F D'Heygere

Lymphocytic colitis: a distinct clinical entity? A clinicopathological confrontation of lymphocytic and collagenous colitis

BACKGROUND AND AIMS It is not known whether lymphocytic colitis and collagenous colitis represent different clinical entities or constitute part of a spectrum of disease. METHODS Detailed clinical features and histological findings were compared in a large series of patients with confirmed lymphocytic and collagenous colitis. RESULTS Histological diagnosis was confirmed in 96 patients with collagenous colitis and 80 with lymphocytic colitis. Twenty eight per cent of patients with collagenous colitis and 26% of patients with lymphocytic colitis had overlapping but less pronounced histological features. Both groups were equal in terms of age, use of aspirin and non-steroidal anti-inflammatory drugs, associated autoimmune conditions, arthritis, diarrhoea, and abdominal pain. The male:female ratio was 27:73 for collagenous colitis and 45:55 for lymphocytic colitis (p=0.013). Twenty five per cent of patients with collagenous colitis compared with 14% of patients with lymphocytic colitis were active smokers; only 8.3% of patients with collagenous colitis had stopped smoking compared with 23% of patients with lymphocytic colitis (p=0.013). Drug induced disease was suspected for ticlopidine (two collagenous colitis, four lymphocytic colitis) and flutamide (four lymphocytic colitis). Mean duration of symptoms before diagnosis was two months for lymphocytic colitis and four months for collagenous colitis. Overall prognosis was generally mild; 84% of patients with lymphocytic colitis and 74% of patients with collagenous colitis reported resolution or significant improvement (p=0.033). CONCLUSIONS Collagenous and lymphocytic colitis are similar but not identical. Patients with lymphocytic colitis present somewhat earlier and are less likely to be active smokers. Symptoms are milder and more likely to disappear in lymphocytic colitis. Ticlopidine and flutamide should be added to the list of drugs inducing colitis.

Efficacy of interferon‐based antiviral therapy in patients with chronic hepatitis C infected with genotype 5: A meta‐analysis of two large prospective clinical trials

The characteristics and response rate to pegylated interferon and ribavirin (PEG‐INF + RBV) of patients with chronic hepatitis C infected with genotype 5 are poorly documented. A meta‐analysis of two large phase III/IV prospective randomized clinical trials conducted in Belgium in patients with chronic hepatitis C (n = 1,073 patients) was performed in order to compare the response to antiviral therapy of hepatitis C virus (HCV) genotype 5 with that of other HCV genotypes. A subset of HCV‐1 infected patients selected from within the study database were selected to match the HCV‐5 sample for known prognostic factors. In Belgium HCV‐5 is responsible for a significant minority of cases of chronic hepatitis C CHC (4.5%) and is characterized by a more advanced age (58.4 years), a high frequency of cirrhosis (27.7%), a specific mode of HCV acquisition, and a particular geographic origin (66.7% of patients from West Flanders). The primary comparative analysis showed that response to treatment with PEG‐INF + RBV of HCV‐5 is similar to HCV‐1 and lower compared to HCV‐2/3. The analysis of the matched patient subgroup demonstrates that the HCV‐5 “intrinsic sensitivity” to PEG‐IFN + RBV therapy is identical to HCV‐1, with a sustained virological response of 55% in both groups. In contrast to previous publications, this meta‐analysis suggests that HCV‐5 response to treatment is closer to HCV‐1 than to HCV‐2/3 and suggests that in Belgium HCV‐5 infection should be treated with the same antiviral regimen as HCV‐1. J. Med. Virol. 83:815–819, 2011.

Clinical trial: a randomized trial of pegylated-interferon-alpha-2a plus ribavirin with or without amantadine in treatment-naive or relapsing chronic hepatitis C patients

Background  The combination therapy of pegylated‐interferon‐α2a plus ribavirin is considered as the standard of care for patients with chronic hepatitis C. A sustained viral response is obtained in 40–50% of naïve patients with genotype 1 and in around 80% of naïve patients with genotype 2 or 3.

Hepatitis B virus and hepatitis C virus infections in Belgium: similarities and differences in epidemics and initial management.

Introduction Nationwide studies comparing patients with hepatitis B and C virus (HBV and HCV) infections are mandatory for assessing changes in epidemiology. Aim The aim of this study was to compare epidemiological data and initial management of newly diagnosed patients with persistent HBV (HBsAg positive) or HCV (detectable HCV RNA) infection in Belgium. Patients and methods Data were extracted from two Belgian observational databases. Results A total of 655 patients (387 HBV and 268 HCV) were included. Compared with HCV patients, HBV patients were younger, more frequently men, more often of Asian or African origin (43 vs. 10%, P<0.0001), and less frequently contaminated by transfusion or intravenous drug use (9 and 6% vs. 34 and 44%, P<0.0001). Viral replication was assessed in 89% of HBV patients. Compared with HCV patients, HBV patients more frequently had normal alanine aminotransferase (ALT) levels (65 vs. 29%, P<0.0001), less frequently underwent liver biopsy (29 vs. 67%, P<0.0001), and were less often considered for antiviral therapy (25 vs. 54%, P<0.0001). When taking only HBV patients with detectable viral replication into consideration, results remained unchanged. During the multivariate analysis, ALT was a major factor for performing liver biopsy or considering antiviral therapy in both groups. Conclusion HBV and HCV screening policies should be targeted toward immigrants and intravenous drug users, respectively. Guidelines recommending systematic search for viral replication should be reinforced in HBV patients. HBV patients less frequently underwent liver biopsy and were less often considered for antiviral therapy compared with HCV patients. Despite the lack of sensitivity and specificity, ALT remains a pivotal decision-making tool for liver biopsy and antiviral therapy in both infections.

Belgian experience with direct acting antivirals in people who inject drugs

BACKGROUND AND AIM Hepatitis C viral infection (HCV) has become a curable disease due to the development of direct acting antivirals (DAA). The WHO has set a target to eliminate HCV completely. Therefore, people who inject drugs (PWID) also need to be treated. In this study, we compared the real-life uptake and outcome of DAA treatment for HCV in PWID and non-PWID. METHODS We performed a nation-wide, retrospective cohort study in 15 hospitals. All patients who were treated with simeprevir-sofosbuvir, daclatasvir-sofosbuvir, or ombitasvir/paritaprevir ritonavir-dasabuvir between December 2013 and November 2015 were included. RESULTS The study population consisted of 579 patients: 115 PWID (19.9%) and 464 non-PWID (80.1%). Of the PWID 18 were active PWID (15.6%), 35 still received opiate substitution therapy (OST) (30.4%) and 62 were former PWID without OST (53.9%). PWID were more infected with genotype 1a and 3 (p=0.001). There were equal rates of side-effects (44.7% vs. 46.6%; p=0.847), similar rates of treatment completion (95.7% vs 98.1%; p=0.244) and SVR (93.0% vs 94.8%; p=0.430) between PWID and non-PWID, respectively. CONCLUSION PWID, especially active users, are underserved for DAA treatment in real life in Belgium. Reimbursement criteria based on fibrosis stage make it difficult to treat PWID. Treatment adherence is similar in PWID and the general population, even in patients with active abuse. DAA were safe and effective in PWID despite the higher prevalence of difficult-to-treat genotypes. Based on these data more efforts to treat PWID are needed and policy changes are necessary to reach the WHO targets.

Belgian experience with triple therapy with boceprevir and telaprevir in genotype 1 infected patients who inject drugs

No data have been reported yet on treatment outcome in persons who inject drugs (PWID) infected with hepatitis C virus treated with boceprevir or telaprevir in combination with peginterferon (Peg IFN) and ribavirin (RBV). Additionally, there are concerns about the safety of boceprevir and telaprevir in some subgroups of patients with hepatitis C (HCV). In a cohort of HCV patients infected with genotype 1 in Belgium, treatment outcome of patients infected due to IV drug use was analyzed and compared with patients who have no history of substance use. The study population consisted of 179 patients: 78 PWID and 101 controls treated with boceprevir (n = 79) or telaprevir (n = 100) additional to Peg IFN and RBV; 53 (30%) had advanced disease (F3, F4) and 79 (44%) had an antiviral therapy previously. There were no significant differences in the baseline characteristics between both groups, except that PWID patients were more frequently infected with genotype 1a (67% vs 21%), were younger and were predominantly male. Psychiatric complaints during follow‐up occurred more frequently in the PWID patients: 24% versus 11% (P = .02). Treatment failure for other reasons than absence of viral response was 70% and 64% in PWID and non‐PWID respectively. The sustained viral response (SVR) rates were similar in both groups (71% in PWID vs 72% in non‐PWID); with a non‐inferiority test with −5% margin there is a difference of −1% (95% CI [−15%, 13%]) and P = 0.30. There are no reasons to exclude PWID from treatment with boceprevir, telaprevir and novel antiviral therapies. J. Med. Virol. 88:94–99, 2016.

Preference for a prefilled syringe or an auto-injection device for delivering golimumab in patients with moderate-to-severe ulcerative colitis: a randomized crossover study

Purpose Simponi® (golimumab, MSD) is a fully human monoclonal antibody against tumor necrosis factor alpha administered subcutaneously using an autoinjector or a prefilled syringe. This study examined preference for administration of golimumab by autoinjector or prefilled syringe in patients with moderate-to-severe ulcerative colitis (UC). Patients and methods This was a multicenter, open-label, randomized crossover trial (EudraCT no 2014-000656-29). Patients with moderate-to-severe UC were randomized 1:1 to receive 2 subcutaneous injections of 50 mg golimumab with the autoinjector followed by 2 injections of 50 mg with the prefilled syringe or the same 4 injections administered in the opposite order. Patients assessed preference, ease of use, and discomfort immediately after the injections and 2 weeks later. Results Ninety-one patients were included (median age=42.7 years [range, 19.7–93.7]; 58% male). The autoinjector was preferred by 76.9% of patients immediately after injections and by 71.4% 2 weeks later. The autoinjector was more often considered extremely easy or easy to use (94.5%) than the prefilled syringe (73.6%). Moderate discomfort or worse was reported by more patients when using the prefilled syringe (20.9%) than when using the autoinjector (5.5%), and severe discomfort or discomfort preventing injection of future doses was reported by 8.8% for the pre-filled syringe but not at all when using the autoinjector. A favorable or extremely favorable overall impression was reported by 89.0% for the autoinjector and 72.5% for the prefilled syringe. Conclusion Most patients with moderate-to-severe UC preferred to self-administer golimumab with the autoinjector over a prefilled syringe.

711 HEPATITIS B VIRUS (HBV) INFECTION IN BELGIUM: RESULTS OF THE BELGIAN ASSOCIATION FOR THE STUDY OF THE LIVER (BASL) REGISTRY OF 1421 HBSAG CHRONIC CARRIERS

response and improved clinical outcome in HBeAg positive patients. In previous studies, age, gender, ALT, AFP, fibrosis, HBV-DNA, precore/core promoter mutation, HLA, and genotype are considered to be important factors for HBeAgSC. The aim of our study is to identify predicting factors for HBeAgSC within a year. Methods: From 1991 to 2005, liver biopsies were performed on 851 Hepatitis B s antigen positive patients in our hospital. From this group, 234 HBeAg positive patients were chosen to be subjects for this study. In 60 (26%) patients, HBeAgSC was observed within a year after liver biopsy, but in the remaining 174 (74%) patients, HBeAgSC was not observed. We compared the following factors between the two groups; age; gender; ALT; platelets; albumin; AFP; pathological features; HBeAg; HBV DNA; HBcrAg levels; mutations in the precore (G1896A) / core promoter (A1762T / G1764A) domain; and antiviral treatments. Results: Age (37 vs. 37: n.s.); gender (M/F) (43/17 vs. 118/56: n.s.); median ALT level (213 vs.125 IU/L: p = 0.004); median platelets level (171 vs. 186×103/ml: n.s.); median albumin level (4.1 vs. 4.1 g/dl: n.s.); median AFP level (12.0 vs. 6.0: p = 0.048); F0–1/2–4 (13/47 vs. 75/99: 0.043); cell infiltration in portal area 0–1/2–4 (12/48 vs. 59/115: 0.043); piecemeal necrosis 0–1/2–4 (20/40 vs. 91/83: 0.011); lobular inflammation 0–1/2–4 (15/45 vs. 80/94: p = 0.004); median HBeAg level (99 vs. 888 s/co: p< 0.000); median HBV DNA level (7.2 vs.8.0 log copies/ml: p< 0.000); median HBcrAg level (7.2 vs. 8.1 LogU/ml: p < 0.000), antiviral treatment (yes/no) (29/31 vs. 62/112: n.s.). Under multivariate analysis, HBeAg (<500 s/co), lobular inflammation (≥2), precore mutant, core promoter mutant were identified as independent factors for HBeAgSC. Especially, the patients with 2 favorable predictors (HBeAg and lobular inflammation) achieved HBeAgSC in 55% of cases. But, the patients without 2 favorable factors experienced HBeAgSC in only 6 % of cases. Conclusions: Low serum HBeAg level (<500) and severe lobular inflammation (≥2) are independent factors for HBeAgSC within a year. HBeAgSC could be predicted by evaluation for these two factors.