Antiviral Therapy in Patients With Crohn's Disease and Chronic Hepatitis C
Antiviral Therapy in Patients With Crohn's Disease and Chronic Hepatitis C
Background: Efficacy and safety of antiviral combination therapy in patients with Crohn's disease (CD) and chronic hepatitis C (CHC) is presently not established and consequently CHC is rarely treated in CD patients.
Aim: To analyse the efficacy and tolerability of antiviral interferon/ribavirin therapy in patients with CHC and CD.
Methods: Eleven HCV-infected CD patients received either 3 × 1.5 µg/kg/week interferon-α-2b or 180 µg/week peginterferon-α-2a (PEGASYS; Roche, Basel, Switzerland) as monotherapy (n = 1) or in combination with 800–1200 mg/day ribavirin (COPEGUS; Roche) (n = 10) for 24–54 weeks according to HCV-genotype and initial response respectively. Eight patients were under CD-specific therapy.
Results: Five (46%) patients (HCV-1: n = 3; HCV-2: n = 0; HCV-3: n = 1; unknown: n = 1) achieved a sustained virological response, three (27%) patients relapsed, three (27%) were nonresponders (all GT 1b). At baseline, the Harvey–Bradshaw Index was 0 (0–8) [median (range)], increased on antiviral therapy to 4 (1–15) (P = 0.005) and decreased to baseline level 0 (0–6) after 6-month follow-up.
Conclusions: This preliminary experience demonstrates that treatment of CHC in patients with CD is comparable to the treatment of CHC in those without CD. However, gastrointestinal symptoms may be temporarily exacerbated and haemopoietic growth factors may be required.
About 123 million people are infected by the hepatitis C virus (HCV) worldwide. In Western Europe, the prevalence of chronic HCV infection varies from about 0.1% in the North to 1% of the population in the South and ranges from 0.4 to 4.9% in Eastern Europe. The main risk factors for HCV infection are blood transfusions, intravenous drug abuse, unsafe therapeutic injections and other health care related procedures. HCV infection (chronic hepatitis C) is a slowly progressive disease, which may lead to severe liver cirrhosis with a high risk of hepatocellular carcinoma (HCC). Therefore, antiviral treatment with pegylated interferon (IFN)-alpha and ribavirin is recommended in patients with chronic HCV infection.
Patients with longstanding inflammatory bowel disease (IBD) including Crohn's disease (CD) and ulcerative colitis (UC) have an increased risk for infections with the hepatitis B virus (HBV) and the HCV because of the need for blood transfusions during surgery or for severe anaemia. In Italy, in one study investigating 332 patients with CD and UC, the prevalence of either hepatitis B or C was 24.7%. Furthermore, the incidence of HCV infection is higher in CD patients undergoing surgery (7.4%) than in UC patients.
Current treatment regimes in patients with IBD include immunosuppressive drugs. Nevertheless, three-quarter of CD patients have to undergo surgery during lifetime. Chronic viral infections in immunosuppressed patients are topics of great interest. Several cases of reactivation of hepatitis B (HBV) infections in IBD patients receiving infliximab have been reported, including one who died. Infliximab should not be given in HBV infection without antiviral therapy contrary to HCV infection. Therefore, a screening for infectious diseases is recommended in IBD patients. However, guidelines for antiviral therapy on IBD-specific treatment would be very useful. Studies investigating the impact of immunosuppression in HCV patients after liver transplantation suggested that immunosuppression may augment liver damage ultimately leading to cirrhosis, portal hypertension and HCC. The effect of immunosuppression on the course of HCV infection in IBD patients remains unclear.
Interferon-alpha was used to treat UC, and CD with limited success was generally well tolerated, but some IBD flares were reported during or after IFN-alpha therapy. Therefore, gastroenterologists are reluctant in treating IBD patients with IFN-alpha. Only a few case reports of successfully treated IBD/HCV patients have been published, using various older or current standard regimes using pegylated IFN-alpha and ribavirin.
In this retrospective analysis, we present the largest group of CD patients with chronic hepatitis C receiving antiviral therapy, most of them treated with currently recommended HCV regimes with pegylated IFN and ribavirin. Efficacy and safety of this therapy were investigated. Several patients were under ongoing immunomodulatory therapy.
Abstract
Background: Efficacy and safety of antiviral combination therapy in patients with Crohn's disease (CD) and chronic hepatitis C (CHC) is presently not established and consequently CHC is rarely treated in CD patients.
Aim: To analyse the efficacy and tolerability of antiviral interferon/ribavirin therapy in patients with CHC and CD.
Methods: Eleven HCV-infected CD patients received either 3 × 1.5 µg/kg/week interferon-α-2b or 180 µg/week peginterferon-α-2a (PEGASYS; Roche, Basel, Switzerland) as monotherapy (n = 1) or in combination with 800–1200 mg/day ribavirin (COPEGUS; Roche) (n = 10) for 24–54 weeks according to HCV-genotype and initial response respectively. Eight patients were under CD-specific therapy.
Results: Five (46%) patients (HCV-1: n = 3; HCV-2: n = 0; HCV-3: n = 1; unknown: n = 1) achieved a sustained virological response, three (27%) patients relapsed, three (27%) were nonresponders (all GT 1b). At baseline, the Harvey–Bradshaw Index was 0 (0–8) [median (range)], increased on antiviral therapy to 4 (1–15) (P = 0.005) and decreased to baseline level 0 (0–6) after 6-month follow-up.
Conclusions: This preliminary experience demonstrates that treatment of CHC in patients with CD is comparable to the treatment of CHC in those without CD. However, gastrointestinal symptoms may be temporarily exacerbated and haemopoietic growth factors may be required.
Introduction
About 123 million people are infected by the hepatitis C virus (HCV) worldwide. In Western Europe, the prevalence of chronic HCV infection varies from about 0.1% in the North to 1% of the population in the South and ranges from 0.4 to 4.9% in Eastern Europe. The main risk factors for HCV infection are blood transfusions, intravenous drug abuse, unsafe therapeutic injections and other health care related procedures. HCV infection (chronic hepatitis C) is a slowly progressive disease, which may lead to severe liver cirrhosis with a high risk of hepatocellular carcinoma (HCC). Therefore, antiviral treatment with pegylated interferon (IFN)-alpha and ribavirin is recommended in patients with chronic HCV infection.
Patients with longstanding inflammatory bowel disease (IBD) including Crohn's disease (CD) and ulcerative colitis (UC) have an increased risk for infections with the hepatitis B virus (HBV) and the HCV because of the need for blood transfusions during surgery or for severe anaemia. In Italy, in one study investigating 332 patients with CD and UC, the prevalence of either hepatitis B or C was 24.7%. Furthermore, the incidence of HCV infection is higher in CD patients undergoing surgery (7.4%) than in UC patients.
Current treatment regimes in patients with IBD include immunosuppressive drugs. Nevertheless, three-quarter of CD patients have to undergo surgery during lifetime. Chronic viral infections in immunosuppressed patients are topics of great interest. Several cases of reactivation of hepatitis B (HBV) infections in IBD patients receiving infliximab have been reported, including one who died. Infliximab should not be given in HBV infection without antiviral therapy contrary to HCV infection. Therefore, a screening for infectious diseases is recommended in IBD patients. However, guidelines for antiviral therapy on IBD-specific treatment would be very useful. Studies investigating the impact of immunosuppression in HCV patients after liver transplantation suggested that immunosuppression may augment liver damage ultimately leading to cirrhosis, portal hypertension and HCC. The effect of immunosuppression on the course of HCV infection in IBD patients remains unclear.
Interferon-alpha was used to treat UC, and CD with limited success was generally well tolerated, but some IBD flares were reported during or after IFN-alpha therapy. Therefore, gastroenterologists are reluctant in treating IBD patients with IFN-alpha. Only a few case reports of successfully treated IBD/HCV patients have been published, using various older or current standard regimes using pegylated IFN-alpha and ribavirin.
In this retrospective analysis, we present the largest group of CD patients with chronic hepatitis C receiving antiviral therapy, most of them treated with currently recommended HCV regimes with pegylated IFN and ribavirin. Efficacy and safety of this therapy were investigated. Several patients were under ongoing immunomodulatory therapy.
