Pascal Perney

Are preoperative patterns of alcohol consumption predictive of relapse after liver transplantation for alcoholic liver disease

Predictive factors for alcoholic relapse after liver transplantation (LT) performed for alcoholic liver disease (ALD) have been assessed in numerous studies, often with contradictory results. The aim of the study was to assess pretransplantation alcohol consumption characteristics on alcoholic relapse after LT. Patients transplanted for ALD for at least 6 months were included. An anonymous questionnaire assessed socio‐demographic characteristics, medical history, and alcohol consumption before and after LT. Relapse was defined as any alcohol use after LT. Severe relapse was defined by heavy drinking: more than 21 units/week for males and 14 units/week for females. A total of 61 patients were studied. The mean follow up after LT was 49 ± 34 months. Alcoholic relapse occurred in 32 of 61 patients (52%) and severe relapse in eight of 61 patients (13%). Risk factors for severe relapse were: length of abstinence before LT (P = 0.0001), more than one alcohol withdrawal before LT (P = 0.001), alcohol dependence (P = 0.05), alcohol abuse in first relatives (P = 0.05), and younger age (P = 0.05). Information on previous alcohol consumption (dependence, number of withdrawals, family history) helps to predict severe relapse after LT in patients with ALD, allowing early awareness and specific postoperative care.

Staphylococcus aureus nasal carriage in 104 cirrhotic and control patients A prospective study

Abstract Background/Aims: Bacterial infections, specially Staphylococcus aureus (S. aureus) septicemia, remain a leading cause of death following liver transplantation. It has been demonstrated that nasal carriage of S. aureus is associated with invasive infections in patients undergoing hemodialysis and could be decreased by use of antibiotic nasal ointment. However, in cirrhotic patients, the frequency of nasal carriage is unknown. The aims of this study were to determine the prevalence of S. aureus nasal carriage in cirrhotic patients and to assess nosocomial contamination. Methods: One hundred and four patients were included in a prospective study, 52 cirrhotic and 52 control (hospitalized patients without cirrhosis or disease which might increase the rate of nasal carriage of S. aureus ). On admission and after a few days of hospitalization, nasal specimens from each anterior naris were obtained for culture. S. aureus was identified by the gram strain, positive catalase and coagulase reactions; antibiotic susceptibility was determined using a disk-diffusion test. Results: Both groups were similar with regard to age and sex. The prevalence of nasal colonization on hospital admission was 56% in cirrhotic patients and 13% in control patients ( p =0.001). After an average of 4 days, 42% of cirrhotics and 8% of control patients were colonized ( p =0.001), without any nosocomial contamination. Three strains out of 29 were oxacillin-resistant in cirrhotic patients, and none in controls ( p >0.05). There was no statistical difference in carriage rate according to sex, age, cause of cirrhosis and Child-Pugh score. Previous hospitalization (OR, 6.3; 95% CI, 2.3 to 19.9; p =0.0006) and cirrhosis (OR, 4.4; 95% CI, 1.5 to 13.4; p =0.0048) were independent predictors of colonization. Conclusion: Cirrhotic patients had a higher S. aureus nasal carriage rate than control subjects. Previous hospitalization and cirrhosis diagnosis were correlated to nasal colonization. Further studies are necessary to determine if nasal decontamination could reduce S. aureus infections after liver transplantation.

Impact of Hepatitis C Virus (HCV) Genotypes on Quantification of HCV RNA in Serum by COBAS AmpliPrep/COBAS TaqMan HCV Test, Abbott Antiretroviral Therapy HCV RealTime Assay, and VERSANT HCV RNA Assay

ABSTRACT The VERSANT HCV RNA 3.0 (bDNA), COBAS AmpliPrep/COBAS TaqMan HCV, and Abbott ART HCV RealTime assays were compared for hepatitis C virus RNA quantification in 158 clinical specimens (genotypes 1 to 5). RNA values differed significantly between methods (P < 0.0001), and mean titer differences ranged from 0.01 to 0.50 log10 IU/ml depending on the genotypes.

Merkel Cell Carcinoma in a Liver Transplant Patient

Merkel cell carcinoma (MCC) is an aggressive tumor, the incidence of which is seemingly increased in immunocompromised patients. We report on a new case of MCC occurring in a 69-year-old male liver transplant recipient 6.5 years after transplantation. The outcome was marked by early skin and lymph node relapses treated by radiotherapy alone, and the patient ultimately died 30 months after first diagnosis. Together with data from the literature, this case emphasizes the importance of early diagnosis and adequate management of this aggressive disease for which wide initial surgical excision, accurate staging, and close follow-up are of critical importance to outcome, especially in this setting of immunosuppressive treatment, which is usually associated with a higher rate of recurrence.

A prospective randomized study comparing high- and low-dose leucovorin combined with same-dose 5-fluorouracil in advanced colorectal cancer.

Although the efficacy of 5-fluorouracil (5-FU) modulated by leucovorin is well established for advanced colorectal cancer, the question of the most effective regimen and optimal dose of leucovorin remains unanswered. This prospective randomized trial compares low-dose (group 1) and high-dose (group 2) leucovorin, combined with the same dose of 5-FU to determine whether high-dose leucovorin was more beneficial than low-dose on overall survival. Inclusion criteria were: unresectable metastatic colorectal carcinoma, with or without evaluable tumor response; a performance status of less than grade 3 (World Health Organization classification); and no previous chemotherapy for metastases. Forty-two patients were randomized in group 1 (leucovorin, 20 mg/m2/day, days 1 through 5) and 41 patients in group 2 (leucovorin, 200 mg/m2/day, days 1-5). All the patients in the two groups received a 1-hour infusion of 400 mg/m2/day 5-FU every 4 weeks. The two groups were matched with no statistically significant differences in gender ratio, site of primary tumor, performance status, and tumor extent. Toxicity in the two regimens was low and not significantly different between the two groups. Overall median survival was 346 days in group 1 and 323 days in group 2 and was not significantly different between the two groups. At 1 year, the test of equivalence was significant (p < 0.01), demonstrating an absence of more than 20% benefit in 1-year survival for the high-dose regimen. The use of high-dose leucovorin combined with 5-FU in the 5-day regimen does not significantly improve overall survival for patients who have metastatic colorectal cancer.

Plasma and CSF benzodiazepine receptor ligand concentrations in cirrhotic patients with hepatic encephalopathy: relationship to severity of encephalopathy and to pharmaceutical benzodiazepine intake.

Increased plasma and CSF concentrations of substances which bind to brain benzodiazepine receptors have previously been reported in cirrhotic patients with hepatic encephalopathy (HE). However, their relationship to previous intake of pharmaceutical benzodiazepines has not been clearly established. In the present study, plasma levels of benzodiazepine receptor ligands (BZRLs) were measured using a sensitive radioreceptor assay in 12 control subjects with no evidence of hepatic, neurological or psychiatric illness, 11 cirrhotic patients without HE, 24 cirrhotic patients with moderate (grade I-II) HE and in 45 cirrhotic patients with severe (grade II-IV) HE. In addition, CSF concentrations of BZRLs were measured in 8 cirrhotic patients with HE and an equal number of age-matched controls. Recent intake (within 10 days) of pharmaceutical benzodiazepines was assessed by detailed review of medical files, and interviews with the patient, at least one family member as well as the pharmacist. Significantly increased plasma concentrations of BZRLs were observed in cirrhotic patients with severe encephalopathy (p<0.02) compared to controls and to cirrhotic patients without (or with mild) neurological impairment. Increased plasma BZRLs could be accounted for by prior exposure to benzodiazepine medication in all cases. CSF concentrations of BZRLs in cirrhotic patients were not significantly different from control values. These findings do not support a role for “endogenous” benzodiazepines in the pathogenesis of HE in chronic liver disease but suggest that pharmaceutic benzodiazepines administered to cirrhotic patients as sedatives or as part of endoscopic work-up could have contributed to the neurological impairment in some patients.

Liver transplantation for alcoholic liver disease.

Although increasing numbers of alcoholic patients are being referred to liver transplant centres, liver transplantation for alcoholic liver disease still remains controversial, essentially because we are in an era of organ shortage. In fact, the main issue is the likelihood of relapse and its influence on outcome, because it is the possibility of returning to alcohol use that separates patients with alcoholic liver disease from those with other forms of chronic liver disease. In all proposed clinical guidelines of indications for referral and assessment for liver transplantation for alcoholic liver disease, the authors emphasize the risk of alcoholism recurrence and, thus, a multidisciplinary approach is required to select patients who are likely to comply with follow‐up and not return to a damaging pattern of alcohol consumption after transplantation. It emerges from all clinical studies that when we take into account the usual criteria of success for liver transplantation, i.e. patient and graft survival, rejection rate and infection rate, alcoholic liver disease is a good indication for liver transplantation. Predictive factors for alcoholic relapse after liver transplantation have been assessed in numerous studies, often with contradictory results making these difficult to analyse and compare. Several predictive factors for alcoholic relapse have been studied: length of abstinence before transplantation, associated psychiatric problems, social conditions, associated drug addiction, age. Abstinence after transplantation is the goal, but the necessary treatment for alcoholic disease can result in considerable improvement, even when complete abstinence is not achieved. Finally, the good results obtained with liver transplantation for alcoholic liver disease should help us to educate the general population about alcoholic disease.

Doppler study of fasting and postprandial resistance indices in the superior mesenteric artery in healthy subjects and patients with cirrhosis

We assessed the resistance index (RI) in the superior mesenteric artery under fasting and postprandial conditions in healthy subjects and in patients with cirrhosis to determine whether the amount of change in the RI reflects the presence or severity of liver dysfunction.

Alcoolodépendance : diagnostic et traitement

PURPOSE Prevalence of alcohol dependence remains stable across time between 5-7% in men and 2-3% in women, corresponding to at least 1.5 million patients in France. A review about alcohol dependence is warranted, not only as prevalence of this disease is high, but also because of recent significant improvement in caring for these patients. CURRENT KNOWLEDGE AND KEY POINTS Management of alcohol withdrawal is well codified and chiefly entails the prescription of long half-life benzodiazepines, thiamin, and appropriate rehydratation. The objective is to prevent withdrawal syndrome, which can result in delirium tremens and seizures. Several drugs and therapies have proven efficacy to maintain abstinence. Cognitive behavioral therapies evaluate those factors triggering alcohol consumption, and involve behavioral techniques to promote a change. Motivational interviewing enhances individual effectiveness of treatment, and capacity to maintain abstinence. Three molecules used in France have proven efficacy through several mechanisms: acamprosate which interacts with GABAergic and glutamatergic central transmission; naltrexone, an antagonist of opiate receptors; disulfiram which has antabuse-like effect through inhibition of acetaldehyde dehydrogenase. FUTURE PROSPECTS AND PROJECTS Main research strategies currently developed are: (i) investigating consumption of multiple psychoactive substances, and (ii) understanding the neurobiology of dependence, which may lead to new therapeutic discoveries.

Are drugs a risk factor of post-ERCP pancreatitis?

BACKGROUND Pancreatitis is the most severe complication of ERCP. The aim of this study was to assess whether the use of potentially pancreatotoxic drugs is a risk factor for post-ERCP pancreatitis. METHODS Risk factors for post-ERCP pancreatitis and all drugs taken during the month before ERCP were recorded retrospectively in a database. Patients with other causes of acute pancreatitis or chronic pancreatitis were excluded from the analysis. Post-ERCP pancreatitis was defined as abdominal pain and/or vomiting associated with amylase/lipase plasma levels equal to or greater than twice the upper normal value. RESULTS A total of 173 patients (95 men, 78 women; mean age, 68 [16] years) were included. Post-ERCP pancreatitis occurred in 31 patients (18%). Several risk factors were identified in a multivariate analysis: difficulty in cannulation (p<0.001), endoscopic sphincterotomy (p<0.005), and female gender (p=0.02). Having taken potent pancreatotoxic drugs increased the occurrence of post-ERCP pancreatitis: odds ratio 3.7: 95% confidence intervals [1.1,12.4], p=0.04. CONCLUSIONS Use of pancreatotoxic drugs before or during ERCP significantly increased the risk of post-ERCP pancreatitis. Thus, discontinuation of the use of such drugs before ERCP seems justified whenever possible.