[Show abstract][Hide abstract] ABSTRACT: Background Alpha 1 antitrypsin (A1AT) deficiency (A1ATD) is potentially associated with a high degree of liver and/or lung disease. Apart from the most frequent deficiency alleles, Pi S and Pi Z, some A1AT alleles of clinical significance may be easily misdiagnosed. This is typically the case of the Pi Mmalton variant which shares the same ‘gain-of-function’ liver toxicity than Pi Z and the same ‘loss of function’ lung disease as well. Methods The biological diagnosis of A1ATD typically relies on a low serum concentration associated with an abnormal isoelectric focusing (IEF) pattern of migration. However, Sanger direct DNA sequencing may be required for deficiency alleles without biochemical expression (Null alleles) or for A1AT variants whose IEF profiles resemble the wild-type and sub-types M allele but with a low concentration. Results We report four cases of A1ATD involving the deficient Pi Mmalton allele with very different clinical expressions: (i) one Mmalton/Mmalton with liver fibrosis and cirrhosis, (ii) two Mmalton/Z with chronic pulmonary obstructive disease in one case and (iii) one M/Mmalton without liver or lung disease. In both cases, the correct diagnosis has necessitated a genetic analysis. Conclusions Our study provides another example of Pi Mmalton homozygosity associated with a severe liver disease that emphasizes the necessity of a not delayed diagnosis. The great clinical heterogeneity of the other genotypes (which is in agreement with the literature data) questions about the role of environmental and other modifier genes in the pathogenicity of A1ATD.
[Show abstract][Hide abstract] ABSTRACT: Background and aims:
First generation protease inhibitors (PI) with peg-interferon (PEG-IFN) and ribavirin (RBV) have been the only therapy available for hepatitis C virus (HCV) genotype 1 infection in most countries for 3 years. We have investigated the efficacy and tolerance of this triple therapy in transplanted patients experiencing a recurrence of HCV infection on the liver graft.
This cohort study enrolled 81 liver transplant patients (Male: 76%, mean age: 55.8±9.7 years) with severe HCV recurrence (F3 or F4: n = 34 (42%), treatment experienced: n = 44 (54%)), treated with boceprevir (n = 36; 44%) or telaprevir (n = 45; 56%). We assessed the percentages of patients with sustained virological responses 24 weeks after therapy (SVR24), and safety.
The SVR24 rate was 47% (telaprevir: 42%; boceprevir: 53%, P = ns). At baseline, a normal bilirubin level (p = 0.0145) and albumin level >35g/L (p = 0.0372) and an initial RBV dosage of ≥800 mg/day (p = 0.0033) predicted SVR24. During treatment, achieving an early virological response after 12 weeks was the strongest independent factor to predict SVR24 (p<0.0001). A premature discontinuation of anti-HCV therapy due to a serious adverse event (SAE) was observed in 22 patients (27%). Hematological toxicity, infections and deaths were observed in 95%, 28% and 7% of patients, respectively. A history of post-LT antiviral therapy and thrombocytopenia (<50G/L) during treatment were both independent predictors of the occurrence of infections or SAE (p = 0.0169 and p = 0.011).
The use of first generation PI after liver transplantation enabled an SVR24 rate of 47% in genotype 1 patients, but induced a high rate of SAE. The identification of predictive factors for a response to treatment, and the occurrence of SAE, have enabled us to establish limits for the use of this anti-HCV therapy in the transplant setting.
PLoS ONE 09/2015; 10(9):e0138091. DOI:10.1371/journal.pone.0138091 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Alcoholic liver disease (ALD) is a major indication for liver transplantation (LT). Recurrent alcoholic cirrhosis (RAC) after LT can occur but has not been studied. The aims of this study were to estimate the prevalence, predictive factors, and natural history of RAC after LT.
All patients transplanted for ALD between 1990 and 2007 in three French centers were included. The diagnosis of RAC was based on histological evidence or a series of features combined with severe alcoholic relapse.
Among 1,894 adult LT patients, 712 were transplanted for alcoholic cirrhosis and survived >6 months. After a mean follow-up of 9 years, 128 patients (mean age at LT 47.2±7.1 years old, 78.9% men) experienced severe alcoholic relapse (18.0% of cases). Severe alcoholic relapse occurred after a median delay of 25 months (range 4-157) after LT. RAC was diagnosed in 41 patients with severe relapse (32%). The diagnosis of RAC was made after a median delay of 5.1 years (range 1.8-13.9) after LT and of 4.0 years (range 1.2-11.5) after relapse. RAC was significantly associated with younger age and a shorter period of pre-LT abstinence. One-, 5-, 10-, and 15-year survival was 100, 87.6, 49.7, and 21.0%, respectively, for RAC patients vs. 100, 89.4, 69.9, and 41.1%, respectively, for the patients without RAC (P<0.001).
RAC occurs in <6% of ALD transplant patients. One-third of severe alcoholic relapse patients develop RAC <5 years after transplantation with a very poor prognosis.Am J Gastroenterol advance online publication, 14 July 2015; doi:10.1038/ajg.2015.204.
The American Journal of Gastroenterology 07/2015; 110(8). DOI:10.1038/ajg.2015.204 · 10.76 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
Long lasting elevation is a key factor during endoscopic submucosal dissection (ESD) and can be obtained by water jet injection of saline solution or by viscous macromolecular solutions. In a previous animal study, we assessed the Nestis Enki II system to combine jet injection and viscous solutions. In the present work, we used this combination in humans in different sites of the digestive tract.
We retrospectively report all of the consecutive ESD procedures performed with jet injection of viscous solutions in four centers. Information was collected about the lesion, the procedure, the histological result, and the outcomes for the patient.
In total, 45 resections were completed by six operators: five experts and one beginner with only one previous experience in human ESD. Lesions were located in the esophagus (10), the stomach (11), the duodenum (1), the colon (1) and the rectum (22). Average maximal lesion diameter was 4.8 cm (SD 2.4, range 2 - 11 cm), average lesion surface area was 19.8 cm(2) (SD 17.7, range 2.2 - 72 cm(2)), and average duration of procedure was 79.9 min (SD 50.3 min, range 19 - 225 min). ESD could be conducted while the endoscope was retroflexed at its maximum in 26 cases. Four adverse events were observed: two diminutive perforations and two delayed bleeding occurrences treated conservatively. The R0 resection rate was 91.1 %. The catheter was obstructed in six occurrences of bleeding.
Endoscopic submucosal dissection using high pressure injection of viscous macromolecular solutions is safe and effective in different parts of the digestive tract. It does not impede working with the endoscope in the maximal retroflexed position.
[Show abstract][Hide abstract] ABSTRACT: ESD is the reference method to achieve en bloc resections for large digestive lesions. Nevertheless, it is a difficult and risky technique. Animal models exist to teach the initial skills, particularly in Japan, where pigs' stomachs are dedicated models to gastric ESD. In Europe, we have to develop different strategies of teaching with dedicated colon models. A pig colon is a good model but thinner and narrower than a human's. In this present work, we evaluated a bovine colon model to perform rectal ESD in retroflexion.
First, we prepared six bowels to precise the preparation protocol. Then, two endoscopists unexperienced in ESD performed 64 procedures on eight models. Learning curves and factors of variation were studied.
A precise protocol to prepare the colon was defined. The two students achieved en bloc resection in 89.1 % of cases with a rate of 6.2 % of perforations. A large heterogeneity appeared between the speed and the success rate depending mainly on the age of the animal bowel. Using calf colons, the failure rates were higher (p = 0.002) and the speed was lower (p < 0.001) than for adult bovine ones. A learning curve appeared with, respectively, 0.49 and 0.59 cm(2)/min throughout the study. No significant difference appeared between measured and calculated specimen areas.
Bovine colon is a new model to teach ESD in colorectal conditions. The bovine age is important to homogenize the model. A learning curve existed with a time procedure decreasing throughout the study. Further studies are needed to evaluate the precise learning curve with more students.
A bovine colon model is a suitable model to teach colorectal ESD. Nevertheless, an adult bovine colon model is more homogeneous than a calf one.
[Show abstract][Hide abstract] ABSTRACT: Background: The aim of this retrospective study was to evaluate the prognostic value of different scores (including Child-Pugh and Model for End Stage Liver Diseases) in cirrhotic patients treated with transjugular intrahepatic porto-systemic shunt for refractory ascites. Methods: Overall, 111 patients with transjugular intrahepatic porto-systemic shunt insertion between January 1998 and July 2012 were included. Results: Survival rates (without transplantation) were 82.0% at 3 months, and 59.4% at 1 year. In addition to standard parameters, a new simple classification based on platelet count and glomerular filtration rate showed strong prognostic ability and could distinguish 3 groups of patients (Log-rank test, p < 0.001): a "good-prognosis" group with platelet counts above 125 x 10(9) L-1 and a glomerular filtration rate above 90 mL/min (1-year survival rate 92%), a "poor-prognosis" group with platelet counts below 125 x 10(9) L-1 and a glomerular filtration rate below 90 mL/min (1-year survival rate 34.8%), and an "intermediateprognosis" group (1-year survival rate 58.2%). Multivariate analysis showed a hazard ratio of 6.34 for the intermediate class and of 12.623 for the high class. Conclusions: A new and simple classification including platelet count and glomerular filtration rate is highly predictive of survival in patients with refractory ascites treated with transjugular intrahepatic porto-systemic shunt and could be used to select patients for this procedure.
[Show abstract][Hide abstract] ABSTRACT: De novo malignancies are a main cause for late death after liver transplantation (LT). Everolimus (ERL) is an immunosuppressive agent with anti-tumoral properties. The aim of the present retrospective study was to identify prognostic factors, including conversion to ERL, for patients presenting non cutaneous de novo solid organ malignancy after LT for alcoholic cirrhosis. The study population consisted in 83 patients (presenting 100 tumours, including 75% of upper aero-digestive tract cancers), among the 398 patients who underwent LT for alcoholic cirrhosis in our centre. After diagnosis, ERL was introduced in 38 patients and calcineurin-inhibitor was discontinued in 64.1% of them. Tumour stage was a significant prognostic factor with a 1-year survival at 82.6% for early stages, 63.4% for intermediate stages (N+) and 27.4% for disseminated diseases (p<0.001). Associated relative risk factor was 2.202 (95%CI 1.044-4.644) for intermediate stages and 5.743 (95%CI 2.436-13.541) for metastatic stages. One and 5-year survival was 77.4% and 35.2% in ERL group vs. 47.2% and 19.4% in the non-ERL group, respectively (p=0.003). The relative risk factor for ERL was 0.447 (95%CI 0.257-0.778). Our results strongly suggest that conversion to ERL improves the prognosis of de novo malignancies after LT for alcoholic cirrhosis. Prospective studies are needed to confirm this benefit. This article is protected by copyright. All rights reserved.
[Show abstract][Hide abstract] ABSTRACT: Recurrent hepatitis C after liver transplantation (LT) is associated with rapid fibrosis progression. The aim of this study was to evaluate the cumulative risk for severe fibrosis and the factors influencing it.
Two hundred and fifty LT patients were included 1 to 15years after LT. Recurrence of chronic hepatitis C on liver graft was classified according to Metavir score.
Kaplan-Meyer estimates for actuarial progression to severe fibrosis (Metavir>F3) showed a probability of 15.2% and 44.5% at 5 and 10years, respectively. Predictive factors for progression to severe fibrosis were: use of tacrolimus as main CNI, recipient age at time of biopsy<55, donor age ≥45, graft HCV re-infection<3months, biologically suspected graft re-infection and lack of response to antiviral treatment after LT. Multivariate analysis disclosed that only donor age ≥45 (hazard ratio 2.243, 95%CI 1.264-3.983, P=0.0058) and lack of response to antiviral treatment (hazard ratio 2.816, 95%CI 1.227-6.464, P=0.0146) were associated to severe fibrosis.
Our study confirms that donor age ≥45 and lack of response to antiviral treatment after LT are major predictive factors of progression of HCV recurrence on liver graft.
[Show abstract][Hide abstract] ABSTRACT: We sought to evaluate the frequency of cardiovascular risk factors in a cohort of patients 10 years after a liver transplant, and to assess their 10-year risk of fatal cardiovascular disease using Systematic COronary Risk Evaluation (SCORE) charts.
Between January 1990 and June 1996, one hundred eighty-nine adults underwent a first liver transplant in our center. Fifty-nine patients (31%) died before reaching their tenth year, and 115 patients were available with complete clinical data at 10 years.
The main indications for liver transplant were alcoholic (38%) and viral cirrhosis (40%). The median age of patients was 56 (range, 29-73 y), 80% were men, 23% were obese, 16% were active smokers, 18% were diabetic, 40% had hypercholesterolemia, and 77% had hypertension. Before the tenth year after transplant, 6 deaths were because of cardiovascular diseases, which represents the third cause of late death (> 1 year after liver transplant). After liver transplant, 5% of the surviving patients underwent ischemic cardiovascular events during the first decade. At a 10-year assessment, the median estimated 10-year risk of fatal cardiovascular disease was 1% (range, 0%-9%) and 10% of the patients had a high risk (ie, SCORE ≥ 5%).
Our results suggest that the frequency of cardiovascular events is relatively low after a liver transplant, even if most of the patients had 1 or more cardiovascular risk factors. Nevertheless, clinicians should perform a similar evaluation 15 or 20 years after the liver transplant because cardiovascular risk exponentially increases with age.
[Show abstract][Hide abstract] ABSTRACT: Long-lasting lifting is a key factor during endoscopic submucosal dissection (ESD) and can be obtained by water-jet injection of saline solution or by injection of viscous macromolecular solutions. Combination of the jet injection and the macromolecular viscous solutions has never been used yet. We assessed the ability of a new water-jet system to inject viscous solutions in direct viewing and in retroflexion. We compared jet injection of saline solution and hyaluronate 0.5 % to perform ESD on ex vivo pig stomachs in order to evaluate the benefits of macromolecular solutions when injected by a jet-injector system.
This is a prospective comparative study in pig stomachs. Using the jet injector, four viscous solutions were tested: hydroxyethyl starch, glycerol mix, hyaluronate sodic (0.5 %), and poloxamer mix. Ten ESDs larger than 25 mm (five in direct viewing and five in retroflexion) and one larger than 10 cm were performed with each solution. ESD with hyaluronate jet injection was then compared with ESD with saline jet injection by performing 50 ESDs in each group. A single, minimally-experienced operator conducted all the procedures.
All 145 resections were complete, including all marking points with two perforations. Eleven jet ESDs per solution were conducted without any injection issue. In the second part of the study, when compared with saline, significant benefit of hyaluronate was observed on dissection speed (0.80 vs. 1.08 cm(2)/min, p < 0.001).
This is the first report on a jet-injector system allowing injection of macromolecular viscous solutions even with retroflexed endoscope. Jet injection of macromolecular solutions can speed up dissection in comparison with saline, and should now be tested on humans.