Burden and Cost of Gastrointestinal, Liver, and Pancreatic Diseases in the United States: Update 2021.

BACKGROUND & AIMS: Gastrointestinal diseases account for considerable health care use and expenditures. We estimated the annual burden, costs, and research funding associated with gastrointestinal, liver, and pancreatic diseases in the United States. METHODS: We generated estimates using data from the National Ambulatory Medical Care Survey; National Hospital Ambulatory Medical Care Survey; Nationwide Emergency Department Sample; National Inpatient Sample; Kids' Inpatient Database; Nationwide Readmissions Database; Surveillance, Epidemiology, and End Results program; National Vital Statistics System; Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research; MarketScan Commercial Claims and Encounters data; MarketScan Medicare Supplemental data; United Network for Organ Sharing registry; Medical Expenditure Panel Survey; and National Institutes of Health (NIH). RESULTS: Gastrointestinal health care expenditures totaled $119.6 billion in 2018. Annually, there were more than 36.8 million ambulatory visits for gastrointestinal symptoms and 43.4 million ambulatory visits with a primary gastrointestinal diagnosis. Hospitalizations for a principal gastrointestinal diagnosis accounted for more than 3.8 million admissions, with 403,699 readmissions. A total of 22.2 million gastrointestinal endoscopies were performed, and 284,844 new gastrointestinal cancers were diagnosed. Gastrointestinal diseases and cancers caused 255,407 deaths. The NIH supported $3.1 billion (7.5% of the NIH budget) for gastrointestinal research in 2020. CONCLUSIONS: Gastrointestinal diseases are responsible for millions of health care encounters and hundreds of thousands of deaths that annually costs billions of dollars in the United States. To reduce the high burden of gastrointestinal diseases, focused clinical and public health efforts, supported by additional research funding, are warranted.

Systematic Review and Meta-Analysis on the Effects of Lactulose and Rifaximin on Patient-Reported Outcomes in Hepatic Encephalopathy.

INTRODUCTION: Patients with hepatic encephalopathy (HE) suffer from significant symptoms and impaired quality of life. Improved understanding on the potential benefits of first-line HE therapies may aid patient-provider discussions regarding expected benefits of HE treatments. We aimed to perform a systematic review to assess the effects of lactulose and rifaximin on patient-reported outcomes (PROs). METHODS: We searched MEDLINE, EMBASE, and Cochrane Library databases for randomized trials or prospective cohort studies using lactulose and/or rifaximin for the management of HE and assessing changes in PRO using PRO instruments. Physician reviewers independently reviewed titles, abstracts, and full texts and extracted data independently. We performed random-effects meta-analyses to examine the effects of lactulose and rifaximin on PROs. RESULTS: We identified 16 studies representing 1,376 patients that met inclusion criteria. Most studies assessed treatment of covert HE. In patients with covert HE, lactulose significantly improved overall patient-reported health-related quality of life measured by the Sickness Impact Profile with an estimated pooled mean difference of 6.92 (95% confidence interval: 6.66-7.18) and showed improvements in several subscales. Conversely, rifaximin demonstrated a nonstatistically significant mean difference in the total Sickness Impact Profile of 4.76 (95% confidence interval: -4.23 to 13.76), with strong evidence of heterogeneity between these studies. Studies examining other PRO instruments showed improvements in overall health-related quality of life, social functioning, and sleep from both lactulose and rifaximin. DISCUSSION: Patients with HE treated with lactulose or rifaximin reported improvements in important PROs. These results may inform provider-patient communication and help manage patient expectations regarding the potential benefits of HE therapies.

Active coping, resilience, post-traumatic growth, and psychiatric symptoms among early and late liver transplant survivors.

Understanding survivorship experiences at different stages postliver transplantation (poat-LT) is essential to improving care. Patient-reported concepts including coping, resilience, post-traumatic growth (PTG), and anxiety/depression, have been implicated as important predictors of quality of life and health behaviors after LT. We aimed to descriptively characterize these concepts at different post-LT survivorship stages. This cross-sectional study featured self-reported surveys measuring sociodemographic, clinical characteristics, and patient-reported concepts including coping, resilience, PTG, anxiety, and depression. Survivorship periods were categorized as early (1 y or below), mid (1-5 y), late (5-10 y), and advanced (10 y or above). Univariable and multivariable logistic and linear regression modeling examined factors associated with patient-reported concepts. Among 191 adult LT survivors, the median survivorship stage was 7.7 years (interquartile range: 3.1-14.4) and median age was 63 years (range: 28-83); most were male (64.2%) and Caucasian (84.0%). High PTG was more prevalent in the early survivorship period (85.0%) than late survivorship (15.2%). High trait resilience was only reported by 33% of survivors and associated with higher income. Lower resilience was seen among patients with longer LT hospitalization stays and late survivorship stages. About 25% of survivors had clinically significant anxiety and depression, which was more frequent among early survivors and females with pre-LT mental health disorders. In multivariable analysis, factors associated with lower active coping included survivors ≥65 years, non-Caucasian race, lower levels of education, and nonviral liver disease. In a heterogeneous cohort including early and late LT survivors, there was variation in levels of PTG, resilience, anxiety, and depression at different survivorship stages. Factors associated with positive psychological traits were identified. Understanding determinants of LT survivorship has important implications for how we should monitor and support LT survivors.

Association between sustained virological response and clinical outcomes in patients with hepatitis C infection and hepatocellular carcinoma.

BACKGROUND: Sustained viral response (SVR) improves survival for patients with hepatitis C (HCV) and hepatocellular carcinoma (HCC) after curative treatment; however, the benefit of SVR in those with active HCC with a significant competing risk of mortality is unknown. This study aimed to evaluate the association between SVR and outcomes in patients with active HCC. METHODS: The authors performed a multicenter, retrospective cohort study including consecutive adults with HCV cirrhosis and treatment-naive HCC diagnosed between 2014 and 2018. Patients were stratified into two groups: active viremia (n = 431) and SVR before HCC diagnosis (n = 135). All patients underwent nonsurgical therapy as their initial treatment and were followed until liver transplantation, last follow-up, or death. The primary outcome was incident or worsening hepatic decompensation within 6 months and the secondary outcome was overall survival. All analyses used inverse probability of treatment weights (IPTW) to account for differences between the nonrandomized cohorts. RESULTS: Post-SVR patients had significantly lower odds of hepatic decompensation compared to viremic patients (odds ratio [OR], 0.18; 95% confidence interval [CI], 0.06-0.59). Results were consistent among subgroups of patients with Child Pugh A cirrhosis (OR, 0.22; 95% CI, 0.04-0.77), Barcelona Clinic Liver Cancer stage B/C HCC (OR, 0.20; 95% CI, 0.04-0.65), and those receiving nonablative HCC therapies (OR, 0.21; 95% CI, 0.07-0.67). However, in IPTW multivariable Cox regression, SVR was not associated with improved survival (hazard ratio, 0.79; 95% CI, 0.56-1.12). CONCLUSIONS: Patients with HCV-related HCC and SVR are less likely to experience hepatic decompensation than viremic patients, suggesting patients with HCC who are undergoing nonsurgical therapies may benefit from DAA treatment.

Successful liver transplantation in patients with active SARS-CoV-2 infection.

The Coronavirus Disease 2019 (COVID-19) pandemic has substantially impacted solid organ transplantation, including temporary inactivation of waitlist candidates with COVID-19 infection. We report two cases of liver transplantation (LT) in individuals with asymptomatic COVID-19 infection. The first patient is a 68-year-old female with decompensated cirrhosis complicated by worsening frailty and sarcopenia. The second patient is a 22-year-old female with acute liver failure likely secondary to drug/toxin exposure. Both patients were treated with COVID-19-directed therapies and neither patient developed symptomatic disease. These cases demonstrate that LT can be safely performed in select patients with asymptomatic COVID-19 infection at the time of transplant.

Early Survivorship After Liver Transplantation: A Qualitative Study Identifying Challenges in Recovery From the Patient and Caregiver Perspective.

Survivorship after liver transplantation (LT) is a novel concept providing a holistic view of the arduous recovery experienced after transplantation. We explored components of early survivorship including physical, emotional, and psychological challenges to identify intervention targets for improving the recovery process of LT recipients and caregivers. A total of 20 in-person interviews were conducted among adults 3 to 6 months after LT. Trained qualitative research experts conducted interviews, coded, and analyzed transcripts to identify relevant themes and representative quotes. Early survivorship comprises overcoming (1) physical challenges, with the most challenging experiences involving mobility, driving, dietary modifications, and medication adherence, and (2) emotional and psychological challenges, including new health concerns, financial worries, body image/identity struggles, social isolation, dependency issues, and concerns about never returning to normal. Etiology of liver disease informed survivorship experiences including some patients with hepatocellular carcinoma expressing decisional regret or uncertainty in light of their post-LT experiences. Important topics were identified that framed LT recovery including setting expectations about waitlist experiences, hospital recovery, and ongoing medication requirements. Early survivorship after LT within the first 6 months involves a wide array of physical, emotional, and psychological challenges. Patients and caregivers identified what they wish they had known prior to LT and strategies for recovery, which can inform targeted LT survivorship interventions.

Roux-en-Y Gastric Bypass Is Associated With Increased Hazard for De Novo Alcohol-related Complications and Liver Disease.

GOAL: The goal of this study was to determine if bariatric surgeries are associated with de novo alcohol-related complications. BACKGROUND: Bariatric surgery is associated with an increased risk of alcohol use disorders. The effect of bariatric surgeries on other alcohol-related outcomes, including liver disease, is understudied. MATERIALS AND METHODS: Using the IMS PharMetrics database, we performed a cohort study of adults undergoing bariatric surgery or cholecystectomy, excluding patients with an alcohol-related diagnosis within 1 year before surgery. The primary outcome was any alcohol-related diagnosis after surgery. We fit a multivariable Cox proportional hazards model to determine independent associations between bariatric surgeries [Roux-en-Y gastric bypass (RYGB); adjustable gastric band; sleeve gastrectomy] versus cholecystectomy and the development of de novo alcohol-related outcomes. We further fit complication-specific models for each alcohol-related diagnosis. RESULTS: RYGB was significantly associated with an increased hazard of any de novo alcohol-related diagnosis [adjusted hazard ratio (AHR)=1.51, 95% confidence interval (CI): 1.40-1.62], while adjustable gastric band (AHR=0.55, 95% CI: 0.48-0.63) and sleeve gastrectomy (AHR=0.77, 95% CI: 0.64-0.91) had decreased hazards. RYGB was associated with a 2- to 3-fold higher hazard for alcoholic hepatitis (AHR=1.98, 95% CI: 1.17-3.33), abuse (AHR=2.05, 95% CI: 1.88-2.24), and poisoning (3.14, 95% CI: 1.80-5.49). CONCLUSIONS: RYGB was associated with higher hazards of developing de novo alcohol-related hepatitis, abuse, and poisoning compared with a control group. Patients without a history of alcohol use disorder should still be counseled on the increased risk of alcohol use and alcohol-related complications, including alcohol-related liver disease, following RYGB, and should be monitored long term for the development of alcohol-related complications.

"If I Get Cured, My Whole Quality of Life Will Change": Patients' Anticipated and Actualized Benefits Following Cure from Chronic Hepatitis C.

BACKGROUND: Patients' motivations for undergoing direct-acting antiviral (DAA) therapy for chronic hepatitis C may include anticipation of treatment benefits not well described in the literature. AIMS: Evaluate patients' anticipated and actualized improvements in several domains of functioning before and after viral cure. METHODS: Pre-post-study utilizing in-depth interviews with 28 patients prior to, and several months after, DAA therapy. Interviews were audio-recorded, transcribed, coded, and analyzed by two qualitative experts. RESULTS: Patients had a median age of 54 years, 43% were male, 57% white, 25% had cirrhosis, and 71% were treated with sofosbuvir/ledipasvir. Pre-treatment, patients hoped for improvements in several domains including psychological, emotional, physical, social, and occupational functioning. After viral cure, increased energy and less fear of transmission were pathways to better quality of life. Psychological and emotional improvements positively affected physical, social, and occupational functioning. Social improvements were due to better mood and motivation, fewer symptoms, and reduced fear of stigma and transmission. Occupational benefits were linked to increased stamina, self-confidence, and less pain, anxiety, and stigma. Reduced fear of stigma had a pervasive impact on all life improvements after cure. Patient characteristics such as the presence of cirrhosis or psychiatric issues influence treatment motivations. Qualitative data correspond with change in pre-post-survey scores. CONCLUSIONS: Tremendous hope is placed on the ability of DAA therapy to bring about substantial improvements in life functioning after viral cure. Highly interconnected effects on quality of life worked synergistically through improved physical and psychological well-being. Stakeholders should appreciate the multi-dimensional benefits that viral eradication bestows upon individuals and society.

The Clinical Spectrum and Diagnosis of Oxaliplatin Liver Injury in the Era of Nonalcoholic Fatty Liver Disease.

Oxaliplatin is an alkylating agent given with fluorouracil and leucovorin as a mainstay adjuvant chemotherapy for stage III colorectal cancer (CRC). Liver injury from oxaliplatin ranges from mild liver enzyme increases in 42% to 57% of patients in clinical trials1 to rare severe injury leading to acute liver failure.2 Chronic injury from endothelial cell damage and architectural distortion may manifest years later with nodular regenerative hyperplasia (NRH), portal sclerosis, and noncirrhotic portal hypertension (NCPH).2,3 Chronic subclinical injury occurs in up to 78% of patients.3 Diagnosis may be confounded by nonalcoholic fatty liver disease (NAFLD), and long-term outcomes from chronic injury are unclear.

What Survivorship Means to Liver Transplant Recipients: Qualitative Groundwork for a Survivorship Conceptual Model.

Survivorship is a well-established concept in the cancer care continuum with a focus on disease recurrence, quality of life, and the minimization of competing risks for mortality; however, survivorship has not been well studied in liver transplantation (LT). We investigated what survivorship means to LT patients and identified motivations and coping strategies for overcoming challenges after LT. A total of 20 in-depth home interviews were conducted among adults 3 to 6 months after LT. Interviews were conducted by trained qualitative research experts and coded and analyzed using an inductive approach. A majority of LT recipients (75%) identified themselves as survivors. Integral to the definition of survivorship was overcoming hardship (including experiences on the waiting list) and the unique experience of being given a "second chance" at life. Motivations to survive included a new chance at life (55%), family (40%), spirituality/faith (30%), and fear of rejection (15%). LT recipients and caregivers identified multiple strategies to cope with post-LT challenges, including relying on a large network of community, spiritual, and virtual support. These findings informed a conceptual model of LT survivorship based on socioecological theory, which identified the following variables influencing survivorship: (1) pretransplant experiences, (2) individual attributes and challenges, (3) interpersonal relationships with caregivers and other social support, (4) community relationships, and (5) large-scale factors including neighborhood and financial issues. LT recipients identified themselves as survivors, and post-LT identities were greatly influenced by pre-LT experiences. These perspectives informed an in-depth conceptual model of survivorship after transplantation. We identified sources of motivation and coping strategies used in LT recovery that could be targets of survivorship interventions aimed at improving post-LT outcomes.

A Quality Improvement Initiative Results in Improved Rates of Timely Postvariceal Bleeding Surveillance Endoscopy.

OBJECTIVES: We performed a study to assess the effects of a quality improvement (QI) initiative on the rates of postvariceal bleeding surveillance upper endoscopy (EGD). METHODS: We identified patients with cirrhosis hospitalized with variceal bleeding and assessed the rates of timely (≤4 weeks) EGD before and after a QI initiative. RESULTS: Preintervention: 16% (5 of 32) of patients underwent timely surveillance EGD. We developed a standardized ordering template for gastroenterology fellows and reserved postvariceal EGD scheduling slots. Postintervention: 43% (12 of 28) of patients underwent timely surveillance EGD. DISCUSSION: A QI intervention was associated with a 27% absolute increase in timely surveillance EGDs.

A phenotypic analysis shows that eosinophilic esophagitis is a progressive fibrostenotic disease.

BACKGROUND: Phenotypes of eosinophilic esophagitis (EoE) are not well-characterized. OBJECTIVE: To describe clinical features of patients with EoE with predefined phenotypes, determine predictors of these phenotypes, and make inferences about the natural history of EoE. DESIGN: Retrospective study. SETTING: Tertiary-care center. PATIENTS: Incident EoE cases from 2001 to 2011 that met consensus diagnostic guidelines. INTERVENTION: Review of records. MAIN OUTCOME MEASUREMENTS: Endoscopic phenotypes, including fibrostenotic, inflammatory, or mixed. Other groups of clinical characteristics examined included atopy, level of esophageal eosinophilia, and age of symptom onset. Multinomial logistic regression assessed predictors of phenotype status. RESULTS: Of 379 cases of EoE identified, there were no significant phenotypic differences by atopic status or level of eosinophilia. Those with the inflammatory phenotype were more likely to be younger than those with mixed or fibrostenotic (13 vs 29 vs 39 years, respectively; P < .001) and less likely to have dysphagia, food impaction, and esophageal dilation (P < .001 for all). The mean symptom length before diagnosis was shorter for inflammatory (5 vs 8 vs 8 years; P = .02). After multivariate analysis, age and dysphagia independently predicted phenotype. The odds ratio (OR) for fibrostenosis for each 10-year increase in age was 2.1 (95% CI, 1.7-2.7). The OR for dysphagia was 7.0 (95% CI, 2.6-18.6). LIMITATIONS: Retrospective, single-center study. CONCLUSION: In this large EoE cohort, the likelihood of fibrostenotic disease increased markedly with age. For every 10-year increase in age, the odds of having a fibrostenotic EoE phenotype more than doubled. This association suggests that the natural history of EoE is a progression from an inflammatory to a fibrostenotic disease.

Safety and efficacy of endoscopic mucosal therapy with radiofrequency ablation for patients with neoplastic Barrett's esophagus.

BACKGROUND & AIMS: The goal of radiofrequency ablation (RFA) for patients with Barrett's esophagus (BE) is to eliminate dysplasia and metaplasia. The efficacy and safety of RFA for patients with BE and neoplasia are characterized incompletely. METHODS: We performed a retrospective study of 244 patients treated with RFA for BE with dysplasia or intramucosal carcinoma. Efficacy outcomes were complete eradication of intestinal metaplasia (CEIM), complete eradication of dysplasia, total treatments, and RFA sessions. Safety outcomes included death, perforation, stricture, bleeding, and hospitalization. We identified factors associated with incomplete EIM and stricture formation. RESULTS: CEIM was achieved in 80% of patients, and complete eradication of dysplasia was achieved in 87%; disease progressed in 4 patients. A higher percentage of patients with incomplete EIM were female (40%) than those with CEIM (20%; P = .045); patients with incomplete EIM also had a longer segment of BE (5.5 vs 4.0 cm; P = .03), had incomplete healing between treatment sessions (45% vs 15%; P = 0.004), and underwent more treatment sessions (4 vs 3; P = .007). Incomplete healing was associated independently with incomplete EIM. Twenty-three patients (9.4%) had a treatment-related complication during 777 treatment sessions (3.0%), including strictures (8.2%), postprocedural hemorrhages (1.6%), and hospitalizations (1.6%). Patients who developed strictures were more likely to use nonsteroidal anti-inflammatory drugs than those without strictures (70% vs 45%; P = .04), have undergone antireflux surgery (15% vs 3%; P = .04), or had erosive esophagitis (35% vs 12%; P = .01). CONCLUSIONS: RFA is highly effective and safe for treatment of BE with dysplasia or early stage cancer. Strictures were the most common complications. Incomplete healing between treatment sessions was associated with incomplete EIM. Nonsteroidal anti-inflammatory drug use, prior antireflux surgery, and a history of erosive esophagitis predicted stricture formation.

Burden of gastrointestinal disease in the United States: 2012 update.

BACKGROUND & AIMS: Gastrointestinal (GI) diseases account for substantial morbidity, mortality, and cost. Statistical analyses of the most recent data are necessary to guide GI research, education, and clinical practice. We estimate the burden of GI disease in the United States. METHODS: We collected information on the epidemiology of GI diseases (including cancers) and symptoms, along with data on resource utilization, quality of life, impairments to work and activity, morbidity, and mortality. These data were obtained from the National Ambulatory Medical Care Survey; National Health and Wellness Survey; Nationwide Inpatient Sample; Surveillance, Epidemiology, and End Results Program; National Vital Statistics System; Thompson Reuters MarketScan; Medicare; Medicaid; and the Clinical Outcomes Research Initiative's National Endoscopic Database. We estimated endoscopic use and costs and examined trends in endoscopic procedure. RESULTS: Abdominal pain was the most common GI symptom that prompted a clinic visit (15.9 million visits). Gastroesophageal reflux was the most common GI diagnosis (8.9 million visits). Hospitalizations and mortality from Clostridium difficile infection have doubled in the last 10 years. Acute pancreatitis was the most common reason for hospitalization (274,119 discharges). Colorectal cancer accounted for more than half of all GI cancers and was the leading cause of GI-related mortality (52,394 deaths). There were 6.9 million upper, 11.5 million lower, and 228,000 biliary endoscopies performed in 2009. The total cost for outpatient GI endoscopy examinations was $32.4 billion. CONCLUSIONS: GI diseases are a source of substantial morbidity, mortality, and cost in the United States.

Intestinal metaplasia recurs infrequently in patients successfully treated for Barrett's esophagus with radiofrequency ablation.

OBJECTIVES: Radiofrequency ablation (RFA) of Barrett's esophagus (BE) is safe and effective in eradicating dysplasia and intestinal metaplasia, and may reduce rates of esophageal adenocarcinoma (EAC). We assessed rates of and risk factors for disease recurrence after successful treatment of BE with RFA. METHODS: We performed a retrospective cohort study of patients who completed RFA for dysplastic BE or intramucosal carcinoma (IMC), achieved complete eradication of dysplasia (CE-D) or intestinal metaplasia (CE-IM), and underwent subsequent endoscopic surveillance at a single center. Rates of disease recurrence and progression were determined. Patients with and without recurrent disease were compared to determine risk factors for recurrence. RESULTS: Two hundred and sixty-two subjects underwent RFA during the study period. Of these, 119 and 112 patients were retained in endoscopic surveillance after CE-D and CE-IM, respectively. Median observation time was 397 days (range: 54-1,668 days). Eight patients (7% of those with CE-IM) had recurrent disease after a median of 235 days (range 55-1,124 days). Progression to IMC (n=1) or EAC (n=2) occurred in three of these eight patients, all of whom had pre-ablation high-grade dysplasia (HGD). Five patients had recurrence of non-dysplastic BE (n=3), low-grade dysplasia (n=1), and HGD (n=1). During 155 patient-years of observation, recurrence occurred in 5.2%/year, and progression occurred in 1.9%/year. No clinical characteristics were associated with disease recurrence. CONCLUSIONS: In patients with BE and dysplasia or early cancer who achieved CE-IM, BE recurred in ≈ 5%/year. Patient characteristics did not predict recurrence. Subjects undergoing RFA for dysplastic BE should be retained in endoscopic surveillance.

Early life exposures as risk factors for pediatric eosinophilic esophagitis.

OBJECTIVES: Few etiologic studies of eosinophilic esophagitis (EoE) have been conducted. Early life exposures have been shown to predispose to other allergic disease, but their role has not been assessed in EoE. The present study sought to explore early life exposures as possible risk factors for developing EoE in the pediatric population. METHODS: This was a 2-phase case-control study conducted at the University of North Carolina. The first phase consisted of survey development for early life exposures via cognitive interview. In the second phase, a telephone-based questionnaire was administered to cases with EoE (n = 31) and 2 sets of controls, patients with gastroesophageal reflux disease, and siblings of nonsyndromic cleft lip/palate patients (n = 26 in each). Different controls were explored to identify controls reflective of the source population of the cases. Siblings of cleft lip/palate patients were identified as the more suitable control population. Odds ratios were calculated to evaluate the association between early life exposures and the development of pediatric EoE. RESULTS: Early life exposures were associated with increased odds of developing pediatric-onset EoE. Antibiotic use in infancy was associated with 6 times the odds of having EoE (95% confidence interval 1.7-20.8). Cesarean delivery, preterm birth, and formula-only or mixed (infant formula and breast milk) feeding also have trends toward increased odds for developing EoE. CONCLUSIONS: A number of early life exposures may be associated with the development of EoE. These are potentially modifiable risk factors that if confirmed would have implications for improved understanding of EoE pathogenesis and disease prevention.