Christian Jacquelinet

Noninvasive prediction of fibrosis in C282Y homozygous hemochromatosis

BACKGROUND & AIMSnThe diagnosis of hemochromatosis is now possible for C282Y homozygous patients using noninvasive molecular genetic tests. The aim of this study was to define noninvasive factors predictive of severe fibrosis (bridging fibrosis or cirrhosis) to avoid unnecessary liver biopsies in such patients.nnnMETHODSnClinical and biological data were recorded at the time of diagnosis in 197 French C282Y homozygous patients, 52 (26%) of whom had severe fibrosis. Variables significantly linked to severe fibrosis using univariate analysis were entered into a multivariate stepwise analysis. These variables were combined to obtain a simple index allowing for prediction of severe fibrosis.nnnRESULTSnSerum ferritin, hepatomegaly, and serum aspartate aminotransferase were selected using multivariate analysis. Their combination applied to the 96 patients with ferritin level of </=1000 microgram/L, normal aspartate aminotransferase values, and absence of hepatomegaly showed that no severe fibrosis was encountered in this subgroup of patients. The results were validated in 113 C282Y homozygous patients in Canada with a good reproducibility of negative prediction but a poor reproducibility of the positive prediction of severe fibrosis.nnnCONCLUSIONSnIn C282Y homozygous patients, the diagnosis of severe fibrosis relies on liver biopsy, but absence of severe fibrosis can be accurately predicted in most patients on the basis of simple clinical and biochemical variables.

Molecular adsorbent recirculating system dialysis in patients with acute liver failure who are assessed for liver transplantation

ObjectiveTo assess the usefulness of dialysis with the molecular adsorbent recirculating system (MARS) in patients with acute liver failure who fulfil criteria for liver transplantation.DesignObservational cohort study.SettingICU at axa0liver transplantation centre.PatientsTwenty-two patients (23 episodes) received MARS dialysis. They were either listed for LT (nu202f=u202f14), delayed (nu202f=u202f1), or not listed (contra-indication, nu202f=u202f7).InterventionsAxa0total of 56 MARS treatments (median per patient 2; mean duration 7.6u202f±u202f2.6u202fh) were performed on haemodialysis.Measurements and resultsClinical and biological variables were assessed before and 24u202fh after MARS therapy. The rate of recovery of liver function without transplantation was compared with an expected rate and survival was analysed.Following MARS dialysis, we observed an improvement in the grade of hepatic encephalopathy (Pu202f=u202f0.02) and the Glasgow coma score (Pu202f=u202f0.02), axa0decrease in conjugated bilirubin (Pu202f=u202f0.05) and INR (Pu202f=u202f0.006), and an increase in prothrombin index (Pu202f=u202f0.005). Overall, liver function improved in seven patients (32%): four listed patients in whom transplantation could be avoided and three patients among those not listed due to contra-indications. The transplant-free recovery rate in listed patients was 29% (vs. expected 9%, Pu202f=u202f0.036). Listed patients (nu202f=u202f14) had axa0higher 30-day survival rate [86% (12/14) vs 38% (3/8), Pu202f=u202f0.05] and axa0higher long-term survival rate (Pu202f=u202f0.02).ConclusionsAxa0statistically significant improvement of liver function was observed after MARS therapy. Transplant-free recovery was more frequent than expected. The apparent benefit of MARS dialysis to treat acute liver failure needs to be confirmed by axa0controlled study.

Magnetic resonance imaging and assessment of liver iron content in genetic hemochromatosis.

Computed tomography (CT) scanning is not highly sensitive in the assessment of liver iron content and magnetic resonance imaging (MRI) appears to be more efficient. The aim of this study was to determine the effectiveness of MRI in the evaluation of liver iron content using a standard spin-echo technique. The study included 23 patients with genetic hemochromatosis and 24 non-iron-overloaded patients as controls. A comparison was made of: (a) MRI signal intensity of liver, spleen, paravertebral muscles and subcutaneous adipose tissue using two different spin-echo sequences (SE 500/28; SE 2000/28,56); (b) liver attenuation determined by a single energy CT scan; and (c) a biochemical determination of hepatic iron. There was a significant decrease in liver signal intensity in the genetic hemochromatosis group (256 +/- 201, mean +/- S.D.) compared with the control group (801 +/- 413, p less than 0.001), but there was no correlation with liver iron concentration. However, such a correlation was found and was even more highly significant than in CT when the ratio between the liver and another organ was taken into account. For a lower limit of liver/spleen ratio calculated at 0.46 (mean 2 S.D. in the control group), the specificity (0.96) of MRI was satisfactory, but the sensitivity (0.78) remained insufficient (MRI being unable to detect an iron overload of up to 125 mumol/g). Hopefully, these results might be improved in the near future by using more sensitive sequences such as gradient echo sequences.

A new approach for measuring gender disparity in access to renal transplantation waiting lists.

Background Gender inequity in access to renal transplantation waiting lists, in favor of men, has long since been demonstrated in a number of studies. Discrepancies between the results of the available studies might be explained by different analytical approaches or different national contexts. In this study we analyzed French end-stage renal disease registry data using a novel model to determine whether the female gender is associated with a lower probability of being listed on the transplant waiting list or with a longer time from dialysis start until registration, or both. Methods The effect of gender on access to the national renal transplantation waiting list was assessed in 9497 men and 5386 women aged 18 to 74 years who started dialysis between 2002 and 2009. We used a semiparametric regression cure model adjusted for age, work status, and 11 comorbidities or disabilities. Results Women were younger and less likely to work or have associated comorbidities. At the study endpoint, 33.8% of the men and 34.1% of the women were placed on the renal transplantation waiting list. After taking potential confounders into account, our model shows that women demonstrated a lower probability of being registered on the national transplant waiting list (odds ratio=0.69; 95% confidence interval, 0.62–0.78) and a longer time from dialysis start to registration (hazard ratio=0.89; 95% confidence interval, 0.84–0.95) than men. This disparity affects predominantly older women who do not work or have diabetes and is more pronounced in some geographic areas. Conclusions These poorly understood gender-based inequities require further consideration.

Hepatitis B virus infection markers in genetic haemochromatosis: A study of 272 patients

Serum hepatitis B virus (HBV) infection markers were studied in 272 patients with homozygous genetic haemochromatosis complicated (n = 33) or not (n = 239) with primary liver cancer (PLC). Controls consisted of 255 029 healthy blood donors from whom age- and sex-matched control groups were extracted for statistical evaluation using the Fisher exact test. In blood donors, HBsAg was positive in 0.075% of males and 0.04% of females. This population was not screened for anti-Hbs. Anti-Hbc alone (without HBsAg) was present in 3.7% of men and 1.8% of women. In patients with genetic haemochromatosis without liver cancer (183 males, 45.6 +/- 11.3 yrs and 56 women, 48 +/- 12.4 yrs), HBsAg was found in 1.1% of men and in none of the women. Anti-HBs was present in 7.3% of males and 1.8% of females. Anti-HBc alone was found in 13% of males (p less than 0.005 vs. controls) and 2.1% of females. From male patients with primary liver cancer complicating genetic haemochromatosis (32 males, 61.7 +/- 6.8 yrs and one female), 6.2% were HBsAg positive, 3.4% were anti-HBs positive and 16.6% anti-HBc positive (p = 0.05 vs. controls). No serum HBV marker was found in the woman. In conclusion, the prevalence of HBV infection markers--especially anti-HBc--is significantly increased in patients with genetic haemochromatosis complicated or not with primary liver cancer.

Liver Transplantation Avoided in Patients With Fulminant Hepatic Failure Who Received Albumin Dialysis With the Molecular Adsorbent Recirculating System While on the Waiting List: Impact of the Duration of Therapy

Eighteen patients with fulminant hepatic failure due to various medical causes were listed for emergency liver transplantation and treated with extracorporeal albumin dialysis sessions using the molecular adsorbent recirculating system (MARS) at our center over a 74‐month period. Due to improvement of liver function, transplantation could be avoided in 9 patients (50%, 95% confidence interval 29% to 71%) who fully recovered afterwards. This improvement rate was higher than the rate of improvement in the French cohort of fulminant hepatic failure patients with similar etiologies (19.3%, 95% confidence interval 14.9% to 24.6%, Pu2003=u20030.002). In our 18 patients, there were no statistically significant differences in any baseline characteristics or in the time with liver failure meeting transplant criteria between the patients who improved while waiting and those who did not. However, the patients who improved received a greater number of sessions and a longer total duration of MARS therapy (all Pu2003<u20030.001). In the whole study population, a MARS therapy duration ≥15u2003h was significantly associated with improvement of liver function without transplantation (adjusted adds ratio [OR] 65.76, 2.48–1743.11, Pu2003=u20030.01). Tolerance of therapy was acceptable. These results suggest that MARS therapy could contribute to native liver recovery and is safe in patients on the waiting list for fulminant hepatic failure. A minimum duration of therapy (≥15u2003h) could be necessary to expect significant liver function improvement.

SIMS@REIN : un système d’information multi-sources pour l’insuffisance rénale terminale

In France, the prevalence of End-Stage Renal Disease (ESRD) is not precisely known. The sources of information are scattered and not coordinated. Consequently, care is ill adapted to meet the demand. The Multi-Source Information System is the basis of the Renal Epidemiology and Information Network (REIN). It is dedicated to improve and organise our medical and epidemiological knowledge of ESRD and to aid public health decision-making in this area. The proposed approach is based on the datawarehouses. This model allows a unified vision of scattered data into distinct databases, for a better management, be it particular (patient follow-up) or global (regional follow-up), with a finality of aid in decision-making. Several categories of problems were considered: the global conception of the information system, the organisation of the datawarehouse, which offers different viewpoints of the data, the integration of heterogeneous data coming from different sources, data exchange and definition of a specific ontology.

High rate of long‐term virological response after a 1‐year course of interferon ± ribavirin in chronic hepatitis C relapsers. Results of a 191 patients randomized trial

We investigated the long‐term efficacy of a 12‐month course of interferon (IFN)+ribavirin in chronic hepatitis C relapsers. We randomized 191 relapsers with a 2:1 ratio to receive 3 million units three times a week of interferon alpha (IFN α)‐2b+ribavirin (1–1.2u2003g/day) (group A=127 patients) or IFN α‐2b (group B=60 patients) of same dosage and duration for 1 year. General and hepatitis C data of group A and B patients were similar. The main goal of the study was to determine the rate of sustained virological response evaluated 1 year after treatment.

External Validation of the Donor Risk Index and the Eurotransplant Donor Risk Index on the French Liver Transplantation registry

A major limitation to liver transplantation is organ shortage leading to the use of non‐optimal liver grafts. The Donor Risk Index has been validated and recommended to select donors/organs. The Eurotransplant Donor Risk Index was derived from the Donor Risk Index. The objective of our study was to perform an external validation of both Donor Risk Index and Eurotransplant‐Donor Risk Index against the French liver transplantation Cristal registry according to recommendations of the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis.

Short-term prednisolone followed by recombinant human α-interferon alone or combined with adenine-arabinoside in chronic hepatitis B: A prospective and randomized trial

Twenty-nine patients with chronic hepatitis B, presenting both hepatitis B surface antigen and hepatitis B virus deoxyribonucleic acid in serum, were studied in a randomized trial treatment consisting of oral prednisolone for 28 days followed 14 days after steroid withdrawal, by either a 55 s.c. injection course of 5 M unit recombinant human alpha-interferon (group 1, 14 patients) or by adenine-arabinoside (for 21 days) combined from the fourteenth day on with the same 55 s.c. injection schedule of interferon (IFN) (group 2, 15 cases). The two groups were well matched with respect to demographic, biochemical, virological and histologic features. Significant side-effects leading to premature discontinuation of interferon were observed in only four cases in group 2 and were always reversible. Efficacy was judged on a mean follow-up period of 17 months. For the whole population, 17 patients (59%) exhibited a sustained serum hepatitis B virus deoxyribonucleic acid disappearance which corresponded to a marked improvement in liver function as demonstrated by a quasi-normalization of their serum transaminase values (ALT with n less than 22 UI/l: 23 +/- 24 vs. 139 +/- 115 before treatment; P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)