Effect of Chondroitin Sulphate on Pro-Inflammatory Mediators and Disease Activity in Patients with Inflammatory Bowel Disease.

BACKGROUND/AIMS: To evaluate the incidence rate of relapse in patients with inflammatory bowel disease (IBD) undergoing chondroitin sulphate (CS) treatment and its effect on the concentrations of several pro-inflammatory proteins. METHODS: Prospective, observational, 12-month follow-up study in patients with IBD in remission, starting CS (Condrosan®, Bioiberica S.A.) treatment for osteoarthritis (OA). Crohn's Disease Activity Index and modified Truelove-Witts severity index were calculated for Crohn's disease and ulcerative colitis (UC) respectively. Levels of vascular endothelial growth factor (VEGFA), -C, fibroblast growth factor 2, hepatocyte growth factor, angiopoietin (Ang)-1, Ang-2, transforming growth factor beta, tumour necrosis factor alpha, interleukin (IL)-1ß, IL-6, IL-12, IL-17, IL-23, intracellular adhesion molecule-1, vascular adhesion molecule-1, matrix metalloproteinase-3 and PGE2 were quantified by ELISA. OA joint pain was evaluated using a visual analogue scale. RESULTS: A total of 37 patients (19 UC and 18 Crohn's disease) were included. The mean values for OA joint pain decreased after 12 months from 5.9 ± 2.8 to 3.0 ± 2.3 (p < 0.05). Only 1 patient (with UC) flared during follow-up. The incidence rate of relapse was 3.4% per patient-year of follow-up. Mean serum VEGFA levels increased between baseline (492 pg/ml) and 12-month treatment (799 pg/ml; p < 0.05). CONCLUSION: The incidence of IBD relapse in patients under CS treatment was lower than that generally reported. This treatment might modulate VEGFA. CS decreases OA-related pain in patients with IBD.

Third-line rescue therapy with bismuth-containing quadruple regimen after failure of two treatments (with clarithromycin and levofloxacin) for H. pylori infection.

BACKGROUND: Helicobacter pylori eradication therapy with a proton pump inhibitor (PPI), clarithromycin, and amoxicillin fails in >20 % of cases. A rescue therapy with PPI-amoxicillin-levofloxacin still fails in >20 % of patients. AIM: To evaluate the efficacy and tolerability of a bismuth-containing quadruple regimen in patients with two consecutive eradication failures. METHODS: Prospective multicenter study of patients in whom 1st treatment with PPI-clarithromycin-amoxicillin and 2nd with PPI-amoxicillin-levofloxacin had failed. A 3rd eradication regimen with a 7- to 14-day PPI (standard dose b.i.d.), bismuth subcitrate (120 mg q.i.d. or 240 mg b.i.d.), tetracycline (from 250 mg t.i.d. to 500 mg q.i.d.) and metronidazole (from 250 mg t.i.d. to 500 mg q.i.d.). Eradication was confirmed by (13)C-urea-breath-test 4-8 weeks after therapy. Compliance was determined through questioning and recovery of empty medication envelopes. Adverse effects were evaluated by means of a questionnaire. RESULTS: Two hundred patients (mean age 50 years, 55 % females, 20 % peptic ulcer/80 % uninvestigated-functional dyspepsia) were initially included, and two were lost to follow-up. In all, 97 % of patients complied with the protocol. Per-protocol and intention-to-treat eradication rates were 67 % (95 % CI 60-74 %) and 65 % (58-72 %). Adverse effects were reported in 22 % of patients, the most common being nausea (12 %), abdominal pain (11 %), metallic taste (8.5 %), and diarrhea (8 %), none of them severe. CONCLUSION: A bismuth-containing quadruple regimen is an acceptable third-line strategy and a safe alternative after two previous H. pylori eradication failures with standard clarithromycin- and levofloxacin-containing triple therapies.

[Characteristics of deep sedation in gastrointestinal endoscopic procedures performed by intensivists]. / Características de la sedación profunda en procesos endoscópicos gastrointestinales, realizada por médicos intensivistas.

OBJECTIVE: To determine tolerance, pain intensity, percentage of tests completed successfully and complications of deep sedation controlled by intensivists during gastrointestinal endoscopic procedures. DESIGN: A one-year, prospective observational study was carried out. SETTING: Department of Intensive Care intervention in the Endoscopy Unit of Hospital Universitario del Tajo (Spain). PATIENTS: Subjects over 15 years of age subjected to endoscopic procedures under deep sedation. RESULTS: A total of 868 patients were sedated during the study period, with the conduction of 1010 endoscopic procedures. The degree of tolerance was considered adequate («Very good¼/«Good¼) in 96.9% of the patients (95%CI: 95.7-98.1%), with a median score of 0 on the pain visual analog scale. A total of 988 endoscopic procedures were successfully completed (97.8%; 95%CI: 96.9-98.8%): 675 colonoscopies (97.1%) and 305 endoscopies (99.7%). Complications were recorded in 106 patients (12.2%; 95%CI: 10.0-14.5%). The most frequent being desaturation (6.1%), rhythm disturbances (5.1%) and hypotension (2.4%). CONCLUSION: Gastrointestinal endoscopic procedures under sedation controlled by intensivists are well tolerated and satisfactory for the patient, and are successfully completed in a very large percentage of cases. The procedures are associated with frequent minor complications that are resolved successfully.

Health care costs of complex perianal fistula in Crohn's disease.

AIM: To evaluate the use of health care resources and the associated costs of complex perianal Crohn's disease (CD) from the National Health System perspective. METHODS: We conducted a multicenter, retrospective, observational study in which gastroenterologists from 11 hospitals in the Community of Madrid took part. Data was collected on the direct healthcare resources (pharmacological treatments, surgical procedures, laboratory/diagnostic tests, visits to specialists and emergency departments, and hospitalizations) consumed by 97 adult patients with complex perianal CD which was active at some point between January 1, 2005, and case history review. RESULTS: We recorded 527 treatments: 73.1% pharmacological (32.3% antibiotic, 20.5% immunomodulator, 20.3% biological) and 26.9% surgical. Mean annual global cost was €8,289/patient, 75.3% (€6,242) of which was accounted for by pharmacological treatments (€13.44 antibiotics; €1,136 immunomodulators; €5,093 biological agents), 12.4% (€1,027) by hospitalizations and surgery, 7.7% (€640) by medical visits, 4.2% (€350) by laboratory/diagnostic tests, and 0.4% (€30) by emergency department visits. CONCLUSIONS: Pharmacological therapies, and in particular biological agents, are the main cost driver in complex perianal CD; costs due to surgery and hospitalizations are much lower.

[Alveolar recruitment maneuvers in respiratory distress syndrome]. / Maniobras de reclutamiento alveolar en el síndrome de distrés respiratorio agudo.

In patients with acute respiratory distress syndrome, heterogeneity in filling of the lung parenchyma results in collapsed or distended lung areas. Protective ventilation strategies based on the use of low volumes have been shown to increase survival in this context. For opening the lung, and in addition to PEEP, recruitment maneuvers are used-this practice remaining the subject of debate. The present review offers an update on the alveolar recruitment techniques, considering the great variability that exists in the application of these maneuvers, and the different factors that influence the response to maneuvering.

Evaluation of liver fibrosis by transient elastography (Fibroscan®) in patients with inflammatory bowel disease treated with methotrexate: a multicentric trial.

BACKGROUND: Methotrexate is an effective treatment for inflammatory bowel disease (IBD). However, long-term treatments have been associated with the development of liver fibrosis. FibroScan® is a noninvasive, safe, and effective technique to evaluate liver fibrosis. AIM: To evaluate the presence of significant liver fibrosis by transient elastography (FibroScan®) in IBD patients treated with methotrexate. METHODS: Cross-sectional study including IBD patients treated with methotrexate from different hospitals. Clinical and analytical data, duration of treatment, and cumulative dose of methotrexate were obtained. Liver stiffness was assessed by FibroScan®. The cutoff value for significant liver fibrosis (according to METAVIR) was F ≥ 2: 7.1 kPa. Results. In the study, 46 patients were included, 30 women (65%), with a mean age of 43 ± 10 years. 31 patients had Crohn's disease (67.4%), 13 ulcerative colitis (28.3%), and 2 indeterminate colitis (4.3%). The mean cumulative dose of methotrexate was 1242 ± 1349 mg, with a mean treatment duration of 21 ± 24 months. The mean value of liver stiffness was 4.7 ± 6.9 kPa. There were 35 patients (76.1%) with F01, 8 patients (17.4%) with F = 2, and 3 patients with F ≥ 3 (6.5%). There were no differences in liver stiffness depending on sex, age, type of IBD, or cumulative dose of methotrexate. CONCLUSIONS: (1) Development of advanced liver fibrosis in IBD patients treated with methotrexate is exceptional. (2) There were no differences in liver stiffness depending on the type of IBD or the cumulative dose of methotrexate. (3) FibroScan® may be potentially useful for evaluation and follow-up of liver fibrosis in methotrexate-treated patients.

[Pituitary apoplexy. A review]. / Apoplejía pituitaria. Revisión del tema.

Pituitary apoplexy constitutes a syndrome that is characterized by the ischemic infarction or hemorrhage into a pituitary tumour. Clinically the patient develops sudden headache, meningismus, visual disturbances, even blindness, and occasionally decrease in level of consciousness. To diagnose it is basic to perform a cerebral MRI. Treatment consists in urgent sellar decompression by transsphenoidal surgery and substitute therapy with steroids.

[Intracranial injury caused by captive bolt gun]. / Lesiones intracraneales originadas con pistola de bala cautiva.

Guns bullet or captive bolt is used as a weapon for stunning animals as a prelude to sacrifice. Placed in front of it induce an immediate loss of consciousness, thus achieving a "humanization" of process. It's use for suicide is rare, almost exclusively of people who have access to them because of their occupation, causing severe injuries to the brain. We analyse three cases presented in our service. One of them dies as a result of injuries.

[Isolated hypoglossal nerve palsy secondary to an atlantoccipital joint synovial cyst. Case report and literature review]. / Parálisis aislada del nervio hipogloso secundaria a quiste articular atlanto-occipital. Presentación de un caso y revisión de la literatura.

Hypoglossal nerve palsy is commonly associated with the involvement of other cranial nerves. His injury is rarely isolated. We present a patient in which paralysis is due to the presence of a "juxtafacet cyst" of the atlanto-occipital joint. We review the anatomy of the hypoglossal nerve, different therapeutic options, the differential diagnosis and papers published to date.

[Chronic subdural hematoma associated with arachnoid cyst. Report of 12 cases]. / Hematoma subdural crónico asociado a quiste aracnoideo. Presentación de 12 casos.

INTRODUCTION: We designed this study to investigate the clinical, neurological, and radiological outcome of patients with chronic subdural hematoma related to an intracranial arachnoid cysts. PATIENTS AND METHODS: Medical records of 12 cases of patients with arachnoids cyst complicated with chronic subdural hematoma were retrospectively reviewed. RESULTS: Between January 1984 and April 2008, 12 patients (0.9%) of 1.253 cases of chronic subdural hematoma surgically treated in our hospital had associated arachnoid cyst. Arachnoid cysts were located in the middle fossa (10 cases) and convexity (2 cases). The most frequent symptom was headache (6 cases), followed by seizures (3 cases). Eleven patients underwent burr hole and drainage; the oldest patient was treated conservatively. CONCLUSIONS: Patients with AC, especially when these are located in temporal fossa, appear to harbour a life-long risk of contracting subdural hematoma. Hematoma evacuation is adequate at first operation and if arachnoid cyst is symptomatic or preoperative symptoms persist, additional arachnoid cyst surgery should be considered.

[Scedosporium apiospermum brain abscess. Report of one case with literature review]. / Absceso cerebral por Scedosporium apiospermum. Presentación de un caso con revisión de la literatura.

Scedosporium apiospermum is a fungus found in the soil and in contaminated water and commonly cause cutaneous infections and is a rare cause of central nervous system infection. Invasive infection is usually associated with immunosuppresion. The authors present a 73-year-old woman with chronic renal disease who presented with headache for 2 weeks. Computerized tomography scans revealed a ring-enhancing lesion in left temporal lobe. An urgent craniotomy was performed and the lesion was totally removed. The patient died 5 days later. Scedosporium apiospermum was isolated in the culture of the extirpated lesion. The authors review the previously reported cases of brain abscess for Scedosporium apiospermum.

[Filum terminale ependymomas. Analysis of a serie of 20 consecutive cases]. / Ependimomas del filum terminal. Análisis de 20 casos consecutivos.

OBJECTIVE: to analyze the clinical, radiological and surgical outcome of a series of filum terminale ependymomas. Patients and methods. This retrospective study involved 20 patients with 21 ependymomas of the filum terminale encountered during a 21 year period (1988- 2008). All patients were diagnosed using MRI and surgically treated. RESULTS: the male: female ratio was 1:1.5, and the mean age at diagnosis was 44.8 years (range 15-64). First symptom included radicular pain (12 cases) and lumbar pain in the other 8 cases, with average symptom duration of 8.7 years (range 0-6-32). All patients underwent open biopsy, seventeen tumours received gross-total resection and 4 received subtotal resection. Histologically, 20 tumours were myxopapillary ependymomas (grade I) and 1 case a grade II ependymoma. The mean follow-up period was 8 years (range 1-18 years). CONCLUSIONS: filum terminale ependimomas are slow growing tumours of the cauda equina with a high incidence in young adults. The most common presentation is with low back pain long time evolution. Although ependymomas of the filum terminale are thought to be benign, local recurrence is not uncommon.

[Epidural haematoma due to an headrest in an adult]. / Hematoma epidural secundario al empleo de cabezal autoestático en un adulto.

A head fixation device with pins is commonly used for immobilization of the patients during neurosurgical procedures. Despite its appropriate management, it may be the cause of some serious complications such as skull perforation and intracranial injuries.We report the case of a 19-years-old young admitted for a endoscopic third ventriculostomy who developed an epidural haematoma due to the penetration of the skull by a pin.

Prevalence and Factors Associated With Fatigue in Patients With Inflammatory Bowel Disease: A Multicentre Study.

BACKGROUND AND AIMS: The aims of this study were to determine the prevalence of fatigue in patients with inflammatory bowel disease [IBD], to identify the factors associated with fatigue and its severity, to assess the impact of fatigue on quality of life [QoL], and to evaluate the relationship between fatigue and sleep disorders. METHODS: This was a prospective multicentre study conducted at 22 Spanish centres. Consecutive patients followed at IBD Units were included. Fatigue was evaluated with the Fatigue Severity Scale [FSS] and the Fatigue Impact Scale [FIS]. Quality of life and sleep quality were assessed using the IBD Questionnaire-Short Form [IBDQ-9] and the Pittsburgh Sleep Quality Index [PSQI], respectively. RESULTS: A total of 544 consecutive adult IBD patients were included [50% women, mean age 44 years, 61% Crohn's disease]. The prevalence of fatigue was 41% (95% confidence interval [CI] = 37-45%). The variables associated with an increased risk of fatigue were: anxiety [OR = 2.5, 95% CI = 1.6-3.7], depression [OR = 2.4, 95% CI = 1.4-3.8], presence of extraintestinal manifestations [EIMs] [OR = 1.7, 95% CI = 1.1-2.6], and treatment with systemic steroids [OR = 2.8, 95% CI = 1.4-5.7]. The presence of EIMs [regression coefficient, RC = 8.2, 95% CI = 2.3-14.2], anxiety [RC = 25.8, 95% CI = 20.0-31.5], depression [RC = 30.6, 95% CI = 24.3-37.0], and sleep disturbances [RC = 15.0, 95% CI = 9.3-20.8] were associated with severity of fatigue. Patients with fatigue had a significantly decreased IBDQ-9 score [p < 0.001]. CONCLUSIONS: The prevalence of fatigue in IBD patients is remarkably high and has a negative impact on QoL. Therapy with systemic steroids is associated with an increased risk of fatigue. The severity of fatigue is associated with anxiety, depression, sleep disorders, and the presence of EIMs. Fatigue was not associated with anaemia, disease activity or anti-TNF therapy.

Helicobacter pylori second-line rescue therapy with levofloxacin- and bismuth-containing quadruple therapy, after failure of standard triple or non-bismuth quadruple treatments.

BACKGROUND: The most commonly used second-line Helicobacter pylori eradication regimens are bismuth-containing quadruple therapy and levofloxacin-containing triple therapy, both offering suboptimal results. Combining bismuth and levofloxacin may enhance the efficacy of rescue eradication regimens. AIMS: To evaluate the efficacy and tolerability of a second-line quadruple regimen containing levofloxacin and bismuth in patients whose previous H. pylori eradication treatment failed. METHODS: This was a prospective multicenter study including patients in whom a standard triple therapy (PPI-clarithromycin-amoxicillin) or a non-bismuth quadruple therapy (PPI-clarithromycin-amoxicillin-metronidazole, either sequential or concomitant) had failed. Esomeprazole (40 mg b.d.), amoxicillin (1 g b.d.), levofloxacin (500 mg o.d.) and bismuth (240 mg b.d.) was prescribed for 14 days. Eradication was confirmed by (13) C-urea breath test. Compliance was determined through questioning and recovery of empty medication envelopes. Incidence of adverse effects was evaluated by questionnaires. RESULTS: 200 patients were included consecutively (mean age 47 years, 67% women, 13% ulcer). Previous failed therapy included: standard clarithromycin triple therapy (131 patients), sequential (32) and concomitant (37). A total of 96% took all medications correctly. Per-protocol and intention-to-treat eradication rates were 91.1% (95%CI = 87-95%) and 90% (95%CI = 86-94%). Cure rates were similar regardless of previous (failed) treatment or country of origin. Adverse effects were reported in 46% of patients, most commonly nausea (17%) and diarrhoea (16%); 3% were intense but none was serious. CONCLUSIONS: Fourteen-day bismuth- and levofloxacin-containing quadruple therapy is an effective (≥90% cure rate), simple and safe second-line strategy in patients whose previous standard triple or non-bismuth quadruple (sequential or concomitant) therapies have failed.

Intensification of infliximab therapy in Crohn's disease: efficacy and safety.

INTRODUCTION: The response of Crohn's disease (CD) to infliximab is initially good, although a loss of efficacy is observed over time. Dose escalation has been recommended in such cases. AIMS: To study the response to an intensified infliximab regimen in patients with CD; and to evaluate the adverse effects associated with intensification of therapy and identify predictors of loss of response. METHODS: We performed a retrospective multicenter survey of all patients with CD who had been treated with at least the 3 induction doses of standard infliximab therapy, and for whom treatment had to be intensified due to loss of response. We analyzed the efficacy of the intensified regimen. RESULTS: Thirty-three patients were included. After the first intensification dose, 79% of patients had a clinical response (33.5% complete response, 45.5% partial response). In the long term, 83%, 69%, 47%, and 29% of patients who had an initial response to the intensification maintained the response at 6, 12, 18, and 36 months, respectively. The loss of efficacy after escalation was 43% per patient-year of follow-up. One patient had an infusion reaction after 36 doses. One patient developed a herpes zoster infection. CONCLUSIONS: A high proportion of patients whose dose of infliximab is increased due to loss of efficacy respond initially. However, nearly half lose the response after one year. The safety profile of an intensified infliximab regimen is good.

Surgical repair and biological therapy for fecal incontinence in Crohn's disease involving both sphincter defects and complex fistulas.

BACKGROUND AND AIMS: Surgeons have traditionally tried to avoid any complex surgical procedures in Crohn's patients with complex perianal diseases because of the fear of complications, worsening the patient's condition and risking an eventual proctectomy. The introduction of biological therapy has changed the management of Crohn's disease. This study assesses the long-term success of addressing defects in anal sphincter and complex fistula when patients receive anti-TNF-α antibodies. METHODS: Ten consecutive patients were prospectively scheduled for induction therapy with 5mg/kg Infliximab at week 0, 2 and 6 and maintenance every 8 weeks associated with azathioprine. Elective surgery was performed conducting a simultaneous approach to the sphincter defect and fistula tracts. Outcomes were long-term continence, complications which were assessed by a Wexner's score along with a complementary questionnaire. Statistical analysis was performed using general linear model of repeated measures. RESULTS: Three patients had complications related to surgery: two abscesses and low intersphincteric fistula and one case of rectal stenosis causing fecal urgency. There was no suture dehiscence. Wexner's score improved at 12 months (10.0±2.4 vs. 18.0±2.6; p=0.003) and over time (48 month 9.5±2.8; p=0.001). These scores were significantly worse when patients had urgency before treatment (12.8±1.2 vs. 9.5±2.8; p=0.03) but not when the urgency appeared later. No patient remained incontinent to solid stools. Three patients had occasional incontinence to liquid stools associated to disease reactivation. CONCLUSION: Surgical repair and immunomodulator therapy with infliximab could be an option in incontinent patients with Crohn's disease involving both a sphincter defect and severe or refractory fistulas.

[Intracranial gangliogliomas. A review of a series of 20 patients]. / Gangliogliomas intracraneales. Revisión de una serie de 20 pacientes.

INTRODUCTION: A ganglioglioma is a type of primary central nervous system low grade tumour composed of mixed populations of glial and neuroepithelial elements. They accounts for 0.4 to 2% of all intracranial tumours and appear more commonly in children and young adults. Seizures, which are the most important symptom in these tumours, improve significantly after surgical excision. METHODS: Between 1995 and 2008, 20 patients with (12 adults and 8 children) with intracranial ganglioglioma were treated at our hospital. Clinical information obtained by chart review included sex, age at onset of symptoms, clinical history, results of neurological examination, tumour location, CT and MRI appearance, surgical results and follow-up. All patients underwent tumour resection and the extent of surgery was determined from the surgical reports and postoperative imaging studies. RESULTS: The median age of patients was 26.4 years (range, 1-75 years), and the female to male ratio was 1.5:1. Except in one case, all patients had seizures with a median duration before diagnosis of 7.4 years (range 1-29). Seventeen tumours were located in the temporal lobe (9 right and 8 left). Macroscopically complete excision was performed in 17 patients and subtotal in the remaining 3. There were 4 cases of recurrence treated by surgery and radiotherapy being added in one case. The mean follow up was 8.5 years (range 22 months-14 years) and disease free survival at 5 years was 85% and an overall survival of 95%. CONCLUSIONS: The seizures, which are the most frequent symptoms, significantly improved after surgical removal. Surgery is the first choice of therapy in these tumours, and in the presence of subtotal resection or tumour recurrence the best indication for treatment is repeat surgery. Radiotherapy should be reserved only for malignant forms.

Thiopurine methyl-transferase activity and azathioprine metabolite concentrations do not predict clinical outcome in thiopurine-treated inflammatory bowel disease patients.

BACKGROUND: Low thiopurine-methyl-transferase (TPMT) activity and high 6-thioguanine-nucleotide (6TGN) concentrations have been linked to therapeutic success in inflammatory bowel disease patients treated with thiopurines; however, this has not been implemented in clinical practice. AIM: To identify a therapeutic threshold value for TPMT or 6TGN concentrations, and their capability to predict treatment safety and efficacy. METHODS: Prospective multicentre study including steroid-resistant/dependent patients starting thiopurines. The TPMT activity was determined at inclusion (>5 U/mL required). Azathioprine metabolites [6TGN, 6-methyl-mercaptopurine ribonucleotides (6MMP), and 6TGN/6MMP and 6TGN/TPMT ratios] were periodically monitored during steroid tapering and after withdrawal for 6 months or until a new flare occurred. RESULTS: A total of 113 patients were analysed (62% clinical response). Areas under the receiver operating characteristic (ROC) curve (AUC) relating clinical response and metabolite levels at 2, 4 and 6 months after steroid withdrawal were less than 0.7. The AUCs relating final response and initial TPMT activity or metabolite concentrations at 2, 4, 8 and 16 weeks after starting thiopurines were less than 0.7. No cut-off point with worthwhile sensitivity/specificity was found. Eight (7%) patients developed thiopurine-related toxicity that could not be linked to TPMT activity or 6TGN levels. CONCLUSIONS: Our results do not support determination of TPMT activity or 6TGN concentrations to predict treatment outcome, and no useful serum metabolites threshold value to adjust the drug's dose was identified.

Mercaptopurine rescue after azathioprine-induced liver injury in inflammatory bowel disease.

BACKGROUND: Azathioprine (AZA) liver toxicity arises in approximately 3% of inflammatory bowel disease patients and may result in treatment discontinuation. AIM: To describe the tolerance to mercaptopurine (MP) in patients with previous AZA-related liver injury. METHODS: Retrospective description of 31 patients (14 Crohn's, 17 ulcerative colitis), in which AZA therapy was interrupted because of liver injury, with MP started as alternative therapy. RESULTS: Mean AZA dose was 2.2 +/- 0.4 mg x kg/day. Median (interquartile range) of AZA exposure when liver injury was detected was 2 months (1-5.2). The type of AZA-related injury was cytolitic in 32%, cholestatic in 39% and mixed in 29%. After a median of 2.5 months (0.7-5.2), the therapy was switched to MP at a mean dose of 1.3 +/- 0.2 mg x kg/day. Median of follow-up of MP therapy was 32 months (8-54). In 87.1% of patients (95%CI: 70-96%), MP was tolerated without further liver injury; of these, 77.4% tolerated full MP doses and 9.7% tolerated lower doses. In a further cohort of 12.9% of patients, (95%CI: 3-29%), liver injury reappeared (two cholestasis, two mixed), 1-3 months after the onset of MP exposure. CONCLUSION: The administration of MP is a good alternative in patients with AZA-related liver injury, before thiopurines are definitely discarded.