BMI (p = 0.034). When regression analysis was repeated on patients divided according to viral genotype (that is, 3 v non-3) to identify type specific risk factors, steatosis was associated with ongoing alcohol abuse (p<0.001) and age (p = 0.01) only in non-3 genotype infected patients and with Metavir activity (p = 0.044) only in genotype 3 infected patients. Similarly, fibrosis was associated with steatosis only in genotype 3 infected individuals (p = 0.018), and with past alcohol abuse (p = 0.003) and (marginally) diabetes (p = 0.078) only in non-3 genotype infected patients. CONCLUSIONS: Steatosis influences chronic hepatitis C progression in a genotype specific way. Patients infected with genotype 3 and histologically confirmed steatosis should not be deferred from effective antiviral therapy.

Adult↗
PubMed2002

Galectin-3, a marker of well-differentiated thyroid carcinoma, is expressed in thyroid nodules with cytological atypia.

AIMS: The distribution of galectin-3, a widely recognized marker of well-differentiated thyroid carcinoma, was investigated in 95 thyroid lesions including nodules with foci of cytoarchitectural atypia. METHODS AND RESULTS: Twenty-eight papillary carcinomas, five follicular carcinomas, one Hurthle cell carcinoma, three poorly differentiated carcinomas, one anaplastic carcinoma, 25 nodular hyperplasias and 27 follicular adenomas, including nodules with atypical features, three neoplasms of undetermined malignant potential and two thyroiditis cases were examined. By immunohistochemistry, galectin-3 was consistently found in carcinomas; otherwise benign nodules exhibited galectin-3-positive clusters of cells with poorly developed features of differentiated carcinoma (mainly of papillary type) such as nuclear chromatin clearing, nuclear clefting, pseudoinclusions, which, in each case, were not histologically sufficient to warrant a definitive diagnosis of malignancy. In other nodules galectin-3 staining was negative. The latter were either clearly benign or showed constantly a minor degree of chromatin clearing and of other atypical features when compared with galectin-3-positive cases. CONCLUSIONS: Galectin-3, a reliable marker of differentiated thyroid carcinoma as confirmed in our series of malignant neoplasms, appears expressed in nodules with an overall benign appearance but with focal areas suspicious for malignancy. The significance of such findings needs to be further investigated.

Antigens, Differentiation↗
PubMed2001

Nosocomial outbreak of multiple bloodborne viral infections.

In resource-limited countries, nosocomial transmission of bloodborne pathogens is a major public health concern. After a major outbreak of human immunodeficiency virus (HIV) infection in approximately 400 children in 1998 in Libya, we tested HIV, hepatitis C virus (HCV), and hepatitis B virus (HBV) markers in 148 children and collected epidemiological data in a subgroup of 37 children and 46 parents. HIV infection was detected in all children but one, with HCV or HBV coinfection in 47% and 33%, respectively. Vertical transmission was ruled out by analysis of parents' serology. The children visited the same hospital 1-6 times; at each visit, invasive procedures with potential blood transmission of virus were performed. HIV and HCV genotypic analyses identified a HIV monophyletic group, whereas 4 clusters of HCV sequences were identified. To our knowledge, this is the largest documented outbreak of nosocomial HIV transmission.

Adult↗
PubMed2001

Detection of the negative-strand hepatitis C virus RNA in tissues: implications for pathogenesis.

The replication of hepatitis C virus (HCV) RNA is believed to occur via its transcription into a complementary, genomic-length RNA, the so-called negative-strand HCV RNA. This is based on the comparison with the replication of other members of the Flaviviridae family. Detection of the negative-strand HCV RNA in human tissues by semi-quantitative, strand-specific RT-PCR has contributed to the understanding of the HCV cell tropism and of the pathogenesis of HCV-associated disease manifestations. In particular, it was shown that the levels of intrahepatic HCV RNA are not correlated to the extent of the necroinflammation, but that a significant correlation was found with the liver steatosis. These results suggest that most liver disease associated with HCV infection is mediated by the host immune response. However, in some patients, most notably those infected with HCV genotype 3, HCV may cause a cytopathic effect, consisting in the lipid accumulation within hepatocytes.

Carcinoma, Hepatocellular↗