Dear Sir,

Infliximab is the only biological agent approved for the treatment of ulcerative colitis (UC). 1 Its efficacy is only counterbalanced by the increased risk of severe infections and its own immunogenicity that may limit its applicability because of acute infusion reactions and loss of efficacy. Since most clinical data come from RCTs, there is limited experience with the use of infliximab among patients with UC and concomitant conditions that may increase the risk of infections. We report the case of a patient with alcoholic cirrhosis with portal hypertension, chronic pancreatitis, and ulcerative colitis treated with infliximab.

A 45-year-old Caucasian male was admitted in our hospital because of a moderate acute flare of UC. He was a smoker and had been a heavy drinker until two years before, when he was diagnosed of alcoholic cirrhosis and portal hypertension because of his first ascites episode which was successfully treated with diuretics. He remained asymptomatic and teetotaller thereafter. He was diagnosed of distal UC when he was 42-year-old, and successfully treated with mesalazine until four weeks before when he was admitted because an endoscopically proven moderate attack of UC. The patient did not respond to i.v. steroids (≡ 1 mg/kg/day prednisone) and topical mesalazine. After ruling out CMV infection, i.v. cyclosporine A was started, resulting in a slow but progressive clinical and biological improvement. During this admission, he was also diagnosed of chronic pancreatitis with both exocrine and endocrine insufficiency, requiring insulin and pancreatic enzyme replacement therapy. He was discharged on azathioprine 2 mg/kg/day and tapering dose of steroids. However, two weeks later he came back because of clinical worsening with increased stool movements, rectal bleeding, diffuse abdominal pain, and fever. A complete work-up to rule-out systemic infections was negative, and i.v. steroids were re-started, without clinical improvement. Infliximab was started at conventional doses (5 mg/kg) once latent tuberculosis (negative tuberculin skin test plus booster test, normal chest X-ray) and viral hepatitis infections were ruled out. The clinical and biological response was excellent already after the first infusion. The patient completed a 3-infusion schedule together with oral cotrimoxazole to prevent Pneumocystis jirovecii infection. Afterwards, cotrimoxazole was discontinued and the patient was put on azathioprine maintenance therapy. Three months after discharge, he remains in clinical remission, without either infectious or cirrhosis-related complications.

Cirrhotic patients are particularly prone to infections due to several reasons including increased bacterial translocation, decreased hepatic complement production and impaired phagocytic function of both circulating neutrophils and resident liver macrophages (Kupffer cells). This high risk of infections in cirrhosis could even increase in case of immunosuppressant therapies. In this sense, our positive experience with this patient is noteworthy and quite unique. Indeed, after an extensive literature search we have been able to find out only the case of one patient α1-antitrypsin deficiency-associated cirrhosis treated with infliximab for psoriatic arthritis, who did not develop any infection. 2 However, it should be stressed that this and our patient were abstinent and without clinical or biological signs suggestive of associated alcoholic hepatitis. In spite that tumour necrosis factor-alpha (TNFα) has been demonstrated to play an important role the pathophysiology of alcoholic hepatitis, 3 the experience with anti-TNFα monoclonal antibodies in this setting has been somewhat disappointing. Two preliminary trials suggested that a single infusion of infliximab, either alone or in combination with steroids, could be useful and safe in the treatment of severe alcoholic hepatitis. 4 , 5 However, a larger trial where patients with severe alcoholic hepatitis were randomly assigned to receive i.v. infusions of infliximab (10 mg/kg) or placebo at weeks 0, 2, and 4, in addition to prednisolone (40 mg/day) for 28 days, was prematurely stopped only 36 patients had been randomised due to a significantly higher rate of adverse events, mainly infections, in the infliximab group. 6 It can be argued that the dose of infliximab used might be too high, but anyway this negative experience has prevented the performance of further trials using this strategy in alcoholic hepatitis.

In summary, the case reported here suggests that infliximab might be safely used in IBD patients with associated alcoholic cirrhosis, provided that there is no suspicion of associated alcoholic hepatitis. Of course, one must be also very cautious in those patients with cirrhosis of viral etiology in whom signs of viral replication have to be searched for and treated appropriately.

References

1
Rutgeerts
P.
Sandborn
W.J.
Brian
G.F.
et al
Infliximab for induction and maintenance therapy for ulcerative colitis
N Engl J Med
 
353
2005
2462
2476
2
Lehnen
M.
Franckson
T.
Knab
J.
Hoeft
D.
Grabbe
S.
Dissemond
J.
Successful infliximab therapy of psoriasis vulgaris and psoriatic arthritis in a patient with cirrhosis
Br J Dermatol
 
153
2005
212
214
3
Tilg
H.
Diehl
A.M.
Cytokines in alcoholic and nonalcoholic steatohepatitis
N Engl J Med
 
343
2000
1467
1476
4
Spahr
L.
Rubbia-Brandt
L.
Frossard
J.
et al
Combination of steroids with infliximab or placebo in severe alcoholic hepatitis: a randomized controlled pilot study
J Hepatol
 
37
2002
448
455
5
Tilg
H.
Jalan
R.
Kaser
A.
et al
Anti-tumor necrosis factor-alpha monoclonal antibody therapy in severe alcoholic hepatitis
J Hepatol
 
38
2003
419
425
6
Naveau
S.
Chollet-Martin
S.
Dharancy
S.
et al
A double-blind randomized controlled trial of infliximab associated with prednisolone in acute alcoholic hepatitis
Hepatology
 
39
2004
1390
1397