Evaluación del seguimiento de niños con hallazgo de hipertransaminasemia

IntroductionAlthough changes in liver function tests can be non-specific in numerous clinical conditions, they can be the first sign of a potentially serious disease in an asymptomatic patient.Material and methodsRetrospective cohort study, performed by reviewing the records of children of a reference hospital central laboratory with alanine aminorransferase enzyme (ALT) elevation during a 6 month aleatory period.Results572 blood tests with serum ALT elevation corresponding to 403 patients had been assessed during the period studied. 98 patients were excluded for presenting abnormal liver test before the study period of comorbidity that could produce ALT elevation. The remaining 305 patients, 22.6% were diagnosed with a medical condition during the first blood test that explained the ALT elevation, although only 33.3% of them were followed up until verifying their normalization. Final study sample consists of 236 patients with abnormal liver test without apparent liver disease. Adequate follow-up was found only in 29% of them. From this group, 9 patients (13%) were diagnosed with liver disease. The rest of the sample were not properly monitored. In patients with higher serum ALT levels, follow-up was early and more appropiate.ConclusionsIn our area, most children without apparent liver disease are no properly monitored. Therefore, an opportunity to diagnosis and treat a potential liver disease was lost in a great number of children. All children with unexplainedhypertransaminasaemia must be studied.     

Hyperoxaluria and systemic oxalosis: current therapy and future directions

Excessive urinary oxalate excretion, termed hyperoxaluria, may arise from inherited or acquired diseases. The most severe forms are caused by increased endogenous production of oxalate related to one of several inborn errors of metabolism, termed primary hyperoxaluria. Recurrent kidney stones and progressive medullary nephrocalcinosis lead to the loss of kidney function, requiring dialysis or transplantation, accompanied by systemic oxalate deposition that is termed systemic oxalosis. For most primary hyperoxalurias, accurate diagnosis leads to the use of therapies that include pyridoxine supplementation, urinary crystallisation inhibitors, hydration with enteral fluids and, in the near future, probiotic supplementation or other innovative therapies. These therapies have varying degrees of success, and none represent a cure. Organ transplantation results in reduced patient and organ survival when compared with national statistics. Exciting new approaches under investigation include the restoration of defective enzymatic activity through the use of chemical chaperones and hepatocyte cell transplantation, or recombinant gene therapy for enzyme replacement. Such approaches give hope for a future therapeutic cure for primary hyperoxaluria that includes correction of the underlying genetic defect without exposure to the life-long dangers associated with organ transplantation.     

Variations in alanine aminotransferase levels within the normal range predict metabolic and androgenic phenotypes in women of reproductive age

Abstract

Background and aims. Obesity plays pathogenetic roles in nonalcoholic fatty liver disease (NAFLD) and hyperandrogenic states like polycystic ovary syndrome (PCOS). We tested the hypothesis that alanine aminotransferase (ALT), a marker of NAFLD, is associated with endocrine and metabolic abnormalities in women with normal ALT. Methods and results. Fasting glucose, insulin, total testosterone, DHEA-S, 17-hydroxyprogesterone, prolactin, leptin, soluble leptin receptor, free leptin index (FLI), lipid profile, ALT, gonadotropins, and sex hormone binding globulin (SHBG) were measured in 200 women aged 18–48 years. Beta cell function (%B), insulin sensitivity (%S) and insulin resistance were calculated using the homeostasis model assessment (HOMA-IR). Ninety-two women had PCOS (Rotterdam criteria); 64 had idiopathic hyperandrogenism; 44 were normal controls. ALT showed significant positive correlations with waist circumference (WC), systolic blood pressure, glucose, leptin, FLI, triglycerides, HOMA-IR and androgens and significant inverse correlations with leptin receptor, HDL-C, %S and SHBG. Correcting for WC and fat% showed that the associations between ALT and glucose, HOMA-IR, testosterone and free androgen index are independent of obesity. Binary logistic regression analyses showed significant association of ALT with PCOS and hyperandrogenemia. ALT ≥ 18 IU/L showed significant association with PCOS with Odds Ratio = 2.28 (95% Confidence Interval = 1.03–5.08), p = 0.043. Conclusions. In women of reproductive age, normal levels of ALT are associated with metabolic and androgenic phenotypes. We suggest a paradigm shift and extension of the routine use of ALT beyond the diagnosis of liver disease.     

Expression of muscarinic acetylcholine receptors in hepatocytes from rat fibrotic liver

The pathological changes of parasympathetic nerve are considered as an independent prognostic factor of the survival rate of patients with chronic liver disease. The non-selective muscarinic acetylcholine receptors (mAchR) agonists and antagonists can affect the proliferation of hepatocytes and hepatic stellate cells, but the subtypes of mAchR expressions in HCs are still uncertain. Here, we investigate the expression of mAchR in hepatic fibrosis on rats. 3 ml/kg 40% carbon tetrachloride (CCL4) was given to induce hepatic fibrosis on rats and the hepatocytes were isolated. Compared to the normal state, the expression levels of m1, 3, 5 in fibrotic liver tissues or hepatocytes were obviously increased, while m2, 4 decreased. 10 μM pilocarpine or 10 μM acetylcholine could increase the alanine aminotransferase (ALT), hydroxyproline (Hyp), collagen I, III in the hepatocytes, and decreased albumin (ALB). They also changed the expressions of mAchR similarly as the fibrotic hepatocytes and livers. However, atropine could ameliorate the state of fibrotic hepatocytes. These data indicate that mAchR played an important role in the regulation of hepatic fibrosis process. Targeting mAchR would have therapeutic potential for hepatic fibrosis.     

石家庄市灌溉用污水对大鼠肝功能的影响

目的研究石家庄市灌溉用污水对大鼠肝功能的影响,以期为污水灌溉的安全性评价提供参考。方法采用气相色谱-质谱联用仪和电感耦合等离子体质谱仪测定石家庄市农田污灌水样中的重金属含量和有机污染物成分。将80只SD大鼠随机分成4组,每组20只,雌雄各半,其中3个染毒组分别为25%,50%及100%污水,采用自由饮水方式进行染毒,连续28 d;并以蒸馏水为阴性对照组。分别于染毒前及染毒第7、28天采集大鼠血样,通过全自动生化分析仪测定血清中天门冬氨酸氨基转移酶(AST)和丙氨酸氨基转移酶(ALT)活力。结果水样中铬和铅含量分别超过国标0.78、0.43倍,共检出30种有机化学物,主要为多环芳烃类化合物、邻苯二甲酸酯类、杂环类化合物及苯胺类化合物等。与对照组相比,饮用灌溉用污水28 d时,50%和100%剂量组雄、雌性大鼠血清ALT活力升高,差异有统计学意义(P0.05)。结论石家庄灌溉用污水可引起大鼠肝损伤。     

Serum ornithine carbamyltransferase reflects hepatic damage in diabetic obese mice

Background and Aim: As ornithine carbamyltransferase (OCT) has proved to be a sensitive serum marker in the detection of hepatotoxicity in several models, it is important to confirm its application to the diagnosis of non‐alcoholic fatty liver disease. Methods: C57BL/6, KK‐Ta and KK‐Ay mice were fed a high‐fat diet for 8 weeks and serum enzyme markers were examined. Serum OCT and alanine aminotransferase (ALT) were also measured in diabetic obese ob/ob and db/db mice fed a normal diet. Liver damage in these mice was evaluated by the hepatic content of tumor necrosis factor‐alpha. Results: Serum levels of OCT increased in KK‐Ay fed a high‐fat diet compared with the normal diet‐fed group, whereas C57BL/6 and KK‐Ta mice were not affected. In ob/ob mice, the relative increase was always greater in OCT than in ALT. In contrast, in db/db mice, the relative increase was always greater in ALT. Hepatic tumor necrosis factor‐alpha was significantly elevated in ob/ob mice, but not in db/db mice. Conclusions: Serum OCT seemed to reflect tumor necrosis factor‐alpha‐mediated hepatic damage when compared with ALT in diabetic obese mice and could be useful in the application for non‐alcoholic fatty liver disease with features of metabolic syndrome, such as obesity and diabetes.