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Biomedical subjects

Didier Samuel

Publications and source records attributed to Didier Samuel.

At least 37 records · Page 2Linked to original sources
PubMed2005

Treatment of hepatitis B and C after liver transplantation. Part 2, hepatitis C.

End-stage liver disease caused by the hepatitis C virus is a major indication for liver transplantation. However, recurrence of hepatitis in the graft is a major issue. HCV re-infection after transplantation is almost constant, and recent data confirm that it significantly impairs patient and graft survival. Factors that may influence disease severity and consequent progression of HCV graft injury remain unclear. Chronic HCV infection develops in 60%-80% of patients, and 6%-28% ultimately progress to cirrhosis within 5 years. Pre-transplantation antiviral treatment is not easily related to poor tolerance. Attempts to administer prophylactic post-transplantation antiviral treatment are under evaluation but are limited by antiviral drug side effects. Treatment of established graft lesions with interferon or ribavirin as single agents has been disappointing. Combination therapy gave promising results, with sustained virological response in 25% of patients, but indications, modality and duration of treatment should be assessed.

Antiviral Agents↗
PubMed2005

Male cell microchimerism in normal and diseased female livers from fetal life to adulthood.

Male microchimerism is frequent in the adult female liver and is attributed to fetal cells originating from previous male offspring. It has never been studied in pregnant women, female children, or fetuses. We examined its frequency and cellular nature in normal and diseased female livers from fetal life to adulthood. Forty-six liver samples from 29 women, 6 female children, and 11 female fetuses were screened for the Y chromosome via polymerase chain reaction (PCR) assay and fluorescent in situ hybridization (FISH). The X chromosome was used as an internal control. A third PCR assay was used for Y genotyping. The Y chromosome was detected in 5 of 6 children, 7 of 11 fetuses, 3 of 9 women with normal liver, 7 of 10 women with chronic hepatitis C, 5 of 6 women with acute liver disease during pregnancy with male offspring, and 2 of 4 nonpregnant women with fulminant hepatitis. In positive samples, the mean XY/XX ratio was 0.012 (+/-0.004). In women, male microchimerism was correlated with previous male offspring. Male hepatocytes, detected via FISH combined with anti-hepatocyte immunohistochemistry, were observed only in fetuses (4/9) and in postpartem women (4/6). Y genotypes were different from each other in 4 of 5 female livers. In conclusion, male liver microchimerism is frequent in normal and diseased female livers. The presence of male cells in the liver of female children and fetuses is probably due to the transplacental transmission of fetal cells preexisting in the mother and acquired either from previous pregnancy with male offspring or during the mother's own fetal life.

Adult↗
PubMed2005

Herpes simplex virus-associated acute liver failure: a difficult diagnosis with a poor prognosis.

We report 5 cases of acute liver failure related to herpes simplex (HSV) infection in 1 immunocompetent and 4 immunosuppressed patients. One patient was too ill for liver transplantation indication. Three patients, among the 4 listed, underwent liver transplantation. Three patients died 11 days to 1 year after transplantation and 2 patients died 2 to 3 days after admission. All presented with fever and none with skin lesions. The diagnosis of HSV-related hepatitis was made antemortem in only 2 patients on the basis of positive blood cultures and/or immunohistochemic findings. In the remaining patients, HSV diagnosis was made retrospectively on further histologic and virologic investigations. Primary HSV infection was certain or likely in all cases, including an HSV2 superinfection of an anti-HSV1-positive patient and two HSV superinfections of hepatitis B virus (HBV)-related chronic liver disease. In these latter patients, HSV diagnosis was totally unsuspected, despite fever. HSV superinfection has significantly contributed to liver dysfunction aggravation and death. In conclusion, the diagnosis of HSV hepatitis is difficult to establish in the absence of specific clinical signs. This may suggest the need for early administration of acyclovir in patients with suspected HSV hepatitis, without waiting for virologic confirmation. Diagnosis methods providing fast results (real-time polymerase chain reaction [PCR]) should be implemented.

Acyclovir↗
PubMed2005

Hepatitis C virus viral recurrence and liver mitochondrial damage after liver transplantation in HIV-HCV co-infected patients.

BACKGROUND/AIMS: As life expectancy in HIV-HCV co-infected patients improves, end stage liver disease requiring liver transplantation (LT) may become an emerging problem. We report the Paul Brousse Hospital experience of transplantation for end stage cirrhosis in HIV-HCV co-infected patients. METHODS: Seven consecutive HIV-HCV co-infected patients were transplanted between December 1999 and December 2002 for end stage liver disease due to HCV. All patients were treated by highly active antiretroviral therapy (HAART), HIV plasma viral load was <400 copies/ml and median CD4 lymphocyte count was 306 cells/mm3 (range, 103-510) before LT. At the time of evaluation (March 2003), the median follow-up was 21 months (range, 4-40). RESULTS: Two patients died, 4 and 22 months, respectively after LT. At the last biopsy, METAVIR score was staged F4 in two patients, F3 in two, and F1 in one. Microvesicular steatosis was noted in nearly all patients. The ratio of mitochondrial to nuclear DNA was low in three of four patients examined as compared with the amount of liver mtDNA found in eight HIV-negative, HCV-infected controls (P=0.01). CONCLUSIONS: A significant defect in the activity of the respiratory chain complex IV was noted in all five patients studied. Mitochondrial hepatotoxicity and severe HCV recurrence occur in HIV-HCV co-infected patients after LT.

Adult↗
PubMed2005

[Auxiliary partial orthotopic liver transplantation using small grafts. A way to avoid small-for-size syndrome?].

If the ratio liver graft weight/recipient body weight ratio is below 0.8%, there is a high risk of primary non function of the graft in almost 50% of cases. We report the first elective Auxiliary Partial Orthotopic Liver Transplantation using a small cadaveric left graft for cirrhosis. The graft weight/recipient body weight rate was 0.6%. This technique avoided the small-for-size syndrome in the early postoperative period. The native right liver was resected two months later. With a follow-up of 5 years, the patient is in good condition. This original technique could be a solution to increase the number of transplantations using small grafts, especially left grafts, provided by splits or living donors.

Body Weight↗
PubMed2005

The histologic pattern of "biliary tract pathology" is accurate for the diagnosis of biliary complications.

A histologic pattern comprising centrilobular cholestasis and portal changes including edema, predominantly neutrophil polymorph infiltration, cholangiolar proliferation, and cholangiolitis is well known to correspond to biliary obstruction. This pattern, referred as biliary tract pathology (BTP) in this text, remains unclear in terms of its clinical significance. We aimed to assess the incidence, timing, and diagnostic accuracy of BTP after liver transplantation. All 248 liver biopsies and clinical records, from 94 patients, including 30 living donor, 17 split, 15 domino, and 32 cadaveric full-size primary liver transplantation, were reviewed. BTP was diagnosed in 21% of biopsies from 31% of patients at a median of 28 days after transplantation (range, 5-763 days). When radiologic imaging of the biliary tree was taken as the gold standard, biopsy was found to have a sensitivity of 87% (95% confidence interval, 73%-100%) and a specificity of 87% (95% confidence interval, 80%-95%) for the diagnosis of biliary complications. An underlying clinical condition was found in 86% of cases, which included biliary complications (69%), arterial thrombosis (3%), sepsis (10%), and recurrent disease (3%). In 14% of cases, BTP remained unexplained. In conclusion, BTP after liver transplantation has clinical significance in most cases, with a particular emphasis for true biliary complications. This pattern must incite radiographic verification of the biliary tract.

Bile Ducts, Intrahepatic↗
PubMed2005

Could post-liver transplantation course be helpful for the diagnosis of so called cryptogenic cirrhosis?

Cryptogenic cirrhosis (CC) is diagnosed in 5-30% of cirrhotic patients overall and 7% of patients who undergo liver transplantation for cirrhosis. In our series of patients transplanted for CC, pre-transplant clinical and histological data and the post-transplant course were reexamined in an attempt to identify the aetiology. Among the 881 patients transplanted in our centre between 1987 and 2000, 28 patients with a median age of 46 yr (range: 18-69) at transplantation were initially classified as having CC. Two patients were excluded because of intense ischaemic lesions caused by chemoembolization prevented histological analysis of the native liver (n = 1) and because of cryptic HBV infection (n = 1). Among the remaining 26 patients, four groups were individualized: (i) patients with chronic inflammatory liver disease with autoimmune features (n = 14, 54%); (ii) patients with features suggestive of non-alcoholic fatty liver disease (n = 3, 11.5%); (iii); patients with incomplete septal cirrhosis (ISC) and vascular liver disease (n = 3), and (iv) patients with unresolved CC (n = 6, 23%). In the autoimmune liver disease group, the median International Autoimmune Hepatitis score was 12.5 (range: 11-19) after reevaluation and review of the post-transplantation course was helpful to confirm the diagnosis with the occurrence of active graft hepatitis in nine patients, with autoantibodies in five patients. The vascular group was characterized by lesions of obliterative portal venopathy and ISC in all native livers. Diagnosis of NAFLD was based on the clinical background of obesity and/or type 2 diabetes and the presence of steatosis or steatohepatitis in native livers and graft biopsies. A definite aetiological diagnosis can be achieved in the majority of patients initially diagnosed with CC. Autoimmune liver disease emerged as the main aetiology (14 of 26 patients, 54%) and frequently recurred on the grafted liver (nine cases). In all cases a precise diagnosis is obviously of practical interest for better management of post-transplant survey and treatment.

Adolescent↗
PubMed2005

Compartmentalization of hepatitis C virus genotypes between plasma and peripheral blood mononuclear cells.

Differences in hepatitis C virus (HCV) variants of the highly conserved 5' untranslated region (UTR) have been observed between plasma and peripheral blood mononuclear cells (PBMC). The prevalence and the mechanisms of this compartmentalization are unknown. Plasma and PBMC HCV variants were compared by single-strand conformation polymorphism (SSCP) and by cloning or by genotyping with a line probe assay (LiPA) in 116 chronically infected patients, including 44 liver transplant recipients. SSCP patterns differed between compartments in 43/109 analyzable patients (39%). Differences were significantly more frequent in patients with transplants (21/38 [55%] versus 22/71 [31%]; P < 0.01) and in those who acquired HCV through multiple transfusions before 1991 (15/20; 75%) or through drug injection (16/31; 52%) than in those infected through an unknown route (7/29; 24%) or through a single transfusion (5/29; 17%; P < 0.001). Cloning of the 5' UTR, LiPA analysis, and nonstructural region 5B sequencing revealed different genotypes in the two compartments from 10 patients (9%). In nine patients, the genotype detected in PBMC was not detected in plasma and was weak or undetectable in the liver in three cases. This genotypic compartmentalization persisted for years in three patients and after liver transplantation in two. The present study shows that a significant proportion of HCV-infected subjects harbor in their PBMC highly divergent variants which were likely acquired through superinfections.

5' Untranslated Regions↗
PubMed2004

[Increased long-term permeability of transjugular intrahepatic portosystemic shunt (TIPS) in 218 cirrhotic patients, with strict monitoring].

OBJECTIVE: To measure the impact of strict monitoring on long term permeability of TIPS. METHODS: From November 1991 to December 2002, 208 patients (152 men and 66 women managed for the placing of a TIPS following failure with sclerotherapy or refractory ascites were included. The permeability of the prosthesis was controlled on the surgical piece. Revision of the TIPS was performed at the same time as the diagnosis of obstruction using trans-jugular angiography. The TIPS permeability was classified into 3 categories: primary permeability (duration of permeability recorded up until any intervention); assisted primary permeability (duration of continuous permeability with or without percutaneous intervention); secondary permeability (total duration of permeability with or without treated occlusion). RESULTS: Among the 218 patients in the study, 108 had been monitored for less than one year (49.5%), 29 for between 1 and 2 years (13.5%), 27 between 2 and 3 years (12.5%), 16 between 3 and 4 years (7.5%), 15 between 4 and 5 years (7%) and 23 for more than 5 years (10%). The mean follow-up period was of 24.1 +/- 27.2 months (median: 13.7). Current survival of these patients was of 81.2 +/- 2.9% at 1 year, 62.9 +/- 4.2% at 3 years and 52 +/- 4.9% at 5 years. Thirty-four patients were lost to follow-up (16%), after a mean follow-up of 22.9 +/- 26.7 months (median: 9.7). All these patients exhibited a permeable TIPS during their last control. One hundred and thirty-five patients (62%) had never presented obstruction of the TIPS, with a mean follow-up of 19.5 +/- 26.2 months (median: 7.4); 83 patients (38%) exhibited 117 episodes of obstruction; 24 two episodes, 7 three and 3 more than three; 4 exhibited thrombosis provoked by an invalidating encephalopathy and contraindicating transplantation, 2 of them following a first episode of thrombosis. The current primary, primary assisted and secondary permeability rates were respectively: 67.7 +/- 3 and 514 +/- 3.7%, 79.9 +/- 2.3% and 69.3 +/- 3.4%, 94.4 +/- 1.8% and 91 +/- 2.6% at 1 and 3 years (p = 0.0001, Log Rank = 65.3). Univariate analysis revealed a relationship between the onset of an episode of early or late obstruction and the patients' age at the time the TIPS was inserted, Child's score before, and the pre- and post-surgical gradient. In multivariate analysis, none of these elements reached significance. CONCLUSION: Although the use of TIPS in the treatment of portal hypertension follows the course of development of all surgery towards minimally invasive methods, it should not be considered as a surgical portal shunt or as a permanent treatment: long-term permeability is only obtained with strict and regular monitoring and the possibility of rapid intervention in the case of obstruction.

Adult↗
PubMed2004

Results of lis2t, a multicenter, randomized study comparing cyclosporine microemulsion with C2 monitoring and tacrolimus with C0 monitoring in de novo liver transplantation.

This is the first multicenter, randomized, open-label study to compare the efficacy and safety of cyclosporine A microemulsion (CsA-ME) (Neoral, Novartis, Basel, Switzerland ) with C2 monitoring versus tacrolimus in de novo liver transplant recipients. Patients were stratified according to hepatitis C virus status and randomized to receive CsA-ME (n= 250) or tacrolimus (n= 245) with steroids, with or without azathioprine. The primary endpoint was the incidence of biopsy-proven acute rejection (BPAR) at 3 months. Secondary endpoints included death or graft loss and safety evaluations at 6 months. The incidence of BPAR at 3 months was 26% in the CsA-ME group and 24% in the tacrolimus group (not significant). At 6 months, 89% of patients receiving CsA-ME and 88% of patients receiving tacrolimus were alive with a functioning graft. Among the hepatitis C virus-positive patients, there was no difference in BPAR, but death or graft loss was more frequent in those receiving tacrolimus (15% vs. 6%, P <0.05). Diabetes mellitus (14% vs. 7%, P <0.02) and diarrhea (29% vs. 14%, P <0.001) were significantly more often reported in patients receiving tacrolimus. The incidence of hypertension was similar in both groups. At 6 months, the median total cholesterol was 4.7 mmol/L (2.9-7.4 mmol/L) in the CsA-ME arm versus 4.3 mmol/L (2.5-6.4 mmol/L) in the tacrolimus arm; the median serum creatinine was 106 micromol/L (52-238 micromol/L) in the CsA-ME arm versus 103 micromol/L (44-477 micromol/L) in the tacrolimus arm. Efficacy is equivalent with CsA-ME using C2 monitoring or tacrolimus in liver transplant recipients. The incidence of adverse events is comparable except for a significantly higher incidence of diabetes mellitus and diarrhea in the tacrolimus group. Both agents are effective primary immunosuppressants in liver transplant recipients.

Adult↗
PubMed2004

Changes in renal function in patients with familial amyloid polyneuropathy treated with orthotopic liver transplantation.

BACKGROUND: Familial amyloid polyneuropathy (FAP) is an autosomal dominant disease caused by a point mutation in the gene encoding transthyretin, which is secreted by the liver. Orthotopic liver transplantation (OLT) has been proposed to prevent disease progression. Little is known about long-term changes in renal function and lesions after OLT. METHODS: The renal function of 33 patients with FAP was evaluated (proteinuria, serum creatinine, creatinine clearance) before OLT and over a period of at least 5 years afterwards. A pre-transplantation renal biopsy was performed in 14 patients and a follow-up biopsy in eight patients. RESULTS: Before transplantation, mean serum creatinine concentration was 86 micromol/l (47-126 micromol/l) and creatinine clearance was 71.9+/-31.6 ml/min/1.73 m(2). Proteinuria was detected in 54% of patients (0.3-4 g/day). Pre-transplant renal biopsies (n = 14) revealed glomerular, tubular and vascular amyloid deposits in 90, 58 and 66% of patients, respectively. Eleven patients (33%) died after OLT. Death occurred most frequently in patients having weight losses >7 kg (P<0.05). After transplantation, 25 patients (76%) suffered acute renal failure but only one required dialysis. One month after transplantation, the mean serum creatinine concentration was 134.1+/-73 micromol/l and remained constant during follow-up. Eight patients underwent a second renal biopsy 2 years after transplantation. No significant changes in deposits or renal toxicity due to calcineurin inhibitors were detected. CONCLUSION: Although liver transplantation in FAP does not affect existing renal amyloid deposits, it prevents the progression of renal disease.

Adult↗
PubMed2004

The MTHFR 677C > T polymorphism is associated with an increased risk of hepatocellular carcinoma in patients with alcoholic cirrhosis.

Methylenetetrahydrofolate reductase (MTHFR), a key enzyme in folate metabolism, plays a major role in the provision of methyl groups for DNA methylation and in the production of dTMP for DNA synthesis. Different polymorphisms have been described for this enzyme, the most studied being the C677T, which has been shown to be associated with predisposition to colorectal cancer in patients who consume a high alcohol diet. The aim of this study was to determine whether the MTHFR polymorphism is related to hepatocellular carcinoma (HCC) in patients with alcoholic cirrhosis. MTHFR genotypes were determined in 300 liver transplant patients, 72 of whom had alcoholic cirrhosis with HCC and 122 of whom had alcoholic cirrhosis without HCC. The remaining patients were transplanted for HCC on normal liver (n = 27) or viral cirrhosis with HCC (n = 49) or without HCC (n = 30). We also tested 80 healthy subjects. Among the group of patients transplanted for alcoholic cirrhosis, the frequency of MTHFR variants CC versus CT and TT was significantly higher in patients with HCC than in patients without macroscopic evidence of HCC (P = 0.02). This difference was not observed between patients with and without HCC developed either on viral cirrhosis or on non-cirrhotic liver. If we considered all the patients transplanted for HCC, the MTHFR CC genotype was significantly higher in patients who had developed HCC on alcoholic cirrhosis rather than on viral cirrhosis (P = 0.002) or on non-cirrhotic livers (P = 0.02). The relative risk for HCC in subjects with alcoholic cirrhosis and the CC genotype was 2.03. These results suggest that the MTHFR CC genotype increases the risk to develop HCC in patients who consume a high alcohol diet.

Adult↗