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Biomedical subjects

M Beaugrand

Publications and source records attributed to M Beaugrand.

At least 55 records · Page 3Linked to original sources
PubMed1997

Predictive value of serum sex hormone binding globulin for the occurrence of hepatocellular carcinoma in male patients with cirrhosis.

BACKGROUND/AIMS: The incidence of hepatocellular carcinoma is higher in males, presumably due to the influence of sex steroids. Therefore, to further assess the role of sex steroids in the occurrence of hepatocellular carcinoma, this study investigated the predictive value of different sex hormones and their binding protein. METHODS: Among 101 male patients with cirrhosis included in a prospective screening study, 29 developed hepatocellular carcinoma. We assessed the predictive value of 17 clinico-biological and 4 serum hormonal variables collected at enrollment, by the log-rank test and the Cox model. RESULTS: Age (p = 0.003), bilirubin (p = 0.04), sex-hormone-binding-globulin (p = 0.006) and albumin (p = 0.08) were predictive using the log-rank test, while estradiol and total and free testosterone were not. The Cox model showed age (p = 0.0003; relative risk = 7.52), sex-hormone-binding globulin (p = 0.001, relative risk = 3.37) and albumin (p = 0.02, relative risk = 2.94) as the most predictive parameters. CONCLUSION: We conclude that high serum sex-hormone-binding-globulin levels have an independent predictive value for the occurrence of hepatocellular carcinoma. Serum sex-hormone-binding-globulin could be used to define patients at high risk for hepatocellular carcinoma and could hypothetically play a role in hepatocarcinogenesis.

Carcinoma, Hepatocellular↗
PubMed1997

Multiple hepatic mitochondrial DNA deletions suggest premature oxidative aging in alcoholic patients.

BACKGROUND/AIMS: A 4977-base pair deletion has been detected in the hepatic mitochondrial DNA of alcoholic patients with microvesicular steatosis, a lesion ascribed to impaired mitochondrial beta-oxidation. However, only a single deletion had been looked for in this previous study, and it could not be determined whether the deletion was preexisting or acquired. Alcohol abuse increases the formation of reactive oxygen species in hepatic mitochondria. If this effect accelerates the oxidative aging of mitochondrial DNA, several other mutations would be expected. METHODS: The mtDNA region extending from nucleotide 8167 to nucleotide 14246 was screened for the presence of large mitochondrial DNA deletions in 58 alcoholic patients and 67 age-matched non-alcoholic controls. Hepatic DNA was subjected to polymerase chain reactions that amplified non-deleted and deleted mitochondrial DNA, respectively, and the boundaries of the mitochondrial DNA deletions were sequenced. RESULTS: Only 3% of the non-alcoholic controls carried a mitochondrial DNA deletion, whereas 24% of all alcoholic patients and 85% of the 13 alcoholic patients with microvesicular steatosis exhibited either single or multiple 4977, 5385, 5039 and 5556-base pair mitochondrial DNA deletions. No deletion(s) were observed, however, in 13 patients with microvesicular steatosis due to other causes. CONCLUSIONS: Diverse mitochondrial DNA rearrangements are observed in alcoholic patients with microvesicular steatosis. We suggest that alcohol abuse leads to premature oxidative aging of mitochondrial DNA. Hypothetically, oxidative damage to mitochondrial constituents (DNA, proteins and lipids) may favor microvesicular fat deposition.

Adult↗
PubMed1996

Needle biopsy of hepatocellular carcinoma: assessment of prognostic contribution of histologic parameters including proliferating cell nuclear antigen labeling and correlations with clinical outcomes. Group d'Etude et de Traitement du Carcinoma Hépatocellulaire.

BACKGROUND: Although many studies concerning the prognostic factors of resected hepatocellular carcinoma have been performed, the prognostic information provided by needle biopsy of these tumors has not yet been extensively studied. METHODS: One hundred twenty-four white patients with histologically-confirmed hepatocellular carcinoma were entered into a prospective study from 1990 to 1992 with followed-up through October 1994. Most of the patients had cirrhosis (79%). Patients were classified according to Okuda's staging: Stage I (50%), Stage II (47%), and Stage III (3%). The one-year survival rate was estimated at 58% in Okuda's Stage I, and 15% in Stages II and III. Edmondson's grading, mitotic index, and proliferating cell nuclear antigen labeling index were studied on each biopsy. Univariate and multivariate analyses were performed to determine the prognostic significance of the different parameters. RESULTS: According to Edmondson's critera, 13 of the hepatocellular carcinomas were Grade I, 63 Grade II, 42 Grade III, and 6 Grade IV. There was a significant correlation between Edmondson's grade, mitotic index, and proliferating cell nuclear antigen labeling index (P < 0.01). Univariate analysis showed both the histologic grade (P < 0.001) and mitotic index (P < 0.05) correlated with survival. Cox's model indicated that Edmondson's grading yields additional prognostic information for Okuda's staging (P < 0.001). The one-year survival rate for Okuda's Stage I was 76% for Edmondson's Grades I + II versus 23% for Grades III + IV. CONCLUSIONS: Edmondson's grading appears to be an important prognostic parameter for patients with hepatocellular carcinoma, and could help stratify patients for clinical trials.

Adult↗
PubMed1996

Predictive score for the development of hepatocellular carcinoma and additional value of liver large cell dysplasia in Western patients with cirrhosis.

The aim of this study was to identify high-risk patients for hepatocellular carcinoma (HCC). Among 151 patients with histologically proven cirrhosis hospitalized from 1987 to 1990 and prospectively followed-up until June 1994, 31 developed HCC. We assessed the predictive value of 22 variables recorded at enrollment for HCC occurrence by the log rank test and the Cox proportional hazards model. Six clinical and biological variables summarized predictive information of HCC: age > or = 50 years (P = .01), male (P = .01), large esophageal varices (EV) (P = .03), prothrombin activity < 70% (P = .04), serum alpha-fetoprotein (AFP) > or = 15 ng/L (P = .06), and anti-hepatitis C virus antibodies (P = .08). A clinicobiological predictive score identified two groups of patients at low (n = 67; 3-year cumulative incidence, 0%) and high risk for HCC (n = 84; 3-year cumulative incidence, 24%). The predictive value of this score was confirmed using an independent population of 49 patients with cirrhosis. Furthermore, liver large-cell dysplasia (LCD) had an additional predictive value in high-risk patients (P = 10(-4), which thus helped to define a subgroup at very high risk for HCC (n = 12; 3-year cumulative incidence, 72%). In Western patients with cirrhosis, a limited number of usual variables can identify a group of patients at high risk for HCC. Among these patients, liver biopsy allows for the determination a subgroup of patients at very high risk for HCC requiring intensive screening or preventive measures.

Age Factors↗
PubMed1996

Transjugular renal biopsy in the treatment of patients with cirrhosis and renal abnormalities.

When renal lesions are suspected in patients with cirrhosis, clotting disorders often preclude percutaneous renal biopsy. This study was undertaken to determine whether transjugular renal biopsy is possible, safe, and useful in such patients. From 1987 to 1994, 70 patients with cirrhosis and clotting disorders underwent transjugular renal biopsies, providing renal tissue in 55. Of these 55 patients, 41 were Child-Pugh class B or C, 35 were alcoholic, serum creatinine levels were > or = 130 micromol/L in 46, and proteinuria was > or = 0.5 g/d in 37. Clinically significant complications of transjugular renal biopsy were persistent hematuria in 4 and perirenal hematoma in 4, requiring blood transfusions in 1 and 2 cases, respectively. There were no deaths related to renal biopsy. Renal lesions were identified as glomerular in 41 (74.5%), interstitial in 7, and end-stage in 2 and were absent in 5. Transjugular renal biopsy influenced treatment in 21 patients (38%), including 11 who were proposed for liver transplantation and 4 who had chronic liver rejection. Decisions based on results of transjugular renal biopsy were to perform liver transplantation in 8 and combined renal and liver transplantation in 5, whereas 2 were refused. In 6 other patients, the results of renal biopsy modified the medical regimen. We conclude that transjugular renal biopsy may be a useful procedure in patients with cirrhosis and clotting disorders. This technique does not entail undue risks and may influence treatment decisions, particularly in patients proposed for liver transplantation.

Adult↗
PubMed1996

Antimitochondrial antibodies in patients with chronic hepatitis C.

Although autoantibodies have been found in the serum of patients with chronic hepatitis C virus (HCV) there has been no convincing evidence of the presence of antimitochondrial antibodies, until now. Sera from 460 untreated patients with chronic hepatitis C were tested for antimitochondrial antibodies, using an indirect immunofluorescence technique; and if they tested positive for the antibodies (titer more than 1:50), they also were treated by Western blot analysis. Seven (1.5%) sera were positive. None of the patients had biological or histological evidence of primary biliary cirrhosis. Antimitochondrial antibodies recognized one of the oxo-dehydrogenase multienzyme complexe's epitopes by Western blot assay in three patients only. All seven patients were then treated by interferon alpha for six months. None showed exacerbation of liver disease during treatment. HCV-RNA disappeared from the serum in one patient who became negative for anti-M2 antibodies. The four patients who did not respond to interferon-alpha therapy, and the two who relapsed after treatment withdrawal, had sustained positive antimitochondrial antibodies. These data suggest that: 1) antimitochondrial antibodies present in patients with chronic hepatitis C do not always recognize the same epitopes as in primary biliary cirrhosis; 2) these antibodies may disappear after eradication of HCV, suggesting that the production of antimitochondrial antibodies is linked to the presence of the virus and 3) the clinical and biological course of chronic hepatitis C, and the response to interferon-alpha therapy, does not seem to be different in patients who are positive for antimitochondrial antibodies.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗
PubMed1996

[Fibrosing cholestatic hepatitis by B virus reactivation in AIDS].

We report an Hepatitis B Virus reactivation, in a patient with an end-stage Human Immunodeficiency Virus infection who developed a rapidly progressive liver failure in four months. The main histological features include ballooning of hepatocytes and ground glass transformation, without significant inflammation. Immunohistochemical staining showed a high expression of viral antigens. This case can be related to "Fibrosing Cholestatic Hepatitis", first described after liver transplantation for cirrhosis B. The mechanism of hepatocellular damage is likely to be a direct cytotoxicity of hepatitis B virus.

Acquired Immunodeficiency Syndrome↗
PubMed1996

High prevalence of diabetes mellitus in patients with chronic hepatitis C. A case-control study.

OBJECTIVES AND METHODS: Extrahepatic manifestations have been reported in hepatitis C virus infection. To assess the relationship between diabetes mellitus and hepatitis C virus, we studied 152 patients with chronic hepatitis C and 152 controls hospitalized during the same period with hepatitis B virus (n = 51) or alcohol-induced (n = 101) liver diseases matched for age, sex, and the presence of cirrhosis (prevalence: 58%). Patients with jaundice, ascites, encephalopathy, prothrombin activity < 65%, or serum albumin < 35 g/L were excluded. RESULTS: Diabetes, defined by fasting serum glycemia > 1.4 g/L on at least two separate occasions or previously treated overt diabetes, was present in 38 patients with chronic hepatitis C (24%) and in 13 patients in the control group (9%, P < 0.002). In the 51 diabetic patients, irrespective of serum anti-hepatitis C virus status, 41 (81%) had non insulin dependent diabetes and 45 (88%) had cirrhosis. Family history of diabetes or obesity was observed in 2 (5%) of the diabetic patients with chronic hepatitis C and in 6 (46%) of the diabetic controls (P = 0.002). Plasma C-peptide (855 +/- 448 pmol/L versus 1,152 +/- 491 pmol/L, NS) and insulin levels (83 +/- 40 pmol/L versus 184 +/- 86 pmol/L, NS), assayed in 17 diabetic patients with chronic hepatitis C and in 9 diabetic controls, were lower in the former. The prevalence of HLA B8, DR3 or DR4 antigens, which was searched for in 77 patients with chronic hepatitis C, was not different in diabetic and non diabetic patients, and, was similar to the reference population. Serum islet-cell antibodies were found in 5 patients with chronic hepatitis C (3 with diabetes) and in 2 controls. CONCLUSION: Diabetes mellitus is more prevalent in patients with chronic hepatitis C than in patients with other liver diseases, and usually occurs in the absence of predisposing factors. These results suggest a role of hepatitis C virus infection in the pathogenesis of diabetes.

Adult↗
PubMed1995

HCV-associated liver cancer without cirrhosis.

Chronic infection with hepatitis C virus (HCV) is regarded as a risk factor for hepatocellular cancer, mostly in patients with liver cirrhosis. We looked for HCV genomes in the livers of patients with hepatocellular cancer who did not have cirrhosis to see whether HCV was directly oncogenic. Cancerous and non-cancerous liver tissue, and serum samples from 19 patients negative for hepatitis B surface antigen were analysed by polymerase chain reaction for the presence of HCV genome, HCV replication, HCV genotyping, and HBV genome. 13 of 19 patients were HCV RNA-positive in cancerous and non-cancerous liver tissue; 8 of 17 tested were anti-HCV positive. Among the 13 HCV RNA-positive patients, 11 had genotype 1b and 2 had genotype 2a. 7 of 13 serum samples were HCV RNA positive. 7 of 19 patients were HBV DNA positive in cancerous and non-cancerous liver tissue, 5 of them anti-HBc positive. 4 patients were both HCV RNA and HBV DNA positive and 3 were both HCV RNA and HBV DNA negative. Our results provide evidence for the association of HCV, mostly genotype 1b, with hepatocellular cancer without the intermediate step of cirrhosis.

Adult↗
PubMed1995

Hepatic mitochondrial DNA deletion in alcoholics: association with microvesicular steatosis.

BACKGROUND/AIMS: Alcohol abuse may lead to microvesicular steatosis, a lesion ascribed to impaired mitochondrial function. Because alcohol abuse leads to reactive oxygen species in the hepatic mitochondria, it may damage mitochondrial DNA. The aim of this study was to look for the presence of the "common" 4977-base pair deletion in the hepatic mitochondrial DNA of alcoholic patients and age-matched, nonalcoholic controls. METHODS: Hepatic DNA was subjected to two polymerase chain reactions that amplified non-deleted and deleted mitochondrial DNA, respectively. RESULTS: The deletion was found in 6 of 10 alcoholics with microvesicular steatosis, 2 of 17 alcoholic patients with macrovacuolar steatosis, but in none of 12 patients with acute alcoholic hepatitis, 11 patients with alcoholic cirrhosis, or 62 nonalcoholic patients of comparable ages with various other liver diseases or normal liver histology. In all patients with the deletion, restriction fragments of deleted mitochondrial DNA co-migrated with those of reference Pearson bone marrow-pancreas syndrome patients with the common mitochondrial DNA deletion. CONCLUSIONS: The common deletion is frequent in the hepatic DNA of alcoholic patients with microvesicular steatosis. Alcohol-induced mitochondrial DNA damage may contribute to the occurrence of this lesion in some alcoholics.

Adult↗
PubMed1995

Absence of anti-LKM-1 antibody in hepatitis C viral infection in the United States of America.

Several studies from Europe have observed a relationship between hepatitis C virus infection and anti-liver/kidney microsome-1 (anti-LKM-1) positive chronic hepatitis. It has been suggested that hepatitis C may induce an autoimmune phenomenon that leads to the development of a specific type (type II anti-LKM-1 positive) autoimmune chronic hepatitis. We evaluated 204 sera from patients with well-documented hepatitis C infection from two centres in the United States of America and compared them with sera from 428 French patients from three centres. We evaluated the serological prevalence of anti-smooth muscle antibodies, anti-nuclear antibodies, anti-liver cytosol antibodies, and anti-mitochondrial antibodies subtype anti-M2 in patients with chronic hepatitis C. The two groups were matched in their ages, gender, mode of transmission of hepatitis C infection and severity of liver disease. Anti-LKM-1 was not observed in the patients from the USA at a time when it was noted in 3.7% of French patients. There were no differences, however, in the expression of other auto-antibodies, which were often in low titres. Absence of anti-LKM-1 in USA sera in comparison with French sera suggests that there may be differences in induction of anti-LKM-1 related to environmental and/or host genetic factors, and/or genomic variation in the hepatitis C virus.

Age Factors↗
PubMed1995

Identification of the T cell antigen receptor V beta gene products in labial salivary glands from patients with primary Sjögren's syndrome.

T lymphocytes are predominantly involved in the development of Sjögren's syndrome. Their repertoire has recently been claimed to be restricted. Analysis of T cell receptor V beta gene products within the labial salivary glands led us to identify V beta 2 and V beta 8. This study, using a new panel of anti-V beta product monoclonal antibodies and a tissue triple-staining technique, examined the distribution of V beta gene family products in activated as well as non-activated CD4+ or CD8+ T cells subsets in the salivary gland tissue of SS patients. Our results suggest that the V beta genes used by the T CD4+ or T CD8+ cells in situ are similar, irrespective of the activation status of these cells. T lymphocytes homing into exocrine tissues might thus be selected on the basis of their V beta repertoire rather than their activation state.

Adult↗