A case of non-cirrhotic portal hypertension related to azathioprine therapy in a patient with Crohn’s disease

Medical therapy for Crohn’s disease has changed significantly over the past 20 years with the increasing use of immunosuppressants. In contrast, surgery rates are still high and evidence about the the changes in the outcome of Crohn’s disease over the past decades is scarce. Aims: The objective of this study was to analyze the evolution of the surgical rates and medical therapy in the population-based Veszprém county database. Methods: Data of 506 Crohn’s disease patients were analyzed (age at diagnosis: 31.5 years, SD: 13.8 years). Both hospital and outpatient records were collected and comprehensively reviewed. The study population was divided into three groups based on the year of diagnosis (cohort A: 1977–1989, cohort B: 1990–1998 and cohort C: 1999–2008). Results: Overall azathioprine, systemic steroid, and biological (only available after 1998) exposure was 45.8, 68.6, and 9.5%, respectively. The 1 and 5-year probabilities of azathioprine use were 3.2 and 6.2% in cohort A, 11.4 and 29.9% in cohort B, and 34.8 and 46.2% in cohort C. In multivariate analysis, decade of diagnosis (P<0.001), age at onset (P = 0.008), disease behavior at diagnosis (P<0.001), and need for systemic steroids (P<0.001) were significantly associated with the time to initiation of azathioprine therapy. Early azathioprine use was significantly associated with the time to intestinal surgery in Crohn’s disease patients; in a multivariate Cox analysis (HR: 0.43, 95% confidence interval (CI): 0.28–0.65) and after matching on propensity scores for azathioprine use (HR: 0.42,95% CI:0.26–0.67). Conclusions: This population-based inception cohort showed that reduction in surgical rates was independently associated with increased and earlier azathioprine use. Orv. Hetil., 2012, 153, 541–552.

Download Full-text

Early Azathioprine Therapy Is No More Effective Than Placebo for Newly Diagnosed Crohn's Disease

Gastroenterology ◽

10.1053/j.gastro.2013.06.009 ◽

2013 ◽

Vol 145 (4) ◽

pp. 766-774.e1 ◽

Cited By ~ 164

Author(s):

Julián Panés ◽

Antonio López–SanRomán ◽

Fernando Bermejo ◽

Valle García–Sánchez ◽

Maria Esteve ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Newly Diagnosed ◽

Azathioprine Therapy

Download Full-text

Metastatic Hepatocellular Carcinoma in a Patient with Crohn’s Disease Treated with Azathioprine and Infliximab: A Case Report and Literature Review

Case Reports in Gastrointestinal Medicine ◽

10.1155/2014/340836 ◽

2014 ◽

Vol 2014 ◽

pp. 1-4 ◽

Cited By ~ 3

Author(s):

Kyle J. Fortinsky ◽

Ali Alali ◽

Khursheed Jeejeebhoy ◽

Sandra Fischer ◽

Morris Sherman ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Crohn’S Disease ◽

Liver Disease ◽

Crohn's Disease ◽

Case Reports ◽

Future Research ◽

Azathioprine Therapy ◽

Additional Risk ◽

Early Imaging ◽

History Of

Hepatocellular carcinoma most commonly occurs in patients with underlying liver disease or cirrhosis. We describe a case of hepatocellular carcinoma in a 34-year-old man with Crohn’s disease treated with azathioprine and infliximab. The patient had no history of liver disease and a complete autoimmune and viral workup was unremarkable. Unfortunately, the patient developed widespread metastatic disease and passed away 5 months after his initial diagnosis. The mechanism of hepatocellular carcinoma in patients’ with Crohn’s disease is poorly understood and may include both autoimmunity and treatment-related complications. Previous case reports suggest the possibility of a concerning association between azathioprine therapy and the development of hepatocellular carcinoma in patients with Crohn’s disease. Clinicians may consider early imaging in patients with Crohn’s disease presenting with concerning symptomatology or abnormal liver enzymes, especially in those being treated with azathioprine alone or in combination with infliximab. Future research may help to uncover additional risk factors for this exceedingly rare diagnosis in this patient population.

Download Full-text

Severe complication during remission of Crohn’s disease: hemophagocytic lymphohistiocytosis due to acute cytomegalovirus infection

Zeitschrift für Gastroenterologie ◽

10.1055/s-0043-123999 ◽

2018 ◽

Vol 56 (03) ◽

pp. 259-263 ◽

Cited By ~ 1

Author(s):

Jan Miechowiecki ◽

Waltraud Stainer ◽

Gertraud Wallner ◽

Herwig Tuppy ◽

Walter Aichinger ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Hemophagocytic Lymphohistiocytosis ◽

Killer Cell ◽

Immunosuppressive Treatment ◽

Symptomatic Therapy ◽

Cmv Infection ◽

Azathioprine Therapy ◽

Elevated Liver Enzymes ◽

Acute Cytomegalovirus

Abstract Introduction Immunosuppressive therapy is today’s standard treatment of patients with moderate to severe inflammatory bowel disease (IBD). The risk for opportunistic infections is increased due to this therapy and is a concern in the management of patient with IBD undergoing such a treatment. Case report In this paper, we describe a case of an acute cytomegalovirus (CMV) infection in a 35-year-old male patient with Crohn’s disease being in remission while receiving azathioprine therapy. His clinical presentation was high-grade fever, night sweats, skin rash, and abdominal pain.Laboratory findings showed pancytopenia, elevated liver enzymes, and high ferritin levels. Sonographic examination revealed splenomegaly and serological analysis proved an acute CMV infection. The severity of the acute illness and these results in the setting of immunosuppressive treatment with azathioprine were highly suspicious of hemophagocytic lymphohistiocytosis (HLH).Further investigations including bone marrow biopsy, analysis of natural killer cell function, and measurement of T-cell activity confirmed the suspected diagnosis. Treatment consisted of antiviral and symptomatic therapy. Discussion and conclusion HLH is a rare and severe condition triggered by uncontrolled stimulation of histiocytes and lymphocytes, resulting in abnormal cytokine production. The causes can be primary (genetic) or secondary due to acquired immunodeficiency or viral infections such as CMV. Several symptoms of this condition are unspecific, but the summary of clinical symptoms and signs are diagnostic. Treatment consists of specific intervention if possible and application of immunosuppressive drugs such as corticosteroids.

Download Full-text

P066 Human intestinal Vδ2+ T-cells promote mucosal inflammation in Crohn's disease and are selectively ablated by azathioprine therapy

Journal of Crohn s and Colitis ◽

10.1016/s1873-9946(13)60088-4 ◽

2013 ◽

Vol 7 ◽

pp. S35-S36

Author(s):

N. McCarthy ◽

C. Hedin ◽

Z. Bashir ◽

A. Vossenkämper ◽

E. Giles ◽

...

Keyword(s):

T Cells ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Mucosal Inflammation ◽

Azathioprine Therapy

Download Full-text

6-Thioguanosine Diphosphate and Triphosphate Levels in Red Blood Cells and Response to Azathioprine Therapy in Crohn’s Disease

Clinical Gastroenterology and Hepatology ◽

10.1016/s1542-3565(05)00697-x ◽

2005 ◽

Vol 3 (10) ◽

pp. 1007-1014 ◽

Cited By ~ 64

Author(s):

M NEURATH ◽

R KIESSLICH ◽

U TEICHGRABER ◽

C FISCHER ◽

U HOFMANN ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Red Blood Cells ◽

Blood Cells ◽

Azathioprine Therapy

Download Full-text

Azathioprine therapy selectively ablates human Vδ2+ T cells in Crohn’s disease

Journal of Clinical Investigation ◽

10.1172/jci80840 ◽

2015 ◽

Vol 125 (8) ◽

pp. 3215-3225 ◽

Cited By ~ 27

Author(s):

Neil E. McCarthy ◽

Charlotte R. Hedin ◽

Theodore J. Sanders ◽

Protima Amon ◽

Inva Hoti ◽

...

Keyword(s):

T Cells ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Azathioprine Therapy

Download Full-text

Predictors of efficacy, mucosal healing and dose intensification during the first year of adalimumab therapy in patients with luminal and fistulizing Crohn’s disease. National data from Hungary

Orvosi Hetilap ◽

10.1556/oh.2011.29200 ◽

2011 ◽

Vol 152 (36) ◽

pp. 1433-1442 ◽

Cited By ~ 1

Author(s):

Lajos Sándor Kiss ◽

Tamás Szamosi ◽

Tamás Molnár ◽

Pál Miheller ◽

László Lakatos ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Clinical Efficacy ◽

Mucosal Healing ◽

C Reactive Protein ◽

Medium Term ◽

Dose Intensification ◽

Azathioprine Therapy ◽

Reactive Protein ◽

Adalimumab Therapy

Adalimumab is a fully human monoclonal antibody targeting tumor necrosis factor with proven efficacy in the treatment of Crohn’s disease in clinical trials. The aim of the present study was to investigate the predictors of medium term clinical efficacy and mucosal healing during adalimumab therapy in patients with Crohn’s disease in specialized centers approved for biological therapy in Hungary. Methods: Data of 201 Crohn’s disease patients were prospectively captured (male/female: 112/89, median age: 24 years, duration: 8 years). Previous infliximab therapy was given in 97 (48.3%) patients, concomitant steroids in 41.3% and azathioprine in 69.2% (combined: 26.4%) of patients. Results: Overall clinical response and remission rates at 24 and 52 weeks were 78% and 52%, and 69.4% and 44.4%, respectively. Endoscopic improvement and healing was achieved in 43.1% and 23.6%, respectively. In a logistic regression model, clinical efficacy and normalized C-reactive protein at week 12, need for combined immunosuppression at induction, shorter disease duration and smoking were identified as independent predictors for 12-month clinical outcome, while normalized C-reactive protein at week 12, clinical remission at week 24, frequency of previous relapses and smoking were associated to endoscopic improvement/healing. Dose intensification to weekly dosing was needed in 16.4%. Parallel azathioprine therapy and clinical remission at week 12 was inversely associated to dose escalation to weekly dosing. Conclusion: Clinical efficacy and normalized C-reactive protein at week 12, need for combined immunosuppression, luminal disease and smoking are predictors for medium term clinical efficacy/mucosal healing during adalimumab therapy, while parallel azathioprine therapy may decrease the probability for dose escalation. Orv. Hetil., 2011, 152, 1433–1442.

Download Full-text