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1.
Liver Int ; 44(3): 823-830, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38238897

RESUMEN

BACKGROUND AND AIMS: Alcohol-related hepatitis (AH) is the most severe form of acute alcohol-related liver disease. Maddrey's discriminant function ≥32 defines the severe form of AH, which is associated with a high mortality. Steroid therapy represents the main medical treatment that may reduce short-term mortality. Lille score at day 7 assesses the therapeutic response to steroid therapy. At present, no parameters able to predict the response to steroid therapy have been highlighted. The aim of the present study was to evaluate if baseline prothrombin time (BPT) could predict the response to steroid in severe AH (sAH). METHODS: Patients consecutively admitted in two Italian Liver Units, from 2017 to 2022, suffering from sAH were included. Data were collected prospectively. In order to evaluate if BPT could predict steroid response, we assessed the correlation between BPT using the Lille score at day 7. RESULTS: A total of 52 patients received steroid treatment were enrolled in the study. The response to therapy was assessed by Lille score at day 7. Responders were 34 patients (65%), non-responders 18 patients (34%). BPT significantly predicted the steroid response (p < .001). The likelihood of not responding to the steroid therapy was significantly higher in patients with higher BPT (OR = 2.954). CONCLUSIONS: BPT value predicted steroid response in patients with sAH. BPT could quickly identify non-responder patients to steroid therapy, reducing the risk of infections and it could allow the early evaluation for liver transplantation.


Asunto(s)
Hepatitis Alcohólica , Humanos , Tiempo de Protrombina , Hepatitis Alcohólica/tratamiento farmacológico , Hepatitis Alcohólica/complicaciones , Prednisolona/uso terapéutico , Esteroides/uso terapéutico , Índice de Severidad de la Enfermedad
2.
Clin Gastroenterol Hepatol ; 21(8): 2124-2134, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-36858144

RESUMEN

Alcohol-associated liver disease (ALD) is the most common cause of cirrhosis and liver-related mortality in many regions worldwide. Around 75% of patients with cirrhosis are unaware of their disease until they are referred to the emergency department. An innovative, noninvasive screening approach is required for an earlier diagnosis of liver fibrosis. In patients with ALD the physician is inevitably dealing with 2 major disorders: the liver disease itself and the alcohol use disorder (AUD). Focus only on the liver disease will inevitably lead to failure because transient improvements in liver function are rapidly overturned if the patient returns to alcohol consumption. For this reason, integrated models of care provided by hepatologists and addiction specialists are an effective approach, which are, however, not widely available. There are multiple pharmacologic and non-pharmacologic therapies for AUD. Progress has recently been made in the management of patients with severe AH who have improved survival through better understanding of the concept of response to medical treatment, improved survival prediction, and the advent of early liver transplantation. The emerging concept is that listing for transplantation a patient with severe ALD could lead to adjusting the duration of abstinence according to the severity and evolution of liver dysfunction and the patient's addictive profile.


Asunto(s)
Alcoholismo , Hepatopatías Alcohólicas , Trasplante de Hígado , Humanos , Alcoholismo/complicaciones , Hepatopatías Alcohólicas/complicaciones , Hepatopatías Alcohólicas/diagnóstico , Hepatopatías Alcohólicas/terapia , Consumo de Bebidas Alcohólicas , Cirrosis Hepática/complicaciones
3.
Alcohol Alcohol ; 58(2): 125-133, 2023 Mar 10.
Artículo en Inglés | MEDLINE | ID: mdl-36617267

RESUMEN

AIMS: The estimated effect of sodium oxybate (SMO) in the treatment of alcohol dependence is heterogeneous. Population severity and treatment duration have been identified as potential effect modifiers. Population severity distinguishes heavy drinking patients with <14 days of abstinence before treatment initiation (high-severity population) from other patients (mild-severity population). Treatment duration reflects the planned treatment duration. This study aimed to systematically investigate the effect of these potential effect moderators on SMO efficacy in alcohol-dependent patients. METHODS: Network meta-regression allows for testing potential effect modifiers. It was selected to investigate the effect of the above factors on SMO efficacy defined as continuous abstinence (abstinence rate) and the percentage of days abstinent (PDA). Randomized controlled trials for alcohol dependence with at least one SMO group conducted in high-severity and mild-severity populations were assigned to a high-severity and mild-severity group of studies, respectively. RESULTS: Eight studies (1082 patients) were retained: four in the high-severity group and four in the mild-severity group. The high-severity group was associated with larger SMO effect sizes than the mild-severity group: abstinence rate risk ratio (RR) 3.16, P = 0.004; PDA +26.9%, P < 0.001. For PDA, longer treatment duration was associated with larger SMO effect size: +11.3% per extra month, P < 0.001. In the high-severity group, SMO showed benefit: abstinence rate RR 2.91, P = 0.03; PDA +16.9%, P < 0.001. In the mild-severity group, SMO showed benefit only in PDA for longer treatment duration: +23.9%, P < 0.001. CONCLUSIONS: In the retained studies with alcohol-dependent patients, high-severity population and longer treatment duration were associated with larger SMO effect sizes.


Asunto(s)
Alcoholismo , Oxibato de Sodio , Humanos , Alcoholismo/complicaciones , Duración de la Terapia , Etanol , Análisis de Regresión , Oxibato de Sodio/efectos adversos , Resultado del Tratamiento
4.
Semin Liver Dis ; 42(2): 138-150, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35292951

RESUMEN

Alcohol use disorder (AUD) is one of the main causes of global death and disability. The liver represents the main target of alcohol damage, and alcohol-associated liver disease (ALD) represents the first cause of liver cirrhosis in Western countries. Alcohol abstinence is the main goal of treatment in AUD patients with ALD, as treatments for ALD are less effective when drinking continues. Moreover, the persistence of alcohol consumption is associated with higher mortality, increased need for liver transplantation, and graft loss. The most effective treatment for AUD is the combination of psychosocial interventions, pharmacological therapy, and medical management. However, the effectiveness of these treatments in patients with ALD is doubtful even because AUD patients with ALD are usually excluded from pharmacological trials due to concerns on liver safety. This narrative review will discuss the treatment options for AUD-ALD patients focusing on controversies in pharmacological therapy.


Asunto(s)
Alcoholismo , Hepatopatías Alcohólicas , Trasplante de Hígado , Abstinencia de Alcohol , Consumo de Bebidas Alcohólicas/efectos adversos , Alcoholismo/complicaciones , Alcoholismo/tratamiento farmacológico , Humanos , Hepatopatías Alcohólicas/complicaciones , Hepatopatías Alcohólicas/tratamiento farmacológico , Trasplante de Hígado/efectos adversos
5.
Am J Transplant ; 22(4): 1191-1200, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-34954874

RESUMEN

There is increasing evidence that early liver transplantation (eLT), performed within standardized protocols can improve survival in severe alcoholic hepatitis (sAH). The aim of the study was to assess outcomes after eLT for sAH in four Italian LT centers and to compare them with non-responders to medical therapy excluded from eLT. Patients admitted for sAH (2013-2019), according to NIAAA criteria, were included. Patients not responding to medical therapy were placed on the waiting list for eLT after a strict selection. Histological features of explanted livers were evaluated. Posttransplant survival and alcohol relapse were evaluated. Ninety-three patients with severe AH were evaluated (65.6% male, median [IQR] age: 47 [42-56] years). Forty-five of 93 patients received corticosteroids, 52 of 93 were non-responders and among these, 20 patients were waitlisted. Sixteen patients underwent LT. Overall, 6-, 12-, and 24-month survival rates were 100% significantly higher compared with non-responders to medical therapy who were denied LT (45%, 45%, and 36%; p < .001). 2/16 patients resumed alcohol intake, one at 164 days and one at 184 days. Early LT significantly improves survival in sAH non-responding to medical therapy, when a strict selection process is applied. Further studies are needed to properly assess alcohol relapse rates.


Asunto(s)
Hepatitis Alcohólica , Trasplante de Hígado , Femenino , Hepatitis Alcohólica/cirugía , Humanos , Masculino , Persona de Mediana Edad , Selección de Paciente , Recurrencia , Listas de Espera
6.
Dig Dis ; 40(6): 701-709, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-34923490

RESUMEN

BACKGROUND: Several psychological disorders have been described in patients affected by inflammatory bowel disease (IBD). Few studies have focused on the relationship between IBD and post-traumatic stress disorder (PTSD) symptoms, and no data are available on the relationship between IBD and dissociative symptoms. The aim of the present study was to evaluate the prevalence of PTSD and dissociative symptoms in a sample of IBD patients compared to healthy controls. A possible relationship with disease activity was also investigated. METHODS: A total of 112 IBD patients, 55 Crohn's disease (CD) and 57 ulcerative colitis (UC), and 114 healthy individuals were evaluated. IBD patients were divided into 3 subgroups according to disease activity (remission, mild, and moderate). The revised version of the Impact of Event Scale (IES-R) and the Dissociative Experience Scale (DES) were administered to patients and controls. RESULTS: IBD patients showed significantly higher rates of PTSD and dissociative symptoms compared to healthy controls. No differences were found between CD and UC patients. PTSD and dissociative symptoms were higher among CD patients with mild to moderate-severe activity compared to the remission group. No differences were found among UC patients with different activity levels. CONCLUSION: IBD patients show a high prevalence of dissociative and traumatic affective disorders. Future studies are needed to investigate the role of these disorders in the clinical course and management of IBD patients according to the different disease activity phase.


Asunto(s)
Colitis Ulcerosa , Enfermedad de Crohn , Enfermedades Inflamatorias del Intestino , Trastornos por Estrés Postraumático , Humanos , Trastornos por Estrés Postraumático/epidemiología , Trastornos por Estrés Postraumático/etiología , Estudios de Casos y Controles , Colitis Ulcerosa/complicaciones , Colitis Ulcerosa/epidemiología , Colitis Ulcerosa/diagnóstico , Enfermedad de Crohn/diagnóstico , Enfermedades Inflamatorias del Intestino/complicaciones , Enfermedades Inflamatorias del Intestino/epidemiología , Enfermedad Crónica
7.
Dig Dis Sci ; 67(6): 1975-1986, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-34142284

RESUMEN

BACKGROUND: Coronavirus Disease 2019 (COVID-19), firstly reported in China last November 2019, became a global pandemic. It has been shown that periods of isolation may induce a spike in alcohol use disorder (AUD). In addition, alcohol-related liver disease (ALD) is the most common consequence of excessive alcohol consumption worldwide. Moreover, liver impairment has also been reported as a common manifestation of COVID-19. AIMS: The aim of our position paper was to consider some critical issues regarding the management of ALD in patients with AUD in the era of COVID-19. METHODS: A panel of experts of the Italian Society of Alcohology (SIA) met via "conference calls" during the lockdown period to draft the SIA's criteria for the management of ALD in patients with COVID-19 as follows: (a) liver injury in patients with ALD and COVID-19 infection; (b) toxicity to the liver of the drugs currently tested to treat COVID-19 and the pharmacological interaction between medications used to treat AUD and to treat COVID-19; (c) reorganization of the management of compensated and decompensated ALD and liver transplantation in the COVID-19 era. RESULTS AND CONCLUSIONS: The COVID-19 pandemic has rapidly carried us toward a new governance scenario of AUD and ALD which necessarily requires an in-depth review of the management of these diseases with a new safe approach (management of out-patients and in-patients following new rules of safety, telemedicine, telehealth, call meetings with clinicians, nurses, patients, and caregivers) without losing the therapeutic efficacy of multidisciplinary treatment.


Asunto(s)
Alcoholismo , COVID-19 , Hepatopatías Alcohólicas , Alcoholismo/complicaciones , Alcoholismo/epidemiología , Alcoholismo/terapia , Control de Enfermedades Transmisibles , Humanos , Hepatopatías Alcohólicas/epidemiología , Hepatopatías Alcohólicas/terapia , Pandemias
8.
Alcohol Clin Exp Res ; 45(9): 1722-1734, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34418121

RESUMEN

BACKGROUND: There is considerable unexplained variability in alcohol abstinence rates (AR) in the placebo groups of randomized controlled trials (RCTs) for alcohol dependence (AD). This is of particular interest because placebo responses correlate negatively with treatment effect size. Recent evidence suggests that the placebo response is lower in very heavy drinkers who show no "spontaneous improvement" prior to treatment initiation (high-severity population) than in a mild-severity population and in studies with longer treatment duration. We systematically investigated the relationship between population severity, treatment duration, and the placebo response in AR to inform a strategy aimed at reducing the placebo response and thereby increasing assay sensitivity in RCTs for AD. METHODS: We conducted a systematic literature review on placebo-controlled RCTs for AD.We assigned retained RCTs to high- or mild-severity groups of studies based on baseline drinking risk levels and abstinence duration before treatment initiation. We tested the effects of population severity and treatment duration on the placebo response in AR using meta-regression analysis. RESULTS: Among the 19 retained RCTs (comprising 1996 placebo-treated patients), 11 trials were high-severity and 8 were mild-severity RCTs. The between-study variability in AR was lower in the high-severity than in the mild-severity studies (interquartile range: 7.4% vs. 20.9%). The AR in placebo groups was dependent on population severity (p = 0.004) and treatment duration (p = 0.017) and was lower in the high-severity studies (16.8% at 3 months) than the mild-severity studies (36.7% at 3 months). CONCLUSIONS: Pharmacological RCTs for AD should select high-severity patients to decrease the magnitude and variability in the placebo effect and and improve the efficiency of drug development efforts for AD.


Asunto(s)
Alcoholismo/terapia , Efecto Placebo , Ensayos Clínicos Controlados Aleatorios como Asunto , Proyectos de Investigación , Abstinencia de Alcohol , Humanos
9.
Int J Clin Pract ; 75(11): e14755, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34449957

RESUMEN

BACKGROUND AND AIMS: The COVID-19 pandemic represents a source of stress and potential burnout for many physicians. This single-site survey aimed at assessing perceived stress and risk to develop burnout syndrome among physicians operating in COVID wards. METHODS: This longitudinal survey evaluated stress and burnout in 51 physicians operating in the COVID team of Gemelli Hospital, Italy. Participants were asked to complete the Maslach Burnout Inventory (MBI) and the Perceived Stress Questionnaire on a short run (PSQs) (referring to the past 7 days) at baseline (T0) and then for four weeks (T1-T4). Perceived Stress Questionnaire on a long run (PSQl) (referring to the past 2 years) was completed only at T0. RESULTS: Compared with physicians board-certified in internal medicine, those board-certified in other disciplines showed higher scores for the Emotional Exhaustion (EE) score of the MBI scale (P < .001). Depersonalisation (DP) score showed a reduction over time (P = .002). Attending physicians scored lower than the resident physicians on the DP scale (P = .048) and higher than resident physicians on the Personal Accomplishment (PA) scale (P = .04). PSQl predicted higher scores on the EE scale (P = .003), DP scale (P = .003) and lower scores on the PA scale (P < .001). PSQs showed a reduction over time (P = .03). Attending physicians had a lower PSQs score compared with the resident physicians (P = .04). CONCLUSIONS: Medical specialty and clinical position could represent risk factors for the development of burnout in a COVID team. In these preliminary results, physicians board-certified in internal medicine showed lower risk of developing EE during the entire course of the study.


Asunto(s)
COVID-19 , Médicos , Agotamiento Psicológico/epidemiología , Estudios Transversales , Humanos , Estudios Longitudinales , Pandemias , SARS-CoV-2 , Encuestas y Cuestionarios
10.
Medicina (Kaunas) ; 57(4)2021 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-33915819

RESUMEN

Background: The management of septic patients hospitalized in Internal Medicine wards represents a challenge due to their complexity and heterogeneity, and a high mortality rate. Among the available prognostic tools, procalcitonin (PCT) is considered a marker of bacterial infection. Furthermore, an association between vitamin D deficiency and poor sepsis-related outcomes has been described. Objectives: To evaluate the prognostic accuracy of two consecutive PCT determinations (Delta-PCT) and of vitamin D levels in predicting mortality in a population of patients with microbiological identified sepsis admitted to Internal Medicine wards. Methods: This is a sub-analysis of a previous prospective study. A total of 80 patients had at least two available consecutive PCT determinations, while 63 had also vitamin D. Delta-PCT was defined as a reduction of PCT > 50% after 48 h, >75% after 72 h, and >85% after 96 h. Mortality rate at 28- and 90-days were considered as main outcome. Results: Mortality rate was 18.7% at 28-days and 30.0% at 90-days. Baseline PCT levels did not differ between survived and deceased patients (28-days: p = 0.525; 90-days: p = 0.088). A significantly higher proportion of survived patients showed Delta-PCT (28-days: p = 0.002; 90-days: p < 0.001). Delta-PCT was associated with a lower 28-days (p = 0.007; OR = 0.12, 95%CI 0.02-0.46) and 90-days mortality (p = 0.001; OR = 0.17, 95%CI 0.06-0.48). A significantly higher proportion of deceased patients showed severe vitamin D deficiency (28-days: p = 0.047; 90-days: p = 0.049). Severe vitamin D deficiency was associated with a higher 28-days (p = 0.058; OR = 3.95, 95%CI 1.04-19.43) and 90-days mortality (p = 0.054; OR = 2.94, 95%CI 1.00-9.23). Conclusions: Delta-PCT and vitamin D represent two useful tests for predicting prognosis of septic patients admitted to Internal Medicine wards.


Asunto(s)
Polipéptido alfa Relacionado con Calcitonina , Sepsis , Biomarcadores , Humanos , Pronóstico , Estudios Prospectivos , Curva ROC , Sepsis/diagnóstico , Vitamina D
11.
Liver Int ; 40(4): 878-888, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-31951082

RESUMEN

BACKGROUND & AIMS: Alcohol use disorder (AUD) represents the most common cause of liver disease. The gut microbiota plays a critical role in the progression of alcohol-related liver damage. Aim of this study was to characterize the gut microbial composition and function in AUD patients with alcohol-associated liver disease (AALD). METHODS: This study included 36 AUD patients (14 with cirrhosis) who were active drinkers and an equal number of matched controls. Stool microbial composition, serum levels of lipopolysaccharide, cytokines/chemokines and gut microbiota functional profile were assessed. RESULTS: AUD patients had a decreased microbial alpha diversity as compared to controls (0.092 vs 0.130, P = .047) and a specific gut microbial signature. The reduction of Akkermansia and the increase in Bacteroides were able to identify AUD patients with an accuracy of 93.4%. Serum levels of lipopolysaccharide (4.91 vs 2.43, P = .009) and pro-inflammatory mediators (tumour necrosis factor alpha 60.85 vs 15.08, P = .001; interleukin [IL] 1beta 4.43 vs 1.72, P = .0001; monocyte chemoattractant protein 1 225.22 vs 16.43, P = .006; IL6 1.87 vs 1.23, P = .008) were significantly increased in AUD patients compared to controls and in cirrhotic patients compared to non-cirrhotic ones (IL6 3.74 vs 1.39, P = .019; IL8 57.60 vs 6.53, P = .004). The AUD-associated gut microbiota showed an increased expression of gamma-aminobutyric acid (GABA) metabolic pathways and energy metabolism. CONCLUSIONS: AUD patients present a specific gut microbial fingerprint, associated with increased endotoxaemia, systemic inflammatory status and functional alterations that may be involved in the progression of the AALD and in the pathogenesis of AUD.


Asunto(s)
Alcoholismo , Microbioma Gastrointestinal , Hepatopatías Alcohólicas , Alcoholismo/complicaciones , Heces , Humanos , Cirrosis Hepática
12.
Dig Dis ; 38(3): 204-210, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31408862

RESUMEN

BACKGROUND: Takotsubo syndrome (TTS) is an acute cardiac dysfunction in the absence of viral causes or obstructive coronary disease completely reversible within 4-8 weeks. Inflammatory bowel diseases (IBD) are a group of diseases caused by the interaction between immune system, genetic, and environmental factors against intestinal mucosa. Both these syndromes are characterized by complex mechanisms involving endothelial dysfunction and affective disorders. AIM: To assess the possibility of an association between IBD and TTS. METHODS: First, we present a case of TTS in a patient affected by active stenosing Crohn's disease. Articles in English language were collected from PubMed and Google Scholar databases with the search terms "takotsubo," "IBD," "crohn disease," "ulcerative colitis". RESULTS: Both TTS and IBD show multiple common features: preference for female patients, recurrent course of disease, association with endothelial dysfunction, and affective disorders. Patients affected by IBD could show specific triggers for TTS, such as malabsorption, electrolytes disturbances, and affective disorders. CONCLUSIONS: Despite pathophysiological similarities between TTS and IBD in active phase, future studies are needed to confirm this apparently possible association and to assess the presence of a pathophysiological link between these diseases.


Asunto(s)
Enfermedades Inflamatorias del Intestino/complicaciones , Cardiomiopatía de Takotsubo/complicaciones , Anciano , Anciano de 80 o más Años , Enfermedad de Crohn/complicaciones , Femenino , Humanos
13.
Alcohol Alcohol ; 55(5): 547-553, 2020 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-32533164

RESUMEN

AIM: People experiencing homelessness are often excluded from treatment programs for alcohol use disorder (AUD). The goal of this study was to describe the impact of a multidisciplinary treatment program on alcohol consumption and social reintegration in individuals with AUD experiencing homelessness. METHODS: Thirty-one individuals with AUD experiencing homelessness were admitted to an inpatient unit for 5-6 days for clinical evaluation and to treat potential alcohol withdrawal syndrome. A group of volunteers, in collaboration with the Community of Sant'Egidio, provided social support aimed to reintegrate patients. After inpatient discharge, all patients were followed as outpatients. Alcohol intake (number drinks/day), craving and clinical evaluation were assessed at each outpatient visit. Biological markers of alcohol use were evaluated at enrollment (T0), at 6 months (T1) and 12 months (T2). RESULTS: Compared with T0, patients at T1 showed a significant reduction in alcohol consumption [10 (3-24) vs 2 (0-10); P = 0.015] and in γ-glutamyl-transpeptidase [187 (78-365) vs 98 (74-254); P = 0.0021]. The reduction in alcohol intake was more pronounced in patients with any housing condition [10 (3-20) vs 1 (0-8); P = 0.008]. Similarly, compared with T0, patients at T2 showed significant reduction in alcohol consumption [10 (3-24) vs 0 (0-15); P = 0.001], more pronounced in patients with any housing condition [10 (3-20) vs 0 (0-2); P = 0.006]. Moreover, at T2 patients showed a significant reduction in γ-glutamyl-transpeptidase [187 (78-365) vs 97 (74-189); P = 0.002] and in mean cell volume [100.2 (95-103.6) vs 98.3 (95-102); P = 0.042]. CONCLUSION: Patients experiencing homelessness may benefit from a multidisciplinary treatment program for AUD. Strategies able to facilitate and support their social reintegration and housing can improve treatment outcomes.


Asunto(s)
Alcoholismo/terapia , Personas con Mala Vivienda/psicología , Grupo de Atención al Paciente , Adulto , Consumo de Bebidas Alcohólicas/terapia , Alcoholismo/sangre , Ansia , Índices de Eritrocitos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Sistemas de Apoyo Psicosocial , Apoyo Social , Síndrome de Abstinencia a Sustancias/rehabilitación , gamma-Glutamiltransferasa/sangre
16.
Alcohol Clin Exp Res ; 42(12): 2313-2325, 2018 12.
Artículo en Inglés | MEDLINE | ID: mdl-30320890

RESUMEN

BACKGROUND: There is strong evidence that alcoholism leads to dysbiosis in both humans and animals. However, it is unclear how changes in the intestinal microbiota (IM) relate to ethanol (EtOH)-induced disruption of gut-liver homeostasis. We investigated this issue using selectively bred Sardinian alcohol-preferring (sP) rats, a validated animal model of excessive EtOH consumption. METHODS: Independent groups of male adult sP rats were exposed to the standard, home-cage 2-bottle "EtOH (10% v/v) versus water" choice regimen with unlimited access for 24 h/d (Group Et) for 3 (T1), 6 (T2), and 12 (T3) consecutive months. Control groups (Group Ct) were composed of matched-age EtOH-naïve sP rats. We obtained samples from each rat at the end of each experimental time, and we used blood and colon tissues for intestinal barrier integrity and/or liver pathology assessments and used stool samples for IM analysis with 16S ribosomal RNA gene sequencing. RESULTS: Rats in Group Et developed hepatic steatosis and elevated serum transaminases and endotoxin/lipopolysaccharide (LPS) levels but no other liver pathological changes (i.e., necrosis/inflammation) or systemic inflammation. While we did not find any apparent alteration of the intestinal colonic mucosa, we found that rats in Group Et exhibited significant changes in IM composition compared to the rats in Group Ct. These changes were sustained throughout T1, T2, and T3. In particular, Ruminococcus, Coprococcus, and Streptococcus were the differentially abundant microbial genera at T3. The KEGG Ortholog profile revealed that IM functional modules, such as biosynthesis, transport, and export of LPS, were also enriched in Group Et rats at T3. CONCLUSIONS: We showed that chronic, voluntary EtOH consumption induced liver injury and endotoxemia together with dysbiotic changes in sP rats. This work sets the stage for improving our knowledge of the prevention and treatment of EtOH-related diseases.


Asunto(s)
Consumo de Bebidas Alcohólicas/psicología , Endotoxemia/microbiología , Microbioma Gastrointestinal/efectos de los fármacos , Hepatopatías Alcohólicas/microbiología , Consumo de Bebidas Alcohólicas/genética , Animales , Colon/microbiología , Hígado Graso Alcohólico/microbiología , Hígado Graso Alcohólico/patología , Intestinos/patología , Lipopolisacáridos/sangre , Hígado/patología , Pruebas de Función Hepática , Masculino , ARN Ribosómico 16S , Ratas , Transaminasas/sangre
17.
Alcohol Alcohol ; 53(2): 151-156, 2018 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-29206894

RESUMEN

AIM: Alcoholic liver disease (ALD) is the most common liver disease in the Western World. Liver transplantation (LT) is the treatment for end-stage ALD. However, many transplant centers are still reluctant to transplant these patients because of the risk of alcohol relapse, recurrence of the primary liver disease and associated post-transplant complications. We examined survival rate, prevalence of primary liver disease recurrence, re-transplantation and post-transplant complications among transplanted patients for alcoholic cirrhosis compared with those transplanted for viral cirrhosis. METHODS: data about patients transplanted for alcoholic and viral cirrhosis at the Gemelli Hospital from January 1995 to April 2016 were retrospectively collected. Survival rate was evaluated according to the Kaplan-Meier method. Recurrence was defined as histological evidence of primary liver disease. Data on the onset of complication, causes of death and graft failure after liver transplant were analyzed. RESULTS: There was no statistically significant difference regarding survival rate between the two groups. Only patients transplanted for viral cirrhosis presented with primary liver disease recurrence. There was a higher rate of cancer development in patients transplanted for alcoholic cirrhosis. Cancer was the major cause of death in this population. Risk factors associated with the onset of cancer were a high MELD score at the transplant time and smoking after transplantation. CONCLUSION: ALD is a good indication for LT. Patients transplanted for alcoholic cirrhosis should receive regular cancer screening and should be advised against smoking. SHORT SUMMARY: No difference was found between patients transplanted for alcoholic cirrhosis and viral cirrhosis in term of survival rate. Only patients transplanted for viral cirrhosis presented primary liver disease recurrence. A higher rate of cancer development was found in patients transplanted for alcoholic cirrohosis. This complication was associated with post-trasplant smoking.


Asunto(s)
Hepatopatías Alcohólicas/cirugía , Trasplante de Hígado/métodos , Adulto , Anciano , Abstinencia de Alcohol , Causas de Muerte , Femenino , Estudios de Seguimiento , Supervivencia de Injerto , Humanos , Estimación de Kaplan-Meier , Cirrosis Hepática/mortalidad , Cirrosis Hepática/cirugía , Cirrosis Hepática/virología , Cirrosis Hepática Alcohólica/mortalidad , Cirrosis Hepática Alcohólica/cirugía , Hepatopatías Alcohólicas/mortalidad , Neoplasias Hepáticas/mortalidad , Trasplante de Hígado/efectos adversos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/epidemiología , Recurrencia , Reoperación/estadística & datos numéricos , Estudios Retrospectivos , Análisis de Supervivencia
18.
Addict Biol ; 23(4): 969-986, 2018 07.
Artículo en Inglés | MEDLINE | ID: mdl-30043457

RESUMEN

Medication development for alcohol relapse prevention or reduction of consumption is highly challenging due to methodological issues of pharmacotherapy trials. Existing approved medications are only modestly effective with many patients failing to benefit from these therapies. Therefore, there is a pressing need for other effective treatments with a different mechanism of action, especially for patients with very high (VH) drinking risk levels (DRL) because this is the most severely affected population of alcohol use disorder patients. Life expectancy of alcohol-dependent patients with a VH DRL is reduced by 22 years compared with the general population and approximately 90 000 alcohol-dependent subjects with a VH DRL die prematurely each year in the EU (Rehm et al. ). A promising new medication for this population is sodium oxybate, a compound that acts on GABAB receptors and extrasynaptic GABAA receptors resulting in alcohol-mimetic effects. In this article, a European expert group of alcohol researchers and clinicians summarizes data (a) from published trials, (b) from two new-as yet unpublished-large clinical trials (GATE 2 (n = 314) and SMO032 (n = 496), (c) from post hoc subgroup analyses of patients with different WHO-defined DRLs and (d) from multiple meta-analyses. These data provide convergent evidence that sodium oxybate is effective especially in a subgroup of alcohol-dependent patients with VH DRLs. Depending on the study, abstinence rates are increased up to 34 percent compared with placebo with risk ratios up to 6.8 in favor of sodium oxybate treatment. These convergent data are supported by the clinical use of sodium oxybate in Austria and Italy for more than 25 years. Sodium oxybate is the sodium salt of γ-hydroxybutyric acid that is also used as a recreational (street) drug suggestive of abuse potential. However, a pharmacovigilance database of more than 260 000 alcohol-dependent patients treated with sodium oxybate reported very few adverse side effects and only few cases of abuse. We therefore conclude that sodium oxybate is an effective, well-tolerated and safe treatment for withdrawal and relapse prevention treatment, especially in alcohol-dependent patients with VH DRL.


Asunto(s)
Disuasivos de Alcohol/uso terapéutico , Alcoholismo/rehabilitación , Oxibato de Sodio/uso terapéutico , Adolescente , Adulto , Ensayos Clínicos como Asunto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevención Secundaria , Adulto Joven
19.
J Hepatol ; 65(3): 618-30, 2016 09.
Artículo en Inglés | MEDLINE | ID: mdl-27155530

RESUMEN

Alcohol use disorders (AUDs) is one of the leading causes of disease and disability in almost all European countries. Among the alcohol-related diseases, alcoholic liver disease (ALD) is the most common. At present, alcohol is the most frequent cause of liver cirrhosis in the Western world. The cornerstone of treatment for ALD is achieving total alcohol abstinence and preventing relapse; medical and surgical treatments for ALD are limited when drinking continues. This narrative review summarizes current treatments for AUDs with a particular emphasis to the treatment of AUDs in patients with ALD. Medical management, psychosocial and pharmacological interventions are analyzed, underlying limits and options in AUD patients. Finally, this review discusses the most appropriate setting for the management of AUD patients with advanced liver disease as well as the indications for liver transplantation in AUD patients.


Asunto(s)
Trastornos Relacionados con Alcohol , Consumo de Bebidas Alcohólicas , Europa (Continente) , Humanos , Hepatopatías Alcohólicas , Trasplante de Hígado
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