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While traditionally employed to manage malignant gastrointestinal (GI) obstruction, a variety of luminal stents have been employed in the management of refractory benign GI strictures with varying safety and efficacy profiles. These include: self-expanding metal stents (SEMS), self-expanding plastic stents (SEPS), biodegradable stents and lumen-apposing metal stents (LAMS). LAMS have become instrumental as an alternate strategy to treat benign gastric outlet obstruction in the setting of native and postsurgical anatomy. This includes transpyloric placement as well as EUS-guided gastrojejunostomy creation as an alternative to laparoscopic gastrojejunostomy and endoluminal stenting. The novel application of LAMS for complete endoscopic management with anastomotic decompression of afferent loop syndrome has also been met with success in case reports and series. This approach with LAMS obviates the need for external drains and complex repeat surgeries. Finally, SEMS have been used to address benign and malignant strictures of the small bowel. However, SEMS use for this indication has been hindered by limitations in endoscopic accessibility of target sites and the current state of stent delivery systems. Whereas the role of colonic stenting for malignant colonic obstruction is well-established, the use of stents to treat benign colonic strictures continues to evolve. While the existing armamentarium of GI luminal stents has revolutionized the management of a variety of clinical conditions, additional advances could further broaden the potential applications of these devices.

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.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.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).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.

With over 100000 hospital admissions per annum, acute pancreatitis remains the leading gastrointestinal cause of hospitalization in the United States and has far-reaching impact well beyond. It has become increasingly recognized that drug-induced pancreatitis (DIP), despite accounting for less than 3% of all cases, represents an important and growing though often inconspicuous cause of acute pancreatitis. Nevertheless, knowledge of DIP is often curtailed by the limited availability of evidence needed to implicate given agents, especially for non-prescription medications. Indeed, the majority of available data is derived from case reports, case series, or case control studies. Furthermore, the mechanism of injury and causality for many of these drugs remain elusive as a definitive correlation is generally not established (< 10% of cases). Several classification systems have been proposed, but no single system has been widely adopted, and periodic updates are required in light of ongoing pharmacologic expansion. Moreover, infrequently prescribed medications or those available over-the-counter (including herbal and other alternative remedies) are often overlooked as a potential culprit of acute pancreatitis. Herein, we review the ever-increasing diversity of DIP and the potential mechanisms of injury with the goal of raising awareness regarding the nature and magnitude of this entity. We believe this manuscript will aid in increasing both primary and secondary prevention of DIP, thus ultimately facilitating more expedient diagnosis and a decrease in DIP-related morbidity.

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).

In the United States, the fight to eradicate hepatitis C virus (HCV) infection has been ongoing for many years, but the results have been less than ideal. Historically, patients with chronic hepatitis C (CHC) were treated with interferon-based regimens, which were associated with frequent adverse effects, suboptimal response rates, and long durations of treatment – of up to 48 weeks. Expertise from specialist-physicians, such as hepatologists and gastroenterologists, was needed to closely follow patients on these medications so as to monitor laboratory values and manage adverse effects. However, the emergence of direct-acting antiviral (DAA) agents against HCV infection have heralded outstanding progress in terms of safety, tolerability, lack of adverse effects, efficacy, and truncated duration of therapy – 12 weeks or less – thereby making the need for close monitoring by specialist-physicians obsolete. With the recent approval of DAA agents by the Food and Drug Administration, the treatment model for CHC no longer relies on the limited number of specialist-physicians, which represented a major barrier to treatment access in the past, especially in underserved areas of the United States. We propose and share our experiences in adapting a task-shifting treatment model, one that utilizes a relatively larger pool of non-specialist healthcare providers, such as nursing staff (medical assistants, vocational licensed nurses, registered nurses, etc.) and advanced practice providers (nurse practitioners and physician assistants), to perform a variety of important clinical functions in an effort to make DAA-based antiviral therapy widely available against HCV infection. Most recently, task-shifting was implemented by the United States and World Health Organization in the fight against the human immunodeficiency virus and showed encouraging results. Based on our experiences in implementing this model at our outreach clinics, the majority of HCV-infected patients treated with DAA agents can be easily monitored by non-specialist healthcare providers and physician extenders. Task-shifting can effectively address one of the major rate-limiting factors in expanding treatment access for HCV infection.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide. The rising incidence, genetic heterogeneity, multiple etiologies, and concurrent chronic liver diseases make diagnosis, staging, and selection of treatment options challenging in patients with HCC. The best approach to optimize the management of HCC is one that utilizes a core multidisciplinary liver tumor board, consisting of hepatologists, pathologists, interventional radiologists, oncologists, hepatobiliary and transplant surgeons, nurses, and general practitioners. In most cases, HCC is diagnosed by abdominal imaging studies, preferably with a triphasic computed tomography scan of the abdomen or magnetic resonance imaging of the abdomen. Histopathological diagnosis using a guided liver biopsy may be needed in noncirrhotic patients or when radiological diagnostic criteria are not fulfilled in the setting of cirrhosis. The Barcelona Clinic Liver Cancer staging system facilitates a standardized therapeutic strategy based on the tumor burden, extent of metastasis, severity of hepatic decompensation, comorbid medical illnesses, functional status of patient, HCC-related symptoms, and preference of the patient. Treatment options include curative surgery (hepatic resection and liver transplantation) and palliative measures (radiofrequency ablation, transarterial chemoembolization, and chemotherapy with sorafenib). The role of the multidisciplinary team is crucial in promptly reconfirming the diagnosis, staging the HCC, and formulating an individualized treatment plan. In potential liver transplant candidates, timely liver transplant evaluation and coordinating bridging/downsizing treatment modalities, such as radiofrequency ablation and transarterial chemoembolization, can be time-consuming. In summary, a multidisciplinary team approach provides a timely, individualized treatment plan, which can vary from curative surgery in patients with early-stage HCC to palliative/hospice care in patients with metastatic HCC. In most tertiary care centers in the US, a multidisciplinary liver tumor board has become the standard of care and a key component of best practice protocol for patients with HCC.

Hepatic encephalopathy (HE) is a complex disease requiring a multidisciplinary approach among specialists, primary care team, family, and caregivers. HE is currently a diagnosis of exclusion, requiring an extensive workup to exclude other possible etiologies, including mental status changes, metabolic, infectious, traumatic, and iatrogenic causes. The categorization of HE encompasses a continuum, varying from the clinically silent minimal HE (MHE), which is only detectable using psychometric tests, to overt HE, which is further divided into four grades of severity. While there has been an increased effort to create fast and reliable methods for the detection of MHE, screening is still underperformed due to the lack of standardization and efficient methods of diagnosis. The management of HE requires consultation from various disciplines, including hepatology, primary care physicians, neurology, psychiatry, dietician/nutritionist, social workers, and other medical and surgical subspecialties based on clinical presentation and clear communication among these disciplines to best manage patients with HE throughout their course. The first-line therapy for HE is lactulose with or without rifaximin. Following the initial episode of overt HE, secondary prophylaxis with lactulose and/or rifaximin is indicated with the goal to prevent recurrent episodes and improve quality of life. Recent studies have demonstrated the negative impact of MHE on quality of life and clinical outcomes. In light of all this, we emphasize the importance of screening and treating MHE in patients with liver cirrhosis, particularly through a multidisciplinary team approach.

Although currently available therapies for chronic hepatitis B virus infection can suppress viremia and provide long-term benefits for patients, they do not lead to a functional cure for most patients. Advances in our understanding of the virus-host interaction and the recent remarkable success of immunotherapy in cancer offer new and promising strategies for developing immune modulators that may become important components of a total therapeutic approach to hepatitis B, some of which are now in clinical development. Among the immunomodulatory agents currently being investigated to combat chronic HBV are toll-like receptor agonists, immune checkpoint inhibitors, therapeutic vaccines, and engineered T cells. The efficacy of some immune modulatory therapies is compromised by high viral antigen levels. Cutting edge strategies, including RNA interference and CRISPR/Cas9, are now being studied that may ultimately be shown to have the capacity to lower viral antigen levels sufficiently to substantially increase the efficacy of these agents. The current advances in therapies for chronic hepatitis B are leading us toward the possibility of a functional cure.

The rate of colorectal foreign bodies is increasing. Endoscopists must be creative in order to remove the foreign objects safely in the most minimally invasive manner as these objects could vary greatly in size and shape. We present a case of the novel use of an esophageal overtube to aid in the removal of a difficult-to-remove Tide-To-Go cap.

Background Automated drying may help prevent endoscopically transmitted infections. We aimed to assess the efficacy of an automated drying and storage cabinet compared to a standard storage cabinet in achieving endoscope dryness postreprocessing and in reducing the risk of microbial growth. Methods Drying times of bronchoscopes, colonoscopes, and duodenoscopes using 2 drying platforms (an automated drying and storage cabinet vs a standard storage cabinet) were measured using cobalt chloride paper. Drying assessments occurred at: 30 minutes, 1 hour, 2 hours, 3 hours, and 24 hours. A simple linear regression analysis compared rates of microbial growth after inoculation with Pseudomonas aeruginosa following high-level disinfection at: 0, 3 hours, 12 hours, 24 hours, and 48 hours. Results Using the automated drying and storage cabinet, internal channels were dry at 1 hour and external surfaces at 3 hours in all endoscopes. With the standard storage cabinet, there was residual internal fluid at 24 hours, whereas external surfaces were dry at 24 hours. For bronchoscopes, colonoscopes, and duodenoscopes, the standard cabinet allowed for an average rate of colony forming unit growth of 8.1 × 106 per hour, 8.3 × 106 per hour, and 7.0 × 107 per hour, respectively; the automated cabinet resulted in colony forming unit growth at an average rate of –28.4 per hour (P = .02), –38.5 per hour (P = .01), and –200.2 per hour (P = .02), respectively. Conclusions An automated cabinet is advantageous for rapid drying of endoscope surfaces and in reducing the risk of microbial growth postreprocessing.

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.

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

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.

We report safety, tolerability, and 12-week sustained virologic response with half-standard dose sofosbuvir and standard-dose simeprevir combination therapy in a hepatitis C virus genotype 1a-infected liver transplant recipient on hemodialysis - uncharted territory for sofosbuvir-based therapy. The patient was a non-responder to prior treatment with pegylated interferon plus ribavirin. Sofosbuvir efficacy was maintained despite pill-splitting and administration of half-standard dose, 200 mg per day. No drug-drug interactions were noted with tacrolimus-based immunosuppression. Laboratory tests remained stable or improved during therapy. Our observation, if reproduced in a larger study, may lead to significant improvement in clinical outcomes and cost savings in this patient population.

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.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.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).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.

We aim to study the impact of the baby boomer (BB) generation, a birth-specific cohort (born 1945-1965) on hepatocellular carcinoma (HCC)-related liver transplantation (LT) in patients with chronic hepatitis C virus (HCV), alcoholic liver disease (ALD), and non-alcoholic steatohepatitis (NASH). We performed a retrospective analysis using the United Network for Organ Sharing (UNOS)/Organ Procurement Transplant Network (OPTN) database from 2003 to 2014 to compare HCC-related liver transplant surgery trends between two cohorts-the BB and non-BB-with a secondary diagnosis of HCV, ALD, or NASH. From 2003-2014, there were a total of 8313 liver transplant recipients for the indication of HCC secondary to HCV, ALD, or NASH. Of the total, 6658 (80.1%) HCC-related liver transplant recipients were BB. The number of liver transplant surgeries for the indication of HCC increased significantly in NASH (+1327%), HCV (+382%), and ALD (+286%) during the study period. The proportion of BB who underwent LT for HCC was the highest in HCV (84.7%), followed by NASH (70.3%) and ALD (64.7%). The recommendations for birth-cohort specific HCV screening stemmed from a greater understanding of the high prevalence of chronic HCV and HCV-related HCC within BB. The rising number of HCC-related LT among BB with ALD and NASH suggests the need for increased awareness and improved preventative screening/surveillance measures within NASH and ALD cohorts as well.

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. 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. 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

Background & Aims Chronic hepatitis C virus (HCV) infection is the leading indication for liver transplantation (LT) and liver re-transplantation (re-LT) in the United States (US). Following LT, the recurrence of HCV infection is universal, with 40% of grafts developing cirrhosis within five years, often necessitating re-LT. Until recently, treatment strategies for liver transplant recipients with recurrent HCV infection were less than ideal; however, the recent development and approval of direct-acting antiviral (DAA) agents have shifted the treatment paradigm in this difficult-to-treat cohort. Methods Using the United Network for Organ Sharing Database, we analyzed adults in the US who underwent re-LT from 2005 to 2014. We performed multivariate logistic analyses to determine the predictors of re-LT among patients with post-transplant recurrent HCV infection. Results The annual HCV re-LT rate (per 100 HCV-related LT) declined from 8.8 in 2005 to 3.8 in 2014. Moreover, the proportion of HCV-related re-LT within 1 year of LT declined from 20.4% in 2005 to 1.2% in 2014. Conclusion Our analysis demonstrated that the reduction in the rate of re-LT was independently associated with the era of DAA-based treatment. This article is protected by copyright. All rights reserved.

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.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.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.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.

Background and Aims: Nonalcoholic steatohepatitis (NASH) is the most rapidly growing indication for liver transplantation (LT) in the United States and is on a trajectory to become the leading indication for LT in the next decade. We aimed to study the trends in NASH-related LT among persons born between 1945 and 1965, the baby boomer (BB) generation. Methods: We performed a retrospective cohort analysis using population-based data from the United Network for Organ Sharing/Organ Procurement and Transplantation Network registry from 2004–2015 to evaluate the birth cohort-specific trends in liver transplant waitlist registrations and liver transplant surgeries in patients with NASH. We stratified our study population into three birth cohorts: 1) birth before 1945, 2) birth between 1945 and 1965, and 3) birth after 1965. Results: The overall rates of NASH-related waitlist registrations and liver transplant surgeries steadily increased from 2004 to 2015 and were reflective of a sharp rise noted in the NASH BB sub-group. From 2004 to 2015, the proportion of BB patients with NASH added to LT waitlist demonstrated an incremental growth, 60.6% in 2004 versus 83.2% in 2015 (p < 0.01). Among the liver transplant recipients with NASH, the proportion represented by the BB cohort increased from 56.3% in 2004 to 80.0% in 2015 (p < 0.01). Conclusions: We report rising rates of waitlist registration and LT for the indication of NASH. More importantly, the BB sub-cohort was mainly responsible for these alarming trends.

Background and Aims: Patients with chronic hepatitis C (CHC) and end-stage renal disease (ESRD) who are dialysis-dependent form a unique group, in which safety, tolerability and efficacy of sofosbuvir (SOF)-based direct-acting antivirals (DAAs) need further evaluation. Methods: We performed a retrospective analysis of 14 patients with CHC and ESRD on dialysis who received 15 courses of SOF-based therapy. We evaluated dose escalation to standard-dose SOF in this proof-of-principle experience. Results: Sustained virological response (defined as undetectable viral load at 12 weeks, SVR-12) was achieved in 13 out of the 15 (86.7%) treatment courses. Seven (46.6%) patients received reduced half dose as conservative proof-of-principal to mitigate potential toxicity. In 13 out of 15 treatment courses, patients completed the designated treatment duration. One patient was treated twice and developed SVR-12 with the retreatment. One patient was lost to follow-up and counted as a non-responder. Premature discontinuations were not due to DAA-related adverse effects. There were no reports of severe adverse effects or drug interactions. Conclusion: We treated CHC patients with ESRD using dose escalation to standard-dose SOF in this proof-of-principle experience and achieved SVR rates comparable to general population.

Background and Aims: The current paradigm of specialist physician-managed treatment of chronic hepatitis C virus infection (HCV) is inefficient in absorbing the approximately 3 million patients awaiting treatment in the United States. Task shifting—whereby specialist physicians screen patients for treatment eligibility but on-treatment monitoring is devolved to more abundant non-physician clinicians—achieves non-inferior treatment outcomes with second generation direct-acting antivirals (2nd Gen DAAs), may increase treatment capacity, and may facilitate greater treatment access. We determined the cost effectiveness of 2nd Gen DAAs with respect to interferon-based first-generation DAAs (1st Gen DAAs) within a task-shifted treatment model. Methods: Using a previously described decision-analytic Markov structure, we modeled a hypothetical cohort of 1,000 patients with HCV genotype 1 infection over a lifetime horizon, based upon our outreach clinic’s HCV treatment protocol. Treatment-naïve and treatment-experienced HCV cohorts were modeled separately, based upon our outr8each clinic’s demographics. Treatment response to 2nd Gen DAAs was modeled based on our outreach clinic’s data. Adverse events, utility, costing, and transition probabilities were sourced from the literature. Results: Driven by improved effectiveness and safety, as well as an expected increase in treatment capacity, 2nd Gen DAAs treatment monitored by non-physician clinicians was projected to improve health outcomes and be dominant from a cost-effective perspective versus that of 1st Gen DAAs. Trends were consistent across all assessed patient subpopulations. Conclusions: Based on an assumption of increased treatment capacity accompanying a task-shifted treatment model, 2nd Gen DAAs-based treatment was cost effective and cost saving as compared to 1st Gen DAAs-based treatment for all HCV patient subgroups assessed.

Patients with Down syndrome who received blood transfusions, likely in conjunction with cardiothoracic surgery for congenital heart disease and prior to the implementation of blood-donor screening for hepatitis C virus infection, face a substantial risk of acquiring the infection. In the past, interferon-based therapy for chronic hepatitis C infection in patients with Down syndrome was noted to have lower efficacy and potentially higher risk of adverse effects. Recently, the treatment for chronic hepatitis C has been revolutionized with the introduction of interferon-free direct acting antivirals with favorable safety, tolerability, and efficacy profile. Based on our experiences, the newly approved sofosbuvir-based direct acting antiviral therapy is well tolerated and highly efficacious in this subpopulation of hepatitis C virus infected patients with Down syndrome.

Background and Aims: Utilization of living donor liver transplantation (LDLT) and its relationship with recipient Model for End-Stage Liver Disease (MELD) needs further evaluation in the United States (U.S.). We evaluated the association between recipient MELD score at the time of surgery and survival following LDLT. Methods: All U.S. adult LDLT recipients with MELD < 25 were evaluated using the 1995–2012 United Network for Organ Sharing registry. Survival following LDLT was stratified into three MELD categories (MELD < 15 vs. MELD 15–19 vs. MELD 20–24) and evaluated using Kaplan-Meier methods and multivariate Cox proportional hazards models. Results: Overall, 2,258 patients underwent LDLT. Compared to patients with MELD < 15, overall 5-year survival following LDLT was similar among patients with MELD 15–19 (80.9% vs. 80.3%, p = 0.77) and MELD 20–24 (81.2% vs. 80.3%, p = 0.73). When compared to patients with MELD < 15, there was no significant difference in long-term post-LDLT survival among those with MELD 15–19 (HR: 1.11, 95% CI: 0.85−1.45, p = 0.45) and a non-significant trend towards lower survival in patients with MELD 20–24 (HR: 1.28, 95% CI: 0.91−1.81, p = 0.16). Only 14% of LDLTs were performed in patients with MELD 20–24 and the remaining 86% in patients with MELD < 20. Conclusion: LDLT is underutilized in patients with MELD 20 and higher.

Magnetic resonance elastography (MRE) can noninvasively measure the stiffness of liver tissue and display this information in anatomic maps. Magnetic resonance imaging (MRI) guidance has not previously been used to biopsy segments of heterogeneous stiffness identified on MRE. Dedicated study of MRE in post-liver transplant patients is also limited. In this study, the ability of real-time MRI to guide biopsies of segments of the liver with different MRE stiffness values in the same post-transplant patient was assessed.MRE was performed in 9 consecutive posttransplant patients with history of hepatitis C. Segments of highest and lower stiffness on MRE served as targets for subsequent real-time MRI-guided biopsy using T2-weighted imaging. The ability of MRI-guided biopsy to successfully obtain tissue specimens was assessed. The Wilcoxon signed-rank test was used to compare mean stiffness differences for highest and lower MRE stiffness segments, with α = 0.05.MRI guidance allowed successful sampling of liver tissue for all (18/18) biopsies. There was a statistically significant difference in mean MRE stiffness values between highest (4.61 ± 1.99 kPa) and lower stiffness (3.03 ± 1.75 kPa) (P = .0039) segments biopsied in the 9 posttransplant patients.Real-time MRI can guide biopsy in patients after liver transplantation based on MRE stiffness values. This study supports the use of MRI guidance to sample tissue based on functional information.

To the Editor: Hepatitis E is a viral hepatitide that is endemic in many developing countries. In its classic form, it results from ingesting fecally contaminated water that carries hepatitis E virus (HEV), and it frequently resolves without treatment. When hepatitis E is imported to the United States, it originates mainly from persons who have acquired HEV genotype 1 infection from South Asia (1). We report imported HEV genotype 4 infection (Technical Appendix Figure, panel A) in a patient during which cirrhosis and fatal hepatic decompensation ensued. The patient was a 68-year-old man of Chinese ethnicity who had been a California resident since 1985. He sought treatment for mild jaundice in April 2013 in Hong Kong, where he had been staying for 7 weeks. Sixteen years before, he had undergone orthotopic liver transplantation at Stanford University Medical Center (Palo Alto, California, USA) for hepatitis B cirrhosis. Since then, he had received entecavir and tacrolimus for maintenance and had been vaccinated against hepatitis A virus. Until his current illness, routine liver function tests had not indicated hepatic dysfunction (values in November 2012: alanine aminotransferase 2 IU/L, aspartate aminotransferase 24 IU/L, alkaline phosphatase 67 IU/L, total bilirubin 0.5 mg/dL). When the patient returned to the United States, 3 weeks after onset of jaundice, the initial work-up showed the following values: alanine aminotransferase 149 IU/L, aspartate aminotransferase 59 IU/L, alkaline phosphatase 193 IU/L, total bilirubin 2.8 mg/dL (Technical Appendix Figure, panel B). Hepatitis B virus DNA and antinuclear antibodies were not detected, and the tacrolimus level was stable. Ultrasound revealed a normal transplanted liver. A liver biopsy specimen showed mild portal, biliary, and lobular inflammation and early biliary injury (Figure, panels A, B). The prednisone dosage was escalated, and mycophenolate mofetil was added. Liver enzyme activity showed some improvement, but the bilirubin level continued to rise (Technical Appendix Figure, panel B). Figure Serial histologic changes in liver of the patient who received a diagnosis of hepatitis E after a visit to Hong Kong in 2013 (A and B: at first biopsy; C and D: second biopsy; E and F: third biopsy. A) Mild mixed portal infiltration; minimal lobular inflammation; ... A biopsy specimen taken 3 months later showed grade 3 hepatitis with bile ductular reaction, bridging hepatocytic necrosis and fibrosis, and regenerative nodule formation (Figure, panels C, D). A blood sample taken about this time tested positive for HEV RNA. The patient was then given ribavirin (1,000 mg/d). Before hepatitis E was diagnosed, tacrolimus was given (1 mg 2×/d); when the diagnosis was confirmed, the tacrolimus dose was reduced to 0.5 mg every other day. Four months after the patient sought treatment, ascites was noted. Ribavirin was stopped because of pancytopenia. Blood samples subsequently tested negative for HEV RNA, but HEV IgM and IgG were found. Hepatic function did not improve. Eight months after onset of the patient’s condition, marked hepatic decompensation occurred (Technical Appendix Figure), culminating in esophageal variceal hemorrhage. The patient was placed on a waiting list and then underwent liver transplantation, but he died during the operation from complications of hemorrhage. Biopsy of the liver explant revealed intense lobular inflammation with the hepatocellular reactive changes persisting and stage IV fibrosis (Figure, panels E, F). The patient had lived and worked in Hong Kong before he became a resident of the United States. He had not visited Hong Kong in the 3 years preceding his most recent trip, nor had he traveled to Europe. Review of his medical records revealed no evidence of hepatic dysfunction after his previous travels. Considering that his most recent visit to Hong Kong coincided with the incubation period of hepatitis E (2), he most likely acquired HEV genotype 4 infection during that visit. In China over the past decade, national notifications of HEV infection have risen, with 28,232 cases reported in 2013 (3). In Hong Kong, where a rising trend in hepatitis E notifications also has been observed (150 cases reported in 2012 [4]), HEV infections are almost all associated with HEV genotype 4 (5). This patient’s HEV subgenomic sequence was closely related to human and porcine HEV genotype 4 sequences reported from mainland China and Hong Kong (Technical Appendix Figure, panel A). Porcine liver has been implicated as a possible HEV transmission vehicle in that region (6); although we do not know whether the patient ate food that carried HEV, the possibility underscores the importance of avoiding eating inadequately cooked animal-derived food products during international travel (2). Chronic hepatitis with accelerated cirrhosis has been reported in solid-organ transplant recipients infected with HEV genotype 3, but not with genotype 4 (7). Serial liver biopsy specimens from the patient showed persistent and worsening hepatitis and rapid onset of fibrosis that intensified (Technical Appendix Figure, panel B). Testing for HEV infection is recommended during initial assessments of posttransplant hepatic dysfunction because histologic appearances in liver biopsy specimens may not clearly distinguish between graft rejection and acute viral hepatitis (Figure, panels A, B). Early diagnosis of hepatitis E should lead to prompt administration of antiviral therapy and appropriate adjustments to the immunosuppressant drug regimen, particularly because some drugs can exert opposing effects on HEV replication (8). Technical Appendix. A) Phylogenetic tree comparing a 258-nt sequence within hepatitis E virus (HEV) open reading frame 1 (​(1)1) of the patient who visited Hong Kong in 2013 with corresponding, representative GenBank sequences. Included is a corresponding sequence from patient A, a 63-year-old Caucasian man, a resident of Alabama, in whom acute, self-resolving hepatitis developed 5 weeks after he returned from a 2-week visit to Shandong, China. Numerals beside each sequence denote year of sequence reporting; alphanumerics denote GenBank accession numbers. GT, genotype; CH, China; HK, Hong Kong; MX, Mexico; US, United States. B) Chronology of changes in liver function and hepatitis E markers in the patient. Click here to view.(215K, pdf)

To the Editor: The Centers for Disease Control and Prevention and US Preventive Services Task Force recommend a one-time screening for hepatitis C virus (HCV) infection in adults born during 1945–1965 (birth cohort), a demographic group with a disproportionately high prevalence of HCV infection (1,2). However, some experts have warned against routine HCV screening of persons in the birth cohort, stating that this recommendation is based on unproven assumptions about the benefit of screening in reducing HCV-related mortality, given that only a minority of infected persons develop end-stage liver disease (ESLD) (3). To determine the relative effect of the birth cohort on HCV-related ESLD incidence in the United States, we analyzed trends in liver transplantation (LT) waitlist registrations and LT surgeries during 1995–2012. Using data from the United Network for Organ Sharing national registry, we evaluated birth cohort–specific (birth cohort vs. non–birth cohort) and etiology-specific (HCV vs. non-HCV) trends in LT waitlist registrations and LT surgeries performed in the United States during that 18-year period. The proportion of HCV-infected persons born during 1945–1965 among all persons with LT waitlist registrations in the United States increased from 17.8% in 1995 to 35.2% in 2012 (Table). The highest proportion of LT waitlist registrations for HCV-related ESLD was for persons in the birth cohort and increased incrementally from 61.2% in 1995 to 90.5% in 2012. The proportion of LT waitlist registrations for HCV-related ESLD among persons younger than the birth cohort was 1.0% in 1995 and 3.6% in 2012; among persons older than the birth cohort, the proportion was 37.8% in 1995 and 5.9% in 2012. Table Liver transplant waitlist additions and liver transplant recipients, United States* Similarly, among LT recipients, the proportion of HCV-infected persons born during 1945–1965 doubled from 17.4% in 1995 to 35.4% in 2012 (Table). The proportion of LT surgeries performed for HCV-related ESLD among persons in the birth cohort increased from 60.2% in 1995 to 90.7% in 2012. Among persons younger than the birth cohort, the proportion of LT surgeries performed for HCV-related ESLD was 0.7% in 1995 and 5.0% in 2012; among persons older than the birth cohort, the proportion was 39.1% in 1995 and 4.3% in 2012. During 1995–2012, the ratio of new LT waitlist registrations to LT surgeries performed for HCV-infected persons in the birth cohort remained unchanged at 1.9:2.0 despite the aging of this birth cohort. Overall trends in HCV-related LT waitlist registrations and LT surgeries stabilized during 2001–2012; the proportion of HCV-infected persons in the birth cohort increased, and the proportion of HCV-infected persons not in the birth cohort decreased. To exclude the possibility that HCV-related ESLD has always simply affected persons 50–70 years of age, we performed a subanalysis examining the proportion of LT waitlist registrations and LT surgeries for persons 50–70 years of age in each year from 1995 through 2012. During this 18-year period, among persons 50–70 years of age, new HCV-related LT waitlist registrations increased from 43.9% to 93.0%, and LT surgeries performed increased from 47.1% to 86.2%. This finding suggests that persons born during 1945–1965 are a distinct birth cohort that is increasingly affected by HCV-related ESLD. Although persons born during 1945–1965 make up an estimated 27% of the US population, they account for ≈75% of all HCV infections and 73% of HCV-associated deaths in the United (1). Our findings are consistent with those of an earlier modeling study by Davis et al. (4), which suggested that the age of persons with HCV-related cirrhosis and its complications will continue to increase. Limitations of our study include inherent limitations of retrospective design and registry data. The designation of HCV infection and birth cohort status is based entirely on data entered into the database, which are not necessarily subject to cross-checking confirmatory measures. However, any errors in data entry that may have occurred are probably nondifferential. Despite these limitations, our analysis demonstrates that >90% of HCV-infected persons registered for LT or undergoing LT surgeries in 2012 were in the birth cohort. Earlier diagnosis and preemptive cure of HCV infection with highly effective and safe direct-acting antiviral drugs may delay or reduce the need for LT among persons in the birth cohort (5). Testing and linkage to care for HCV-infected persons, particularly persons in the birth cohort, can be expected to reduce HCV-related illness and death (1,2). In response to the approval of higher efficacy antiviral drugs and rapidly rising liver failure–related death among this cohort (6,7), the use of HCV-infected donors has increased, resulting in truncated wait times for HCV-infected LT recipients in many regions (8), whereas HCV-uninfected persons are generally waiting considerably longer, often years, for HCV-uninfected donors (9). This phenomenon is another index of the extent of HCV-related ESLD in the United States.

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. 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. 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. 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