To describe the current epidemiology of bloodstream infection (BSI) in patients with cirrhosis; and to analyse predictors of 30-day mortality and risk factors for antibiotic resistance.
Cirrhotic ...patients developing a BSI episode were prospectively included at 19 centres in five countries from September 2014 to December 2015. The discrimination of mortality risk scores for 30-day mortality were compared by area under the receiver operator risk and Cox regression models. Risk factors for multidrug-resistant organisms (MDRO) were assessed with a logistic regression model.
We enrolled 312 patients. Gram-negative bacteria, Gram-positive bacteria and Candida spp. were the cause of BSI episodes in 53%, 47% and 7% of cases, respectively. The 30-day mortality rate was 25% and was best predicted by the Sequential Organ Failure Assessment (SOFA) and Chronic Liver Failure–SOFA (CLIF-SOFA) score. In a Cox regression model, delayed (>24 hours) antibiotic treatment (hazard ratio (HR) 7.58; 95% confidence interval (CI) 3.29–18.67; p < 0.001), inadequate empirical therapy (HR 3.14; 95% CI 1.93–5.12; p < 0.001) and CLIF-SOFA score (HR 1.35; 95% CI 1.28–1.43; p < 0.001) were independently associated with 30-day mortality. Independent risk factors for MDRO (31% of BSIs) were previous antimicrobial exposure (odds ratio (OR) 2.91; 95% CI 1.73–4.88; p < 0.001) and previous invasive procedures (OR 2.51; 95% CI 1.48–4.24; p 0.001), whereas spontaneous bacterial peritonitis as BSI source was associated with a lower odds of MDRO (OR 0.30; 95% CI 0.12–0.73; p 0.008).
MDRO account for nearly one-third of BSI in cirrhotic patients, often resulting in delayed or inadequate empirical antimicrobial therapy and increased mortality rates. Our data suggest that improved prevention and treatment strategies for MDRO are urgently needed in the liver cirrhosis patients.
The aim of this study was to evaluate the risk factors for candidaemia in patients with liver cirrhosis.
This was a case–control–control (1:2:2) study performed in four Italian tertiary centres from ...2006 to 2015. Cases were patients with liver cirrhosis developing candidaemia. For every case of candidaemia we enrolled two additional patients undergoing blood cultures for suspected infection yielding isolation of a bacterial pathogen (control A) and two additional patients undergoing blood cultures for suspected infection yielding negative results (control B). Patients were matched according to age, sex and model for end stage liver disease at hospital admission.
During the study period 90 cases, 180 controls A and 180 controls B were included. At multivariate analysis assessed by means of multinomial conditional regression models, factors independently associated with candidaemia were previous (<30 days) acute-on-chronic liver failure (relative risk ratio (RRR) 2.22 (95% confidence interval (CI) 1.09–4.54), p = 0.046), previous(<30 days) gastrointestinal endoscopy (RRR 2.38 (95% CI 1.19–4.78) p = 0.014), previous(<30 days) antibiotic treatment for at least 7 days (RRR 2.74 (95% CI 1.00–7.48), p = 0.049), presence of central venous catheter (RRR 2.77 (95% CI 1.26–6.09, p = 0.011), total parenteral nutrition (RRR 3.90 (95% CI 1.62–9.40), p = 0.002) at infection onset and length of in-hospital stay >15 days (RRR 4.63 (95% CI 2.11–10.18), p <0.001 Conversely, rifaximin treatment was associated with lower rate of candidaemia (RRR 0.38 (95% CI 0.19–0.77), p = 0.007). Multivariable analysis for 30-day mortality showed that patients with isolation of Candida spp. from blood cultures had worse outcome when compared with controls even though the difference did not reach a statistical significance (hazard ratio 1.64 (95% 0.97–2.75) p = 0.06).
We identified previous antibiotic use, gastrointestinal endoscopy or acute-on-chronic liver failure and presence of central venous catheter especially for parenteral nutrition as independent factors associated with candidaemia. Surprisingly, chronic rifaximin use was a protective factor.
Abstract The literature on hepatitis B virus (HBV) in immunocompromised patients is heterogeneous and referred mainly to the pre-antivirals era. Today a rational approach to the problem of hepatitis ...B in these patients provides for: (a) the evaluation of HBV markers and of liver condition in all subjects starting immunosuppressive therapies ( baselin e), (b) the treatment with antivirals ( therapy ) of active carriers, (c) the pre-emptive use of antivirals ( prophylaxis ) in inactive carriers, especially if they are undergoing immunosuppressive therapies judged to be at high risk, (d) the biochemical and hepatitis B surface antigen (HBsAg) monitoring ( or universal prophylaxis , in case of high risk immunosuppression) in subjects with markers of previous contact with HBV (HBsAg negative and anti-HBc positive), in order to prevent reverse seroconversion. Moreover it is suggested a strict adherence to criteria of allocation based on the virological characteristics of both recipients and donors in the general setting of transplants and in liver transplantation the universal prophylaxis with nucleos(t)ides analogues (frequently combined with specific anti-HBV immunoglobulins) in HBsAg positive candidates and in HBsAg negative recipients of anti-HBc positive grafts.
Summary
The availability of direct‐acting antiviral agents (DAA) regimens has expanded the pool of patients eligible for treatment. However, data on the virologic response and tolerability of DAAs in ...elderly patients are lacking. We evaluated the efficacy and safety of DAAs in patients with advanced fibrosis/cirrhosis in real‐life practice with the focus on those aged ≥65 years. Between January and December 2015, all consecutive patients with HCV‐related advanced fibrosis/cirrhosis treated with DAA at eleven tertiary referral centres in Emilia Romagna (Italy) were enrolled. Regimen choice was based on viral genotype and stage of disease, according to guidelines. The primary end point was sustained virologic response 12 weeks after the end of treatment (SVR12). Overall, 282 of 556 (50.7%) patients evaluated were elderly, most of them with cirrhosis. Antiviral therapy was stopped prematurely in four (1.4%) patients. Two patients, both with cirrhosis, died during treatment due to worsening of liver/renal function. SVR12 was achieved by 94.7% and was comparable to that obtained in patients aged <65 (P=.074). Similar data were also reported in subgroup of patients aged ≥75 years. All patients with advanced fibrosis achieved virologic response. SVR12 was 80.8% in Child‐Pugh‐Turcotte (CTP)‐B cirrhosis and 95.4% in CTP‐A (P=.013). According to genotype, the SVR12 was achieved in 172 of 181 (95%) with genotype 1b cirrhosis and in 44 of 48 (91.7%) with genotype 2 cirrhosis. In conclusions, in a real‐world setting, DAAs are safe and effective in elderly patients with HCV‐related advanced fibrosis/cirrhosis, but SVR12 is lower with worsening CTP class.
ABSTRACT
Background Little is known about nitric oxide (NO) metabolism and redox changes with hepatocyte adipocytic transformation. The aims of this study were to investigate the changes occurring ...in plasma and hepatic NO metabolites and redox balance in a rat experimental model of simple fatty liver, and to relate plasma with hepatic and mitochondrial changes at different degrees of steatosis.
Materials and methods Circulating and hepatic redox active and nitrogen regulating molecules thioredoxin, glutathione, protein thiols (PSH), mixed disulfides (PSSG), NO metabolites nitrosothiols, nitrite plus nitrate (NOx), and lipid peroxides (TBARs) were measured in rats fed a choline deprived (CD) diet for 30 days.
Results At histology, the CD diet resulted in hepatocellular steatosis (75% of liver weight at day 30) with no signs of necro‐inflammation. In plasma, thioredoxin, nitrosothiols and NOx were unchanged, while TBARs levels increased significantly and were positively related with hepatic TBARs (r = 0·87, P < 0·001) and lipid content (r = 0·90, P < 0·001). In the liver, glutathione initially increased (day 3) and then decreased. From day 14, PSH decreased and NO derivatives increased. Thioredoxin 1 had initially increased (days 7–14) and then decreased. In the mitochondria, on day 14, nitrosothiols were inversely related to thioredoxin 2 (r = 0·988, P < 0·05); on day 30, PSH were decreased by 70%, PSSG were doubled and related with nitrosothiols levels (r = 0·925, P < 0·001).
Conclusion Adipocytic transformation of hepatocytes is accompanied by major interrelated modifications of redox parameters and NO metabolism especially at mitochondrial level, suggesting an early adaptive protective response but also an increased predisposition towards pro‐oxidant insults.
The Endocannabinoid System and Liver Diseases Caraceni, P.; Domenicali, M.; Bernardi, M.
Journal of neuroendocrinology,
20/May , Letnik:
20, Številka:
s1
Journal Article, Conference Proceeding
Recenzirano
Odprti dostop
Endogenous cannabinoids (EC) are ubiquitous lipid signalling molecules provided by a number of central and peripheral effects, which are mainly mediated by the specific cannabinoid receptors CB1 and ...CB2. Although the expression of these receptors is very low or even absent in the healthy liver, a considerable series of experimental studies and some clinical observations have recognised the EC system as an important player in the pathophysiology of liver diseases. The EC system is highly up‐regulated during chronic liver diseases and, to date, it has been implicated in the pathogenesis of non‐alcoholic fatty liver disease, progression of fibrosis to cirrhosis and the development of the cardiovascular abnormalities of cirrhosis, such as the hyperdynamic circulatory syndrome and cirrhotic cardiomiopathy. Furthermore, the EC system influences the mechanisms responsible for cell damage and the inflammatory response during acute liver injury, such as that resulting from ischaemia‐reperfusion. Thus, molecules targeting the CB1 and CB2 receptors may represent potential therapeutic agents for the treatment of liver diseases. At present, the CB1 antagonists represent the most attractive pharmaceutical tool to resolve fat accumulation in patients with non‐alcoholic fatty liver disease and to treat patients with cirrhosis, as they may slow the progression of fibrosis and attenuate the cardiovascular alterations associated with the advanced stage of the disease.
Endotoxaemia can complicate hepatic ischaemia-reperfusion (IR) injury. Endocannabinoids appear to modulate the haemodynamic alterations and cytokine response induced by lipopolysaccharide (LPS). ...Thus, we aimed to determine the effect of the endocannabinoid CB1-receptor antagonist Rimonabant in a model of hepatic IR injury complicated by endotoxaemia.
Sprague-Dawley rats pre-treated with Rimonabant 3 or 10 mg/kg or vehicle underwent partial hepatic IR and lipopolysaccharide (LPS) injection at reperfusion. Liver injury was evaluated by serum alanine aminotransferase (ALT) and necrotic-cell count. The inflammatory response was investigated by assessing hepatic neutrophil infiltration, tumour necrosis factor alpha (TNFalpha), interferon gamma (IFNgamma), interleukin 6 (IL6), and suppressor of cytokine signalling (SOCS) 1 and SOCS3 gene expression by real-time polymerase chain reaction (RT-PCR). Systolic blood pressure and hepatic blood flow were measured as haemodynamic parameters. Finally, lipid peroxidation, glutathione status, and immunoreactive CB1 receptor expression in the liver were also determined.
Liver injury and neutrophil infiltration occurring in the late-phase of LPS-enhanced IR were significantly reduced by CB1-receptor antagonism. Rimonabant-treated rats showed significantly higher gene expression of IFNgamma, IL6, SOCS1 and SOCS3 in "early" reperfusion, while that of TNFalpha was reduced. These findings were associated with increased STAT3 phosphorylation. Furthermore, CB1-receptor antagonism significantly improved the oxidative injury and haemodynamic alterations occurring during reperfusion in untreated rats. Finally, CB1-receptor immunoreactivity was upregulated early after reperfusion.
This study demonstrates that CB1-receptor antagonism protects the liver against LPS-enhanced IR injury by interfering with the inflammatory response that causes the late, neutrophil-dependent phase of reperfusion injury, although the prevention of the transient endotoxin-related hypotension occurring early during reperfusion may be also involved.
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