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Biomedical subjects

Vlad Ratziu

Publications and source records attributed to Vlad Ratziu.

51 records · Page 3Linked to original sources
PubMed2003

Fibrogenic impact of high serum glucose in chronic hepatitis C.

BACKGROUND/AIMS: There is considerable variability in the rate of fibrosis progression in patients with chronic hepatitis C, most of which is related to factors so far unknown. We tested the hypothesis that high serum glucose and overweight might contribute to this variability. METHODS: Seven hundred and ten patients with chronic hepatitis C with a known duration of infection and no hepatitis B virus or human immunodeficiency virus coinfection were studied. Significant fibrosis was defined as bridging fibrosis including cirrhosis. Variables were tested for their association with significant fibrosis. RESULTS: In univariate analyses both serum glucose and body mass index were associated with fibrosis. In multivariate analyses, age at infection, duration of infection, serum glucose and daily alcohol intake but not body mass index were independently associated with significant fibrosis. Patients with high serum glucose had been contaminated at an older age and had features of the metabolic syndrome, including steatosis more frequently, as well as faster fibrosis progression rates. High serum glucose was associated with intermediate and advanced, but not with early, fibrosis stages. A high serum glucose was associated with a higher relative risk for significant fibrosis than overweight. CONCLUSIONS: High serum glucose, is an independent co-factor of fibrosis in chronic hepatitis C with a higher pro-fibrogenic impact than overweight.

Adolescent↗
PubMed2003

Biochemical markers of fibrosis in patients with chronic hepatitis C: a comparison with prothrombin time, platelet count, and age-platelet index.

As an alternative to liver biopsy, an index of five biochemical markers (alpha2-macroglobulin, apolipoprotein A1, haptoglobin, total bilirubin, gamma-glutamyl-transpeptidase) has been shown to predict the severity of hepatitis C-related fibrosis. The objective of this study was to compare this index with other markers frequently used for this purpose (prothrombin time, platelets, age-platelet index). In 323 hepatitis C-infected patients, the discriminative values of these markers for F2-F4 fibrosis (by the METAVIR classification) were compared. By multiple logistic regression analysis, only the five-marker index (P < 0.0001) and prothrombin time (P = 0.02) were independently predictive of F2-F4 fibrosis. For this outcome, the area under the receiver operating characteristic curve was significantly higher for the five-marker index (0.836 +/- 0.024) than the age-platelet index (P = 0.002), and the platelet count and prothrombin time (P < 0.001), indicating greater diagnostic value. The addition of the latter markers to the five-marker index proved unhelpful for increasing its accuracy. In conclusion, an index of five biochemical markers accurately predicts significant hepatitis C-related fibrosis and is superior to traditional markers.

Adult↗
PubMed2003

Effect of treatment with peginterferon or interferon alfa-2b and ribavirin on steatosis in patients infected with hepatitis C.

It has been suggested that hepatitis C virus (HCV) and especially genotype 3 is associated with steatosis. We assess the effect of treatment with peginterferon or interferon alfa-2b and ribavirin on steatosis. We analyzed 1,428 naïve patients included in a randomized trial. A single pathologist scored steatosis at baseline and 24 weeks after the treatment. At baseline, steatosis was present in 935 of 1,428 patients (65%), including 175 (83%) of 210 patients with genotype 3 versus 760 (62%) of 1,218 with other genotypes (P <.001). The variables associated with steatosis in logistic regression were genotype 3 (P <.001), triglycerides greater than 1.7 mmol/L (P <.001), body mass index greater than 27 (P <.04), age greater than 40 years (P <.001), and septal fibrosis (P =.007). In genotype 3-infected patients, steatosis was associated with high viral load and with lower serum cholesterol. Steatosis was associated with lower sustained response rate, even after taking into account other factors (P <.001). Among virologic responders, steatosis was much improved in genotype 3, improvement of at least 1 grade in 77%, and disappearance in 46% compared with other genotypes, 46% and 29%, respectively (P <.001 both comparisons). In genotype 3 responders, the baseline low serum cholesterol was corrected by treatment (P <.001). Steatosis was associated with HCV genotype 3, triglycerides, high body mass index, age, fibrosis stage, and lower virologic response to treatment. In conclusion, sustained disappearance of the virus is associated with reduction of steatosis in genotype 3 as well as a correction of baseline low serum cholesterol.

Adult↗
PubMed2002

Transcriptional activation of endoglin and transforming growth factor-beta signaling components by cooperative interaction between Sp1 and KLF6: their potential role in the response to vascular injury.

Endoglin is an endothelial membrane glycoprotein involved in cardiovascular morphogenesis and vascular remodeling. It associates with transforming growth factor-beta (TGF-beta) signaling receptors to bind TGF-beta family members, forming a functional receptor complex. Arterial injury leads to up-regulation of endoglin, but the underlying regulatory events are unknown. The transcription factor KLF6, an immediate-early response gene induced in endothelial cells during vascular injury, transactivates TGF-beta, TGF-beta signaling receptors, and TGF-beta-stimulated genes. KLF6 and, subsequently, endoglin were colocalized to vascular endothelium (ie, expressed in the same cell type) following carotid balloon injury in rats. After endothelial denudation, KLF6 was induced and translocated to the nucleus; this was followed 6 hours later by increased endoglin expression. Transient overexpression of KLF6, but not Egr-1, stimulated endogenous endoglin mRNA and transactivated the endoglin promoter. This transactivation was dependent on a GC-rich tract required for basal activity of the endoglin promoter driven by the related GC box binding protein, Sp1. In cells lacking Sp1 and KLF6, transfected KLF6 and Sp1 cooperatively transactivated the endoglin promoter and those of collagen alpha1(I), urokinase-type plasminogen activator, TGF-beta1, and TGF-beta receptor type 1. Direct physical interaction between Sp1 and KLF6 was documented by coimmunoprecipitation, pull-down experiments, and the GAL4 one-hybrid system, mapping the KLF6 interaction to the C-terminal domain of Sp1. These data provide evidence that injury-induced KLF6 and preexisting Sp1 may cooperate in regulating the expression of endoglin and related members of the TGF-beta signaling complex in vascular repair.

Animals↗
PubMed2002

Non-invasive detection of liver fibrosis: Is superparamagnetic iron oxide particle-enhanced MR imaging a contributive technique?

The purpose of our study was to evaluate the ability of superparamagnetic iron oxide (SPIO)-enhanced MR imaging to detect liver fibrosis in patients with chronic liver disease and to compare the findings with histopathological data. Sixty-seven patients with chronic hepatitis ( n=58) or focal nodular hyperplasia (FNH; n=9) were studied using a 1.5-T MR system. The protocol included proton density-weighted, T2-weighted spin-echo (SE) and fast SE (FSE) sequences before and after SPIO administration and T2*-weighted gradient-recalled-echo (GRE) sequences after SPIO. Pre- and post-contrast T2-weighted and T2*-weighted sequences were retrospectively evaluated by three independent observers for evidence of non-tumor hypersignal intensities. Three liver patterns were considered: thick reticulations; thin reticulations; and/or multiple areas of hypersignal intensities. Unenhanced or enhanced patterns were compared with histopathological specimens, which had been obtained by percutaneous biopsy of the right lobe within a maximum of 12 months of MR examination. Liver fibrosis was histologically graded using a five-level scale (F0-F4), according to the METAVIR classification. Histopathology demonstrated significant fibrosis (F2-F4) in 57 patients, non-significant fibrosis in 1 patient (F1), and normal liver surrounding FNH in 9 patients (F0). After SPIO administration, at least one pattern of non-tumor hypersignal intensities was seen in 43 (76%) of the 57 patients with F>/=2 with good agreement (kappa=0.68) compared with 2 (20%) of the 10 F0/1 patients ( p<0.01). Attenuated non-homogeneous liver-signal intensities with persistent thick reticulations, thin reticulations, or multiple areas of hypersignals were observed in, respectively, 30, 52, and 56% of patients with F>/=2 with moderate agreement (kappa=0.51). Before SPIO, MR images were positive in 21 of 57 (37%) F>/=2 and zero F0/1 patients. Post-contrast proton-density-weighted and T2*-weighted GRE were the most sensitive sequences for detecting non-tumor hypersignal intensities. In patients with chronic liver diseases, SPIO-enhanced MR imaging exhibits non-tumor hypersignal intensities indicative of liver fibrosis by decreasing the signal from the non-fibrotic areas where Kupffer cells are present.

Adult↗
PubMed2002

Truth survival in clinical research: an evidence-based requiem?

PURPOSE: Factors associated with the survival of truth of clinical conclusions in the medical literature are unknown. The authors hypothesized that conclusions derived from studies using better methodology should have a longer half-life. DATA SOURCES: MEDLINE and hand searches of journals with studies on cirrhosis and hepatitis. STUDY SELECTION: Original articles and meta-analyses published from 1945 to 1999 about cirrhosis or hepatitis in adults. DATA SYNTHESIS: In 2000, 285 of 474 conclusions (60%) were still considered to be true, 91 (19%) were considered to be obsolete, and 98 (21%) were considered to be false. The half-life of truth was 45 years. The 20-year survival of conclusions derived from meta-analysis was lower (57% +/- 10%) than that from nonrandomized studies (87% +/- 2%) (P < 0.001) or randomized trials (85% +/- 3%) (P < 0.001). The survival of conclusions was not different when studies of high methodologic quality were compared with those of low quality. In randomized trials, the 50-year survival rate was higher for 52 negative conclusions (68% +/- 13%) than for 118 positive conclusions (14% +/- 4%) (P < 0.001). CONCLUSIONS: Contrary to the authors' hypothesis, conclusions based on recognized, good methodology had no clear survival advantage. To better convince clinicians of the long-term utility of evidence-based medicine, better prognostic factors should be developed.

Clinical Trials as Topic↗
PubMed2002

Impact of treatment on extra hepatic manifestations in patients with chronic hepatitis C.

BACKGROUND/AIMS: Fatigue and other extra hepatic manifestations of hepatitis C have never been studied prospectively in a large cohort. The aim was to assess the prevalence of these symptoms prior to any treatment, and on prolonged follow-up in treated and untreated patients. METHODS: A single-center cohort of consecutive patients with chronic hepatitis C was investigated prior to any treatment. A questionnaire was completed every 6 months for 18 months of follow-up. RESULTS: Of 1614 patients, 431 met the inclusion criteria (56% male; age 49 years; 60% with significant fibrosis or cirrhosis; 46% with cryoglobulinemia). Seventy-six were untreated; of the treated patients, 83 were sustained responders, 47 relapsers and 225 non-responders. At baseline, fatigue and other extrahepatic manifestations were present in 254 (59%) and 225 (52%) patients. Fatigue was improved in 29 of 83 (35%) responders versus 75 of 348 (22%) patients with detectable hepatitis C virus (HCV)-RNA (P=0.01). The impact of virologic response on fatigue persisted after adjusting for age, gender, fibrosis stage, and depression (odds ratio: 0.34, P<0.001). A cryoglobulin was detectable in two of 34 (6%) responders versus 38 of 115 (33%) patients with detectable HCV-RNA (P<0.001). CONCLUSIONS: In hepatitis C, a sustained virologic response is associated with a reduction in fatigue and cryoglobulin, but fatigue frequently persists despite a virologic response.

Adult↗
PubMed2002

Portal lymphocytic infiltrate in alcoholic liver disease.

The aim of this study was to estimate the frequency of lymphocytic portal infiltrate in human alcoholic liver disease and to determine whether it was correlated with liver injury. This retrospective study included 200 consecutive patients referred between February 1996 and March 2001 to the Service Central d'Hépato-Gastroentérologie at Groupe Hospitalier Pitié-Salpêtrière Hospital, Paris, France. The inclusions criteria were as follows: (1) daily alcohol consumption greater than 40 g; (2) appropriate serological exclusion of B and C viral hepatitis; and (3) available liver biopsy specimen. Autoimmune hepatitis was excluded in all patients with the aid of a consensus scoring system. Forty percent of the patients had a predominantly lymphocytic portal infiltrate. On stepwise logistic regression of the predictive value of the 5 variables (gender, age, daily alcohol consumption, steatosis, and portal and septal fibrosis index), only 2 statistically independent predictors of predominant lymphocytic portal infiltrate were identified: portal and septal fibrosis index (P <.05) and age (P <.05). In conclusion, predominantly portal lymphocytic infiltrate occurs frequently in alcoholic liver disease, even in patients without serological markers of B and C viral hepatitis. Moreover, after adjustment for age, portal and septal fibrosis index remains significantly associated with the presence of a predominantly lymphocytic portal infiltrate. These results suggest that lymphocytes may play a role in the pathogenesis of alcohol-induced liver fibrosis.

Aged↗
PubMed2002

Survival, liver failure, and hepatocellular carcinoma in obesity-related cryptogenic cirrhosis.

Despite the rising incidence of obesity and diabetes, there is little emphasis on morbidity and mortality from obesity-related cirrhosis, usually considered a rare and asymptomatic condition. Our aim was to assess survival and the occurrence of hepatocellular carcinoma and complications of hepatic insufficiency in obesity-related cryptogenic cirrhosis compared with cirrhosis of other origins. We analyzed retrospectively 27 overweight patients with cryptogenic cirrhosis (CC-O), 10 lean patients with cryptogenic cirrhosis (CC-L) and 391 patients with hepatitis C virus-related cirrhosis (C-HCV). In CC-O patients, cirrhosis was detected later in life than in C-HCV and CC-L patients. Severe liver disease was as frequent in CC-O as in C-HCV patients as indicated by the proportion of Child B or C or of episodes of hepatic decompensation. Survival of CC-O patients was lower than that of untreated, age- and sex-matched C-HCV controls (P <.02 at 30 months), with a higher mortality of Child B or C patients. Hepatocellular carcinoma was detected in 8 of 27 (27%) CC-O patients versus 21% of matched C-HCV controls with a similar age cumulated incidence, suggesting a comparable carcinogenic potential. In conclusion, obesity-related cirrhosis should now be recognized as a distinct entity that can cause severe liver disease and death. Increased awareness of and better diagnostic strategies for nonalcoholic steatohepatitis in overweight patients are urgently needed.

Adult↗
PubMed2002

Biochemical markers of liver fibrosis: a comparison with historical features in patients with chronic hepatitis C.

OBJECTIVES: Liver fibrosis in chronic hepatitis C is related to sex, age at infection, duration of infection, and alcohol consumption. Several noninvasive biochemical markers are highly predictive for the discrimination of significant fibrosis. The aims of this study were: 1) to compare an index of five biochemical markers with historical features; and 2) to determine the utility of combining these features with the five-marker index for the prediction of significant fibrosis. METHODS: Untreated patients with chronic hepatitis C and a known duration of infection had a liver biopsy and serum tested for markers of fibrosis. The discriminative values of the markers and an index of historical features for the diagnosis of clinically significant fibrosis (F2-F4 by the Metavir system) were compared using areas under receiver operating characteristic (ROC) curves. A modified index was constructed combining the five-marker index and historical features. RESULTS: A total of 211 patients were included. Of these, 52% were male, and 19% consumed > or = 50 g of alcohol daily. The median age at infection was 28 +/- 13 yr and the median duration of infection was 17 +/- 8 yr (range 1-48 yr). By multivariate logistic regression analysis, sex (p = 0.003), age at biopsy (p = 0.004), and alcohol consumption (p = 0.042) were independently predictive of F2-F4 fibrosis. For the discrimination of F2-F4 fibrosis, the areas under the ROC curves were 0.796 +/- 0.033 for the five-marker index versus 0.709 +/- 0.037 for the historical index (p = 0.079). For diagnosis of advanced fibrosis (F3 and F4), the areas under the curves were 0.920 +/- 0.032 and 0.762 +/- 0.049 (p = 0.007), respectively. The discriminative value of the combined biochemical and historical index was not statistically significantly different from that of the five-marker index alone (p = ns). CONCLUSIONS: A simple index including age, sex, and five biochemical markers accurately predicts significant hepatitis C-related fibrosis. This index is more accurate than an index of historical features, the addition of which to the existing index was not helpful.

Adult↗