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C Brechot

Publications and source records attributed to C Brechot.

At least 37 records · Page 2Linked to original sources
PubMed1998

[Prevalence and genotypes of hepatitis C virus in blood donors and in patients with chronic liver disease and hepatocarcinoma in a Chilean population].

BACKGROUND: The impact of hepatitis C virus infection in Chile has not been well established. AIM: To assess hepatitis C virus infection in normal Chileans and in patients with liver disease. SUBJECTS AND METHODS: Antibodies against hepatitis C virus were investigated in 21,000 blood donors, 133 patients with non alcoholic chronic liver disease and in 50 patients with hepatocarcinoma. Viral RNA was studied by polymerase chain reaction in all positive blood donors, in 51 patients with chronic liver disease and in all patients with hepatocarcinoma. Hepatitis C virus genotype was established using restriction fragment length polymorphism in 118 RNA positive samples. RESULTS: In blood donors, a 0.3% prevalence of positive antibodies was found. The figure for chronic liver disease was 53% and for hepatocarcinoma, 48%. Viral RNA was detected in 100% of patients with chronic liver disease and hepatocarcinoma and in 68% of blood donors with positive antibodies. Genotype 1b was identified in all infected patients with hepatocarcinoma, in 86% of patients with chronic liver disease and in 46% of blood donors. CONCLUSIONS: Hepatitis C virus infection is an important etiologic agent for chronic liver disease in Chile. The predominance of genotype 1b among patients with the most severe form of liver disease is in agreement with observations made abroad.

Adult↗
PubMed1997

Hepatitis C virus genome complexity correlates with response to interferon therapy: a study in French patients with chronic hepatitis C.

Recent studies performed in Japan have suggested that hepatitis C virus (HCV) genome heterogeneity might be taken as a predictive virological parameter of response to interferon alfa (IFN-alpha) treatment. However, there is presently no information on the impact of this virological parameter in patients from Western countries infected by different HCV genotypes. We have investigated this issue by using amplification of HCV E2 hypervariable region 1, followed by single-strand conformation polymorphism assay (PCR-SSCP). We have studied 95 French patients infected with various genotypes and treated with IFN-alpha-2b. We analyzed the impact of the following parameters by univariate and multivariate analyses: HCV heterogeneity, HCV genotype, viral load, and liver histology in response to therapy. Age >40 years (P < .01), viral load >35 x 10(5) Eq/mL (P < .01), genotype 1 (P < .01), and a number of SSCP bands >3 (P < .001) were significantly associated with nonresponse or relapse; cirrhosis was associated with nonresponse. In multivariate analysis, three variables were independently associated with the absence of long-term response: SSCP bands >3, genotype 1, and viral load >35 x 10(5) with odds ratios of 19, 7.5, and 11.8, respectively. Our data establish the major importance of HCV genome heterogeneity in patients infected with both HCV types associated with low (genotype 1b) or high (genotype 3a) response to IFN-alpha.

Adult↗
PubMed1996

The long-term virologic and pathologic impact of renal transplantation on chronic hepatitis B virus infection.

In an attempt to evaluate the long-term reciprocal impact of renal transplantation on hepatitis B virus infection, we analyzed the clinical, virologic, and pathologic features of 151 HBsAg-positive kidney transplant recipients. The spontaneous disappearance rates of HBsAg, HBeAg, and HBV DNA during a median follow-up of 125 months (range 1 to 320) were 3, 30.6, and 3%, respectively, figures lower than in the general population. A high rate of persistent viral replication (50%) and reactivation (30%) was noted. Noteworthy was the high frequency of histologic deterioration (85.3%), accompanied by cirrhosis in 28% and by hepatocellular carcinoma in 23% of the patients with cirrhosis. Co-infection by hepatitis C and B viruses was significantly associated with histologic worsening. Liver disease was the leading cause of death (36.6%), especially in patients with cirrhosis. Despite persistent viral replication, histopathologic deterioration, and liver-related overmortality, there were paradoxically no significant differences in the survival of these 151 HBsAg-positive compared with 1247 HBsAg-negative kidney recipients--however, allograft actuarial survival was better in the former than in the latter group (P=0.0006). Chronic hepatitis B infection is not a contraindication to renal transplantation in the absence of cirrhosis. The presence of cirrhosis should lead either to dialysis continuation or to a combined liver/kidney transplantation, in the absence of viral replication.

Adult↗
PubMed1996

Azathioprine hepatitis in kidney transplant recipients. A predisposing role of chronic viral hepatitis.

Influence of viral liver diseases on the occurrence of azathioprine hepatitis was evaluated in 21 kidney transplant recipients. Diagnosis of azathioprine hepatitis was always based on jaundice, which disappeared after azathioprine withdrawal in 18 patients and after azathioprine dose reduction in 3 patients. Histopathological diagnosis of azathioprine toxicity was ascertained in 14 patients. Rechallenge with azathioprine performed in 4 patients, within 2-4 months after the first jaundice episode, resulted in relapse of jaundice in all cases. Viral hepatitis B virus and hepatitis C markers were present in all 20 tested patients (serum hepatitis B surface antigen in 6 patients and anti-HCV antibodies in 17 patients). Biopsy-proven chronic hepatitis was observed in 18 patients, including 14 chronic active hepatitis, 3 chronic persistent hepatitis and cirrhosis in 1. In kidney transplant recipients, azathioprine hepatitis seems to be facilitated or induced by hepatitis B virus or hepatitis C virus chronic hepatitis. Azathioprine reduction or withdrawal should therefore be combined with the diagnostic evaluation and the treatment of viral liver diseases.

Adult↗
PubMed1996

Liver hepatocyte growth factor does not always correlate with hepatocellular proliferation in human liver lesions: its specific receptor c-met does.

Increased levels of expression of hepatocyte growth factor (HGF) and its specific receptor c-met have been shown in the liver of several benign and malignant pathologies, both in experimental models and humans. We investigated by immunohistochemistry the presence of both HGF and c-met protoocogene product (c-met pp) in 20 hepatocellular carcinomas (HCCs), 5 focal nodular hyperplasias (FNHs), 4 cases of fulminant hepatitis (FH), and 1 case of regenerated liver. The c-met protooncogene product was expressed in all cases with marked overexpression in the HCCs and in ductular metaplasia. HGF was detected in the Ito cells of all cases and in neoplastic hepatocytes of 9 of 20 HCCs (45%). The proliferative index of each lesion was evaluated by means of the polyclonal antibody anti-cyclin A. When the level of expression of HGF and c-met protooncogene product with the percentage of cyclin A+ nuclei were compared, the closest relationship was between c-met protooncogene product and cyclin A+ nuclei were compared, the closest relationship was between c-met protooncogene product and cyclin A. In 11 of 20 HCCs (55%), there wa no correlation between HGF positivity and cyclin A. This seems to suggest that, independently of the levels of native liver HGF, c-met protooncogene product is the most active modulator of liver cell proliferation.

Biomarkers↗
PubMed1996

Hepatitis B and C viruses and primary liver cancer.

The data presented indicate that viral agents (namely, HBV and HCV) are major environmental aetiological factors for human primary liver cancer. It is important to elucidate the molecular mechanisms further because HCC is one of the few examples of virus-related human cancers. In addition, the available evidence points to the possibility of at least partial prevention of the tumour by large-scale vaccination.

Carcinoma, Hepatocellular↗
PubMed1996

In vivo selection of a hepatitis B virus mutant with abnormal viral protein expression.

We have investigated the molecular basis for the in vivo selective advantage of a hepatitis B virus (HBV) mutant. We have determined the complete nucleotide sequences of the major HBV forms identified at the beginning (B1-83) and end (B1-89) of a 6 year follow-up of a chronically infected patient. The B1-89 sequence showed marked nucleotide rearrangements (a nucleotide divergence of 11.3 % compared with the adw2 subtype), but sequence comparison showed that both viral molecules were of common origin (62/138 mutations were found on both molecules, compared to adw2). In vitro transfection of Huh7 cells showed important modifications in B1-89 viral protein expression. We observed a decrease in B1-89 envelope protein expression associated with a modification of the migration pattern of the large envelope protein. For the B1-89 capsid protein, an insertion of 36 nucleotides at the 5' end of the C gene resulted in increased expression of a core-specific protein of abnormal size (24 kDa versus 22 kDa). Finally, our data also suggest an increase in the transcomplementation efficiency of the mutated B1-89 polymerase protein. Thus, we were able to demonstrate distinct intrinsic properties of HBV DNA molecules isolated from a chronic carrier with virus multiplication at different times during infection. Modifications of viral protein expression in the mutated form illustrate strategies used by the virus to prevent clearance and to contribute to viral persistence.

Amino Acid Sequence↗
PubMed1996

HIP/PAP is an adhesive protein expressed in hepatocarcinoma, normal Paneth, and pancreatic cells.

Human hepatocarcinoma-intestine-pancreas (HIP) cDNA, isolated from a hepatocellular carcinoma, encodes a C-type lectin. According to published cDNA sequences, HIP protein is identical to human pancreatitis-associated protein (PAP). In these sequences, a putative signal peptide and the carbohydrate recognition domain (CRD) can be recognized. In the present study, we established transgenic mice to drive the production of soluble recombinant HIP/PAP protein in the milk of lactating animals; using this model, we showed that HIP/PAP protein was secreted after suitable cleavage of the potential signal peptide. Moreover, we also produced HIP/PAP protein by Escherichia coli cultures performed to generate specific antibodies. These antibodies enabled the detection of HIP/PAP protein in normal intestine and pancreas (both in endocrine and exocrine cells), e.g., intestinal neuroendocrine and Paneth cells, pancreatic islets of Langerhans, and acinar cells. HIP/PAP protein was also identified in the cytoplasm of tumoral hepatocytes but not in nontumoral hepatocytes. Finally, HIP/PAP protein activity was tested and we showed that HIP/PAP induced the adhesion of rat hepatocytes and bound strongly to extracellular matrix proteins (laminin-1, fibronectin), less strongly to type I and IV collagen, and not at all to heparan sulfate proteoglycan. In conclusion, these results showed that HIP/PAP protein was matured on secretion. We also demonstrated that HIP/PAP protein was specifically expressed in hepatocarcinoma cells and interacted with rat hepatocytes and the extracellular matrix. Taken overall, these results suggest that HIP/PAP protein may be of potential importance to liver cell differentiation/proliferation.

Acute-Phase Proteins↗
PubMed1996

In vivo cell lineage analysis during chemical hepatocarcinogenesis using retroviral-mediated gene transfer.

We have studied the proliferation of cells in two models of chemical hepatocarcinogenesis. The cells were genetically labeled in vivo using retrovirally mediated transfer of the Escherichia coli beta-galactosidase marker gene coupled to a nuclear localization signal (nls-lacZ gene). In the first carcinogenic model, rats were fed a choline-deficient diet containing 2-acetylaminofluorene, and their livers were perfused with recombinant retrovirus at the onset of oval cell proliferation. The second model was based on the administration of diethylnitrosamine coupled with a partial hepatectomy and is thought to induce cancer with no involvement of oval cells. Analysis of beta-galactosidase expression in the liver at various times after gene transfer revealed the presence of large clusters of positive cells in both models. Moreover, the beta-galactosidase-positive cells displayed morphologic, antigenic, and enzymatic profiles consistent with a hepatocyte phenotype. Our results, therefore, provide evidence for a strikingly similar clonal proliferation of apparently normal hepatocytes during the course of 2-acetylaminofluorene- as well as diethylnitrosamine-induced liver carcinogenesis.

2-Acetylaminofluorene↗
PubMed1996

Interactions between alcohol and hepatitis viruses in the liver.

There is a high frequency of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections among individuals with alcoholic liver disease (ALD) and alcohol-associated hepatocellular carcinoma (HCC), suggesting that these viruses are implicated in the pathogenesis of these diseases. Alcohol may act synergistically by promoting the development and progression of liver disease. The interactions of alcohol with infected hepatocytes and with antiviral immunity may result in altered patterns of virus gene expression and replication, making diagnosis difficult in some cases of ALD and HCC. The potential association of ALD and alcoholic HCC with serologically negative virus variants raises major difficulties in the epidemiologic assessment of cause and effect, providing major challenges for the future.

Animals↗
PubMed1996

Alpha-interferon for chronic active hepatitis B in human immunodeficiency virus-infected patients.

OBJECTIVES: A pilot study was conducted to evaluate the efficiency of alpha-interferon treatment in chronic active hepatitis B in anti-HIV-positive patients. METHODS: Twenty-five patients with chronic active hepatitis (23 men and 2 women, mean age: 33 years) were included in the study. Viral infections were acquired by intravenous drug addiction in 2, homosexual relations in 22, and multiple heterosexual contacts in one. The mean CD4 cell count was 480 +/- 234/mL, 7 patients had p24 antigenemia, but none belonged to class C of the CDC classification. All patients were serum HBs Ag and HBV DNA-positive, and delta antigen and antibody negative. Patients received a 6-month course of alpha-interferon 2a, 6 MU subcutaneously three times per week. The mean follow-up after treatment was 15 months. Eighteen patients with serum anti-HIV antibodies, HBsAg and HBV DNA-positive, and chronic active hepatitis, who were not treated with interferon, were included as controls (mean follow-up: 29 months). RESULTS: Nine of the 25 patients (36%) lost serum HBV DNA (1, 2, 4, 6, and 8 months after the beginning of treatment in 1, 4, 1, 2 and 1 cases, respectively), and were considered responders. Only one of the responders developed serum anti-HBe during follow-up, despite the disappearance of HBe Ag in 2 and of HBs Ag in one. Loss of HBV DNA was not clearly associated with the immune status, since 3 of the 9 responders had p24 antigenemia and the 9 responders had a lower mean CD4 count (283 +/- 246/mm3) than non responders (454 +/- 437/mm3, NS). Three of the 18 patients (16.7%) in the control group had spontaneous loss of serum HBV DNA during follow-up. Thus, there was a 2.15-fold increase in HBV DNA loss in the anti-HIV-positive patients who received alpha-interferon, compared to those who did not. CONCLUSION: In HIV-positive patients treated with alpha-interferon, the rate of HBV DNA loss was not clearly different from that reported in immunocompetent patients. As severe HBV-related liver disease has previously been described in anti-HIV positive patients, at least in drug users, these results suggest that this treatment may be proposed whatever the immune status, at least in the absence of AIDS.

Adult↗
PubMed1995

[In situ hybridization for the detection of hepatitis C virus RNA in mononuclear cells of peripheral blood from infected patients].

In situ hybridization was used to investigate hepatitis C virus infection in peripheral blood mononuclear cells in 11 patients with chronic hepatitis. Using 35S labeled HCV-RNA probe, HCV-RNA positive and negative strands were observed in unstimulated cells of 3/11 patients; all 3 being treated with immunosuppressive drugs after orthotopic liver transplantation. HCV-RNA sequences were also identified in mononuclear cells obtained from 3 patients without immunosuppression, after stimulation of the cells with either phytohemagglutinin or pokeweed mitogen. In contrast, HCV-RNA was not found in 5 cases, where there was no liver transplantation or cell stimulation by mitogens. These results definitely assess infection of mononuclear cells by HCV. In addition, they demonstrate that mitogenic stimulation of infected cells increases HCV-RNA replication.

Adult↗
PubMed1995

The changing relative prevalence of hepatitis C virus genotypes: evidence in hemodialyzed patients and kidney recipients.

BACKGROUND/AIMS: Hepatitis C virus (HCV) infection by the genotype 1b is significantly associated with a lower rate of response to interferon alfa and with severe liver disease (cirrhosis and hepatocellular carcinoma). This may reflect different intrinsic properties of this genotype 1b and/or chronological differences in the epidemiology of HCV genotypes. To address the issue of variations in genotypes prevalence, we studied in the present report the HCV genotypes of 60 hemodialyzed and kidney recipients according to the date of hemodialysis. METHODS: Anti-HCV antibodies were tested by a second-generation assay (enzyme-linked immunosorbent assay 2 and recombinant immunoblot assay 2). HCV RNA was detected by reverse-transcription polymerase chain reaction. Genotyping was performed by hybridization of type-specific probes to the amplified product from the 5' untranslated region. RESULTS: Genotype 1b accounted for more than two thirds of HCV infection in patients who underwent dialysis before 1977 but less than one third in those hemodialyzed after 1985. In contrast, other genotypes (3a, 4a, 5a) appeared in the 1980s. CONCLUSIONS: These data, obtained in an homogenous group of patients, show a changing pattern of HCV genotype prevalence over time and should be considered when discussing the potential clinical implications of HCV genetic variability.

Female↗