Bacterial infections in acute variceal hemorrhage despite antibiotics-a multicenter study of predictors and clinical impact.

BACKGROUND AND AIMS: Current guidelines recommend antibiotic prophylaxis in all patients presenting with cirrhosis and acute variceal hemorrhage (AVH). We aimed to evaluate the characteristics and clinical impact of "early" infections (developing within 14 days) of AVH in a real-world setting. METHODS: We analyzed retrospective data from a cohort of 371 adult patients with cirrhosis and AVH all of whom had received antibiotic prophylaxis (74% men; mean age 56 years), admitted to tertiary care hospitals in Edmonton, Alberta, Canada, and Barcelona, Spain. Sensitivity analyses were presented for culture-positive (confirmed) infections. RESULTS: The mean MELD was 16. Fifty-two percent of patients received quinolones, 45% third-generation cephalosporins and 3% other antibiotics. Fourteen percent (51/371) developed an infection within 14 days of AVH. Seventy-five percent of infections were culture positive and occurred at a mean of six days from AVH. When all infections were considered, respiratory infections were the most common (53%) followed by urinary tract infections (17%) and bacteremia (16%). Resistance patterns differed between countries. Outpatient antibiotic prophylaxis (OR 5.4) and intubation (OR 2.6) were independent predictors of bacterial infection. Bacterial infection (OR 2.6) and the MELD (OR 1.2) were independent predictors of six-week mortality. CONCLUSIONS: Early bacterial infections develop in 14% of cirrhotic patients with AVH despite antibiotic prophylaxis, and have a negative impact on six-week mortality. Intubation and outpatient antibiotic prophylaxis are associated with increased risk of early bacterial infections. Patients at risk should be followed closely with prompt infection workup and local antibiogram-based expansion of antibiotic therapy in case of clinical decline.

Hyponatremia in patients treated with terlipressin for severe gastrointestinal bleeding due to portal hypertension.

UNLABELLED: Terlipressin is frequently used in acute variceal bleeding due to its powerful effect on vasopressin V1 receptors. Although terlipressin is also a partial agonist of renal vasopressin V2 receptors, its effects on serum sodium concentration have not been specifically investigated. To examine the effects of terlipressin on serum sodium concentration in patients with acute portal-hypertensive bleeding, 58 consecutive patients with severe portal-hypertensive bleeding treated with terlipressin were investigated. In the whole population, serum sodium decreased from 134.9 ± 6.6 mEq/L to 130.5 ± 7.7 mEq/L (P = 0.002). Thirty-nine patients (67%) had a decrease in serum sodium ≥ 5 mEq/L during treatment: in 18 patients (31%), between 5 and 10 mEq/L and in 21 patients (36%), greater than 10 mEq/L. In this latter group, serum sodium decreased from 137.2 ± 5 to 120.5 ± 5 mEq/L (P < 0.001). In multivariate analysis, the reduction in serum sodium was related to baseline serum sodium and Model for End-Stage Liver Disease (MELD) score; patients with low MELD and normal or near-normal baseline serum sodium had the highest risk of hyponatremia. Serum sodium returned to baseline values in most patients shortly after cessation of therapy. Three of the 21 patients with marked reduction in serum sodium developed neurological manifestations, including osmotic demyelination syndrome in one patient due to a rapid recovery of serum sodium (serum sodium in these three patients decreased from 135, 130, and 136 to 117, 114, and 109 mEq/L, respectively). CONCLUSION: An acute reduction in serum sodium concentration is common during treatment with terlipressin for severe portal-hypertensive bleeding. It develops rapidly after start of therapy, may be severe in some patients and is associated with neurological complications, and is usually reversible after terlipressin withdrawal.

Characterization of γδ T cell subsets in organ transplantation.

γδ T cells are innate-type lymphocytes that preferentially act as regulators of local effector immune responses. Recent reports found an altered distribution of the two main subpopulations of blood γδ T cells (Vδ1 and Vδ2) in operationally tolerant liver transplant recipients. Based on this, γδ T cells subset quantification was proposed as a biomarker of immunologic risk in liver transplantation. The specific characteristics of γδ T cell subsets in transplantation remain however unknown. We have investigated here the phenotype, repertoire and functional properties of γδ T cell subsets in a large population of allograft recipients. Our results indicate that alterations in the γδ T cell compartment are not restricted to tolerant liver recipients. In fact, most immunosuppressed liver and kidney recipients also display an enlarged peripheral blood γδ T cell pool mainly resulting from an expansion of Vδ1 T cells exhibiting an oligoclonal repertoire and different phenotypic and cytokine production traits than Vδ2 T cells. We propose that persistent viral infections are likely to contribute to these alterations. Our data provide novel insight in the biology of γδ T cells and a rationale for exploring these lymphocytes in more depth into the pathogenesis of viral infections in transplantation.

Recombinant factor VIIa for upper gastrointestinal bleeding in patients with cirrhosis: a randomized, double-blind trial.

BACKGROUND & AIMS: Upper gastrointestinal bleeding (UGIB) is a severe and frequent complication of cirrhosis. Recombinant coagulation factor VIIa (rFVIIa) has been shown to correct the prolonged prothrombin time in patients with cirrhosis and UGIB. This trial aimed to determine efficacy and safety of rFVIIa in cirrhotic patients with variceal and nonvariceal UGIB. METHODS: A total of 245 cirrhotic patients (Child-Pugh < 13; Child-Pugh A = 20%, B = 52%, C = 28%) with UGIB (variceal = 66%, nonvariceal = 29%, bleeding source unknown = 5%) were randomized equally to receive 8 doses of 100 microg/kg rFVIIa or placebo in addition to pharmacologic and endoscopic treatment. The primary end point was a composite including: (1) failure to control UGIB within 24 hours after first dose, or (2) failure to prevent rebleeding between 24 hours and day 5, or (3) death within 5 days. RESULTS: Baseline characteristics were similar between rFVIIa and placebo groups. rFVIIa showed no advantage over standard treatment in the whole trial population. Exploratory analyses, however, showed that rFVIIa significantly decreased the number of failures on the composite end point (P = 0.03) and the 24-hour bleeding control end point (P = 0.01) in the subgroup of Child-Pugh B and C variceal bleeders. There were no significant differences between rFVIIa and placebo groups in mortality (5- or 42-day) or incidence of adverse events including thromboembolic events. CONCLUSIONS: Although no overall effect of rFVIIa was observed, exploratory analyses in Child-Pugh B and C cirrhotic patients indicated that administration of rFVIIa significantly decreased the proportion of patients who failed to control variceal bleeding. Dosing with rFVIIa appeared safe. Further studies are needed to verify these findings.

Nitric oxide and portal hypertension.

In liver cirrhosis, an increase in hepatic resistance is the initial phenomenon leading to portal hypertension. This is primarily due to the structural distortion of the intrahepatic microcirculation caused by cirrhosis. However, similar to other vascular conditions, architectural changes in the liver are associated with a deficient nitric oxide (NO) production, which results in an increased vascular tone with a further increase in hepatic resistance and portal pressure. New therapeutic strategies are being developed to selectively provide the liver with NO, overcoming the deleterious effects of systemic vasodilators. On the other hand, a strikingly opposite process occurs in splanchnic arterial circulation, where NO production is increased. This results in splanchnic vasodilatation and subsequent increase in portal inflow, which contributes to portal hypertension. Systemic blockade of NO in portal hypertension attenuates the hyperdynamic circulation, but its effects increasing hepatic resistance may offset the benefit of reducing portal inflow, thus preventing an effective reduction of portal pressure. Moreover, it cannot be ruled out that NO blockade may have a deleterious action on cirrhosis progression, which raises caution about their use in patients with cirrhosis.