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Biomedical subjects

M Beaugrand

Publications and source records attributed to M Beaugrand.

At least 37 records · Page 2Linked to original sources
PubMed2000

Hepatitis C virus related cirrhosis: time to occurrence of hepatocellular carcinoma and death.

BACKGROUND: In patients with hepatitis C virus (HCV) infection and cirrhosis, long term outcome and the incidence of hepatocellular carcinoma (HCC) are still debated. DESIGN: From January 1987 to January 1997, 416 patients (240 male, median age 57 years) with uncomplicated Child-Pugh A HCV related cirrhosis were followed in two Paris area centres from diagnosis of cirrhosis until death or reference date (1 June 1998). The analysis used a three state disability model generalising the Cox model. RESULTS: Of the 416 patients, 60 developed HCC with a five year rate of 13.4% (95% confidence interval (CI) 9.0-17.8%) and 83 died (including 34 with HCC), with a five year death rate of 15.3% (95% CI 12.6-18.0%). By multivariable analysis, time to HCC relied on age (hazard ratio (HR) 1.05 per year; p=0.0005), male sex (HR 2.13; p=0.01), oesophageal varices (HR 2.36; p= 0.008), decreased platelet count (HR 0.99; p=0. 03), and bilirubin level (HR 1.01; p=0.003), while death after HCC was mainly related to tobacco consumption (HR 1.04; p=0.0006). In contrast, death free of HCC was dependent on age (HR 1.04; p=0.01), oesophageal varices (HR 2.75; p=0.001), low platelet count (HR 0.99; p=0.006), and albumin level (HR 0.90; p=0.0001). CONCLUSION: The incidence of HCC and mortality should be higher in these patients than previously stated, and prognostic factors of HCC and death are closely related age and symptoms of portal hypertension.

Biomarkers, Tumor↗
PubMed2000

[Prevalence and prognostic value of serum anti-p53 antibodies in hepatocellular carcinoma. A study of 159 patients].

OBJECTIVES: Genetic alterations in the p53 protein may induce serum anti-p53 antibodies. The aim of this study was to assess the prevalence of serum anti-p53 antibodies in a large series of Western patients with hepatocellular carcinoma and the prognostic value of these antibodies on survival. METHODS: Serum anti-p53 antibodies were assayed in 159 patients with hepatocellular carcinoma, at diagnosis, using an immunoenzymatic method. The initial patient characteristics were compared according to anti-p53 status. The prognostic value of these antibodies on survival was determined by univariate and multivariate analysis. RESULTS: One hundred fifty nine patients with hepatocellular carcinoma were included in the study (129 men, mean age: 68 years). The main associated causes of chronic liver disease were alcohol (n=86), virus C (n=34), and virus B (n=18); 151 patients had cirrhosis. Median follow-up was 306 days. Among the 159 patients, 19 (12%) had serum anti-p53 antibodies. Detection of serum anti-p53 antibodies was significantly correlated with the presence of a multinodular or infiltrative tumor (P<0.03). Survival was not influenced by the presence of anti-p53 antibodies. Serum albumin, ALAT, and alfa-fetoprotein levels were independent prognostic variables. CONCLUSION: In our study, anti-p53 antibodies were rarely found in the serum of patients with hepatocellular carcinoma. Although they were correlated with multinodular or infiltrative tumors, they had no prognostic influence on survival. Thus, assaying serum anti-p53 antibodies does not seem to have any clinical value in those patients.

Aged↗
PubMed1999

Expression of mutated hepatitis B virus X genes in human hepatocellular carcinomas.

To explore the role of hepatitis B virus (HBV) X protein in liver carcinogenesis, independently from its role in viral replication, we have analyzed X gene structure and expression in tumorous and non-tumorous tissues obtained from 9 hepatitis B surface antigen (HBsAg)-negative, HBV DNA-positive patients. HBV replication was undetectable in tumorous tissues. HBV X gene was truncated at its 3' end in 5 of 9 tumorous tissues and 1 of 8 non-tumorous livers. Sequence analysis performed on uninterrupted X genes from 3 tumors and 3 surrounding non-tumorous tissues showed a high rate of mutations, selectively in the tumorous livers. In 1 of the 3 tumors, a frameshift mutation induced a new stop at codon 129. HBV RNAs were tested by reverse transcriptase-polymerase chain reaction (RT-PCR) with surface (S), core (C) and X specific primers. X, but not S and C, RNA expression was found in 6 of 8 tumors and in 6 of 7 non-tumorous tissues. This finding was consistent with immunohistochemical detection of X, but not S and C, antigens in all tumors also expressing X RNA. Our results provide evidence for selective expression of HBV X, but not S and C, RNA and protein in the tumorous and non-tumorous tissue of HBsAg-negative, HBV DNA-positive patients. It also shows that the structure of the X gene is modified (interrupted or highly mutated) in the majority of tumorous livers. Taken together, our findings are consistent with a potential role of mutated X proteins in HBV-related liver oncogenesis.

Adolescent↗
PubMed1999

Hepatocellular carcinoma without cirrhosis in the West: epidemiological factors and histopathology of the non-tumorous liver. Groupe d'Etude et de Traitement du Carcinome Hépatocellulaire.

BACKGROUND/AIM: In the West, hepatocellular carcinoma rarely occurs in patients without cirrhosis. In these patients, epidemiological factors and the histopathology of the non-neoplastic liver are not well known. The aim of this study was to clarify these points. METHODS: We studied 30 patients (26 men, 28-87 years) with hepatocellular carcinoma and histologically-proven non-cirrhotic livers. Serological markers of HBV and HCV infection, as well as alcohol and tobacco consumption were evaluated. Pathological changes in the non-tumorous liver (fibrosis, inflammation, steatosis, alcoholic hepatitis lesions, iron overload, and large cell dysplasia) were systematically assessed using semi-quantitative scores. RESULTS: Twenty patients had alcohol intake > or =30 g/d and 16 were smokers. Serological HBV or HCV markers were positive in 10 patients. Only four patients had no exposure to alcohol or tobacco and no serological markers of HBV or HCV Histological examination showed that all livers had pathological changes. Seventeen patients (57%) had clearly-identified chronic liver disease: chronic hepatitis (n = 10) or alcoholic liver disease (n = 7). Non-specific and moderate pathological changes were observed in the 13 other patients (43%), with different degrees of fibrosis, activity, steatosis, and iron overload. Large cell dysplasia was present in 12 patients (40%). CONCLUSIONS: In our study, all patients with hepatocellular carcinoma and non-cirrhotic livers had non-tumorous pathological liver changes, especially iron overload and large cell dysplasia. These results suggest that hepatocellular carcinoma originates from an abnormal histological background, even in non-cirrhotic liver.

Adult↗
PubMed1999

A new prognostic classification for predicting survival in patients with hepatocellular carcinoma. Groupe d'Etude et de Traitement du Carcinome Hépatocellulaire.

BACKGROUND/AIMS: In patients with hepatocellular carcinoma, prediction of survival is difficult. The aim of this prospective study was to provide a simple classification for predicting survival of patients with hepatocellular carcinoma, based on a multivariable Cox model. METHODS: Seven hundred and sixty-one patients who presented with hepatocellular carcinoma from 24 Western medical centers were enrolled over a 30-month period. Patients were randomly assigned to either a training sample (n=506, with 418 deaths) from which a classification system was established, or a test sample (n=255, with 200 deaths) for validating its prognostic significance. RESULTS: Five prognostic factors were selected at the 0.0001 level: Karnofsky index <80% (relative risk of death=2.2, 95% confidence interval: 1.7-2.7), serum bilirubin >50 micromol/l (relative risk=2.1, 95% confidence interval: 1.7-2.6), serum alkaline phosphatase at least twice the upper limit of normal range (relative risk=1.6, 95% confidence interval: 1.3-2.0), serum alpha-fetoprotein >35 microg/l (relative risk=1.7, 95% confidence interval: 1.4-2.1), and ultrasonographic portal obstruction (relative risk=1.3, 95% confidence interval: 1.1-1.7). Three risk groups with different 1-year survival rates (72%, 34%, 7%) were derived, and independently validated in the test sample (79%, 31%, 4%). CONCLUSION: This classification could be useful in the assessment of prognosis from homogeneous groups of patients with respect to their expected outcome.

Adult↗
PubMed1998

Perforin and granzyme B lytic protein expression during chronic viral and autoimmune hepatitis.

BACKGROUND: Cytotoxic T lymphocytes and Kupffer cells are essential components of the immune response during liver diseases. Recent studies have highlighted the role of cytotoxic T lymphocytes using Fas and its ligand in induced hepatocyte death during acute and chronic hepatitis. METHODS: In the present work, the main purpose was to investigate perforin and granzyme B expression in liver biopsies of patients with chronic hepatitis (10 HBV, 14 HCV and 10 autoimmune hepatitis) using immunohistochemistry. The liver biopsies of two normal individuals were also studied in the same conditions. RESULTS: Few intrahepatic T lymphocytes expressed perforin and granzyme B, while a large number of Kupffer cells were positive for both proteins in all the patients tested. The co-localization of perforin and granzyme B, and CD3 or CD68 antigens was visualized, respectively, in T cells and Kupffer cells, using confocal microscopy. In situ hybridization assays confirmed that perforin and granzyme B mRNAs were present in the liver during chronic hepatitis. The results were similar among the three groups of patients and whatever the activity of the disease. Perforin and granzyme B expression was lacking in liver samples from normal individuals. CONCLUSIONS: These data suggest a minor role for the T cell-mediated perforin/granzyme B death pathway, and a putative role for Kuppfer cells via lytic protein release, during chronic hepatitis.

Adolescent↗
PubMed1998

Intra-arterial chemoembolization in patients with hepatocellular carcinoma.

Hepatocellular carcinoma occurs almost exclusively in patients with cirrhosis, at least in the West. In most of these patients, potential curative treatments, such as resection or percutaneous alcohol injection, are usually contra-indicated. Transarterial chemoembolization may induce tumor necrosis. In order to avoid massive necrosis of the non tumoral liver, two major contra-indications have been identified: inadequate portal flow and liver failure. The influence of chemoembolization on survival was thought to be high on the basis of non randomized trials. However, no beneficial effects on survival were observed in three randomized trials. In these trials, the beneficial effect on tumor necrosis was counterbalanced by frequent deleterious effects on liver function. Moreover, progressive liver atrophy may follow repeated procedures. As there is no alternative treatment for most of these patients and chemoembolization can still be beneficial in selected cases, efforts have been made to improve patient selection and method to improve the results. Good liver function, a normal portal flow, and a well limited hypervascularized tumor are necessary conditions for treatment, which may even be curative when used in association with percutaneous alcohol injection. Moreover, arterial embolization can be performed without chemotherapy, and the procedure should not be repeated in the short term.

Carcinoma, Hepatocellular↗
PubMed1998

[Adult multi-nuclear cell hepatitis. A study in 17 patients].

OBJECTIVES: Giant-cell hepatitis is rare in adults and its significance has not been clarified. We report the clinical and histological characteristics and outcome in a group of adult patients with giant-cell hepatitis. METHODS: Seventeen patients with giant-cell hepatitis, hospitalized in our unit between 1976 and 1992, were studied retrospectively. Giant-cell hepatitis was defined as at least two hepatocytes with four or more nuclei per cell on liver biopsy. Clinical and biochemical parameters, liver histology, and the serological profile of HAV, HBV, HCV, HIV, HSV, EBV, CMV, and paramyxovirus were evaluated. Paramyxovirus immunochemistry was performed in 6 liver biopsies. RESULTS: There were 11 females and 6 males, an average of 48 years old (range: 29-80). Four patients had a well-defined etiology: acute hepatitis B infection with a favorable outcome in 2 cases, clometacine induced-hepatitis resulting in death from liver failure in one case, and chronic hepatitis B and C in one patient with AIDS. Among the 13 patients in which the etiology could not be determined, histologically defined acute hepatitis was observed in 8 and chronic hepatitis in 5. Nine patients were treated with immunosuppressive drugs. One patient was lost to follow-up. Eight patients responded to treatment, but 5 patients progressed to cirrhosis between 5 months and 7 years. Two of the 4 patients with unexplained liver disease who did not receive any treatment died of liver failure. CONCLUSION: In patient with acute or chronic hepatitis without an identified cause (with or without autoimmune abnormalities), the presence of giant-cell hepatitis seems to have a similar evolution as active autoimmune hepatitis. The poor prognosis of these patients suggests that early immunosuppressive treatment is justified.

Adult↗
PubMed1998

[Autoimmune hepatitis induced by fibrates].

AIM: Long term treatment by fibrates could induce chronic hepatitis associated with auto-antibodies. The aim of this study was to assess the features of this hepatitis. METHODS: Baseline clinical and biological features, and liver biopsy in 5 patients with fibrate-induced chronic hepatitis were studied, as well as their outcome. RESULTS: At enrollment, patients (4 men, mean age 65 years) had highly (n = 3) or mildly (n = 2) increased serum aminotransferase activity, hypergammaglobulinemia and high titers of anti-nuclear antibodies (with homogenous fluorescence in 3 cases). Liver biopsies demonstrated a lympho-plasmocytic infiltrate in all cases. Hepatocellular necrosis was multilobular in 2 cases, and mild to moderate, located in lobular and periportal areas in 3 cases. Cirrhosis was found at presentation in 3 cases and developed within a few months in the 2 other patients. After discontinuation of fibrates, aminotransferase activity normalized within 6 weeks either spontaneously (n = 3) or under immunosuppressive treatment (n = 2). Immunosuppression was rapidly withdrawn in 2 patients (< 18 months) without relapse, while one patient was treated for 4 years because of relapse after early withdrawal. A second liver biopsy performed 6 months after discontinuation of fibrates in an untreated-patient showed no inflammation or necrosis. CONCLUSION: These observations suggest that fibrates could trigger chronic liver disease resembling type I auto-immune chronic hepatitis, which resolves after drug withdrawal.

Aged↗
PubMed1997

[Diagnosis of cirrhosis in adults].

The diagnosis of cirrhosis relies on the histological analysis of a liver sample provided by biopsy made by transparietal or transjugular route according to the haemostasis of the patient. The histological study allows also to characterize the causative process and the severity of the disease. In the absence of histological proof a high probability of cirrhosis could be assumed when a firm liver with a narrow inferior edge is associated or not with signs of hepatic failure or portal hypertension. The most common causes of cirrhosis in France are alcohol abuse, C and B viruses, genetic haemochromatosis, chronic active autoimmune hepatitis, primary biliary cirrhosis. The prevalence of viral causes is increasing.

Adult↗
PubMed1997

Spontaneous and iatrogenic spreading of liver-derived cells into peripheral blood of patients with primary liver cancer.

The prognosis for patients with primary liver cancer (PLC) often depends on tumor recurrence and the development of extrahepatic metastases, particularly after liver transplantation. We have developed a sensitive test to detect both spontaneous circulation of tumor cells and the spread of liver cells due to chemoembolization and alcoholization. Reverse-transcription polymerase chain reaction was used to search for cells expressing alpha-fetoprotein (AFP) messenger RNA in the peripheral blood of 84 patients with PLC and 102 controls (55 patients with chronic hepatitis and/or cirrhosis, 10 patients with benign liver tumors or liver metastases from intestinal cancers, and 37 healthy individuals). By spiking the blood of healthy volunteers with HepG2 cells, we assessed the sensitivity limit: one HepG2 cell mixed with 10(7) leukocytes. All 102 controls tested negative. In contrast, 28 patients (33.3%) with PLC tested positive. Positivity for the test was significantly associated with portal thrombosis, tumor size, intravascular tumor emboli, serum AFP level, and extrahepatic metastases. Patients were followed up for a mean period of 39 +/- 51 weeks: the probability of developing extrahepatic metastases was significantly higher in positive than in negative patients. Eighteen negative patients with PLC were tested before, 1 hour after, and 24 hours after locoregional therapy: 9 tested positive either 1 or 24 hours after alcoholization or chemoembolization. In conclusion, we have developed a highly specific and sensitive test to detect circulating tumor cells in patients with PLC. This test is likely to be clinically useful in evaluating the risk of developing extrahepatic metastases and the possibility of iatrogenic spreading of liver-derived, possibly tumorous, cells.

Female↗