High efficacy of direct-acting anti-viral agents in hepatitis C virus-infected cirrhotic patients with successfully treated hepatocellular carcinoma.

BACKGROUND: The efficacy of direct-acting anti-viral (DAA) therapy in patients with a history of hepatocellular carcinoma (HCC) is unknown. AIM: We prospectively evaluated whether previously treated HCC affects DAA efficacy in a large real-life cohort of cirrhotic patients. METHODS: From January to December 2015 all consecutive HCV mono-infected patients with cirrhosis and/or history of HCC attending 10 Italian tertiary liver centres were enrolled. Baseline characteristics and response to therapy were recorded. 1927 patients were enrolled (mean age: 62.1 ± 10.9 years; 1.205 males). Genotype 1 was the most frequent (67.9%) followed by genotypes 3 (12.4%), 2 (11.2%) and 4 (8.6%). 88.4% and 10.9% of cases were classified Child A and B, respectively, and 14 (<1%) cases were classified Child C. Ascites and hepatic encephalopathy occurred in 10.7% and 3.2% of patients, respectively. Varices were detected in 39.3% of patients. Suboptimal and optimal treatment was prescribed: 15.9% of patients received sofosbuvir/simeprevir, 33.4% sofosbuvir/ledipasvir, 20.2% a Viekirax + Exviera regimen, 15.7% sofosbuvir/ribavirin, 9.9% sofosbuvir/daclatasvir and 3.4% Viekirax; 1.3% of patients received an interferon-based regimen. RESULTS: The sustained virologic response (SVR) rate at intention-to-treat analysis was 95.1%. It differed significantly across Child classes, that is, 96.3%, 86.1% and 71.4% Child A, B and C, respectively (P < 0.0001) and across genotypes (P = 0.002). The SVR rate did not differ between patients with (95.0%) and those without previous HCC (95.1%). At multivariable analysis, SVR was significantly associated with HCV genotype, Child class. CONCLUSION: This large real-life study proves that the efficacy of DAA in cirrhotic patients is not impaired by successfully treated HCC.

Undetectable HCV-RNA at treatment-week 8 results in high-sustained virological response in HCV G1 treatment-experienced patients with advanced liver disease: the International Italian/Spanish Boceprevir/Peginterferon/Ribavirin Name Patients Program.

In many countries, first-generation protease inhibitors (PIs)/peginterferon/ribavirin (P/R) still represent the only treatment option for HCV-infected patients. Subjects with advanced disease and previous failure to P/R urgently need therapy, but they are under-represented in clinical trials. All treatment-experienced F3/4 Metavir patients who received boceprevir (BOC)+P/R in the Italian-Spanish Name Patient Program have been included in this study. Multivariate logistic regression analysis (MLR) was used to identify baseline and on-treatment predictors of SVR and adverse events (AEs). Four hundred and sixteen patients, mean age 57.7 (range 25-78 years), 70% males, 69.5% (289/416) F4, 14% (41/289) Child-Pugh class A6, 24% (70/289) with varices and 42% (173/416) prior null responders to P/R, were analysed. Overall, SVR rate (all 381 patients who received one dose of BOC) was 49%, (58% in F3, 45% in F4, 61% in relapsers, 51% in partial, 38% in null responders, and 72% in subjects with undetectable HCV-RNA at treatment-week (TW)8. Among patients with TW8 HCV-RNA ≥ 1000 IU/L, SVR was 8% (negative predictive value = 92%). Death occurred in 3 (0.8%) patients, while decompensation and infections were observed in 2.9% and 11%, respectively. At MLR, SVR predictors were TW4 HCV-RNA ≥ 1log10 -decline from baseline, undetectable TW8 HCV-RNA, prior relapse, albumin levels ≥3.5 g/dL and platelet counts ≥100 000/µL. Metavir F4, Child-Pugh A6, albumin, platelets, age and female gender were associated with serious and haematological AEs. Among treatment-experienced patients with advanced liver disease eligible for IFN-based therapy, TW8 HCV-RNA characterised the subset with either high or poor likelihood of achieving SVR. Using TW8 HCV-RNA as a futility rule, BOC/P/R appears to have a favourable benefit-risk profile.

Natural history of gastro-oesophageal reflux disease without oesophagitis (NERD)--a reappraisal 10 years on.

BACKGROUND AND AIM: Ten years ago we published a study describing the 6-month outcome of 33 outpatients with typical gastro-oesophageal reflux disease symptoms and pH-metry proven excess gastro-oesophageal reflux but without endoscopical evidence of oesophagitis, currently referred to as patients with gastro-oesophageal reflux disease without oesophagitis. We now present an update of that report concerning morbidity, drug consumption and quality of life of the original patients 10 years after the initial diagnosis. METHODS: The study consisted of the retrieval and revision of all clinical and instrumental records concerning the cohort of 33 above-mentioned patients. Data are available regarding annual intervals within the first 5 years from original diagnosis and, subsequently, with a follow-up ranging from 7 to 14 years (median 10 years). The records of these 33 patients were reviewed, including the results of clinical visits at the outpatients department, of oesophagogastroduodenoscopies and pH- metries. Finally, a telephonic interview was conducted by means of a structured questionnaire, aiming at evaluating present symptoms, actual therapy if any, health-related quality of life and other information regarding any gastro-oesophageal reflux disease symptoms. RESULTS: Of the original 33 patients, 31 are still alive and 2 were lost to follow-up. Of the 29 remaining, only 1 is definitively not complaining of any gastro-oesophageal reflux disease-related symptoms. Within 5 years of the first diagnosis, oesophagitis was found in all but one of the 18 subjects who underwent repeated endoscopy. At the latest follow-up check, after a median of 10 years, out of the 28 still complaining of gastro-oesophageal reflux disease symptoms, 21 (75%) were presently taking antisecretory drugs (proton pump inhibitors and H-2 receptor antagonists) because of gastro-oesophageal reflux disease symptoms/lesions, 12 of whom intermittently or on demand and the remaining 9 continuously. Two patients (2/28) underwent antireflux surgery, but despite this were still taking antisecretory drugs (in one case H2-RA; in the other proton pump inhibitor). The health-related quality of life, self-evaluated by the patient by means of a VAS scoring from 0 (worst possible) to 10 (best possible) increased significantly from 3.2 to 6.5 from baseline (before therapy) to present time, possibly due to the positive effect of present therapy. CONCLUSIONS: Our study conducted on a cohort of endoscopy-negative patients with pH-metry-confirmed reflux disease has shown that after a median time of 10 years following the original diagnosis, the majority of patients have, in fact, developed reflux oesophagitis and are on prolonged antisecretory therapy because of recurrent gastro-oesophageal reflux disease symptoms/lesions. The study confirms that gastro-oesophageal reflux disease without oesophagitis, as well as gastro-oesophageal reflux disease at large, is a chronic disease characterised by increasing severity with time, which requires protracted medical therapy in a vast proportion of patients. Absence of endoscopic oesophagitis at presentation does not represent a positive prognostic factor.

Inflammatory bowel disease versus irritable bowel syndrome: a hospital-based, case-control study of disease impact on quality of life.

BACKGROUND: Inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) are intestinal diseases perceived differently by patients and doctors: the former is considered essentially as an 'organic' disease (i.e. an illness in which the role of stress or psychological factors is at best secondary to the disease itself), whereas the latter is acknowledged as a 'functional' disorder (i.e. illness thought to be more in the 'mind' than in the body of the patient). Accordingly, the respective impact of the two diseases on patients' health-related quality of life (HRQOL) is perceived to be very different. We aimed to compare the relative impact of the disease on HRQOL, psychological profile and perceived burden of stressful life events in two groups of outpatients suffering from IBS and IBD and attending our outpatient department at an Italian university hospital. Eighty patients with IBD (26 with ulcerative colitis and 54 with Crohn disease) and 85 controls with IBS formed the patient samples of the study. METHODS: Three questionnaires were given to the patients while they were attending the outpatient department because of their previously diagnosed disease, namely the SF-36 (a generic well-validated tool for measuring HRQOL), the SCL-90 (for assessing the psychological profile of patients), and the Holmes & Rahe schedule (for the assessment of stressful life experiences). The results were then compared by means of analysis of variance (ANOVA) and Bonferroni-adjusted t test, when appropriate. RESULTS: HRQOL appeared to be similarly reduced in both disease groups (SF-36 overall mean value: 58.2 +/- 16.1 in IBS patients versus 56.4 +/- 22.3 in IBD patients: P > 0.05) in comparison with normative Italian data. Furthermore, the overall severity of psychological symptoms was not statistically different between patients suffering from IBD versus IBS, as shown by SCL-90 mean scores of 0.89 + 0.45 versus 0.83 +/- 0.48, respectively (P > 0.05). On the contrary, the severity of recent stressful life experiences was perceived to be higher by IBS than by IBD patients (mean SRE score: 110.8 = 110.2 versus 61.6 +/- 78.8; P < 0.05). CONCLUSION: Our study supports the notion that, at least in referral centres, patients with IBS show health-related quality of life, psychological distress and recent occurrence of stressful life events of severity at least comparable with age-matched IBD patients.

Comparison between methotrexate and azathioprine in the treatment of chronic active Crohn's disease: a randomised, investigator-blind study.

BACKGROUND AND AIMS: The efficacy of azathioprine in the treatment of chronic active Crohn's disease is well established. However, this drug has a long onset of action. Methotrexate has also been shown to be effective in chronic active Crohn's disease. The aim of this study was to evaluate the efficacy and safety of methotrexate in comparison with azathioprine, and to establish whether methotrexate has a shorter onset of action in this setting. METHODS: Patients with chronic active Crohn's disease were admitted to this investigator-blind study. Chronicity was defined as the need for steroid therapy of > or = 10 mg/day for at least 4 months during the preceding 12 months, with at least one attempt to discontinue treatment. The disease had to be clinically active at entry, with a Crohn's Disease Activity Index of > or = 200. Six patients treated with azathioprine and methotrexate, respectively, were found to have enterocutaneous and perianal fistulas. At entry, all patients received prednisolone (40 mg once a day) which was tapered over a period of 12 weeks unless their clinical condition deteriorated. All patients were randomised to receive i.v. methotrexate 25 mg/week, or oral azathioprine 2 mg/kg per day, for a 6-month follow-up period. After the first 3 months, methotrexate was switched to oral administration maintaining the same dose. The primary efficacy outcome considered was the proportion of patients entering first remission after 3 and 6 months of therapy. Clinical remission was defined as the lack of need for steroid treatment and a Crohn's Disease Activity Index score of < or = 150 points at each scheduled visit. RESULTS: In the 54 patients (26 F, 28 M, mean age 34 years, range 18-60) randomly assigned to methotrexate (n=27) or azathioprine (n=27), no statistically significant difference was found between the two treatment regimens with respect to remission rate after 3 (methotrexate 44%, azathioprine 33%, p=0.28, (95% CI, 0.369-0.147), and 6 months (methotrexate 56%, azathioprine 63%, p=0.39, 95% CI, 0.187-0.335), respectively. Six patients withdrew from therapy due to adverse events: 3/27 (11%) in methotrexate and 3/27 (11%) in azathioprine. Drug-related adverse events (asthenia, nausea and vomiting) that did not require withdrawal from therapy were more frequent in the methotrexate group (azathioprine: 2/27 (7%); methotrexate: 12/27 (44%), p=0.00009). The frequency of these adverse events was comparable during the intravenous or oral administration of the drug. CONCLUSIONS: This study confirms that methotrexate is effective in inducing remission in patients with chronic active Crohn's disease, therapeutic efficacy being comparable, but not faster, than that of azathioprine.

[Efficacy of medical therapy in preventing the post-surgical recurrence in Crohn's disease]. / Efficacia della terapia medica nella prevenzione della recidiva post-chirurgica della malattia di Crohn.

Crohns Disease (CD) is a chronic intestinal inflammatory disease of unknown origins that cannot be definitely resolved with surgical intervention. Therefore, pharmacologic therapies are of great importance both in preventing relapses and by determining remissions. In this paper the authors analyse the different drugs available for the treatment of Crohns disease, and focus on their efficacy and tollerability.

Discordance between the degree of osteopenia and the prevalence of spontaneous vertebral fractures in Crohn's disease.

BACKGROUND: A high prevalence of osteoporosis has been noted in Crohn's disease, but data about fractures are scarce. METHODS: The relationship between low bone mineral density and the prevalence of vertebral fractures was studied in 271 patients with ileo-caecal Crohn's disease in a large European/Israeli study. One hundred and eighty-one currently steroid-free patients with active Crohn's disease (98 completely steroid-naive) and 90 steroid-dependent patients with inactive or quiescent Crohn's disease were investigated by dual X-ray absorptiometry scan of the lumbar spine, a standardized posterior/anterior and lateral X-ray of the thoracic and lumbar spine, and an assessment of potential risk factors for osteoporosis. RESULTS: Thirty-nine asymptomatic fractures were seen in 25 of 179 steroid-free patients (14.0%; 27 wedge, 12 concavity), and 17 fractures were seen in 13 of 89 steroid-dependent patients (14.6%; 14 wedge, three concavity). The prevalence of fractures in steroid-naive patients was 12.4%. The average bone mineral density, expressed as the T-score, of patients with fractures was not significantly different from that of those without fractures (-0.759 vs. -0.837; P=0.73); 55% of patients with fractures had a normal T-score. The bone mineral density was negatively correlated with lifetime steroids, but not with previous bowel resection or current disease activity. The fracture rate was not correlated with the bone mineral density (P=0.73) or lifetime steroid dose (P=0.83); in women, but not in men, the fracture rate was correlated with age (P=0.009). CONCLUSIONS: The lack of correlation between the prevalence of fractures on the one hand and the bone mineral density and lifetime steroid dose on the other necessitates new hypotheses for the pathogenesis of the former.

Infliximab in treatment of Crohn's disease: the Milan experience.

BACKGROUND: Efficacy of infliximab in treatment of patients with moderate-to-severe refractory and fistulizing Crohn's disease has been shown in controlled clinical trials. Moreover, audit data from North America and North Europe have confirmed efficacy in clinical practice comparable to that in clinical trials. AIM: To report clinical experience using infliximab in treatment of Crohn's disease in Italy, comparing efficacy and safety with those reported in clinical trials and other published series. PATIENTS AND METHODS: The study population comprised 63 patients (31 males and 32 females, median age 33 years) treated with infliximab for refractory/inflammatory (31 patients) and/or fistulizing Crohn's disease (32 patients). All patients received an infusion of infliximab at a dose of 5 mg/kg at weeks 0, 2 and 6. After the first infusion, clinical and laboratory assessments were repeated at weeks 2, 6 and 10. For refractory inflammatory Crohn's disease, clinical remission was defined as a Crohn's Disease Activity Index of < or = 150 at each scheduled visit, clinical response as a reduction in the Crohn's Disease Activity Index score of > or = 70 points in comparison to baseline. For fistulizing Crohn's disease, a complete response was defined as closure of any draining fistulae at week 10. A fistula was defined as closed when it no longer drained despite gentle finger pressure. A partial response was defined as reduction in number, size or drainage of fistulae, at the same visit. RESULTS: According to an intention-to-treat evaluation on the 31 patients with refractory/inflammatory Crohn's disease, at week 2, 42.5% (14 patients) had a clinical response and 31.3% of patients (10 patients) were in clinical remission. At week 10 (4 weeks after the end of third infusion), 80.6% (25 patients) had a clinical response and 71% (22 patients) were in clinical remission and 14/19 (74%) had discontinued steroid treatment. Of the 32 patients with fistulizing Crohn's Disease, 15 (46.9%) had a complete response, 8 (25%) a partial response, and 9 (28.1%) no response at week 10 check-up. The incidence of side-effects was low (16%) and not influenced by concurrent immunomodulatory therapy. CONCLUSION: The present experience with infliximab in clinical practice confirms its efficacy, in particular in inflammatory/refractory Crohn's disease and its safety, at least, in short-term follow-up.

Bowel ultrasound in assessment of Crohn's disease and detection of related small bowel strictures: a prospective comparative study versus x ray and intraoperative findings.

BACKGROUND AND AIM: Despite the fact that bowel ultrasound (US) has recently been proved to be useful in the assessment of bowel diseases, uncertainty persists as to its diagnostic role in patients with complicated Crohn's disease (CD). Therefore, we have prospectively investigated the accuracy of US compared with x ray procedures and intraoperative findings in detecting small bowel strictures complicating CD as well as its reliability in assessing disease extent and location within the bowel. METHODS: A series of 296 consecutive patients with proven CD admitted to L Sacco University Hospital between 1997 and 1999, having undergone complete radiographic evaluation (including small bowel x ray, colonoscopy, or double contrast barium enema), were enrolled in the study. Bowel US was performed in each patient by two experienced operators unaware of the results of other diagnostic procedures. The accuracy of US in detecting strictures compared with x ray studies was determined separately in two different groups of patients: 211 patients treated conservatively (non-operative CD) and 85 patients who were candidates for surgery for CD complications or unresponsiveness to medical therapy (operative CD). RESULTS: Overall sensitivity and specificity of US in assessing the anatomical distribution of CD were 93% and 97%, respectively. The extent of ileal disease measured at US correlated well with that determined by x ray (r=0.52, p<0.001) in medically treated patients as well as with that measured intraoperatively in surgical patients (r=0.64, p<0.001). One or more stenoses were detected in 75 patients (35.5%) at small bowel enteroclysis in the non-operative CD group compared with 70 (82%) in the operative CD series. Sensitivity, specificity, and positive predictive values of bowel US in the detection of strictures were 79%, 98%, and 95% in non-operative CD patients and 90%, 100%, and 100% in operative CD cases, respectively. CONCLUSIONS: In experienced hands, bowel US is an accurate technique for assessing CD extent and location and is very helpful in detecting small bowel strictures, especially in very severe cases that are candidates for surgery. The use of bowel US is therefore justified as a primary investigation in CD patients in whom complications are suspected.

The vascularity of internal fistulae in Crohn's disease: an in vivo power Doppler ultrasonography assessment.

AIM: To evaluate the efficacy of power Doppler sonography (US) in depicting internal fistulae and their vascularity, and to study the characteristics of blood flow within the fistula wall. PATIENTS AND METHODS: The study involved 45 consecutive patients with Crohn's disease and suspected internal fistulae detected by grey scale US. The fistulae were subsequently evaluated using power Doppler US to reveal any areas of increased vascularity, and the results were compared with radiographic, endoscopic, or intraoperative findings. Whenever feasible, we also performed spectral analysis of blood flow revealed by power Doppler US, calculated its resistance index (RI), and analysed its characteristics, reproducibility, and relationship with biochemical and clinical variables (Crohn's disease activity index, disease duration, location, and abdominal complications). RESULTS: Power Doppler US revealed vascularity in all of the internal fistulae that where subsequently confirmed by diagnostic procedures. In the case of intra-abdominal abscesses in the vicinity of the fistula, vascular signals were detected mostly around and not within the lesions. The intensity and distribution of the signals differed within the fistulae tracks and had only slight day to day reproducibility; furthermore, there was no significant correlation with clinical or biochemical variables. Spectral analyses of blood flow within the fistulae revealed arterial flow in 96.7% of patients (median RI 0.715). RI was a more reproducible parameter and significantly correlated with clinical (r= 0.54) and biochemical activity (r= 0.56) of CD. It was also higher in fistulae complicated by abscesses. CONCLUSION: Power Doppler US can reveal the presence of vasculature within the wall of internal fistulae and therefore enhance grey scale US performance. The RI characteristics of blood flow within the fistulae are reproducible and correlate with biochemical and clinical disease activity.

Epidemiological aspects of irritable bowel syndrome in Europe and North America.

The epidemiology of irritable bowel syndrome (IBS) in Europe and North America was analyzed from published material. The percentage of the population of Western civilisation with IBS symptoms is between 10 and 15% in most studies. The proportion of a Western population visiting a doctor for IBS symptoms is around 5%. The prevalence of IBS and the proportion of consulters do not seem to depend on age in an adult population. The female-to-male ratio of IBS in the population is close to 2. It is higher in IBS consulters in primary care and may be as high as 3 or 4 in tertiary referral centers. At least in patients from these centers, the number of physician visits and colonoscopies is considerable. Most of the consulters get a drug prescription.

Long-term results and multivariate analysis of prognostic factors in 138 consecutive patients operated on for Crohn's disease using "bowel-sparing" techniques.

BACKGROUND: Conservative surgery has become accepted as a useful option for the surgical treatment of complicated Crohn's disease (CD). METHODS: One hundred thirty-eight consecutive patients treated with strictureplasty or miniresections for complicated CD have been observed prospectively. The possible influence of a number of variables on the risk of recurrence was investigated using the Cox proportional hazard model, and a time-to-event analysis was made using the Kaplan-Meier function. RESULTS: There was no perioperative mortality; the morbidity rate was 5.7%. A close correlation was found between the risk of recurrence and the time between diagnosis and first surgery. The overall 5-year recurrence rate was 24%, being 36% in the patients requiring surgery within 1 year of diagnosis and 14% in those operated on more than 1 year after diagnosis. CONCLUSIONS: Risk factor analysis highlighted a group of patients at high risk of surgical recurrence. Given that our results are similar to those reported in other series, we consider strictureplasty and miniresections safe and effective procedures for the treatment of complicated CD.

Focal gastric inflammatory infiltrates in inflammatory bowel diseases: prevalence, immunohistochemical characteristics, and diagnostic role.

OBJECTIVES: To date, few studies have evaluated gastric histology in patients with inflammatory bowel disease (IBD). The aim of this prospective controlled study was to establish the frequency of focal gastritis in Crohn's disease (CD) and ulcerative colitis (UC) patients, as well as to evaluate its immunohistochemical characteristics and clinicoanatomical determinants. METHODS: We evaluated 141 consecutive patients with known CD of the large and/or small bowel, 79 patients with UC, and 141 CD- and UC-free controls; all underwent upper gastrointestinal (GI) endoscopy and 13C urea-breath test. Biopsy specimens taken from the antrum, angulus, and gastric body were evaluated by histology and immunohistochemistry. A series of variables, including CD activity index, duration, extent and location of disease, intestinal resection, number of recurrences, and previous and current medical therapy, as well as the presence of dyspeptic symptoms and mucosal lesions at endoscopy, were determined in all CD patients and correlated with the presence or absence of focal gastritis. RESULTS: Helicobacter pylori-associated gastritis was found in 47 patients with CD (33%), in 37 patients with UC (47%), and in 60% of CD-/UC-free controls (p < 0.01). In H. pylori-negative CD patients focal gastritis was found in 43% of cases (40/94), compared with 12% (5/42) of UC patients and 19% (11/57) of controls (p < 0.05). Specificity and positive predictive value of focal gastritis in CD were 84% and 71%, respectively. It was characterized by a focal perifoveolar or periglandular lymphomonocytic infiltrate, with CD8+/CD4+ cells predominant both in CD and UC patients. There were no significant correlations between the occurrence of focal gastritis and any clinicoanatomical CD features. CONCLUSIONS: Focal gastritis is relatively common in CD patients although it is not exclusive to this condition. Its recognition could be useful in the diagnostic workup of any patient with suspected or indeterminate inflammatory bowel disease, as it makes a diagnosis of CD more likely.

Altered bone metabolism in inflammatory bowel disease: there is a difference between Crohn's disease and ulcerative colitis.

OBJECTIVES: The aims of this study were to assess bone metabolism in inflammatory bowel disease (IBD) patients and to evaluate potential differences between Crohn's disease (CD) and ulcerative colitis (UC) with respect to the mechanisms underlying bone loss in this group of diseases. DESIGN AND SETTING: This was a cross-sectional study which started in 1992. Patients were randomly selected for invitation to participate and were examined during the years 1992-95 in one research clinic in Milan. SUBJECTS AND METHODS: Fifty-one patients suffering from CD (30 women and 21 men, mean age 38.7 +/- 13.2 years) and 40 with UC (15 women and 25 men, mean age 34.4. +/- 12.5 years) entered the study. Thirty healthy subjects were selected as sex- and age-matched controls (C). Spine and femoral neck bone mineral density (expressed as T score), calciotropic hormones (parathyroid hormone, PTH; 25-hydroxycholecalciferol, 25(OH)D3; 1,25-hydroxycholecalciferol, 1, 25(OH)D3) and biochemical markers of bone turnover (ostecalcin, OC; total alkaline phosphatase, ALP; type I collagen C-terminal telopeptide, ICTP) were evaluated. RESULTS: Spine and femur T scores were similar in the two groups (spine: CD = -1.49 +/- 1.46; UC = -1. 67 +/- 1.13; femur: CD = -1.80 +/- 1.36; UC = -1.60 +/- 1.03). Based upon the WHO guidelines, only 8% of CD patients and 15% of UC patients had a normal bone mineral density (BMD), 55% (CD) and 67% (UC) were osteopenic, and 37% (CD) and 18% (UC) were osteoporotic. The distribution amongst the three different diagnostic groups was not significantly different between CD and UC groups (P = 0.11). PTH and 25(OH)D3 concentrations were not significantly different between CD and UC patients and controls, whilst 1,25(OH)D3 concentrations were significantly lower in both CD and UC patients compared with controls (P < 0.05). Bone turnover was increased in UC but not in CD patients, as shown by significantly increased concentrations in UC patients of both OC (CD = 7.77 +/- 5.06, UC = 10.03 +/- 6.24, C = 6. 58 +/- 2.87, P < 0.05 vs. C) and ICTP (CD = 5.74 +/- 3.94, UC = 10.2 +/- 8.47, C = 3.48 +/- 0.95, P < 0.05 vs. CD and C). In a stepwise regression that included age, sex, disease duration and cumulative prednisolone dose as independent variables, the femur T score was significantly inversely related to disease duration (r2 = 0.125, F = 6.06) in CD patients. In UC patients, the spine T score was inversely related to age (r2 = 0.107, F = 5.49) and significantly related to sex (more negative in males: r2 = 0.3, F = 16.1); the femur T score was significantly related to sex (more negative in males) and inversely related to the cumulative prednisolone dose (r2 = 0.283, F = 7.3). CONCLUSIONS: These data show that IBD patients have a diffuse osteopenia, the degree of which is not different in CD and UC; however, bone turnover is significantly higher in UC. Finally, osteopenia is related to disease duration in CD, whilst it is related to the male sex and glucocorticoid treatment in UC.

Inflammatory bowel disease approaching the 3rd millennium: pathogenesis and therapeutic implications?

The aetiology of inflammatory bowel disease remains unknown, but genetic, immuno-inflammatory, infectious, vascular and neural factors play an important role. All effective treatments in use today were introduced empirically and most have multiple action. Targeted therapy is very attractive, either with cell and gene therapy or by using specific cytokine inhibitors and inhibitory cytokines. The role of the intestinal milieu, and enteric flora in particular, appears to have a much greater significance than previously appreciated. The reduction of any changes leading to pro-coagulant activity may be a promising line of therapeutic investigation, and measures to reduce platelet aggregation and endothelial cell adhesiveness are examples of therapeutic potentials. Finally, there has been tangible demonstration of the ability of nerves to alter the inflammatory process which will lead to new therapeutic approaches in inflammatory bowel disease.

Is maintenance therapy always necessary for patients with ulcerative colitis in remission?

BACKGROUND: The efficacy of sulphasalazine and mesalazine in preventing relapse in patients with ulcerative colitis is well known. It is less clear how long such maintenance should be continued, and if the duration of disease remission is a factor that affects the risk of recurrence. AIM: To determine whether the duration of disease remission affects the relapse rate, by comparing the efficacy of a delayed-release mesalazine (Asacol, Bracco S.p.A., Milan, Italy) against placebo in patients with ulcerative colitis with short- and long-duration of disease remission. METHODS: 112 patients (66 male, 46 female, mean age 35 years), with intermittent chronic ulcerative colitis in clinical, endoscopic and histological remission with sulphasalazine or mesalazine for at least 1 year, were included in the study. Assuming that a lower duration of remission might be associated with a higher relapse rate, the patients were stratified according to the length of their disease remission, prior to randomization into Group A (Asacol 26, placebo 35) in remission from 1 to 2 years, or Group B (Asacol 28, placebo 23) in remission for over 2 years, median 4 years. Patients were treated daily with oral Asacol 1.2 g vs. placebo, for a follow-up period of 1 year. RESULTS: We employed an intention-to-treat analysis. In Group A, whilst no difference was found between the two treatments after 6 months, mesalazine was significantly more effective than placebo in preventing relapse at 12 months [Asacol 6/26 (23%), placebo 17/35 (49%), P = 0.035, 95% Cl: 48-2.3%]. In contrast, in Group B no statistically significant difference was observed between the two treatments, either at 6 or 12 months [Asacol 5/28 (18%), placebo 6/23 (26%), P = 0.35, 95% Cl: 31-14%] of follow-up. Patients in group B were older, and had the disease and remission duration for longer, than those in Group A. CONCLUSIONS: Mesalazine prophylaxis is necessary for the prevention of relapse by patients with ulcerative colitis in remission for less than 2 years, but this study casts doubt over whether continuous maintenance treatment is necessary in patients with prolonged clinical, endoscopic and histological remission, who are at very low risk of relapse.

Factors affecting splanchnic haemodynamics in Crohn's disease: a prospective controlled study using Doppler ultrasound.

BACKGROUND: Current knowledge on splanchnic haemodynamics in Crohn's disease is limited. AIMS: To investigate which features of Crohn's disease affect splanchnic haemodynamics, and to establish whether portal vein (PV) and superior mesenteric artery (SMA) blood supply reflects clinical or biochemical activity of Crohn's disease. METHODS: Seventy nine patients with Crohn's disease and 40 controls were evaluated by Doppler ultrasound (US). The mean velocity of PV and SMA flow, the volume of blood flow of the PV and SMA, and the resistance index of SMA were studied. A series of clinical, biochemical, and US variables including Crohn's disease activity index, serum C reactive protein concentrations, disease duration and its anatomical location, smoking habits, abdominal complications, and current medical therapy, as well as the maximum bowel wall thickness as measured by US, were determined. The relation between PV and SMA blood flow and these variables was assessed by univariate and multivariate analysis. RESULTS: Patients with Crohn's disease had significantly higher PV and SMA flow and a lower SMA resistance index than controls. Stepwise multiple regression analysis identified bowel wall thickness and location of the disease as the main predictive variables of both PV and SMA blood flow variation, accounting for 36% and 45% of their variability, respectively. No relation was found between splanchnic haemodynamics and disease activity. CONCLUSION: A hyperdynamic mesenteric circulation does exist in Crohn's disease; however splanchnic blood flow does not reflect the clinical or biochemical activity of the disease, but seems to be linked more to other Crohn's disease characteristics, such as maximum bowel thickness and anatomical location.

Audit of reflux oesophagitis at 4 years.

BACKGROUND: Data on the natural history of reflux oesophagitis are few and conflicting: it is not clear whether in the long-term, patients still require therapy for controlling symptoms and preventing endoscopic relapse. AIMS: To assess, in reflux oesophagitis patients followed up for a median period of 4 years: a) clinical conditions throughout follow-up period (i.e., frequency of relapses, need and type of treatment, satisfaction with therapy; b) present state, including quality of life, mode of treatment, presence of residual symptoms or invalidity. PATIENTS: A series of 288 consecutive outpatients, diagnosed as having reflux oesophagitis during the period 1986-1990, and followed up for at least 48 months. METHODS: The study was carried out in two parts. The first, retrospective, assessing the outcome throughout follow-up during which it was suggested that patients assume a maintenance therapy with H2-receptor antagonists, proton pump inhibitors or other drugs for the first year, and to continue only if desired. Patients returned for follow-up every six months, and endoscopy was repeated after the first year or in the case of symptom recurrence. In the second part, after a median follow-up of 4 years, patients were submitted to a telephone interview by means of a structured questionnaire, assessing type and severity of current symptoms (if any), type of current therapy, degree of satisfaction with treatment, and overall evaluation of quality of life. RESULTS: Data are available from 132 patients (M/F = 85/47) of whom 119 (90%) were still on treatment and 31% still presented symptoms. During follow-up, 21% had more than 3 endoscopic relapses, 23% between 2 and 3, 28% one, and 28% zero, respectively and 79% were still adopting non-pharmacological measures (diet, posture, etc.). Only two (1.5%) had been submitted to surgery to control untractable symptoms/mucosal lesions. Finally, 64% and 11%, respectively, considered the present quality of life as good or excellent. CONCLUSIONS: Contrary to many reports, the prognosis of reflux oesophagitis is not favourable showing a marked trend to chronicity; the disease leads to almost continuous drug assumption for symptom control, and is associated with a high relapse risk after treatment withdrawal. Despite (or due to) these unfavourable features, patient compliance to both pharmacological and non-pharmacological therapy is excellent and, correspondingly, also the quality of life is acceptable or improved.

Continuous maintenance with low-dose lansoprazole versus Helicobacter pylori eradication in the prevention of duodenal ulcer recurrence.

BACKGROUND/AIMS: Reduction of gastric acid secretion by maintenance treatment with antisecretory agents and eradication of H. pylori by antibiotics constitute the most effective therapeutic options in preventing duodenal ulcer relapse. The aim of this study was to compare the effect of a 12-month low-dose lansoprazole maintenance treatment with H. pylori eradication on the rate of ulcer relapse in H. pylori-positive duodenal ulcer patients. METHODOLOGY: After a healing phase with lansoprazole 30 mg/die or lansoprazole 30-60 mg/die plus antibiotics (amoxycillin, tinidazole and colloidal bismuth subcitrate), 84 patients with healed duodenal ulcer entered the follow-up phase. Thirty-eight patients with persistent H. pylori infection received lansoprazole 15 mg at bedtime, whereas 46 in whom H. pylori was eradicated during the acute phase received no active therapy during the 12-month follow-up. The two groups were well balanced concerning all demographic characteristics. Clinical controls were performed every 3 months or sooner in the event of symptomatic relapse. RESULTS: In terms of per protocol analysis, the overall rate of ulcer relapse at 6 months was 5.5% (2/36) in the maintenance group and 0 (0/42) in the antibiotic group. The corresponding figures at 12 months were 20.5% (7/34) and 5.7% (2/35), respectively (p:ns, 95% CI for the difference -0.30+0.02). On intent to treat analysis, the rate of ulcer relapse at 6 months was 5.2% (2/38) in the first group and 0% (0/46) in the second group: at 12 months the corresponding figures were 19.4% (7/36) and 4.3% (2/46), respectively (p=0.06; CI 95%: +0.016+0.28). No significant side effects were observed during long-term maintenance with lansoprazole. CONCLUSIONS: Continuous maintenance with low-dose lansoprazole may constitute a valuable alternative to H. pylori eradication for the prevention of relapse and complications in duodenal ulcer patients not suitable for, or who have failed, H. pylori eradication.