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.

Candesartan, rather than losartan, improves motor dysfunction in thioacetamide-induced chronic liver failure in rats

Minimal hepatic encephalopathy is more common than the acute syndrome. Losartan, the first angiotensin-II receptor blocker (ARB), and candesartan, another widely-used ARB, have protected against developing fibrogenesis, but there is no clear data about their curative antifibrotic effects. The current study was designed to examine their effects in an already-established model of hepatic fibrosis and also their effects on the associated motor dysfunction. Low-grade chronic liver failure (CLF) was induced in 3-month old Sprague-Dawley male rats using thioacetamide (TAA, 50 mg·kg−1·day−1) intraperitoneally for 2 weeks. The TAA-CLF rats were randomly divided into five groups (n=8) treated orally for 14 days (mg·kg−1·day−1) as follows: TAA (distilled water), losartan (5 and 10 mg/kg), and candesartan (0.1 and 0.3 mg/kg). Rats were tested for rotarod and open-field tests. Serum and hepatic biochemical markers, and hepatic histopathological changes were evaluated by H&E and Masson's staining. The TAA-CLF rats showed significant increases of hepatic malondialdehyde, hepatic expression of tumor necrosis factor-α (TNF-α), and serum ammonia, alanine aminotransferase, γ-glutamyl transferase, TNF-α, and malondialdehyde levels as well as significant decreases of hepatic and serum glutathione levels. All treatments significantly reversed these changes. The histopathological changes were moderate in losartan-5 and candesartan-0.1 groups and mild in losartan-10 and candesartan-0.3 groups. Only candesartan significantly improved TAA-induced motor dysfunction. In conclusion, therapeutic antifibrotic effects of losartan and candesartan in thioacetamide-induced hepatic fibrosis in rats are possibly through angiotensin-II receptor blocking, antioxidant, and anti-inflammatory activities. Improved motor dysfunction by candesartan could be attributed to better brain penetration and slower "off-rate" from angiotensin-II receptors. Clinical trials are recommended.

The influence o end-stage liver disease and liver transplantation on thyroid hormoess / Avaliação do impacto da cirrose e do transplante hepático na função tireoidiana

Background Thyroid dysfunction has been reported in most chronic illnesses including severe liver disease. These defects in thyroid hormone metabolism result in the sick euthyroid syndrome, also known as low T3 syndrome. Objectives Our objective was to evaluate the thyroid function in patients with end stage liver disease prior and after deceased donor liver transplantation and to correlate thyroid hormonal changes with the MELD score (Model for End stage Liver Disease). Methods In a prospective study, serum levels of thyrotropin (thyroid stimulating hormone TSH), total thyroxine (tT4), free thyroxine (fT4) and triiodothyronine (T3) from 30 male adult patients with end stage liver disease were measured two to four hours before and 6 months after liver transplantation (LT). MELD was determined on the day of transplant. For this analysis, extra points were not added for patients with hepatocellular carcinoma. Results The patients had normal TSH and fT4 levels before LT and there was no change after the procedure. Total thyroxine and triiodothyronine were within the normal range before LT, except for four patients (13.3%) whose values were lower. Both hormones increased to normal values in all four patients after LT (P=0.02 and P<0.001, respectively). When the patients were divided into two groups (MELD <18 and MELD >18), it was observed that there was no change in the TSH, freeT4, and total T4 levels in both groups after LT. Although there was no significant variation in the level of T3 in MELD <18 group (P=0.055), there was an increase in the MELD >18 group after LT (P=0.003). Conclusion Patients with end stage liver disease subjected to liver transplantation had normal TSH and fT4 levels before and after LT. In a few patients with lower tT4 and T3 levels before LT, the level of these hormones increased to normal after LT. .

Contexto A disfunção tireoidiana tem sido relatada em associação com a maioria das doenças crônicas, incluindo a doença hepática terminal. Estes defeitos no metabolismo dos hormônios tireoidianos resultam na síndrome do doente eutireoideo ou, também conhecida como síndrome do T3 baixo. Objetivos Avaliar a função tireoidiana em pacientes com doença hepática avançada, antes e depois de serem submetidos ao transplante hepático cadavérico (THC) e, correlacionar as alterações hormonais da tireóide com o MELD. Métodos Em um estudo prospectivo, os níveis séricos de tireotropina (hormônio estimulante da tireóide TSH), tiroxina total (T4 total), tiroxina livre (T4 livre) e triiodotironina (T3) de 30 pacientes adultos do sexo masculino com doença hepática terminal foram dosados 2 e 4 horas antes e 6 meses após o THC. O valor do MELD foi determinado no dia do procedimento. Para esta análise, os pontos extras não foram adicionados para os pacientes com carcinoma hepatocelular. Resultados Os pacientes apresentaram níveis de TSH e T4 livre normais antes do THC e não houve nenhuma alteração após o procedimento. As dosagens de T4 total e T3 no início do estudo estavam dentro da faixa normal, exceto por quatro pacientes (13,3%), os quais apresentavam valores abaixo da referência. Ambos os hormônios apresentaram um aumento 6 meses após o THC (P=0,02 e P<0,001, respectivamente). Quando os pacientes foram divididos em dois grupos (MELD <18 e MELD >18) não observamos diferença nos níveis de TSH, T4 total e T4 livre entre os grupos após THC. Apesar de não haver variação nos níveis de T3 no grupo com MELD <18 (P=0,055), houve um aumento no grupo MELD >18 após THC (P=0,003). Conclusão Os pacientes com cirrose hepática submetidos a transplante hepático tinham valores normais de TSH e T4 livre antes e após o THC. Nos poucos pacientes que apresentavam valores baixos de T4 total e T3 antes do THC, houve normalização destes hormônios após o THC. .

Albumin for End-Stage Liver Disease

Albumin has been widely used in patients with cirrhosis in an attempt to improve circulatory and renal functions. The benefits of albumin infusions in preventing the deterioration in renal function associated with large-volume paracentesis, spontaneous bacterial peritonitis, and established hepatorenal syndrome in conjunction with a vasoconstrictor are well established. While some of these indications are supported by the results of randomized studies, others are based only on clinical experience and have not been proved in prospective studies. The paucity of well-designed trials, the high cost of albumin, the lack of a clear-cut survival benefit, and fear of transmitting unknown infections make the use of albumin controversial. The recent development of the molecular adsorbent recirculating system, an albumin dialysis, is an example of the capacity of albumin to act by mechanisms other than its oncotic effect. Efforts should be made to define the indications for albumin use, the dose required, and predictors of response, so that patients gain the maximum benefit from its administration.