Cirroses hepáticas metabólicas / Hepatic cirrhosis metabolic

A cirrose hepática é importante causa de morbidade e mortalidade em todo o mundo. Entre as principais etiologias destacam-se as hepatites crônicas pelos vírus da hepatite C (HCV) e B (HBV) e o consumo e abuso do álcool. Destacamos, também, as hepatites crônicas e cirroses de natureza autoimune, medicamentosas, dentre outras.

Liver cirrhosis is the most important cause of mortality and morbidity all over the world. Among the mainly etiologies, chronic hepatites highlight due hepatite C (HCV) and B (HBV) and alcohol abuse. We also emphasize chronic hepatitis and cirrhosis from autoimmune and medical origins, among others.

Producción endógena de alcohol en pacientes con cirrosis hepática, alteración motora y sobrecrecimiento bacteriano / Endogenous ethanol production in patients with liver cirrhosis, motor alteration and bacterial overgrowth

BACKGROUND: Small intestinal bacterial overgrowth generates endogenous ethanol production both in experimental animals and humans. Patients with cirrhosis have small intestinal bacterial overgrowth, but endogenous ethanol production has not been studied in them. AIM: To investigate endogenous ethanol production in patients with cirrhosis, altered intestinal motility and small intestinal bacterial overgrowth. PATIENTS AND METHODS: Eight patients with cirrhosis of different etiologies and altered gastrointestinal motility, consisting in changes in the migrating motor complex, were studied. All had also small intestinal bacterial overgrowth, measured by means of the H2 breath test with lactulose. Plasma ethanol levels were measured by gas liquid chromatography in fasting conditions and 120 min after a carbohydrate rich meal. RESULTS: In fasting conditions, no patient had endogenous ethanol production. Alter the meal, ethanol in concentrations of 11.3 and 8.2 mg/del were detected in two patients. Negligible amounts of ethanol were detected in 4 patients and two patients had undetectable alcohol levels. CONCLUSIONS: A low endogenous production of ethanol was demonstrated in six of eight patients with cirrhosis.

Oxidative stress in alcoholic liver disease.

We report on the prooxidant (lipid peroxides) and antioxidant levels (ascorbic acid, reduced glutathione, superoxide dismutate activity) in healthy individuals (30) and patients with cirrhosis (37; 22 alcoholic cirrhosis and 15 non alcoholic cirrhosis). A significant increase in plasma lipid peroxide (P < 0.05) and ascorbic acid (P < 0.01) and a significant decrease in reduced glutathione (P < 0.001) and superoxide dismutase activity (P < 0.05) in haemolysate was observed in cirrhosis patients compared to the control group. A significant decrease in reduced glutathione (P < 0.01) and superoxide dismutase (P < 0.05) activity was also observed when the alcoholic cirrhosis group was compared to non alcoholic group. A significant increase in aspartate transaminase (P < 0.05), gamma glutamyl transaminase (P < 0.01) and aspartate transaminase/alanine transaminase (P < 0.05) ratio was seen in alcoholic cirrhosis group. A significant positive correlation between gamma glutamyl transferase and lipid peroxides (r = 0.48, P < 0.05) was observed in alcoholic cirrhosis.

Plasma levels of transthyretin and retinol-binding protein in child-A cirrhotic patients in relation to protein-calorie status and plasma amino acids, zinc, vitamin A and plasma thyroid hormones

Transthyretin and retinol-binding protein are sensitive markers of acute protein-calorie malnutrition both for early diagnosis and dietary evaluation. A preliminary study showed that retinol-binding protein is the most sensitive marker of protein-calorie malnutrition in cirrhotic patients, even those with the mild form of the disease (Child A). However, in addition to being affected by protein-calorie malnutrition, the levels of these short half-life-liver-produced proteins are also influenced by other factors of a nutritional (zinc, tryptophan, vitamin A, etc) and non-nutritional (Sex, aging, hormones, renal and liver functions and inflammatory activity) nature. These interactions were investigated in 11 adult male patients (49.9 + 9.2 years of age) with alcoholic cirrhosis (Child-Pugh grade A) and with normal renal function. Both transthyretin and retinol binding protein were reduced below normal levels in 55 percent of the patients, in close agreement with their plasma levels of retinol. In 67 percent of the patients (4/6), the reduced levels of transthyretin and retinol-binding protein were caused by altered liver function and in 50 percent (3/6) they were caused by protein-calorie malnutrition. Thus, the present data, taken as a whole, indicate that reduced transthyretin and retinol-binding protein levels in mild cirrhosis of the liver are mainly due to liver failure and/or vitamin A status rather than representating an isolated protein-calorie malnutrition indicator.

Diabetes mellitus, resistencia a la insulina y enfermedades crónicas del hígado / Diabetes mellitus, resistance to insulin and chronic diseases of the liver

Se analizan los cambios que ocurren en el metabolismo de la glucosa en pacientes con hepatopatías crónicas. La sensibilidad a la insulina está disminuida en los pacientes con cirrosis hepática, incluso antes de que la intolerancia a la glucosa se haga manifiesta. La resistencia a la insulina reside en el músculo y mayormente resulta de un defecto en la síntesis del glucógeno. La diabetes mellitus en los pacientes con cirrosis y resistencia a la insulina es el resultado de un defecto progresivo en la secreción de insulina con el desarrollo de resistencia a la insulina por el hígado, lo que conduce a la hiperglucemia de ayuno.

Alteraçöes imunitárias na cirrose hepática alcoólica / Immunologic changes in alcoholic liver cirrhosis

A cirrose hepática alcoólica cursa com alteraçöes imunitárias que podem ser atribuídas à hepatopatia em si, ao alcool e à desnutriçäo do paciente. Tais alteraçöes envolvem a imunidade celular e humoral, caracterizando-se por aumento de imunoglobulinas, diminuiçäo da resposta cutânea tardia e da resposta linfoproliferativa aos mitógenos, diminuiçäo de proteínas do sistema complemento (C3 C4) e queda (IL2 e çIF), ou elevaçäo (IL1, TNF, IL6, E IL8) de citoquinas. Paralelamente à imunossupressäo sistêmica comum a todos os pacientes, há uma imunoestimulaçäo, a nível hepático, com provável predisposiçäo genética, que norteia as características do curso da auto-agressäo hepática, em cada paciente. A imunossupressäo sistêmica poderia ser responsabilizada pelas infecçöes periódicas e neoplasias que invariavelmente acometem estes pacientes e pode ser fundamentada, genericamente, na exaustäo da defesa sistêmica: a) pelo menor clearance de bactérias e/ou toxinas; b) pela menor produçäo hepática de componentes do sistema complemento; c) pela deficiência de citoquinas (IL2 e çIF), e d) pela deficiência de nutrientes antioxidantes e/ou participantes dos mecanismos da defesa imune. A imunoestimulaçäo hepática, responsável pela autoagressäo e perpetuaçäo da doença, é caracterizada pela migraçäo preferencial de linfócitos T citotóxicos e de neutrófilos, ao fígado, estimulados por fatores, como os corpos de Mallory, acetaldeído ou mesmo autoanticorpos. Além disso, a elevaçäo local das citoquinas, (IL1, TNF, IL6 E IL8) poderia responder pela maior quimiotaxia aos fagócictos (IL8) ou por parte do dano hepático (TNF) facilitado pela menor defesa antioxidante do fígado cirrótico. As possíveis intervençöes atenuadoras ou revertedoras destas alteraçöes imunitárias passam, obrigatoriamente, pela retirada do álcool e recuperaçäo nutricional do paciente, particularmente nos aspectos protéico-energético e antioxidante. Ainda necessitando de maiores estudos, há a possibilidade do uso de anticorpos monoclonais contra as citoquinas de açäo catabólica

Centellografía hepatobiliar cuantitativa con 99m Tc DISIDA en sujetos normales y en cirróticos alcohólicos / Quantitative Tc 99m - DISIDA hepatobiliary scintigraphy in normal and cirrhotic alcoholic subjects

Quantitative hepatobiliary scintigraphy (Q.H.S.), with 99m Tc-DISIDA was performed on 15 control subjects and 32 alcoholic cirrhotic patients (A.C.). We used a dynamic planar scintigraphy (30 sec/ frame, up to 45 min) technique following injection intravenously of 99m TC-DISIDA. Time/activity curves were obtained from the right upper lobe of the liver and the: 1) slope uptake, 2) half-time (T 1/2 min) uptake, 3) excretion half-time (T 1/2 min), were measured from the curve. The A.C. were divided in two groups, IIA (n = 32) and IIB (n = 6) if the excretory curve show negative slope or not respectively. Results: The mean value (+/- 1 D.S. 95 percent confidence interval) of the slope uptake of the A.C. IIB (1.2 +/- 0.40) was significantly slower than a.C. IIA (2.8 +/- 0.39) and control (4.5 +/- 1.17, p = 0,0001 respectively). The difference also was significantly when the mean of A.C. IIA was compared to control (p = 0.007). The mean of T 1/2 uptake of A.C.IIB (62.2 +/- 22.2) was significantly longer than A.C. IIA (28.4 +/- 4.4 p = 0.011) and control (17.9 +/- 3.87, p = 0.003) The mean T 1/2 excretory of the A.C. IIA (90.0 +/- 17.8) was also significant delayed compared to the mean of normal control (35.6 +/- 7.6 p = 0,001). In the A.C. IIB the excretion plateau curve was associated with visualization of the gallbladder and bowel activity suggesting that the excretion of the IDA preferentially came from the left hepatic lobe. We conclude that alcoholic cirrhotic patients have impaired the mechanism related with the uptake/excretion transport of organic anion, and suggest that noninvasive Q.H.S. with 99m TC-DISIDA, can be a useful clinical technique to be used for the quantification of hepatic function in cirrhotic alcoholic patients.

Estado nutricional de pacientes portadores de cirrose hepática: relaçäo entre a gravidade da doença com a piora nutricional avaliada por indicadores antropométricos e bioquímicos / Nutritional status of patients carrier of liver cirrhosis: relationship betweem the severity of the disease and the nutritional aggravation evaluated by anthropometric and biochemical indicators

Com o objetivo de relacionar a gravidade do comprometimento hepático com o grau de desnutriçäo proteico-calórica foram estudados 53 pacientes, e sua maioria (75,5%), homens, todos acima de 26 anos, portadores de cirrose hepática, de etiologia preodmiantemente (81%) alcoólica. De acordo com a gravidade da doença os pacientes foram classificados, mediante parâmetros clínicos e laboratoriais, em Child A (19% dos casos), Child B (32%) e Child C (49%). A avaliaçäo do estado nutricional, feita por ocasiäo da primeira consulta, envolveu inquérito alimentar (recordatório de 24 horas), atropometria e exames laboratoriais. Quando comparados com os valores de referência verificou-se pela associaçäo dos indicadores antropométricos e bioquímicos que 57% dos pacientes eram desnutridos, ou com risco nutricional. Os indicadores ingestäo calórica, prega cutânea tricipital e pré-albumina sérica foram os que se mostraram mais intensamente relacionados com a piora da funçäo hepática seguidos da albumina, triptofano livre e linfócitos totais. O indicador nutricional mais fracamente relacionado com o estágio clínico da doença foi a ingestäo protéica; por outro lado 90% dos pacientes Child A apresentaram níveis baixos de proteína ligadora do retinol (RBP), esta taxa foi de 50% para a pré- albumina e para a circunferência muscular do braço. Portando, conclui-se que a desnutriçäo do cirrótico se caracteriza nos estágios clínicos iniciais como sendo protéica afetando tanto as proteínas viscerais como as somáticas. A deficiência calórica é progressiva, acompanhando o agravamento da disfunçäo hepática

Evaluación hormonal hipofiso-gonadal en pacientes masculinos con cirrosis hepática alcoholica / Pituitary-gonadal hormonal evaluation in male patients with alcoholic liver cirrhosis

Se midieron los valores hormonales séricos hipofisogonadales en 26 cirróticos alcohólicos y 20 sujetos controles. Los valores medios de testosterona total y hormona luteinizante fueron más bajos en los cirróticos (p < 0.05); los valores de estradiol y prolactinemia fueron significativamente más altos (p < 0.05 y p < 0.001, respectivamente) en dicho grupo. El valor medio de la hormona folículo estimulante fue igual en ambos grupos. Los ejes hipofisogonadales hormona luteinizante-testosterona y hormona folículo estimulante estradiol estuvieron alterados en los cirróticos al no funcionar el mecanismo de retroalimentación en cada uno de ellos. Estos resultados muestran una variada alteración de la función hormonal sexual en nuestros pacientes, lo que contribuye a hacer más complejo el espectro clínico y el manejo de este tipo de enfermos