Nafld epidemiology, emerging pharmacotherapy, liver transplantation implications and the trends in the United States

© 2020 Authors. Nonalcoholic fatty liver disease (NAFLD) is a hepatic mani-festation of metabolic syndrome. The spread of obesity worldwide in pandemic proportions has led to a rapid rise of NAFLD in developed and developing countries alike. There are no approved pharmacological agents to treat steatohepatitis or advanced fibrosis but obeticholic acid recently has shown some promise in phase III trial. Currently, NAFLD is the number one etiology for simultaneous liver and kidney transplantation in the USA, second most common indication for liver transplantation (LT) and projected to become number one very soon. LT for NAFLD poses unique challenges, as these patients are generally older, obese and more likely to have a number of metabolic risk factors. Bariatric surgery is an option and can be considered if a structured weight loss program does not achieve the sustained weight loss goal. Comprehensive cardiovascular risk assessment and aggres-sive management of comorbid conditions are crucial in the LT evaluation process to improve post-transplant survival. Re-current nonalcoholic steatohepatitis after LT is not uncom-mon, and thus warrants primary and secondary prevention strategies through a multidisciplinary approach. Prevalence of NAFLD in a donor population is a unique and growing concern that limits the access to quality liver grafts

Opioid Use Disorder in Admissions for Acute Exacerbations of Chronic Pancreatitis and 30-day Readmission Risk: A Nationwide Matched Analysis

BACKGROUND: The opioid epidemic in the United States has been on the rise. Acute exacerbations of chronic pancreatitis (AECP) patients are at higher risk for Opioid Use Disorder (OUD). Evidence on OUD\u27s impact on healthcare utilization, especially hospital re-admissions is scarce. We measured the impact of OUD on 30-day readmissions, in patients admitted with AECP from 2010 to 2014. METHODS: This is a retrospective cohort study which included patients with concurrently documented CP and acute pancreatitis as first two diagnoses, from the National Readmissions Database (NRD). Pancreatic cancer patients and those who left against medical advice were excluded. We compared the 30-day readmission risk between OUD-vs.-non-OUD, while adjusting for other confounders, using multivariable exact-matched [(EM); 18 confounders; n = 28,389] and non-EM regression/time-to-event analyses. RESULTS: 189,585 patients were identified. 6589 (3.5%) had OUD. Mean age was 48.7 years and 57.5% were men. Length-of-stay (4.4 vs 3.9 days) and mean index hospitalization costs ($10,251 vs.$9174) were significantly higher in OUD-compared to non-OUD-patients (p \u3c 0.001). The overall mean 30-day readmission rate was 27.3% (n = 51,806; 35.3% in OUD vs. 27.0% in non-OUD; p \u3c 0.001). OUD patients were 25% more likely to be re-admitted during a 30-day period (EM-HR: 1.25; 95%CI: 1.16-1.36; p \u3c 0.001), Majority of readmissions were pancreas-related (60%), especially AP. OUD cases\u27 aggregate readmissions costs were $23.3 ± 1.5 million USD (n = 2289). CONCLUSION: OUD contributes significantly to increased readmission risk in patients with AECP, with significant downstream healthcare costs. Measures against OUD in these patients, such as alternative pain-control therapies, may potentially alleviate such increase in health-care resource utilization

Opioid Use Disorder in Admissions for Acute Exacerbations of Chronic Pancreatitis and 30-Day Readmission Risk: A Nationwide Matched Analysis

Background: The opioid epidemic in the United States has been on the rise. Acute exacerbations of chronic pancreatitis (AECP) patients are at higher risk for Opioid Use Disorder (OUD). Evidence on OUD\u27s impact on healthcare utilization, especially hospital re-admissions is scarce. We measured the impact of OUD on 30-day readmissions, in patients admitted with AECP from 2010 to 2014. Methods: This is a retrospective cohort study which included patients with concurrently documented CP and acute pancreatitis as first two diagnoses, from the National Readmissions Database (NRD). Pancreatic cancer patients and those who left against medical advice were excluded. We compared the 30-day readmission risk between OUD-vs.-non-OUD, while adjusting for other confounders, using multivariable exact-matched [(EM); 18 confounders; n = 28,389] and non-EM regression/time-to-event analyses. Results: 189,585 patients were identified. 6589 (3.5%) had OUD. Mean age was 48.7 years and 57.5% were men. Length-of-stay (4.4 vs 3.9 days) and mean index hospitalization costs ($10,251 vs.$9174) were significantly higher in OUD-compared to non-OUD-patients (p \u3c 0.001). The overall mean 30-day readmission rate was 27.3% (n = 51,806; 35.3% in OUD vs. 27.0% in non-OUD; p \u3c 0.001). OUD patients were 25% more likely to be re-admitted during a 30-day period (EM-HR: 1.25; 95%CI: 1.16–1.36; p \u3c 0.001), Majority of readmissions were pancreas-related (60%), especially AP. OUD cases’ aggregate readmissions costs were $23.3 ± 1.5 million USD (n = 2289). Conclusion: OUD contributes significantly to increased readmission risk in patients with AECP, with significant downstream healthcare costs. Measures against OUD in these patients, such as alternative pain-control therapies, may potentially alleviate such increase in health-care resource utilization

Opioid Use Disorder Increases 30-Day Readmission Risk in Inflammatory Bowel Disease Hospitalizations: A Nationwide Matched Analysis

Background and Aims: The opioid epidemic has become increasingly concerning, with the ever-increasing prescribing of opioid medications in recent years, especially in inflammatory bowel disease [IBD] patients with chronic pain. We aimed to isolate the effect of opioid use disorder [OUD] on 30-day readmission risk after an IBD-related hospitalization. Methods: We retrospectively extracted IBD-related adult hospitalizations and 30-day, any-cause, readmissions from the National Readmissions Database [period 2010-2014]. OUD and 30-day readmission trends were calculated. Conventional and exact-matched [EM] logistic regression and time-to-event analyses were conducted among patients who did not undergo surgery during the index hospitalization, to estimate the effect of OUD on 30-day readmission risk. Results: In total, 487 728 cases were identified: 6633 [1.4%] had documented OUD And 308 845 patients [63.3%] had Crohn\u27s disease. Mean age was 44.8 ± 0.1 years, and 54.3% were women. Overall, 30-day readmission rate was 19.4% [n = 94,546], being higher in OUD patients [32.6% vs 19.2%; p \u3c 0.001]. OUD cases have been increasing [1.1% to 1.7%; p-trend \u3c 0.001], while 30-day readmission rates were stable [p-trend = 0.191]. In time-to-event EM analysis, OUD patients were 47% more likely (hazard ratio 1.47; 95% confidence interval [CI]:1.28-1.69; p \u3c 0.001) to be readmitted, on average being readmitted 32% earlier [time ratio 0.68; 95% CI: 0.59-0.78; p \u3c 0.001]. Conclusion: OUD prevalence has been increasing in hospitalized IBD patients from 2010 to 2014. On average, one in five patients will be readmitted within 30 days, with up to one in three among the OUD subgroup. OUD is significantly associated with increased 30-day readmission risk in IBD patients and further measures relating to closer post-discharge outpatient follow-up and pain management should be considered to minimize 30-day readmission risk

Hepatocellular Carcinoma is Leading in Cancer-Related Disease Burden Among Hospitalized Baby Boomers

INTRODUCTION AND OBJECTIVES: Three fourths of chronic hepatitis C virus (HCV) infected adult patients in the United States (US) are born between 1945 and 1965, also known as baby boomers (BB). Prevalence of hepatocellular carcinoma (HCC) is raising in BB due to their advancing age and prolonged HCV infection. We evaluated inpatient hospitalization and mortality in BB associated with HCC. MATERIALS AND METHODS: It is a retrospective cohort study utilizing the Healthcare Utilization Project-National Inpatient Sample (HCUP-NIS) database. From 2003 to 2012, top five primary cancer related hospitalization and mortality among BB were studied. RESULTS: Among 48,733 hospitalizations related to HCC in HCUP-NIS database from 2003 to 2012, BB accounted for 49.6% (24,210) whereas non-BB 50.4% (24,523). Within BB cohort, the top five cancers with the highest proportion of hospitalizations were HCC (46%), prostate (43%), kidney (41%), pancreas (33%), and bladder (21%). From 2003 to 2012, the proportion of HCC related hospitalizations represented by BB almost doubled (33.5 to 57.8%) whereas there was one-third reduction (66.4 to 42.1%) among non-BB. Similarly, HCC-related inpatient mortality in BB decreased by 28% (6.1 to 2.7 per 100,000 hospitalization) but it remained unchanged in non-BB (11.1 to 10.6). HCC accounted for 2nd highest mortality (4960 total deaths) among hospitalized BB behind pancreatic cancer. HCC related to HCV was disproportionately higher in BB compared to non-BB (50.6% vs. 19%; P\u3c0.001). CONCLUSION: HCC ranks number one among the top five cancers with highest proportion of inpatient burden. Future studies should focus on understanding the underlying reasons for this ominous trend

Targeted inhibition of Stat3 with a decoy oligonucleotide abrogates head and neck cancer cell growth

The transcription factor signal transducer and activator of transcription 3 (Stat3) is constitutively activated in a variety of cancers including squamous cell carcinoma of the head and neck (SCCHN). Previous investigations have demonstrated that activated Stat3 contributes to a loss of growth control and transformation. To investigate the therapeutic potential of blocking Stat3 in cancer cells, we developed a transcription factor decoy to selectively abrogate activated Stat3. The Stat3 decoy was composed of a 15-mer double-stranded oligonucleotide, which corresponded closely to the Stat3 response element within the c-fos promoter. The Stat3 decoy bound specifically to activated Stat3 and blocked binding of Stat3 to a radiolabeled Stat3 binding element. By contrast, a mutated version of the decoy that differed by only a single base pair did not bind the activated Stat3 protein. Treatment of head and neck cancer cells with the Stat3 decoy inhibited proliferation and Stat3-mediated gene expression, but did not decrease the proliferation of normal oral keratinocytes. Thus, disruption of activated Stat3 by using a transcription factor decoy approach may serve as a novel therapeutic strategy for cancers characterized by constitutive Stat3 activation