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F Negro

Publications and source records attributed to F Negro.

At least 37 records · Page 2Linked to original sources
PubMed2001

Prevention of hepatitis B virus recurrence after liver transplantation in cirrhotic patients treated with lamivudine and passive immunoprophylaxis.

BACKGROUND/AIMS: Treatment with hepatitis B virus immune globulins (HBIG) or lamivudine has reduced the rate of hepatitis B recurrence after liver transplantation to approximately 50%. METHODS: To further decrease hepatitis B recurrence, 33 hepatitis B virus (HBV)-related cirrhotic patients were treated with lamivudine before liver transplantation and with lamivudine together with low-dose HBIG (46 500 IU the first month followed by 5,000 lU/monthly) after surgery. RESULTS: While on lamivudine, serum HBV DNA level decreased significantly in all patients and in 11 (33%) the Child-Pugh score improved. Twenty-six patients were transplanted. Among the 25 who survived for longer than 12 months, only one (4%) experienced a hepatitis B recurrence over an average follow-up of 31 months, a rate significantly lower (P = 0.0002) than the 50% recurrence rate among a historical control group of 12 patients. However, low-level HBV replication was detected sporadically throughout the follow-up in 64% of patients. CONCLUSIONS: Over the medium-term, combined prophylaxis with lamivudine and HBIG significantly decreases the risk of hepatitis B recurrence after liver transplantation. Though low-level HBV infection recurred in two thirds of patients, the pathogenic expression of HBV was prevented.

Adult↗
PubMed2001

Acute valproate-associated microvesicular steatosis: could the [13C]methionine breath test be useful to assess liver mitochondrial function?

Microvesicular steatosis is a potentially severe manifestation of valproic acid hepatotoxicity due to an acquired impairment of mitochondrial function. Tests currently used to investigate mitochondrial fonction are cumbersome and cannot be used routinely. We report on a noninvasive breath test using [13C]methionine for estimation of mitochondrial function in a case of pure severe valproic acid overdose-induced microvesicular changes. The initially abnormal breath test improved together with the recovery of liver failure. In conclusion, this observation suggests that the [13C]methionine breath test may provide a noninvasive estimate of hepatic mitochondrial function in vivo.

Adult↗
PubMed2001

Liver steatosis in chronic hepatitis C: a morphological sign suggesting infection with HCV genotype 3.

AIMS: To identify factors associated with liver steatosis in chronic hepatitis C. METHODS AND RESULTS: Occurrence and severity of liver steatosis in 254 chronic hepatitis C patients were compared with presence of alcohol abuse, body mass index (BMI) >26, history of intravenous drug addiction and hepatitis C virus (HCV) genotype. Steatosis was found in 109 (43%) patients. The occurrence of steatosis was significantly associated with ongoing alcohol abuse (P=0.03) or HCV genotype 3 (P= 0.003), but not with BMI >26. A moderate to severe steatosis was present in 60% of patients infected with HCV genotype 3, irrespective of the presence of alcohol abuse, BMI >26 or history of intravenous drug addiction. Using a multivariable stepwise logistic regression analysis, infection with genotype 3 had an odds ratio (OR) of 10 (95% confidence interval (CI)=4.56-22) for a liver steatosis, whereas the presence of a cirrhosis at histology had an OR=0.256 (95% CI=0.07-0.92). CONCLUSIONS: A moderate to severe degree of steatosis of the liver is a morphological sign suggestive of infection with HCV genotype 3, independent of other risk factors of a fatty liver, but it may disappear at late stages of the disease.

Adult↗
PubMed2000

[Hepatitis C virus infection. Overview. SEVHEP (Swiss Experts on Viral Hepatitis)].

The hepatitis C virus (HCV) shows a pronounced polymorphism with six genotypes and many subtypes. The virus is generally not cytopathogenic. Immunological defence mechanisms are probably essential for the pathogenecity. An acute hepatitis is relatively rare; the infection becomes chronic in over 70%. The data on the occurrence of chronic hepatitis, cirrhosis and hepatocellular carcinoma are conflicting. The age at infection, the gender, coinfections with HBV and HIV and alcohol consumption play a role. The basis of diagnostics is the anti-HCV screening test with clear indications for the measurement of the genotype and of HCV-RNA. The combination of interferon-alpha and Ribavirin is the therapy of choice with improved success. HCV is most often transmitted through contaminated syringes and needles, i.v. drug users having the greatest incidence and prevalence. Vertical and sexual HCV transmission is relatively rare. It is estimated that the HCV prevalence in Switzerland is 0.75-1%, afflicting 50,000-70,000 individuals. Over the next years the number of HCV associated decompensated liver cirrhosis, liver transplantation and death will grow. Efforts of collaboration in the field are undertaken including the establishment of a Swiss HCV cohort study.

Drug Therapy, Combination↗
PubMed2000

Thyroglobulin mRNA expression helps to distinguish anaplastic carcinoma from angiosarcoma of the thyroid.

The existence of angiosarcoma (AS) of the thyroid has been a matter of debate for many years, because some authors believe that most if not all ASs are in fact "angiomatoid" anaplastic carcinomas (ACs). Immunohistochemistry alone was not successful in solving the problem, since cytokeratin expression is a known occurrence in AS. Therefore, we wanted to compare nine cases of AS with ten cases of AC, assessing whether thyroglobulin (TG) mRNA was still transcribed in undifferentiated tumors and could be helpful to distinguish AC from AS. The cases were analyzed for TG mRNA expression by means of radioactive in situ hybridization. The silver grains were counted using an automated device, and their amount was compared with that of stroma, background, and peritumoral thyroid. A weak signal was present in all AC but not in AS (mean counts 35.7 and 9.6 arbitrary units, respectively: P<0.01). In two cases of AC, residual areas of poorly differentiated insular carcinoma had a strong signal (similar to that of peritumoral thyroid). These findings further confirm that AC and AS of the thyroid are unrelated malignant tumors.

Adult↗
PubMed2000

Hepatocyte steatosis is a cytopathic effect of hepatitis C virus genotype 3.

BACKGROUND/AIMS: Patients infected with the hepatitis C virus (HCV) often have liver steatosis, suggesting the possibility of a viral cytopathic effect. The aim of this study was to correlate the occurrence and severity of liver steatosis with HCV RNA type, level and sequence of the core-encoding region. METHODS: We scored the liver steatosis in 101 HCV-infected individuals carefully selected to exclude other risk factors of a fatty liver. Results were compared with HCV RNA genotype and level in serum and liver. In selected patients, we assessed the effect of antiviral therapy on steatosis and the relationship between nucleocapsid sequence heterogeneity and fat infiltration. RESULTS: Steatosis was found in 41 (40.6%) patients, irrespective of sex, age or route of infection. HCV genotype 3 was associated with higher steatosis scores than other genotypes. A significant correlation between steatosis score and titer of intrahepatic HCV RNA was found in patients infected with genotype 3, but not in those infected with genotype 1. In selected patients, response to alpha-interferon was associated with the disappearance of steatosis. Analysis of the nucleocapsid of 14 HCV isolates failed to identify a sequence specifically associated with the development of steatosis. CONCLUSIONS: We provide virological and clinical evidence that the steatosis of the liver is the morphological expression of a viral cytopathic effect in patients infected with HCV genotype 3. At variance with published evidence from experimental models, the HCV nucleocapsid protein does not seem to fully explain the lipid accumulation in these patients.

Adult↗
PubMed2000

A novel hepatitis C virus (HCV) subtype from Somalia and its classification into HCV clade 3.

Hepatitis C virus (HCV) sequences from throughout the world have been grouped into six clades, based on recently proposed criteria. Here, the partial sequences and clade assignment are reported for three HCV isolates from chronic hepatitis C patients from Somalia, for whom conventional assays failed to identify the genotype. Phylogenetic analysis of the sequences of the core, envelope 1 and part of the non- structural 5b regions suggests that all three isolates belong to a distinct HCV genetic group, tentatively classified as subtype 3h. This novel HCV subtype shows the highest sequence similarity with HCV isolates from Indonesia. Despite the fact that these patients were infected with HCV clade 3, none of them responded to standard interferon treatment.

Adult↗
PubMed2000

Hemochromatosis gene mutations in chronic hepatitis C patients with and without liver siderosis.

Chronic hepatitis C is often associated with liver iron overload, which may affect the long-term prognosis and the response to antiviral treatment. The occurrence of hemochromatosis (HFE) mutations were studied to determine whether may contribute to the liver iron overload of chronic hepatitis C patients. The prevalence of two HFE mutations (C282Y and H63D) in 120 chronic hepatitis C patients was determined and the findings were correlated with clinical, histological and virological features. Hepatic iron was determined semiquantitatively by a histochemical hepatic iron index, defined as the ratio of a histochemical staining score to the patient's age, after correction for heterogeneous lobular iron distribution. Serum hepatitis C virus (HCV) RNA was measured by bDNA assay and typed by restriction fragment length polymorphism. Liver HCV RNA was measured by a semi-quantitative strand-specific reverse transcription-polymerase chain reaction (RT-PCR). Excess liver iron was stained in the liver of 36 patients (30%). Siderotic patients had the same geographic origin, serum and liver HCV RNA levels and H63D and C282Y mutations frequency as non-siderotic patients. However, siderotic patients were older (P = 0.015), more frequently males (P = 0.02), less frequently infected with HCV genotype 3 (P = 0.037) and had a higher liver fibrosis score (P = 0.008). The liver iron content did not correlate with the serum or liver HCV RNA titers. Ten of the 36 patients with liver siderosis had neither a history of excess alcohol intake, multiple transfusions, or HFE mutations. In conclusion, the pathogenesis of the liver iron overload in chronic hepatitis C patients cannot be fully explained by the occurrence of HFE mutations. The exact mechanism of iron accumulation in these patients therefore remains unexplained.

Adult↗
PubMed2000

Papillary carcinoma in amyloid goitre.

Amyloid goitre is a rare lesion characterized by a diffuse and bilateral enlargement of the thyroid gland due to amyloid deposition. It is uncommon that a massive and widespread amount of adipose tissue deposition is found within these lesions and only in exceptional cases a differentiated carcinoma can develop. We describe the third example of thyroid carcinoma, arising in a 74-year old female who had also massive adipose thyroidal metaplasia, within amyloid goitre. The Congo red stain confirmed the diagnosis of amyloid goitre. Immunohistochemistry showed reactivity with MoAb against amyloid fibril protein A. The patient suffered from renal failure of undetermined aetiology for three years, but neither systemic amyloidosis nor risk factors for its development were found. It is important to correctly diagnose amyloid goitre both to rule out the presence of a differentiated thyroidal carcinoma and to search for amyloid infiltration in other organs in view of an early appropriate therapy.

Aged↗
PubMed1999

Lack of hepatitis C virus replication intermediate RNA in diseased skin tissue of chronic hepatitis C patients.

The extent of extrahepatic hepatitis C virus (HCV) replication seems to be low-level and confined to cells of hematopoietic lineage. However, given the spectrum of extrahepatic manifestations associated with HCV, several tissues other than the liver have been suggested as targets of HCV replication and damage. The presence and level of HCV RNA were examined in 19 skin tissue samples from patients chronically infected with HCV and referred for lichen ruber planus (n = 11) or cutaneous vasculitis associated with mixed cryoglobulinemia (n = 8). Serum HCV RNA was quantitated and genotyped by assays that are available commercially. Tissue HCV RNA of genomic- and minus-strand polarity was titrated by a strand-specific semiquantitative RT-PCR. Low titers of genomic-strand HCV RNA were found in three skin specimens from patients with cutaneous vasculitis due to mixed cryoglobulinemia, but in none with lichen ruber planus. The replication intermediate HCV RNA was not detected in any of the skin tissues examined, independent of the serum HCV RNA level or genotype. It is concluded that the occurrence of cutaneous vasculitis and lichen ruber planus in chronic hepatitis C patients is unlikely to be due to HCV replication in the skin.

Adult↗
PubMed1999

Detection of genomic- and minus-strand of hepatitis C virus RNA in the liver of chronic hepatitis C patients by strand-specific semiquantitative reverse-transcriptase polymerase chain reaction.

Studies aimed at correlating the intrahepatic hepatitis C virus (HCV)-RNA level and anatomo-clinical features have been difficult because of sensitivity and specificity shortcomings of available techniques. We titered the genomic- and minus-strand HCV RNAs by a strand-specific, semiquantitative, genotype-independent reverse-transcriptase polymerase chain reaction (RT-PCR) in the liver tissue of 61 patients with chronic hepatitis C. Findings were correlated with the levels of HCV RNA in the serum, the HCV genotype, the expression of intrahepatic HCV antigens, the histological activity (using separate scores for the lobular and the portal/periportal necroinflammatory activity and for the fibrosis), and the response to interferon alfa (IFN-alpha) treatment. Genomic- and minus-strand HCV RNA were detected in 59 and 57 liver specimens, respectively. The HCV-RNA level in the serum correlated with the genomic-strand, but not with the minus-strand, HCV-RNA titer in the liver. No correlations were found between either strand of the intrahepatic HCV RNA and the level of expression of HCV antigens in the liver, or with the grading/staging of the underlying liver disease. The response to IFN-alpha treatment could be predicted by the serum HCV-RNA level and genotype, but not by the intrahepatic level of genomic- or minus-strand HCV RNA. These results suggest that, although the detection of the minus-strand HCV RNA reliably identifies the presence of replicating HCV in its target organ, the quantitative measurement of viremia remains the clinically meaningful "golden standard" for assessing the level of HCV replication.

Adult↗
PubMed1999

Interferon alfa-2b alone or in combination with ketoprofen as treatment for interferon-naive chronic hepatitis C patients.

BACKGROUND: Non-steroidal anti-inflammatory drugs may amplify the anti-viral effect of alpha-interferon in vitro but in vivo data are still controversial. AIM: : To test the hypothesis that ketoprofen may increase the rate of response to alpha-interferon of chronic hepatitis C patients. METHODS: Fifty patients with chronic hepatitis C who had never received alpha-interferon were randomly assigned to receive 3-8 MU of alpha2b-interferon, three times weekly for 6 months, alone or in association with ketoprofen at a dose of 200 mg/day five times weekly. The virological response to treatment (undetectable HCV RNA in serum) was evaluated after 3 months and at the end of treatment, and 6 and 12 months after therapy withdrawal. RESULTS: One patient under combination therapy stopped the ketoprofen for persisting epigastric pain. Complete response under treatment was observed in 15 out of 24 (62.5%) patients receiving alpha2b-interferon alone and in 14 out of 26 (53.8%) patients under combination therapy (P=N.S.). One year after the end of treatment, a sustained response was seen in 4 out of 24 (16.2%) patients treated with alpha2b-interferon and in 5 out of 26 (19.2%) patients having received the combination (P=N.S.). CONCLUSION: Administration of ketoprofen does not increase either the primary or the sustained response to alpha2b-interferon therapy of interferon-naive chronic hepatitis C patients.

Adult↗
PubMed1999

Primary hepatic diffuse large B-cell lymphoma in a patient with chronic hepatitis C.

Epidemiological and experimental data suggest that the hepatitis C virus infection might be associated with the development of distinct types of non-Hodgkin's lymphomas. Here, we report a case of a patient with chronic hepatitis C and type II mixed cryoglobulinemia, who developed a primary hepatic non-Hodgkin's B-cell lymphoma. A diffuse, large B-cell lymphoma was diagnosed based on morphological, immunophenotypical and molecular genetic findings. Hepatitis C virus replication, as evaluated by strand-specific reverse transcriptase-polymerase chain reaction, was detected in the nonneoplastic liver, but not in the lymphomatous tissue. High grade non-Hodgkin's lymphomas, although rare complications, have to be considered as part of the spectrum of hepatitis C virus-related hepatic lesions.

Cryoglobulinemia↗