Bariatric Surgery Is Associated with Alcohol-Related Liver Disease and Psychiatric Disorders Associated with AUD

Bariatric surgery can increase the risk of addictive disorders and nutritional deficiencies. The aim of this study was to evaluate the association between bariatric surgery and alcohol use disorder (AUD), alcohol-related liver disease (ALD), and psychiatric disorders associated with AUD. The impact of vitamin D deficiency in these associations was also investigated. A cross-sectional study was performed using the National Inpatient Sample database and its ICD-9 codes information. Diagnostic and comorbidity data from hospital discharges were obtained from patients with bariatric surgery and other abdominal surgeries between 2005 and 2015. The two groups were then compared for alcohol-related outcomes after propensity-score matching. The final study cohort included 537,757 patients with bariatric surgery and 537,757 with other abdominal surgeries. The bariatric surgery group had an increased risk of AUD [odds ratio (OR): 1.90; 95% CI: 1.85-1.95], ALD [OR: 1.29; 95% CI: 1.22-1.37], cirrhosis [OR, 1.39; 95% CI: 1.37-1.42], and psychiatric disorders associated with AUD [OR, 3.59; 95% CI: 3.37-3.84]. Vitamin D deficiency did not impact in the association between bariatric surgery and AUD, ALD, or psychiatric disorders associated with AUD. Bariatric surgery is associated with an increased prevalence of AUD, ALD, and psychiatric disorders associated with AUD. These associations appear to be independent from vitamin D deficiency. The online version contains supplementary material available at 10.1007/s11695-023-06490-w

Toll-like receptor 4 polymorphisms and bacterial infections in patients with cirrhosis and ascites

Altres ajuts: Cofinanced by Fondos FEDER (Fondo Europeo de Desarrollo Regional), "Una manera de hacer Europa", European Union, and CERCA Programme, Generalitat de Catalunya; Silvia Vidal was supported by Fondode Investigaciones Sanitarias (FIS) and is a participant in the Program for Stabilization of Investigators of the Direcció d'Estrategia i Coordinació del Departament de Salut, Generalitat de Catalunya.To assess the relationship between the presence of toll-like receptor 4 (TLR4) polymorphisms and bacterial infections in cirrhotic patients with ascites. We prospectively included consecutive patients with cirrhosis and ascites hospitalized during a 6-year period. Patients with human immunodeficiency virus (HIV) infection or any other immunodeficiency, patients with advanced hepatocellular carcinoma (beyond Milan's criteria) or any other condition determining poor short-term prognosis, and patients with a permanent urinary catheter were excluded. The presence of D299G and/or T399I TLR4 polymorphisms was determined by sequencing and related to the incidence and probability of bacterial infections, other complications of cirrhosis, hepatocellular carcinoma, and mortality during follow-up. A multivariate analysis to identify predictive variables of mortality in the whole series was performed. We included 258 patients: 28 (10.8%) were carriers of D299G and/or T399I TLR4 polymorphisms (polymorphism group) and 230 patients were not (wild-type group). The probability of developing any bacterial infection at one-year follow-up was 78% in the polymorphism group and 69% in the wild-type group (P = 0.54). The one-year probability of presenting infections caused by gram-negative bacilli (51% vs 44%, P = 0.68), infections caused by gram-positive cocci (49% vs 40%, P = 0.53), and spontaneous bacterial peritonitis (29% vs 34%, respectively, P = 0.99) did not differ between the two groups. The one-year probability of transplant-free survival was 55% in the polymorphism group and 66% in the wild-type group (P = 0.15). Multivariate analysis confirmed that age, Child-Pugh score, active alcohol intake, previous hepatic encephalopathy, hepatocellular carcinoma and serum creatinine were associated with a higher risk of death during follow-up. Genetic polymorphisms D299G and/or T399I of TLR4 do not seem to play a relevant role in the predisposition of cirrhotic patients with ascites to bacterial infections

Impact of ornithine phenylacetate (OCR-002) in lowering plasma ammonia after upper gastrointestinal bleeding in cirrhotic patients

Ornithine phenylacetate (OP) has been proven effective in lowering ammonia plasma levels in animals, and to be well tolerated in cirrhotic patients. A trial to assess OP efficacy in lowering plasma ammonia levels versus placebo in cirrhotic patients after an upper gastrointestinal bleeding was performed. The primary outcome was a decrease in venous plasma ammonia at 24 hours. A total of 38 consecutive cirrhotic patients were enrolled within 24 hours of an upper gastrointestinal bleed. Patients were randomized (1:1) to receive OP (10 g/day) or glucosaline for 5 days. The primary outcome was not achieved. A progressive decrease in ammonia was observed in both groups, being slightly greater in the OP group, with significant differences only at 120 hours. The subanalysis according to Child-Pugh score showed a statistically significant ammonia decrease in Child-Pugh C-treated patients at 36 hours, as well as in the time-normalized area under the curve (TN-AUC) 0-120 hours in the OP group [40.16 μmol/l (37.7-42.6); median (interquartile range) (IQR)] versus placebo group [65.5 μmol/l (54-126); p = 0.036]. A decrease in plasma glutamine levels was observed in the treated group compared with the placebo group, and was associated with the appearance of phenylacetylglutamine in urine. Adverse-event frequency was similar in both groups. No differences in hepatic encephalopathy incidence were observed. OP failed to significantly decrease plasma ammonia at the given doses (10 g/day). Higher doses of OP might be required in Child-Pugh A and B patients. OP appeared well tolerated

Phase angle by electrical bioimpedance is a predictive factor of hospitalisation, falls and mortality in patients with cirrhosis

The phase angle is a versatile measurement to assess body composition, frailty and prognosis in patients with chronic diseases. In cirrhosis, patients often present alterations in body composition that are related to adverse outcomes. The phase angle could be useful to evaluate prognosis in these patients, but data are scarce. The aim was to analyse the prognostic value of the phase angle to predict clinically relevant events such as hospitalisation, falls, and mortality in patients with cirrhosis. Outpatients with cirrhosis were consecutively included and the phase angle was determined by electrical bioimpedance. Patients were prospectively followed to determine the incidence of hospitalisations, falls, and mortality. One hundred patients were included. Patients with phase angle ≤ 4.6° (n = 31) showed a higher probability of hospitalisation (35% vs 11%, p = 0.003), falls (41% vs 11%, p = 0.001) and mortality (26% vs 3%, p = 0.001) at 2-year follow-up than patients with PA > 4.6° (n = 69). In the multivariable analysis, the phase angle and MELD-Na were independent predictive factors of hospitalisation and mortality. Phase angle was the only predictive factor for falls. In conclusion, the phase angle showed to be a predictive marker for hospitalisation, falls, and mortality in outpatients with cirrhosis

Phase angle by electrical bioimpedance is a predictive factor of hospitalisation, falls and mortality in patients with cirrhosis

The phase angle is a versatile measurement to assess body composition, frailty and prognosis in patients with chronic diseases. In cirrhosis, patients often present alterations in body composition that are related to adverse outcomes. The phase angle could be useful to evaluate prognosis in these patients, but data are scarce. The aim was to analyse the prognostic value of the phase angle to predict clinically relevant events such as hospitalisation, falls, and mortality in patients with cirrhosis. Outpatients with cirrhosis were consecutively included and the phase angle was determined by electrical bioimpedance. Patients were prospectively followed to determine the incidence of hospitalisations, falls, and mortality. One hundred patients were included. Patients with phase angle¿=¿4.6° (n¿=¿31) showed a higher probability of hospitalisation (35% vs 11%, p¿=¿0.003), falls (41% vs 11%, p¿=¿0.001) and mortality (26% vs 3%, p¿=¿0.001) at 2-year follow-up than patients with PA¿>¿4.6° (n¿=¿69). In the multivariable analysis, the phase angle and MELD-Na were independent predictive factors of hospitalisation and mortality. Phase angle was the only predictive factor for falls. In conclusion, the phase angle showed to be a predictive marker for hospitalisation, falls, and mortality in outpatients with cirrhosis.Postprint (published version

PREDICT identifies precipitating events associated with the clinical course of acutely decompensated cirrhosis

Background & Aims: Acute decompensation (AD) of cirrhosis may present without acute-on-chronic liver failure (ACLF) (ADNo ACLF), or with ACLF (AD-ACLF), defined by organ failure(s). Herein, we aimed to analyze and characterize the precipitants leading to both of these AD phenotypes. Methods: The multicenter, prospective, observational PREDICT study (NCT03056612) included 1,273 non-electively hospitalized patients with AD (No ACLF = 1,071; ACLF = 202). Medical history, clinical data and laboratory data were collected at enrolment and during 90-day follow-up, with particular attention given to the following characteristics of precipitants: induction of organ dysfunction or failure, systemic inflammation, chronology, intensity, and relationship to outcome. Results: Among various clinical events, 4 distinct events were precipitants consistently related to AD: proven bacterial infections, severe alcoholic hepatitis, gastrointestinal bleeding with shock and toxic encephalopathy. Among patients with precipitants in the AD-No ACLF cohort and the AD-ACLF cohort (38% and 71%, respectively), almost all (96% and 97%, respectively) showed proven bacterial infection and severe alcoholic hepatitis, either alone or in combination with other events. Survival was similar in patients with proven bacterial infections or severe alcoholic hepatitis in both AD phenotypes. The number of precipitants was associated with significantly increased 90day mortality and was paralleled by increasing levels of surrogates for systemic inflammation. Importantly, adequate first-line antibiotic treatment of proven bacterial infections was associated with a lower ACLF development rate and lower 90-day mortality. Conclusions: This study identified precipitants that are significantly associated with a distinct clinical course and prognosis in patients with AD. Specific preventive and therapeutic strategies targeting these events may improve outcomes in patients with decompensated cirrhosis. Lay summary: Acute decompensation (AD) of cirrhosis is characterized by a rapid deterioration in patient health. Herein, we aimed to analyze the precipitating events that cause AD in patients with cirrhosis. Proven bacterial infections and severe alcoholic hepatitis, either alone or in combination, accounted for almost all (96-97%) cases of AD and acute-on-chronic liver failure. Whilst the type of precipitant was not associated with mortality, the number of precipitant(s) was. This study identified precipitants that are significantly associated with a distinct clinical course and prognosis of patients with AD. Specific preventive and therapeutic strategies targeting these events may improve patient outcomes. (c) 2020 European Association for the Study of the Liver. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

The PREDICT study uncovers three clinical courses of acutely decompensated cirrhosis that have distinct pathophysiology

Acute decompensation (AD) of cirrhosis is defined as the acute development of ascites, gastrointestinal hemorrhage, hepatic encephalopathy, infection or any combination thereof, requiring hospitalization. The presence of organ failure(s) in patients with AD defines acute-on-chronic liver failure (ACLF). The PREDICT study is a European, prospective, observational study, designed to characterize the clinical course of AD and to identify predictors of ACLF. A total of 1,071 patients with AD were enrolled. We collected detailed pre-specified information on the 3-month period prior to enrollment, and clinical and laboratory data at enrollment. Patients were then closely followed up for 3 months. Outcomes (liver transplantation and death) at 1 year were also recorded. Three groups of patients were identified. Pre-ACLF patients (n = 218) developed ACLF and had 3-month and 1-year mortality rates of 53.7% and 67.4%, respectively. Unstable decompensated cirrhosis (UDC) patients (n = 233) required ≥1 readmission but did not develop ACLF and had mortality rates of 21.0% and 35.6%, respectively. Stable decompensated cirrhosis (SDC) patients (n = 620) were not readmitted, did not develop ACLF and had a 1-year mortality rate of only 9.5%. The 3 groups differed significantly regarding the grade and course of systemic inflammation (high-grade at enrollment with aggravation during follow-up in pre-ACLF; low-grade at enrollment with subsequent steady-course in UDC; and low-grade at enrollment with subsequent improvement in SDC) and the prevalence of surrogates of severe portal hypertension throughout the study (high in UDC vs. low in pre-ACLF and SDC). Acute decompensation without ACLF is a heterogeneous condition with 3 different clinical courses and 2 major pathophysiological mechanisms: systemic inflammation and portal hypertension. Predicting the development of ACLF remains a major future challenge. ClinicalTrials.gov number: NCT03056612. Lay summary: Herein, we describe, for the first time, 3 different clinical courses of acute decompensation (AD) of cirrhosis after hospital admission. The first clinical course includes patients who develop acute-on-chronic liver failure (ACLF) and have a high short-term risk of death - termed pre-ACLF. The second clinical course (unstable decompensated cirrhosis) includes patients requiring frequent hospitalizations unrelated to ACLF and is associated with a lower mortality risk than pre-ACLF. Finally, the third clinical course (stable decompensated cirrhosis), includes two-thirds of all patients admitted to hospital with AD - patients in this group rarely require hospital admission and have a much lower 1-year mortality risk

Alcohol-related liver disease phenotype impacts survival after an acute variceal bleeding episode

[Background & Aims] Alcohol-related hepatitis (AH) encompasses a high mortality. AH might be a concomitant event in patients with acute variceal bleeding (AVB). The current study aimed to assess the prevalence of AH in patients with AVB and to compare the clinical outcomes of AH patients to other alcohol-related liver disease (ALD) phenotypes and viral cirrhosis.[Methods] Multicentre, observational study including 916 patients with AVB falling under the next categories: AH (n = 99), ALD cirrhosis actively drinking (d-ALD) (n = 285), ALD cirrhosis abstinent from alcohol (a-ALD) (n = 227) and viral cirrhosis (n = 305). We used a Cox proportional hazards model to calculate adjusted hazard ratio (HR) of death adjusted by MELD.[Results] The prevalence of AH was 16% considering only ALD patients. AH patients exhibited more complications. Forty-two days transplant-free survival was worse among AH, but statistical differences were only observed between AH and d-ALD groups (84 vs. 93%; p = 0.005), when adjusted by MELD no differences were observed between AH and the other groups. At one-year, survival of AH patients (72.7%) was similar to the other groups; when adjusted by MELD mortality HR was better in AH compared to a-ALD (0.48; 0.29–0.8, p = 0.004). Finally, active drinkers who remained abstinent presented better survival, independently of having AH.[Conclusions] Contrary to expected, AH patients with AVB present no worse one-year survival than other patients with different alcohol-related phenotypes or viral cirrhosis. Abstinence influences long-term survival and could explain these counterintuitive results.Meritxell Ventura-Cots is a recipient of Juan Rodés grant from the Instituto de Salud Carlos III (ISCIII), Joan Genescà is a recipient of grants PI18/00947 and PI21/00691 from ISCIII.Peer reviewe

Preemptive-TIPS improves outcome in high-risk variceal bleeding : An observational study

Objective Patients admitted with acute variceal bleeding (AVB) and Child Pugh C score (CP\u2010C) or Child Pugh B plus active bleeding at endoscopy (CP\u2010B+AB) are at high risk for treatment failure, rebleeding and mortality. Preemptive TIPS (p\u2010TIPS) has been shown to improve survival in these patients but its use in clinical practice has been challenged and not routinely incorporated. The present study aimed to further validate the role of preemptive TIPS in a large number of high\u2010risk patients. Design Multicenter, international, observational study including 671 patients from 34 centers admitted for AVB and high\u2010risk of treatment failure. Patients were managed according to current guidelines and use of drugs and endoscopic therapy (D+E) or preemptive TIPS (p\u2010TIPS) was based on individual center policy. Results p\u2010TIPS in the setting of AVB is associated with a lower mortality in Child C patients compared to D+E (1 year mortality 22% vs 47% in D+E group; P=0.002). Mortality rate in CP\u2010B+AB patients was low and p\u2010TIPS did not improve it. In CP\u2010C and CP\u2010B +AB patients, p\u2010TIPS reduces treatment failure and rebleeding (1 year CIF\u2010probability of remaining free of the composite endpoint: 92% vs 74% in the D+E group; P=0.017), development of \u201cde novo\u201d or worsening of previous ascites without increasing rates of hepatic encephalopathy. Conclusion p\u2010TIPS must be the treatment of choice in CP\u2010C patients with AVB. Due to the strong benefit in preventing further bleeding and ascites, p\u2010TIPS could be a good treatment strategy for CP\u2010B+AB patients

Estadio compensado y descompensado de la cirrosis: implicaciones pronósticas y factores relacionados con la progresión de la enfermedad

En la historia natural de la cirrosis, se reconocen dos estadios bien diferenciados con pronósticos diferentes. En los pacientes con cirrosis compensada, el objetivo es retrasar la progresión de la enfermedad y evitar la descompensación. En el paciente con cirrosis descompensada el objetivo es prevenir la muerte. La circulación hiperdinámica juega un papel fundamental en el perfil hemodinámico sistémico y hepático, sobre todo en la respuesta a BBNS. El objetivo principal de esta tesis, es describir y comparar los perfiles hemodinámicos de los pacientes con cirrosis compensada con respecto a los pacientes con cirrosis descompensada, para identificar factores predictivos de descompensación (en los compensados), su capacidad predictiva en el tiempo; y evaluar si en los pacientes con cirrosis descompensada la respuesta hemodinámica a BBNS hepática y sistémica afecta la supervivencia. METODOS: Estudio observacional, retrospectivo con seguimiento prospectivo en el que se incluyeron pacientes derivados a la unidad de hemodinámica para el inicio de profilaxis primaria de hemorragia varicosa con BBNS. Se realizaron 2 estudios hemodinámicos, uno basal con respuesta aguda a BBNS (propranolol EV) y una segunda medición de 1-3 meses bajo tratamiento con BBNS. RESULTADOS: 403 pacientes fueron incluídos, de los cuales 213 eran compensados y 190 descompensados (todos con ascitis). Los pacientes descompensados tenían basalmente peor función hepática con respecto a los compensados (MELD 12.83±3.72 vs 9.39±2.10, P≤ 0.001), mayor presión portal (HVPG= 19.4 ± 5 mmHg vs 17.4 ± 4 mmHg, P≤ 0.001) y peor respuesta a BBNS (Descenso del GPVH = 14 ± 13% vs 10 ± 15%, P5 L/min ( 19% vs 5% , P< 0.001 by log-rank). CONCLUSION: En los pacientes compensados, la ausencia de respuesta hemodinámica y el Child-Pugh son factores predictivos independientes de descompensación. Factores predictivos como el MELD; albúmina y respuesta aguda a BBNS pierden capacidad predictiva a partir del 2º año. Los BBNS tienen más efecto sistémico en los pacientes descompensados con mayor descenso de GC/PAM y menor efecto sobre el GPVH. Sugiriéndose que los efectos beneficiosos de los BBNS en pacientes descompensados va más allá de la presión portal. Una titulación más dirigida a través de métodos cardiovasculares que permitan estimar el GC podría optimizar su empleo en estos pacientes.In the natural history of cirrhosis, two well differentiated stages with different prognoses are recognized. In patients with compensated cirrhosis, the goal is to delay the progression of the disease and prevent decompensation. In the patient with decompensated cirrhosis the goal is to prevent death. Hyperdynamic circulation plays a fundamental role in the systemic and hepatic hemodynamic profile, especially in the response to NSBB. The main objective of this thesis is to describe and compare the hemodynamic profiles of patients with compensated cirrhosis with respect to patients with decompensated cirrhosis, to identify predictors of decompensation (in those compensated), their predictive capacity over time; and to evaluate if in patients with decompensated cirrhosis the hemodynamic response to hepatic and systemic BBNS affects survival. METHODS: Observational, retrospective study with prospective follow-up in which patients referred to the hemodynamic unit were included for the start of primary prophylaxis of varicose hemorrhage with NSBB. Two hemodynamic studies were performed, one baseline with acute response to propranolol EV and a 2º measurement 1-3 months under treatment with NSBB. RESULTS: 403 patients were included, of which 213 were compensated and 190 decompensated (all with ascites). Decompensated patients had baseline worse liver function with respect to those compensated (MELD 12.83 ± 3.72 vs 9.39 ± 2.10, P≤ 0.001), higher portal pressure (HVPG = 19.4 ± 5 ​​mmHg vs 17.4 ± 4 mmHg, P≤ 0.001) and worse hemodynamic response to NSBB (GPVH decrease = 14 ± 13% vs 10 ± 15%, P 5 L / min (19% vs. 5%, P <0.001 by log-rank) CONCLUSION: In compensated patients, the absence of response hemodynamics and the Child-Pu gh are independent predictors of decompensation. Predictive factors such as MELD; albumin and acute response to NSBB lose predictive capacity as of the 2nd year. The NSBB have more systemic effect in decompensated patients with greater decrease in CO / MAP and less effect on HVPG. Suggesting that the beneficial effects of NSBB in decompensated patients goes beyond portal pressure. A more directed titration through cardiovascular methods that allow estimating the CG could optimize its use in these patients