Post-banding ulcer bleeding is a rare complication of endoscopic band ligation of esophageal varices with high morbidity and mortality. There exist no management guidelines for this complication.
To ...determine the incidence, outcome and risk factors of post-banding ulcer bleeding.
Data for cirrhotic patients with acute variceal bleeding during a six-year period were prospectively collected, and all band ligation sessions performed were retrospectively analyzed. Demographic, analytic and endoscopic data were recorded, as well as complications, outcome and management of each episode of post-banding ulcer bleeding.
The study includes 521 band ligation sessions performed on 175 patients. There were 24 cases of post-banding ulcer bleeding in 21 patients (incidence 4.6%). Independent risk factors for post-banding ulcer bleeding were MELD score, hepatocellular carcinoma and total beta-blocker dose. Mortality during the bleeding episode was 23.8%. Active bleeding or adherent clots at the time of endoscopy was associated with treatment failure or death.
Post-banding ulcer bleeding is an uncommon but severe complication of esophageal banding. Patients with hepatocellular carcinoma, poor liver function and a low beta-blocker dose have higher risk of post-banding ulcer bleeding. An aggressive treatment should be considered in case of active bleeding at endoscopy.
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•Circulatory dysfunction is a key pathogenic factor in complications of cirrhosis.•Improvement in circulatory function may prevent complications of cirrhosis.•We assessed the effects ...of the oral vasoconstrictor midodrine associated with albumin.•Midodrine plus albumin decreased renin and aldosterone levels.•However, midodrine plus albumin did not prevent complications or improve survival.
Patients with decompensated cirrhosis on the waiting list for liver transplantation (LT) commonly develop complications that may preclude them from reaching LT. Circulatory dysfunction leading to effective arterial hypovolemia and activation of vasoconstrictor systems is a key factor in the pathophysiology of complications of cirrhosis. The aim of this study was to investigate whether treatment with midodrine, an alpha-adrenergic vasoconstrictor, together with intravenous albumin improves circulatory dysfunction and prevents complications of cirrhosis in patients awaiting LT.
A multicenter, randomized, double-blind, placebo-controlled trial (NCT00839358) was conducted, including 196 consecutive patients with cirrhosis and ascites awaiting LT. Patients were randomly assigned to receive midodrine (15–30 mg/day) and albumin (40 g/15 days) or matching placebos for one year, until LT or drop-off from inclusion on the waiting list. The primary endpoint was incidence of any complication (renal failure, hyponatremia, infections, hepatic encephalopathy or gastrointestinal bleeding). Secondary endpoints were mortality, activity of endogenous vasoconstrictor systems and plasma cytokine levels.
There were no significant differences between both groups in the probability of developing complications of cirrhosis during follow-up (p = 0.402) or one-year mortality (p = 0.527). Treatment with midodrine and albumin was associated with a slight but significant decrease in plasma renin activity and aldosterone compared to placebo (renin −4.3 vs. 0.1 ng/ml.h, p < 0.001; aldosterone −38 vs. 6 ng/dl, p = 0.02, at week 48 vs. baseline). Plasma norepinephrine only decreased slightly at week 4. Neither arterial pressure nor plasma cytokine levels changed significantly.
In patients with cirrhosis awaiting LT, treatment with midodrine and albumin, at the doses used in this study, slightly suppressed the activity of vasoconstrictor systems, but did not prevent complications of cirrhosis or improve survival.
Patients with cirrhosis who are on the liver transplant waiting list often develop complications which prevent them from receiving a transplant. Circulatory dysfunction is a key factor behind a number of complications. This study was aimed at investigating whether treating patients with midodrine (a vasoconstrictor) and albumin would improve circulatory dysfunction and prevent complications. This combined treatment, at least at the doses administered in this study, did not prevent the complications of cirrhosis or improve the survival of these patients.
The aim of this study was to evaluate whether the placement of a coaxial double-pigtail plastic stent (DPS) within a lumen-apposing metal stent (LAMS) may improve the safety of endoscopic ultrasound ...(EUS)-guided drainage of pancreatic fluid collections (PFCs).
This was a retrospective cohort study including patients with PFCs and an indication for transmural drainage. Two strategies (LAMS alone or LAMS plus DPS) were used at the endoscopist's discretion.
A total of 41 patients were treated (21 LAMS alone; 20 LAMS plus DPS). The characteristics of the PFCs, and the technical and clinical success rates did not differ between groups. The LAMS alone group had a significantly higher rate of adverse events than the LAMS plus DPS group (42.9 % vs. 10.0 %;
= 0.04). Bleeding was the most frequent adverse event observed.
The addition of a coaxial DPS to LAMS was associated with a lower rate of adverse events in EUS-guided drainage of PFCs.
Background & Aims The recent emergence of third-generation cephalosporin resistance in spontaneous bacterial peritonitis is of great concern, although neither the risk factors for resistance nor its ...real impact on mortality have been well defined. Methods We conducted a retrospective study of all spontaneous bacterial peritonitis episodes with positive blood and/or ascitic culture at our center (2001–2009). Episodes were classified according to the place of acquisition: community, healthcare system, or nosocomial. Results Two hundred and forty-six episodes were analyzed in 200 patients (150 males, 57.3 years): 34.6% community-acquired, 38.6% healthcare system-acquired, and 26.8% nosocomially-acquired. Third-generation cephalosporin resistance occurred in 21.5% (7.1% community-acquired, 21.1% healthcare system-acquired, 40.9% nosocomially-acquired). These resistant cases were categorized as extended-spectrum β-lactamase-producing Gram-negative bacilli, other resistant Gram-negative bacilli, and Enterococci . Risk factors for resistance were previous use of cephalosporins, diabetes mellitus, upper gastrointestinal bleeding, nosocomial acquisition, and a low polymorphonuclear count in ascites. Regarding third-generation cephalosporin resistance, adequate empirical treatment was 80.7%. Independent predictors of mortality were nosocomial acquisition, poor hepato-renal function, immunosuppressive therapy, a marked inflammatory response during the episode and either third-generation cephalosporin-resistance or low rates of adequate empirical treatment. Conclusions The risk of third-generation cephalosporin resistance was particularly high in nosocomially-acquired episodes of spontaneous bacterial peritonitis, but also occurred in healthcare system-acquired cases. The extent of resistance and the adequacy of empirical antibiotics had a significant effect on mortality along with the patient’s hepato-renal function. These data can help determine the most suitable empirical antimicrobial treatments in these patients.
Cytochrome P450 3A4 (CYP3A4) metabolizes about half of all drugs on the market; however, the impact of CYP3A4 loss-of-function variants on drug exposures remains poorly characterized. Here, we report ...the effect of the CYP3A4*20 frameshift allele in two Spanish liver transplant patients treated with tacrolimus.
A series of 90 transplanted patients (with DNA available for 89 of the recipients and 76 of the liver donors) treated with tacrolimus were included in the study. The genotypes of liver donors and of the recipients for CYP3A4*20 (rs67666821), CYP3A4*22 (rs35599367) and CYP3A5*3 (rs776746) were compared with weight-adjusted tacrolimus dose (D), tacrolimus trough concentration (C0), and dose-adjusted tacrolimus trough concentrations (C0/D) using the Mann-Whitney U-nonparametric test.
The CYP3A4*20 allele was detected in two of the liver donors. This genotype yielded at all times higher C0/D (2.6-fold, average) than intermediate CYP3A metabolizers (CYP3A4*1/*1 and CYP3A5*3/*3) (P=0.045, 90 days after transplantation). CYP3A4*22 carriers showed a 1.9-fold average increase in C0/D (P=0.047, 0.025, and 0.053; at days 7, 14, and 30 after transplantation, respectively) compared with intermediate metabolizers. In terms of recipients' genotype, CYP3A5*1 had reduced (P=0.025) and CYP3A4*22 increased C0/D (P=0.056) 7 days after transplantation. The incidence of biopsy-proven acute rejection was 0, 12, and 20% for livers with poor, intermediate, and extensive CYP3A-metabolizing capacity, respectively (P=0.0995).
This first description of CYP3A4*20 null genotype in liver-transplanted patients, supports the relevance of CYP3A genotyping in tacrolimus therapy.
Abstract Objectives Spontaneous bacterial peritonitis is a frequent severe complication in cirrhotic patients with ascites. Carbapenem antibiotics are currently the treatment of choice for patients ...with hospital-acquired or healthcare-related infections. However, there is limited evidence available on the efficacy of ertapenem in cirrhotic patients with spontaneous bacterial peritonitis. As a result, the pharmacokynetics and pharmacodynamics of this antibiotic are still unknown. The objective of this study was to develop and validate measurement procedures based on liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) to determine ertapenem concentrations in plasma and ascitic fluid. Methods Samples were pretreated by acetronile protein-precipitation. Chromatographic separation is performed on a C 18 reversed-phase Acquity ® -UPLC ® -BEH TM column (2.1 × 100 mm id, 1.7 µm) using a non-linear gradient of water/acetonitrile containing 0.1 % of formic acid at a flow rate of 0.4 mL/min. Ertapenem and its internal standard (ertapenem-D 4 ) are detected by tandem mass spectrometry using positive electrospray ionization and multiple reaction monitoring, and using 476.2 → 346.0/432.2 as mass transition for ertapenem and 480.2 → 350.0 for its internal standard. Results No significant interferences or carry-over contamination were observed. Imprecisions, absolute relative bias, matrix effects and normalized recoveries were ≤14.5 %, ≤9.3 % (92.8–104.5) % and (98.8–105.8) %, respectively. Chromatographic measurement procedures were linear from (0.50–100) mg/L. Conclusions The measurement procedures based on UHPLC-MS/MS developed and validated in this study could be useful in pharmacokynetic and pharmacodynamic studies in subjects with liver cirrhosis who develop spontaneous bacterial peritonitis treated with ertapenem.
ABSTRACT
Background and objective: Pleural transudates are most commonly due to heart failure (HF) or hepatic hydrothorax (HH), but a number of these effusions are misclassified as exudates by ...standard (Light's) criteria. The aim of this study was to determine the prevalence of mislabelled transudates and to establish simple alternative parameters to correctly identify them.
Methods: We retrospectively analysed the pleural fluid and serum protein, lactate dehydrogenase and albumin concentrations from 364 cardiac effusions and 102 HH. The serum–to–pleural fluid protein and albumin gradients (serum concentration minus pleural fluid concentration), as well as the pleural fluid–to–serum albumin ratio (pleural fluid concentration divided by the serum concentration) were calculated for the mislabelled transudates.
Results: Light's criteria had misclassified more HF‐associated effusions than HH (29% vs 18%, P = 0.002). A serum–to–pleural fluid protein gradient >3.1 g/dL correctly identified 55% and 61% of the HF and HH false exudates, respectively. The figures for an albumin gradient >1.2 g/dL were 83% and 62%. Finally, a pleural fluid–to–serum albumin ratio <0.6 had identical accuracy for labelling miscategorized cardiac and liver‐related effusions (78% and 77%, respectively).
Conclusions: If the clinical picture is consistent with HF but the pleural fluid meets Light's exudative criteria, the measurement of the albumin rather than the protein gradient is recommended. In the context of cirrhosis, a potentially ‘false’ exudate is identified better by the pleural fluid–to–serum albumin ratio.
Contrary to common belief, the albumin gradient performs significantly better than the protein gradient to correctly classify ‘false’ exudates of cardiac origin. In contrast, in patients with cirrhosis whose pleural fluid meets Light's exudative criteria, the use of the albumin ratio is preferred.
The "rods and rings" (RR) antinuclear antibody (ANA) pattern is believed to be restricted to hepatitis C virus (HCV) infection and related to the treatment. This is a 4-year retrospective study of ...all patients with RR pattern from the 20 000 serum samples received at the Hospital Universitari de Bellvitge for ANA testing. Two control groups with HCV patients without RR pattern: ANA-positive (n = 74) and ANA negative (n = 75) were included. Eighty-seven patients had samples with the RR pattern. Seventy-three were infected with HCV (prevalence of 15% in the HCV population). The RR pattern could not be related to ribavirin treatment, clinical status, biochemistry data, hepatic fibrosis, IL28B genotype, HCV genotype or the presence of autoantibodies related with autoimmune hepatitis. As 14 cases presented other diseases, mainly of autoimmune origin, the presence of RR antibodies may also be explained by alterations in immune regulation caused by autoimmunity or HCV in a particular genetic background.
Studies of liver transplant (LT) patients, mainly in Asians, have evaluated the influence of the CYP3A5*1 allele and P-glycoprotein gene ABCB1 on tacrolimus pharmacokinetics or biopsy-proven acute ...rejection (BPAR) incidence, with no conclusive results. To investigate these issues, 98 Caucasian Spanish LT patients with tacrolimus, mycophenolate mofetil and steroids and 88 cadaveric donors were genotyped for the SNPs CYP3A5 6986G>A, ABCB1 1236C>T, ABCB1 2677G>A/T and ABCB1 3435C>T;. On day 7 post-LT, patients with a native CYP3A5*1 allele had significantly lower tacrolimus trough concentrations C0 (P = .03) and dose-adjusted concentrations C0 /D (P = .02) than CYP3A5 *3/*3 homozygotes. Three months post-LT, patients carrying a liver with CYP3A5*1 had significantly lower C0 /D (P = .03) and took significantly higher tacrolimus doses (P = .03) than the corresponding *3/*3 homozygotes. ABCB1 SNPs showed no significant association with tacrolimus variables. The 3-month incidence of BPAR was 10.2%, with no statistically significant differences related to CYP3A5 (14.3% in expresser vs. 9.5% in non-expresser) or ABCB1 genotype of either patient or donor. We conclude that in Caucasian Spanish LT patients, a native or graft-borne CYP3A5*1 allele tends to lower tacrolimus concentrations and increase dosage needs, but has no significant impact on the incidence of BPAR.
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