Treatment with non-selective beta-blockers affects the systemic inflammatory response to bacterial DNA in patients with cirrhosis.

BACKGROUND & AIMS: The use of non-selective beta-blockers has been associated with lower rates of infection and reduced infection-associated morbidity in patients with cirrhosis. However, it is unknown if these drugs modify the systemic inflammatory response to circulating bacterial DNA. METHODS: Sixty-three patients with cirrhosis were included during an episode of decompensation by ascites. Thirty of those patients were on beta-blockers. Blood samples were obtained after each patient had been in the supine position for at least 30 minutes in a quiet atmosphere. Bacterial DNA, serum cytokines, nitric oxide, and LPS were determined. Phagocytic and oxidative burst activities were determined in polymorphonuclear cells from the patients. RESULTS: The detection rate of bacterial DNA in the blood was the same (33%) for patients not treated and treated with non-selective beta-blockers. Patients naive to non-selective beta-blockers showed significantly higher serum levels of IL6, IFN-gamma and IL10 in response to the presence of bacterial DNA. Patients treated with non-selective beta-blockers showed higher basal inflammatory activity that did not change with the presence of bacterial DNA. Monocytes and granulocytes from patients treated with non-selective beta-blockers showed a significantly increased phagocytic capacity in the presence of bacterial DNA. CONCLUSIONS: In patients with cirrhosis, chronic treatment with beta-blockers is associated with a higher unstimulated production of serum cytokines and an increased phagocytic activity in the presence of bacterial DNA.

Immune changes over time and survival in patients with cirrhosis treated with non-selective beta-blockers: A prospective longitudinal study.

BACKGROUND: Treatment with non-selective beta-blockers (NSBB) has been associated with anti-inflammatory and anti-cancer effects in patients with cirrhosis. This study aims to analyze the impact of chronic NSBB treatment on immune activation and disease progression in stable outpatients with cirrhosis. METHODS: In this prospective follow-up of 150 patients with cirrhosis, 39 received treatment with NSBB. Blood samples were taken every 6-9 months, and immune and adrenergic variables were measured. Mixed linear models were used to assess the effect of NSBB on these variables over time. Multivariate Cox regression was used to study associations with adverse clinical events (hepatocellular carcinoma, death, or liver transplant). RESULTS: Median follow-up was 1635 days. NSBB treatment was associated with significantly lower levels of IL-6 (ß - 4.7; 95% confidence interval [CI] -6.9, -2.6) throughout the study. During follow-up, 11 patients developed hepatocellular carcinoma, 32 died, and 4 underwent liver transplant. Patients with higher concentrations of IL-10, IL-6 and IFN-γ developed more clinical events. Event-free survival was significantly better in patients treated with NSBB (hazard ratio 0.36, 95% CI 0.18, 0.71) in a multivariate Cox regression adjusted for Child-Pugh-Score, esophageal varices, and platelets. CONCLUSION: Chronic treatment with NSBB in patients with stable cirrhosis gives rise to a different state of immune activation, characterized by lower concentrations of IL-6 over time, and it is associated with a reduced risk of adverse event (death, hepatocellular carcinoma, or transplant), after controlling for disease severity.

Textbook outcome among patients undergoing enhanced recovery after liver transplantation stratified by risk. A single-center retrospective observational cohort study.

BACKGROUND & AIMS: Liver transplantation (LT) is one of the most complex surgical procedures. Enhanced recovery after surgery (ERAS) aims to reduce the risk of postoperative complications. When patients achieve all desirable outcomes after a procedure, they are considered to have experienced a textbook outcome (TO). METHODS: Two cohorts of patients undergoing low (n = 101) or medium risk (n = 15) LT were identified. The remaining patients (n = 65) were grouped separately. The ERAS protocol included pre-, intra-, and post-operative steps. TO was defined as the absence of complications, prolonged length of hospital stays, readmission and mortality during the first 90 days. RESULTS: One third of patients who underwent ERAS after LT experienced a TO. On multivariable analysis, age (OR, 1.05 [95% CI, 1.01-1.09]; P = .02), and having hepatocellular carcinoma (OR, 2.83 [95% CI, 1.37-6.03]; P = .005) were individually associated with a greater probability of achieving a TO. Belonging to the cohorts of medium risk or outside the selection criteria was associated with a lower probability of achieving a TO (OR, 0.46 [96% CI, 0.22-0.93]; P = .03). Patients less likely to experience TO required more hospital resources. Patients who achieved TO were more likely to remain free of chronic kidney disease (achieved TO, 83.8% [82.7-85.6]; failed TO, 67.9% [66.9-70.2]; P < .05). Tacrolimus dose and trough levels were similar. CONCLUSIONS: A novel finding of our study is that short and medium-term kidney function is better preserved in patients who experience a TO. Better kidney function of patients who achieve TO is not due to lower tacrolimus dosage.

Functionality of beta-adrenergic receptors in patients with cirrhosis treated chronically with non-selective beta-blockers.

BACKGROUND: In patients with cirrhosis, beta-adrenoceptors expressed on peripheral blood mononuclear cells have a reduced response to catecholamine stimulation. This study aimed to determine if chronic treatment with beta-blockers influences these changes. METHODS: Blood samples were collected from patients with cirrhosis treated in outpatient clinics. Differences in cyclic AMP production before and after stimulation of mononuclear cells with epinephrine and/or N-Formylmethionine-leucyl-phenylalanine (fMLP) was used as a marker of beta-adrenoceptors activity in patients treated (N = 19) versus not treated (N = 55) with beta-blockers. In addition, we studied the gene expression of different types of adrenoceptors and possible associations with the activity of beta-adrenoceptors, the serum concentrations of catecholamines and cytokines, and the presence of bacterial antigens such as DNA or gram-negative bacterial endotoxin in patients' blood. RESULTS: The increase in intracellular cAMP concentrations after stimulation of adrenergic receptors with epinephrine was significantly higher in samples from patients treated with beta-blockers. Older patients showed lower responses to epinephrine stimulus, while the response increased linearly with the duration of the beta-blocker treatment. mRNA expression levels of adrenoceptors ß1, ß2, ß3 and α1-A, B and D showed no significant differences according to treatment with beta-blockers. Neither serum cytokines nor catecholamines levels were significantly associated with the intracellular production of cAMP after adrenergic stimulation. CONCLUSION: Chronic treatment with beta-blockers in patients with cirrhosis enables beta-adrenoceptors to respond to catecholamine stimulation irrespective of the degree of systemic adrenergic or immune activations of the patient at the time of sampling.

Surveillance and diagnosis of hepatocellular carcinoma: A systematic review.

BACKGROUND: Hepatocellular carcinoma (HCC) appears in most of cases in patients with advanced liver disease and is currently the primary cause of death in this population. Surveillance of HCC has been proposed and recommended in clinical guidelines to obtain earlier diagnosis, but it is still controversial and is not accepted worldwide. AIM: To review the actual evidence to support the surveillance programs in patients with cirrhosis as well as the diagnosis procedure. METHODS: Systematic review of recent literature of surveillance (tools, interval, cost-benefit, target population) and the role of imaging diagnosis (radiological non-invasive diagnosis, optimal modality and agents) of HCC. RESULTS: The benefits of surveillance of HCC, mainly with ultrasonography, have been assessed in several prospective and retrospective analysis, although the percentage of patients diagnosed in surveillance programs is still low. Surveillance of HCC permits diagnosis in early stages allows better access to curative treatment and increases life expectancy in patients with cirrhosis. HCC is a tumor with special radiological characteristics in computed tomography and magnetic resonance imaging, which allows highly accurate diagnosis without routine biopsy confirmation. The actual recommendation is to perform biopsy only in indeterminate nodules. CONCLUSION: The evidence supports the recommendation of performing surveillance of HCC in patients with cirrhosis susceptible of treatment, using ultrasonography every 6 mo. The diagnosis evaluation of HCC can be established based on noninvasive imaging criteria in patients with cirrhosis.

Trasplante hepático por hemangioendotelioma hepático difuso / Liver transplantation for diffuse epithelioid hemangioendothelioma

RESUMEN El hemangioendotelioma epiteloide hepático (HEH) es un tumor vascular, de etiología no aclarada, extraordinariamente infrecuente. La ausencia de características clínicas, analíticas y radiológicas especificas dificulta su correcto diagnóstico. El tratamiento del HEH depende del tamaño y localización tumoral, la extensión extrahepática y la condición médica del paciente. Entre las posibles opciones se encuentra el trasplante hepático, que obtiene unos buenos resultados clínicos, aunque el riesgo de recidiva no es despreciable. Presentamos un nuevo caso de HEH tratado mediante trasplante hepático.

ABSTRACT Hepatic epithelioid hemangioendothelioma (HEHE) is an extremely rare vascular tumor of unclear etiology. The diagnosis is difficult due to the absence of specific clinical characteristics, laboratory tests results and radiological findings. The management of HEHE depends on tumor size, location, extrahepatic extension, and patients' medical status. Liver transplantation is one of the possible options with good clinical results, although the risk of recurrence is not negligible. We present a new case of HEHE managed with liver transplantation.