Clinical and microbiological characteristics of bacterial infections in patients with cirrhosis. A prospective cohort study from Argentina and Uruguay.

INTRODUCTION AND OBJECTIVES: there is insufficient data regarding bacterial infections in patients with cirrhosis to support recommendations for empiric antibiotic treatments, particularly in Latin America. This study aimed to evaluate bacterial infection's clinical impact and microbiological characteristics, intending to serve as a platform to revise current practices. MATERIALS AND METHODS: multicenter prospective cohort study of patients with cirrhosis and bacterial infections from Argentina and Uruguay. Patient and infection-related information were collected, focusing on microbiology, antibiotic susceptibility patterns, and outcomes. RESULTS: 472 patients were included. Spontaneous bacterial infections and urinary tract infections (UTIs) were registered in 187 (39.6%) and 116 (24.6%) patients, respectively, representing the most common infections. Of the 256 culture-positive infections, 103 (40.2%) were caused by multidrug-resistant organisms (reaching 50% for UTI), and 181 (70.7%) received adequate initial antibiotic treatment. The coverage of cefepime and ceftriaxone was over 70% for the empirical treatment of community-acquired spontaneous infections, but ceftazidime´s coverage was only 40%. For all UTI cases and for healthcare-associated or nosocomial spontaneous bacterial infections, the lower-spectrum antibiotics that covered at least 70% of the isolations were imipenem and meropenem. During hospitalization, a second bacterial infection was diagnosed in 9.8% of patients, 23.9% required at least one organ support, and 19.5% died. CONCLUSIONS: short-term mortality of bacterial infections in patients with cirrhosis is very high, and a high percentage were caused by multidrug-resistant organisms, particularly in UTIs. The information provided might serve to adapt recommendations, particularly related to empirical antibiotic treatment in Argentina and Uruguay. The study was registered in Clinical Trials (NCT03919032).

Norfloxacin prophylaxis effect on multidrug resistance in patients with cirrhosis and bacterial infections.

It is unclear whether norfloxacin predisposes to infections by multidrug-resistant organisms (MDROs). We aimed to evaluate if patients with cirrhosis receiving norfloxacin prophylaxis at the time of the diagnosis of bacterial infections were more likely to present a multidrug-resistant isolate than those without prophylaxis. This is a cross-sectional study of hospitalized patients with cirrhosis and bacterial infections from Argentina and Uruguay (NCT03919032) from September 2018 to December 2020. The outcome variable was a multidrug-resistant bacterial infection. We used inverse probability of treatment weighting to estimate the odds ratio (OR) of norfloxacin on infection caused by MDROs considering potential confounders. Among the 472 patients from 28 centers, 53 (11%) were receiving norfloxacin at the time of the bacterial infection. Patients receiving norfloxacin had higher MELD-sodium, were more likely to have ascites or encephalopathy, to receive rifaximin, beta-blockers, and proton-pump inhibitors, to have a nosocomial or health-care-associated infection, prior bacterial infections, admissions to critical care units or invasive procedures, and to be admitted in a liver transplant center. In addition, we found that 13 (24.5%) patients with norfloxacin and 90 (21.5%) of those not receiving it presented infections caused by MDROs (adjusted OR 1.55; 95% CI: 0.60-4.03; p = 0.360). The use of norfloxacin prophylaxis at the time of the diagnosis of bacterial infections was not associated with multidrug resistance. These results help empiric antibiotic selection and reassure the current indication of norfloxacin prophylaxis in well-selected patients.Study registration number: NCT03919032.

Liver transplantation in adults with acute liver failure: Outcomes from the Argentinean Transplant Registry.

INTRODUCTION AND AIM: Liver transplantation (LT) for acute liver failure (ALF) still has a high early mortality. We aimed to evaluate changes occurring in recent years and identify risk factors for poor outcomes. MATERIAL AND METHODS: Data were retrospectively obtained from the Argentinean Transplant Registry from two time periods (1998-2005 and 2006-2016). We used survival analysis to evaluate risk of death. RESULTS: A total of 561 patients were listed for LT (69% female, mean age 39.5±16.4 years). Between early and later periods there was a reduction in wait-list mortality from 27% to 19% (p<0.02) and 1-month post-LT survival rates improved from 70% to 82% (p<0.01). Overall, 61% of the patients underwent LT and 22% died on the waiting list. Among those undergoing LT, Cox regression analysis identified prolonged cold ischemia time (HR 1.18 [1.02-1.36] and serum creatinine (HR 1.31 [1.01-1.71]) as independent risk factors of death post-LT. Etiologies of ALF were only available in the later period (N=363) with indeterminate and autoimmune hepatitis accounting for 28% and 26% of the cases, respectively. After adjusting for age, gender, private/public hospital, INR, creatinine and bilirubin, and considering LT as the competing event, indeterminate etiology was significantly associated with death (SHR 1.63 [1.06-2.51] and autoimmune hepatitis presented a trend to improved survival (SHR 0.61 [0.36-1.05]). CONCLUSIONS: Survival of patients with ALF on the waiting list and after LT has significantly improved in recent years. Indeterminate cause and autoimmune hepatitis were the most frequent etiologies of ALF in Argentina and were associated with mortality.

Cyproterone acetate induces a wide spectrum of acute liver damage including corticosteroid-responsive hepatitis: report of 22 cases.

BACKGROUND & AIMS: Cyproterone acetate (CPA), an anti-androgenic drug for prostate cancer, has been associated with drug-induced liver injury (DILI). We aim to expand the knowledge on the spectrum of phenotypes and outcomes of CPA-induced DILI. METHODS: Twenty-two males (70 ± 8 years; range 54-83) developing liver damage as a result of CPA therapy (dose: 150 ± 50 mg/day; range 50-200) were included. Severity index and causality by RUCAM were assessed. RESULTS: From 1993 to 2013, 22 patients were retrieved. Latency was 163 ± 97 days. Most patients were symptomatic, showing hepatocellular injury (91%) and jaundice. Liver tests at onset were: ALT 18 ± 13 × ULN, ALP 0.7 ± 0.7 × ULN and total serum bilirubin 14 ± 10 mg/dl. International normalized ratio values higher than 1.5 were observed in 14 (66%) patients. Severity was mild in 1 case (4%), moderate in 7 (32%), severe in 11 (50%) and fatal in 3 (14%). Five patients developed ascitis, and four encephalopathy. One patient had a liver injury that resembled autoimmune hepatitis. Eleven (50%) were hospitalized. Nineteen patients recovered after CPA withdrawal, although three required steroid therapy (two of them had high ANA titres). Liver biopsy was performed in seven patients (two hepatocellular collapse, one submassive necrosis, two cholestatic hepatitis, one cirrhosis with iron overload and one autoimmune hepatitis). RUCAM category was 'highly probable' in 19 (86%), 'probable' in 1 (4%), and 'possible' in 2 (9%). CONCLUSIONS: CPA-induced liver injury is severe and can be fatal, and may occasionally resemble autoimmune DILI. The benefit/risk ratio of this drug should be thoroughly assessed in each patient.

Natural history of hepatitis C virus infection in a cohort of asymptomatic post-transfused subjects.

UNLABELLED: BACKGROUND & AIMS. Studies about the natural history of hepatitis C virus (HCV) infection report variable progression to cirrhosis depending on study design. Retrospective cross-sectional liver clinic studies overestimate the rate of fibrosis progression due to inclusion of patients with more severe disease leaving mild and asymptomatic patients underrepresented. We evaluated fibrosis progression in a group of "healthy" asymptomatic subjects, attending to a voluntary campaign for the detection of HCV infection. MATERIAL AND METHODS: A detection campaign was launched on subjects transfused before 1993. Of 1699 volunteers, 61(3.6%) had HCV infection. A liver biopsy was performed in 40 (65%). Assessed risk factors for liver fibrosis were: sex, body mass index, alcohol consumption (> 20 g/d - > 40g/d ), genotype, HLA-DRB1 alleles, present age, age at infection and duration of infection. RESULTS: 25 (62.5%) were women with a median age of 52.5 years. The median duration of infection was 21.5 years with a median age at infection of 27 years. As regards fibrosis, 25 (62.5%) had a Low Stage (F0-F1), 8 patients, 20%, had severe fibrosis, one patient (2.5%) had cirrhosis. Alcohol consumption was the only risk factor associated with fibrosis progression. CONCLUSIONS: The low progression to cirrhosis may be explained by the clinical characteristics of our population: asymptomatic middle-aged "healthy" subjects infected at young age. The progression to severe fibrosis was noticeable; hence a longer follow-up might demonstrate changes in this outcome. Significant alcohol consumption clearly worsens the natural history of HCV infection; this is no so evident for occasional or mild alcohol consumers.

Los huesos son estructuras genéticas, metabólicas, biomecánicas, o todo a la vez? / The bones are genetic structures, metabolic, biomechanical, or all at once?

En las últimas décadas, nuestro grupo de trabajo ha contribuido a desarrollar algunas de las nuevas ideas sobre las verdaderas características estructurales que definen la llamada ôcalidad óseaõ, y sus relaciones con sus determinantes genéticos y con la influencia de los entornos mecánico y sistémico que afectan a las células óseas.La moderna corriente es suficientementeimportante como para haber desviadoel interés de los sponsors internacionales de estudios clínicos controlados. El antiguo estudio densitométrico de masas mineralizadas, y el análisis bioquímico de indicadores del turnover óseo, ceden prioridad hoy al estudio de imágenes seccionales osteo-musculares con criterio biomecánico, y al análisis de las interacciones músculo-hueso. Este conocimiento configura ya una unidadconceptual suficientemente coherentecomo para ser divulgado en forma integrada, para uso del médico práctico. Pese a la obvia complejidad del marco teórico del tema en cuestión, los aspectos más relevantes de la nueva corriente de pensamiento para la correcta interpretación de la Osteología moderna pueden resumirse en 13 puntos críticos, cada uno de ellos defácil comprensión si se lo analiza por separado. A continuación se expone una secuencia didáctica de esos 13 puntos, que enumera y describe, para cada uno de ellos, una triada de aspectos fundamentales para su comprensióny asimilación a la nueva corriente, y deriva de ellos un mensaje práctico para su aplicación fisiopatológica, clínica, o terapéutica.

Octreotide enhances portal pressure reduction induced by propranolol in cirrhosis: a randomized, controlled trial.

BACKGROUND: In vitro, octreotide potentiates vasoconstriction in isolated, preconstricted, mesenteric arterial vessels. In cirrhotic patients, portal pressure (HVPG) reduction induced by propranolol is partly due to splanchnic vasoconstriction. AIM: To evaluate HVPG effects of octreotide administration in cirrhotic patients receiving long-term propranolol. PATIENTS AND METHODS: A randomized, controlled trial. First study: a total of 28 patients were studied at baseline and 30 and 60 minutes after octreotide (200 mug) (N = 14) or placebo (N = 14) and then treated with propranolol for approximately 30 days (106 +/- 5 mg/day). Second study: after baseline evaluation patients received octreotide or placebo as they were assigned to in the first study and measurements repeated 30 and 60 minutes later. RESULTS: In the first study baseline HVPG was 18.7 +/- 0.9 mmHg and decreased to 17.1 +/- 1.1 mmHg and 17.1 +/- 1.0 mmHg (both P < 0.05 vs baseline) at 30 and 60 minutes after octreotide, respectively. Eight patients decreased their HVPG after octreotide. In the second study baseline HVPG was 15.6 +/- 1.3 mmHg (P < 0.01 vs baseline HVPG in first study) and decreased to 14.1 +/- 1.2 mmHg and 14.1 +/- 1.3 mmHg (25.7 +/- 5% lower than baseline HVPG in the first study, P < 0.01) (both P < 0.05 vs baseline) at 30 and 60 minutes after octreotide, respectively. Nine patients (2 responders/7 nonresponders to propranolol) decreased their HVPG after octreotide. Octreotide effects may be mediated by potentiation and additive mechanisms. CONCLUSIONS: Octreotide enhances HVPG reduction induced by propranolol in cirrhotic patients.

Absorptiometric assessment of muscle-bone relationships in humans: reference, validation, and application studies.

This report summarizes some preliminary absorptiometric (DXA, QCT/pQCT) studies from our laboratory, supporting the following assumptions. 1. In Homo sapiens at all ages, natural proportionality between DXA-assessed bone mineral mass (bone mineral content, BMC) and muscle mass (lean mass, LM) of the whole body or limbs is specific for ethnicity, gender, and reproductive status, but not for body weight, height, or body mass index. 2. This proportionality is sensitive to many kinds of endocrine-metabolic perturbations. 3. Percentilized or Z-scored charts of the BMC/LM correlations as determined in large samples of healthy individuals can provide a diagnostic reference for evaluating proportionality in different conditions. 4. Employing exclusively DXA, this methodology can be applied to discriminate between "disuse-related" and "metabolic" osteopenias based on the finding of normal or low BMC/LM percentiles or Z-scores respectively, with important therapeutic and monitoring implications.