AGA Clinical Practice Guideline on Endoscopic Eradication Therapy of Barrett's Esophagus and Related Neoplasia.

BACKGROUND & AIMS: Barrett's esophagus (BE) is the precursor to esophageal adenocarcinoma (EAC). Endoscopic eradication therapy (EET) can be effective in eradicating BE and related neoplasia and has greater risk of harms and resource use than surveillance endoscopy. This clinical practice guideline aims to inform clinicians and patients by providing evidence-based practice recommendations for the use of EET in BE and related neoplasia. METHODS: The Grading of Recommendations Assessment, Development and Evaluation framework was used to assess evidence and make recommendations. The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients, conducted an evidence review, and used the Evidence-to-Decision Framework to develop recommendations regarding the use of EET in patients with BE under the following scenarios: presence of (1) high-grade dysplasia, (2) low-grade dysplasia, (3) no dysplasia, and (4) choice of stepwise endoscopic mucosal resection (EMR) or focal EMR plus ablation, and (5) endoscopic submucosal dissection vs EMR. Clinical recommendations were based on the balance between desirable and undesirable effects, patient values, costs, and health equity considerations. RESULTS: The panel agreed on 5 recommendations for the use of EET in BE and related neoplasia. Based on the available evidence, the panel made a strong recommendation in favor of EET in patients with BE high-grade dysplasia and conditional recommendation against EET in BE without dysplasia. The panel made a conditional recommendation in favor of EET in BE low-grade dysplasia; patients with BE low-grade dysplasia who place a higher value on the potential harms and lower value on the benefits (which are uncertain) regarding reduction of esophageal cancer mortality could reasonably select surveillance endoscopy. In patients with visible lesions, a conditional recommendation was made in favor of focal EMR plus ablation over stepwise EMR. In patients with visible neoplastic lesions undergoing resection, the use of either endoscopic mucosal resection or endoscopic submucosal dissection was suggested based on lesion characteristics. CONCLUSIONS: This document provides a comprehensive outline of the indications for EET in the management of BE and related neoplasia. Guidance is also provided regarding the considerations surrounding implementation of EET. Providers should engage in shared decision making based on patient preferences. Limitations and gaps in the evidence are highlighted to guide future research opportunities.

Preloaded 22-gauge fine-needle system facilitates placement of a higher number of fiducials for image-guided radiation therapy compared with traditional backloaded 19-gauge approach.

BACKGROUND AND AIMS: Image-guided radiation therapy (IGRT) often relies on EUS-guided fiducial markers. Previously used manually backloaded fiducial needles have multiple potential limitations including safety and efficiency concerns. Our aim was to evaluate the efficacy, feasibility, and safety of EUS-guided placement of gold fiducials using a novel preloaded 22-gauge needle compared with a traditional, backloaded 19-gauge needle. METHODS: This was a single-center comparative cohort study. Patients with pancreatic and hepatobiliary malignancy who underwent EUS-guided fiducial placement (EUS-FP) between October 2014 and February 2018 were included. The main outcome was the technical success of fiducial placement. Secondary outcomes were mean procedure time, fiducial visibility during IGRT, technical success of IGRT delivery, and adverse events. RESULTS: One hundred fourteen patients underwent EUS-FP during the study period. Of these, 111 patients had successful placement of a minimum of 2 fiducials. Fifty-six patients underwent placement using a backloaded 19-gauge needle and 58 patients underwent placement using a 22-gauge preloaded needle. The mean number of fiducials placed successfully at the target site was significantly higher in the 22-gauge group compared with the 19-gauge group (3.53 ± .96 vs 3.11 ± .61, respectively; P = .006). In the 22-gauge group, the clinical goal of placing 4 fiducials was achieved in 78%, compared with 23% in the 19-gauge group (P < .001). In univariate analyses, gender, age, procedure time, tumor size, and location did not influence the number of successfully placed fiducials. Technical success of IGRT with fiducial tracking was high in both the 19-gauge (51/56, 91%) and the 22-gauge group (47/58, 81%; P = .12). CONCLUSIONS: EUS-FP using a preloaded 22-gauge needle is feasible, effective, and safe and allows for a higher number of fiducials placed when compared with the traditional backloaded 19-gauge needle.

Disparate Trends in Mortality of Etiology-Specific Chronic Liver Diseases Among Hispanic Subpopulations.

BACKGROUND & AIMS: Little is known about trends in mortality among Hispanic subpopulations and etiologies of chronic liver disease (CLD). We investigated trends in mortality of CLD among the 3 largest Hispanic subgroups based on origin (Mexicans, Puerto Ricans, and Cubans) in the United States (US) from 2007 to 2016. METHODS: We collected data from the US Census and national mortality database, calculated age-standardized mortalities for CLD among Hispanic subgroups, and compared these with non-Hispanic whites. We determined mortality rate patterns by joinpoint analysis with estimates of annual percentage change. RESULTS: Hispanics were relatively younger with a lower likelihood of high school education than non-Hispanic whites at time of death. Puerto Ricans had the highest rates of age-standardized hepatitis C virus-related mortality in 2016, followed by non-Hispanic whites, Mexicans, and Cubans. Age-standardized mortality rates associated with hepatitis B virus infection decreased steadily among all subjects. Age-standardized mortality rates from alcoholic liver disease and nonalcoholic fatty liver disease among non-Hispanic whites and all Hispanics increased and accelerated. Mexicans had the highest rates of age-standardized alcoholic liver disease-related mortality, followed by non-Hispanic whites, Puerto Ricans, and Cubans. Cirrhosis- and hepatocellular carcinoma-related mortality rates increased steadily from 2007 to 2016, with the highest among Puerto Ricans and non-Hispanic whites and Mexicans, and lowest in Cubans. CONCLUSIONS: We found high levels of heterogeneity in CLD-related mortality patterns among the 3 largest Hispanic subgroups. Therefore, combining Hispanics as an aggregate group obscures potentially meaningful heterogeneity in etiology-specific CLD-related mortality rates among Hispanic subgroups.

Inpatient Outcomes for Gastrointestinal Bleeding Associated With Percutaneous Coronary Intervention.

GOALS: The goal of this study was to evaluate the impact of inpatient outcomes of gastrointestinal bleeding (GIB) related to percutaneous coronary intervention (PCI). BACKGROUND: With all-cause mortality increasing in patients undergoing PCIs, outcomes for GIB associated with PCI may be adversely impacted. STUDY: Using the National Inpatient Sample (2007 to 2012), we performed a nested case-control study assessing inpatient outcomes including incidence and mortality for PCI-related GIB hospitalizations. Multivariate logistic regression analyses were performed to determine significant predictors for GIB incidence and mortality. RESULTS: A total of 9332 (1.2%) of PCI hospitalizations were complicated by GIB with the age-adjusted incidence rate increasing 13% from 2007 (11.3 GIB per 1000 PCI) to 2012 (12.8). Patients ≥75 years of age experienced the steepest incline in GIB incidence, which increased 31% during the study period. Compared with non-GIB patients, mean length of stay (9.4 d vs. 3.3 d) and median cost of care ($29,236 vs. $17,913) was significantly higher. Significant demographic risk factors for GIB included older age and comorbid risk factors included gastritis or duodenitis, and Helicobacter pylori infection.In total, 1044 (11%) of GIB patients died during hospitalization with the GIB mortality rate increasing 30% from 2007 (95 deaths per 1000 GIB) to 2012 (123). Older age had the strongest association with inpatient mortality. CONCLUSIONS: Inpatient incidence and mortality for PCI-related GIB has been increasing particularly with a large increase in incidence among older patients. A multidisciplinary approach focused on risk-stratifying patients may improve preventable causes of GIB.

Treatment of patients waitlisted for liver transplant with all-oral direct-acting antivirals is a cost-effective treatment strategy in the United States.

All-oral direct acting antivirals (DAAs) have been shown to have high safety and efficacy in treating patients with hepatitis C virus (HCV) awaiting liver transplant (LT). However, there is limited empirical evidence comparing the health and economic outcomes associated with treating patients pre-LT versus post-LT. The objective of this study was to analyze the cost-effectiveness of pre-LT versus post-LT treatment with an all-oral DAA regimen among HCV patients with hepatocellular carcinoma (HCC) or decompensated cirrhosis (DCC). We constructed decision-analytic Markov models of the natural disease progression of HCV in HCC patients and DCC patients waitlisted for LT. The model followed hypothetical cohorts of 1,000 patients with a mean age of 50 over a 30-year time horizon from a third-party US payer perspective and estimated their health and cost outcomes based on pre-LT versus post-LT treatment with an all-oral DAA regimen. Transition probabilities and utilities were based on the literature and hepatologist consensus. Sustained virological response rates were sourced from ASTRAL-4, SOLAR-1, and SOLAR-2. Costs were sourced from RedBook, Medicare fee schedules, and published literature. In the HCC analysis, the pre-LT treatment strategy resulted in 11.48 per-patient quality-adjusted life years and $365,948 per patient lifetime costs versus 10.39 and $283,696, respectively, in the post-LT arm. In the DCC analysis, the pre-LT treatment strategy resulted in 9.27 per-patient quality-adjusted life years and $304,800 per patient lifetime costs versus 8.7 and $283,789, respectively, in the post-LT arm. As such, the pre-LT treatment strategy was found to be the most cost-effective in both populations with an incremental cost-effectiveness ratio of $74,255 (HCC) and $36,583 (DCC). Sensitivity and scenario analyses showed that results were most sensitive to the utility of patients post-LT, treatment sustained virological response rates, LT costs, and baseline Model for End-Stage Liver Disease score (DCC analysis only). CONCLUSION: The timing of initiation of antiviral treatment for HCV patients with HCC or DCC relative to LT is an important area of clinical and policy research; our results indicate that pre-LT treatment with a highly effective, all-oral DAA regimen provides the best health outcomes and is the most cost-effective strategy for the treatment of HCV patients with HCC or DCC waitlisted for LT. (Hepatology 2017;66:46-56).

Liver Transplantation for Nonalcoholic Steatohepatitis in the US: Temporal Trends and Outcomes.

BACKGROUND AND AIMS: Nonalcoholic steatohepatitis (NASH) is a rapidly growing etiology of end-stage liver disease in the US. Temporal trends and outcomes in NASH-related liver transplantation (LT) in the US were studied. METHODS: A retrospective cohort study utilizing the United Network for Organ Sharing and Organ Procurement and Transplantation (UNOS/OPTN) 2003-2014 database was conducted to evaluate the frequency of NASH-related LT. Etiology-specific post-transplant survival was evaluated with Kaplan-Meier methods and multivariate Cox proportional hazards models. RESULTS: Overall, 63,061 adult patients underwent LT from 2003 to 2014, including 20,782 HCV (32.96%), 9470 ALD (15.02%), and 8262 NASH (13.11%). NASH surpassed ALD and became the second leading indication for LT beginning in 2008, accounting for 17.38% of LT in 2014. From 2003 to 2014, the number of LT secondary to NASH increased by 162%, whereas LT secondary to HCV increased by 33% and ALD increased by 55%. Due to resurgence in ALD, the growth in NASH and ALD was comparable from 2008 to 2014 (NASH +50.15% vs. ALD +41.87%). The post-transplant survival in NASH was significantly higher compared to HCV (5-year survival: NASH -77.81%, 95% CI 76.37-79.25 vs. HCV -72.15%, 95% CI 71.37-72.93, P < .001). In the multivariate Cox proportional hazards model, NASH demonstrated significantly higher post-transplant survival compared to HCV (HR 0.75; 95% CI 0.71-0.79, P < .001). CONCLUSIONS: Currently, NASH is the most rapidly growing indication for LT in the US. Despite resurgence in ALD, NASH remains the second leading indication for LT.

The Role of e-Health in Optimizing Task-Shifting in the Delivery of Antiviral Therapy for Chronic Hepatitis C.

PURPOSE: Recently, we reported the successful application of task-shifting to improve the management of patients with chronic hepatitis C virus (HCV) infection receiving treatment with direct-acting antiviral (DAA) agents in underserved areas of California. We assessed the impact of e-health on task-shifting in our treatment model. METHODS: In a retrospective analysis, we reviewed the impact of e-health on optimizing the delivery of DAA-based regimen to HCV-infected patients in outreach clinics in medically underserved areas of California. A nonphysician healthcare provider worked in close conjunction with a hepatologist to monitor the patients during the course of antiviral therapy. We exclusively used our institution-based, secured e-health portal as the means of communication with the local staff and patients in outreach clinics. RESULTS: From January 2015 to June 2016, we treated over 100 HCV-infected patients with DAA-based regimens using the task-shifting model. During the study period, we did not experience any delay in the care of our patients undergoing treatment with DAA agents. Communication with the patient and staff using e-health was prompt, secured, and documented in electronic medical records. Due to the optimization of task-shifting by e-health and safety/tolerability of DAA, 95% patients did not need a follow-up clinic visit during the treatment. Return clinic visits during the treatment were unrelated to DAA use or associated with ribavirin-related anemia. In addition, we noted improvement in access and capacity of our outreach clinic. CONCLUSIONS: We report a positive impact of e-health in optimizing task-shifting for DAA in HCV-infected patients in underserved outreach clinics. More importantly, a secondary improvement in access and capacity of our clinic was noted.

Nonalcoholic steatohepatitis is the second leading etiology of liver disease among adults awaiting liver transplantation in the United States.

BACKGROUND & AIMS: Nonalcoholic steatohepatitis (NASH) has been predicted to become the leading indication for liver transplantation (LT) in the United States. However, few studies have evaluated changes in the etiology of liver diseases among patients awaiting LT, and none have focused on the effects of NASH on liver transplant waitlists in the United States. METHODS: We collected data from the United Network for Organ Sharing and Organ Procurement and Transplantation Network registry from 2004 through 2013, on liver transplant waitlist registrants with hepatitis C virus (HCV) infection, NASH, alcoholic liver disease (ALD), or a combination of HCV infection and ALD. We compared differences in survival within 90 days of registration (90-day survival) and probability of LT among patients with different diseases using Kaplan-Meier and multivariate logistic regression models. RESULTS: Between 2004 and 2013, new waitlist registrants with NASH increased by 170% (from 804 to 2174), with ALD increased by 45% (from 1400 to 2024), and with HCV increased by 14% (from 2887 to 3291); registrants with HCV and ALD decreased by 9% (from 880 to 803). In 2013, NASH became the second-leading disease among liver transplant waitlist registrants, after HCV. Patients with ALD had a significantly higher mean Model for End-Stage Liver Disease score at time of waitlist registration than other registrants. However, after multivariate adjustment, patients with ALD were less likely to die within 90 days when compared with patients with NASH (odds ratio [OR] = 0.77; 95% confidence interval [CI]: 0.67-0.89; P < .001); patients with HCV infection or HCV and ALD had similar odds for 90-day survival compared with NASH patients. Compared with patients with NASH, patients with HCV (OR = 1.45; 95% CI: 1.35-1.55; P < .001), ALD (OR = 1.15; 95% CI: 1.06-1.24; P < .001), or HCV and ALD (OR = 1.29; 95% CI: 1.18-1.42; P < .001) had higher odds for 90-day survival. CONCLUSIONS: Based on data from US adult LT databases, since 2004 the number of adults with NASH awaiting LTs has almost tripled. However, patients with NASH are less likely to undergo LT and less likely to survive for 90 days on the waitlist than patients with HCV, ALD, or HCV and ALD.

Chronic Hepatitis B Is Associated with Higher Inpatient Resource Utilization and Mortality Versus Chronic Hepatitis C.

BACKGROUND: Chronic hepatitis B virus (HBV) and chronic hepatitis C virus (HCV) infections remain one of the leading causes of chronic liver disease and hepatocellular carcinoma. Healthcare initiatives for chronic viral hepatitis to facilitate early diagnosis and linkage to care in an effort to reduce inpatient resource utilization associated with late diagnosis and end-stage liver disease have been partially successful. AIMS: Our objective was to determine the impact of liver-related complications from chronic HBV and HCV infections on inpatient cost of care, length of stay, and mortality. METHODS: Using the Healthcare Cost and Utilization Project, National Inpatient Sample (HCUP-NIS), we studied the impact of chronic HBV and HCV infections on inpatient healthcare system following hospitalizations from 2003 to 2012. RESULTS: Of the 79,185,729 million hospitalizations among adult patients in the USA from 2003 to 2012, 143,896 (0.18 %) hospitalizations were HBV related and 1,073,269 (1.36 %) hospitalizations HCV related. HBV hospitalizations had a higher inpatient mortality (OR 1.34; 95 % CI 1.30, 1.38), median cost of care per hospitalization (+$2100.33; 95 % CI 1982.53, 2217.53), and increased length of hospitalization stay (+0.64 days; 95 % CI 0.60, 0.68; p < 0.01) compared to HCV. CONCLUSIONS: Despite higher per case resource utilization following hospitalization, HBV-infected patients demonstrate a lower inpatient survival in comparison with chronic HCV infection. These disparate observations underscore the need for early diagnosis of chronic HBV infection in at-risk population and prompt linkage to care.

HCV infection is associated with lower survival in simultaneous liver kidney transplant recipients in the United States.

BACKGROUND: The frequency of simultaneous liver kidney transplantation (SLKT) has been increasing over the past decade. Hepatitis C virus (HCV) infection is the most common indication for liver transplantation in the United States. Given the rising prevalence of HCV-related SLKT, it is important to understand the impact of HCV in this patient population. METHODS: We conducted a retrospective cohort study using data from the United Network for Organ Sharing registry to assess adult patients undergoing SLKT in the United States from 2003 to 2012. Patient survival following SLKT was assessed using Kaplan-Meier methods and multivariate Cox proportional hazards models. RESULTS: Patients infected with non-HCV have significantly lower survival following SLKT compared to non-HCV patients at three (three-yr survival: 71.0% vs. 78.9%, p < 0.01) and five yr (five-yr survival: 61.4% vs. 72.5%, p < 0.01). The results of multivariate regression analyses demonstrated that patients infected with HCV had significantly lower survival following SLKT than patients with non-HCV disease (HR 1.41, 95% CI, 1.19-1.67, p < 0.001). In addition, lower post-SLKT survival was noted among patients with diabetes (HR 1.34, 95% CI, 1.13-1.58, p < 0.001) and hepatocellular carcinoma (HR 1.60, 95% CI, 1.17-2.18, p < 0.01). CONCLUSIONS: Hepatitis C infection is associated with lower patient survival following SLKT.

Hepatocellular Carcinoma in the Setting of Non-cirrhotic Nonalcoholic Fatty Liver Disease and the Metabolic Syndrome: US Experience.

BACKGROUND: Type 2 diabetes mellitus, obesity, and the metabolic syndrome (MS) have been growing in prevalence in the USA and are independent risk factors for the development of hepatocellular carcinoma (HCC). Nonalcoholic fatty liver disease (NAFLD), the hepatic manifestation of the MS, with or without nonalcoholic steatohepatitis (NASH) can predispose to HCC in the absence of cirrhosis or advanced fibrosis. Nevertheless, the US literature investigating non-cirrhotic HCC in the setting of NAFLD/NASH and MS is lacking. AIM: To describe a retrospective case series of patients who developed HCC without cirrhosis in the setting of NAFLD/NASH or features of the MS. METHODS: We identified NAFLD/NASH-associated HCC cases arising in the absence of cirrhosis between January 2010 and September 2012 from a tumor board database at Brooke Army Medical Center (BAMC). RESULTS: Of 44 cases of HCC reviewed, six cases of non-cirrhotic HCC associated with NAFLD/NASH and/or MS were identified. Only one patient underwent partial hepatectomy with curative intent. The other five might have been candidates for potential curative partial hepatectomy or liver transplantation had they been diagnosed earlier. CONCLUSION: Our case series highlights the development of NAFLD/NASH and MS-associated HCC in the absence of cirrhosis in the US population and raises the important question of HCC screening for this at-risk group.

Diabetes mellitus, and not obesity, is associated with lower survival following liver transplantation.

BACKGROUND AND AIMS: The impact of obesity on survival following liver transplantation is unclear, and existing studies report conflicting results. Our current study aims to further delineate the impact of obesity using population-based registry data from the USA. METHODS: All US adult liver transplant recipients from 2003 to 2012 were evaluated using the United Network for Organ Sharing registry. The impact of obesity on survival following liver transplantation was further stratified into class I obesity [body mass index (BMI) 30.0-34.9 kg/m(2)], class II obesity (BMI 35.0-39.9 kg/m(2)), and class III obesity (BMI ≥ 40 kg/m(2)) and evaluated using Kaplan-Meier methods and multivariate Cox proportional hazards models. RESULTS: Overall, 57,255 patients with chronic liver disease underwent liver transplantation, among which 32.9 % had BMI ≥ 30 kg/m(2). While patients in all obesity classes had similar survival to patients with BMI 18.0-24.9 kg/m(2), the presence of concurrent diabetes mellitus resulted in significantly lower post-transplant survival. After multivariate regression, post-transplant survival in patients with class II obesity (HR 0.97; 95 % CI 0.89-1.05) or class III obesity (HR 0.99; 95 % CI 0.90-1.09) was not significantly lower than patients with BMI 18.0-24.9 kg/m(2), but diabetes mellitus was independently associated with lower post-transplant survival (HR 1.29; 95 % CI 1.21-1.36). CONCLUSION: In conclusion, obesity alone was not associated with lower post-transplant survival. However, DM, either alone or comorbid with obesity, is associated with significantly greater post-transplant mortality.

Task-Shifting: An Approach to Decentralized Hepatitis C Treatment in Medically Underserved Areas.

BACKGROUND: Despite the availability of safe and effective direct-acting antiviral drugs (DAAs), the vast majority of patients with chronic hepatitis C (HCV) in the USA remain untreated, in part due to lack of access to specialist providers. AIMS: To determine the effectiveness of DAA-based treatment in medically underserved areas in California, in a healthcare model dependent on task-shifting--wherein a visiting hepatologist assesses patients for treatment eligibility, but subsequent routine follow-up evaluation of patients prescribed treatment is devolved to a part-time licensed vocational nurse under remote supervision of the hepatologist. METHODS: We retrospectively determined rates of sustained virologic response 12 weeks after treatment completion (SVR-12), adverse events, and treatment discontinuations in patients who received sofosbuvir-based DAA regimens between December 2013 and November 2014. RESULTS: Despite limited specialist provider involvement in medically underserved areas, all but two of 58 patients completed treatment, and 88 % of patients achieved the curative endpoint of undetectable HCV RNA 12 weeks after completing treatment (sustained virologic response, SVR-12). Almost 80 % of patients with cirrhosis and 85 % of patients with prior treatment experience achieved SVR-12. CONCLUSIONS: Treatment effectiveness with sofosbuvir-based regimens in medically underserved areas utilizing task-shifting from a specialist to a mid-level provider is comparable to those achieved in pivotal clinical trials for these regimens, and to "real-world" experiences of tertiary care centers in the USA.