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Sirs,

We read with great interest the studies by Sandhu et al.[1] and Mohabbat et al.,[2] which evaluated antitumour necrosis factor-alpha (TNFα) therapy for patients with refractory inflammatory bowel disease (IBD) post orthotopic liver transplant (OLT). To date, there have been only 18 patients treated with anti-TNF for relapsing IBD following OLT; this number includes patients with UC, CD, indeterminate colitis and pouchitis.[1-5] Such data are often not homogeneous in terms of administered therapy and outcomes.

We have evaluated the efficacy and safety of infliximab therapy in a homogeneous series of patients with refractory UC following OLT for advanced-stage primary sclerosing cholangitis (PSC). Four patients (all male patients; median age 39 years, range 22–54 years) with UC (n = 3) or pouchitis (n = 1) who underwent OLT were identified (Table 1). The median duration of infliximab therapy was 18 months (range: 3–30).

Table 1. Case serials of patients treated with infliximab therapy for UC and pouchitis following orthotopic liver transplantation
CaseAge (years)GenderIndication for OLTAge at PSCAge at OLTAnti rejection therapyAge at UCDuration of IFX therapy (months)Pre-anti- IFX MSSPost-anti-IFX MSSPre-anti-IFX PDAIPost-anti-IFX PDAIPre-anti-IFX MCESIPost-anti-IFX MCSIAdverse events after IFXHepatic rejection
  1. a

     Significative median MMS score decreased after infliximab therapy it was observed, from 9 (range: 7–10) to 1.0 (range: 0–3) (P < 0.0001).

  2. b

     No significant difference in PDAI after infliximab therapy it was observed, from 14 to 12 (P = NS).

130MalePSC1224Tacrolimus 1 mg + 1.5 mg/day; Azathiprine 75 mg/day; Prednisone 5 mg/day53010030 Molluscum contagiosum No
248MalePSC2342Tacrolimus 3.5 mg + 3.5 mg/day21289322NoneNo
322MalePSC1516, 21Ciclosporine 250 mg + 200 mg/day123712Wait endoscopyNone 
454MalePSC4245Tacrolimus 1 mg + 1.5 mg/day; Sirolimus 3 mg/day3212 14 12NoneNo
Tot.Median age, range (years)GenderPSCMedian age, range (years)Median age, range (years) Median age, range (years)Median age, range (months)Median Pre-anti-IFX MSS, rangeMedian Post-anti-IFX MSS, rangePre-anti-IFX PDAIPost-anti-IFX PDAIMedian Pre-anti IFX MCESI, range

Median Post-anti-IFX

MCSI, range

Number, percentageNumber, percentage
439 (22–54)4/4 Male4/419 (12–42)33 (24–45) 16.5 (5–32)18 (3–30)9 (7–10)1.0a (0–3)1412b2 (2–3)1 (0–2)1/4 (25%)0/4 (0%)

Three patients (75%) experienced sustained improvement of IBD. A significant decrease in Mayo score was observed after infliximab therapy, from a mean score of 9.0 (range: 7–10) to a mean score of 1.0 (range: 0–3) (P < 0.0001) (Figure 1). At week 54, complete mucosal healing (defined as absence of lesions) was observed in one of three patients (33%). In the one patient with refractory pouchitis, a nonstatistically significant decrease in pouch disease activity index was observed (from 14 to 12). Subsequently, this patient presented with worsening of endoscopic lesions after interruption of infliximab therapy, and he underwent ileostomy.

image

Figure 1. MSS score before and after IFX therapy. Significant decrease in median Mayo score system (MMS) after infliximab therapy was observed from 9.0 (range 7–10) to 1.0 (range 0–3) (P < 0.0001)*.

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Steroid treatment was successfully withdrawn during infliximab therapy in all patients. Adverse events included only one infection by Molluscum contagiosum, which resolved without sequelae. No malignancies were observed in any patient following infliximab therapy. No cases of hepatic rejection were documented. One patient (25%) presented with a recurrence of PSC 2 years before infliximab therapy (3 years after OLT) and he underwent a second OLT 5 years after the first.

Our results are consistent with the studies of Sandhu and Mohabbat and are in line with data on IBD patients who have not previously undergone liver transplantation. We assessed a homogenous series of refractory UC patients, who were treated with the same anti-TNFα agent. In previous studies, some patients were treated with infliximab[3-5] others with adalimumab[5] and others patients with adalimumab for secondary loss of response to infliximab.[4] Mucosal healing has been previously evaluated in only three studies.[1, 3-5] Moreover, in contrast to previous reports, we objectively assessed clinical response, utilising a clinical score for UC and pouchitis, and assessed mucosal healing using an endoscopic score.

In conclusion, our small study supports previous data on the efficacy and safety of infliximab therapy in patients with refractory UC after OLT, and adds new data on a homogenous population with UC and previous OLT, all treated by infliximab. Although no cases of hepatic graft dysfunction or rejection were observed, larger studies are need to evaluate the safety profile of biological therapy combined with anti rejection treatment in patients with refractory IBD following liver transplantation.

Acknowledgement

  1. Top of page
  2. Acknowledgement
  3. References

Declaration of personal and funding interests: None.

References

  1. Top of page
  2. Acknowledgement
  3. References
  • 1
    Sandhu A, Alameel T, Dale CH, Levstik M, Chande N. The safety and efficacy of antitumor necrosis factor-alpha therapy for inflammatory bowel disease in patients post liver transplantation: a case series. Aliment Pharmacol Ther 2012; 36: 15965.
  • 2
    Mohabbat AB, Sandborn WJ, Loftus EV Jr, Wiesner RH, Bruining DH. Anti-tumor necrosis factor treatment of inflammatory bowel disease in liver transplant recipients. Aliment Pharmacol Ther 2012; 36: 56974.
  • 3
    Lal S, Steinhart AH. Infliximab for ulcerative colitis following liver transplatation. Eur J Gastroenterol Hepatol 2007; 19: 27780.
  • 4
    El-Nachef N, Terdiman J, Mahdevan U. Anti-tumor necrosis factor therapy for inflammatory bowel disease in the setting of immunosuppression for solid organ transplantation. Am J Gastroenterol 2010; 105: 12101.
  • 5
    Indriolo A, Fagiuoli S, Pasulo L, et al. Infliximab in patients with ulcerative colitis and primary sclerosing cholangitis before and after liver transplantation. JCC 2012; 6(Suppl. 1): S117.