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Biomedical subjects

J P Richardet

Publications and source records attributed to J P Richardet.

At least 19 recordsLinked to original sources

Epidemiology of hospital-acquired infections in cirrhotic patients: effect of carriage of methicillin-resistant Staphylococcus aureus and influence of previous antibiotic therapy and norfloxacin prophylaxis.

We assessed the prevalence of carriage of methicillin-resistant Staphylococcus aureus (MRSA) in anterior nares and stools, and of third-generation cephalosporin resistant enterobacteriaceae and non-fermenting gram-negative bacilli (RE/RNF) in stools of 748 hospitalized long-stay cirrhotic patients. We also evaluated the consequences of carriage on the epidemiology of hospital-acquired spontaneous bacterial peritonitis, bacteraemia and urinary tract infection (UTI) in these patients. The prevalence of carriage of MRSA and RE/RNF was 16.7% and 14.7% respectively. Whereas RE/RNF carriage did not lead to an increased risk of infection due to RE/RNF, the overall risk of infections caused by MRSA was more than tenfold higher in MRSA carriers. MRSA and RE/RNF carriers had received prior antibiotic therapy to a greater extent than non-carriers (P < 0.001) and MRSA carriers had received prior norfloxacin prophylaxis to a greater extent than the two other groups (P < 0.02). The mortality rate during hospital stay was higher in MRSA and RE/RNF carriers than in non-carriers (P < 0.001). Pugh score (P < 0.0001), age (P < 0.0001), MRSA carriage (P = 0.0018) and bacteraemia (P = 0.0017) were associated independently with mortality. MRSA carriage in hospitalized cirrhotic patients leads to the emergence of infections due to this strain, mainly SBP and bacteraemia. Prior antibiotic therapy and norfloxacin prophylaxis increase the risk of carriage of MRSA.

Anti-Infective Agents↗

Serum leptin levels in alcoholic liver cirrhosis: relationship with gender, nutritional status, liver function and energy metabolism.

OBJECTIVE: To determine serum leptin levels in alcoholic liver cirrhosis and the relationship with gender, nutritional status, liver function, energy metabolism, inflammatory state and refeeding. SUBJECTS: Thirty-seven hospitalized alcoholic cirrhotic patients (M/F: 24/13), 27 hospitalized patients at risk of malnutrition but with normal liver function (M/F: 15/12) as control patients, and 31 healthy control subjects (M/F: 17/14) participated. DESIGN: Liver function was assessed from Child-Pugh classification; anthropometric parameters and resting energy expenditure (REE) were measured; caloric intake was evaluated over 5 days; and serum leptin and insulin were assayed. The same protocol was performed after 1 month refeeding in 22 patients. Healthy subjects were studied as controls for anthropometric parameters and serum leptin levels. RESULTS: Serum leptin levels were higher in male cirrhotic patients than in the other two male groups (P=0.0079) and in the same range in the female groups. They were higher in female than in male subjects in the three groups. In female cirrhotic patients, logarithmically transformed serum leptin levels correlated significantly with fat mass (P=0.0043), insulin levels (P=0.0072), REE (P=0.0133), bilirubin levels (P<0.0001), prothrombin time (P=0.0003) and Pugh score (P=0.0266) in simple regression analysis and with insulin levels (P=0.0137), but not with fat mass (P=0.0761), Pugh score (P=0.4472) and REE (P=0.4576) in multiple regression analysis. In the male cirrhotic and control patients, log (leptin) levels correlated with CRP (C reactive protein) (r=0.365, P=0.0223). Log (leptin) levels did not correlate with caloric intake in any of the groups. Leptin levels (P<0.05) and fat mass (P<0.02) increased with refeeding while liver function improved (P<0.01). CONCLUSION: There is a gender difference in regulation of serum leptin level in alcoholic liver cirrhosis. Insulin level is the best determinant of leptin level in female patients while inflammatory state related to alcoholic hepatitis seems to have a greater influence in male patients. Although leptin levels positively correlated with REE in female patients, there is no evidence that leptin reduces caloric intake and fat stores in these patients.

Adult↗

Carriage of Staphylococcus aureus and of gram-negative bacilli resistant to third-generation cephalosporins in cirrhotic patients: a prospective assessment of hospital-acquired infections.

OBJECTIVE: To study the relation between Staphylococcus aureus nasal and stool colonization, stool carriage of gram-negative bacilli resistant to third-generation cephalosporins (CephR), and subsequent infections during hospitalization. DESIGN: Prospective study. PATIENTS: 551 cirrhotic patients with 589 consecutive hospital stays. All patients were screened within 48 hours of admission; 589 nasal swabs, 417 stool specimens, and 589 urine samples were analyzed. RESULTS: Carriage rates were 18.8% for methicillin-sensitive S aureus (MSSA), 16.3% for methicillin-resistant S aureus (MRSA), and 13.7% for CephR. We observed 87 episodes of spontaneous bacterial peritonitis, 63 cases of bacteremia, and 167 urinary tract infections occurred. Only 1 case of bacteremia and 4 urinary tract infections due to CephR occurred in patients carrying the same organism in their stools. The risk of MRSA ascitic fluid infections, bacteremia, and urinary tract infections was 3.1% versus 1% (not significant), 8.3% versus 0.8% (P<.001), and 11.4% versus 0.6% (P<.001) in carriers and noncarriers, respectively. Pulsed-field gel electrophoresis (PFGE) of isolates from 16 patients infected by MSSA (3 cases) and MRSA (13 cases) demonstrated that the colonizing strains matched the invasive strains in the 3 MSSA cases and in 8 of 13 MRSA cases. CONCLUSION: Carriage of CephR strains is not associated with subsequent infection by these organisms in hospitalized cirrhotic patients. In contrast, MRSA carriage was an important risk factor for MRSA bacteremia and urinary tract infection.

Adult↗

Serum laminin and type IV collagen are accurate markers of histologically severe alcoholic hepatitis in patients with cirrhosis.

BACKGROUND/AIMS: Severe alcoholic hepatitis occurs mainly in patients with cirrhosis, and has a high death rate. Corticosteroid therapy has been particularly advocated as reducing mortality in patients with severe histologic lesions. However, identification of these patients is difficult, requiring transvenous liver biopsy. Extracellular matrix serum markers have been proposed as non-invasive diagnostic tools in alcoholic liver disease. The aim of this study was to determine the accuracy of 5 extracellular matrix serum markers, i.e. laminin (Lam), N-terminal peptide of type III procollagen (PIIINP), type I (CI), type III (CIII) and type IV (CIV) collagens in identifying patients with severe histologic alcoholic hepatitis from among those with cirrhosis and suspected alcoholic hepatitis. METHODS: We studied 80 consecutive patients with alcoholic cirrhosis and clinical suspicion of alcoholic hepatitis referred for transvenous liver biopsy. Clinical severity of alcoholic hepatitis was assessed according to Maddrey's score. Histological severity was scored using the sum of the 3 following items: polynuclear infiltration (0-3); hepatocytes alterations (0-3); Mallory bodies (0-2). According to this score, patients were divided into 3 groups: mild (1-3), moderate (4-6), and severe (7-8) alcoholic hepatitis. Serum levels of the 5 extracellular matrix serum markers were measured at the time of biopsy using radioimmunoassays. Diagnostic value for histologically severe alcoholic hepatitis of the 5 extracellular matrix serum markers was assessed using receiver operating characteristic curves. RESULTS: Histological alcoholic hepatitis was present in 67 patients (mean alcoholic hepatitis score: 3.4+/-2.3). Maddrey's score was 66% sensitive and 69% specific for the diagnosis of severe histologic alcoholic hepatitis. The serum Lam and CIV concentrations were the most accurate in identifying correctly patients with severe histologic alcoholic hepatitis. At a cut-off of 4.1 UI/ml, Lam was 90% sensitive and 77% specific, whereas at a cut-off of 150 ng/ml, CIV was 89% sensitive and 77% specific. Combination of markers did not result in improved diagnostic value. CONCLUSION: In patients with cirrhosis, determination of serum Lam or CIV could represent a simple and accurate non-invasive method for identification of patients with histologically severe alcoholic hepatitis eligible for corticosteroid treatment.

Adult↗

Increased incidence of oropharyngeal squamous cell carcinomas after liver transplantation for alcoholic cirrhosis.

BACKGROUND: THE aim of this study was to describe the features of posttransplantation tumors observed in a series of liver transplant recipients with special reference to patients receiving a transplant for alcoholic cirrhosis. METHODS: Among 171 consecutive liver transplant recipients, 90 patients who had received a first liver allograft for cirrhosis were studied. After liver transplantation, detection of de novo malignancies was prospectively undertaken and the characteristics of the patients in whom tumors occurred were compared with those in whom tumors did not develop. RESULTS: With a follow-up of 45.2+/-21.2 months, 11 tumors were observed in 90 patients (overall incidence of 12.2%). The incidence of tumors was higher in patients receiving a transplant for alcoholic cirrhosis than in patients receiving a transplant for nonalcoholic cirrhosis (26.7% vs. 5.0%, P<0.01). Squamous cell carcinoma (SCC) of the oropharynx or esophagus and posttransplant lymphoproliferative disorders were mainly observed. SCC (uvula in two cases, tongue in one case, esophagus in one case, pharynx in one case) occurred exclusively in patients transplanted for alcoholic cirrhosis (16.7% vs. 0%, P=0.001). The incidence of posttransplant lymphoproliferative disorders was similar in alcoholics and nonalcoholics (6.7% vs. 5%, NS). Survival was not influenced by the occurrence of SCC. CONCLUSION: The incidence of oropharyngeal SCC could be high in patients receiving a transplant for alcoholic cirrhosis. This could be due to an additional effect of posttransplantation immunosuppression in patients exposed to alcohol and tobacco before transplant. Careful posttransplantation screening of oropharyngeal SCC is warranted after liver transplantation for alcoholic cirrhosis.

Carcinoma, Squamous Cell↗

A short induction regimen of interferon-alpha is not effective for treatment of relapse in chronic hepatitis C: a randomized trial. For the multicentre GER-CYT-01 group.

The aim of this work was to assess the effect of a high-dose (10 million units, MU) short-duration (14 weeks) interferon-alpha2b (IFN-alpha2b) regimen in relapsers compared with the standard IFN regimen of 3 MU three times weekly (t.i.w.) for 6 months. Fifty-eight non-cirrhotic patients (who had relapsed after previous treatment with IFN) with chronic hepatitis were randomized: 29 to the high-dose, short-duration regimen and 29 to the standard regimen. By the end of IFN therapy, in the high-dose, short-duration group alanine aminotransferase (ALT) normalization was observed in 23 (79%) of 29 patients, and undetectable hepatitis C virus (HCV) RNA in eight (28%) vs 25 (86%) and 11 (38%) of the 29 patients in the standard group, respectively (P = NS). At the end of the 72-week follow-up, in the high-dose, short-duration group a sustained ALT normalization was observed in two (7%) patients, and undetectable HCV RNA in 0 (0%) vs five (17%) and four (14%) patients in the standard group (P = NS). There was less fibrosis improvement in the high-dose, short-duration group (two of 26 patients, 8%) than in the standard group (eight of 25 patients, 32%) (P = 0.04). Tolerance to IFN was good and similar in the two groups. In conclusion, in IFN relapsers, high-dose, short-duration treatment with IFN-alpha has no advantage when compared to a 6-month treatment with 3 MU IFN t.i.w.

Adult↗

Intestinal permeability in liver cirrhosis: relationship with severe septic complications.

OBJECTIVES: Patients with liver cirrhosis are at high risk of severe septic complications such as spontaneous bacterial peritonitis (SBP) and bacteraemia. The aims of this study were to assess intestinal permeability in patients with liver cirrhosis and to search for a relationship between an impaired intestinal permeability and the occurrence of severe septic complications. METHODS: Intestinal permeability was assessed in a group of 80 cirrhotic patients (Child A, n = 13; Child B, n = 26; Child C, n = 41) and 28 healthy control subjects. A severe septic complication (bacteraemia and/or SBP) occurred in 16 patients, within 10 days before (n = 8 cases) or after (n = 8 cases) the test was performed. Lactulose (LAC) 10 g was given orally together with mannitol (MAN) 5 g, and urinary excretion rates were determined. RESULTS: Urinary mannitol excretion (MAN%) was lower while the LAC/MAN ratio was higher in patients than in control subjects (P < 0.001); these abnormalities were more marked in Child C patients (Child C patients vs control subjects: MAN%, 8.20 +/- 0.79 vs 14.59 +/- 0.58, P < 0.001; LAC/MAN, 0.066 +/- 0.026 vs 0.017 +/- 0.001, P < 0.02). When compared with non-infected patients, septic patients had a lower MAN% and an increased LAC/ MAN ratio (5.45 +/- 1.12 vs 9.83 +/- 0.87, P < 0.02; 0.130 +/- 0.063 vs 0.029 +/- 0.005, P < 0.02). CONCLUSION: Although the main mechanism involved in the decrease in MAN% is likely a reduction in area of the intestinal absorptive surface, these results argue in favour of an increased intestinal permeability in liver cirrhosis, especially in patients with severe infectious complications. The impairment of intestinal function barrier may contribute to severe septic complications in these patients.

Bacteremia↗

Norfloxacin primary prophylaxis of bacterial infections in cirrhotic patients with ascites: a double-blind randomized trial.

BACKGROUND/AIMS: Norfloxacin is useful to prevent infections in hospitalized cirrhotic patients with low ascitic fluid protein concentrations. It is also effective in preventing the recurrence of spontaneous bacterial peritonitis. The aim of our study was to determine the efficacy of norfloxacin in the primary prophylaxis of gram-negative bacilli infections in cirrhotic patients with low ascitic fluid protein levels (<15 g/l). METHODS: One hundred and seven patients were randomized to receive norfloxacin (400 mg/day; n=53) or placebo (n=54) for 6 months. The patients had no history of infection since cirrhosis diagnosis and no active infection. RESULTS: The probability of gram-negative infection was significantly lower among patients treated with norfloxacin than among those treated with placebo. Six gram-negative bacilli infections occurred in the placebo group and none in the treatment group. Severe infections (spontaneous bacterial peritonitis, neutrocytic ascites and bacteremia) developed in nine patients in the placebo group (17%) and in one patient in the norfloxacin group (2%; p<0.03). There was no between-group difference in the overall rate of infection or in survival. In ten patients from the norfloxacin group, gram-negative bacilli not present in baseline stool cultures were transiently isolated in follow-up cultures. CONCLUSIONS: These data show that primary prophylaxis with norfloxacin for 6 months is effective in the prevention of infections caused by gram-negative bacilli in cirrhotic patients with low ascitic fluid total protein levels.

Adult↗

Epidemiology of severe hospital-acquired infections in patients with liver cirrhosis: effect of long-term administration of norfloxacin.

We performed a 5-year retrospective study to evaluate the effect of long-term administration of norfloxacin on the epidemiology of severe hospital-acquired infections in patients with advanced cirrhosis. Sixty-seven episodes of spontaneous bacterial peritonitis and 60 episodes of bacteremia occurred in, respectively, 46 patients (group 1a) and 52 patients (group 1b) who did not receive norfloxacin, while 23 and 17 episodes occurred in 21 patients (group 2a) and 17 patients (group 2b) during or within 10 days after long-term administration of norfloxacin. Enterobacteriaceae were more prevalent in groups 1a and 1b than in the other two groups (P < .001 and P < .01, respectively); conversely, staphylococci were more prevalent in groups 2a and 2b (P < .001 and P < .05, respectively). The rate of staphylococcal resistance to methicillin was 53.6% in groups 1a and 1b and 77.3% in groups 2a and 2b. We conclude that long-term norfloxacin administration to cirrhotic patients reduces the risk of gram-negative infections but increases the risk of severe hospital-acquired staphylococcal infections and of high-level resistance to antibiotics.

Aged↗

Changes in nature and antibiotic resistance of bacteria causing peritonitis in cirrhotic patients over a 20 year period.

AIM: To assess all clinically and bacteriologically documented episodes of spontaneous bacterial peritonitis diagnosed in a single unit over a 20 year period, to identify changes in the nature and antibiotic resistance of the causative bacteria. SETTING: A specialist liver disease unit in a tertiary care centre. MATERIAL: Cultured ascitic fluid obtained in the course of 240 consecutive episodes of clinically and bacteriologically proven spontaneous bacterial peritonitis. Patient recruitment remained stable during the 20 year period in terms of the number of cirrhotic patients admitted and the severity of their condition. RESULTS: 78.7% of isolates were Enterobacteriaceae (Escherichia coli in 51%) and 19% were Gram positive cocci. Until 1979 all the Enterobacteriaceae had the wild phenotype, compared with only 50% at the end of the study period. Since 1993, 22% of Enterobacteriaceae have been resistant to third generation cephalosporins. Methicillin resistant staphylococci were only isolated after 1989. CONCLUSIONS: Changes in the epidemiology and antibiotic resistance of bacteria causing spontaneous bacterial peritonitis must be monitored for optimal treatment.

Ascitic Fluid↗

[Hepatic transplantation for severe ductopenia related to ingestion of thiabendazole].

We report a case of severe cholestasis and sicca syndrome after thiabendazole administration for Strongyloides stercoralis infection in a 26-year-old patient. Liver biopsy, performed 15 days after the onset of jaundice, revealed a marked paucity of bile ducts, and cholestasis rapidly progressed to biliary cirrhosis. Because of the progression of jaundice and the development of esophageal varices, orthotopic liver transplantation was performed, 18 months after the beginning of disease. The mechanism responsible for thiabendazole-induced biliary injury is unknown. The association between sicca syndrome and biliary disease suggests an immunoallergic mechanism against an antigen which could be common to the biliary, lacrimal and salivary duct epithelium.

Adult↗

High prevalence of diabetes mellitus in patients with chronic hepatitis C. A case-control study.

OBJECTIVES AND METHODS: Extrahepatic manifestations have been reported in hepatitis C virus infection. To assess the relationship between diabetes mellitus and hepatitis C virus, we studied 152 patients with chronic hepatitis C and 152 controls hospitalized during the same period with hepatitis B virus (n = 51) or alcohol-induced (n = 101) liver diseases matched for age, sex, and the presence of cirrhosis (prevalence: 58%). Patients with jaundice, ascites, encephalopathy, prothrombin activity < 65%, or serum albumin < 35 g/L were excluded. RESULTS: Diabetes, defined by fasting serum glycemia > 1.4 g/L on at least two separate occasions or previously treated overt diabetes, was present in 38 patients with chronic hepatitis C (24%) and in 13 patients in the control group (9%, P < 0.002). In the 51 diabetic patients, irrespective of serum anti-hepatitis C virus status, 41 (81%) had non insulin dependent diabetes and 45 (88%) had cirrhosis. Family history of diabetes or obesity was observed in 2 (5%) of the diabetic patients with chronic hepatitis C and in 6 (46%) of the diabetic controls (P = 0.002). Plasma C-peptide (855 +/- 448 pmol/L versus 1,152 +/- 491 pmol/L, NS) and insulin levels (83 +/- 40 pmol/L versus 184 +/- 86 pmol/L, NS), assayed in 17 diabetic patients with chronic hepatitis C and in 9 diabetic controls, were lower in the former. The prevalence of HLA B8, DR3 or DR4 antigens, which was searched for in 77 patients with chronic hepatitis C, was not different in diabetic and non diabetic patients, and, was similar to the reference population. Serum islet-cell antibodies were found in 5 patients with chronic hepatitis C (3 with diabetes) and in 2 controls. CONCLUSION: Diabetes mellitus is more prevalent in patients with chronic hepatitis C than in patients with other liver diseases, and usually occurs in the absence of predisposing factors. These results suggest a role of hepatitis C virus infection in the pathogenesis of diabetes.

Adult↗

[Prevalence and characteristics of anti-tissue antibodies in chronic hepatitis caused by hepatitis C virus].

OBJECTIVES: The prevalence and significance of antiorganelle antibodies in the serum of patients with chronic hepatitis C is a subject of controversy. We studied prospectively these characteristics in patients with chronic hepatitis C. METHODS AND RESULTS: Among 156 patients (age: 55 +/- 14 years; 83 females), 30 (19%) had significant titers of antiorganelle antibodies: anti-nuclear antibodies in 18, anti-smooth muscle antibodies in 8 (no anti-actin or anti-vimentine subtypes), anti-LKM1 in 2, type 2 anti-mitochondrial antibodies in 2 patients. Anti-organelle antibodies were not detected in 126 patients. Patients with anti-organelle antibodies were significantly older but no difference was found between the two groups for sex ratio, serum amino-transferases or gammaglobulins, histopathological liver activity or prevalence of lymphocytic sialadenitis. The presence of anti-organelle antibodies was not related to HLA phenotype, especially B8 DR3, or DR4. Response to alpha interferon, estimated by serum aminotransferase levels after six months of treatment, was the same in both groups. CONCLUSIONS: These results suggest that serum anti-organelle antibodies are prevalent in during chronic hepatitis C but do not indicate a distinct autoimmune mechanism. Furthermore, the typing of anti-smooth muscle antibodies might help distinguish chronic hepatitis C from type 1 autoimmune chronic hepatitis.

Adult↗

[Secondary sclerosing cholangitis and chemo-embolization with lipiodol].

Two cases of sclerosing cholangitis after oily arterial chemoembolization are reported. In one patient angiocholitis with liver abscesses, in the other patient gradual cholestasis were the main clinical features. In both cases, endoscopic retrograde cholangiogram showed a stricture of the common hepatic bile duct and, in one case, irregularities of intrahepatic biliary tree. Histologic examination of the liver in the two patients pointed out the involvement of small bile ducts and arteriolar endarteritis obliterans. Ischaemia is likely to be the main mechanism of these two cases of sclerosing cholangitis as well as in those described after FUDR intra-arterial chemotherapy. The prevalence of sclerosing cholangitis after arterial oily chemoembolization is probably underestimated because of a non specific clinical presentation and need to be precise by further study.

Carcinoma, Hepatocellular↗

[Severe hepatic steatosis: a cause of sudden death in the alcoholic patient].

The authors report the cases of 4 patients with heavy chronic alcoholic intake who presented with hepatomegaly and jaundice without obvious hepatic failure and who died rapidly. In all 4 cases, histological examination of the liver showed massive microvesicular and macrovesicular steatosis involving approximately 100% of hepatocytes and, in 2 cases, minimal lesions of alcoholic hepatitis. Histochemical study, performed in 3 cases, showed that steatosis was constituted of triglycerides only, and that hepatic glycogen was completely depleted in 2 of 3 cases. No obvious cause of death was found in these 4 patients. Shortly, before their death, the 4 patients had increased their ethanol and decreased their food intake. The authors suggest that death as well as microvesicular steatosis could have be due to acute mitochondrial dysfunction.

Death, Sudden↗