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A 54 year old man was treated with pegylated interferon alpha 2a 180 μg weekly and ribavirin 1000 mg daily for chronic hepatitis C genotype 3a (>5×105 IU/ml). There was no history of gastrointestinal disease or morbidity.
At week 12, hepatitis C virus-polymerase chain reaction (HCV-PCR) was negative and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels remained elevated at 2–3 times above the upper limit. Continuation of this well tolerated therapy was planned until week 24.
However, at week 14, the patient reported a sudden onset of watery and sometimes bloody diarrhoea. Colonoscopy showed continuous pancolitis, macroscopically suggestive of inflammatory bowel disease (IBD). Histology revealed a severe highly active pancolitis with basal plasmocytosis, crypt abscesses, and crypt distortion, as seen in ulcerative colitis.
The antiviral treatment was stopped and treatment with prednisone and mesalazine (5-ASA) was initiated. Steroids were tapered over four weeks, which had been ongoing with clinical remission. 5-ASA was continued at a dose of 3 g daily for eight weeks followed by 2 g daily.
Three months later (receiving 5-ASA 2 g daily) there was complete clinical and endoscopic remission. Histology showed a mild residual increase in mononuclear inflammatory cells. PCR revealed a virological relapse of HCV (high viraemia >6×105 IU/ml) and an unchanged twofold elevation in ALT and AST.
We suspect that the ulcerative colitis-like severe pancolitis in this patient with no history of IBD was probably an adverse effect of the antiviral treatment with interferon/ribavirin rather than a concomitant disease. Similar observations have been made by others.1–3 To our knowledge, the present case is the fourth reported in the literature. Interferon has immune stimulating properties4 and may trigger autoimmune diseases and transplant rejections.5
Hence, in light of this, the report on interferon treatment in active ulcerative colitis (Gut 2003;52:1728–33) seems interesting and warrants further research.
As interferon alpha (IFN alpha) suppresses the synthesis of proinflammatory cytokines and induces various anti-inflammatory cytokines, it may show efficacy in chronic inflammatory disorders of the gut. In Crohn’s disease, lamina propria cells manifest increased secretion of IFN-γ whereas in ulcerative colitis lamina propria cells and natural killer T cells demonstrate increased secretion of the Th2 cytokines interleukin 5 (IL-5) and IL-13.1,2
IFN alpha has been demonstrated to potently suppress synthesis of both IL-5 and IL-13 in human leucocytes, making it an attractive agent for the treatment of ulcerative colitis. IFN alpha therapy showed no benefit in patients with Crohn’s disease.3 This may be explained by the fact that Crohn’s disease is thought to be a Th1 linked disease. IFN alpha therapy seems to be more successful in chronic active ulcerative colitis, a more Th2 linked disorder. Sumer and Palabiyikoglu reported that more than 80% of patients with active ulcerative colitis responded to high dose IFN alpha therapy within two weeks of treatment and were in complete clinical and endoscopic remission after six months of therapy.4 Madsen et al recently presented a study comparing systemic IFN alpha therapy and prednisolone enemas in the treatment of left sided ulcerative colitis.5 Ulcerative colitis is accompanied by high levels of IL-5 in colonic tissue and IFN alpha effectively suppresses IL-5 synthesis in leucocytes. IFN beta has been used in a pilot study investigating its role in patients with steroid refractory active UC.6 In this study, a high responder rate was observed with a mean time to response of three weeks.
Another IFN beta study in ulcerative colitis has been presented recently.7 In this small, placebo controlled, randomised, dose escalating study, clinical improvement was observed in 50% of IFN beta treated patients compared with 14% in the placebo group. We recently presented data on the first placebo controlled use of IFN alpha in the treatment of active UC in patients with or without corticosteroid and/or immunosuppressive treatment.8 We observed no significant advantage of any IFN group over placebo but did not observe worsening of disease in any IFN treated patient.
The mechanisms of action of IFN alpha are probably multiple but the possible interactions of IFN alpha with the cytokine cascade and immune system are usually not considered. Favouring Th1 responses and suppressing Th2 type immune responses could imply that type I IFNs may be therapeutic in diseases such as ulcerative colitis or allergic disorders. We agree with the authors that IFN alpha might have the potential to enhance inflammatory reactions and alloreactivity in certain situations but are also convinced that it has strong immunomodulatory and anti-inflammatory properties. Larger controlled trials with IFN alpha in ulcerative colitis are eagerly awaited.
Conflict of interest: None declared.
Conflict of interest: None declared.
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