The End-Organ Impairment in Liver Cirrhosis: Appointments for Critical Care

Liver cirrhosis (LC) can lead to a clinical state of liver failure, which can exacerbate through the course of the disease. New therapies aimed to control the diverse etiologies are now more effective, although the disease may result in advanced stages of liver failure, where liver transplantation (LT) remains the most effective treatment. The extended lifespan of these patients and the extended possibilities of liver support devices make their admission to an intensive care unit (ICU) more probable. In this paper the LC is approached from the point of view of the pathophysiological alterations present in LC patients previous to ICU admission, particularly cardiovascular, but also renal, coagulopathic, and encephalopathic. Infections and available liver detoxifications devices also deserve mentioning. We intend to contribute towards ICU physician readiness to the care for this particular type of patients, possibly in dedicated ICUs

Quantitation of absolute 2H enrichment of plasma glucose by 2H NMR analysis of its monoacetone derivative

A simple 2H NMR method for quantifying absolute 2H-enrichments in all seven aliphatic positions of glucose following its derivatization to monoacetone glucose is presented. The method is based on the addition of a small quantity of 2H-enriched formate to the NMR sample. When the method was applied to [2-2H]monoacetone glucose samples prepared from [2-2H]glucose standards of known enrichments in the range of 0.2-2.5%, enrichment estimates derived by the NMR method were in good agreement with the real enrichment values of the [2-2H]glucose precursors. The measurement was also applied to monoacetone glucose derived from human plasma glucose samples following administration of 2H2O and attainment of isotopic steady state, where glucose H2 and body water enrichment are equivalent. In these studies, the absolute H2 enrichment of plasma glucose estimated by the formate method was in good agreement with the 2H-enrichment of body water measured by an independent method. Magn Reson Med 48:535-539, 2002. © 2002 Wiley-Liss, Inc

Tet2 Controls the Responses of β cells to Inflammation in Autoimmune Diabetes.

β cells may participate and contribute to their own demise during Type 1 diabetes (T1D). Here we report a role of their expression of Tet2 in regulating immune killing. Tet2 is induced in murine and human β cells with inflammation but its expression is reduced in surviving β cells. Tet2-KO mice that receive WT bone marrow transplants develop insulitis but not diabetes and islet infiltrates do not eliminate β cells even though immune cells from the mice can transfer diabetes to NOD/scid recipients. Tet2-KO recipients are protected from transfer of disease by diabetogenic immune cells.Tet2-KO β cells show reduced expression of IFNγ-induced inflammatory genes that are needed to activate diabetogenic T cells. Here we show that Tet2 regulates pathologic interactions between β cells and immune cells and controls damaging inflammatory pathways. Our data suggests that eliminating TET2 in β cells may reduce activating pathologic immune cells and killing of β cells

A Cross-Sectional Study

Publisher Copyright: © 2022 The Author(s). Published by S. Karger AG, Basel. This article is licensed under the Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC). Usage and distribution for commercial purposes requires written permission.Background: Listing patients with alcohol-associated liver disease (ALD) for liver transplant (LT) remains challenging especially due to the risk of alcohol resumption post-LT. We aimed to evaluate post-LT alcohol consumption at a Portuguese transplant center. Methods: We conducted a cross-sectional study including LT recipients from 2019 at Curry Cabral Hospital, Lisbon, Portugal. A pretested survey and a validated Portuguese translation of the Alcohol Use Disorder Identification Test (AUDIT) were applied via a telephone call. Alcohol consumption was defined by patients' self-reports or a positive AUDIT. Results: In 2019, 122 patients underwent LT, and 99 patients answered the survey (June 2021). The mean (SD) age was 57 (10) years, 70 patients (70.7%) were males, and 49 (49.5%) underwent ALD-related LT. During a median (IQR) follow-up of 24 (20-26) months post-index LT, 22 (22.2%) recipients consumed any amount of alcohol: 14 had a drink monthly or less and 8 drank 2-4 times/month. On drinking days, 18 patients usually consumed 1-2 drinks and the remainder no more than 3-4 drinks. One patient reported having drunk ≥6 drinks on one occasion. All post-LT drinking recipients were considered low risk (score <8) as per the AUDIT score (median [IQR] of 1 [1-2]). No patient reported alcohol-related problems, whether self-inflicted or toward others. Drinking recipients were younger (53 vs. 59 years, p = 0.020), had more non-ALD-related LT (72.7 vs. 44.2%, p = 0.018) and active smoking (31.8 vs. 10.4%, p = 0.037) than abstinent ones. Conclusion: In our cohort, about a quarter of LT recipients consumed alcohol early posttransplant, all with a low-risk pattern according to the AUDIT score.publishersversionepub_ahead_of_prin

A Cohort Analysis

Publisher Copyright: © 2022Background and Aims: The donor risk index (DRI) quantifies donor-related characteristics potentially associated with increased risk of early graft failure. We aimed to assess the impact of the DRI, recipient and perioperative factors on post liver transplant (LT) outcomes. Methods: This was a single-center retrospective cohort study including all adult (≥18 years) patients who underwent LT from 01/2019 to 12/2019 at Curry Cabral Hospital, Lisbon, Portugal. Primary endpoint was 1-year graft failure post LT. Associations were studied with logistic regression. Results: A total of 131 cadaveric donor LT procedures were performed in 116 recipients. Recipients' median (IQR) age was 57 (47-64) years and 101/131 (77.1%) were males. Cirrhosis was the underlying etiology in 95/131 (81.2%) transplants. Based on 8 predefined donors' characteristics, median (IQR) DRI was 1.96 (1.67-2.16). Following adjustment for MELDNa score pre LT and SOFA score (adjusted odds ratio [aOR], 95% confidence interval [CI] = 0.91 [0.56-1.47]) or lactate (aOR [95% CI] = 2.76 [0.71-10.7]) upon intensive care unit (ICU) admission post LT, DRI was not associated with 1-year graft failure. However, higher SOFA score (aOR [95% CI] = 1.20 [1.05-1.37]) or lactate (aOR [95% CI] = 1.27 [1.10-1.46]) upon ICU admission post LT were independently associated with higher odds of 1-year graft failure. Conclusions: In a recent cohort of patients who underwent LT, DRI, despite being high, was not associated with 1-year graft failure, but SOFA score or lactate upon ICU admission post LT were.publishersversionepub_ahead_of_prin

A Gene Expression Signature to Select Hepatocellular Carcinoma Patients for Liver Transplantation

Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.OBJECTIVE: To propose a new decision algorithm combining biomarkers measured in a tumor biopsy with clinical variables, to predict recurrence after liver transplantation (LT). SUMMARY BACKGROUND DATA: Liver cancer is one of the most frequent causes of cancer-related mortality. LT is the best treatment for hepatocellular carcinoma (HCC) patients but the scarcity of organs makes patient selection a critical step. Additionally, clinical criteria widely applied in patient eligibility decisions miss potentially curable patients while selecting patients that relapse after transplantation. METHODS: A literature systematic review singled out candidate biomarkers whose RNA levels were assessed by quantitative PCR in tumor tissue from 138 HCC patients submitted to LT (>5 y follow up, 32% beyond Milan criteria). The resulting four gene signature was combined with clinical variables to develop a decision algorithm using machine learning approaches. The method was named HepatoPredict. RESULTS: HepatoPredict identifies 99% disease-free patients (>5 y) from a retrospective cohort, including many outside clinical criteria (16%-24%), thus reducing the false negative rate. This increased sensitivity is accompanied by an increased positive predictive value (88,5%-94,4%) without any loss of long-term overall survival or recurrence rates for patients deemed eligible by HepatoPredict; those deemed ineligible display marked reduction of survival and increased recurrence in the short and long term. CONCLUSIONS: HepatoPredict outperforms conventional clinical-pathologic selection criteria, (Milan, UCSF) providing superior prognostic information. Accurately identifying which patients most likely benefit from LT enables an objective stratification of waiting lists and information-based allocation of optimal versus suboptimal organs.publishersversionepub_ahead_of_prin

Autoimmune hepatitis in an Internal Medicine ward

Introdução: A hepatite auto-imune (HAI) é uma inflamação hepática de causa desconhecida, caracterizada pela presença de hepatite de interface na biopsia hepática, de hipergamaglobulinemia e de auto-anticorpos característicos. Objectivo: Avaliar as características clínicas, laboratoriais e histológicas, a resposta à terapêutica e o prognóstico da hepatite auto-imune. Métodos: Análise dos processos clínicos dos doentes com hepatite auto-imune admitidos no Serviço de Medicina III dos HUC entre 1987 e 2002. Resultados – Foram diagnosticados 29 casos, 28 do sexo feminino e 1 do masculino, com a idade média de 34,2±16,4 anos. A forma de apresentação foi fulminante em 6,9% dos doentes, aguda em 20,7% e insidiosa ou crónica em 72,4%. Os sintomas mais comuns foram: astenia (65,6%), anorexia (48,3%), náuseas e vómitos (48,3%); 24,1% dos doentes eram assintomáticos. Pelo score do International Autoimmune Hepatitis Group, o diagnóstico era definitivo em 69% dos casos e provável em 31%. Tinham HAI tipo I 86,2% dos doentes, 3,5% eram do tipo II e 10,3% não apresentavam auto-anticorpos convencionais. O anti-VHC era positivo em 2 doentes, o AgHBs em 1 e o IgM anti-VHA em 1. Apresentavam cirrose 27,6% dos doentes. Treze iniciaram terapêutica com prednisolona e 15 com prednisolona + azatioprina, com resposta completa em 39,3% dos casos, parcial em 7,1%, ausência de resposta em 25% e resposta seguida de recaída em 28,6%. O transplante hepático foi realizado em 4 doentes (13,8%). Com um período médio de seguimento de 69 meses (variando entre 1 e 213 meses), a mortalidade foi de 13,8%: 2 doentes por falência hepática, 1 por sepsis e 1 por meningite herpética. Conclusões: À data do diagnóstico, 24,1% dos doentes eram assintomáticos e 27,6% tinham cirrose; a terapêutica com prednisolona e azatioprina foi mais eficaz que a prednisolona isolada; houve necessidade de transplante hepático em 13,8% dos doentes; a evolução foi favorável na maioria dos casos.Introduction: Autoimmune Hepatitis (AIH) is a hepatocellular inflammation of unknown cause, characterised by the presence of interface hepatitis on liver biopsy, and hypergammaglobulinaemia and autoantibodies in serum. Objective: To characterise clinical, laboratory and histological features, as well as the outcome, of AIH. Methods - Retrospective analysis of AIH cases admitted between 1987 and 2002 in an Internal Medicine Ward. Results: Twenty nine patients (pts), with a mean age of 34.2 ±16.4 years and a male-to-female ratio 1:28. The onset was fulminant in 6.9%, acute in 20.7% and insidious or chronic in 72.4%. Asthenia (65.6%), anorexia (48.3%), nausea and vomiting (48.3%), were the most common symptoms; 24.1% were asymptomatic. Applying the scoring system of the International Autoimmune Hepatitis Group, the diagnosis was definitive in 69% and probable in 31%. HAI type I was diagnosed in 86.2%, 3.5% were type II and in 10.3% none of the standard antibodies were found. Two pts were positive for anti-VHC, 1 for HbsAg and 1 had a recent history of hepatitis A. Initial therapy was prednisolone in 13 pts and prednisolone + azathioprine in 15. Complete response was achieved in 39.3%, partial response in 7.1%, failure in 25% and relapse in 28.6%. Four patients underwent liver transplantation. During a mean follow-up period of 69 months (range, 1 to 213 months), the mortality was 13.8%: 2 pts died from hepatic failure, 1 from sepsis and 1 from herpetic meningitis. Conclusions: At the time of diagnosis, 24.1% of the patients were asymptomatic and 27.1% had cirrhosis; therapy with prednisolone and azathioprine was more effective than prednisolone monotherapy; liver transplantation was required in 4 patients; the evolution was favourable in the majority of cases

Continuous passive paracentesis versus large-volume paracentesis in the prevention and treatment of intra-abdominal hypertension in the critically ill cirrhotic patient with ascites (COPPTRIAHL): study protocol for a randomized controlled trial

Abstract Background Critically ill patients with cirrhosis and ascites are at high risk for intra-abdominal hypertension (IAH) which increases mortality. Clinical guidelines recommend maintaining intra-abdominal pressure (IAP) below 16 mmHg; nonetheless, more than three quarters of critically ill patients with cirrhosis develop IAH during their first week of ICU stay. Standard-of-care intermittent large-volume paracentesis (LVP) relieves abdominal wall tension, reduces IAP, optimizes abdominal perfusion pressure, and is associated with short-term improvement in renal and pulmonary dysfunction. However, there is no evidence of the superiority of different paracentesis strategies in the prevention and treatment of IAH in critically ill patients with cirrhosis. This trial aims to compare the outcomes of continuous passive paracentesis versus LVP in the prevention and treatment of IAH in patients with cirrhosis and ascites. Methods An investigator-initiated, open label, randomized controlled trial, set in a general ICU specialized in liver disease, was initiated in August 2022, with an expected duration of 36 months. Seventy patients with cirrhosis and ascites will be randomly assigned, in a 1:1 ratio, to receive one of two methods of therapeutic paracentesis. A stratified randomization method, with maximum creatinine and IAP values as strata, will homogenize patient baseline characteristics before trial group allocation, within 24 h of admission. In the control group, LVP will be performed intermittently according to clinical practice, with a maximum duration of 8 h, while, in the intervention group, continuous passive paracentesis will drain ascitic fluid for up to 7 days. The primary endpoint is serum creatinine concentration, and secondary endpoints include IAP, measured creatinine clearance, daily urine output, stage 3 acute kidney injury and multiorgan dysfunction assessed at day 7 after enrollment, as well as 28-day mortality rate and renal replacement therapy-free days, and length-of-stay. Prespecified values will be used in case of renal replacement therapy or, beforehand ICU discharge, liver transplant and death. Safety analysis will include paracentesis-related complication rate and harm. Data will be analyzed with an intention-to-treat approach. Discussion This is the first trial to compare the impact of different therapeutic paracentesis strategies on organ dysfunction and outcomes in the prevention and treatment of IAH in critically ill patients with cirrhosis and ascites. Trial registration ClinicalTrials.gov NCT04322201 . Registered on 20 December 201