Research Spotlight

Asrani, S. K., L. Hall, M. Hagan, S. Sharma, S. Yeramaneni, J. Trotter, J. Talwalkar and F. Kanwal (2019). “Trends in Chronic Liver Disease-Related Hospitalizations: A Population-Based Study.” Am J Gastroenterol 114(1): 98-106.

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OBJECTIVES: In a population-based study, we examined time trends in chronic liver disease (CLD)-related hospitalizations in a large and diverse metroplex. METHODS: We examined all CLD-related inpatient encounters (2000-2015) in Dallas-Fort Worth (DFW) using data from the DFW council collaborative that captures claims data from 97% of all hospitalizations in DFW (10.7 million regional patients). RESULTS: There were 83,539 CLD-related hospitalizations in 48,580 unique patients across 84 hospitals. The age and gender standardized annual rate of CLD-related hospitalization increased from 48.9 per 100,000 in 2000 to 125.7 per 100,000 in 2014. Mean age at hospitalization increased from 54.0 (14.1) to 58.5 (13.5) years; the proportion of CLD patients above 65 years increased from 24.2% to 33.1%. HCV-related hospitalizations plateaued, whereas an increase was seen in hospitalizations related to alcohol (9.1 to 22.7 per 100,000) or fatty liver (1.4 per 100,000 to 19.5 per 100,000). The prevalence of medical comorbidities increased for CLD patients: coronary artery disease (4.8% to 14.3%), obesity (2.8% to 14.6%), chronic kidney disease (2.8% to 18.2%), and diabetes (18.0% to 33.2%). Overall hospitalizations with traditional complications of portal hypertension (ascites, varices, and peritonitis) remained stable over time. However, hospitalization with complications related to infection increased from 54.7% to 66.4%, and renal failure increased by sevenfold (2.7% to 19.5%). CONCLUSIONS: CLD-related hospitalizations have increased twofold over the last decade. Hospitalized CLD patients are older and sicker with multiple chronic conditions. Traditional complications of portal hypertension have been superseded by infection and renal failure, warranting a need to redefine what it means to have decompensated CLD.

Asrani, S. K., H. Devarbhavi, J. Eaton and P. S. Kamath (2019). “Burden of liver diseases in the world.” J Hepatol 70(1): 151-171.

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Liver disease accounts for approximately 2 million deaths per year worldwide, 1 million due to complications of cirrhosis and 1million due to viral hepatitis and hepatocellular carcinoma. Cirrhosis is currently the 11th most common cause of death globally and liver cancer is the 16th leading cause of death; combined, they account for 3.5% of all deaths worldwide. Cirrhosis is within the top 20 causes of disability-adjusted life years and years of life lost, accounting for 1.6% and 2.1% of the worldwide burden. About 2 billion people consume alcohol worldwide and upwards of 75 million are diagnosed with alcohol-use disorders and are at risk of alcohol-associated liver disease. Approximately 2 billion adults are obese or overweight and over 400 million have diabetes; both of which are risk factors for non-alcoholic fatty liver disease and hepatocellular carcinoma. The global prevalence of viral hepatitis remains high, while drug-induced liver injury continues to increase as a major cause of acute hepatitis. Liver transplantation is the second most common solid organ transplantation, yet less than 10% of global transplantation needs are met at current rates. Though these numbers are sobering, they highlight an important opportunity to improve public health given that most causes of liver diseases are preventable.

Asmundson, G. J. G., A. S. Thorisdottir, J. W. Roden-Foreman, S. O. Baird, S. M. Witcraft, A. T. Stein, J. A. J. Smits and M. B. Powers (2019). “A meta-analytic review of cognitive processing therapy for adults with posttraumatic stress disorder.” Cogn Behav Ther 48(1): 1-14.

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Numerous studies have demonstrated the efficacy of cognitive processing therapy (CPT) for treating posttraumatic stress disorder (PTSD). Two prior meta-analyses of studies are available but used approaches that limit conclusions that can be drawn regarding the impact of CPT on PTSD outcomes. The current meta-analysis reviewed outcomes of trials that tested the efficacy of CPT for PTSD in adults and evaluated potential moderators of outcomes. All published trials comparing CPT against an inactive control condition (i.e. psychological placebo or wait-list) or other active treatment for PTSD in adults were included, resulting in 11 studies with a total of 1130 participants. CPT outperformed inactive control conditions on PTSD outcome measures at posttreatment (mean Hedges’ g = 1.24) and follow-up (mean Hedges’ g = 0.90). The average CPT-treated participant fared better than 89% of those in inactive control conditions at posttreatment and 82% at follow-up. Results also showed that CPT outperformed inactive control conditions on non-PTSD outcome measures at posttreatment and follow-up and that CPT outperformed other active treatments at posttreatment but not at follow-up. Effect sizes of CPT on PTSD symptoms were not significantly moderated by participant age, number of treatment sessions, total sample size, length of follow-up, or group versus individual treatment; but, older studies had larger effect sizes and percent female sex moderated the effect of CPT on non-PTSD outcomes. These meta-analytic findings indicate that CPT is an effective PTSD treatment with lasting benefits across a range of outcomes.

Askar, M., D. Sayer, T. Wang, M. Haagenson, S. R. Spellman, S. J. Lee, A. Madbouly, K. Fleischhauer, K. C. Hsu, M. R. Verneris, D. Thomas, A. Zhang, R. M. Sobecks and N. S. Majhail (2018). “Analysis of Single Nucleotide Polymorphisms in the Gamma Block of the Major Histocompatibility Complex in Association with Clinical Outcomes of Hematopoietic Cell Transplantation: A Center for International Blood and Marrow Transplant Research Study.” Biol Blood Marrow Transplant Dec 8. [Epub ahead of print].

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HLA haplotype mismatches have been associated with an elevated risk of acute graft-versus-host disease (aGVHD) in patients undergoing HLA-matched unrelated donor (URD) hematopoietic cell transplantation (HCT). The gamma block (GB) is located in the central MHC region between beta and delta blocks (encoding HLA-B and -C and HLA-DQ and -DR antigens, respectively) and contains numerous inflammatory and immune regulatory genes, including Bf, C2, and C4 genes. A single-center study showed that mismatches in SNPs c.2918+98G, c.3316C, and c.4385C in the GB block (C4 SNPs) were associated with higher risk of grade III-IV aGVHD. We investigated the association of GB SNP (GBS) mismatches with outcomes after 10/10 and 9/10 URD HCT (n=714). The primary outcome was acute GVHD. Overall survival, disease-free survival, transplantation-related mortality, relapse, chronic GVHD, and engraftment were also analyzed. DNA samples were GBS genotyped by identifying 338 SNPs across 20 kb using the Illumina NGS platform. The overall 100-day incidence of aGVHD grade II-IV and II-IV were 41% and 17%, respectively. The overall incidence of matching at all GBSs tested and at the C4 SNPs were 23% and 81%, respectively. Neither being matched across all GB SNPs tested (versus mismatched) nor having a higher number of GBS mismatches was associated with transplantation outcomes. There was no association between C4 SNP mismatches and outcomes except for an unexpected significant association between having 2 C4 SNP mismatches and a higher hazard ratio (HR) for relapse (association seen in 15 patients only; HR, 3.38, 95% confidence interval, 1.75 to 6.53; P=.0003). These data do not support the hypothesis that mismatching at GB is associated with outcomes after HCT.

Ailawadi, G., D. S. Lim, M. J. Mack, A. Trento, S. Kar, P. A. Grayburn, D. D. Glower, A. Wang, E. Foster, A. Qasim, N. J. Weissman, J. Ellis, L. Crosson, F. Fan, I. L. Kron, P. J. Pearson and T. Feldman (2019). “One-Year Outcomes After MitraClip for Functional Mitral Regurgitation.” Circulation 139(1): 37-47.

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BACKGROUND: Secondary mitral regurgitation (SMR) occurs in the absence of organic mitral valve disease and may develop as the left ventricle dilates or remodels or as a result of leaflet tethering with impaired coaptation, most commonly from apical and lateral distraction of the subvalvular apparatus, with late annular dilatation. The optimal therapy for SMR is unclear. This study sought to evaluate the 1-year adjudicated outcomes of all patients with SMR undergoing the MitraClip procedure in the EVEREST II (Endovascular Valve Edge-to-Edge Repair Study) Investigational Device Exemption program, which is comprised of the randomized clinical trial, the prospective High-Risk Registry, and the REALISM Continued Access Registry (Multicenter Study of the MitraClip System). METHODS: Patients with 3+/4+ SMR enrolled in EVEREST II were stratified by non-high surgical risk (non-HR) and high surgical risk (HR) status (defined as Society of Thoracic Surgeons risk of mortality >/=12% or predefined risk factors). Clinical, echocardiographic, and functional outcomes at 1 year were evaluated. RESULTS: A total of 616 patients (482 HR, 134 non-HR; mean age, 73.3+/-10.5 years; Society of Thoracic Surgeons risk, 10.2+/-6.9%) with SMR underwent the MitraClip procedure. At baseline, 80.5% of patients were in New York Heart Association class III/IV. Major adverse events at 30 days included death (3.6%), stroke (2.3%), and renal failure (1.5%). At discharge, 88.8% had MR