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Hematological abnormalities are common in cirrhosis and are associated with various pathophysiological mechanisms. Studies have documented a prevalence of thrombocytopenia, leukopenia, and anemia in patients with compensated cirrhosis of 77.9%, 23.5%, and 21.1%, respectively. These abnormalities carry significant clinical implications, including considerations for invasive procedures, infection risk, bleeding risk, and prognosis. Previously, cirrhosis was believed to predispose patients to bleeding due to alterations observed in classical coagulation tests such as prothrombin time, partial thromboplastin time, international normalized ratio, and thrombocytopenia. However, this understanding has evolved, and cirrhosis patients are now also acknowledged as being at a high risk for thrombotic events. Hemostasis in cirrhosis patients presents a complex phenotype, with procoagulant and anticoagulant abnormalities offsetting each other. This multifactorial phenomenon is inadequately reflected by routine laboratory tests. Thrombotic complications are more prevalent in decompensated cirrhosis and may correlate with disease severity. Bleeding is primarily associated with portal hypertension, endothelial dysfunction, mechanical vessel injury, disseminated intravascular coagulation, endotoxemia, and renal injury. This review comprehensively outlines hematologic index abnormalities, mechanisms of hemostasis, coagulation, and fibrinolysis abnormalities, limitations of laboratory testing, and clinical manifestations of bleeding and thrombosis in patients with liver cirrhosis.
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The assessment of nutrition status, sarcopenia, and frailty holds significant relevance in the context of adult transplantation, as these factors are associated with an unfavorable prognosis; thus, transplant candidates must undergo a full nutrition assessment. Screening tools may be used to prioritize patients, this can be done using the Nutrition Risk Screening 2002 or Royal Free Hospital-Nutritional Prioritizing Tool. Subsequently, a thorough nutrition-focused physical examination should be conducted to evaluate clinical signs of nutrition deficiencies, fat and muscle loss, and fluid overload; dietary history and current intake must also be assessed. Apart from physical examination, specific testing for sarcopenia and frailty are recommended. For sarcopenia assessment, specifically for muscle quantification, the gold standard is the cross-sectional measurement of the muscle at L3 obtained from a computed tomography scan or magnetic resonance imaging; dual-energy x-ray absorptiometry is also a good tool especially when appendicular skeletal muscle index is calculated. Other more readily available options include phase angle from bioelectrical impedance or bioimpedance spectroscopy. In the sarcopenia assessment, muscle function evaluation is required, handgrip strength stands as the primary test for this purpose; this test is also part of the subjective global assessment and is included in some frailty scores. Finally, for frailty assessment, the Short Physical Performance Battery is useful for evaluating physical frailty, and for a multidimensional evaluation, the Fried frailty phenotype can be used. Specifically for liver transplant candidates, the use of Liver Frailty Index is recommended.
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Fragilidad , Sarcopenia , Adulto , Humanos , Sarcopenia/etiología , Sarcopenia/complicaciones , Fragilidad/diagnóstico , Evaluación Nutricional , Estado Nutricional , Receptores de Trasplantes , Fuerza de la Mano , Estudios TransversalesRESUMEN
Background & Aims: Acute-on-chronic liver failure (ACLF) has been linked to different pathophysiological mechanisms, including systemic inflammation and mitochondrial dysfunction. Sarcopenia has also been proposed as a potential mechanism; myostatin is a key factor inducing sarcopenia. Therefore, this study aimed to evaluate the association of myostatin levels with the development of ACLF and mortality in patients with cirrhosis. Methods: We performed a prospective cohort study, including both outpatient and hospitalized patients with cirrhosis. Clinical, biochemical, and nutritional parameters were evaluated, and the development of acute decompensation (AD) or ACLF during follow-up was recorded. ACLF was defined according to the EASL-CLIF criteria. Receiver-operating characteristic, Kaplan-Meier and Cox regression analyses were performed. Results: A total of 186 patients with the whole spectrum of cirrhosis were included; mean age was 53.4 ± 14 years, mean Child-Pugh score was 8 ± 2.5 and mean MELD score was 15 ± 8. There was a stepwise decrease in myostatin levels from a compensated stage to AD and ACLF. Myostatin correlated positively with nutritional markers and negatively with severity scores. The prevalence of sarcopenia was 73.6%. During follow-up, 27.9% of patients developed AD and 25.8% developed ACLF. Most episodes were grade 2-3, mainly (62.5%) precipitated by infections. The most common organ failures observed were in the liver (63.3%) and the kidney (64.6%). Receiver-operating characteristic analysis yielded <1,280 pg/ml as the best serum myostatin cut-off for the prediction of ACLF. In Kaplan-Meier curves and multivariate analysis, myostatin levels remained independently associated with the incidence of ACLF and survival. Conclusions: There is a progressive decrease in myostatin levels as cirrhosis progresses, demonstrating an association of sarcopenia with the development of ACLF and increased mortality. Impact and implications: Myostatin is a muscle hormone, it is decreased in patients with muscle loss and is a marker of impaired muscle function. In this study we show that myostatin levels are decreased in patients with cirrhosis, with lower levels in patients with acute decompensation and acute-on chronic liver failure (ACLF). Low myostatin levels in cirrhosis predict the development of ACLF and mortality independently of liver disease severity and sex.
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BACKGROUND: Metabolic associated fatty liver disease (MAFLD) is associated with complications and mortality in patients with coronavirus disease 2019 (COVID-19). However, there are no prognostic scores aimed to evaluate the risk of severe disease specifically in patients with MAFLD, despite its high prevalence. Lactate dehydrogenase, aspartate aminotransferase and alanine aminotransferase have been used as markers of liver damage. Therefore, we propose an index based on lactate dehydrogenase, aspartate aminotransferase and alanine aminotransferase for the prediction of complications and mortality in patients with MAFLD and COVID-19. AIM: To evaluate the prognostic performance of an index based on lactate dehydrogenase and transaminases (aspartate aminotransferase/alanine aminotransferase) in patients with COVID-19 and MAFLD [liver fibrosis and nutrition (LNF)-COVID-19 index]. METHODS: In this retrospective cohort study, two cohorts from two different tertiary centers were included. The first was the derivation cohort to obtain the score cutoffs, and the second was the validation cohort. We included hospitalized patients with severe COVID-19 and MAFLD. Liver steatosis was evaluated by computed tomography scan. Area under the receiver operating characteristic (ROC) curve analysis and survival analysis were used. RESULTS: In the derivation cohort, 44.6% had MAFLD; ROC curve analysis yielded a LFN-COVID-19 index > 1.67 as the best cutoff, with a sensitivity of 78%, specificity of 63%, negative predictive value of 91% and an area under the ROC curve of 0.77. In the multivariate analysis, the LFN-COVID-19 index > 1.67 was independently associated with the development of acute kidney injury (odds ratio: 1.8, 95% confidence interval: 1.3-2.5, P < 0.001), orotracheal intubation (odds ratio: 1.9, 95% confidence interval: 1.4-2.4, P < 0.001), and death (odds ratio: 2.86, 95% confidence interval: 1.6-4.5, P < 0.001) in both cohorts. CONCLUSION: LFN-COVID-19 index has a good performance to predict prognosis in patients with MAFLD and COVID-19, which could be useful for the MAFLD population.
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COVID-19 , Hígado Graso , Enfermedad del Hígado Graso no Alcohólico , Humanos , COVID-19/complicaciones , Alanina Transaminasa , Estudios Retrospectivos , Hígado Graso/complicaciones , Aspartato Aminotransferasas , Pronóstico , Lactato Deshidrogenasas , Oxidorreductasas , Enfermedad del Hígado Graso no Alcohólico/complicacionesRESUMEN
BACKGROUND: The global coronavirus disease 2019 (COVID-19) pandemic has caused more than 5 million deaths. Multiorganic involvement is well described, including liver disease. In patients with critical COVID-19, a new entity called "post-COVID-19 cholangiopathy" has been described. CASE SUMMARY: Here, we present three patients with severe COVID-19 that subsequently developed persistent cholestasis and chronic liver disease. All three patients required intensive care unit admission, mechanical ventilation, vasopressor support, and broad spectrum antibiotics due to secondary infections. Liver transplant protocol was started for two of the three patients. CONCLUSION: Severe COVID-19 infection should be considered a potential risk factor for chronic liver disease and liver transplantation.
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OBJECTIVE: Describe the histological findings of minimally ultrasound-guided invasive autopsies in deceased patients with severe SARS-CoV-2 and compare the diagnostic yield with open autopsies. DESIGN: Observational post-mortem cohort study. Minimally invasive ultrasound-guided autopsies were performed in fourteen deceased patients with a confirmed diagnosis of SARS-CoV-2 pneumonia. Histological and clinical findings of lung, kidney, and liver tissue are described and contrasted with those previously reported in the literature. SETTING: Single-center COVID-19 reference center in Mexico City. RESULTS: Fourteen minimally invasive autopsies revealed a gross correlation with open autopsies reports: 1) Lung histology was characterized mainly by early diffuse alveolar damage (12/13). Despite low lung compliances and prolonged mechanical ventilation, the fibrotic phase was rarely observed (2/13). 2) Kidney histopathology demonstrated acute tubular injury (12/13), interstitial nephritis (11/13), and glomerulitis (11/13) as the predominant features 3) Liver histology was characterized by neutrophilic inflammation in all of the cases, as well as hepatic necrosis (8/14) despite minimal alterations in liver function testing. Hepatic steatosis was observed in most cases (12/14). SARS-CoV-2 positivity was widely observed throughout the immunohistochemical analysis. However, endothelitis and micro thrombosis, two of the hallmark features of the disease, were not observed. CONCLUSION: Our data represents the largest minimally invasive, ultrasound-guided autopsy report. We demonstrate a gross histological correlation with large open autopsy cohorts. However, this approach might overlook major histologic features of the disease, such as endothelitis and micro-thrombosis. Whether this represents sampling bias is unclear.
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COVID-19RESUMEN
Hepatocellular carcinoma (HCC) is the most frequent primary liver cancer and presents together with cirrhosis in most cases. In addition to commonly recognized risk factors for HCC development, such as hepatitis B virus/hepatitis C virus infection, age and alcohol/tobacco consumption, there are nutritional risk factors also related to HCC development including high intake of saturated fats derived from red meat, type of cooking (generation of heterocyclic amines) and contamination of foods with aflatoxins. On the contrary, protective nutritional factors include diets rich in fiber, fruits and vegetables, n-3 polyunsaturated fatty acids and coffee. While the patient is being evaluated for staging and treatment of HCC, special attention should be paid to nutritional support, including proper nutritional assessment and therapy by a multidisciplinary team. It must be considered that these patients usually develop HCC on top of long-lasting cirrhosis, and therefore they could present with severe malnutrition. Cirrhosis-related complications should be properly addressed and considered for nutritional care. In addition to traditional methods, functional testing, phase angle and computed tomography scan derived skeletal muscle index-L3 are among the most useful tools for nutritional assessment. Nutritional therapy should be centered on providing enough energy and protein to manage the increased requirements of both cirrhosis and cancer. Supplementation with branched-chain amino acids is also recommended as it improves response to treatment, nutritional status and survival, and finally physical exercise must be encouraged and adapted to individual needs.
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Metabolic diseases are highly prevalent worldwide and have been associated with adverse clinical outcomes, including mortality, in patients developing coronavirus disease (COVID-19). Because of the close relationship between metabolic diseases such as type 2 diabetes mellitus and obesity and the presence of metabolic-associated fatty liver disease (MAFLD), a high number of cases of patients affected by both MAFLD and COVID-19 would be expected, especially in high-risk populations. Some studies have shown an increased risk of adverse clinical outcomes, viral shedding, and deep vein thrombosis, especially in patients with MAFLD- related liver fibrosis. The predisposition to poor outcomes and severe acute respiratory syndrome coronavirus 2 infection in patients with MAFLD could be secondary to mechanisms common to both, including preexisting systemic chronic inflammation, endothelial dysfunction, and involvement of the renin-angiotensin system. Because of the increased risk of adverse outcomes, MAFLD should be screened in all patients admitted for COVID-19. Available computed tomography scans could be of help, assessment of liver fibrosis is also recommended, favoring noninvasive methods to limit the exposure of healthcare workers. Liver involvement in this population ranges from abnormalities in liver chemistry to hepatic steatosis in postmortem biopsies. Finally, preventive measures should be strongly advocated in patients already known to have MAFLD, including the use of telemedicine and vaccination in addition to general measures.
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COVID-19 , Diabetes Mellitus Tipo 2 , Hígado Graso , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/epidemiología , Hígado Graso/epidemiología , Hígado Graso/etiología , Humanos , SARS-CoV-2RESUMEN
BACKGROUND: Metabolic diseases are risk factors for severe Coronavirus disease (COVID-19), which have a close relationship with metabolic dysfunction-associated fatty liver disease (MAFLD). AIMS: To evaluate the presence of MAFLD and fibrosis in patients with COVID-19 and its association with prognosis. METHODS: Retrospective cohort study. In hospitalized patients with COVID-19, the presence of liver steatosis was determined by computed tomography scan (CT). Liver fibrosis was assessed using the NAFLD fibrosis score (NFS score), and when altered, the AST to platelet ratio index (APRI) score. Mann-Whitney U, Student´s t-test, logistic regression analysis, Kaplan-Meier curves and Cox regression analysis were used. RESULTS: 432 patients were analyzed, finding steatosis in 40.6%. No differences in pulmonary involvement on CT scan, treatment, or number of days between the onset of symptoms and hospital admission were found between patients with and without MAFLD. The presence of liver fibrosis was associated with higher severity scores, higher levels of inflammatory markers, requirement of mechanical ventilation, incidence of acute kidney injury (AKI), and higher mortality than patients without fibrosis. CONCLUSION: The presence of fibrosis rather than the presence of MAFLD is associated with increased risk for mechanical ventilation, development of AKI, and higher mortality in COVID-19 patients.
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COVID-19 , Hígado Graso , Cirrosis Hepática , Hígado , Respiración Artificial/estadística & datos numéricos , Aspartato Aminotransferasas/sangre , Biomarcadores/sangre , Plaquetas/patología , COVID-19/sangre , COVID-19/complicaciones , COVID-19/mortalidad , COVID-19/terapia , Hígado Graso/diagnóstico , Hígado Graso/epidemiología , Hígado Graso/metabolismo , Femenino , Humanos , Hígado/diagnóstico por imagen , Hígado/metabolismo , Hígado/patología , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/epidemiología , Cirrosis Hepática/metabolismo , Pruebas de Función Hepática/métodos , Masculino , México/epidemiología , Persona de Mediana Edad , Pronóstico , Proyectos de Investigación , Estudios Retrospectivos , Factores de Riesgo , Índice de Severidad de la Enfermedad , Tomografía Computarizada por Rayos X/métodosRESUMEN
BACKGROUND AND AIMS: Skeletal muscle index (SMI) from computed tomography (CT) reliably assesses sarcopenia, however, it is expensive and involves serial radiation exposure. Phase angle (PhA) from bioimpedance analysis (BIA) is a noninvasive, low cost, bedside nutritional tool used to monitor changes to nutritional interventions. We aimed to compare the performance of PhA with SMI to assess sarcopenia in cirrhosis. METHODS: Ambispective cohort study. Consecutive patients with cirrhosis and available images from abdominal CT scan were included. Monofrequency BIA was performed within 2 weeks CT. Spearman's correlation, ROC curve, and survival analysis with Kaplan-Meier, Cox and competing-risk regression were performed. RESULTS: 136 patients were included with a mean age of 54.5 years (60% female). Most had decompensated disease (66%) with ascites in 47%, and a mean MELD of 14 ± 6. We found positive correlations between SMI and PhA (r = 0.58 , P < .001), irrespective of the presence of ascites. The AUROC of PhA-sarcopenia in all patients was 0.702; (0.748 in males,0.677 in females). The best cutoffs of PhA for diagnosing sarcopenia were ≤5.6° in males and ≤5.4° in females. SMI and PhA were significantly associated with survival in Kaplan-Meier curves. In multivariable analyses, SMI was outperformed by age and MELD, whereas PhA remained independently associated with mortality. Considering transplantation as a competing risk, regression analysis showed both SMI and PhA to be independent predictors of mortality (sHR:0.95 [0.90-0.99] and sHR:0.61 [0.42-0.88]). CONCLUSION: PhA moderately correlates with SMI for the identification of sarcopenia in patients with cirrhosis. However, its prognostic accuracy is comparable to that of SMI, and it is not influenced by ascites.
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Sarcopenia , Ascitis/diagnóstico , Estudios de Cohortes , Impedancia Eléctrica , Femenino , Humanos , Cirrosis Hepática/complicaciones , Cirrosis Hepática/diagnóstico , Masculino , Persona de Mediana Edad , Sarcopenia/diagnósticoRESUMEN
Non-alcoholic fatty liver disease (NAFLD) is among the most frequent etiologies of cirrhosis worldwide, and it is associated with features of metabolic syndrome; the key factor influencing its prognosis is the progression of liver fibrosis. This review aimed to propose a practical and stepwise approach to the evaluation and management of liver fibrosis in patients with NAFLD, analyzing the currently available literature. In the assessment of NAFLD patients, it is important to identify clinical, genetic, and environmental determinants of fibrosis development and its progression. To properly detect fibrosis, it is important to take into account the available methods and their supporting scientific evidence to guide the approach and the sequential selection of the best available biochemical scores, followed by a complementary imaging study (transient elastography, magnetic resonance elastography or acoustic radiation force impulse) and finally a liver biopsy, when needed. To help with the selection of the most appropriate method a Fagan's nomogram analysis is provided in this review, describing the diagnostic yield of each method and their post-test probability of detecting liver fibrosis. Finally, treatment should always include diet and exercise, as well as controlling the components of the metabolic syndrome, +/- vitamin E, considering the presence of sleep apnea, and when available, allocate those patients with advanced fibrosis or high risk of progression into clinical trials. The final end of this approach should be to establish an opportune diagnosis and treatment of liver fibrosis in patients with NAFLD, aiming to decrease/stop its progression and improve their prognosis.
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Diagnóstico por Imagen de Elasticidad , Enfermedad del Hígado Graso no Alcohólico , Biopsia , Humanos , Hígado/diagnóstico por imagen , Hígado/patología , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/patología , Cirrosis Hepática/terapia , Enfermedad del Hígado Graso no Alcohólico/diagnóstico por imagen , Enfermedad del Hígado Graso no Alcohólico/terapia , PronósticoRESUMEN
Systemic lupus erythematosus (SLE) is a multi-organic autoimmune disease with a wide variety of clinical manifestations. However, hepatic dysfunction is not included in the diagnostic criteria for the disease and has not been recognized properly. The spectrum of hepatic involvement described in these patients ranges from abnormalities in liver function tests (LFTs) to fulminant hepatic failure. Usually, abnormalities in LFTs are only mild and transient, have a hepatocellular pattern and are not related to SLE but rather are mostly drug related. The most frequent finding on liver biopsy is steatosis (non-alcoholic fatty liver disease). Patients do not frequently progress to advanced chronic liver disease, and their outcome is favourable. Those who develop cirrhosis have traditional risk factors, such as other non-SLE-related conditions. In this work, we aim to review hepatic manifestations in patients with SLE, as well as the diagnostic and therapeutic approaches used for different liver diseases in these patients.
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Hepatopatías/complicaciones , Lupus Eritematoso Sistémico/complicaciones , Humanos , Hígado/patología , Hepatopatías/etiología , Hepatopatías/terapia , Pruebas de Función Hepática , Lupus Eritematoso Sistémico/fisiopatologíaRESUMEN
Ferroptosis has emerged as a new type of cell death in different pathological conditions, including neurological and kidney diseases and, especially, in different types of cancer. The hallmark of this regulated cell death is the presence of iron-driven lipid peroxidation; the activation of key genes related to this process such as glutathione peroxidase-4 (gpx4), acyl-CoA synthetase long-chain family member-4 (acsl4), carbonyl reductase [NADPH] 3 (cbr3), and prostaglandin peroxidase synthase-2 (ptgs2); and morphological changes including shrunken and electron-dense mitochondria. Iron overload in the liver has long been recognized as both a major trigger of liver damage in different diseases, and it is also associated with liver fibrosis. New evidence suggests that ferroptosis might be a novel type of non-apoptotic cell death in several liver diseases including non-alcoholic steatohepatitis (NASH), alcoholic liver disease (ALD), drug-induced liver injury (DILI), viral hepatitis, and hemochromatosis. The interaction between iron-related lipid peroxidation, cellular stress signals, and antioxidant systems plays a pivotal role in the development of this novel type of cell death. In addition, integrated responses from lipidic mediators together with free iron from iron-containing enzymes are essential to understanding this process. The presence of ferroptosis and the exact mechanisms leading to this non-apoptotic type of cell death in the liver remain scarcely elucidated. Recognizing ferroptosis as a novel type of cell death in the liver could lead to the understanding of the complex interaction between different types of cell death, their role in progression of liver fibrosis, the development of new biomarkers, as well as the use of modulators of ferroptosis, allowing improved theranostic approaches in the clinic.
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Apoptosis , Ferroptosis , Hígado/patología , Animales , Autofagia , Biomarcadores/metabolismo , Humanos , Hierro/metabolismoRESUMEN
BACKGROUND: A significant number of patients with liver cirrhosis concomitantly develop some type of solid or hematological cancer, including lymphoma. Treatment of patients with lymphoma and cirrhosis is challenging for physicians due to the clinical characteristics related to cirrhosis, including biochemical and functional abnormalities, as well as portal hypertension and lack of scientific evidence, limiting the use of chemotherapy. Currently, experts recommend only offering oncological treatment to patients with compensated cirrhosis. AIM: To evaluate the clinical characteristics and treatment outcomes in patients with cirrhosis and lymphoma treated with chemotherapy. METHODS: This was a case-control study conducted at a tertiary care center in Mexico. Data was recorded from medical files and from 8658 possible candidates with cirrhosis and/or lymphoma (2000 to 2018). Only 23 cases had both diseases concomitantly; 10 patients with cirrhosis and lymphoma (cases) met the selection criteria and were included, and 20 patients with lymphoma (controls) were included and matched according to age, sex, and date of diagnosis, type and clinical stage of lymphoma. All patients received treatment with chemotherapy. For statistical analysis, descriptive statistics, Shapiro-Wilk test, Mann-Whitney U test, chi-square test and Fisher's exact test were used. Survival was evaluated using Kaplan-Meier curves and Log-rank test. RESULTS: There were differences in biochemical variables inherent to liver disease and portal hypertension in patients with cirrhosis. The most frequent etiology of cirrhosis was hepatitis C virus (50%); 80% were decompensated, the median Child-Turcotte-Pugh score was 7.5 (6.75-9.25), and mean Model for End-stage Liver Disease was 11.5 ± 4.50. Regarding lymphomas, non-Hodgkin's were the most common (90%), and diffuse large B cell subtype was the most frequent, with a higher International Prognostic Index in the cases (3 vs 2, P = 0.049). The chemotherapy regimens had to be adjusted more frequently in the case group (50% vs 5%, P = 0.009). The complications derived from chemotherapy were similar between both groups (80% vs 90%, P = 0.407); however, non-hematological toxicities were more common in the case group (30% vs 0%, P = 0.030). There was no difference in the response to treatment between groups. Survival was higher in the control group (56 wk vs 30 wk, P = 0.269), although it was not statistically significant. CONCLUSION: It may be possible to administer chemotherapy in selected cirrhotic patients, regardless of their severity, obtaining satisfactory clinical outcomes. Prospective clinical trials are needed to generate stronger recommendations.
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BACKGROUND: The implementation of nutritional strategies targeting several variables at once could benefit patients with cirrhosis. Non-alcoholic beer has different compounds that exert antioxidant, anti-inflammatory and nutritional properties. AIM: To evaluate the effect of diet + exercise and non-alcoholic beer on nutritional status, endothelial function and quality of life in patients with cirrhosis. METHODS: In this randomized open clinical trial, patients with cirrhosis were randomized into two groups: The intervention (non-alcoholic beer + diet + exercise) and control (water + diet + exercise) group. Treatment consisted of 330 mL non-alcoholic beer/day or the same amount of water, plus an individualized dietary plan and an exercise program with a pedometer-based bracelet to reach at least 5000 steps/d and > 2500 above the baseline during 8 wk. Endothelial function (flow-mediated dilation, plethysmography), biochemical and nutritional variables and quality of life (CLDQ) were evaluated. RESULTS: Forty-three patients were included in the study, 21 in the control group and 22 in the intervention group. The mean age was 53.5 ± 7.8 years, 60% were women, the median MELD score was 8 (7-10) and most patients were Child-Pugh A (88%). Adherence to the interventions was > 90% in both groups, there were no adverse events and all biochemical parameters remained stable in both groups. Endothelial function improved in both groups. All measured nutritional parameters improved in the intervention group, compared to only 2 in the control group and quality of life improved in both groups; however, more domains improved in the intervention group. CONCLUSION: The intervention consisting of non-alcoholic beer, diet and exercise seems to be safe and well tolerated in patients with cirrhosis, and shows improvement in nutritional status, endothelial function, and quality of life. These results need to be further confirmed.
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Improvement in cognitive function after orthotopic liver transplantation (LT) has been demonstrated in the acute setting immediately after LT and in acute liver failure. However, the longterm changes in cerebral hemodynamics after LT remain unexplored. Therefore, we aimed to evaluate the longterm changes in cerebral hemodynamics of patients with cirrhosis after LT. In this prospective cohort study, we performed transcranial Doppler ultrasonography (TCD) measuring the pulsatility index (PI), resistance index (RI), and breath-holding index (BHI) to evaluate cerebrovascular structural integrity and reactivity, respectively, in both middle cerebral arteries before and after LT. Neuropsychometric tests and West-Haven criteria were used for hepatic encephalopathy (HE) characterization. Interleukin 6 and tumor necrosis factor α plasma levels were measured. Descriptive statistics and Wilcoxon's test were used. There were 27 patients who were included. Median follow-up after LT was 6 months, mean age before LT was 46.3 ± 10.3 years, the main etiology was hepatitis C virus (59%), and most of the patients were Child-Pugh B (15/27). Model for End-Stage Liver Disease (MELD) score was 16 ± 7.5, MELD-Na was 19.3 ± 7.1, Psychometric Hepatic Encephalopathy Score was -3.48 ± 3.66, and critical flicker fusion (CFF) was 40.28 ± 5.70 Hz. Before LT, 17/27 patients had HE and 11/27 ascites. A decrease of 20.8% and 13.5% in PI and RI was observed after LT (P < 0.001, both), together with an increase in BHI (32.4%, P = 0.122). These changes in cerebral hemodynamics paralleled those in systemic inflammation. Clinical improvement in cognition was observed in all patients with overt HE after LT. In conclusion, these results show a significant improvement in cerebral hemodynamics after LT, obtained through TCD, indicating less arterial cerebral vasoconstriction together with a decrease in systemic inflammation. Changes in cerebral vasoconstriction can be the basis for the improvement in cognitive function after LT in the long term.
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Circulación Cerebrovascular/fisiología , Hemodinámica/fisiología , Encefalopatía Hepática/diagnóstico , Cirrosis Hepática/cirugía , Trasplante de Hígado , Adulto , Encéfalo/irrigación sanguínea , Encéfalo/diagnóstico por imagen , Encéfalo/fisiopatología , Cognición/fisiología , Femenino , Estudios de Seguimiento , Encefalopatía Hepática/etiología , Encefalopatía Hepática/fisiopatología , Humanos , Cirrosis Hepática/complicaciones , Pruebas de Función Hepática , Masculino , Persona de Mediana Edad , Arteria Cerebral Media/diagnóstico por imagen , Arteria Cerebral Media/fisiología , Estudios Prospectivos , Psicometría , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Ultrasonografía Doppler TranscranealRESUMEN
Acute-on-chronic liver failure (ACLF) develops in acute decompensation (AD) of cirrhosis and shows high mortality. In critically ill patients, early diagnosis of ACLF could be important for therapeutic decisions (eg, renal replacement, artificial liver support, liver transplantation). This study evaluated fibroblast growth factor 21 (FGF21) as a marker of mitochondrial dysfunction in the context of ACLF. The study included 154 individuals (112 critically patients and 42 healthy controls) divided into a training and a validation cohort. In the training cohort of 42 healthy controls and 34 critically ill patients (of whom 24 were patients with cirrhosis), levels of FGF21, interleukin (IL) 6, and IL8 were measured. In the validation cohort of 78 patients with cirrhosis, 17 patients were admitted with or developed ACLF during follow-up and underwent daily clinical and nutritional assessment. Levels of FGF21 were higher in critically ill patients, especially in patients with cirrhosis admitted to the intensive care unit (ICU). Moreover, FGF21 as well as IL6 and IL8 levels were higher in patients with ACLF, but they did not increase with the severity of ACLF. Interestingly, in the validation cohort, FGF21 was also elevated in the patients who developed ACLF in the next 7 days. In these patients, FGF21 levels were an independent predictor of ACLF presence and development in multivariate analysis together with Child-Pugh score. FGF21 levels had no impact on the survival of critically ill patients with cirrhosis. In conclusion, this study demonstrates that FGF21 levels are of specific diagnostic value regarding the presence and development of ACLF in patients admitted to ICU for AD of liver cirrhosis. Further studies are warranted to address pathophysiological and possible therapeutic implications. Liver Transplantation 24 595-605 2018 AASLD.
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Insuficiencia Hepática Crónica Agudizada/sangre , Factores de Crecimiento de Fibroblastos/sangre , Cirrosis Hepática/sangre , Insuficiencia Hepática Crónica Agudizada/diagnóstico , Insuficiencia Hepática Crónica Agudizada/etiología , Insuficiencia Hepática Crónica Agudizada/mortalidad , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Área Bajo la Curva , Biomarcadores/sangre , Estudios de Casos y Controles , Distribución de Chi-Cuadrado , Enfermedad Crítica , Femenino , Alemania , Humanos , Interleucina-6/sangre , Interleucina-8/sangre , Estimación de Kaplan-Meier , Cirrosis Hepática/complicaciones , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/mortalidad , Modelos Logísticos , Masculino , México , Persona de Mediana Edad , Análisis Multivariante , Valor Predictivo de las Pruebas , Pronóstico , Curva ROC , Reproducibilidad de los Resultados , Factores de Riesgo , Factores de Tiempo , Regulación hacia Arriba , Adulto JovenRESUMEN
OBJECTIVES: Exercise has been scarcely studied in patients with cirrhosis, and prior evidence showed hepatic venous pressure gradient (HVPG) to be increased in response to exercise. The aim of this study was to investigate the effects of a supervised physical exercise program (PEP) in patients with cirrhosis. METHODS: In an open-label, pilot clinical trial, patients with cirrhosis were randomized to PEP (cycloergometry/kinesiotherapy plus nutritional therapy, n=14) or control (nutritional therapy, n=15); for 14 weeks. Primary outcomes were: the effect of PEP in HVPG, and quality of life (chronic liver disease questionnaire, CLDQ). As secondary outcomes we investigated changes in physical fitness (cardiopulmonary exercise testing), nutritional status (phase angle-bioelectrical impedance), ammonia levels, and safety. RESULTS: Twenty-two patients completed the study (11 each). HVPG decreased in subjects allocated to PEP (-2.5 mm Hg (interquartile range: -5.25 to 2); P=0.05), and increased in controls (4 mm Hg (0-5); P=0.039), with a significant between-groups difference (P=0.009). No major changes were noted in CLDQ in both groups. There was significant improvement in ventilatory efficiency (VE/VCO2) in PEP group (-1.9 (-3.12 to -0.1); P=0.033), but not in controls (-0.4 (-5.7 to 1.4); P=0.467). Phase angle improvement and a less-pronounced exercise-induced hyperammonemia were noted only in PEP group. No episodes of variceal bleeding or hepatic encephalopathy were observed. CONCLUSIONS: A supervised PEP in patients with cirrhosis decreases the HVPG and improves nutritional status with no changes in quality of life. Further studies evaluating physical training in cirrhosis are eagerly awaited in order to better define the benefits of sustained exercise. ClinicalTrials.gov:NCT00517738.
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BACKGROUND: Malnutrition is a frequent complication of cirrhosis and it has been associated to more severe disease and development of complications. Phase angle is a bedside reliable tool for nutritional assessment based on conductivity properties of body tissues. AIM: To evaluate the association between malnutrition assessed through phase angle and mortality in patients with liver cirrhosis. METHODS: We performed a prospective cohort study in a tertiary care centre; 249 patients were enrolled with 48 months of follow-up. Clinical, nutritional (malnutrition = phase angle ≤ 4.9°) and biochemical evaluations were performed. Student's t-test and χ(2) method were used as appropriate. Kaplan-Meier curves and multivariate Cox regression were used to evaluate mortality. RESULTS: Mean follow-up was 33.5 months. Survival analysis showed higher mortality in the malnourished group compared to the well-nourished group (p = 0.076), Kaplan-Meier curves were further stratified according to compensated and decompensated status showing higher mortality in compensated patients according to Child-Pugh (p = 0.002) and Model for End-Stage Liver Disease score (p = 0.008) when malnutrition was present. Multivariate analysis showed that malnutrition was independently associated with mortality (HR = 2.15, 1.18-3.92). CONCLUSIONS: In our cohort, malnutrition was independently associated with mortality. This is the first study showing higher mortality in malnourished compensated cirrhotic patients.
Asunto(s)
Cirrosis Hepática/etiología , Desnutrición/complicaciones , Evaluación Nutricional , Estado Nutricional , Adolescente , Adulto , Anciano , Impedancia Eléctrica , Femenino , Estudios de Seguimiento , Humanos , Hígado/fisiopatología , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/fisiopatología , Masculino , Desnutrición/diagnóstico , Desnutrición/mortalidad , México/epidemiología , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Tasa de Supervivencia/tendencias , Factores de Tiempo , Adulto JovenRESUMEN
BACKGROUND: Glutamine synthetase (GS) plays a central role in the inter-organ metabolism of ammonia and hepatic encephalopathy. The main objective of the present work was to disclose the possible effect of exercise on GS mRNA expression in peripheral blood mononuclear cells (PBMC) within a group of healthy volunteers. MATERIAL AND METHODS: PBMC were studied instead of skeletal muscle because of ethical concerns. Characterization of GS in lymphocytes was carried out by indirect immunofluorescence and Western blot. After a pilot trial, expression of GS mRNA in PBMC was assayed by serial measurements in healthy volunteers who had exercised on a treadmill, and on a control group who had not. Muscle mass was estimated by bioimpedance. RESULTS: Cytoplasmic GS had a molecular weight of 44 kDa. Serial measurements of its mRNA demonstrated an increase in the treadmill (n = 29), but not in the control group (n = 13) (p < 0.05). Peak expression occurred at 1 h in males and at 6 h in females. There was a positive correlation between muscle mass and the increase of the enzyme mRNA after exercise. CONCLUSION: Exercise can increase the expression of GS mRNA in PBMC in healthy volunteers. Based on these preliminary results and on well-established physiological concepts, a hypothesis for non-hepatic ammonia metabolism is conceived. In the future could become part of the treatment of low-grade hepatic encephalopathy.