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Biomedical subjects

M Bourliere

Publications and source records attributed to M Bourliere.

17 recordsLinked to original sources

Validation and comparison of indexes for fibrosis and cirrhosis prediction in chronic hepatitis C patients: proposal for a pragmatic approach classification without liver biopsies.

Noninvasive indexes have been developed to predict fibrosis staging. The aim of this study was to assess the diagnostic accuracy of these indexes in comparison with liver histology in hepatitis C virus (HCV)-infected patients. A total of 235 consecutive patients with HCV infection from the Fibropaca multicentre independent study were included in this paper. FibroTest (FT), aspartate aminotransferase to platelet ratio index (APRI) and Forns score were assessed in the cohort and compared with liver histology performed on the same day. The main end point was the area under characteristic curves (AUCs) for the diagnosis of significant fibrosis (F2-F4) and cirrhosis (F4) by the METAVIR classification. Mean age was 46 (+/-11) years, 55% were males, 42% (n = 99) had significant fibrosis (F2-F4) and 7% (n = 16) had cirrhosis (F4). For the diagnosis of significant fibrosis, respective AUCs of FT, APRI and Forns score were 0.81 (95% confidence interval: 0.76-0.86), 0.71 (0.67-0.79) and 0.76 (0.70-0.82); for cirrhosis prognosis, AUCs of FT and APRI were 0.82 (0.77-0.87) and 0.81 (0.76-0.86) (AUCs not significantly different). Using each index independently, all patients were classified by FT, 214 (91%) patients were classified by APRI and 129 (55%) by Forns score. There were significantly more cases of discordances between APRI and liver biopsy than between FT or Forns score and liver biopsy (P < 0.05). Performing all scores (FT, Forns and APRI) without liver biopsy allowed fibrosis to be well evaluated in 191 patients (81.3%), including patients with FT failure. Liver biopsy remained mandatory to evaluate fibrosis in 44 patients (18.7%). Our study shows that performing all the tests and liver biopsy improves the diagnostic accuracy for liver fibrosis in chronic hepatitis C patients without patent comorbidities. The combination of all tests with liver biopsy allowed 225/235 (96%) patients to be correctly classified. The combination of all tests without liver biopsy allowed 191/235 (81.3%) patients to be correctly classified; liver biopsy remained mandatory in some patients (18.7%).

Adult↗

Adefovir dipivoxil alone or in combination with lamivudine in patients with lamivudine-resistant chronic hepatitis B.

BACKGROUND AND AIMS: Adefovir dipivoxil possesses potent in vitro and in vivo antiviral activity in wild-type hepatitis B. This study assessed the safety and efficacy of adefovir dipivoxil alone and in combination with lamivudine compared with ongoing lamivudine therapy in patients with chronic hepatitis B with compensated liver disease and lamivudine-resistant hepatitis B virus (HBV). METHODS: Fifty-nine hepatitis B e antigen (HBeAg)-positive patients with genotypic evidence of lamivudine-resistant HBV, serum alanine aminotransferase (ALT) level > or =1.2 times the upper limit of normal, and serum HBV DNA level > or =6 log(10) copies/mL despite ongoing treatment with lamivudine were randomized to adefovir dipivoxil 10 mg, lamivudine 100 mg, or addition of adefovir dipivoxil to ongoing lamivudine daily. The primary end point was the time-weighted average change from baseline in serum HBV DNA level (DAVG) up to week 16. RESULTS: Rapid reductions in serum HBV DNA level were seen by 4 weeks in all recipients of adefovir dipivoxil; DAVG(16) was -0.07 in the lamivudine group compared with -2.45 and -2.46 log(10) copies/mL in the adefovir dipivoxil/lamivudine and adefovir dipivoxil monotherapy groups, respectively (P < 0.001). Median change from baseline in serum HBV DNA level at week 48 was 0.0, -3.59, and -4.04 log(10) copies/mL in the lamivudine, adefovir dipivoxil/lamivudine, and adefovir dipivoxil groups, respectively. ALT level normalized in 10 of 19 (53%) and 9 of 18 (47%) recipients of adefovir dipivoxil/lamivudine and adefovir dipivoxil, respectively, compared with 1 of 19 (5%) recipients of lamivudine. Three patients receiving adefovir dipivoxil or adefovir dipivoxil/lamivudine and none receiving lamivudine monotherapy were HBeAg negative at week 48 and one became hepatitis B surface antigen negative. CONCLUSIONS: These data, limited to patients with compensated liver disease, indicate that adefovir dipivoxil alone or in combination with ongoing lamivudine therapy provides effective antiviral therapy in patients with lamivudine-resistant HBV.

Adenine↗

Kinetics of serum cytokines reflect changes in the severity of chronic hepatitis C presenting minimal fibrosis.

Our aims were to measure the kinetics of serum tumour necrosis alpha (TNF-alpha) and transforming growth factor beta (TGF-beta) levels as markers of progression of disease in nontreated chronic hepatitis C virus (HCV)-infected patients with minimal or no fibrosis and minimal histology activity index (HAI) scores. Our study group consisted of 56 patients diagnosed with minimal (1) or no fibrosis (0) and minimal HAI (0-1) on their first biopsy as defined by Knodell and METAVIR scores. We compared their initial (entry of study) cytokine levels with a group of 103 HCV controls with minimal (0-1) to mild fibrosis (0-3) and mild HAI (5.5). Serum TNF-alpha and TGF-beta levels were measured by enzyme-linked-immunosorbent-assay. A significant difference was seen in TNF-alpha levels at baseline in the study group vs. controls. Regardless of their HAI, there was a correlation between TGF-beta and degree of fibrosis. As shown by their biopsies, during the 3 years (from entry to follow up), many of the patients that initially had minimal fibrosis progressed to higher degree of fibrosis. This progression is paralleled by an increase in TGF-beta levels when comparing initial and follow-up levels. In conclusion, serum TNF-alpha reflects the progression of inflammation as seen in liver biopsies and TGF-beta reflects the degree of fibrosis in HCV patients.

Adult↗

Hepatitis C virus genotyping based on 5' noncoding sequence analysis (Trugene).

Hepatitis C virus (HCV) genotyping of samples from 184 patients with chronic HCV infection by the Trugene 5'NC genotyping kit, based on sequence analysis of the 5' noncoding region (5' NCR), and the InnoLiPA assay was evaluated. In addition to these methods, the 184 samples were also analyzed by sequencing of part of the NS5B of the HCV genome after in-house PCR amplification, as a means of validating results obtained with the 5' NCR. The distribution of the genotypes typed by NS5B sequence analysis was as follows: 1a, 41 samples; 1b, 58 samples; 1d, 1 sample; 2a, 5 samples; 2b, 2 samples; 2c, 7 samples; 3a, 46 samples; 4a, 7 samples; 4c, 1 samples; 4e, 9 samples; 5a, 6 samples; 6a, 1 sample. The Trugene and InnoLiPA assays gave concordant results within HCV types in 100% of cases. The ability to discriminate at the subtype level was 76 and 74% for the Trugene and the InnoLiPA assays, respectively.

5' Untranslated Regions↗

Absence of hepatitis C genome in semen of infected men by polymerase chain reaction, branched DNA and in situ hybridization.

BACKGROUND/AIMS: The presence or absence of hepatitis C virus (HCV) RNA in the semen of infected man remains controversial, mainly due to technical difficulties associated with nucleic acid detection. The aims of this study were to assess the presence of HCV RNA in spermatozoa and in seminal fluid using different polymerase chain reaction (PCR)- and non-PCR-dependent methods and, in the case of HCV presence, to correlate this detection with the viraemia. METHODS: Serum and semen from 25 chronically infected hepatitis C patients were studied. The semen was separated into spermatozoa and seminal fluid and HCV RNA was analysed in the two fractions using RT-PCR and branched DNA. The presence of HCV RNA in pelleted cells was also assessed using in situ hybridization. RESULTS: All three approaches failed to demonstrate HCV RNA in semen. The presence of an inhibitor of the PCR was demonstrated in seminal fluid but not in spermatoza. CONCLUSION: Our results confirmed the lack of detection of HCV RNA in semen by PCR- and non-PCR-dependent techniques and support the view that viral contamination in semen remains, if present, at a very low level. Nevertheless, epidemiological studies are required to definitively assess the absence of sexual transmission of HCV

Adolescent↗

Treatment of hepatitis C virus-related cirrhosis: a randomized, controlled trial of interferon alfa-2b versus no treatment.

To examine the effects of interferon (IFN) therapy on clinical, biochemical, and histological features in patients with compensated hepatitis C virus (HCV)-related cirrhosis, we have conducted a randomized, controlled trial of IFN therapy versus observation. Eight centers included a total of 99 patients with biopsy-proven cirrhosis. IFN-alpha2b, 3 million units three times per week, or no antiviral therapy was given for 48 weeks. Twenty-three patients dropped out. End-of-treatment biochemical response was not observed in any of the 39 controls but was observed in 6 of the 47 treated patients (P <.02); sustained biochemical response was obtained in only 2 treated patients. Controls and treated patients did not significantly differ with regard to the changes in serum level of albumin, bilirubin, alpha-fetoprotein, in plasma prothrombin, in histological activity, or liver collagen content. During trial or follow-up (160 +/- 57 weeks), hepatocellular carcinoma developed in 9 controls and 5 treated patients (NS); decompensation of cirrhosis occurred in 5 controls and 7 treated patients. Seven controls and 10 treated patients died. In conclusion, in patients with compensated HCV-related cirrhosis, a 48-week course of IFN therapy is safe and is able to induce end-of-treatment biochemical response in a significant proportion of patients. However, a 48-week course of IFN therapy usually fails to achieve sustained response and, within the limit of this study, did not significantly improve the 3-year outcome. Therefore, a longer course of IFN therapy or combination therapy with ribavirin should be evaluated in patients with HCV-related cirrhosis.

Adolescent↗

Impact of various handling and storage conditions on quantitative detection of hepatitis C virus RNA.

BACKGROUND/AIMS: Both HCV RNA viral load and HCV genotype have been described as important predicting factors determining the response to interferon in chronic hepatitis C. To investigate whether processing and storage conditions might influence the stability and could alter the concentration of the HCV RNA in serum, quantification of HCV RNA was performed by branched DNA assay. METHODS: We studied serum samples obtained from seven patients with histologically proven chronic hepatitis C. These were subjected to the following physical conditions: (1) immediate quantification, (2) storage at room temperature for 5 days, (3) storage at 4 degrees C for 5 days, (4) storage at -20 degrees C for 5 days, (5) storage at -80 degrees C for 5 days, (6) five freeze-thaw cycles, (7) blood unspun for 4 h at room temperature then centrifuged and stored at -80 degrees C for 5 days, (8) storage at 4 degrees C for 6 months, (9) storage at -20 degrees C for 6 months, (10) storage at -80 degrees C for 6 months. RESULTS: A loss of 100% HCV RNA titers was observed after storage at RT for 5 days and then storage at 4 degrees C for 6 months. A surprising decrease of HCV RNA titer (15.6%) was observed in sera stored for 5 days at -20 degrees C. Five freeze-thaw cycles resulted in a 16% decrease of the HCV RNA level. When centrifugation was performed after a 4 h delay at room temperature, a significant loss of HCV RNA titers of 29.5% was observed. Long-term stability (6 months) was observed at -80 degrees C with a slight loss of about of 10% HCV RNA titers, but a significant decrease in HCV RNA of 23% was observed at -20 degrees C. The reproducibility of the bDNA assay on five patient samples was performed eight times in duplicate and showed an average coefficient of variation of 9.1%. CONCLUSIONS: These data confirm the importance of storage and handling in measuring the amount of HCV RNA in clinical samples.

Blood Preservation↗

Myasthenia gravis and hepatitis C virus infection.

Chronic hepatitis C virus (HCV) infections are often associated with extrahepatic immunological manifestations, including various autoimmune disorders. The aims of this study were to determine the prevalence of HCV markers in patients with myasthenia gravis (MG) and to determine any relationship with HCV infection. Eighty-three patients with MG. 40 men aged 20-93 years and 43 women aged 13-87 years (mean age 54 years) were studied. The MG patients were positive for antibody to acetylcholine receptor in addition, their sera was analysed for antibody to HCV (HCVAb) and HCV RNA, HCVAb was detected in two of the 83 patients (2.4%). Four patients were repeatedly HCV RNA positive. They were infected by HCV genotype 1 (one patient), HCV genotype 2a (two patients) and an undetermined HCV genotype in one patient. They received plasmapheresis or intravenous immunoglobulin treatment. Among the four patients, one was infected after the onset of MG without receiving a blood transfusion or using intravenous drugs. The other three had chronic hepatitis C which was discovered at the same time as MG and only one patient had been exposed to blood products. The prevalence of HCV markers in patients with MG (4.8%) was higher than that reported for the general French population, about 1%. This prevalence is similar to that occurring in patients exposed to plasmapheresis or intravenous immunoglobulin. In conclusion, HCV appears to play little, if any, role in causing MG. The higher prevalence of infection among MG patients may be related to transmission in the course of therapy.

Adolescent↗

Is tobacco a risk factor for chronic pancreatitis and alcoholic cirrhosis?

In a case control study alcohol intake and tobacco use were assessed between 1975 and 1987 in 103 male patients suffering from alcoholic cirrhosis of the liver, in 145 patients with chronic pancreatitis, and in 264 control subjects. The patients with chronic pancreatitis were significantly younger than the patients with cirrhosis (mean (SD) age 41.92 (2.4) v 60.9 (11.6) years). Among the patients with chronic pancreatitis, 94% were both smokers and drinkers compared with 83% of patients with cirrhosis of the liver. The relative risks for each disease were calculated by conditional multiple logistic regression. Whereas daily intake of alcohol was a major risk factor for both cirrhosis of the liver and chronic pancreatitis, smoking was significantly related only to the risk of having chronic pancreatitis. Moreover, the mean age at onset of pancreatitis was lower among smokers.

Adult↗

Pancreatic cysts and pseudocysts associated with acute and chronic pancreatitis.

We reviewed 106 consecutive patients with cysts or pseudocysts of the pancreas associated with pancreatitis. A pancreatic fluid collection (PFC) was defined as a limited collection containing pancreatic juice either pure or with pus or blood. Seventy-seven patients presented with chronic pancreatitis (CP) and 29 patients presented with acute pancreatitis (AP). CP-associated PFC was observed in young alcoholic men (mean age 40.8 years) on a high fat, protein, and carbohydrate diet. None of this group had gallstones. In this population, PFC was located in the head of the pancreas in 68% of the cases, was partly extrapancreatic in 22% of the cases, and resolved spontaneously in 9%. AP-associated PFC was as frequent in nonalcoholic men as in nonalcoholic women and presented with gallstones in 48%. They developed later (mean age 53.0 years), resolved spontaneously in 20%, and were located in the body or tail of the gland in 69%. CP-PFC may be designated retention cysts or retention pseudocysts (extrapancreatic); AP-PFC may be designated necrotic pseudocysts.

Acute Disease↗

Chlormezanone-induced fulminant hepatitis in a pregnant woman: successful delivery and liver transplantation.

The case of a 29 year old woman affected by fulminant hepatitis during the third trimester of pregnancy, after a 3 week administration of chlormezanone is reported. Following induced Caesarean delivery, the patient underwent an orthotopic liver transplantation. The mother and her baby were in good condition 26 months after liver transplantation. In this case, chlormezanone was probably responsible for the fulminant hepatitis.

Acute Disease↗