A. Rispo

Hepatitis B and C Virus Infection in Crohn's Disease

Patients with Crohns disease (CD) are at higher risk of hepatitis C (HCV) and B virus (HBV) infection, because of surgical and/or endoscopic procedures. However, the prevalence of HCV and HBV infection in CD is unknown. This issue may be relevant because of the growing use of immunomodulatory drugs in CD. The purpose of this study was to assess, in a multicenter study, the prevalence and risk factors of HCV and HBV infection in CD. The effect of immunomodulatory drugs for CD on the clinical course of hepatitis virus infections and of interferon-&agr; (IFN-&agr;) on the course of CD was examined in a small number of patients. Sera from 332 patients with CD and 374 control subjects (C) were tested for the following: hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (HBsAb), HBcAb, HBeAg, HBeAb, anti-HCV, and HCV-RNA. An additional 162 patients with ulcerative colitis (UC) were tested as a disease control group. Risk factors were assessed by multivariate statistical analysis. Infection by either HCV or HBV was detected in 24.7% of patients with CD. In the age groups younger than 50 years, HCV prevalence was higher in CD than in C (p = 0.01). HCV infection in CD was associated with surgery (OR 1.71; 95% CI 1.00–2.93; p = 0.04), blood transfusions (OR 3.39; 95% CI 1.04–11.04; p = 0.04), and age (OR 2.3; 95% CI 1.61–3.56; p < 0.001). The event CD-related surgery appeared to be the main risk factor for HCV infection in CD. HCV prevalence was higher in CD (7.4%) than in UC (0.6%) (p = 0.001). HBcAb positivity was higher in CD (10.9%) and UC (11.5%) than in C (5.1%) (CD vs. C: p = 0.016; UC vs. C: p = 0.02), associated with age (OR 2.08; 95% CI 1.37–3.17; p = 0.001) and female gender (OR 2.68; 95% CI 1.37–3.17; p = 0.001) in CD and to UC duration (OR 1.20; 95% CI 1.06–1.36; p = 0.002). Immunomodulatory drugs did not influence the course of HBV or HCV infection in seven patients with CD, and IFN-&agr; for chronic hepatitis C did not affect CD activity in six patients with CD. It is concluded that HBV prevalence is higher in CD than in C at all ages, whereas HCV prevalence is increased in young patients with CD, because of a greater need for surgery. The higher HCV (but not HBV) prevalence in CD than in UC suggests that the host immune response may influence the risk of HCV infection. Although a relatively high proportion of patients with CD showed HBV and/or HCV infections, this should not influence treatment strategies for CD.

Oral contrast-enhanced sonography for the diagnosis and grading of postsurgical recurrence of Crohn's disease.

Background: Postsurgical recurrence (PSR) is very common in patients with Crohns disease (CD) and previous surgery. Endoscopy is crucial for the diagnosis of PSR, also showing high prognostic value. Bowel sonography (BS) with or without oral contrast enhancement (OCBS) is accurate for CD diagnosis but its role in PSR detection and grading is poorly investigated. The aim was to evaluate the diagnostic accuracy of BS and OCBS for PSR compared to the endoscopical Rutgeertss grading system. Methods: We prospectively performed endoscopy, BS, and OCBS in 40 CD patients with previous bowel resection to provide evidence of possible PSR. Endoscopy, BS, and OCBS were executed 1 year after surgery, with PSR diagnosis and grading made in accordance with Rutgeerts. BS and OCBS were considered suggestive for PSR in the presence of bowel wall thickness (BWT) >3 mm. OCBS was performed after ingestion of 750 mL of polyethylene glycol (PEG). Also, a receiver operating characteristic (ROC) curve was constructed in order to define the best cutoff of BWT to discriminate mild from severe PSR (grade 0–2 versus 3–4 of Rutgeerts) for both BS and OCBS. Results: In all, 22 out of the 40 CD showed an endoscopic evidence of PSR (55%). A severe PSR was present in 14 patients (64%). Sensitivity, specificity, and positive and negative predictive values were 77%, 94%, 93%, and 80% for BS, and 82%, 94%, 93%, and 84% for OCBS. On the ROC curve a BWT >5 mm showed sensitivity, specificity, and positive and negative predictive values of 93%, 96%, 88%, and 97% for the diagnosis of severe PSR at BS, while a BWT >4 mm was the best cutoff differentiating the mild from the severe CD recurrence for OCBS, with a sensitivity, specificity, and positive and negative predictive values of 86%, 96%, 97%, and 79%, respectively. Conclusions: Both BS and OCBS show good sensitivity and high specificity for the diagnosis of PSR in CD, with a BWT >5 mm for BS and BWT >4 mm for OCBS strongly indicative of severe endoscopic PSR. Accordingly, these techniques could replace endoscopy for the diagnosis and grading of PSR in many cases.

Antibiotic treatment of small bowel bacterial overgrowth in patients with Crohn's disease

Background : Small bowel bacterial overgrowth is common in Crohns disease but its treatment is not clearly defined. Metronidazole and ciprofloxacin are effective antibiotics in active Crohns disease.

Orocecal transit time and bacterial overgrowth in patients with Crohn's disease.

Bacterial overgrowth is frequent in patients with Crohns disease (CD) and can contribute to symptoms. Motility abnormalities can predispose to bacterial overgrowth. The hydrogen (H2) and methane (CH4) breath test is a sensitive and simple tool for the diagnosis of bacterial overgrowth and for the evaluation of orocecal transit time (OCTT). In this study, we investigated the prevalence of OCTT modifications and bacterial overgrowth in a series of consecutive adult patients with CD. In 43 healthy subjects and 67 patients with CD. we performed the lactulose breath test using a gas analyzer that offers the opportunity of measuring both H2 and CH4. Of the patients, 24 had undergone an ileocolic resection before the test with ablation of the ileocecal valve. At the time of the test 15 patients had active disease, whereas in 52 subjects the disease was quiescent. Fifty-seven patients and forty controls were evaluable for OCTT and bacterial overgrowth. In 10 patients and in 3 controls, no H2 or CH4 peak was recorded during the 8-hour test. Out of 57 patients, 13 (23%) were affected by bacterial overgrowth. The prevalence of bacterial overgrowth was higher in patients with previous surgery (30%) than in nonoperated patients (18%). In all patients with bacterial overgrowth, an antibiotic treatment induced a normalization of the test and an improvement of the symptoms. We observed a longer OCTT in the patients compared to controls, although this difference was not statistically significant (154 +/- 45 vs. 136 +/- 45 minutes). OCTT was significantly longer compared to controls in the 14 CD patients with previous ileocolic resection ( 180 +/- 53 vs. 136 + 45 minutes; p < 0.004). In conclusion, we found that a significant proportion of unselected patients with CD has bacterial overgrowth and prolongation of OCTT. We suggest that the modifications in OCTT in patients with CD can predispose to bacterial overgrowth. The lactulose breath test is a simple method that can be more widely used in patients with CD.

Noninvasive diagnosis of small bowel Crohn's disease: direct comparison of bowel sonography and magnetic resonance enterography.

Background:The diagnosis of small bowel Crohn’s disease (CD) is performed by ileocolonoscopy, whereas the assessment of its extension can be achieved by radiologic studies or, noninvasively, by magnetic resonance (MR) enterography and bowel sonography (BS). However, few comparative studies exist directly comparing the diagnostic accuracy of BS and MRI. The aim of this study was to evaluate the diagnostic accuracy of BS and MRI for the diagnosis of small bowel CD. Methods:We prospectively performed a noninferiority diagnostic study including 234 consecutive subjects with suspected small bowel CD. All patients underwent IC (used as gold standard for diagnosis), BS, and MR enterography performed in random order by physicians who were blinded about the results. Results:The diagnosis of small bowel CD was made in 120 of 249 subjects (48%). Sensitivity, specificity, positive predictive value, and negative predictive value for CD diagnosis were 94%, 97%, 97%, and 94% for BS and 96%, 94%, 94%, and 96% for MR enterography, respectively. BS was less accurate than MR enterography in defining CD extension (r = 0.69), whereas the concordance in terms of CD location between the 2 procedures was high (k = 0.81). Also, MRI showed a fair concordance with BS about strictures (k = 0.82) and abscesses (k = 0.88), with better detection of enteroenteric fistulas (k = 0.67). Conclusions:BS and MR enterography are 2 accurate procedures for the diagnosis of small bowel CD, although MR seems to be more sensitive in defining its extension. BS could be used to select the patients for subsequent MRI examination.

Infliximab in the treatment of extra‐intestinal manifestations of Crohn's disease

Background: Crohns disease (CD) is frequently associated with extra‐intestinal manifestations (EIMs) and infliximab has been recently proposed for the treatment of CD with EIMs. Our aim was to evaluate the short‐term efficacy of infliximab in this treatment. Patients and methods: Thirty CD patients were treated with infliximab. Fifteen patients (50%) showed EIMs before starting therapy. Ten patients presented an arthritis (five sacroiliitis, five spondylitis), with six also reporting peripheral arthralgias. Four patients presented cutaneous EIMs while three patients had an ocular EIM. Results: At week 10, all patients reported an improvement in EIMs. Regarding arthritis, ASAS20 and ASAS40 improvement was observed in 80% and 60% of patients, respectively. In the four patients with cutaneous EIMs and in the three with ocular EIMs, complete healing was observed. Recurrence was observed in 10 out of 15 patients (66%) and a second course of treatment with infliximab was required. This proved to be effective in all cases except for one patient who stopped treatment because of a severe adverse reaction. Conclusions: Infliximab is an effective drug in the short‐term treatment of EIMs complicating CD. Although relapse of EIMs occurs frequently, retreatment ensures effective control of the symptoms.

Bowel Wall Thickness at Abdominal Ultrasound and the One-Year-Risk of Surgery in Patients with Crohn's Disease

OBJECTIVES:Abdominal ultrasound can assess the extent and localization of Crohns disease, and an increased bowel wall thickness is the most common finding. Our aim was to correlate bowel wall thickness at ultrasound, with the risk of short-term surgical outcome in patients with Crohns disease.MATERIALS AND METHODS:From 1997 to 2000 we performed ultrasound in 174 consecutive patients with Crohns disease. Surgical operations were recorded over a 1-yr follow-up. Logistic regression analysis was performed to identify clinical and ultrasound risk factors for surgery.RESULTS:Fifty-two patients underwent surgery within 1 yr. Indication for surgery was strictures in most of the cases. Median bowel wall thickness was higher in patients with surgery (8 mm) than those without surgery (6 mm) (p < 0.0001). A receiver operating characteristic (ROC) curve was constructed taking into account bowel wall thickness for selecting patients with a high risk of surgery. The optimized cut-off for equally important sensitivity and specificity was calculated at 7.008 mm. The binary regression analysis showed that CDAI > 150, absence of previous surgery, stricturing–penetrating pattern, the presence of intestinal complications, and intestinal wall thickness >7 mm were associated with an increased risk of surgery. Patients with intestinal wall thickness >7 mm at ultrasound had the highest risk (OR: 19.521, 95% CI: 5.362–71.065).CONCLUSIONS:Data suggest that bowel wall thickness >7 mm at ultrasound is a risk factor for intestinal resection over a short period of time. Routine use of abdominal ultrasound during evaluation of patients with Crohns disease may identify a subgroup that is at high risk for surgery.

Bowel sonography for the diagnosis and grading of postsurgical recurrence of Crohn's disease.

Background and Aims: Postsurgical recurrence (PSR) is common in patients with Crohns disease (CD) who have undergone surgery. Endoscopy is crucial for the diagnosis of PSR, showing also high prognostic value. Bowel sonography (BS) is accurate for CD diagnosis, but its role in PSR detection and grading has been poorly investigated. The aim of this study was to evaluate the diagnostic accuracy of BS compared to endoscopy in the detection of PSR. Materials and Methods: Between March 2002 and October 2005, to gain evidence of possible PSR, we prospectively performed endoscopy and BS in 45 CD patients who had undergone previous bowel resection. Endoscopy and BS were carried out 1 year after surgery, with diagnosis and grading of PSR made in accordance with Rutgeerts. BS was considered suggestive for PSR in the presence of bowel wall thickness (BWT) >3 mm. Also, an ROC curve was constructed to define the best cutoff value for BWT to differentiate mild from severe PSR (grade 1–2 vs 3–4 of Rutgeerts). Results: Of the 45 patients with CD, 24 showed endoscopic evidence of PSR (53%). Severe endoscopic PSR was present in 16 patients (66%). Sensitivity, specificity, and positive and negative predictive values of BS were 79%, 95%, 95%, and 80%, respectively, with a sensitivity of 93% for severe PSR. On the ROC curve, a BWT >5 mm showed sensitivity, specificity, and positive and negative predictive values of 94%, 100%, 100%, and 96%, respectively, in differentiating mild from severe PSR, in remarkable agreement with endoscopy (&kgr; = 0.90). Conclusions: BS shows good sensitivity and high specificity for the diagnosis of PSR in CD, with a BWT >5 mm being strongly indicative of severe endoscopic PSR. Hence, BS could replace endoscopy for the diagnosis and grading of PSR in patients who comply poorly with the endoscopic examination.

Noninvasive diagnosis of small bowel Crohn's disease: Combined use of bowel sonography and Tc-99m-hmpao leukocyte scintigraphy

Background: Crohns disease (CD) is frequently localized in the small bowel, with the diagnosis of disease and the assessment of its extension made by ileo‐colonoscopy (IC) and small bowel enteroclysis (SBE). Transabdominal bowel sonography (BS) and Tc‐99m‐HMPAO leukocyte scintigraphy (LS) are increasingly used for the diagnosis of CD because of their minimal invasiveness, reproducibility, and acceptable costs. Methods: From March 2000 to July 2003, we performed IC, SBE, BS, and LS in 84 patients with either suspected or known small bowel CD. Results: Small bowel CD was present in 50 patients, whereas the other 34 patients received a different diagnosis. Sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy were, respectively, 98%, 97%, 98%, 97%, and 0.97 for SBE; 92%, 97%, 98%, 88%, and 0.94 for BS; and 90%, 93%, 96%, 85%, and 0.92 for LS. In addition, the combined use of BS and LS led to overall sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy of 100%, 93%, 96%, 100%, and 0.97, respectively. BS showed a fair concordance with SBE in terms of location (k = 0.71) and a correlation with the extension of the disease (r = 0.67, P < 0.001). LS showed a concordance with SBE with regard to location in about one‐half the population (k = 0.54), whereas it was less effective than SBE in defining disease extension. Conclusions: BS and LS are 2 accurate techniques for the diagnosis of small bowel CD, and their combined use can be recommended as an early diagnostic approach to patients in which the disease is suspected. SBE remains the best procedure for the definition of the location and extension of the disease.

Transmural healing evaluated by bowel sonography in patients with Crohn's disease on maintenance treatment with biologics.

Background:Both thiopurines and anti-tumor necrosis factor (TNF) &agr; agents are effective for treating Crohn’s disease (CD) as they can induce clinical remission (CR) and mucosal healing (MH) in most patients. Nevertheless, data on transmural healing (TH) induced by thiopurines and anti-TNF-&agr; agents are still lacking. This study aimed to explore the rate of TH evaluated by bowel sonography in patients with CD treated with biologics and immunosuppressors and its correlation with CR and MH. Methods:We performed an observational longitudinal study evaluating TH, CR, and MH in all patients with CD attending our clinic who would complete 2 years of maintenance treatment with biologics or thiopurines. CR and MH were assessed in accordance with current literature, whereas TH was recorded using bowel sonography. All patients underwent endoscopy and bowel sonography before starting treatment and 2 years later. Results:The study included 66 patients with CD treated with biologics and 67 patients receiving thiopurines. Finally, TH was present in 17 patients on biologics and only 3 patients treated with thiopurines (25% versus 4%; P < 0.01; odds ratio = 6.2). CR was achieved in 37 patients on biologics and in 34 patients on thiopurines (59.7% versus 53%; P = not significant), whereas MH was more frequent in patients treated with anti-TNF-&agr; agents even though without statistical significance (38% versus 25%; P = not significant). Conclusions:TH can be achieved in approximately 25% of patients with CD treated with anti-TNF-&agr; agents and significantly correlates with MH. Further studies are needed to define the potential role of TH as long-term prognostic factor.