ASSOCIATION BETWEEN FATIGUE AND EXERCISE CAPACITY IN PATIENTS WITH CHRONIC LIVER DISEASE AWAITING LIVER TRANSPLANTATION.

BACKGROUND: Fatigue is highly prevalent in end stage liver disease, the studies about its association with exercise capacity in cirrhotic patients before liver are scarse. OBJECTIVE: In this study, we evaluated fatigue in 95 in end stage liver disease patients awaiting transplantation, compared to healthy volunteers, and tested the association between exercise capacity and fatigue. METHODS: Cross-sectional study of patients with chronic liver disease treated at a referral center in Fortaleza, Brazil. Fatigue was quantified with the Fatigue Severity Scale. The patients were submitted to the 6-min walk test, the 6-min step test, the Hospital Anxiety and Depression Scale, C-reative protein measurement and hematocrit count, measurement of dyspnea among other tests. Fatigue data were obtained from healthy individuals for comparison with patients. RESULTS: The mean age of patients was 45.9±12.3 years, and 53.7% were male. Fatigue, anxiety and depression levels were higher among end stage liver disease patients than among controls. A negative correlation was observed between 6 min step test and Fatigue Severity Scale score (r= -0.2; P=0.02) and between hematocrit count and Fatigue Severity Scale score (r= -0.24; P=0.002). Dyspnea on the Borg scale and fatigue were positively correlated (r=31; P=0.002). In the multivariate analysis, low 6-min step test values and high levels of dyspnea were associated with fatigue. CONCLUSION: Fatigue was more prevalent and severe in end stage liver disease patients than in healthy controls. Low 6MST values and high levels of dyspnea were associated with fatigue in this scenario.

Associação da fadiga com capacidade do exercício em pacientes hepatopatas crônicos candidatos a transplante hepático / Association between fatigue and exercise capacity in patients with chronic liver disease awaiting liver transplantation

ABSTRACT BACKGROUND: Fatigue is highly prevalent in end stage liver disease, the studies about its association with exercise capacity in cirrhotic patients before liver are scarse. OBJECTIVE: In this study, we evaluated fatigue in 95 in end stage liver disease patients awaiting transplantation, compared to healthy volunteers, and tested the association between exercise capacity and fatigue. METHODS: Cross-sectional study of patients with chronic liver disease treated at a referral center in Fortaleza, Brazil. Fatigue was quantified with the Fatigue Severity Scale. The patients were submitted to the 6-min walk test, the 6-min step test, the Hospital Anxiety and Depression Scale, C-reative protein measurement and hematocrit count, measurement of dyspnea among other tests. Fatigue data were obtained from healthy individuals for comparison with patients. RESULTS: The mean age of patients was 45.9±12.3 years, and 53.7% were male. Fatigue, anxiety and depression levels were higher among end stage liver disease patients than among controls. A negative correlation was observed between 6 min step test and Fatigue Severity Scale score (r= -0.2; P=0.02) and between hematocrit count and Fatigue Severity Scale score (r= -0.24; P=0.002). Dyspnea on the Borg scale and fatigue were positively correlated (r=31; P=0.002). In the multivariate analysis, low 6-min step test values and high levels of dyspnea were associated with fatigue. CONCLUSION: Fatigue was more prevalent and severe in end stage liver disease patients than in healthy controls. Low 6MST values and high levels of dyspnea were associated with fatigue in this scenario.

RESUMO CONTEXTO: A fadiga é uma queixa comum em indivíduos com doença hepática crônica candidatos a transplante hepático. Estudos sobre sua associação com capacidade do exercício são escassos. OBJETIVO: Avaliar a fadiga de pacientes com hepatopia crônica candidatos a transplante hepático comparando com um grupo de indivíduos saudáveis. Avaliar a associação da fadiga com capacidade de exercício. MÉTODOS: Este é um estudo transversal com pacientes hepatopatas crônicos num centro de referência em Fortaleza, Brasil. Foi utilizado o questionário de gravidade da fadiga. Os pacientes realizaram o teste da caminhada dos 6 min, teste do degrau 6 min, foi aplicada a escala de ansiedade e depressão, foram dosados proteína C reativa e hematócrito. RESULTADO: A idade média dos pacientes foi de 45,9±12,3 anos, sendo que 53,7% eram homens. Os níveis de fadiga e ansiedade e depressão eram maiores entre os pacientes hepatopatas crônicos quando comparados ao grupo controle. Uma correlação inversa foi observada entre fadiga e o teste do degrau (r= -0,2; P=0,02) também entre hematócrito e fadiga (r= -0,24; P=0,002). Houve uma correlação positiva entre dispneia, através da escala de Borg, e fadiga (r=31; P=0,002). Na análise multivariada um baixo desempenho no teste do degrau e um nível maior de dispneia mostraram uma associação com fadiga. CONCLUSÃO: A fadiga é mais frequente entre os pacientes hepatopatas crônicos quando comparados ao grupo controle. O baixo desempenho na capacidade de exercício e uma queixa maior de dispneia apresentaram uma associação com fadiga nestes pacientes.

The anti-inflammatory and anti-oxidative actions of eugenol improve lipopolysaccharide-induced lung injury.

Acute lung injury (ALI) remains a major cause of mortality. In lipopolysaccharide (LPS)-stimulated macrophages, eugenol reduces cyclooxygenase-2 expression, NF-κB activation, and inflammatory mediators. We examined the anti-inflammatory and anti-oxidative action of eugenol in an in vivo model of LPS-induced lung injury. Lung mechanics and histology were analyzed in mice 24 h after LPS exposure, with and without eugenol treatment at different doses. Additional animals, submited to the same protocol, were treated with eugenol at 150 mg/kg to determine its effect on inflammatory cytokines (ELISA) and oxidative markers. LPS-induced lung functional and histological changes were significantly improved by eugenol, in a dose-dependent way. Furthermore, eugenol (150 mg/kg) was able to inhibit the release of inflammatory cytokines (TNF-α, IL-1ß and IL-6), NADPH oxidase activity, as well as antioxidant enzymes activity (superoxide dismutase, catalase and glutathione peroxidase). Finally, eugenol reduced LPS-induced protein oxidation. In conclusion, eugenol improved in vivo LPS-induced ALI through both anti-inflammatory and anti-oxidative effects, avoiding damage to lung structure.

Oxidative imbalance in mice intoxicated by microcystin-LR can be minimized.

Microcystins-LR (MC-LR) is a cyanotoxin produced by cyanobacteria. We evaluated the antioxidant potential of LASSBio-596 (LB-596, inhibitor of phosphodiesterases 4 and 5), per os, and biochemical markers involved in lung and liver injury induced by exposure to sublethal dose of MC-LR. Fifty male Swiss mice received an intraperitoneal injection of 60 µL of saline (CTRL group, n = 20) or a sublethal dose of MC-LR (40 µg/kg, TOX group, n = 20). After 6 h the animals received either saline (TOX and CTRL groups) or LB-596 (50 mg/kg, TOX + LASS group, n = 10) by gavage. At 6 h after exposure, respiratory mechanics was evaluated in 10 CTRL and 10 TOX mice: there was a significant increase of all lung mechanics parameters (static elastance, viscoelastic component of elastance and lung resistive and viscoelastic/inhomogeneous pressures) in TOX compared to CTRL. 8 h after saline or MC-LR administration, i.e., 2 h after treatment with LB-596, blood serum levels of alanine aminotransferase and aspartate aminotransferase, activity of superoxide dismutase, catalase, and content of malondialdehyde and carbonyl in lung and liver, NADPH oxidase 2 and 4 mRNA expressions, dual oxidase enzyme activity and H2O2 generation were analyzed in lung homogenates. All parameters were significantly higher in TOX than in the other groups. There was no significant difference between CTRL and TOX + LASS. MC-LR deteriorated lung and liver functions and induced redox imbalance in them, which was prevented by oral administration of LB-596.

Exercise Capacity and Respiratory Profile in Patients after Orthopedic Liver Transplantation: a Follow-up Study.

INTRODUCTION: We sought to describe: 1) The influence of orthotopic liver transplantation (OLT) on exercise capacity, pulmonary function and respiratory muscle strength after surgery, 2) The relationship between exercise capacity and symptoms of anxiety and depression. MATERIAL AND METHODS: This is a prospective follow up study conducted with patients submitted to OLT. All patients were assessed before and 1 month after surgery through measurements: six minute walk test (6MWT), 6 min step test (6MST) and HADS (Hospital Anxiety and Depression Scale). FEV1% (forced expiratory volume), maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP) were measured in the pre-operative and on 1st, 3rd, 5th day and 1 month after surgery. RESULTS: In 77 patients , 6MWD improved 20.2 m (95%CI 8.1-32.3) and 6MST improved 7.8 steps after surgery (95%CI 3.9-11.6). Change in 6 MWD and 6 MST did not correlated with change HADS. The FEV1% at each time point were 88.8 ± 21.3 before surgery, 32.9 ± 9.9 on 1st day, 39.6 ± 11.5 on 3rd day, 46 ± 12.1 on 5th day and 86.6 ± 21.1 one month after surgery. MIP and MEP values at each time point were -67.4 ± 23.2 and 79.7 ± 26 before surgery, -30.8 ± 12.3 and 36.4 ± 15.4 on 1st day, -38.6 ± 14.1 and 43.8 ± 17 on 3rd day, -45.8 ± 15.9 and 49.7 ± 18.7 on 5th day and -67.1 ± 29.4 and 80.9 ± 23.9 one month after surgery. CONCLUSION: Exercise capacity was modestly increased after OLT without any correlation with symptoms of anxiety and depression. Pulmonary function and respiratory muscle strength decreased immediately after liver transplantation, and progressively recovered, returning to baseline values after 1 month.

Risk factors for acute kidney injury and 30-day mortality after liver transplantation.

INTRODUCTION: The aim of this study is to evaluate the risk factors for acute kidney injury (AKI) and 30-day mortality after liver transplantation. MATERIAL AND METHODS: This is a retrospective cohort of consecutive adults undergoing orthotopic liver transplantation (OLT) at a referral hospital in Brazil, from January 2013 to January 2014. Risk factors for AKI and death were investigated. RESULTS: A total 134 patients were included, with median age of 56 years. AKI was found in 46.7% of patients in the first 72 h after OLT. Risk factors for AKI were: viral hepatitis (OR 2.9, 95% CI = 1.2-7), warm ischemia time (OR 1.1, 95% CI = 1.01-1.2) and serum lactate (OR 1.3, 95%CI = 1.02-1.89). The length of intensive care unit (ICU) stay was longer in AKI group: 4 (3-7) days vs. 3 (2-4) days (p = 0.001), as well as overall hospitalization stay: 16 (9-26) days vs. 10 (8- 14) days (p = 0.001). The 30-day mortality was 15%. AKI was an independent risk factor for mortality (OR 4.3, 95% CI = 1.3-14.6). MELD-Na ≥ 22 was a predictor for hemodialysis need (OR 8.4, 95%CI = 1.5-46.5). Chronic kidney disease (CKD) was found in 36 patients (56.2% of AKI patients). CONCLUSIONS: Viral hepatitis, longer warm ischemia time and high levels of serum lactate are risk factors for AKI after OLT. AKI is a risk factor for death and can lead to CKD in a high percentage of patients after OLT. A high MELD-Na score is a predictor for hemodialysis need.

Eugenol attenuates pulmonary damage induced by diesel exhaust particles.

Environmentally relevant doses of inhaled diesel particles elicit pulmonary inflammation and impair lung mechanics. Eugenol, a methoxyphenol component of clove oil, presents in vitro and in vivo anti-inflammatory and antioxidant properties. Our aim was to examine a possible protective role of eugenol against lung injuries induced by diesel particles. Male BALB/c mice were divided into four groups. Mice received saline (10 µl in; CTRL group) or 15 µg of diesel particles DEP (15 µg in; DIE and DEUG groups). After 1 h, mice received saline (10 µl; CTRL and DIE groups) or eugenol (164 mg/kg; EUG and DEUG group) by gavage. Twenty-four hours after gavage, pulmonary resistive (ΔP1), viscoelastic (ΔP2) and total (ΔPtot) pressures, static elastance (Est), and viscoelastic component of elastance (ΔE) were measured. We also determined the fraction areas of normal and collapsed alveoli, amounts of polymorpho- (PMN) and mononuclear cells in lung parenchyma, apoptosis, and oxidative stress. Est, ΔP2, ΔPtot, and ΔE were significantly higher in the DIE than in the other groups. DIE also showed significantly more PMN, airspace collapse, and apoptosis than the other groups. However, no beneficial effect on lipid peroxidation was observed in DEUG group. In conclusion, eugenol avoided changes in lung mechanics, pulmonary inflammation, and alveolar collapse elicited by diesel particles. It attenuated the activation signal of caspase-3 by DEP, but apoptosis evaluated by TUNEL was avoided. Finally, it could not avoid oxidative stress as indicated by malondialdehyde.

In vivo anti-inflammatory action of eugenol on lipopolysaccharide-induced lung injury.

Eugenol, a methoxyphenol component of clove oil, suppresses cyclooxygenase-2 expression, while eugenol dimers prevent nuclear factor-kappaB (NF-kappaB) activation and inflammatory cytokine expression in lipopolysaccharide-stimulated macrophages. Our aim was to examine the in vivo anti-inflammatory effects of eugenol. BALB/c mice were divided into four groups. Mice received saline [0.05 ml intratracheally (it), control (Ctrl) and eugenol (Eug) groups] or Escherichia coli LPS (10 microg it, LPS and LPSEug groups). After 6 h, mice received saline (0.2 ml ip, Ctrl and LPS groups) or eugenol (160 mg/kg ip, Eug and LPSEug groups). Twenty-four hours after LPS injection, pulmonary resistive (DeltaP1) and viscoelastic (DeltaP2) pressures, static elastance (E(st)), and viscoelastic component of elastance (DeltaE) were measured. Lungs were prepared for histology. In parallel mice, bronchoalveolar lavage fluid was collected 24 h after LPS injection. TNF-alpha was determined by ELISA. Lung tissue expression of NF-kappaB was determined by EMSA. DeltaP1, DeltaP2, E(st), and DeltaE were significantly higher in the LPS group than in the other groups. LPS mice also showed significantly more alveolar collapse, collagen fibers, and neutrophil influx and higher TNF-alpha levels and NF-kappaB expression than the other groups. Eugenol treatment reduced LPS-induced lung inflammation, improving lung function. Our results suggest that eugenol exhibits in vivo anti-inflammatory action in LPS-induced lung injury.