Autoimmune hepatitis in pediatric patients]

BACKGROUND: Autoimmune hepatitis (AIH) is an inflammatory disease of unknown origin that is responsible for progressive liver necrosis and ultimately cirrhosis. OBJECTIVE: Our aim was to evaluate the characteristics of autoimmune hepatitis presenting in the pediatric age. MATERIAL AND METHODS: We conducted a retrospective study of all patients diagnosed with AIH in our hospital department during the last 10 years. Variables analyzed included age, sex, clinical presentation, hepatic function, immunoglobulins, autoimmunity markers, histology, treatment, need for transplant, and clinical evolution. According to the positive level of auto-antibodies, AIH patients were classified as type I AIH (ANA and/or smooth-muscle antibodies) and type II (anti-LKM-1). RESULTS: Seven patients were diagnosed in this period -5 girls (71.5%) and 2 boys (28.5%). Five patients presented with type-I serological markers, and two with type-II markers. Age range at diagnosis was from 21 months to 12 years. In the type-I group, 3 patients presented with acute hepatitis while 2 other patients were diagnosed from laboratory findings while asymptomatic. Elevated aminotransferase (10 times the normal level) was observed in 71.5%, and 85% had elevated immunoglobulins. Treatment with azathioprine and prednisone was started after diagnosis with an average time to remission of 14 months. Two patients relapsed following steroid withdrawal. CONCLUSION: AIH can have different forms of clinical presentation, and is sometimes indistinguishable from viral hepatitis. AIH must be ruled out in patients presenting with concomitant elevation of aminotransferases and immunoglobulins. The commonly accepted treatment is a combination of azathioprine and corticosteroids. A high percentage of patients experience a relapse of disease after steroids are withdrawn. Therefore, some patients will need to stay on combined therapy with minimal doses of steroids.     

Model for end stage of liver disease (MELD) is better than the Child-Pugh score for predicting in-hospital mortality related to esophageal variceal bleeding

Aim: The Child Pugh and MELD are good methods for predicting mortality in patients with chronic liver disease. We investigated their performance as risk factors for failure to control bleeding, in-hospital overall mortality and death related to esophageal variceal bleeding episodes. Methods: From a previous collected database, 212 cirrhotic patients with variceal bleeding admitted to our hospital were studied. The predictive capability of Child Pugh and MELD scores were compared using c statistics. Results: The Child-Pugh and MELD scores showed marginal capability for predicting failure to control bleeding (the area under receiver operating characteristics curve (AUROC) values were < 0.70 for both). The AUROC values for predicting inhospital overall mortality of Child-Pugh and MELD score were similar: 0.809 (CI 95%, 0.710 - 0.907) and 0.88 (CI 95% 0.77-0.99,) respectively. There was no significant difference between them (p > 0.05). The AU-ROC value of MELD for predicting mortality related to variceal bleeding was higher than the Child-Pugh score: 0.905 (CI 95% 0.801-1.00) vs 0.794 (CI 95% 0.676 - 0.913) respectively (p < 0.05). Conclusions: MELD and Child-Pugh were not efficacious scores for predicting failure to control bleeding. The Child-Pugh and MELD scores had similar capability for predicting in-hospital overall mortality. Nevertheless, MELD was significantly better than Child-Pugh score for predicting in-hospital mortality related to variceal bleeding.     

Long interval between HCV infection and development of hepatocellular carcinoma

Abstract: A high prevalence of HCV infection has been reported in patients with hepatocellular carcinoma. The progression from acute transfusion-associated hepatitis to hepatic cirrhosis and hepatocellular carcinoma has been suggested in several studies to be very long. We have investigated the prevalence of anti-HCV and the interval between HCV infection and hepatocellular carcinoma among 191 consecutive patients with cirrhosis and liver-cell carcinoma. Serum samples from 191 patients with cirrhosis and hepatocellular carcinoma, consecutively diagnosed in our hospital between 1988 and 1993, were tested for serological markers of HBV and HCV infection. One hundred and forty-eight patients (77.5%; 95% confidence interval (c.i): 76% to 80%) were anti-HCV positive by 2nd generation enzyme immunoassay (confirmed by 2nd generation recombinant immunoblot assay) and 152 patients (79.5%; 95% c.i: 76% to 80%) were anti-HCV positive by 3rd generation enzyme immunoassay, while only 14 (7.4%; 95% c.i: 5% to 10%) were HBsAg positive. Of the 29 anti-HCV positive patients with previous transfusion, the interval between the date of blood transfusion and the diagnosis of hepatic cirrhosis was 24±12.5 years and that of hepatocellular carcinoma was 26.8±12.4 years. These results confirm the high prevalence of HCV infection in patients with hepatocellular carcinoma and the slow sequential progression from HCV infection through cirrhosis and hepatocellular carcinoma.     

Hepatic and splanchnic perfusion and oxygenation after transjugular intrahepatic portosystemic shunt.

OBJECTIVE: in patients with cirrhosis, transjugular intrahepatic portosystemic shunt (TIPS) decreases the pressure in the portal vein by rerouting nearly all the portal blood flow to the systemic circulation. This may lead to hypoperfusion of the liver and worsening function. Our aim was to investigate whether TIPS actually reduced hepatic and splanchnic perfusion. METHODS: we studied 25 patients who required placement of a TIPS (20 for variceal bleeding and 5 for refractory ascites). We evaluated the clinical condition, laboratory results, blood velocity in the portal vein and hepatic artery by echo-Doppler ultrasonography, systemic hemodynamic-oxygenation status and hemodynamic-oxygenation status in the portal and suprahepatic veins before TIPS, 15 min after the procedure, and 30 days later. Hepatic and splanchnic perfusion were evaluated as the arteriovenous difference in O2 content and as the O2 extraction rates in the hepatic and splanchnic territories. RESULTS: TIPS induced an immediate decrease in portal pressure, a significant increase in systemic hyperdynamic state, and an increase in blood flow velocity in the portal vein and hepatic artery. Thirty days after the procedure these changes persisted, although they were somewhat attenuated. Although splanchnic and liver perfusion were not changed 15 min or 30 days after TIPS, there was a slight tendency toward a decrease in liver perfusion during follow-up. CONCLUSIONS: TIPS increased the hyperdynamic state in the systemic side. However, portal blood shunting did not change liver or splanchnic perfusion.     

Acute myocardial infarction secondary to anaphylactic reaction following shellfish ingestion. The need for rescue coronary angioplasty

During anaphylactic (or anaphylactoid) reactions severe cardiovascular events may occur, acute myocardial infarction among them. This etiology of myocardial infarction, is known, although it is infrequent and only sporadically reported in literature. A case of acute myocardial infarction secondary to anaphylactic reaction following shellfish ingestion, treated with subcutaneous epinephrine and in whom a rescue coronary angioplasty was necessary is reported. The mechanism of coronary occlusion in this kind of reaction and the possible influence on the efficacy of treatment is discussed.     

Cell membrane fatty acid composition in Type 1 (insulin-dependent) diabetic patients: relationship with sodium transport abnormalities and metabolic control

Summary We have studied the fatty acid composition of erythrocyte membrane phospholipids in nine Type 1 (insulin-dependent) diabetic patients and nine healthy control subjects. Cell membranes from the diabetic patients showed a marked decrease in the total amount of polyunsaturated fatty acids (19.0%±2.2 vs 24.6%±1.4, p<0.0001) mainly at the expense of docosahexaenoic acid C226(n3) (2.9%±1.1 vs 5.3%±1.3, p<0.001), and arachidonic acid C204 n6 (12.0%±1.6 vs 15.1%±0.6, p<0.0005). Conversely, the total amount of saturated fatty acids was significantly increased (p<0.05) and the polyunsaturated/saturated ratio was decreased in the Type 1 diabetic patients (p<0.00005). Neither the time from diagnosis, nor C-peptide levels, correlated with parameters indicating a poor metabolic control of Type 1 diabetes. However, C226(n–3) and total n–3 content significantly correlated with HbA_1c (r=–0.79 and r=–0.88, respectively, p<0.01), fructosamine (r=–0.71 and r=–0.74, respectively, p<0.05), and Na⁺-K⁺ ATPase activity (maximal rate/K_m quotient) (r=0.78 and r=0.71, respectively, p<0.05). In conclusion we have found marked alterations of cell membrane lipid composition in Type 1 diabetic patients. These cell membrane abnormalities in lipid content were related to sodium transport systems and to poor metabolic control. Either diet, or the diabetic state, might be responsible for the observed cell membrane abnormalities. A dietary intervention study might differentiate the role of diet and diabetes in the reported cell membrane alterations.     

Hodgkin and Reed-Sternberg cells harbor alterations in the major tumor suppressor pathways and cell-cycle checkpoints: analyses using tissue microarrays

Tumoral cells in Hodgkin lymphoma (HL) display an increased growth fraction and diminished apoptosis, implying a profound disturbance of the cell cycle and apoptosis regulation. However, limitations of molecular techniques have prevented the analysis of the tumor suppressor pathways and cell-cycle checkpoints. Tissue microarray (TMA) is a powerful tool for analyzing a large number of molecular variables in a large series of tumors, although the feasibility of this technique has not yet been demonstrated in heterogeneous tumors. The expression of 29 genes regulating the cell cycle and apoptosis were analyzed by immunohistochemistry and in situ hybridization in 288 HL biopsies using TMA. The sensitivity of the technique was validated by comparing the results with those obtained in standard tissue sections. The results revealed multiple alterations in different pathways and checkpoints, including G1/S and G2/M transition and apoptosis. Striking findings were the overexpression of cyclin E, CDK2, CDK6, STAT3, Hdm2, Bcl2, Bcl-X(L), survivin, and NF-kappaB proteins. A multiparametric analysis identified proteins associated with increased growth fraction (Hdm2, p53, p21, Rb, cyclins A, B1, D3, and E, CDK2, CDK6, SKP2, Bcl-X(L), survivin, STAT1, and STAT3), and proteins associated with apoptosis (NF-kappaB, STAT1, and RB). The analysis also demonstrated that Epstein-Barr virus (EBV)-positive cases displayed a characteristic profile, confirming the pathogenic role of EBV in HL. Survival probability depends on multiple biologic factors, including overexpression of Bcl2, p53, Bax, Bcl-X(L), MIB1, and apoptotic index. In conclusion, Hodgkin and Reed-Sternberg cells harbor concurrent and overlapping alterations in the major tumor suppressor pathways and cell-cycle checkpoints. This appears to determine the viability of the tumoral cells and the clinical outcome.     

Sweet's syndrome and intestinal inflammatory disease. A case report and review of the literature

Sweet's syndrome, or febrile neutrophilic dermatosis, is a process characterized by fever, red tender plaques, neutrophilia and neutrophilic dermal infiltrate with papilar edema in the absence of vasculitis. The association with intestinal inflammatory disease is inusual, a new case associated with ulcerative colitis is reported, and we perform a literature review of Sweet's associated intestinal inflammatory disease.     

Assessment of Platelet REACtivity After Transcatheter Aortic Valve Replacement: The REAC-TAVI Trial

Objectives

The REAC-TAVI (Assessment of platelet REACtivity after Transcatheter Aortic Valve Implantation) trial enrolled patients with aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR) pre-treated with aspirin + clopidogrel, aimed to compare the efficacy of clopidogrel and ticagrelor in suppressing high platelet reactivity (HPR) after TAVI.

Electrocardiographic changes and conduction disturbances after transfemoral aortic valve implantation with Edwards Sapien 3 prosthesis

Objectives

The aim of this study is to describe electrocardiographic changes and conduction abnormalities in patients undergoing transcatheter aortic valve implantation (TAVI).