IMPORTANCE OF MEASURING LEVELS OF INFLIXIMAB IN PATIENTS TREATING INFLAMMATORY BOWEL DISEASE IN A BRAZILIAN COHORT.

BACKGROUND: Crohn's disease and ulcerative colitis are chronic inflammatory bowel diseases. In such pathologies, there is an increased production of alpha tumor necrosis factor (TNF-α). Patients, in whom the conventional immunosuppressant treatment fails, require the use of immunobiological therapy, such as anti-TNF-α, a monoclonal antibody. Infliximab is an anti-TNF-α drug, a chimerical immunoglobulin, with a murine component, which is responsible for the generation of immunogenicity against the drug and formation of anti-TNF-α antibodies. The presence of anti-drug antibodies may be responsible for adverse events and reduction of the drug's effectiveness. Patients with inflammatory bowel diseases undergoing therapy with biological medication, such as infliximab, can relapse overtime and this may not be translated into clinical symptoms. Thus, there is a need for a method to evaluate the efficacy of the drug, through the measurement of serum infliximab levels, as well as antibodies research. OBJECTIVE: This study aimed to measure serum infliximab levels and anti-infliximab antibodies in patients with inflammatory bowel diseases post-induction phase and during maintenance therapy, and describe the therapeutic modifications that took place based on the serum levels results. METHODS: It was a retrospective study, that included forty-five patients, with a total of 63 samples of infliximab measurement. RESULTS: Twenty-one patients had an adequate infliximab serum level, 31 had subtherapeutic levels and 11 had supratherapeutic levels. Seven patients had their medication suspended due to therapeutic failure or high levels of antibodies to infliximab. CONCLUSION: In conclusion, only a third of the patients had adequate infliximab levels and 36% presented with subtherapeutic levels at the end of the induction phase. Therapy optimization occurred based in about 46% of the samples results, demonstrating the importance of having this tool to help the clinical handling of patients with inflammatory bowel diseases ongoing biologic therapy.

ACOUSTIC RADIATION FORCE IMPULSE IS EQUIVALENT TO LIVER BIOPSY TO EVALUATE LIVER FIBROSIS IN PATIENTS WITH CHRONIC HEPATITIS C AND NONALCOHOLIC FATTY LIVER DISEASE.

BACKGROUND: Liver biopsy is recommended as the gold standard method for assessing the stage of liver fibrosis in patients with chronic liver disease. However, it is invasive, with potential risks and complications. Elastography is an ultrasound technique that provides information of changes in the liver tissue, evaluating tissue elasticity and acoustic radiation force impulse is one of the available techniques. OBJECTIVE: The main objective of this study was to evaluate the sensitivity and specificity of acoustic radiation force impulse comparing to liver biopsy to evaluate fibrosis in patients with chronic hepatitis C virus and nonalcoholic fatty liver disease. METHODS: Twenty four patients were included, everyone underwent liver biopsy and acoustic radiation force impulse, and the results were compared with values described in the literature by several authors. RESULTS: In the population of patients with chronic hepatitis C, our data were better correlated with data published by Carmen Fierbinteanu-Braticevici et al., with an accuracy of 82.4%, sensitivity of 71.4% and specificity of 90%. For nonalcoholic fatty liver disease, our data were better correlated with data published by Masato Yoneda et al., with an accuracy of 85.7%, sensitivity 80% and specificity of 100%. CONCLUSION: Acoustic radiation force impulse is a method with good accuracy to distinguish initial fibrosis from advanced fibrosis in hepatitis C virus and nonalcoholic fatty liver disease and can replace biopsy in most cases.

Liver transplantation in a patient with complex anomaly of the inferior vena cava.

BACKGROUND: After the introduction of noninvasive imaging exams, congenital anomalies of the inferior vena cava (IVC) have become more commonly recognized. We report the first successful orthotopic liver transplantation (OLT) performed in an asymptomatic adult with complex IVC anomaly: duplication of the infrarenal IVC, azygos continuation of the IVC, agenesia of the hepatic portion of the IVC and presence of several anomalous veins communicating the common iliac vein and the IVC of one side with the contralateral side. METHODS: This complex anomaly was diagnosed with a venous abdominal angio CT. RESULTS: At liver transplantation, the short suprahepatic portion of the IVC was identified and clamped. The right, middle, and left hepatic veins were sectioned and joined in a single, wide cuff, using venoplasty. This single orifice was anastomosed to the suprahepatic IVC of the new liver. No venovenous bypass was employed. The patient had an uneventful postoperative course. A post transplantation venous abdominal angio CT showed normal blood flow at the anastomosis of the hepatic veins of the receptor and the IVC of the new liver. CONCLUSIONS: This report is important to alert liver transplant teams of the possibility of complex IVC in asymptomatic adult individuals. Identification of these anatomical anomalies is vital to reduce the risk of serious hemorrhage and other operative complications during OLT.

Regression of Hypervascular Nodules in a Patient with Wilson's Disease Awaiting Liver Transplantation.

This paper describes the regressive course over one year of hypervascular nodules in a patient with Wilson's disease. CT revealed multiple, enhancing nodules (up to 3 cm in diameter) detected in the liver in the early arterial phase after the administration of intravenous contrast material. Most of these nodules became isodense in the portal venous phase. After one year of efficient therapy combining d-penicillamine and zinc acetate, most of the nodules had disappeared, while the liver contours had become more regular. To our knowledge, the regression of large hypervascular nodules has not previously been reported in patients with Wilson's disease.

Interleukin-4 induces the activation and collagen production of cultured human intrahepatic fibroblasts via the STAT-6 pathway.

Interleukin-4 (IL-4) is overexpressed in liver grafts in a context of severe recurrent hepatitis C, during which the development of fibrosis is dramatically accelerated. In this study, we examined the effects of IL-4 on the activation and collagen production of cultured human intrahepatic (myo)fibroblasts (hIHFs), and investigated the underlying mechanisms. The myofibroblastic nature of cells was evaluated morphologically using activation markers (smooth muscle alpha-actin, vimentin and prolyl 4-hydroxylase). Quiescent hIHFs were obtained by cell incubation in serum-free medium or cell culture on Matrigel. We first analyzed IL-4 receptor expression, STAT-6 activation by IL-4, and STAT-6 inhibition by an anti-IL-4 antibody or by STAT-6 small-interfering RNA (siRNA) transfection. We then focused on collagen production, using quantitative real-time PCR to analyze the effect of IL-4 on the mRNA expression of collagens I, III and IV, and on collagen levels in supernatants of hIHFs, using the Sircol collagen assay. hIHFs cultured in plastic wells appeared to be morphologically activated. The expression of activation markers was reduced by serum deprivation or culture on Matrigel, and restored by IL-4 incubation. The IL-4 receptor was expressed by hIHFs, and STAT-6 was activated following incubation with IL-4. Both anti-IL-4 antibody and STAT-6 siRNA transfection inhibited this activation. The treatment of hIHFs with IL-4 increased the mRNA expression of collagens I, III and IV (P<0.05) and elevated collagen levels in supernatants (P=0.01 vs untreated cells). Therefore, IL-4 exerts profibrotic effects by activating hIHFs and inducing collagen production and secretion. This effect requires IL4-R binding and STAT-6 activation. IL-4 may thus be involved in accelerated course of fibrogenesis during recurrent hepatitis C.

[Recurrent hepatitis C after liver transplantation: Erythropoietin allows maintenance of antiviral treatment]. / Récidive virale C après transplantation hépatique: l'érythropoïétine permet le maintien du traitement antiviral.

INTRODUCTION: Hepatitis C recurs on grafts after liver transplantation and cirrhosis develops more rapidly than in patients without transplants. It is thus essential to develop effective antiviral treatments for these patients. Prolonged virologic response rate after treatment by pegylated interferon and ribavirin of recurrent HVC is limited, because so many patients stop or reduce the treatment because, in particular, of profound anemia. Administration of erythropoietin can enable these patients to continue treatment and thus improve viral eradication. CASES: We report three cases where antiviral treatment continued although the clinical data would, in the absence of erythropoietin, have led us to interrupt it and where prolonged virologic response was obtained. DISCUSSION: These data suggest that the onset of anemia largely explains the failure of previous trials, although response to treatment is at least as good as in non-transplanted patients, despite immunosuppressive treatment.