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Biomedical subjects

Vlad Ratziu

Publications and source records attributed to Vlad Ratziu.

At least 37 records · Page 2Linked to original sources
PubMed2005

FAS promoter polymorphisms correlate with activity grade in hepatitis C patients.

OBJECTIVE: Hepatocytes are susceptible to FAS-mediated apoptosis. The impact of polymorphisms in the FAS gene on histopathological features of HCV infection was therefore investigated. DESIGN/METHODS: Three single-nucleotide polymorphisms in the FAS promoter were assessed in 190 patients with chronic hepatitis C. Associations between FAS haplotypes and fibrosis stage and activity grade were tested by univariate and multivariate analyses. RESULTS: While there was no correlation between FAS promoter genotype and fibrosis stage, patients carrying the GCA haplotype (P=0.03, Fisher's exact test) and those homozygous for the GTG haplotype (P = 0.06) tended to have lower activity scores. Logistic regression showed that these associations were independent of patient age, sex and alcohol consumption. In a logistic regression model incorporating only male gender (odds ratio 2.1, 95% confidence interval 1.1-4.1 P = 0.04), the presence of the GCA haplotype (OR 0.31 95% CI 0.13-0.78 P = 0.01), and GTG homozygosity (OR 0.26 95% CI 0.08-0.83 P = 0.02), all three factors were independently correlated with activity grade. Furthermore, the GTG haplotype appeared to have lower promoter activity than the wild type GTA haplotype in a hepatocellular carcinoma cell line. CONCLUSIONS: Genetic polymorphism in the FAS gene may account for some of the histopathological variability in chronic hepatitis C.

Adult↗
PubMed2005

Chronic calcifying pancreatitis and systemic lupus erythematous.

Gastrointestinal manifestations are common in systemic lupus erythematous (SLE), occurring in 35% to 40% of patients at some stage of their illness. SLE is an uncommon etiology of pancreatic disease. Only 3 cases of chronic pancreatitis associated with SLE have been reported in adults. We report the case of a 59-year-old white woman with a history of mechanic aortic valve replacement and SLE presented to the emergency unit for acute pancreatitis with no other identifiable etiology.

Acute Disease↗
PubMed2005

Longitudinal assessment of histology surrogate markers (FibroTest-ActiTest) during lamivudine therapy in patients with chronic hepatitis B infection.

OBJECTIVES: The noninvasive serum markers, FibroTest-ActiTest (FT-AT), are an alternative to liver biopsy in patients with chronic hepatitis C and B. The aim was to use these markers in a prospective study of patients treated with lamivudine in order to assess the impact of treatment, as well as the factors associated with fibrosis progression. METHODS: Two hundred and ninety-eight patients were included in a prospective longitudinal study in 50 hospitals across France. FT-AT were measured at baseline, and then after 6, 12, and 24 months of lamivudine 100-mg treatment. Epidemiological, clinical, and virologic characteristics were analyzed by univariate and multivariate analysis. RESULTS: Two hundred and eighty-three patients were included for analysis. The accuracy of FT-AT versus biopsy was validated with the area under the ROC curve, 0.77 (SE = 0.03) for bridging fibrosis and 0.75 (SE = 0.06) for severe activity (A3). At baseline, bridging fibrosis (METAVIR stages F2-F3-F4) was highly associated (p < 0.001) in multivariate analysis with male gender and age and marginally associated with anti-HBe presence (p= 0.05) and non-Asian ethnic origin (p= 0.046). Lamivudine treatment had a very significant impact overall. FT decreased significantly from 0.51 at baseline to 0.37 at 24 months (p < 0.001), and 85% of patients had improvement at 24 months. AT also decreased significantly from 0.56 to 0.13 (p < 0.0001), and 91% of patients had improvement at 24 months. A three-phase kinetics was observed for both fibrosis and activity; there was a marked improvement during the first 6 months, followed by a plateau between 6 and 12 months, and another improvement between 12 and 24 months. The occurrence of a YMDD variant does not entirely explain these three-phase variations. The first phase impact on fibrosis rates was higher in Asian patients (p= 0.01) and in patients younger than 40 yr (p < 0.001). CONCLUSIONS: In patients with chronic hepatitis B, a 24-month course of lamivudine treatment leads to a significant decrease in necroinflammatory grades and fibrosis stages as assessed by noninvasive markers, with the occurrence of a three-phase kinetics. FT-AT should be useful in the noninvasive follow-up of lamivudine treatment.

Adult↗
PubMed2005

FibroTest-FibroSURE: towards a universal biomarker of liver fibrosis?

Among the noninvasive alternatives to liver biopsy, several studies have demonstrated the predictive value and superior benefit/risk ratio to biopsy of two combinations of simple serum biochemical markers in patients infected with hepatitis B and C virus. These include FibroTest (BioPredictive) for the quantitative assessment of fibrosis, and ActiTest (BioPredictive) for the quantitative assessment of necroinflammatory activity (HCV-FibroSURE, LabCorp). The possible causes of false negatives and positives are also better identified. These tests, which are now available in 12 countries, can facilitate the screening and management of the most frequent liver diseases.

Biomarkers↗
PubMed2004

Overview of the diagnostic value of biochemical markers of liver fibrosis (FibroTest, HCV FibroSure) and necrosis (ActiTest) in patients with chronic hepatitis C.

SUMMARY: BACKGROUND: Recent studies strongly suggest that due to the limitations and risks of biopsy, as well as the improvement of the diagnostic accuracy of biochemical markers, liver biopsy should no longer be considered mandatory in patients with chronic hepatitis C. In 2001, FibroTest ActiTest (FT-AT), a panel of biochemical markers, was found to have high diagnostic value for fibrosis (FT range 0.00-1.00) and necroinflammatory histological activity (AT range 0.00-1.00). The aim was to summarize the diagnostic value of these tests from the scientific literature; to respond to frequently asked questions by performing original new analyses (including the range of diagnostic values, a comparison with other markers, the impact of genotype and viral load, and the diagnostic value in intermediate levels of injury); and to develop a system of conversion between the biochemical and biopsy estimates of liver injury. RESULTS: A total of 16 publications were identified. An integrated database was constructed using 1,570 individual data, to which applied analytical recommendations. The control group consisted of 300 prospectively studied blood donors. For the diagnosis of significant fibrosis by the METAVIR scoring system, the areas under the receiver operating characteristics curves (AUROC) ranged from 0.73 to 0.87. For the diagnosis of significant histological activity, the AUROCs ranged from 0.75 to 0.86. At a cut off of 0.31, the FT negative predictive value for excluding significant fibrosis (prevalence 0.31) was 91%. At a cut off of 0.36, the ActiTest negative predictive value for excluding significant necrosis (prevalence 0.41) was 85%. In three studies there was a direct comparison in the same patients of FT versus other biochemical markers, including hyaluronic acid, the Forns index, and the APRI index. All the comparisons favored FT (P < 0.05). There were no differences between the AUROCs of FT-AT according to genotype or viral load. The AUROCs of FT-AT for consecutive stages of fibrosis and grades of necrosis were the same for both moderate and extreme stages and grades. A conversion table was constructed between the continuous FT-AT values (0.00 to 1.00) and the expected semi-quantitative fibrosis stages (F0 to F4) and necrosis grades (A0 to A3). CONCLUSIONS: Based on these results, the use of the biochemical markers of liver fibrosis (FibroTest) and necrosis (ActiTest) can be recommended as an alternative to liver biopsy for the assessment of liver injury in patients with chronic hepatitis C. In clinical practice, liver biopsy should be recommended only as a second line test, i.e., in case of high risk of error of biochemical tests.

Journal Article↗
PubMed2004

Intra-individual fasting versus postprandial variation of biochemical markers of liver fibrosis (FibroTest) and activity (ActiTest).

BACKGROUND: Biochemical marker combinations, including alpha2-macroglobulin, haptoglobin, apolipoprotein A1, gamma-glutamyl transpeptidase, and total bilirubin (all part of FibroTest) plus alanine aminotransferase (all part of ActiTest), are being developed as alternatives to liver biopsy in patients with chronic hepatitis C and other various chronic liver diseases. Considering this premise, the primary aim of this study was to assess the impact of meal intake on FibroTest and ActiTest results. Such studies are very important for patients, as many clinical errors have been related to the absence of baseline evidence. RESULTS: Intra-individual variation was assessed for the 6 above components and for FibroTest and ActiTest, by measuring time dependent variations before and one hour after a standard meal in 64 subjects. These consisted of 29 healthy volunteers and 35 patients with chronic liver diseases. Meal intake had no significant impact on any of the six components, or on FibroTest or ActiTest, as assessed by repeated measure variance analyses (ANOVA all p > 0.90); the Spearman correlation coefficient ranged from 0.87 (total bilirubin) to 0.995 (gamma-glutamyl transpeptidase). The coefficients of variation (CV) between fasting and postprandial measurements fluctuated for the six components from 0.09 (apolipoprotein A1) to 0.14 (alpha2-macroglobulin), and from 0.09 for FibroTest to 0.13 for ActiTest. In contrast, meal intake had a significant impact on triglycerides (ANOVA p = 0.01, CV = 0.65) and glucose (ANOVA p = 0.04, CV = 0.31). As for the prediction of liver injury, the concordance between fasting and postprandial predicted histological stages and grades was almost perfect, both for FibroTest (kappa = 0.91, p < 0.001) and ActiTest (kappa = 0.80, p < 0.001). CONCLUSIONS: The intra-individual variation of biochemical markers was low, and it was shown that measurements of FibroTest, ActiTest and their components are not significantly modified by meal intake. This fact makes the screening of patients at risk of chronic liver diseases more convenient.

Journal Article↗
PubMed2004

Prospective analysis of discordant results between biochemical markers and biopsy in patients with chronic hepatitis C.

BACKGROUND: The FibroTest and ActiTest are noninvasive biochemical markers of liver injury that are intended for use as alternatives to liver biopsy in patients with chronic hepatitis C. The aims of this study were to assess the quality of biopsy and the prevalence of discordances between biopsy and markers, to identify factors associated with discordances, and to attribute these discordances to either markers or biopsy failure. METHODS: Fibrosis stage and activity grade were prospectively assessed on the same day by a liver biopsy and by markers. On the basis of risk factors for failure and independent endpoints, discordance was classified as being attributable to biopsy or to markers. RESULTS: Only 74 of 537 patients (14%) had a biopsy size > or =25 mm. Discordance was observed in 154 of 537 patients (29%), including 16% for fibrosis staging and 17% for activity grading. Steatosis, an inflammatory profile, and biopsy size were associated with discordance. Discordance was attributable to failure of markers in 13 patients (2.4%) and to biopsy failure in 97 (18%; P <0.001 vs Fibrotest and Actitest), and was nonattributable in 44 patients (8.2%). The most frequent failures attributable to markers were false negatives (1.3%) attributable to inflammation. The most frequent failures attributable to biopsy were false negatives of activity grading (10.1%) and of fibrosis staging (4.5%), both associated with smaller biopsy size and steatosis. False positives of fibrosis staging (3.5%) were associated with fragmented biopsies. CONCLUSION: In this series, the size of liver biopsy is adequate in only a minor proportion (approximately 14%) of patients with chronic hepatitis C. When biopsy and marker results are discordant, a reason can be identified in more than two-thirds of cases and, in those cases, biopsy failure is >7 times more common than diagnostic failure of markers.

Adult↗
PubMed2004

Fat, diabetes, and liver injury in chronic hepatitis C.

It is increasingly recognized that host factors can modulate the fibrogenic response in patients with chronic hepatitis C. Obesity, because of its prevalence, and diabetes, which seems to occur more frequently in patients infected by the hepatitis C virus (HCV), are often present in patients with chronic hepatitis C. Both conditions result in fatty liver, which in turn is associated with more severe liver damage, especially fibrosis or inflammation. Steatosis can either originate from associated metabolic alterations (insulin resistance resulting in metabolic steatosis) or from a direct cytopathic effect of the virus (genotype 3, resulting in viral steatosis). Metabolic steatosis seems to be a factor in resistance to antiviral therapy, whereas viral steatosis is reduced in sustained responders. Whether metabolic steatosis has a direct role in liver fibrosis progression or is only a surrogate marker of an underlying defect triggering fibrogenesis, such as insulin resistance, is a subject of debate. High serum glucose levels and diabetes have a strong and independent profibrogenic impact. Exciting new data are expanding our understanding of the mechanisms of steatogenesis in HCV infection and providing potential links between insulin resistance or hyperglycemic states and liver fibrogenesis.

Comorbidity↗
PubMed2003

Viral hepatitis B.

More than 400 million people worldwide are chronically infected by the hepatitis B virus. The virus is responsible for more than 300000 cases of liver cancer every year and for similar numbers of gastrointestinal haemorrhage and ascites. Major breakthroughs have been achieved in diagnosis and treatment of this virus. Hepatitis B vaccine reduces incidence of liver cancer. As with hepatitis C, advances have been made in molecular virology, especially for naturally occurring and treatment-induced mutant viruses. The clinical significance of low viral load and genotypes are also under investigation. Currently available monotherapies-interferon, lamivudine, and adefovir dipivoxil-very rarely eradicate the virus, but greatly reduce its replication, necroinflammatory histological activity, and progression of fibrosis. Lamivudine, and presumably other nucleoside analogues, can reverse cirrhosis of the liver.

Adenine↗
PubMed2003

Viral hepatitis C.

More than 170 million people worldwide are chronically infected with the hepatitis C virus (HCV), which is responsible for more than 100000 cases of liver cancer per year, with similar numbers of digestive haemorrhage and ascites episodes. Major breakthroughs have been made in diagnosis and treatment, and advances in molecular biology mean that the replicative state of the virus can now be assessed. Genotype and serum viral load are useful predictors of response to treatment. The combination of pegylated interferon and ribavirin can eradicate the virus in more than 50% of patients. These antiviral treatments reduce liver fibrosis progression and can reverse cirrhosis. Unfortunately, even in developed countries, death due to hepatitis C is increasing because of inadequate detection and treatment.

Adult↗
PubMed2003

Serum biochemical markers accurately predict liver fibrosis in HIV and hepatitis C virus co-infected patients.

OBJECTIVE: Liver biopsy, the gold standard for assessing hepatitis C virus (HCV)-related fibrosis, is invasive and prone to complications. Our aim was to determine the operating characteristics of a non-invasive index of biochemical markers for the prediction of fibrosis in patients with HIV/HCV co-infection. DESIGN: In a cross-sectional, cohort study in a French tertiary-care hospital 130 HIV/HCV-co-infected patients with a liver biopsy and serum were tested for markers of liver fibrosis. METHODS: An index incorporating age, sex, alpha(2)-macroglobulin, apolipoprotein A1, haptoglobin, bilirubin, and gamma-glutamyl-transpeptidase (GGT), derived using multivariate logistic regression, was compared with liver histology. HIV-specific indices including the CD4 cell count and HIV-RNA load were also constructed. The diagnostic values of the indices were compared using receiver operating characteristic (ROC) curves. MAIN OUTCOME MEASURE: Septal fibrosis (F2-F4) by the METAVIR classification. RESULTS: By multivariate analysis, the most informative markers were alpha(2)-macroglobulin, apolipoprotein A1, GGT, and sex. The area under the ROC curve of the five-marker index was 0.856 +/- 0.035; not significantly different from the HIV-specific indices. On a scale from zero to 1.00, the five-marker index had a positive predictive value of 86% for scores greater than 0.60, and a negative predictive value of 93% for scores of 0.20 or less. These thresholds could reduce the necessity for liver biopsy by 55% while maintaining an accuracy of 89%. CONCLUSION: An index including five biochemical markers accurately predicts significant fibrosis in patients with HIV/HCV co-infection, and may substantially reduce the necessity for liver biopsy.

Adult↗
PubMed2003

A comparison of fibrosis progression in chronic liver diseases.

BACKGROUND/AIMS: No study has compared the liver fibrosis progression rates among chronic liver diseases and the risk factors in order to better organize screening strategies. METHODS: A total of 4852 patients were retrospectively studied (chronic hepatitis C (HCV) [n=2313], human immunodeficiency virus (HIV)-HCV co-infection (HIV-HCV [n=180]), hepatitis B (HBV [n=777]), alcoholic liver disease (ALD [n=701]), primary biliary cirrhosis (PBC [n=406]), genetic hemochromatosis (GH [n=383]) auto-immune hepatitis (AIH [n=57]) and delta hepatitis (n=35). The fibrosis progression rates were estimated from birth and from the date of exposure, when known, to the first biopsy. RESULTS: There were highly significant differences in the rates of fibrosis progression, the most rapid being HIV-HCV co-infection (50% cirrhosis percentile at 52 years of age) and the slowest being PBC (50% cirrhosis percentile at 81 years). There was an acceleration of fibrosis progression with aging. Fibrosis progression was slower in females compared with males for HCV, HBV, GH, and PBC. In contrast, in ALD, the fibrosis progression was more rapid in females. CONCLUSIONS: Rates of fibrosis progression differ markedly between the predominant causes of chronic liver disease, and according to age and gender. Patients with HIV-HCV co-infection are at particularly high risk of fibrosis progression.

Adult↗
PubMed2003

Prediction of liver histological lesions with biochemical markers in patients with chronic hepatitis B.

BACKGROUND AIMS: Liver biopsy is the gold standard for assessing hepatitis B virus (HBV)-related histology. The aim was to determine the diagnostic utility of noninvasive serum markers in patients with chronic hepatitis B. METHODS: The aminotransferases and indices including alpha(2)-macroglobulin, apolipoprotein A1, haptoglobin, gamma-glutamyl-transpeptidase (GGT), and total bilirubin (Fibrotest), and ALT (Actitest) were compared with liver histology. The primary outcomes were A2-A3 activity and F2-F4 fibrosis (METAVIR). RESULTS: Two hundred and nine patients were included. Forty-one patients (20%) had A2-A3 activity and 61 (29%) had F2-F4 fibrosis. AST and GGT (P<0.001) were independently associated with A2-A3 activity. AST, ALT, and Actitest accurately predicted activity ((areas under receiver operating characteristic (ROC) curves (AUROC), 0.81-0.82+/-0.04)); an AST or ALT< or =30IU/l excluded significant activity with 96% certainty. Fibrotest accurately predicted F2-F4 fibrosis (AUROC, 0.78+/-0.04). Fibrotest scores (range, 0-1.0) < or =0.20 and >0.80 had negative and positive predictive values of 92%, respectively. Restricting biopsy to patients with intermediate scores (>0.20 and < or =0.80) may prevent liver biopsies in 46% of patients while maintaining 92% accuracy. CONCLUSIONS: The aminotransferases and an index including five biochemical markers are accurate noninvasive markers of HBV-related activity and fibrosis, respectively.

Adult↗