Erika Belard

Prednisolone treatment affects the performance of the QuantiFERON gold in-tube test and the tuberculin skin test in patients with autoimmune disorders screened for latent tuberculosis infection†‡

Background: During screening for latent tuberculosis infection (LTBI), before anti‐tumor‐necrosis‐factor‐&agr; treatment, most patients are already receiving immunosuppressive therapy. The objective was to evaluate the performance of the QuantiFERON Gold In‐Tube (QFT‐IT) and the Tuberculin Skin Test (TST). Methods: A prospective multicenter study included 248 patients with ulcerative colitis (39), Crohns disease (54), rheumatoid arthritis (111), and spondylo‐arthropathy (44). Results: QFT‐IT was positive in 7/248 (3%), negative in 229 (92%), and indeterminate in 12 (5%). TST was positive in 54/238 (23%) patients. Chest x‐ray was suspect for tuberculosis in 5/236 (2%), and 35/167 (21%) had ≥1 risk‐factors for infection with Mycobacterium tuberculosis. The main finding was a pronounced negative effect on QFT‐IT and TST performance associated with prednisolone treatment. During prednisolone treatment interferon gamma (IFN‐&ggr;) response to mitogen stimulation was impaired (median IFN‐&ggr; response 4.9 IU/mL; interquartile range [IQR] 0.8 to ≥10.0) compared to patients 1) not receiving corticosteroids (median ≥10.0; IQR 5.0 to ≥10.0; P = 0.0015) or 2) receiving long‐acting corticosteroids (median >10.0; IQR 9.7 to >10.0; P = 0.0058). Prednisolone treatment was strongly associated with negative TST, adjusted odds ratio (AOR) 0.22 (0.1–0.8; P = 0.018), and with an increased risk of indeterminate QFT‐IT results AOR 16.1 (4.1–63.2; P < 0.001), whereas no negative effect was found for long‐acting corticosteroids. Doses of ≥10 mg prednisolone were associated with a 27% risk of indeterminate results. Single use of azathioprine, methotrexate, or 5‐aminosalicylate (5‐ASA) did not affect the test results. Conclusions: Oral prednisolone severely suppressed QFT‐IT and TST performance, whereas the long‐acting corticosteroids methotrexate, azathioprine, and 5‐ASA did not have a similar detrimental effect. Patients should be screened for LTBI with QFT‐IT or TST prior to initiation of prednisolone therapy and negative QFT‐IT or TST results interpreted with caution in patients treated with any corticosteroid until further data are available. (Inflamm Bowel Dis 2011;)

Fecal Calprotectin Measured By Patients at Home Using Smartphones—A New Clinical Tool in Monitoring Patients with Inflammatory Bowel Disease

Background:Fecal calprotectin is a reliable noninvasive marker for intestinal inflammation usable for monitoring patients with inflammatory bowel disease. Tests are usually performed by enzyme-linked immunosorbent assay (ELISA), which is time consuming and delays results, thus limiting its use in clinical practice. Our aim was to evaluate CalproSmart, a new rapid test for fecal calprotectin performed by patients themselves at home, and compare it to gold standard ELISA. Methods:A total of 221 patients with inflammatory bowel disease (115 ulcerative colitis and 106 Crohns disease) were included. The CalproSmart test involves extraction of feces, application to the lateral flow device, and taking a picture with a smartphone after 10 minutes of incubation. Results appear on the screen within seconds. Patients were instructed at inclusion and had a video guide of the procedure as support. When using CalproSmart at home, patients also sent in 2 fecal samples to be analyzed by ELISA. Results:Totally, 894 fecal calprotectin results were obtained by ELISA, and 632 of them from CalproSmart. The correlation coefficient was 0.685, higher for academics than nonacademics (0.768 versus 0.637; P = 0.0037). The intra-assay and interassay coefficients of variation of the CalproSmart test were 4.42% and 12.49%, respectively. The sensitivity, specificity, positive predictive value, and negative predictive value were 82%, 85%, 47%, and 97%, respectively, with an optimal cutoff at 150 &mgr;g/g. Conclusions:The CalproSmart test performed by patients with inflammatory bowel disease for fast assessment of gut inflammation seems a reliable alternative to ELISA and presents a new way of monitoring patients by eHealth.

Immunosuppressive drugs impairs antibody response of the polysaccharide and conjugated pneumococcal vaccines in patients with Crohn's disease

BACKGROUND Patients with Crohns disease (CD) have a higher risk of infectious diseases including pneumococcal infections, and the risk increases with immunotherapy. The primary endpoint of this study was to investigate the specific antibody response to two pneumococcal vaccines in CD patients with and without immunosuppressive treatment four weeks post vaccination. METHODS In a randomized trial of the 23-valent pneumococcal polysaccharide vaccine (PPV23) and the 13-valent pneumococcal conjugated vaccine (PCV13), a group of CD patients treated with immunosuppressive drugs (IS) alone or in combination with TNF-α antagonists were compared to a group of CD patients not treated with any of these drugs (untreated). Specific pneumococcal antibody concentrations were measured against 12 serotypes common to the two vaccines before and 4 week after vaccination. RESULTS PCV13 induced a significantly higher antibody response for one serotype (23F) in IS treated patients and for two serotypes (9V and 23F) in untreated patients compared to CD patients vaccinated with PPV23. Untreated PPV23 recipients had higher responses for serotypes 9V and 18C compared to IS+TNF-α treated PPV23 recipients. Comparison between treatment groups showed that immunosuppressive treatment impaired the antibody response to both vaccines and that TNF-a treatment further conveyed additional impairment of the response. CONCLUSION PCV13 induces higher antibody response for some serotypes compared to PPV23. In addition, CD patients treated with immunosuppressive drugs alone or in combination with TNF-α antagonists had an impaired antibody response to both PPV23 and PCV13 compared to patients not receiving any of these treatments. The study has been registered in the European Clinical Trials Database (EudraCT, record no 2012-002867-86) and ClinicalTrials.gov (record no. NCT01947010).

Sofosbuvir based treatment of chronic hepatitis C genotype 3 infections: A Scandinavian real-life study

Background and aims Chronic hepatitis C virus (HCV) genotype 3 infection with advanced liver disease has emerged as the most challenging to treat. We retrospectively assessed the treatment outcome of sofosbuvir (SOF) based regimes for treatment of HCV genotype 3 infections in a real life setting in Scandinavia. Methods Consecutive patients with chronic HCV genotype 3 infection were enrolled at 16 treatment centers in Denmark, Sweden, Norway and Finland. Patients who had received a SOF containing regimen were included. The fibrosis stage was evaluated by liver biopsy or transient liver elastography. The following treatments were given according availability and local guidelines: 1) SOF + ribavirin (RBV) for 24 weeks, 2) SOF + daclatasvir (DCV) +/-RBV for 12–24 weeks, 3) SOF + pegylated interferon alpha (peg-IFN-α) + RBV for 12 weeks or 4) SOF/ledipasvir (LDV) + RBV for 12–16 weeks. The primary endpoint was sustained virological response (SVR) assessed at week 12 (SVR12) after end of treatment. Results We included 316 patients with a mean age of 55 years (range 24–79), 70% men, 49% treatment experienced, 58% with compensated cirrhosis and 12% with decompensated cirrhosis.In the modified intention to treat (mITT) population SVR12 was achieved in 284/311 (91%) patients. Among 26 treatment failures, five had non-response, 3 breakthrough and 18 relapse. Five patients were not included in the mITT population. Three patients died from reasons unrelated to treatment and two were lost to follow-up. The SVR12 rate was similar for all treatment regimens, but lower in men (p = 0.042), and in patients with decompensated liver disease (p = 0.004). Conclusion We found that sofosbuvir based treatment in a real-life setting could offer SVR rates exceeding 90% in patients with HCV genotype 3 infection and advanced liver disease.

Liver-related morbidity and mortality in patients with chronic hepatitis C and cirrhosis with and without sustained virologic response

Background Chronic hepatitis C (CHC) causes liver cirrhosis in 5%–20% of patients, leading to increased morbidity and mortality. This study aimed to estimate liver-related morbidity and mortality among patients with CHC and cirrhosis in Denmark with and without antiviral treatment and sustained virologic response (SVR). Furthermore we aimed to estimate the rate of hepatocellular carcinoma (HCC) and decompensation associated with certain prognostic factors. Materials and methods Patients with CHC and cirrhosis registered in the Danish Database for Hepatitis B and C were eligible. Cirrhosis was based on liver biopsy, transient elastography, and clinical cirrhosis. Data were extracted from nationwide registries. The study period was from 2002 until 2013. Results Of 1,038 patients included, 716 (69%) were male and the median age was 52 years. Median follow-up was 3.8 years, 360 patients died, and 233 of 519 treated patients achieved SVR. Alcohol overuse and hepatitis C virus genotype 3 were associated with an increased incidence rate (IR) of HCC, whereas diabetes and alcohol overuse were associated with increased IRs of decompensation. Achieving SVR reduced all-cause mortality (adjusted mortality rate ratio 0.68 [95% CI 0.43–1.09]) and liver-related mortality (mortality rate ratio 0.6 [95% CI 0.36–1]), as well as liver-related morbidity with adjusted IR ratios of 0.37 (95% CI 0.22–0.62) for HCC and 0.31 (95% CI 0.17–0.57) for decompensation. The IRs of HCC and decompensation remained elevated in patients with alcohol overuse after SVR. Conclusion Alcohol overuse, hepatitis C genotype 3, and diabetes were associated with liver-related morbidity in patients with CHC and cirrhosis. SVR markedly reduced liver-related morbidity and mortality; however, special attention to patients with alcohol overuse should continue after SVR.

Direct acting antiviral treatment of chronic hepatitis C in Denmark: factors associated with and barriers to treatment initiation

OBJECTIVES We describe factors associated with and barriers to initiation of Direct Acting Antiviral (DAA) treatment in patients with chronic hepatitis C, who fulfill national fibrosis treatment guidelines in Denmark. MATERIALS AND METHODS In this nationwide cohort study, we included patients with chronic hepatitis C from The Danish Database for Hepatitis B and C (DANHEP) who fulfilled fibrosis treatment criteria. Factors associated with treatment initiation and treatment failure were determined by logistic regression analyses. Medical records were reviewed from patients who fulfilled fibrosis treatment criteria, but did not initiate DAA treatment to determine the cause. RESULTS In 344 (49%) of 700 patients, who fulfilled treatment criteria, factors associated with DAA treatment initiation were transmission by other routes than injecting drug use odds ratio (OR) 2.13 (CI: 1.38-3.28), previous treatment failure OR 2.58 (CI: 1.84-3.61) and ALT above upper limit of normal OR 1.60 (CI: 1.18-2.17). The most frequent reasons for not starting treatment among 356 (51%) patients were non-adherence to medical appointments (n = 107/30%) and ongoing substance use (n = 61/17%). Treatment failure with viral relapse occurred in 19 (5.5%) patients, who were more likely to have failed previous treatment OR 4.53 (CI: 1.59-12.91). CONCLUSIONS In this nationwide cohort study, we found non-adherence to medical appointments and active substance use to be major obstacles for DAA treatment initiation. Our findings highlight the need for interventions that can overcome these barriers and increase the number of patients who can initiate and benefit from curative DAA treatment.

Hepatocellular carcinoma in patients with chronic hepatitis C and cirrhosis in Denmark: a nationwide cohort study

Cirrhosis in patients with chronic hepatitis C increases the risk of hepatocellular carcinoma (HCC), and surveillance with ultrasound (US) and alpha‐fetoprotein (AFP) is recommended. This study aimed to estimate changes in the HCC incidence rate (IR) over time, HCC stage and prognosis, and AFP and US performed in patients with hepatitis C and cirrhosis. Eligible patients were identified in the Danish Database for Hepatitis B and C, and data from national health registries and patient charts were obtained. Tumour stage was based on Barcelona‐Clinic Liver Cancer stage, TNM classification and size and number of lesions combined into stages 0‐3. We included 1075 patients with hepatitis C and cirrhosis, free of HCC and liver transplant at baseline. During 4988 person years (PY), 115 HCC cases were diagnosed. The HCC incidence rate increased from 0.8/100 PY [CI95% 0.4‐1.5] in 2002‐2003 to 2.9/100 PY [2.4‐3.4] in 2012‐2013. One‐year cumulative incidence of at least one AFP or US was 53% among all patients. The positive predictive value of an AFP ≥ 20 ng mL−1 was 17%. Twenty‐three (21%) patients were diagnosed with early‐stage HCC (stage 0/1) and 84 (79%) with late stage. Median survival after HCC for early‐stage HCC disease was 30.1 months and 7.4 months for advanced HCC (stage 2/3). The incidence rate of HCC increased over time among patients with hepatitis C and cirrhosis in Denmark. Application of AFP and US was suboptimal, and most patients were diagnosed with advanced HCC with a poor prognosis.