Treatment of Chronic Hepatitis C in Patients With Crohn's Disease

Patients with Crohn's disease (CD) have an increased prevalence of hepatitis C (HCV) infection as compared to the general population because of the need for blood transfusions and multiple surgical and/or endoscopic procedures.¹ The dilemma facing clinicians is the possibility that HCV therapy could flare a patient with stable CD. However, it is difficult to withhold potentially curative HCV treatment and risk progression to advanced liver disease. The medical literature provides little guidance for the challenge of how to approach this situation or what is the long-term outcome of untreated HCV in an immunosuppressed patient with CD.

Interferon-α has immunomodulatory properties that may impact immune pathways that control and may even induce inflammatory bowel disease (IBD) or other immune-mediated diseases. Patients with autoimmune diseases have been excluded from HCV clinical trials, and in clinical practice, these patients are not usually treated for HCV due to the high likelihood of inducing a flare of the immune-mediated condition.² It is well recognized that in chronic hepatitis B viral infection, corticosteroids, anti –tumor necrosis factor (TNF)-α agents, and other immunosuppressant medications can cause a hepatitis flare, whereas in chronic HCV, there is little information regarding the effect of immunomodulatory drugs on the clinical course of liver disease in CD patients.^1,3

To date, the available information suggests that HCV should not influence treatment strategies for CD. However, immunosuppressive therapies for IBD such as corticosteroids, azathioprine, and 6-mercaptopurine may decrease the therapeutic effects of antiviral therapy. Corticosteroid immunosuppression has been shown to accelerate the progression of fibrosis and the development of cirrhosis in HCV.⁴ Although antiviral therapy for HCV may be utilized in combination with immunosuppression, sustained viral response (SVR) rates in the transplant population are significantly decreased when compared to SVR rates in nonimmunosuppressed individuals.⁵ Scherzer and colleagues⁶ recently reported a series of 11 patients with CD and HCV who were treated for HCV. Four (3 on azathioprine and 1 on mycophenolate mofetil) of the 11 patients were on immunosuppressive therapy, and 2 of these patients achieved sustained virologic response—a rate that was comparable to the patients without immunosuppressive therapy. An increase in CD activity occurred in 6 of the 11 patients (55%) while on HCV therapy, resulting in a short course of corticosteroids in 4 patients. In these patients, corticosteroid treatment did not increase HCV RNA levels while continuing antiviral therapy.

There is a single case report of the use of an anti-TNF-α agent to control a flare of CD while undergoing treatment for HCV.⁷ Anti-TNF-α agents do not generally increase HCV RNA levels in CD patients or rheumatoid arthritis patients^8,9 and do not appear to interfere with treatment of HCV.^7,10 Gupta and Sitrin¹¹ have taken another approach to avoid possible immunosuppressive interference with HCV treatment by taking advantage of the high first-pass hepatic metabolism of budesonide. In their case study, the CD patient experienced a flare of his condition after 13 weeks of treatment for HCV and was treated with 9 mg daily of delayed-release budesonide. He was able to remain on HCV treatment and achieved SVR. The authors reported that the patient had been in remission for 15 years on oral mesalamine; however, he had terminal ileal inflammation and ulceration on colonoscopy 2 years before starting HCV therapy, suggesting persistent active disease. Documentation that a patient is in clinical remission (including C-reactive protein and fecal lactoferrin or calprotectin) and/or endoscopic remission is advisable prior to starting treatment of HCV. After 8 months on budesonide, while continuing treatment for HCV, the patient flared, resulting in 15–20 stools per day and fecal incontinence. Despite these symptoms, he was able to complete his HCV therapy. As the authors noted, budesonide, as with all corticosteroids, has not been shown to maintain remission in CD, though it may delay relapse for several months compared to placebo.¹² One can speculate on the outcome if the patient had been treated intermittently with budesonide as needed through the course of his HCV treatment or if an anti-TNF-α agent had been started, but the literature is too sparse to recommend any standard approach. Not all CD patients experience a CD flare on HCV therapy, as demonstrated in the series by Scherzer and coworkers, in which 45% of the CD patients did not flare, including those who were only on mesalamine.⁶ Thus, for the CD patient in remission, a recommendation to start any particular medication before initiation of HCV therapy to try to keep the CD in remission during HCV therapy does not appear to be justified.

The 2002 National Institutes of Health Consensus Statement on Management of Hepatitis C states that “all patients with chronic hepatitis C are potential candidates for antiviral therapy” and that “treatment is recommended for patients with an increased risk of developing cirrhosis.”¹³ The consensus statement does have a caveat that in some populations, such as those with autoimmune diseases, the risks and benefits of therapy should be determined on an individual basis. Given the potential outcome of severe CD versus developing cirrhosis from untreated HCV, a thorough assessment of the risks and outcomes is required, as well as a planned treatment approach, should treatment of HCV result in a CD flare.