In the Western world, nonalcoholic fatty liver disease(NAFLD) is considered as one of the most significant liver diseases of the twenty-first century. Its development is certainly driven by ...environmental factors, but it is also regulated by genetic background. The role of heritability has been widely demonstratedby several epidemiological, familial, and twin studies and case series, and likely reflects the wide interindividual and inter-ethnic genetic variability in systemic metabolism and wound healing response processes. Consistent with this idea, genome-wide association studies have clearly identified Patatin-like phosholipase domain-containing 3 gene variant I148 M as a major player in the development and progression of NAFLD. More recently, the transmembrane 6 superfamily member 2 E167 K variant emerged as a relevant contributor in both NAFLD pathogenesis and cardiovascular outcomes. Furthermore, numerous casecontrol studies have been performed to elucidate the potential role of candidate genes in the pathogenesis and progression of fatty liver, although findings are sometimes contradictory. Accordingly, we performed a comprehensive literature search and review on the role of genetics in NAFLD. We emphasize the strengths and weaknesses of the available literature and outline the putative role of each genetic variant in influencing susceptibility and/or progression of the disease.
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This article is linked to Caldera et al papers. To view these articles, visit https://doi.org/10.1111/apt.17454 and https://doi.org/10.1111/apt.17519
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
3.
Letter: propensity score—handle with care Macaluso, Fabio Salvatore; Orlando, Ambrogio
Alimentary pharmacology & therapeutics,
January 2021, 2021-01-00, 20210101, Volume:
53, Issue:
2
Journal Article
Peer reviewed
Open access
LINKED CONTENT
This article is linked to Townsend et al and Townsend & Subramanian papers. To view these articles, visit https://doi.org/10.1111/apt.16057 and https://doi.org/10.1111/apt.16211
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Inflammatory bowel disease (IBD) and psoriasis (PS) are associated conditions. The reason for this association lies in the sharing of predisposition genes and common immunological mechanisms.
This ...review will focus on the interplay between IBD and PS, with details on prevalence and phenotype of PS in IBD, genetics, pathogenetic pathways, and therapy. Key Messages: Microbiome seems relevant in both conditions: a reduction of beneficial bacteria has been observed. IBD and PS have in common some comorbidities like cardiovascular disease, similar risk of cancer and psychiatric problems. Many biological therapies such as anti-tumour necrosis factor (TNF) and anti-interleukin 23 are effective in both conditions, underlining the common immunological mechanisms. Paradoxical PS has been mainly observed after anti-TNF therapies, but preliminary reports show that it can also occur with other biologics. Genetic predisposition to this phenomenon has been reported.
Introduction: Colorectal cancer (CRC) is the third most common cancer in males and second in females, and the fourth most common cause of cancer death worldwide. Currently, about 60-70% of diagnosed ...cases in symptomatic patients are detected at an advanced stage of disease. Earlier stage detection through the use of screening strategies would allow for better outcomes in terms of reducing the disease burden.
Areas covered: The aim of this paper is to review the current published evidence from literature which assesses the performance and effectiveness of different screening tests for the early detection of CRC.
Expert commentary: Adequate screening strategies can reduce CRC incidence and mortality. In the last few decades, several tests have been proposed for CRC screening. To date, there is still insufficient evidence to identify which approach is definitively superior, and no screening strategy for CRC can therefore be defined as universally ideal. The best strategy would be the one that can be economically viable and to which the patient can adhere best to over time. The latest guidelines suggest colonoscopy every 10 years or annual fecal immuno-chemical test (FIT) for people with normal risk, while for individuals with high risk or hereditary syndromes specific recommendations are provided.
Inflammatory bowel disease, including both Crohn's disease and ulcerative colitis, are two chronic and progressive disorders affecting the gastrointestinal tract. Research on the molecular mechanisms ...of both diseases has led to the introduction of targeted therapies which are able to selectively block the key inflammatory mediators.
Here, we discuss the current evidence about the mechanism of action with an up to date review of the efficacy and safety of Janus kinase inhibitors in inflammatory bowel disease.
Multiple small molecule drugs have been evaluated for their use in both ulcerative colitis and Crohn's disease. Janus kinase inhibitors represent the most important family of these drugs, as their particular mechanism of action enables a simultaneous and effective blockade of multiple cytokines involved in the pathogenesis of the disease.
Janus kinase inhibitors represent a promising therapeutic strategy, especially in ulcerative colitis. More data are still necessary regarding its efficacy and safety in clinical practice.
Postoperative recurrence (POR) following ileocolonic resection is a major concern in patients with Crohn's disease (CD). The role of ustekinumab (UST) in this setting is poorly known.
All consecutive ...CD patients with a baseline colonoscopy at 6-12 months from ileocolonic resection showing POR (Rutgeerts score ≥ i2) who were treated with UST after the baseline colonoscopy and with an available post-treatment endoscopy, were extracted from the cohort of the Sicilian Network for Inflammatory Bowel Diseases (SN-IBD). The primary outcome was endoscopic success, defined as reduction of at least one point of Rutgeerts score. The secondary outcome was clinical success, assessed at the end of follow-up. Reasons for clinical failure included mild clinical relapse (Harvey-Bradshaw index 5-7), clinically relevant relapse (Harvey-Bradshaw index > 7), and need for new resection.
Forty-four patients were included (mean follow-up: 17.8 ± 8.4 months). The baseline postoperative colonoscopy showed severe POR (Rutgeerts score i3 or i4) in 75.0% of patients. The post-treatment colonoscopy was performed after a mean of 14.5 ± 5.5 months following initiation of UST. Endoscopic success was reported in 22 out of 44 (50.0%) patients, of whom 12 (27.3%) achieved a Rutgeerts score i0 or i1. Clinical success at the end of follow-up was reported in 32 out of 44 patients (72.7%); none of the 12 patients with clinical failure had achieved endoscopic success at post-treatment colonoscopy.
Ustekinumab could be a promising option for the treatment of POR of CD.
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No data on European countries about knowledge and application of immunization strategies in patients with inflammatory bowel disease (IBD) are available.
We designed a questionnaire aimed at ...exploring these issues among Italian gastroenterologists dealing with adult and paediatric IBD.
An anonymous, 24-item, questionnaire was sent via e-mail to all members of the Italian Group for the study of Inflammatory Bowel Disease. Three sets of questions were formulated: (1) Characteristics of respondents; (2) General opinions on the role of vaccines in IBD patients; (3) Immunizations of IBD patients in clinical practice.
Of the 455 total surveys sent, there were 198 respondents (response rate: 43.5%). The great majority of respondents (82.9%) reputed as "very important" to perform the vaccinations recommended by the guidelines in patients with IBD. The indication to immunization is given at the diagnosis of the disease by 55.6% of the respondents. The most frequently recommended vaccine in IBD patients is the annual flu vaccine, while the recommendation rate for the other vaccines is variable depending on the different pathogens.
Efforts carried out by the scientific societies are required to increase the awareness of this relevant topic among physicians.
Background and Aim
There are few clinical data on Adalimumab (ADA) biosimilars in inflammatory bowel disease. We aimed to perform a multicenter, observational, prospective study on safety and ...effectiveness of ADA biosimilar ABP 501 in patients with inflammatory bowel disease.
Methods
All consecutive patients from the cohort of the Sicilian Network for Inflammatory Bowel Disease treated with ADA biosimilar ABP 501 from February 2019 to February 2020 were enrolled. Patients were divided into three groups: group A, naïve to ADA and naïve to anti‐tumor necrosis factors; group B, naïve to ADA and previously exposed to anti‐tumor necrosis factors; and group C: switched from ADA originator to ABP 501.
Results
A total of 559 patients (median age 39 years; Crohn's disease 88.0%, ulcerative colitis 12.0%) were included, with a follow‐up time of 403.4 patient‐years. Thirty‐six serious adverse events occurred in 36 patients (6.4%; incidence rate IR: 8.9 per 100 person‐years PY). The IR of serious adverse events was higher among patients in group A compared with group C (17.4 vs 4.8 per 100 PY; IR ratio = 3.61; P < 0.001) and among patients in group B compared with group C (16.4 vs 4.8 per 100 PY; IR ratio = 3.42; P = 0.041). Among ADA‐naïve patients (group A + B), 188 (85.8%) had a clinical response after 12 weeks, including 165 (75.3%) who achieved steroid‐free remission. Higher treatment persistence estimates were reported for patients in group C compared with groups A and B (log–rank P < 0.001).
Conclusions
Safety and effectiveness of ABP 501 seem to be overall similar to those reported for ADA originator. Switching from originator to ABP 501 was safe and effective.
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Over the past decade, the improvement in the understanding of the molecular mechanisms of Crohn’s disease (CD) led to the development of more targeted therapies, including biologics - i.e. monoclonal ...antibodies that selectively block key mediators of inflammation - and novel small molecule drugs - i.e. compounds with a molecular weight <1 kDa able to diffuse through cell membranes and then fit for the oral route of administration - which will enrich the therapeutic armamentarium of CD soon. In parallel with the expansion of the medical options, the therapeutic targets to be achieved in patients with CD have changed. In particular, we moved from the simple control of symptoms to more ambitious goals which aim to permanently extinguish the inflammation, even the subclinical one. As a consequence, the role of some of the conventional drugs which have been used in CD for several years, such as 5-aminosalicylates and conventional immunosuppressants, is becoming more limited in favor of these new drugs. This profound modification of CD therapy and the intrinsic complexity of the disease are relevant to the point that the management of inflammatory bowel diseases is gradually becoming a subspecialty in the field of gastroenterology or internal medicine.
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