[Hereditary hemorrhagic telangiectasia]. / La maladie de Rendu-Osler (télangiectasie hémorragique héréditaire).

Hereditary hemorrhagic telangiectasia, also known as Rendu-Osler - Weber disease, is a rare, autosomal dominant vascular disease, with prevalence of 1/5,000. The condition is characterized by muco-cutaneous telangiectasias, which are responsible for a hemorrhagic syndrome of variable severity, as well as arteriovenous malformations (AVMs) appearing in the lungs, the liver, and the nervous system. They can be the source of shunts, which may be associated with high morbidity (neurological ischemic stroke, brain abscess, high-output heart failure, biliary ischemia…). It is therefore crucial to establish a clinical diagnosis using the Curaçao criteria or molecular diagnosis based on genetic analysis of the ENG, ACVRL1, SMAD4 and GDF2 genes. In most cases, multidisciplinary management allows patients to have normal life expectancy. Advances in interventional radiology and better understanding of the pathophysiology of angiogenesis have resulted in improved therapeutic management. Anti-angiogenic treatments, such as bevacizumab (BVZ, an anti-VEGF antibody), have proven to be effective in cases involving bleeding complications and severe liver damage with cardiac repercussions. Other anti-angiogenic agents are currently being investigated, including tyrosine kinase inhibitors.

[Brucellosis with hepatic lesions: A diagnosis to keep in mind]. / Brucellose avec abcès hépatiques : un diagnostic à ne pas oublier.

INTRODUCTION: Brucellosis is a rare infection in France and its wide spectrum of clinical presentation can be a diagnostic challenge. CASE REPORT: We report here the case of a 76-year-old Tunisian-born woman referred for fatigue, weight loss, intermittent fever, and pain in the right upper quadrant, along with hepatic lesions on CT-scan, MRI and PET-FDG suggesting malignant lesions. However blood cultures were positive to Brucella melitensis leading to a diagnosis of hepatic brucelloma. CONCLUSION: Hepatic abscesses are rare in brucellosis. This infection has to be evoked in patients coming from endemic areas even with atypical manifestations.

Treatment of unresectable hepatocellular carcinoma with a combination of human recombinant alpha-2b interferon and doxorubicin: results of a pilot study.

Based on the in vitro and in vivo potentiation of the cytotoxic activity of chemotherapeutic agents by the interferons, a pilot study combining human recombinant alpha-2b interferon (IFN) and doxorubicin was conducted for the treatment of unresectable, histologically proven hepatocellular carcinoma. Between March 1988 and May 1990, 21 patients (median age: 60 years, range: 29-76) entered the study. The dose of doxorubicin was fixed at 35 mg/m2, every 3 weeks. The dose of alpha-2b IFN was 6 million U/m2 per day, 5 days a week. 3 patients (14%) obtained a partial response lasting 11, 16 and 30 months, and 1 had a stable disease during 8 months. The other 17 patients died within a median survival time of 4 months. All patients experienced flu-like symptoms. 7 patients experienced WHO grade III-IV haematological toxicity. We conclude that the association of alpha-2b IFN and doxorubicin is feasible, with respect to the use of doxorubicin at an inferior dose level than the same agent used without IFN. The response rate is comparable to that observed with doxorubicin used alone. Further phase I studies and randomised trials are required to confirm the role of this regimen in the treatment of unresectable hepatocellular carcinoma.

Nitric oxide and renal function in cirrhotic patients with ascites: from physiopathology to practice.

Patients with cirrhosis and ascites show systemic and splanchnic arterial vasodilation, which causes a reduction in effective arterial blood volume and the activation of hormonal anti-natriuretic systems. Renal impairment is the most important predictor of hospital mortality in cirrhotic patients with SBP. In patients with SBP, the inflammatory response to the infection (TNF-alpha, IL-6) may be an important mechanism of renal dysfunction. Ascitic-fluid NO metabolites are related independently to the development of renal impairment. Treatment of SBP with intravenous albumin in addition to cefotaxime prevents renal impairment and reduces mortality in comparison with treatment with cefotaxime alone. As soon as ascites develops, liver transplantation should be considered in eligible patients, especially when local mean waiting times exceed life expectancy. Nitric oxide (NO), tumour necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) have been implicated in the pathogenesis of circulatory alterations observed in cirrhotic patients with ascites. Kidney failure is one of the main factors associated with mortality in patients with end-stage liver disease developing complications, particularly severe infections and variceal haemorrhage. Renal impairment occurs in patients with the highest concentration of cytokines in plasma and ascitic fluid and is associated with marked activation of the renin-angiotensin system. In patients with spontaneous bacterial peritonitis (SBP), serum and ascitic fluid levels of NO metabolites (nitrites and nitrates) were higher than those of patients with sterile ascites, and renal impairment is considered to be caused by a decrease in effective arterial blood volume as a result of the infection. The administration of albumin prevents deterioration of renal function and reduces mortality in these patients. However, SBP and renal dysfunction are late complications in the course of liver cirrhosis. As soon as ascites develops, liver transplantation should be considered in eligible patients, especially when local mean waiting times exceed life expectancy. A better knowledge of metabolic disorders associated with the early stage of cirrhosis is essential for the development of optimal therapeutic strategies for the prophylaxis and treatment of portal hypertension and its complications.

[Still disease in adults revealed by a digestive manifestation]. / Maladie de Still de l'adulte révélée par une atteinte digestive.

Adult Still's disease is characterized by typical spiking fever, oligopolyarthritis, neutrophilic leukocytosis and involvement of various organs. We report a case which illustrated typical digestive features of Still's disease as dysphagia, peritonitis and manifests the hitherto unreported complication of gastric ulcerations. Treatment with prednisone was started in order to control arthritis, resulting in improvement of both gastric ulcerations (partially resistant to omeprazole treatment) and arthralgia. After seven years of follow-up, the patient remains clinically and biochemically stable with steroid and methotrexate treatment.

[Interactions between chronic viral hepatitis C and pregnancy]. / Interactions entre l'hépatite virale chronique C et la grossesse.

OBJECTIVES AND METHODS: In France, the positive rate for unit-HCV antibodies in the sera of pregnant women is usually found to be between 0.7 and 3.9%. The aim of our prospective study was to determine the interactions between pregnancy and chronic viral hepatitis C in 12 pregnant women. RESULTS: In our study, chronic viral hepatitis C did not influence maternal or neonatal outcome. The mean gestational age was 38.4 +/- 3 weeks. During follow-up, mean serum ALT levels were significantly lower (36 +/- 17 mU/mL) during the last three months of pregnancy compared to before pregnancy (237 +/- 144 mU/mL, P < 0.002) and after pregnancy (141 +/- 62 mU/mL, P < 0.0005). During the third trimester, serum ALT levels were normal in 90% of the women. However, the persistence of viremia during pregnancy and a rebound in serum ALT during the post-partum period have been noticed. CONCLUSION: The normalization of serum ALT levels during pregnancy, the persistence of viremia, and a rebound in serum ALT during post-partum could be related to pregnancy-induced changes in the immune system.

Antibiotic prophylaxis for the prevention of bacterial infections in cirrhotic patients with gastrointestinal bleeding: a meta-analysis.

In cirrhotic patients with gastrointestinal bleeding, antibiotic prophylaxis decreases the incidence of infections but most randomized trials have not shown an increase in survival. The aim of this meta-analysis was to assess the efficacy of antibiotic prophylaxis in the prevention of infections and its effect on survival rate in cirrhotic patients with gastrointestinal bleeding. Four end points were assessed: infection, bacteremia and/or spontaneous bacterial peritonitis (SBP), incidence of SBP, and death. For each end point, heterogeneity and treatment efficacy were assessed by Der Simonian and Peto methods. Five trials including 534 patients, 264 treated with antibiotic prophylaxis for 4 to 10 days and 270 without, were identified. Mean follow-up was 12 days. Antibiotic prophylaxis significantly increased the mean percentage of patients free of infection (32% mean improvement rate, 95% confidence interval [CI]: 22-42, P <.001), bacteremia and/or SBP (19% mean improvement rate, 95% CI: 11-26, P <.001), and SBP (7% mean improvement rate, 95% CI: 2.1-12.6, P =.006). Antibiotic prophylaxis also significantly increased the mean survival rate (9. 1% mean improvement rate, 95 % CI: 2.9-15.3, P =.004), without significant heterogeneity. In cirrhotic patients with gastrointestinal bleeding, short-term antibiotic prophylaxis significantly increases the mean percentage of patients free of infection and significantly increases short-term survival rate.

Survival after a first episode of spontaneous bacterial peritonitis. Prognosis of potential candidates for orthotopic liver transplantation.

To determine the potential role of orthotopic liver transplantation (OLT) in cirrhotic patients surviving a first episode of spontaneous bacterial peritonitis (SBP), medical records of 79 patients presenting with a first episode of SBP were reviewed. Of these patients, 37 were selected as potential candidates for OLT using the following criteria: absence of hepatocellular carcinoma; no severe organ failure other than the liver; age < or = 66 years; and survival after SBP > 60 days. Survival time was calculated from the day of SBP diagnosis. Prognostic value of clinical, biological and bacteriological data recorded at the time of SBP was determined using univariate and multivariate analysis (Cox's regression model). Survival rate of the potential candidates for OLT at 3 months, 1 year and 2 years was 94, 46 and 30% respectively. Serum creatinine value (P = 0.001) and Pugh score (P = 0.005) were independently correlated with death. The 1 year survival rate was 80% for the 11 patients with a Pugh score < 10, and 26% for the 26 patients with a Pugh score > or = 10. Our results suggest that after SBP, OLT should be considered in patients with severe liver disease. Survival of patients with a moderate liver disease (i.e. Pugh score < 10) might be relatively high.

[Prolonged partial remission of a hepatocellular carcinoma treated with adriamycin and recombinant human alpha-2 interferon]. / Rémission partielle prolongée d'un carcinome hépatocellulaire traité par adriamycine et interféron alpha-2 human recombinant.

Adriamycin is one of the chemotherapeutic agent often administered in the treatment of unresectable hepatocellular carcinoma. On monotherapy, the reported rate response is between 0 to 15 p. cent, without improvement on survival. Its combination with other cytotoxic molecules, such as interferon, has been suggested to improve the percentage of response rates. We present the case of a 73 years old man, who underwent a prolonged partial response of a hepatocellular carcinoma with adriamycin and recombinant human interferon alpha-2.

Amoxicillin-clavulanic acid therapy of spontaneous bacterial peritonitis: a prospective study of twenty-seven cases in cirrhotic patients.

Spontaneous bacterial peritonitis in cirrhosis is a serious complication that demands urgent attention. We report here a prospective study of the treatment of 27 episodes of spontaneous bacterial peritonitis in 22 cirrhotic patients with amoxicillin and clavulanic acid. The infection of ascitic fluid was diagnosed by a positive culture plus an ascitic neutrophil count exceeding 75/microliters, or by an ascitic neutrophil count exceeding 500/microliters. The infection was treated with 1 gm amoxicillin and 0.2 gm clavulanic acid every 6 hr for 14 days. In 17 cases (63%), bacteria were isolated from the ascitic fluid. All the bacteria isolated were sensitive to amoxicillin and clavulanic acid, whereas in five cases they were resistant to amoxicillin alone (Escherichia coli in two cases, Klebsiella pneumoniae in two cases and Bacteroides fragilis in one case). Cure of the infection was achieved in 23 episodes (85%) after 14 days' treatment; 17 patients (63%) were able to leave the hospital. Fourteen of 20 patients (70%) treated for the first episode of infection died within 1 yr: eight from infection, two from gastrointestinal hemorrhage, one from infection and hemorrhage and three from tumors. One patient who had repeated infections underwent liver transplantation and has not had any infectious complications 1.5 yr after surgery. Amoxicillin and clavulanic acid may be an effective first-line therapy for ascitic fluid infection in cirrhosis. Nevertheless, the 1-yr prognosis continues to be grave and the severity of the underlying liver disease remains the most important determinant for survival.

Pharmacokinetics of amoxycillin/clavulanic acid in serum and ascitic fluid in cirrhotic patients.

A combination of amoxycillin and clavulanic acid (Augmentin) might be useful for first-line treatment of spontaneous bacterial peritonitis in patients with cirrhosis. We have studied the pharmacokinetics of amoxycillin/clavulanic acid in serum and ascitic fluid of six cirrhotic patients. A total of 66 simultaneous serum and ascitic samples were analysed. Following iv injection of 1 g amoxycillin plus 0.2 g clavulanic acid, the ascites to serum AUC ratio was 1.38 for amoxycillin and 1.01 for clavulanic acid, indicating a good distribution of these drugs into the ascitic fluid. In this study, experimental data were fitted to a three compartment body model which revealed that the prolonged serum half-lives of amoxycillin (274 min) and clavulanic acid (200 min) were probably due to the slow return from the ascitic compartment.