Genetic Ancestry, Race, and Severity of Acutely Decompensated Cirrhosis in Latin America.

BACKGROUND & AIMS: Genetic ancestry or racial differences in health outcomes exist in diseases associated with systemic inflammation (eg, COVID-19). This study aimed to investigate the association of genetic ancestry and race with acute-on-chronic liver failure (ACLF), which is characterized by acute systemic inflammation, multi-organ failure, and high risk of short-term death. METHODS: This prospective cohort study analyzed a comprehensive set of data, including genetic ancestry and race among several others, in 1274 patients with acutely decompensated cirrhosis who were nonelectively admitted to 44 hospitals from 7 Latin American countries. RESULTS: Three hundred ninety-five patients (31.0%) had ACLF of any grade at enrollment. Patients with ACLF had a higher median percentage of Native American genetic ancestry and lower median percentage of European ancestry than patients without ACLF (22.6% vs 12.9% and 53.4% vs 59.6%, respectively). The median percentage of African genetic ancestry was low among patients with ACLF and among those without ACLF. In terms of race, a higher percentage of patients with ACLF than patients without ACLF were Native American and a lower percentage of patients with ACLF than patients without ACLF were European American or African American. In multivariable analyses that adjusted for differences in sociodemographic and clinical characteristics, the odds ratio for ACLF at enrollment was 1.08 (95% CI, 1.03-1.13) with Native American genetic ancestry and 2.57 (95% CI, 1.84-3.58) for Native American race vs European American race CONCLUSIONS: In a large cohort of Latin American patients with acutely decompensated cirrhosis, increasing percentages of Native American ancestry and Native American race were factors independently associated with ACLF at enrollment.

Severe acute hepatitis of unknown origin.

At the beginning of 2022, in the United Kingdom, and later in several European countries, a group of pediatric patients who developed acute hepatitis of so far unknown origin was reported. Clinical data include nausea, vomiting, jaundice, and liver failure; some patients require liver transplantation. The affected population is younger than 10 years of age. The probable etiological agent is adenovirus genotype F41, and toxic factors have been ruled out, as well as a relationship with COVID-19. There are several theories to explain this phenomenon, which are being investigated.

A inicios de 2022, en Reino Unido, y posteriormente en varios países europeos, se informó sobre un grupo de pacientes pediátricos que desarrollaron hepatitis aguda de origen desconocido hasta ahora. Los datos clínicos consisten en náusea, vómito, ictericia y falla hepática; algunos pacientes necesitan trasplante hepático. La población afectada es menor a los 10 años. El agente etiológico probable es el adenovirus genotipo F41 y se han descartado factores tóxicos, así como la relación con COVID-19. Existen varias teorías para explicar este fenómeno, las cuales se están investigando.

Treatment with metadoxine and its impact on early mortality in patients with severe alcoholic hepatitis.

BACKGROUND & AIM: Despite treatment with glucocorticoids, mortality remains high in patients with severe alcoholic hepatitis. Oxidative stress and depletion of mitochondrial glutathione are implicated factors in liver injury. The aim of this study was to evaluate the impact of the addition of metadoxine, a drug which possesses a multifactorial mechanism of action, including antioxidant properties, to standard treatment with glucocorticoids in patients with severe alcoholic hepatitis. MATERIAL AND METHODS: This randomized open label clinical trial was performed in Mexico's General Hospital (Registry Key DIC/10/107/03/043). We randomized 70 patients with severe alcoholic hepatitis. The first group received prednisone (40 mg/day), and the second group received prednisone (40 mg/day) plus metadoxine tablets (500 mg three times daily). The duration of treatment in both groups was 30 days. Survival at 30 and 90 days, development of complications, adverse events and response to treatment (Lille model) were assessed. RESULTS: In the group receiving metadoxine, significant improvements were observed, as follows: survival at 30 days (74.3 vs. 45.7%, P = 0.02); survival at 90 days (68.6 vs. 20.0%, P = 0.0001). There was less development or progression of encephalopathy (28.6 vs. 60.0%, P = 0.008) and hepatorenal syndrome (31.4 vs. 54.3%, P = 0.05), and the response to treatment (Lille model) was higher in the metadoxine group (0.38 vs. 0.63, P = 0.001; 95% CI 0.11 to 0.40). There were no differences between groups regarding the development or progression of variceal hemorrhage or infection. The incidence of adverse events, mainly gastrointestinal, was similar in both groups. CONCLUSIONS: Addition of metadoxine to glucocorticoid treatment improves the short-term survival of patients with severe alcoholic hepatitis and diminishes the development or progression of encephalopathy and hepatorenal syndrome.

Impact of COVID-19 on pre-existing liver disease.

Patients with chronic liver disease of any etiology who become infected with SARS-CoV-2 have been found to have a higher risk of mortality compared to those patients who do not have chronic liver disease. A literature review was conducted in the relationship between COVID 19 and preexistence of liver disease. The proportion of COVID-19 patients with abnormal liver function on admission ranged from 40 % to 75 % and the proportion with liver injury was close to 30%. Current studies show an important association between preexisting liver disease and COVID-19. The presence of cirrhosis is now an independent predictor of severity for COVID-19 and prolonged hospitalization in this group of patients. Patients with cirrhosis have a higher mortality rate, and this rate rises with increasing severity.

Pacientes con enfermedad hepática crónica de cualquier etiología que se infectan con SARS-CoV-2 tienen un mayor riesgo de mortalidad en comparación con aquellos pacientes que no tienen enfermedad hepática crónica. Se llevó a cabo una revisión de la literatura en relación a lo publicado de COVID 19 y enfermedad hepática pre-existente. La proporción de pacientes con COVID-19 con función hepática anormal al ingreso osciló entre el 40 % y el 75 % y la proporción con daño hepático fue cercana al 30 %. Los estudios actuales muestran una asociación importante entre la enfermedad hepática preexistente y la COVID-19. La presencia de cirrosis es ahora un predictor independiente de gravedad para COVID-19 y hospitalización prolongada en este grupo de pacientes. Los pacientes con cirrosis tienen una mayor tasa de mortalidad y esta tasa se incrementa con el aumento de la gravedad de la enfermedad hepática.

The Age-AST-D Dimer (AAD) Regression Model Predicts Severe COVID-19 Disease.

AIM: Coronavirus disease (COVID-19) ranges from mild clinical phenotypes to life-threatening conditions like severe acute respiratory syndrome (SARS). It has been suggested that early liver injury in these patients could be a risk factor for poor outcome. We aimed to identify early biochemical predictive factors related to severe disease development with intensive care requirements in patients with COVID-19. METHODS: Data from COVID-19 patients were collected at admission time to our hospital. Differential biochemical factors were identified between seriously ill patients requiring intensive care unit (ICU) admission (ICU patients) versus stable patients without the need for ICU admission (non-ICU patients). Multiple linear regression was applied, then a predictive model of severity called Age-AST-D dimer (AAD) was constructed (n = 166) and validated (n = 170). RESULTS: Derivation cohort: from 166 patients included, there were 27 (16.3%) ICU patients that showed higher levels of liver injury markers (P < 0.01) compared with non-ICU patients: alanine aminotrasnferase (ALT) 225.4 ± 341.2 vs. 41.3 ± 41.1, aspartate aminotransferase (AST) 325.3 ± 382.4 vs. 52.8 ± 47.1, lactic dehydrogenase (LDH) 764.6 ± 401.9 vs. 461.0 ± 185.6, D-dimer (DD) 7765 ± 9109 vs. 1871 ± 4146, and age 58.6 ± 12.7 vs. 49.1 ± 12.8. With these finding, a model called Age-AST-DD (AAD), with a cut-point of <2.75 (sensitivity = 0.797 and specificity = 0.391, c - statistic = 0.74; 95%IC: 0.62-0.86, P < 0.001), to predict the risk of need admission to ICU (OR = 5.8; 95% CI: 2.2-15.4, P = 0.001), was constructed. Validation cohort: in 170 different patients, the AAD model < 2.75 (c - statistic = 0.80 (95% CI: 0.70-0.91, P < 0.001) adequately predicted the risk (OR = 8.8, 95% CI: 3.4-22.6, P < 0.001) to be admitted in the ICU (27 patients, 15.95%). CONCLUSIONS: The elevation of AST (a possible marker of early liver injury) along with DD and age efficiently predict early (at admission time) probability of ICU admission during the clinical course of COVID-19. The AAD model can improve the comprehensive management of COVID-19 patients, and it could be useful as a triage tool to early classify patients with a high risk of developing a severe clinical course of the disease.

Primary Prophylaxis to Prevent the Development of Hepatic Encephalopathy in Cirrhotic Patients with Acute Variceal Bleeding.

Background and Aim: Variceal bleeding is the second most important precipitating factor related to the development of episodic hepatic encephalopathy; but to date there are no recommendations to prevent this complication. The aim of this study was to compare if primary prophylaxis with lactulose or L-ornithine L-aspartate or rifaximin, in cirrhotic patients with variceal bleeding, is better than placebo for avoiding the development of hepatic encephalopathy. Methods: A randomized, double-blind, placebo-controlled clinical trial (ClinicalTrials.gov identifier: NCT02158182) which included cirrhotic patients with variceal bleeding, without minimal or clinical hepatic encephalopathy at admission. Findings: 87 patients were randomized to one of four groups. The basal characteristics were similar between groups. Comparatively with placebo, the frequency with regard to the development of hepatic encephalopathy was as follows: lactulose (54.5% versus 27.3%; OR = 0.3, 95% CI 0.09-1.0; P = 0.06); L-ornithine L-aspartate (54.5% versus 22.7%, OR = 0.2, 95% CI 0.06-0.88; P = 0.03); rifaximin (54.5% versus 23.8%; OR = 0.3, 95% CI 0.07-0.9; P = 0.04). There was no significant difference between the three groups receiving any antiammonium drug (P = 0.94). In the group receiving lactulose, 59.1% had diarrhea, and 45.5% had abdominal discomfort, bloating, and flatulence. Two patients (10%) treated with lactulose and a patient (4.5%) in the placebo group developed spontaneous bacterial peritonitis due to E. coli; one of them died due to recurrent variceal bleeding. There were no other adverse effects. Conclusions: Antiammonium drugs, particularly L-ornithine L-aspartate and rifaximin, proved to be effective in preventing the development of hepatic encephalopathy in those cirrhotic patients with variceal bleeding.

PROTON PUMP INHIBITORS INCREASE THE OVERALL RISK OF DEVELOPING BACTERIAL INFECTIONS IN PATIENTS WITH CIRRHOSIS.

BACKGROUND: Acid suppression has been associated with adverse events; such as, enteric infections. Proton pump inhibitors (PPI) are frequently prescribed in patients with cirrhosis, but is unclear if PPI are associated with the development of bacterial infections in these patients. OBJECTIVE: To assess the impact of PPI intake on the development of bacterial, viral and fungal infections in patients with cirrhosis. METHODS: An observational, retrospective, historic cohort study. The exposed cohort included patients with cirrhosis with chronic use of PPI. The non-exposed cohort had not been using PPI. The follow-up period was 3 years, searching in the medical records for any events of bacterial infection confirmed by bacteriological culture. RESULTS: One hundred and thirteen patients met the selection criteria, 44 (39%) had chronic use of PPI; of them, 28 (63.6%) patients had not a clear clinical indication to justify the prescription of PPI. Twenty four (21.2%) patients developed bacterial infections during the follow-up period. In the univariate analysis, decompensated cirrhosis (Child B/C), presence of ascites, history of variceal bleeding, and chronic consumption of PPI were risk factors related to the development of infections. But, in the adjusted multivariate analysis only the chronic use of PPI was associated with development of infections (RR=3.6; 95% CI=1.1-12.3; P=0.04). CONCLUSION: There is an over-prescription of PPI without a justified clinical indication. The long-term consumption of PPI in patients with cirrhosis is associated with the development of bacterial infections; therefore these drugs must be carefully prescribed in this specific population.

Hepatitis aguda grave de origen desconocido / Severe acute hepatitis of unknown origin

Resumen A inicios de 2022, en Reino Unido, y posteriormente en varios países europeos, se informó sobre un grupo de pacientes pediátricos que desarrollaron hepatitis aguda de origen desconocido hasta ahora. Los datos clínicos consisten en náusea, vómito, ictericia y falla hepática; algunos pacientes necesitan trasplante hepático. La población afectada es menor a los 10 años. El agente etiológico probable es el adenovirus genotipo F41 y se han descartado factores tóxicos, así como la relación con COVID-19. Existen varias teorías para explicar este fenómeno, las cuales se están investigando.

Abstract At the beginning of 2022, in the United Kingdom, and later in several European countries, a group of pediatric patients who developed acute hepatitis of so far unknown origin was reported. Clinical data include nausea, vomiting, jaundice, and liver failure; some patients require liver transplantation. The affected population is younger than 10 years of age. The probable etiological agent is adenovirus genotype F41, and toxic factors have been ruled out, as well as a relationship with COVID-19. There are several theories to explain this phenomenon, which are being investigated.

Metadoxine improves the three- and six-month survival rates in patients with severe alcoholic hepatitis.

AIM: To evaluate the impact of metadoxine (MTD) on the 3- and 6-mo survival of patients with severe alcoholic hepatitis (AH). METHODS: This study was an open-label clinical trial, performed at the "Hospital General de México, Dr. Eduardo Liceaga". We randomized 135 patients who met the criteria for severe AH into the following groups: 35 patients received prednisone (PDN) 40 mg/d, 35 patients received PDN+MTD 500 mg three times daily, 33 patients received pentoxifylline (PTX) 400 mg three times daily, and 32 patients received PTX+MTD 500 mg three times daily. The duration of the treatment for all of the groups was 30 d. RESULTS: In the groups treated with the MTD, the survival rate was higher at 3 mo (PTX+MTD 59.4% vs PTX 33.3%, P = 0.04; PDN+MTD 68.6% vs PDN 20%, P = 0.0001) and at 6 mo (PTX+MTD 50% vs PTX 18.2%, P = 0.01; PDN+MTD 48.6% vs PDN 20%, P = 0.003) than in the groups not treated with MTD. A relapse in alcohol intake was the primary independent factor predicting mortality at 6 mo. The patients receiving MTD maintained greater abstinence than those who did not receive it (74.5% vs 59.4%, P = 0.02). CONCLUSION: MTD improves the 3- and 6-mo survival rates in patients with severe AH. Alcohol abstinence is a key factor for survival in these patients. The patients who received the combination therapy with MTD were more likely to maintain abstinence than those who received monotherapy with either PDN or PTX.

Inibidores de bomba protônica aumentam o risco geral de desenvolver infecções bacterianas em pacientes com cirrose / Proton pump inhibitors increase the overall risk of developing bacterial infections in patients with cirrhosis

ABSTRACT BACKGROUND: Acid suppression has been associated with adverse events; such as, enteric infections. Proton pump inhibitors (PPI) are frequently prescribed in patients with cirrhosis, but is unclear if PPI are associated with the development of bacterial infections in these patients. OBJECTIVE: To assess the impact of PPI intake on the development of bacterial, viral and fungal infections in patients with cirrhosis. METHODS: An observational, retrospective, historic cohort study. The exposed cohort included patients with cirrhosis with chronic use of PPI. The non-exposed cohort had not been using PPI. The follow-up period was 3 years, searching in the medical records for any events of bacterial infection confirmed by bacteriological culture. RESULTS: One hundred and thirteen patients met the selection criteria, 44 (39%) had chronic use of PPI; of them, 28 (63.6%) patients had not a clear clinical indication to justify the prescription of PPI. Twenty four (21.2%) patients developed bacterial infections during the follow-up period. In the univariate analysis, decompensated cirrhosis (Child B/C), presence of ascites, history of variceal bleeding, and chronic consumption of PPI were risk factors related to the development of infections. But, in the adjusted multivariate analysis only the chronic use of PPI was associated with development of infections (RR=3.6; 95% CI=1.1-12.3; P=0.04). CONCLUSION: There is an over-prescription of PPI without a justified clinical indication. The long-term consumption of PPI in patients with cirrhosis is associated with the development of bacterial infections; therefore these drugs must be carefully prescribed in this specific population.

RESUMO CONTEXTO: A supressão de ácido tem sido associada a efeitos adversos, tais como infecções entéricas. Inibidores da bomba protônica são frequentemente prescritos em pacientes com cirrose, mas não está claro se o inibidor de bomba de próton (IBP) está associado ao desenvolvimento de infecções bacterianas nesses pacientes. OBJETIVO: Avaliar o impacto da ingestão de IBP no desenvolvimento de infecção bacteriana, viral e fúngica em pacientes com cirrose. MÉTODOS: Foi realizado estudo de coorte observacional, retrospectivo, histórico. A coorte exposta incluiu pacientes com cirrose e com uso crônico de IBP. A coorte de não expostos não estava usando IBP. O período de seguimento foi de 3 anos, procurando-se nos registros médicos qualquer evento de infecção bacteriana, confirmada pela cultura bacteriológica. RESULTADOS: Cento e treze pacientes preencheram os critérios de seleção, 44 (39%) pacientes faziam uso crônico de IBP; deles, 28 (63,6%) não tinham uma indicação clínica clara para justificar a prescrição de IBP. Vinte e quatro (21,2%) pacientes desenvolveram infecções bacterianas durante o período de seguimento. Na análise univariada, cirrose descompensada (Child B/C), presença de ascite, história de hemorragia varicosa e consumo crônico de IBP foram fatores de risco relacionados ao desenvolvimento de infecções. Porém, na análise multivariada ajustada, somente o uso crônico de IBP foi associado ao desenvolvimento de infecções (RR=3,6; 95% CI = 1.1-12.3; P=0,04). CONCLUSÃO: Há uma prescrição excessiva de PPI sem uma indicação clínica justificada. O consumo de longo prazo do IBP em pacientes com cirrose é associado ao desenvolvimento de infecções bacterianas. Portanto, essas drogas devem ser cuidadosamente prescritas nesta população específica.