Abstract Nonalcoholic fatty liver disease (NAFLD) represents one of the most common causes of chronic liver disease, and its prevalence is rising worldwide. The occurrence of nonalcoholic ...steatohepatitis (NASH) is associated with a substantial increase in disease related morbidity and mortality. Accordingly, there has been a surge of innovation surrounding drug development in an effort to off-set the natural progression and long-term risks of this disease. Disease assessment within clinical trials and clinical practice for NAFLD is currently done with liver biopsies. Liver biopsy-based assessments, however, remain imprecise and are not without cost or risk. This carries significant implications for the feasibility and costs of bringing therapeutic interventions to market. A need therefore arises for reliable and highly accurate surrogate end-points that can be used in phase 2 and 3 clinical trials to reduce trial size requirements and costs, while improving feasibility and ease of implementation in clinical practice. Significant advances have now been made in magnetic resonance technology, and magnetic resonance imaging (MRI) and elastrography (MRE) have been demonstrated to be highly accurate diagnostic tools for the detection of hepatic steatosis and fibrosis. In this review article, we will summarize the currently available evidence regarding the use of MRI and MRE among NAFLD patients, and the evolving role these surrogate biomarkers will play in the rapidly advancing arena of clinical trials in NASH and hepatic fibrosis. Furthermore, we will highlight how these tools can be readily applied to routine clinical practice, where the growing burden of NAFLD will need to be met with enhanced monitoring algorithms.
A comprehensive knowledge of the natural history of ulcerative colitis (UC) helps understand disease evolution, identify poor prognostic markers and impact of treatment strategies, and facilitates ...shared decision-making. We systematically reviewed the natural history of UC in adult population-based cohort studies with long-term follow-up.
Through a systematic literature review of MEDLINE through March 31, 2016, we identified 60 studies performed in 17 population-based inception cohorts reporting the long-term course and outcomes of adult-onset UC (n = 15,316 UC patients).
Left-sided colitis is the most frequent location, and disease extension is observed in 10%-30% of patients. Majority of patients have a mild-moderate course, which is most active at diagnosis and then in varying periods of remission or mild activity; about 10%-15% of patients experience an aggressive course, and the cumulative risk of relapse is 70%-80% at 10 years. Almost 50% of patients require UC-related hospitalization, and 5-year risk of re-hospitalization is ∼50%. The 5-year and 10-year cumulative risk of colectomy is 10%-15%; achieving mucosal healing is associated with lower risk of colectomy. About 50% of patients receive corticosteroids, although this proportion has decreased over time, with a corresponding increase in the use of immunomodulators (20%) and anti-tumor necrosis factor (5%-10%). Although UC is not associated with an increased risk of mortality, it is associated with high morbidity and work disability, comparable to Crohn's disease.
UC is a disabling condition over time. Prospective cohorts are needed to evaluate the impact of recent strategies of early use of disease-modifying therapies and treat-to-target approach with immunomodulators and biologics. Long-term studies from low-incidence areas are also needed.
Liver fibrosis is the most important predictor of mortality in nonalcoholic fatty liver disease (NAFLD). Quantitative risk of mortality by fibrosis stage has not been systematically evaluated. We ...aimed to quantify the fibrosis stage–specific risk of all‐cause and liver‐related mortality in NAFLD. Through a systematic review and meta‐analysis, we identified five adult NAFLD cohort studies reporting fibrosis stage–specific mortality (0‐4). Using fibrosis stage 0 as a reference population, fibrosis stage–specific mortality rate ratios (MRRs) with 95% confidence intervals (CIs) for all‐cause and liver‐related mortality were estimated. The study is reported according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses statement. Included were 1,495 NAFLD patients with 17,452 patient years of follow‐up. Compared to NAFLD patients with no fibrosis (stage 0), NAFLD patients with fibrosis were at an increased risk for all‐cause mortality, and this risk increased with increases in the stage of fibrosis: stage 1, MRR = 1.58 (95% CI 1.19‐2.11); stage 2, MRR = 2.52 (95% CI 1.85‐3.42); stage 3, MRR = 3.48 (95% CI 2.51‐4.83); and stage 4, MRR = 6.40 (95% CI 4.11‐9.95). The results were more pronounced as the risk of liver‐related mortality increased exponentially with each increase in the stage of fibrosis: stage 1, MRR = 1.41 (95% CI 0.17‐11.95); stage 2, MRR = 9.57 (95% CI 1.67‐54.93); stage 3, MRR = 16.69 (95% CI 2.92‐95.36); and stage 4, MRR = 42.30 (95% CI 3.51‐510.34). Limitations of the study include an inability to adjust for comorbid conditions or demographics known to impact fibrosis progression in NAFLD and the inclusion of patients with simple steatosis and nonalcoholic steatohepatitis without fibrosis in the reference comparison group. Conclusion: The risk of liver‐related mortality increases exponentially with increase in fibrosis stage; these data have important implications in assessing the utility of each stage and benefits of regression of fibrosis from one stage to another. (Hepatology 2017;65:1557‐1565).
Incidence of IBD is rising in parallel with overweight and obesity. Contrary to conventional belief, about 15-40% of patients with IBD are obese, which might contribute to the development of IBD. ...Findings from cross-sectional and retrospective cohort studies are conflicting on the effect of obesity on natural history and course of IBD. Most studies are limited by small sample size, low event rates, non-validated assessment of disease activity and lack robust longitudinal follow-up and have incomplete adjustment for confounding factors. The effect of obesity on the efficacy of IBD-related therapy remains to be studied, though data from other autoimmune diseases suggests that obesity results in suboptimal response to therapy, potentially by promoting rapid clearance of biologic agents leading to low trough concentrations. These data provide a rationale for using weight loss interventions as adjunctive therapy in patients with IBD who are obese. Obesity also makes colorectal surgery technically challenging and might increase the risk of perioperative complications. In this Review, we highlight the existing literature on the epidemiology of obesity in IBD, discuss its plausible role in disease pathogenesis and effect on disease course and treatment response, and identify high-priority areas of future research.
No unmeasured confounding is often assumed in estimating treatment effects in observational data, whether using classical regression models or approaches such as propensity scores and inverse ...probability weighting. However, in many such studies collection of confounders cannot possibly be exhaustive in practice, and it is crucial to examine the extent to which the resulting estimate is sensitive to the unmeasured confounders. We consider this problem for survival and competing risks data. Due to the complexity of models for such data, we adapt the simulated potential confounder approach of Carnegie et al (2016), which provides a general tool for sensitivity analysis due to unmeasured confounding. More specifically, we specify one sensitivity parameter to quantify the association between an unmeasured confounder and the exposure or treatment received, and another set of parameters to quantify the association between the confounder and the time‐to‐event outcomes. By varying the magnitudes of the sensitivity parameters, we estimate the treatment effect of interest using the stochastic expectation‐maximization (EM) and the EM algorithms. We demonstrate the performance of our methods on simulated data, and apply them to a comparative effectiveness study in inflammatory bowel disease. An R package “survSens” is available on CRAN that implements the proposed methodology.
LINKED CONTENTThis article is linked to Dulai et al and Verstockt and Ferrante papers. To view these articles, visit https://doi.org/10.1111/apt.15609 and https://doi.org/10.1111/apt.15634.
Population Health Management for Inflammatory Bowel Disease Dulai, Parambir S.; Singh, Siddharth; Ohno-Machado, Lucilla ...
Gastroenterology (New York, N.Y. 1943),
January 2018, 2018-01-00, 20180101, Letnik:
154, Številka:
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Inflammatory bowel diseases (IBDs) are chronic and impose significant, multidimensional burdens on patients and health care systems. The increasing prevalence of IBD will only worsen this problem ...globally—population health management (PHM) strategies are needed to increase quality of care and population health outcomes while reducing health care costs. We discuss the key components of PHM in IBD. Effective implementation of PHM strategies requires accurate identification of at-risk patients and key areas of variability in care. Improving outcomes of the at-risk population requires implementation of a multicomponent chronic care model designed to shift delivery of ambulatory care from acute, episodic, and reactive encounters, to proactive, planned, long-term care. This is achieved through team care of an activated patient with the help of remote monitoring, clinical information systems, and integrated decision support, with accompanying changes in delivery systems. Performance measurement is integral to any PHM strategy. This involves developing and implementing meaningful metrics of different phases of quality of IBD care and measuring them efficiently using modern clinical information systems. Such an integrated framework of PHM in IBD will facilitate the delivery of high-value care to patients.
Risks of under‐treating and over‐treating disease Dulai, Parambir S
Journal of gastroenterology and hepatology,
April 2021, 2021-Apr, 2021-04-00, 20210401, Letnik:
36, Številka:
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Article Note: Declaration of conflict of interest Dr Parambir S. Dulai is supported by an AGA Research Scholar Award. He has received consulting and/or research support from Takeda, Pfizer, Janssen, ...AbbVie, Polymedco, Buhlmann, and Prometheus. Byline: Parambir S Dulai
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