Estudio de la citoqueratina- 18 como marcador no invasivo en pacientes con enfermedad de hígado graso no alcohólico

Introducción: La enfermedad por hígado graso no alcohólico es una de las principales causas de afección hepática. La citoqueratina 18 surge como marcador no invasivo para la valoración de fibrosis hepática. El objetivo del trabajo fue validar el uso de la citoqueratina 18 en sangre periférica en el diagnóstico y evolución de los pacientes con enfermedad por hígado graso no alcohólico. Metodología: Para validar la citoqueratina 18 en el diagnóstico se realizó un estudio de tipo caso-control. El grupo caso fueron los pacientes mayores de 18 años, de ambos sexos, con diagnóstico de enfermedad por hígado graso no alcohólico vinculado al síndrome metabólico, captados entre 2/2/2019 al 2/2/2020. El grupo control fueron personas donantes de sangre. Se parearon 1-1 por edad y sexo. Se cuantificó la citoqueratina 18 en sangre periférica de ambos grupos. Para validar la citoqueratina 18 en la evolución de los pacientes con enfermedad de hígado graso no alcohólico se realizó un trabajo prospectivo, longitudinal. El grupo de pacientes captados fueron seguidos durante un año bajo tratamiento estándar, finalizando el mismo se realizó la cuantificación de citoqueratina 18 en sangre periférica. Las variables continuas se expresan con la media y desvío estándar. Se analizó con test de t Student, error α < 5% Resultados: 13 pacientes integran el grupo caso (12 mujeres), de 53 ± 11 años, con IMC 35.01 ± 8.9 kg/m2. El valor de citoqueratina 18 pre-tratamiento fue de 1410 ± 120 UI, y el valor post-tratamiento fue de 117 ± 56, p < 0,005.El grupo control fueron 13 personas (12 mujeres), de 43,4 ± 8,1 años e IMC 28,10 ± 5,4 kg/m2 El valor de citoqueratina 18 fue de 193 ± 7.2 UI, p < 0.005 vs grupo caso pretratamiento. Conclusiones: La citoqueratina 18 es más elevada en los pacientes con enfermedad hígado graso no alcohólico, siendo estadísticamente significativa y disminuye con el tratamiento con significación estadística, pudiendo constituirse en un marcador útil en este grupo de pacientes.

Introduction: Nonalcoholic fatty liver disease is one of the main causes of liver disease. Cytokeratin 18 emerges as a non-invasive marker for the assessment of liver fibrosis. The objective of the work was to validate the use of cytokeratin 18 in peripheral blood in the diagnosis and evolution of patients with non-alcoholic fatty liver disease. Methodology: To validate cytokeratin 18 in the diagnosis, a case-control study was carried out. The case group was patients over 18 years of age, of both sexes, with a diagnosis of non-alcoholic fatty liver disease linked to metabolic syndrome, recruited between 2/2/2019 to 2/2/2020. The control group were blood donors. They were matched 1-1 for age and sex. Cytokeratin 18 was quantified in peripheral blood of both groups. To validate cytokeratin 18 in the evolution of patients with non-alcoholic fatty liver disease, a prospective, longitudinal study was carried out. The group of patients recruited were followed for one year under standard treatment, at the end of which cytokeratin 18 was quantified in peripheral blood. Continuous variables are expressed with the mean and standard deviation. It was analyzed with Student's t test, α error < 5%. Results: 13 patients make up the case group (12 women), 53 ± 11 years old, with BMI 35.01 ± 8.9 kg/m2. The pre-treatment cytokeratin 18 value was 1410 ± 120 IU, and the post-treatment value was 117 ± 56, p < 0.005. The control group was 13 people (12 women), 43.4 ± 8.1 years and BMI 28.10 ± 5.4 kg/m2 The cytokeratin 18 value was 193 ± 7.2 IU, p < 0.005 vs. pretreatment case group. Conclusions: Cytokeratin 18 is higher in patients with non-alcoholic fatty liver disease, being statistically significant, and decreases with treatment with statistical significance, and may become a useful marker in this group of patients.

Introdução: A doença hepática gordurosa não alcoólica é uma das principais causas de doença hepática. A citoqueratina 18 surge como um marcador não invasivo para avaliação de fibrose hepática. O objetivo do trabalho foi validar o uso da citoqueratina 18 no sangue periférico no diagnóstico e evolução de pacientes com doença hepática gordurosa não alcoólica. Metodologia: Para validar a citoqueratina 18 no diagnóstico, foi realizado um estudo caso-controle. O grupo caso foi composto por pacientes maiores de 18 anos, de ambos os sexos, com diagnóstico de doença hepática gordurosa não alcoólica ligada à síndrome metabólica, recrutados entre 02/02/2019 a 02/02/2020. O grupo controle eram doadores de sangue. Eles foram comparados em 1 a 1 por idade e sexo. A citoqueratina 18 foi quantificada no sangue periférico de ambos os grupos. Para validar a citoqueratina 18 na evolução de pacientes com doença hepática gordurosa não alcoólica, foi realizado um estudo prospectivo e longitudinal. O grupo de pacientes recrutados foi acompanhado durante um ano sob tratamento padrão, ao final do qual a citoqueratina 18 foi quantificada no sangue periférico. As variáveis ​​contínuas são expressas com média e desvio padrão. Foi analisado com teste t de Student, erro α < 5%. Resultados: Compõem o grupo caso 13 pacientes (12 mulheres), 53 ± 11 anos, com IMC 35,01 ± 8,9 kg/m2. O valor de citoqueratina 18 pré-tratamento foi de 1410 ± 120 UI e o valor pós-tratamento foi de 117 ± 56, p < 0,005. O grupo controle foi de 13 pessoas (12 mulheres), 43,4 ± 8,1 anos e IMC 28,10 ± 5,4 kg/m2 O valor da citoqueratina 18 foi de 193 ± 7,2 UI, p < 0,005 vs. grupo de casos pré-tratamento. Conclusões: A citoqueratina 18 é maior em pacientes com doença hepática gordurosa não alcoólica, sendo estatisticamente significativa, e diminui com o tratamento com significância estatística, podendo se tornar um marcador útil neste grupo de pacientes.

Lesión hepática asociado a hemoperitoneo masivo secundario a trauma, reporte de caso / Liver injury associated with massive hemoperitoneum secondary to trauma, case report

Resumen Descripción del caso: Paciente de 23 años con hemorragia abdominal de origen no claro, que posteriormente presenta inestabilidad hemodinámica, requiriendo manejo quirúrgico en tres ocasiones con evolución satisfactoria. Hallazgos clínicos: Presentó sangrado cuantificado de 5500 cc en cavidad abdominal (grado IV - clasificación ATLS) con lesiones hepáticas en los segmentos I, IV y VIII, sin hallazgos sugestivos de trauma al examen físico, ni otros hallazgos traumáticos internos. Tratamiento y resultados: Se llevó a cabo una intervención quirúrgica precoz mediante laparotomía exploratoria con hallazgos ya descritos, además de dos tiempos quirúrgicos adicionales que llevaron al control del sangrado, con evolución satisfactoria. Relevancia clínica: El sangrado abdominal y laceración de víscera sólida secundario a trauma cerrado de abdomen es una etiología común en pacientes jóvenes masculinos, siendo contrario a esta afirmación el sangrado de origen hepático sin trauma es una etiología poco común. El presente caso resulta ser una dificultad diagnóstica en cuanto a la etiología, ya que lo evidenciado en la exploración quirúrgica no concuerda con el examen físico externo, sin una historia clínica clara al ingreso se deja la interrogante de la causa.

Summary: Case description: 23-year-old patient with abdominal hemorrhage of unclear origin, who subsequently presented hemodynamic instability, requiring surgical management on three occasions with satisfactory evolution. Clinical findings: she presented quantified bleeding of 5500 cc in the abdominal cavity (grade IV-ATLS classification) with liver lesions in segments I, IV and VIII, without findings suggestive of trauma on physical examination, or other internal traumatic findings. Treatment and results: An early surgical intervention was carried out through exploratory laparotomy with findings already described, in addition to two additional surgical procedures that led to control of bleeding, with satisfactory evolution. Clinical relevance: Abdominal bleeding and solid viscus laceration secondary to blunt abdominal trauma is a common etiology in young male patients, contrary to this statement, bleeding of hepatic origin without trauma is a rare etiology. The present case turns out to be a diagnostic difficulty in terms of etiology, since what was evidenced in the surgical exploration does not agree with the external physical examination, without a clear clinical history at admission, the question of the cause is left.

[Incidence of metastasis and survival in patients with primary uveal melanoma]. / Incidencia de metástasis y sobrevida en pacientes con melanoma uveal primario.

INTRODUCTION: Primary uveal melanoma is the most common intraocular malignancy in adults. Almost 50% of patients die from metastatic disease despite successful local treatment. The objective was to estimate the incidence of metastasis and survival in patients with primary uveal melanoma. The second objective was to determine the independent predictors of metastasis. METHODS: A retrospective, observational, analytical study was carried out using an ambidirectional cohort design in patients from Buenos Aires City between January 2003 to January 2020. Patients with uveal melanoma and potential clinical predictors of metastasis were identified. The density of incidence of metastasis and mortality were determined, and survival curves were analyzed (Kaplan Meir) A univariate and multivariate analysis using Cox proportional hazard models was performed. RESULTS: 143 patients (mean age 57 SD 16) were included. The median thickness was 6.2 mm SD 3.4 mm, the mean tumor diameter was 12.6 mm (SD 3.8). 69.9% of the patients underwent conservative treatment with brachytherapy while 25.9% underwent enucleation. 19.6% presented metastasis, the median time to the event was 26.5 months. The specific mortality due to melanoma was 17.5%. Diameter greater than 12 mm and extension were predictor variables of metastasis in a multivariable model. CONCLUSION: Although the median time to the event (metastasis) is 26.5 moths, it could occur many years after local oncological effective treatment. An early diagnosis would allow finding smaller tumors and would improve the prognosis.

Introducción: El melanoma uveal primario es el tumor intraocular maligno más frecuente del adulto. Cerca del 50% de los pacientes fallecen de enfermedad metastásica, a pesar de un tratamiento local exitoso. El objetivo primario fue estimar la incidencia de metástasis y sobrevida en los pacientes con melanoma uveal primario. Como objetivo secundario se planteó determinar los predictores independientes de metástasis. Métodos: Se realizó un estudio analítico observacional, retrospectivo mediante un diseño de cohorte ambidireccional entre 2003 y 2020 en CABA, en pacientes con melanoma uveal primario y los potenciales factores clínicos predictores de metástasis. Se determinó la densidad de incidencia de metástasis, la mortalidad, y se analizaron las curvas de sobrevida (Kaplan-Meier). Se realizó un análisis uni y multivariado utilizando el modelo de riesgos proporcionales de Cox. Resultados: De los 143 pacientes (edad promedio 57, DS 16), la mediana del espesor fue de 6. 2 mm DS 3.4, la media del diámetro tumoral fue de 12.6 mm (DS 3.8). Un 69.9% realizó tratamiento conservador con braquiterapia, un 25.9% enucleación. Un 19.6% presentaron metástasis (mediana de tiempo al evento: 26.5 meses). La mortalidad específica por melanoma fue de 17.5%. El diámetro mayor a 12 mm y la extensión fueron variables predictoras de metástasis en el modelo multivariado. Conclusión: Si bien la mediana del tiempo al evento metástasis fue de 26.5 meses, puede presentarse muchos años después de un tratamiento local oncológicamente eficaz. Un diagnóstico precoz permitiría pesquisar tumores más pequeños y mejoraría el pronóstico.

[Meningitis and myelitis by hypervirulent Klebsiella pneumoniae]. / Meningitis y mielitis por Klebsiella pneumoniae hipervirulenta.

Invasive liver abscess syndrome caused by hypervirulent Klebsiella. pneumoniae is a rare disease. This type of K. pneumoniae is aggressive and invasive, despite its sensitivity profile. We report the case of a 62-year-old man with diabetes mellitus, who was admitted to our hospital with meningeal syndrome. Within 24 hours of admission, Gram negative bacilli were isolated blood and cerebrospinal fluid cultures, which were later identified as K. pneumoniae. Liver abscess was detected by computed tomography. Despite early antibiotic treatment, the patient developed back pain that prevented him from moving and right hemiparesis. Increased signal from the central region of the spinal medulla compatible with myelitis was identified by magnetic resonance, for which he received methylprednisolone 1 g/day for 5 days. The patient evolved favorably. Infections caused by hypermucoviscous K. pneumoniae are aggressive and invasive, and more common in men with a history of diabetes mellitus, as in this case. These infections require early antibiotic treatment and the search of metastatic infections.

El síndrome de absceso hepático invasivo causado por cepas hipermucoviscosas de Klebsiella pneumoniae es una enfermedad poco frecuente. Esta serovariedad de Klebsiella se caracteriza por ser agresiva e invasiva pese a su perfil de sensibilidad. Se presenta el caso de un varón de 62 años con antecedentes de diabetes mellitus, que ingresó a nuestro centro con síndrome meníngeo. A las 24 horas del ingreso se aislaron en hemocultivos y en líquido cefalorraquídeo (LCR) bacilos Gram negativos que luego fueron tipificados como Klebsiella pneumoniae. Se identificó la presencia de un absceso hepático mediante tomografía computarizada. Pese al tratamiento antibiótico instaurado de manera temprana, el paciente evolucionó con dolor dorsal que le impedía movilizarse y hemiparesia derecha. En la resonancia magnética nuclear de columna se identificó aumento de la señal de la región central de la médula espinal compatible con mielitis por lo cual recibió tratamiento con metilprednisolona 1g/día por 5 días consecutivos. El paciente evolucionó de manera favorable. Las infecciones por K. pneumoniae hipermucoviscosas son agresivas e invasoras y más frecuentes en varones con antecedentes de diabetes mellitus, como en este caso. Su control requiere de un tratamiento antibiótico temprano y búsqueda de focos a distancia.

Survival after liver transplantation from hepatitis B-core positive donors at a quaternary care hospital in Brazil.

BACKGROUND: Liver transplantation is the treatment for many end-stage liver diseases and hepatocellular carcinoma but shortage of available organs poses significant challenge. Many centers have used grafts from donors with positive anti-HBc serology but concerns about potential hepatitis B virus reactivation and de novo hepatitis B infection have raised questions about the safety of this approach. This study aimed to evaluate the survival of liver transplant recipients from anti-HBc-positive-donors and assess the risk of hepatitis B reactivation and de novo hepatitis B. PATIENTS AND METHODS: A retrospective single-center cohort study was conducted from 2002 to 2018, comparing who received grafts from anti-HBc-positive-donors to those from anti-HBc-negative-donors. The primary outcome was survival and description cases of hepatitis B reactivation/de novo hepatitis B. RESULTS: We analyzed 1,111 liver transplants, in which 993 (89 %) received grafts from anti-HBc-negative-donors and 118 (11 %) from anti-HBc-positive-donors. Median age of recipients from anti-HBc-positive donors was 56 years and from anti-HBc-negative donors was of 53 years (p = 0.001). Male sex was predominant in both groups. Factors associated with death in multivariate analysis were retransplantation, early allograft dysfunction, high MELD, recipient over 60 years and female donor. The utilization of grafts from anti-HBc-positive-donors did not increase mortality. The majority of HBV reactivation and de novo hepatitis B occurred in anti-HBc positive recipients. The risk of hepatitis B reactivation/de novo hepatitis B was low and manageable. CONCLUSION: The study supports safety of liver grafts from anti-HBc-positive donors when employing antiviral prophylaxis. These findings contribute to expand donor options and improve patient outcomes.

Toxicological Evaluation of Kaempferol and Linearolactone as Treatments for Amoebic Liver Abscess Development in Mesocricetus auratus.

Several studies with kaempferol (KP) and linearolactone (LL) have demonstrated their antiparasitic activity. However, the toxicity of these treatments is unknown. Therefore, this study aimed to evaluate the possible toxicological effects of intraperitoneal (i.p.) administration of KP or LL on the amoebic liver abscess model (ALA) in Mesocricetus auratus. An ALA was induced in male hamsters with 1.5 × 105Entamoeba histolytica (E. histolytica) trophozoites inoculated in the left hepatic lobe. The lesion evolved for 4 days, and then KP (5 mg/kg body weight/day) or LL (10 mg/kg body weight/day) was administered for 4 consecutive days. Then, magnetic resonance imaging (MRI), paraclinical analyses, and necropsy for histopathological evaluation were performed. There was similar ALA inhibition by KP (19.42%), LL (28.16%), and metronidazole, the antiamoebic control (20.87%) (p ≤ 0.05, analysis of variance [ANOVA]). There were hepatic and renal biochemical alterations in all treatment groups, mainly for KP (aspartate aminotransferase: 347.5 ± 37.5 U/L; blood urea nitrogen: 19.4 ± 1.9 g/dL; p ≤ 0.05, ANOVA). Lesions found in the organs were directly linked to the pathology. In conclusion, KP and LL decreased ALA development and exerted fewer toxicological effects compared with metronidazole. Therefore, both compounds exhibit therapeutic potential as an alternative treatment of amoebiasis caused by E. histolytica. However, additional clinical studies in different contexts are required to reaffirm this assertion.

FLI and FIB-4 in diagnosing metabolic dysfunction-associated steatotic liver disease in primary care: High prevalence and risk of significant disease.

INTRODUCTION AND OBJECTIVES: Public health policies in metabolic dysfunction-associated steatotic liver disease (MASLD) are still lacking. This study aims to estimate the prevalence and severity of MASLD in primary health care (PHC) through non-invasive markers. PATIENTS AND METHODS: Two-phase study, including a retrospective (RETR) and a prospective (PROS) one, was carried out in PHC in Brazil. In RETR, metabolic and hepatic profiles of 12,054 patients, including FIB-4, were evaluated. In PROS, 350 patients were randomly selected and submitted to a clinical and nutritional assessment. RESULTS: RETR (65.4 % women, mean age 55.3 years old): dyslipidemia, hypertension, and type 2 diabetes mellitus (T2DM) present in 40.8 %, 34.3 %, and 12.2 % of the electronic health records, respectively. Fasting glucose >100 mg/dL in 34.5 %, and glycated hemoglobin higher than 5.7 % in 51.5 %, total cholesterol >200 mg/dL and triglycerides >150 mg/dL in 40.8 % and 32.1 %, respectively. Median FIB-4 was of 1.33, 5 % >2.67. No one had MASLD as a diagnostic hypothesis; PROS(71.8 % women, mean age 58 years old): body mass index (BMI) ≥30 kg/m² in 31.8 %. MASLD prevalence (FLI≥ 30 + cardiometabolic features) of 62.1 %; 39.4 % of patients had FLI ≥60, with higher BMI, waist circumference, fasting glucose, triglycerides, AST, ALT and GGT, as well as lower HDL-cholesterol (p < 0.001). FIB-4>1.3 in 40 % and NAFLD Fibrosis Score (NFS)>-1.45 in 59.2 % of steatotic patients. CONCLUSIONS: There is a high prevalence of MASLD in PHC, with a significant risk of liver fibrosis. These findings reinforce we need to develop public policies to defeat MASLD epidemics.

Waiting for a Liver Transplant in New Mexico; Understanding the State's Multi-layered Adversity.

Contrary to the assumption of consistent medical care for patients with specific illnesses in the United States, research reveals vast inconsistencies and inequalities in healthcare delivery, affecting various aspects such as mental illness diagnosis and management, life expectancy differences, overall mortality rates, and healthcare accessibility due to racial, ethnic, and cultural disparities. Liver transplantation, particularly studied in the context of the state of New Mexico (NM), highlights the multilayered inherent disadvantages faced by its citizens. Despite these challenges, the new liver transplantation allocation system implemented by the Organ Procurement and Transplantation Network (OPTN) in 2020, which focuses on geographic concentric circles rather than donor service areas (DSA), cautiously raises hope for reducing these inequities. The future of decades' worth of adversity remains uncertain, but we are optimistic that New Mexicans' systemic difficulty in getting a new liver would eventually be eased.

The Model for End-Stage Liver Disease (MELD) Score Predicting Mortality Due to SARS-CoV-2 in Mexican Patients.

Background/Objectives: Coronavirus Disease 2019 (COVID-19) can cause liver injury and a deterioration of hepatic function. The Model for End-Stage Liver Disease (MELD) score is a good predictor for poor prognosis of hospitalized COVID-19 patients in the United States, Egypt and Turkey. Nevertheless, the best cut-off value for the MELD score to predict mortality in the Mexican population has yet to be established. Methods: A total of 234 patients with COVID-19 were studied in a tertiary-level hospital. Patients were stratified into survivors (n = 139) and non-survivors (n = 95). Receiver operating characteristic curves, Cox proportional hazard models, Kaplan-Meier method, and Bonferroni corrections were performed to identify the predictors of COVID-19 mortality. Results: MELD score had an area under the curve of 0.62 (95% CI: 0.56-0.68; p = 0.0009), sensitivity = 53.68%, and specificity = 73.38%. Univariate Cox proportional hazard regression analysis suggested that the leukocytes > 10.6, neutrophils > 8.42, neutrophil-to-lymphocyte ratio (NLR) > 8.69, systemic immune-inflammation index (SII) > 1809.21, MELD score > 9, and leukocyte glucose index (LGI) > 2.41 were predictors for mortality. However, the multivariate Cox proportional hazard model revealed that only the MELD score >9 (Hazard Ratio [HR] = 1.83; 95% confidence interval [CI]: 1.2-2.8; Pcorrected = 0.03) was an independent predictor for mortality of COVID-19. Conclusions: Although the MELD score is used for liver transplantation, we suggest that a MELD score >9 could be an accurate predictor for COVID-19 mortality at admission to ICU requiring mechanical ventilation.

Domestic cat hepadnavirus genotype B is present in Southern Brazil.

Domestic cat hepadnavirus (DCH) (Orthohepadnavirus felisdomestici) is an emerging virus related to the hepatitis B virus (HBV) already reported in many countries. The molecular prevalence of DCH varies widely in the regions investigated so far. In the present work, we reported the presence of DCH in Brazil. Sixty cat serum samples tested by DCH presence using PCR and 1.67% (1/60) were positive, similar to the low positive molecular rates reported in United States and Japan. The DCH full-length genome was classified in genotype B, which is uncommon since this genotype was only reported once in Japan. The DCH-positive sample was obtained in a stray cat female apparently healthy, presenting ALT, AST, and ALKP normal values, and negative for FIV and FeLV. Due the low positivity rate detected, some factors as alteration in hepatic enzymes and FIV/FeLV infection could not be evaluated. Other works are necessary to statistically validate these observations in Brazil.

Development and external validation of a machine-learning based model to predict pre-sarcopenia in MASLD population: Results from NHANES 2017-2018.

INTRODUCTION AND OBJECTIVES: With rising prevalence of pre-sarcopenia in metabolic dysfunction-associated steatotic liver disease (MASLD), this study aimed to develop and validate machine learning-based model to identify pre-sarcopenia in MASLD population. MATERIALS AND METHODS: A total of 571 MASLD subjects were screened from the National Health and Nutrition Examination Survey 2017-2018. This cohort was randomly divided into training set and internal testing set with a ratio of 7:3. Sixty-six MASLD subjects were collected from our institution as external validation set. Four binary classifiers, including Random Forest (RF), support vector machine, and extreme gradient boosting and logistic regression, were fitted to identify pre-sarcopenia. The best-performing model was further validated in external validation set. Model performance was assessed in terms of discrimination and calibration. Shapley Additive explanations were used for model interpretability. RESULTS: The pre-sarcopenia rate was 17.51 % and 15.16 % in NHANES cohort and external validation set, respectively. RF outperformed other models with area under receiver operating characteristic curve (AUROC) of 0.819(95 %CI: 0.749, 0.889). When six top-ranking features were retained as per variable importance, including weight-adjusted waist, sex, race, creatinine, education and alkaline phosphatase, a final RF model reached an AUROC being 0.824(0.737, 0.910) and 0.732(95 %CI: 0.529, 0.936) in internal and external validation sets, respectively. The model robustness was proved in sensitivity analysis. The calibration curve and decision curve analysis confirmed a good calibration capacity and good clinical usage. CONCLUSIONS: This study proposed a user-friendly model using explainable machine learning algorithm to predict pre-sarcopenia in MASLD population. A web-based tool was provided to screening pre-sarcopenia in community and hospitalization settings.

Assessment of superior vena cava diameter and collapsibility index in liver transplantation: a prospective observational study.

BACKGROUND: Superior Vena Cava (SVC) diameter and collapsibility index, dynamic measures of fluid responsiveness, have been successfully utilized as echocardiographic indices for fluid responsiveness in ventilated septic patients. Whether these measurements are correlated with Central Venous Pressure (CVP) measurements in liver transplant patients is unknown. We sought to assess the correlation of maximum and minimum SVC diameter and SVC collapsibility index measurements obtained intraoperatively by Transesophageal Echocardiography (TEE) with those of simultaneously recorded CVP measurements obtained through a right atrial port of a pulmonary artery catheter. The secondary aim of the study was to assess the correlation between SVC measurements and simultaneously obtained thermodilution cardiac index measurements. METHODS: Single center prospective observational trial of patients with end stage liver disease undergoing liver transplantation in an academic tertiary care center. RESULTS: The minimum SVC exhibited a mild significant correlation with CVP as did the maximum SVC. The correlation between the SVC collapsibility index and CVP was not significantly different from zero. In our secondary analysis, the correlation between minimum SVC diameter and cardiac index was determined to be weak but non-zero as was the correlation between the maximum SVC diameter and cardiac index. The correlation between SVC collapsibility index and cardiac index was not different from zero. CONCLUSION: While statistically significant, the weak clinical correlation of intraoperative SVC measurements obtained by TEE make them unsuitable as a replacement for central venous pressure or thermodilution cardiac index measurements in liver transplant recipients.

Unveiling the impact of TREM-2+ Macrophages in metabolic disorders.

The Triggering Receptor Expressed on Myeloid cells 2 (TREM-2) has been widely known by its anti-inflammatory activity. It can be activated in response to microbes and tissue damage, leading to phagocytosis, autophagy, cell polarization and migration, counter inflammation, and tissue repair. So far, the receptor has been largely explored in neurodegenerative disorders, however, a growing number of studies have been investigating its contribution in different pathological conditions, including metabolic diseases, in which (resident) macrophages play a crucial role. In this regard, TREM-2 + macrophages have been implicated in the onset and development of obesity, atherosclerosis, and fibrotic liver disease. These macrophages can be detected in the brain, white adipose tissue, liver, and vascular endothelium. In this review we discuss how different murine models have been demonstrating the ability of such cells to contribute to tissue and body homeostasis by phagocytosing cellular debris and lipid structures, besides contributing to lipid homeostasis in metabolic diseases. Therefore, understanding the role of TREM-2 in metabolic disorders is crucial to expand our current knowledge concerning their immunopathology as well as to foster the development of more targeted therapies to treat such conditions.

Protective effect of long-chain polyunsaturated fatty acids on hepatorenal syndrome in rats.

BACKGROUND: Hepatorenal syndrome (HRS) is the most prevalent form of acute kidney injury in cirrhotic patients. It is characterized by reduced renal blood flow and represents the most severe complication in cirrhotic patients with advanced disease. Previous research has indicated that antioxidants can delay the onset of a hyperdynamic circulatory state in cirrhosis and improve renal function in HRS patients. Regular omega-3 supplementation has significantly reduced the risk of liver disease. This supplementation could represent an additional therapy for individuals with HRS. AIM: To evaluated the antioxidant effect of omega-3 polyunsaturated fatty acid supplementation on the kidneys of cirrhotic rats. METHODS: Secondary biliary cirrhosis was induced in rats by biliary duct ligation (BDL) for 28 d. We used 24 male Wistar rats divided into the following groups: I (control); II (treated with omega-3, 1 g/kg of body weight); III (BDL treated with omega-3, 1 g/kg of body weight); and IV (BDL without treatment). The animals were killed by overdose of anesthetic; the kidneys were dissected, removed, frozen in liquid nitrogen, and stored in a freezer at -80℃ for later analysis. We evaluated oxidative stress, nitric oxide (NO) metabolites, DNA damage by the comet assay, cell viability test, and apoptosis in the kidneys. Data were analyzed by one-way analysis of variance, and means were compared using the Tukey test, with P ≤ 0.05. RESULTS: Omega-3 significantly decreased the production of reactive oxygen species (P < 0.001) and lipoperoxidation in the kidneys of cirrhotic rats treated with omega-3 (P < 0.001). The activity of the antioxidant enzymes superoxide dismutase and catalase increased in the BDL+omega-3 group compared to the BDL group (P < 0.01). NO production, DNA damage, and caspase-9 cleavage decreased significantly in the omega-3-treated BDL group. There was an increase in mitochondrial electrochemical potential (P < 0.001) in BDL treated with omega-3 compared to BDL. No changes in the cell survival index in HRS with omega-3 compared to the control group (P > 0.05) were observed. CONCLUSION: The study demonstrates that omega-3 can protect cellular integrity and function by increasing antioxidant enzymes, inhibiting the formation of free radicals, and reducing apoptosis.

Human leukocyte antigen compatibility and incidence of donor-specific antibodies in pediatric liver transplant recipients.

BACKGROUND: Antibody-mediated rejection following liver transplantation (LT) has been increasingly recognized, particularly with respect to the emergence of de novo donor-specific antibodies (DSAs) and their impact on graft longevity. While substantial evidence for adult populations exists, research focusing on pediatric LT outcomes remains limited. AIM: To investigate the prevalence of human leukocyte antigen (HLA) mismatches and DSA and evaluate their association with rejection episodes after pediatric LT. METHODS: A cohort of pediatric LT recipients underwent HLA testing at Santa Casa de Porto Alegre, Brazil, between December 2013 and December 2023. Only patients who survived for > 30 days after LT with at least one DSA analysis were included. DSA classes I and II and cross-matches were analyzed. The presence of de novo DSA (dnDSA) was evaluated at least 3 months after LT using the Luminex® single antigen bead method, with a positive reaction threshold set at 1000 MFI. Rejection episodes were confirmed by liver biopsy. RESULTS: Overall, 67 transplanted children were analyzed; 61 received grafts from living donors, 85% of whom were related to recipients. Pre-transplant DSA (class I or II) was detected in 28.3% of patients, and dnDSA was detected in 48.4%. The median time to DSA detection after LT was 19.7 [interquartile range (IQR): 4.3-35.6] months. Biopsy-proven rejection occurred in 13 patients at follow-up, with C4d positivity observed in 5/13 Liver biopsies. The median time to rejection was 7.8 (IQR: 5.7-12.8) months. The presence of dnDSA was significantly associated with rejection (36% vs 3%, P < 0.001). The rejection-free survival rates at 12 and 24 months were 76% vs 100% and 58% vs 95% for patients with dnDSA anti-DQ vs those without, respectively. CONCLUSION: Our findings highlight the importance of incorporating DSA assessment into pre- and post-transplantation protocols for pediatric LT recipients. Future implications may include immunosuppression minimization strategies based on this analysis in pediatric LT recipients.

Contribution of extracellular vesicles to steatosis-related liver disease and their therapeutic potential.

Extracellular vesicles (EVs) are small particles released by many cell types in different tissues, including the liver, and transfer specific cargo molecules from originating cells to receptor cells. This process generally culminates in activation of distant cells and inflammation and progression of certain diseases. The global chronic liver disease (CLD) epidemic is estimated at 1.5 billion patients worldwide. Cirrhosis and liver cancer are the most common risk factors for CLD. However, hepatitis C and B virus infection and obesity are also highly associated with CLD. Nonetheless, the etiology of many CLD pathophysiological, cellular, and molecular events are unclear. Changes in hepatic lipid metabolism can lead to lipotoxicity events that induce EV release. Here, we aimed to present an overview of EV features, from definition to types and biogenesis, with particular focus on the molecules related to steatosis-related liver disease, diagnosis, and therapy.

[Cirrhotic cardiomyopathy ­ Clinically fact or academic curiosity? Review. Part 3: treatment] / Cardiomiopatía cirrótica ­ ¿Realidad clínica o simple curiosidad académica? Revisión.

Hepatic transplantation (HT) is the standard of care of end-stage liver disease with Cirrhotic Cardiomyopathy (CCM), but medical treatment with combination of diuretics and non-selective beta blockers are important before and after that. Owing to its particular pathophysiology unlike another etiologies of heart failure, in CCM angiotensin-converting enzyme inhibitors (ACEI), angiotensin II type I receptor blockers (ARB), and angiotensin receptor neprilysin inhibitor (ARNI) are not recommended. Transjugular intrahepatic porto-systemic shunt (TIPS) has indications in CMM but its potential benefits and risks must be considered and more researh is necessary. HT is a demanding therapy but the most effective one, and showed improvement in QTc, diastolic and systolic dysfunction; in recent decades, in spite of more severe ill patients (more severe MELD score), survival has improved significantly due to better surgical techniques, intensive care, immunosupresive drugs, and images.

El tratamiento de la enfermedad hepática terminal con Cardiomiopatía Cirrótica (CMC) es el trasplante hepático (TH), sin embargo el tratamiento médico con la combinación de diuréticos y beta bloqueantes no selectivos antes y después tienen un rol importante. A diferencia de la insuficiencia cardíaca de otras etiologías, los inhibidores de la enzima convertidora (IECA), los bloqueadores del receptor de angiotensina 2 (ARA-2) o los inhibidores del receptor de angiotensina y de neprilisina (ARNI) no se recomiendan debido a la fisiopatología particular de la CMC. El shunt porto-sistémico intrahepático transyugular (Transjugular intrahepatic porto-systemic shunt: TIPS) tiene sus indicaciones con posibles beneficios y riesgos pero más estudios son necesarios en la CMC. El TH es la opción más eficaz y puede revertir el QTc del ECG y la disfunción diastólica y sistólica; en las últimas décadas, a pesar del aumento de la complejidad en los pacientes (mayor score MELD), con la mejoría de la técnica quirúrgica, cuidados intensivos, drogas inmunosupresoras y diagnóstico por imágenes la sobrevida ha mejorado significativamente.

Comparative evaluation of APRI, FIB-4, HFS, and NFS: Scoring tools for liver fibrosis in a Mexican population with MASLD.

INTRODUCTION AND AIM: Liver fibrosis is a complication of metabolic dysfunction-associated steatotic liver disease (MASLD). Given the limitations and risks of liver biopsy, examining noninvasive scoring systems that are affordable for the population is necessary. Our aim was to evaluate and compare the diagnostic yield of the APRI, FIB-4, NAFLD score, and Hepamet fibrosis score instruments for detecting liver fibrosis in Mexican subjects with MASLD. MATERIAL AND METHODS: A retrospective study was conducted on a sample of subjects with MASLD. Liver fibrosis was calculated through transient liver elastography. Sociodemographic, epidemiologic, and biochemical variables were evaluated. Scores were calculated utilizing the fibrosis-4 (FIB-4) index, the aspartate aminotransaminase-to-platelet ratio index (APRI), the Hepamet fibrosis score (HFS), and the NAFLD score (NFS), and then compared. ROC curves were constructed, and the optimum cutoff points were determined utilizing the Youden index. Sensitivity, specificity, positive predictive value, negative predictive value, and likelihood ratio were calculated. RESULTS: The study included 194 subjects (63% women), of whom 150 (77.3%) were classified with MASLD and 44 (22.7%) as controls with no liver disease. There was a 15.3% prevalence of advanced fibrosis. The cutoff points of 0.57 for APRI, 1.85 for FIB-4, 0.08 for HFS, and -0.058 for NFS showed diagnostic yields with areas under the ROC curves of 0.79, 0.80, 0.70, and 0.68, respectively. CONCLUSION: The APRI, FIB-4, NFS, and HFS scores are useful for evaluating liver fibrosis in Mexican subjects with MASLD. Better diagnostic yield was found with the FIB-4 and APRI scores.

Prognostic Impact of the Cholangiolar Component in Combined Hepatocellular-Cholangiocarcinoma: Insights From a Western Single-Center Study.

INTRODUCTION: Primary liver malignancies, such as hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), and combined hepatocellular-cholangiocarcinoma (cHCC-CCA), represent significant contributors to global cancer-related mortality. The diagnostic challenges associated with distinguishing cHCC-CCA from HCC and ICC stem from their rarity and overlapping histological features. OBJECTIVES: This study aimed to reclassify primary liver tumors resected at a Western center and to compare clinicopathological features and prognosis among patients with HCC, ICC, and cHCC-CCA. METHODS: A retrospective analysis was conducted on patients undergoing resection for HCC, ICC, or cHCC-CCA between 2007 and 2017. Clinical and perioperative data were collected, and pathological specimens were reclassified by a specialized pathologist. Statistical analysis was employed to compare clinical features and survival outcomes among the different tumor types. RESULTS: Out of the initially identified 192 patients, 140 were included in the analysis. Following reclassification, 71.42% were diagnosed with HCC, 12.14% with ICC, and 16.42% with cHCC-CCA. Patients with HCC were predominantly male and exhibited a higher incidence of isolated liver recurrence. ICC patients more frequently underwent open procedures. Additionally, patients with HCC and cHCC-CCA showed higher rates of cirrhosis, elevated alpha-fetoprotein levels, and extrahepatic recurrence, while those with ICC and cHCC-CCA demonstrated elevated CA 19-9 levels. Overall survival and disease-free survival were longer for HCC compared to cases with a cholangiolar component (ICC and cHCC-CCA). CONCLUSIONS: Histological evaluation should actively incorporate the search for a cholangiolar component in primary liver tumors to prevent misdiagnosis, as its presence indicates a poorer prognosis.

Glucose metabolism in the perfused liver did not improve with resistance training in male Swiss mice under caloric restriction.

CONTEXT: Energy homeostasis is a primary factor for the survival of mammals. Many tissues and organs, among which is the liver, keep this homeostasis in varied circumstances, including caloric restriction (CR) and physical activity. OBJECTIVE: This study investigated glucose metabolism using the following groups of eight-week-old male Swiss mice: CS, sedentary and fed freely; RS, sedentary and RT, trained, both under 30% CR (n = 20-23 per group). RESULTS: Organs and fat depots of groups RS and RT were similar to CS, although body weight was lower. CR did not impair training performance nor affected systemic or hepatic glucose metabolism. Training combined with CR (group RT) improved in vivo glucose tolerance and did not affect liver gluconeogenesis. CONCLUSIONS: The mice tolerated the prolonged moderate CR without impairment of their well-being, glucose homeostasis, and resistance training performance. But the higher liver gluconeogenic efficiency previously demonstrated using this training protocol in mice was not evidenced under CR.