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Daniel Dhumeaux

Publications and source records attributed to Daniel Dhumeaux.

35 records · Page 2Linked to original sources
PubMed2002

Risk factors for lymphoproliferative disorders after liver transplantation in adults: an analysis of 480 patients.

BACKGROUND: Posttransplant lymphoproliferative disorder (PTLD) is a well-known complication of organ transplantation that leads to death in more than 50% of cases. The aim of this work was to identify specific risk factors for lymphoproliferative disorders after liver transplantation in adults. METHODS: A total of 480 consecutive patients who underwent transplantation between 1986 and 1997 were studied (323 men, 157 women; mean age: 49.8+/-10.4 years). Demographics, the indication for transplantation, the immunosuppressive regimens, the incidence of rejection episodes, and Epstein-Barr virus infection were analyzed. Univariate and multivariate analysis were used to identify factors predictive of PTLD. RESULTS: Sixteen cases of PTLD (3.3%) occurred at a median of 5.5 (range, 1-39) months after liver transplantation. All 16 cases occurred in patients with evidence of exposure to Epstein-Barr virus before transplantation. In multivariate analysis, the use of antilymphocyte antibodies (P=0.007, relative risk [RR]=4.2, 95% confidence interval [CI]=1.5-11.7), age older than 50 years (P=0.037, RR=3.5, 95% CI=0.95-13.0), liver transplantation for hepatitis C virus cirrhosis (P=0.015, RR=8.7, 95% CI=1-78.3), and liver transplantation for alcoholic cirrhosis (P=0.015, RR=9.6, 95% CI=1.2-77.2) were independently associated with the onset of PTLD. CONCLUSION: Liver transplantation for hepatitis C virus-related and alcoholic cirrhosis and age older than 50 years are three additional risk factors for lymphoproliferative disorder independent of the use of antilymphocyte antibodies. The use of antilymphocyte antibodies after liver transplantation should be avoided in these categories of patients, especially those older than 50 years.

Adult↗
PubMed2002

Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection.

BACKGROUND: Treatment with peginterferon alfa-2a alone produces significantly higher sustained virologic responses than treatment with interferon alfa-2a alone in patients with chronic hepatitis C virus (HCV) infection. We compared the efficacy and safety of peginterferon alfa-2a plus ribavirin, interferon alfa-2b plus ribavirin, and peginterferon alfa-2a alone in the initial treatment of chronic hepatitis C. METHODS: A total of 1121 patients were randomly assigned to treatment and received at least one dose of study medication, consisting of 180 microg of peginterferon alfa-2a once weekly plus daily ribavirin (1000 or 1200 mg, depending on body weight), weekly peginterferon alfa-2a plus daily placebo, or 3 million units of interferon alfa-2b thrice weekly plus daily ribavirin for 48 weeks. RESULTS: A significantly higher proportion of patients who received peginterferon alfa-2a plus ribavirin had a sustained virologic response (defined as the absence of detectable HCV RNA 24 weeks after cessation of therapy) than of patients who received interferon alfa-2b plus ribavirin (56 percent vs. 44 percent, P<0.001) or peginterferon alfa-2a alone (56 percent vs. 29 percent, P<0.001). The proportions of patients with HCV genotype 1 who had sustained virologic responses were 46 percent, 36 percent, and 21 percent, respectively, for the three regimens. Among patients with HCV genotype 1 and high base-line levels of HCV RNA, the proportions of those with sustained virologic responses were 41 percent, 33 percent, and 13 percent, respectively. The overall safety profiles of the three treatment regimens were similar; the incidence of influenza-like symptoms and depression was lower in the groups receiving peginterferon alfa-2a than in the group receiving interferon alfa-2b plus ribavirin. CONCLUSIONS: In patients with chronic hepatitis C, once-weekly peginterferon alfa-2a plus ribavirin was tolerated as well as interferon alfa-2b plus ribavirin and produced significant improvements in the rate of sustained virologic response, as compared with interferon alfa-2b plus ribavirin or peginterferon alfa-2a alone.

Adult↗
PubMed2002

Quasispecies heterogeneity and constraints on the evolution of the 5' noncoding region of hepatitis C virus (HCV): relationship with HCV resistance to interferon-alpha therapy.

Hepatitis C virus (HCV) polyprotein translation depends on direct internal entry of the 40S ribosomal subunit mediated by an internal ribosome entry segment (IRES) located in the 5' noncoding (5'NC) region of the viral genome. HCV is genetically heterogeneous and is characterized by the existence of a quasispecies distribution of the virus population within a single infected individual. Cloning and sequencing strategies were used to characterize 5'NC quasispecies genetically. Similar to coding regions, the HCV 5'NC region was distributed as a quasispecies, but it appeared to be subjected to stronger conservatory constraints than other regions of the HCV genome, probably due to the need for structural (and functional) conservation of the IRES. Indeed, most of the quasispecies substitutions were in unpaired regions of the IRES or clustered such that base-pairing was maintained, whereas only 21% were expected to result in a loss of base-pairing. Quasispecies-related structural changes could be predicted in the core cruciform of IRES domain III composed of the RNA helices which extend from the four-way junction JIIIabc, mostly in minor variants, but sometimes in major ones. The results presented here suggest the simultaneous presence in infected patients of a mixture of genetically distinct but closely related IRES sequences that may have different structures. No significant genetic changes of 5'NC quasispecies were observed after interferon-alpha treatment, except in patients with mixed genotype infection who cleared one of the infecting strains during therapy, suggesting that the quasispecies distribution of IRES sequences does not play a role in HCV resistance to interferon-alpha therapy. In contrast, the overall quasispecies distribution of HCV genomes (including IRES sequences) might participate in regulation of hepatic and extrahepatic HCV replication.

5' Untranslated Regions↗
PubMed2002

Hepatitis C virus (HCV)-related cryoglobulinemia after liver transplantation for HCV cirrhosis.

The aim of this study was to analyze the clinical impact of hepatitis C virus (HCV)-related cryoglobulinemia in patients that had received liver transplants after HCV cirrhosis. Thirty patients who had received transplants between 1990 and 1996 for HCV cirrhosis and who had a follow-up longer than 1 year were studied. Serum HCV RNA levels, HCV genotype, cryoglobulinemia, rheumatoid factor, serum C3 and C4, IgA, IgG, IgM levels, liver tests, and liver histology were studied 30 +/- 16 months post-transplant. Cryoglobulinemia was found in 9 of 30 patients (30.0%) and was symptomatic in 4 of the 9 cases (glomerulonephritis, 1 case; palpable purpura, 3 cases). Age, sex distribution, alanine aminotransferase (ALAT) activity, and Knodell score did not differ, whether cryoglobulinemia was present or not. Rheumatoid factor (209.5 +/- 70.4 IU/l vs 12.0 +/- 4.4 IU/l, P = 0.004) and IgM levels (3.2 +/- 0.5 g/l vs 1.6 +/- 0.9 g/l, P = 0.0001) were significantly higher, and C4 levels (0.16 +/- 0.16 g/l vs 0.30 +/- 0.10 g/l, P = 0.009) were significantly lower in patients with cryoglobulinemia. One patient died from cryoglobulin-related renal failure. We concluded that, after liver transplantation (LT) for HCV cirrhosis, cryoglobulinemia was frequent and often symptomatic. Cryoglobulinemia did not seem to be associated with more severe graft damage. Cryoglobulinemia-associated morbidity must be taken into account in the management of post-transplant HCV infection.

Adult↗
PubMed2002

Clinical utility of total HCV core antigen quantification: a new indirect marker of HCV replication.

Hepatitis C virus (HCV) RNA detection, viral load quantification, and HCV genotyping are widely used in clinical practice. Recently, the availability of an anticore antigen (Ag) monoclonal antibody allowed development of an enzyme-linked immunosorbent assay (ELISA) detecting and quantifying total HCV core Ag in peripheral blood of HCV-infected patients. The aims of the present study were to investigate the biologic significance of this new marker in HCV infection, to establish the intrinsic performance of the current assay, and to determine its potential utility in the management of HCV-infected patients. A panel of infected sera calibrated to the World Health Organization International Standard and 657 serum samples from infected patients receiving antiviral treatment were studied. We showed that total HCV core Ag quantification is an accurate, precise, and specific indirect marker of HCV replication. We estimated that 1 pg/mL of total HCV core Ag is equivalent to approximately 8,000 HCV RNA international units (IU)/mL, although minor between-patient differences may exist. In conclusion, total HCV core Ag quantification can be used in the various indications of viral load monitoring, including the evaluation of baseline viral load before therapy, the assessment of the virologic response to antiviral treatment, and the study of early viral kinetics during therapy. Nevertheless, the total HCV core Ag assay cannot be used as a marker of viral replication for HCV RNA values below 20,000 IU/mL, limiting its use in the monitoring of late events during and after antiviral treatment.

Biomarkers↗
PubMed2002

Effects of noradrenalin and albumin in patients with type I hepatorenal syndrome: a pilot study.

Treatment of hepatorenal syndromes (HRSs) is currently based on vasopressin analogs. The aim of this pilot study was to evaluate the efficacy and safety of noradrenalin (NA) in the treatment of type 1 HRS. Between 1998 and 2000, 12 consecutive patients with type 1 HRS (7 men, 5 women; mean age, 54 +/- 11 years; mean Child-Pugh score, 11.3 +/- 1.7) were treated with intravenous NA (0.5-3 mg/h), in combination with intravenous albumin and furosemide. NA was given for 10 +/- 3 days, at a mean dose of 0.8 +/- 0.3 mg/h. Reversal of HRS was observed in 10 of 12 patients (83%; 95% confidence interval, 52%-98%) after a median of 7 days (range, 5-10 days). Serum creatinine levels fell from 358 +/- 161 to 145 +/- 78 micromol/L (P <.001), creatinine clearance rose from 13 +/- 9 to 40 +/- 15 mL/min (P =.003), and urinary sodium output increased from 8 +/- 14 to 52 +/- 72 mEq/d (P =.002). Changes in renal function under NA treatment were associated with an increase in mean arterial pressure (MAP; 65 +/- 7 to 73 +/- 9 mm Hg, P =.01) and a marked reduction in active renin (565 +/- 989 to 164 +/- 196 ng/L, P =.001) and aldosterone plasma concentrations (1,945 +/- 1,931 to 924 +/- 730 ng/mL, P =.02). There was one episode of reversible myocardial hypokinesia (in a patient on 1.5 mg/h NA) that did not recur after a dose reduction. In conclusion, NA combined with albumin and furosemide appears effective and safe for the treatment of type 1 HRS.

Adrenergic alpha-Agonists↗
PubMed2002

Alpha interferon inhibits hepatitis C virus replication in primary human hepatocytes infected in vitro.

Chronic hepatitis C is a common cause of liver disease, the complications of which include cirrhosis and hepatocellular carcinoma. Treatment of chronic hepatitis C is based on the use of alpha interferon (IFN-alpha). Recently, indirect evidence based on mathematical modeling of hepatitis C virus (HCV) dynamics during human IFN-alpha therapy suggested that the major initial effect of IFN-alpha is to block HCV virion production or release. Here, we used primary cultures of healthy, uninfected human hepatocytes to show that: (i) healthy human hepatocytes can be infected in vitro and support HCV genome replication, (ii) hepatocyte treatment with IFN-alpha results in expression of IFN-alpha-induced genes, and (iii) IFN-alpha inhibits HCV replication in infected human hepatocytes. These results show that IFN-alpha acts primarily through its nonspecific antiviral effects and suggest that primary cultures of human hepatocytes may provide a good model to study intrinsic HCV resistance to IFN-alpha.

Antiviral Agents↗
PubMedDate not supplied

[Congenital cystic diseases of the intra and extrahepatic bile ducts].

Congenital cystic lesions of bile ducts may affect intra or extrahepatic bile ducts. Intrahepatic lesions include five entities: congenital hepatic fibrosis, Caroli's syndrome, von Meyenburg complexes, simple cyst of the liver and polycystic liver disease. Congenital hepatic fibrosis and von Meyenburg complexes are secondary to ductal plate malformation affecting the smallest intrahepatic bile ducts. Cystic dilatations are of small size and only detected at histological examination of the liver. They have few clinical consequences. In congenital hepatic fibrosis, the main manifestations result from portal hypertension. Caroli's syndrome is secondary to ductal plate malformation affecting the largest intrahepatic bile ducts. Cystic dilatations are macroscopic and responsible for cholangitis and may lead to biliary stones and carcinoma which develop within cystic dilatations. Caroli's syndrome may be or not associated with congenital hepatic fibrosis. In case of associated congenital hepatic fibrosis, portal hypertension is present. Simple cyst of the liver and polycystic liver disease are characterized by cystic dilatations which, by contrast to the preceding entities, do not communicate with the rest of biliary tree. As a result, they have only few clinical consequences. In congenital hepatic fibrosis and polycystic liver disease, renal abnormalities are frequently observed. They correspond to renal malformations associated with biliary malformations. In congenital hepatic fibrosis, renal lesions are characterized by ectatic collecting tubules which are present in two thirds of the cases and transmitted as an autosomal recessive trait. In polycystic liver disease, renal lesions are characterized by polycystic disease which is present in half of the cases and transmitted as an autosomal dominant trait. Congenital cystic lesions of extrahepatic bile ducts consist of choledochal cyst, which is secondary to malformation of the pancreato-biliary ductal junction. The major risk of choledochal cyst is the development of intracystic cancer, the prevention of which is total surgical resection of the cyst.

Bile Duct Diseases↗