Brigitte Bernard

Diagnosis, treatment and prophylaxis of spontaneous bacterial peritonitis: a consensus document

bacterial peritonitis (SBP) is a fre- quent and severe complication of cirrhotic patients with ascites. Much information regarding SBP has ap- peared during recent years, particularly on aspects in- volving the management of this complication. There- fore, the International Ascites Club (IAC) com- missioned a panel of experts to prepare a consensus on the diagnosis, therapy and prophylaxis of SBI? A draft consensus document, drawn up by the panel members, was presented and discussed at the regular Meeting of the IAC held during the 33rd Annual Meeting of the European Association for the Study of the Liver, in Lisbon in April 1998, after which a final consensus was reached. This article represents the final consensus document and is divided into three separate sections concerning the diagnosis, treatment and prophylaxis of SBI? Speci- fic recommendations are formulated and each recom- mendation is rated on the basis of strength and quality according to guidelines from the Practice Guidelines Committee of the American Association for the Study of Liver Diseases, with some modifications (1). The rating system is summarized in Table 1.

Prognostic significance of bacterial infection in bleeding cirrhotic patients: a prospective study.

BACKGROUND/AIMS In cirrhotic patients, bacterial infection is frequently associated with gastrointestinal bleeding and seems to increase mortality. The aims of this study were to determine the incidence of bacterial infections in bleeding cirrhotic patients and the influence of infections on the risk of rebleeding and death. METHODS Cirrhotic patients admitted for gastrointestinal bleeding who had not received antimicrobial chemotherapy in the previous 7 days were included. Blood, urine, and ascitic fluid cultures were systematically performed 1, 2, 4, and 7 days after admission. RESULTS Sixty-four patients were enrolled. Forty-two bacterial infections were documented in 23 patients (36%) within 7 days of admission. In patients with bacterial infection, mean Child-Pugh score and mean number of blood units transfused were significantly higher, early rebleeding was more frequent (43.5% vs. 9.8%; P < 0.01), and 4-week mortality was higher (47.8% vs. 14.6%; P < 0.01). Multivariate analysis only identified bacterial infections as predictive of early rebleeding (P < 0.02) and a high Child-Pugh score as predictive of death (P < 0.001). CONCLUSIONS In bleeding cirrhotic patients, bacterial infections only increase the risk of early rebleeding, and mortality is related to the severity of cirrhosis.

Early Administration of Vapreotide for Variceal Bleeding in Patients with Cirrhosis

BACKGROUND In patients with cirrhosis, pharmacologic or endoscopic treatment may control variceal bleeding. However, the effects of early administration of a somatostatin analogue followed by endoscopic treatment are unknown. METHODS We studied the effects of treatment with vapreotide, a somatostatin analogue, begun before endoscopic treatment in 227 patients with cirrhosis who were hospitalized for acute upper gastrointestinal bleeding. The patients were randomly assigned to receive vapreotide (a 50-microg intravenous bolus followed by an infusion at a rate of 50 microg per hour for five days) or placebo within a mean (+/-SD) of 2.3+/-1.5 hours after admission. All the patients received endoscopic treatment a mean of 2.6+/-3.3 hours after the infusion was begun. After the exclusion of 31 patients whose bleeding was not caused by portal hypertension, there were 98 patients in each group. RESULTS At the time of endoscopy, active bleeding was evident in 28 of 91 patients in the vapreotide group (31 percent), as compared with 43 of 93 patients in the placebo group (46 percent) (P=0.03). During the five-day infusion, the primary objective--survival and control of bleeding--was achieved in 65 of 98 patients in the vapreotide group (66 percent) as compared with 49 of 98 patients in the placebo group (50 percent) (P=0.02). The patients in the vapreotide group received significantly fewer blood transfusions (2.0+/-2.2 vs. 2.8+/-2.8 units, P=0.04). Overall mortality rates at 42 days were not significantly different in the two groups. CONCLUSIONS In patients with cirrhosis and variceal bleeding, the combination of vapreotide and endoscopic treatment is more effective than endoscopic treatment alone as a method of controlling acute bleeding. However, the use of combination therapy does not affect mortality rates at 42 days.

Effect of terlipressin (Glypressin) on hepatorenal syndrome in cirrhotic patients: results of a multicentre pilot study.

Objectives Hepatorenal syndrome (HRS) is a severe complication of cirrhosis, leading to death in more than 90% of cases in the absence of liver transplantation. Several treatments have been attempted as a bridge to liver transplantation. Among such treatments, terlipressin has been studied in several reports, two prospective pilot studies and a double-blind, short-term, controlled haemodynamic study. Promising results have been shown with this drug. The purpose of this multicentre retrospective study was to evaluate the effects of terlipressin on renal function and survival of patients with HRS. Patients and methods Eighteen patients recruited in three liver units with type 1 HRS in 16 cases and type 2 HRS in two cases were given 4 mg/day terlipressin (range 1.5–12) for 7 days (range 2–16). Electrolytes, renal function, mean urinary output, natriuresis, liver function tests, and tolerance of the treatment were monitored regularly. Results A total of 13/18 (72%) patients responded with a mean decline in serum creatinine ranging from 31 to 75% from day 0 to day 5. Eight of these 13 patients had a normal serum creatinine level at day 5. Liver function tests remained unaffected by terlipressin administration. Three local necrosis complications were noted in patients receiving terlipressin continuously via an infusion pump. Two responder patients survived: one of these underwent orthotopic liver transplantation with a follow-up of 24 months; the other is alive with a follow-up of more than 36 months. Patients who responded to terlipressin had lower baseline serum bilirubin and significantly higher serum sodium concentrations than patients who did not respond. Conclusion In this pilot study, improvement in renal function was noted in 72% of cases after administration of terlipressin, and was associated with long-term survival in two patients. Parameters associated with response to terlipressin and increased survival should be defined better in a large cohort of cirrhotic patients with HRS.

Blood neutrophil functions and cytokine release in severe alcoholic hepatitis : effect of corticosteroids

BACKGROUND/AIMS Several observations point to an important role of interactions between polymorphonuclear neutrophils and cytokines in severe alcoholic hepatitis. The polymorphonuclear neutrophil activation status and the local and systemic pro- and anti-inflammatory cytokine responses were quantified. The effect of corticosteroids, widely used in this setting, was evaluated using these parameters. METHODS We studied blood polymorphonuclear neutrophil functions in terms of L-selectin and beta2-integrin expression, H2O2 production and IL-8 and tumor necrosis factor alpha synthesis capacity. We also measured IL-8, tumor necrosis factor alpha and IL-10 plasma and liver tissue levels. Fifteen patients with alcoholic hepatitis were compared to 15 patients with alcoholic cirrhosis without alcoholic hepatitis, and to 10 healthy volunteers. The impact of a 28-day course of corticosteroids on blood neutrophils activation status and cytokine levels was evaluated in patients with alcoholic hepatitis. RESULTS Blood polymorphonuclear neutrophils were activated, as shown by increased H2O2 production (48+/-6 vs 29+/-6 MFI in healthy controls), and decreased L-selectin expression (300+/-61 vs 449+/-59 in healthy controls). Upon stimulation, polymorphonuclear neutrophils synthesized large amounts of IL-8 (21.7+/-9.2 ng/ml vs 8.8+/-10 ng/ml in healthy controls) and tumor necrosis factor alpha (524+/-132 pg/ml vs 79+/-144 pg/ml in healthy controls). Tumor necrosis factor alpha and IL-8 plasma and tissue levels were markedly increased as IL-10 was barely detectable in alcoholic hepatitis patients, compared to cirrhotic patients and healthy controls. During steroid therapy, plasma levels of the pro-inflammatory cytokine IL-8 fell as early as day 14, while levels of the anti-inflammatory cytokine IL-10 increased on day 21. Finally, polymorphonuclear neutrophil functions returned to normal after treatment. CONCLUSION Severe alcoholic hepatitis appears to be associated with polymorphonuclear neutrophil activation and an imbalance between pro- and anti-inflammatory cytokines; during steroid therapy a normalization of these parameters was observed.

Flumazenil vs. placebo in hepatic encephalopathy in patients with cirrhosis: a meta-analysis

Randomized controlled trials testing flumazenil in hepatic encephalopathy have shown conflicting results.

Propranolol and sclerotherapy in the prevention of gastrointestinal rebleeding in patients with cirrhosis: a meta-analysis

BACKGROUND/AIMS A meta-analysis of nine selected randomized trials was performed to compare the effects of propranolol and sclerotherapy in the prevention of rebleeding and on survival in patients with cirrhosis. METHODS Five end points were assessed: rebleeding, esophageal rebleeding, death, death due to bleeding, and adverse events. Analyses were performed according to the intention-to-treat method. For each end point, heterogeneity and treatment efficacy were assessed by the Der Simonian and Peto methods. When a significant difference was observed, sensitivity analyses were performed by successive stratification according to treatment duration, type of publication, severity of cirrhosis, and methodological quality. RESULTS The mean percentage of patients free of rebleeding, the mean survival rate and the mean percentage of patients free of death from bleeding were not significantly different between patients treated with propranolol and those treated by sclerotherapy. The mean percentage of patients free of variceal rebleeding was 39% in propranolol group and 55% in sclerotherapy group (mean difference: 17%, 95% confidence interval: 9-25%, p < 0.001). The mean percentage of patients free of adverse events was significantly higher in the propranolol group than in the sclerotherapy group (mean difference: 22%, 95% confidence interval: 6-38%, p < 0.007). CONCLUSION In patients with cirrhosis and esophageal varices, endoscopic sclerotherapy is more effective than propranolol in preventing variceal rebleeding, but the incidence of adverse events is significantly higher with sclerotherapy. There was no difference in survival between the treatments. Propranolol should be considered as a first choice treatment for preventing rebleeding.

Focal neurological signs in hepatic encephalopathy in cirrhotic patients: an underestimated entity?

OBJECTIVES:Focal neurological signs have been poorly documented in the course of hepatic encephalopathy in cirrhotic patients because they are not mentioned in any textbooks of liver diseases. Having the opportunity to observe such cases, we underwent a prospective study to determine incidence, characteristics, associated factors, prognostic significance, and outcome of this rare form of hepatic encephalopathy.METHODS:Over a 12-month period, all cirrhotic patients hospitalized in the intensive care unit of our department for hepatic encephalopathy were prospectively studied. Patients with clinical and electroencephalogram evidences of hepatic encephalopathy were examined by a senior physician and, in cases of focal neurological signs, underwent examination by a neurologist, CT scan, lumbar punction, and cerebral magnetic resonance imaging and echo Doppler examination of neck and head vessels. Clinical and biological parameters were compared in patients during episodes with and without focal neurological signs, and outcome was noted.RESULTS:Thirty-four cirrhotic patients were hospitalized for 48 episodes of hepatic encephalopathy; two of these patients with cerebral hematoma were excluded. Twenty-four patients exhibited 38 hepatic encephalopathy episodes without focal neurological signs (82.6%), and eight patients exhibited eight hepatic encephalopathy episodes with focal neurological signs (17.4%) that were hemiplegia and hemiparesia in six patients (75%). In all patients, cerebral CT scan and cerebrospinal fluid examination disclosed no abnormalities, as neither did cerebral magnetic resonance imaging (n = 5) and echo Doppler examination of neck and head vessels(n = 5). Except for female sex, which was more often encountered in patients with focal neurological signs (p < 0.05), there were no differences between episodes with and without focal neurological signs for any of the parameters studied. In surviving patients who recovered from hepatic encephalopathy (7/8), focal neurological signs disappeared without recurrences after follow up of 6 months (3–12).CONCLUSIONS:Hepatic encephalopathy with focal neurological signs when carefully searched is not uncommon. It could be more frequent in cirrhotic females, is reversible, and has no prognostic significance.

Randomized comparative multicenter study of hydroxyethyl starch versus albumin as a plasma expander in cirrhotic patients with tense ascites treated with paracentesis.

Objective Large-volume paracentesis associated with plasma volume expansion with albumin is an effective, safe, but costly therapy for ascites in patients with cirrhosis. The aim of this study was to compare the use of a synthetic plasma expander, hydroxyethyl starch (HES), with that of albumin. Design Sixty cirrhotic patients with ascites were studied. Patients were randomly assigned to be infused with either albumin (8 g/l of ascites removed, n = 33) or HES (200 ml/I of ascites removed, n = 27). None of the patients was treated with diuretics or had renal impairment or hyponatremia at entry. Clinical and laboratory data were obtained before and 1, 3 and 15 days after treatment Results There were no significant differences in clinical and laboratory parameters between the two groups at entry into the study. None of the patients developed renal impairment during the trial. One patient (HES group) presented with hyponatremia. Plasma atrial natriuretic factor and aldosterone levels did not differ between the two groups at baseline or at 1 and 3 days after paracentesis. The volume of ascites removed did not differ between the albumin (7.9 ± 4.41) and HES (6.9 ± 5.3 I) groups. However, there was a significant difference in weight loss between the albumin and HES groups (7.9 ± 5.2 kg vs 4.7 ± 3.4 kg; p = 0.01). Clinical and laboratory parameters indicated that HES was well tolerated except for hypoalbuminemia. Conclusion HES is well tolerated in patients with cirrhosis. There is no difference between HES and albumin in the prevention of complications related to large-volume paracentesis. The lesser degree of weight loss observed with HES needs further study.

Cyclosporin A-mediated cholestasis in patients with chronic hepatitis after heart transplantation.

Viral chronic hepatitis often occurs in heart transplant recipients receiving cyclosporin. This essential immunosuppressive drug may induce cholestasis. We investigated the effect of treatment with cyclosporin on serum conjugated bile acids in patients with chronic hepatitis developing after heart transplantation. Fifty-nine patients were studied: 17 with chronic hepatitis, 15 heart transplant patients with normal alanine aminotransferase activity, and 27 heart transplant patients with chronic hepatitis, the last two groups receiving cyclosporin. Hepatic biochemical tests and total bile acid concentration were determined on fasting blood samples. The individual glyco- and tauroconjugated bile acids were quantified by high-performance liquid chromatography and direct spectrometry. In patients taking cyclosporin the bilirubin concentration and the alkaline phosphatase activity were increased only when hepatitis was present, in association with a slight increase in cholic acid level (5.13 microM vs. 0.68 microM; P < 0.01). Conjugated lithocholate concentration was dramatically higher when hepatitis and immunosuppression with cyclosporin were associated (1.17 microM vs. 0.03 and 0.04 microM; P < 0.01). Chenodeoxycholate was the main circulating bile acid only in the heart transplant patients treated with cyclosporin but without hepatitis. These results suggest that the mechanisms which explain the cyclosporin-associated modifications of the bile acid pool are different according to the presence or absence of hepatitis. The occurrence of hepatitis in patients on cyclosporin led to an increase in serum lithocholate and primary bile acid concentrations. Further studies are required to assess the effect of ursodeoxycholic acid for this cholestasis.