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BACKGROUND & AIMS: Successful treatment of chronic hepatitis C with oral direct-acting antivirals (DAAs) leads to virological cure, however, the subsequent risk of hepatocellular carcinoma (HCC) persists. Our objective was to evaluate the cost-effectiveness of biannual surveillance for HCC in patients cured of hepatitis C and the optimal age to stop surveillance. METHODS: We developed a microsimulation model of the natural history of HCC in individuals with hepatitis C and advanced fibrosis or cirrhosis who achieved virological cure with oral DAAs. We used published data on HCC incidence, tumor progression, real-world HCC surveillance adherence, and costs and utilities of different health states. We compared biannual HCC surveillance using ultrasound and alpha-fetoprotein for varying durations of surveillance (from 5 years to lifetime) vs. no surveillance. RESULTS: In virologically cured patients with cirrhosis, the incremental cost-effectiveness ratio (ICER) of biannual surveillance remained below $150,000 per additional quality-adjusted life year (QALY) (range: $79,500-$94,800) when surveillance was stopped at age 70, irrespective of the starting age (40–65). Compared with no surveillance, surveillance detected 130 additional HCCs in ‘very early’/early stage and yielded 51 additional QALYs per 1,000 patients with cirrhosis. In virologically cured patients with advanced fibrosis, the ICER of biannual surveillance remained below $150,000/QALY (range: $124,600-$129,800) when surveillance was stopped at age 60, irrespective of the starting age (40–50). Compared with no surveillance, surveillance detected 24 additional HCCs in ‘very early’/early stage and yielded 12 additional QALYs per 1,000 patients with advanced fibrosis. CONCLUSION: Biannual surveillance for HCC in patients cured of hepatitis C is cost-effective until the age of 70 for patients with cirrhosis, and until the age of 60 for patients with stable advanced fibrosis. LAY SUMMARY: Individuals who are cured of hepatitis C using oral antiviral drugs remain at risk of developing liver cancer. The value of lifelong screening for liver cancer in these individuals is not known. By simulating the life course of hepatitis C cured individuals, we found that ultrasound-based biannual screening for liver cancer is cost-effective up to age 70 in those with cirrhosis and up to age 60 in those with stable advanced fibrosis.

Summary Background Alcohol-related liver disease is the leading indication for liver transplantation in the USA. After remaining stable for over three decades, the number of deaths due to alcohol-related liver disease has been increasing as a result of increased high-risk drinking. We aimed to project trends in alcohol-related cirrhosis and deaths in the USA up to 2040 and assess the effect of potential changes in alcohol consumption on those trends. Methods In this modelling study, we developed a multicohort state-transition (Markov) model of high-risk alcohol drinking patterns and alcohol-related liver disease in high-risk drinking populations born in 1900–2016 in the USA projected up to 2040. We used data from the National Epidemiologic Survey on Alcohol and Related Conditions, National Institute of Alcohol Abuse and Alcoholism, US National Death Index, National Vital Statistics System, and published studies. We modelled trends in alcohol-related liver disease under three projected scenarios: the status quo scenario, in which current trends continued; a moderate intervention scenario, in which trends in high-risk drinking reduced to 2001 levels under some hypothetical moderate intervention; and a strong intervention, in which trends in high-risk drinking decreased by 3·5% per year under some hypothetical strong intervention. The primary outcome was to project deaths associated with alcohol-related liver disease from 2019 to 2040 for each pattern of alcohol consumption under the different scenarios. Findings Our model closely reproduced the observed trends in deaths due to alcohol-related liver disease from 2005 to 2018. Under the status quo scenario, age-standardised deaths due to alcohol-related liver disease are expected to increase from 8·23 (95% uncertainty interval [UI] 7·92–9·29) per 100 000 person-years in 2019 to 15·20 (13·93–16·19) per 100 000 person-years in 2040, and from 2019 to 2040, 1 003 400 (95% CI 896 800–1 036 200) people are projected to die from alcohol-related liver disease, resulting in 1 128 400 (1 113 200–1 308 400) DALYs by 2040. Under the moderate intervention scenario, age-standardised deaths due to alcohol-related liver disease would increase to 14·49 (95% UI 12·55–14·57) per 100 000 person-years by 2040, with 968 100 (95% UI 845 600–975 900) individuals projected to die between 2019 and 2040—35 300 fewer deaths than under the status quo scenario (a 3·5% decrease). Whereas, under the strong intervention scenario, age-standardised deaths due to alcohol-related liver disease would peak at 8·65 (95% UI 8·12–9·51) per 100 000 person-years in 2024 and decrease to 7·60 (6·96–8·10) per 100 000 person-years in 2040, with 704 300 (95% CI 632 700–731 500) individuals projected to die from alcohol-related liver disease in the USA between 2019 and 2040—299 100 fewer deaths than under the status quo scenario (a 29·8% decrease). Interpretation Without substantial changes in drinking culture or interventions to address high-risk drinking, the disease burden and deaths due to alcohol-related liver disease will worsen in the USA. Additional interventions are urgently needed to reduce mortality and morbidity associated with alcohol-related liver disease. Funding American Cancer Society and the Robert Wood Johnson Health Policy Research Fellowship.

The practice of transplanting hepatitis C (HCV)-infected livers into HCV-uninfected recipients has not previously been recommended in transplant guidelines, in part because of concerns over uncontrolled HCV infection of the allograft. Direct-acting antivirals (DAAs) provide an opportunity to treat donor derived HCV-infection, and should be administered early in the post-transplant period. However, evidence on the safety and efficacy of an immediate DAA treatment approach, including how to manage logistical barriers surrounding timely DAA procurement, are required prior to broader use of HCV-positive donor organs. We report the results of a trial in which fourteen HCV-negative patients underwent successful liver transplantation from HCV-positive donors. Nine patients received viremic (nucleic acid testing (NAT)-positive) livers, and started a 12-week course of oral glecaprevir-pibrentasvir (GP) within 5 days of transplant. Five patients received livers from HCV antibody-positive non-viremic donors and were followed using a reactive approach. Survival in NAT-positive recipients is 100% at a median follow-up of 46 weeks. An immediate treatment approach for HCV NAT-positive liver transplantation into uninfected recipients is safe and efficacious. Securing payer approval for DAAs early in the post-transplant course could enable need-based allocation of HCV-positive donor organs irrespective of candidate HCV status, while averting chronic HCV allograft infection.

The demand for transplantable kidneys continues to outstrip supply, and the risk of donor-derived infection limits utilization. The effect of donor or recipient HBV status, defined by surface antigen (HBsAg) positivity, on long-term survival outcomes of kidney transplant (KT) is unknown. We conducted a retrospective cohort study based on Organ Procurement and Transplantation Network (OPTN) data from 2000 to 2019. We identified three cohorts based on donor (D) or recipient (R) HBsAg status: D-R-, D-R+, and D+R-. Pairwise comparisons of patient survival (PS) and all-cause graft survival (GS) after propensity score matching were performed to assess the effect of HBV infection in KT recipients. Results showed that there were no statistically significant differences in PS and GS among D-R-, D-R+, and D+R- groups, nor was the patient or graft survival different between donor and recipient HBsAg+ status. Finally, in 2019 kidney discard rates were 15% higher for HBsAg+ deceased donors compared to HBsAg- donors. HBsAg+ status was not associated with worse PS or GS after KT. Prior to broadly advocating utilization of HbsAg+ kidneys, further studies assessing KT recipient morbidity and safety are necessary. This article is protected by copyright. All rights reserved.

Background Participation in scholarship is a requirement for Internal Medicine (IM) residencies, but programs struggle to successfully integrate research into busy clinical schedules. In 2013, the IM residency at Brigham and Women's Hospital implemented the Housestaff Research Project (HRP)- a novel residency-wide research initiative designed to facilitate participation in scholarship. The HRP had two components-a formal research curriculum and an infrastructure that provided funding and mentorship for resident-led, housestaff wide projects. Methods This is a mixed-methods study of 190 IM residents and two HRP-supported research projects. Seventy-seven residents responded to an electronic survey about their interests in research exposure in residency. Fifty-six residents responded to an electronic survey about their participation in the HRP. The success of HRP-supported projects was evaluated through resident comments, interviews with three residents leading the first two HRPs and a description of the success of the projects based on resident involvement and dissemination of the results. Results Eighty-seven percent (n= 67/77) of residents were interested in additional research exposure during residency. Ninety-five percent (n = 53/56) of residents had heard of the HRP, and 77% had participate in at least one aspect of it. Approximately 20 residents were directly involved in the two resident-led projects. HRP-supported projects resulted in presentations at three local and three national conferences, one manuscript in press, and one manuscript in preparation. The resident project leaders felt that a strength and unique aspect of the HRP was the collaboration with co-residents. Conclusion The HRP successfully created a culture of research and scholarship within the residency. The HRP leaders and residents that participated in HRP-supported projects expressed the most direct benefits from the program. All residents were exposed to research concepts and methods. Future directions for the HRP include selecting projects that maximize the number of resident participants and integrating a more robust research curriculum.

Accurate prediction of outcomes for alcohol-associated hepatitis (AH) is critical, as prognosis determines treatment eligibility. Computed tomography (CT) features may provide prognostic information beyond traditional models. Our aim was to identify CT features that predict outcomes in AH. We studied 108 patients retrospectively with definite or probable AH, who underwent admission abdominal CT. A radiologist blinded to outcome evaluated eight CT features. The primary outcome was 90-day mortality. Twenty-five (23.2%) patients died within 90 days. While traditional prognostic tools, including Maddrey discriminant function (DF), predicted 90-day mortality (OR 1.01 [1.00, 1.03], P = 0.02), abdominal CT findings were also accurate predictors. On abdominal CT, patients with severe AH had larger volume of ascites (moderate/large volume: 34.0 vs. 8.2%, P

PURPOSE OF REVIEW: Because of long waitlist times and high waitlist morbidity and mortality, strategies to increase utilization of Hepatitis C viremic deceased donor organs are under investigation in kidney, liver, heart and lung transplantation. RECENT FINDINGS: Direct-acting antiviral medications for Hepatitis C virus infection have high cure rates and are well tolerated. Small, single-center trials in kidney and heart transplant recipients have demonstrated that with early post-transplant direct-acting antiviral therapy, 100% of uninfected recipients of Hepatitis C viremic organs have been cured of infection after transplantation. SUMMARY: In this manuscript, we review the risks and rewards of utilizing Hepatitis C viremic organs for transplantation.

Background The hepatitis C virus (HCV) care cascade has changed dramatically following the introduction of direct-acting anti-virals (DAAs). Up-to-date estimates of the cascade are needed to monitor progress, identify key gaps and inform policy. Aim To estimate the current and future HCV care cascade in the United States, nationally and in select subpopulations of interest. Methods We used a previously validated mathematical model to simulate the landscape of HCV in the United States from 2011 onwards, accounting for HCV screening policy updates, newer HCV treatments and rising HCV incidence. Results By the end of 2018, of 4.29 million HCV persons alive, 2.71 million (63%) were actively viremic, 2.24 million (52%) aware and 1.58 million (37%) cured. By 2030, under the status quo, of 3.65 million HCV persons alive, 1.88 million (51%) would be viremic, 2.25 million (62%) aware and 1.77 million (49%) cured. The HCV care cascade in 2018 differed substantially by subpopulation: of 1.34 million incarcerated HCV persons, 96% were viremic, 36% aware and 4% cured; of 0.87 million HCV persons in Medicare, 31% were viremic, 72% aware and 69% cured; and of 0.37 million HCV persons in Medicaid, 49% were viremic, 54% aware and 51% cured. Implementing universal screening, providing unrestricted treatment and controlling HCV incidence were factors found to have the largest effect on improving the HCV care cascade. Conclusions Since the launch of DAAs, the HCV care cascade has shifted towards higher awareness and treatment rates; however, additional interventions are needed to move towards HCV elimination.

Quantitative assessment of disease progression in patients with nonalcoholic fatty liver disease (NAFLD) has not been systematically examined using competing liver-related and non-liver-related mortality.To estimate long-term outcomes in NAFLD, accounting for competing liver-related and non-liver-related mortality associated with the different fibrosis stages of NAFLD using a simulated patient population.This decision analytical modeling study used individual-level state-transition simulation analysis and was conducted from September 1, 2017, to September 1, 2021. A publicly available interactive tool, dubbed NAFLD Simulator, was developed that simulates the natural history of NAFLD by age and fibrosis stage at the time of (hypothetical) diagnosis defined by liver biopsy. Model health states were defined by fibrosis states F0 to F4, decompensated cirrhosis, hepatocellular carcinoma (HCC), and liver transplant. Simulated patients could experience nonalcoholic steatohepatitis resolution, and their fibrosis stage could progress or regress. Transition probabilities between states were estimated from the literature as well as calibration, and the model reproduced the outcomes of a large observational study.Simulated natural history of NAFLD.Main outcomes were life expectancy; all cause, liver-related, and non-liver-related mortality; and cumulative incidence of decompensated cirrhosis and/or HCC.The model included 1 000 000 simulated patients with a mean (range) age of 49 (18-75) years at baseline, including 66% women. The life expectancy of patients aged 49 years was 25.3 (95% CI, 20.1-29.8) years for those with F0, 25.1 (95% CI, 20.1-29.4) years for those with F1, 23.6 (95% CI, 18.3-28.2) years for those with F2, 21.1 (95% CI, 15.6-26.3) years for those with F3, and 13.8 (95% CI, 10.3-17.6) years for those with F4 at the time of diagnosis. The estimated 10-year liver-related mortality was 0.1% (95% uncertainty interval [UI],0.1%-0.2%) in F0, 0.2% (95% UI, 0.1%-0.4%) in F1, 1.0% (95% UI, 0.6%-1.7%) in F2, 4.0% (95% UI, 2.5%-5.9%) in F3, and 29.3% (95% UI, 21.8%-35.9%) in F4. The corresponding 10-year non-liver-related mortality was 1.8% (95% UI, 0.6%-5.0%) in F0, 2.4% (95% UI, 0.8%-6.3%) in F1, 5.2% (95% UI, 2.0%-11.9%) in F2, 9.7% (95% UI, 4.3%-18.1%) in F3, and 15.6% (95% UI, 10.1%-21.7%) in F4. Among patients aged 65 years, estimated 10-year non-liver-related mortality was higher than liver-related mortality in all fibrosis stages (eg, F2: 16.7% vs 0.8%; F3: 28.8% vs 3.0%; F4: 40.8% vs 21.9%).This decision analytic model study simulated stage-specific long-term outcomes, including liver- and non-liver-related mortality in patients with NAFLD. Depending on age and fibrosis stage, non-liver-related mortality was higher than liver-related mortality in patients with NAFLD. By translating surrogate markers into clinical outcomes, the NAFLD Simulator could be used as an educational tool among patients and clinicians to increase awareness of the health consequences of NAFLD.

Under current guidelines, hepatitis C virus (HCV)-positive livers are not transplanted into HCV-negative recipients because of adverse posttransplant outcomes associated with allograft HCV infection. However, HCV can now be cured post-LT (liver transplant) using direct-acting antivirals (DAAs) with >90% success; therefore, HCV-negative patients on the LT waiting list may benefit from accepting HCV-positive organs with preemptive treatment. Our objective was to evaluate whether and in which HCV-negative patients the potential benefit of accepting an HCV-positive (i.e., viremic) organ outweighed the risks associated with HCV allograft infection. We developed a Markov-based mathematical model that simulated a virtual trial of HCV-negative patients on the LT waiting list to compare long-term outcomes in patients: (1) willing to accept any (HCV-negative or HCV-positive) liver versus (2) those willing to accept only HCV-negative livers. Patients receiving HCV-positive livers were treated preemptively with 12 weeks of DAA therapy and had a higher risk of graft failure than those receiving HCV-negative livers. The model incorporated data from published studies and the United Network for Organ Sharing (UNOS). We found that accepting any liver regardless of HCV status versus accepting only HCV-negative livers resulted in an increase in life expectancy when Model for End-Stage Liver Disease (MELD) was ≥20, and the benefit was highest at MELD 28 (0.172 additional life-years). The magnitude of clinical benefit was greater in UNOS regions with higher HCV-positive donor organ rates, that is, Regions 1, 2, 3, 10, and 11. Sensitivity analysis demonstrated that model outcomes were robust. CONCLUSION Transplanting HCV-positive livers into HCV-negative patients with preemptive DAA therapy could improve patient survival on the LT waiting list. Our analysis can help inform clinical trials and minimize patient harm. (Hepatology 2018;67:2085-2095).

Introduction. Hepatic encephalopathy (HE) following transjugular intrahepatic portosystemic shunt (TIPS) placement remains a leading adverse event. Controversy remains regarding the optimal stent diameter given that smaller stents may decrease the amount of shunted blood and decrease the risk of HE, but stent patency and/or clinical adequacy of portal decompression may also be affected. We aim to provide meta-analysis-based evidence regarding the safety and efficacy of 8 mm vs. 10 mm stents during TIPS placement. Methods. PubMed, Embase, Cochrane Library, and Web of Science were searched for studies comparing 8 mm and 10 mm stents during TIPS placement for portal hypertension decompression in cirrhotic patients. Randomized controlled trials and cohort studies were prioritized for inclusion. Overall evaluation of quality and bias for each study was performed. The outcomes assessed were the prevalence of HE, rebleeding or failure to control refractory ascites, and overall survival. Subgroup analysis based on TIPS indication was conducted. Results. Five studies with a total number of 489 cirrhotic patients were identified. The pooled hazard ratio (HR) of post-TIPS HE was significantly lower in patients in the 8 mm stent group than in the 10 mm stent group (HR: 0.68, 95% CI: 0.51~0.92, p value < 0.0001). The combined HR of post-TIPS rebleeding/the need for paracentesis was significantly higher in patients in the 8 mm stent group than in the 10 mm stent group (HR: 1.76, 95% CI: 1.22~2.55, p value < 0.0001). There was no statistically significant difference in the overall survival between the 8 mm and 10 mm stent groups. The combined risk of HE in the variceal bleeding subgroup was statistically lower (HR: 0.52, CI: 0.34-0.80) with an 8 mm stent compared with a 10 mm stent. The combined risk of both rebleeding/paracentesis and survival was not statistically significant between 8 mm and 10 mm stent use in subgroup analysis. Conclusion. 8 mm stents during TIPS placement are associated with a significant lower risk of HE compared to 10 mm stents (32% decreased risk), as well as a 76% increased risk of rebleeding/paracentesis. Meta-analysis results suggest that there is not one superior stent choice for all clinical scenarios and that the TIPS indication of variceal bleeding or refractory ascites might have different appropriate selection of the shunt diameter.

Background & aimsEarly liver transplantation (without requiring a minimum period of sobriety) for severe alcohol-associated hepatitis (AH) is controversial: many centers delay eligibility until a specific period of sobriety (such as 6 months) has been achieved. To inform ongoing debate and policy, we modeled long-term outcomes of early vs delayed liver transplantation for patients with AH.MethodsWe developed a mathematical model to simulate early vs delayed liver transplantation for patients with severe AH and different amounts of alcohol use after transplantation: abstinence, slip (alcohol use followed by sobriety), or sustained use. Mortality of patients before transplantation was determined by joint-effect model (based on Model for End-Stage Liver Disease [MELD] and Lille scores). We estimated life expectancies of patients receiving early vs delayed transplantation (6-month wait before placement on the waitlist) and life years lost attributable to alcohol use after receiving the liver transplant.ResultsPatients offered early liver transplantation were estimated to have an average life expectancy of 6.55 life years, compared with an average life expectancy of 1.46 life years for patients offered delayed liver transplantation (4.49-fold increase). The net increase in life expectancy from offering early transplantation was highest for patients with Lille scores of 0.50-0.82 and MELD scores of 32 or more. Patients who were offered early transplantation and had no alcohol use afterward were predicted to survive 10.85 years compared with 3.62 years for patients with sustained alcohol use after transplantation (7.23life years lost). Compared with delayed transplantation, early liver transplantation increased survival times in all simulated scenarios and combinations of Lille and MELD scores.ConclusionsIn a modeling study of assumed carefullyselected patients with AH, early vs delayed liver transplantation (6months of abstinence from alcohol before transplantation) increased survival times of patients, regardless of estimated risk of sustained alcohol use after transplantation. These findings support early liver transplantation for patients with severe AH. The net increasein life expectancy was maintained in all simulated extreme scenarios but should be confirmed in prospective studies. Sustained alcohol use after transplantation significantly reduced but did not eliminate thebenefits of early transplantation. Strategies are needed toprevent and treat posttransplantation use of alcohol.

Summary Background Low donor heart availability underscores the need to identify all potentially transplantable organs. We sought to determine whether pre-emptive administration of pangenotypic direct-acting antiviral therapy can safely prevent the development of chronic hepatitis C virus (HCV) infection in uninfected recipients of HCV-infected donor hearts. Methods Patients were recruited for this an open-label, single-centre, proof-of-concept study from Nov 1, 2017, to Nov 30, 2018. Following enrolment, the recipient's status on the heart transplantation waiting list was updated to reflect a willingness to accept either an HCV-positive or HCV-negative heart donor. Patients who underwent transplantation with a viraemic donor heart, as determined by nucleic acid testing (NAT), received pre-emptive oral glecaprevir-pibrentasvir before transport to the operating room followed by an 8-week course of glecaprevir-pibrentasvir after transplantation. Patients receiving HCV antibody-positive donor hearts without detectable circulating HCV RNA were followed using a reactive approach and started glecaprevir-pibrentasvir only if they developed viraemia. The primary outcome was achievement of sustained virological response 12 weeks after completion of glecaprevir-pibrentasvir therapy (SVR12). Patients were followed from study enrolment to 1 year after transplantation. This is an interim analysis, initiated after all enrolled patients reached the primary outcome. Results reflect data from Nov 1, 2017, to May 30, 2019. This trial is registered with ClinicalTrials.gov , number NCT03208244 . Findings 55 patients were assessed for eligibility and 52 consented to enrolment. 25 patients underwent heart transplantation with HCV-positive donor hearts (20 NAT-positive, five NAT-negative), three of whom underwent simultaneous heart–kidney transplantation. All 20 recipients of NAT-positive hearts tolerated glecaprevir-pibrentasvir and showed rapid viral suppression (median time to clearance 3·5 days, IQR 0·0–8·3), with the subsequent achievement of SVR12 by all 20. The five recipients of NAT-negative grafts did not become viraemic. Median pre-transplant waiting time for patients following enrolment in the HCV protocol was 20 days (IQR 8–57). Patient and allograft survival were 100% at a median follow-up of 10·7 months (range 6·5–18·0). Interpretation Pre-emptive administration of glecaprevir-pibrentasvir therapy results in expedited organ transplantation, rapid HCV suppression, prevention of chronic HCV infection, and excellent early allograft function in patients receiving HCV-infected donor hearts. Long-term outcomes are not yet known. Funding American Association for the Study of Liver Diseases, National Institutes of Health, and the Massachusetts General Hospital.

BACKGROUND The AIMS65 score and the Glasgow-Blatchford risk score (GBRS) are validated preendoscopic risk scores for upper gastrointestinal hemorrhage (UGIH). GOALS To compare the 2 scores' performance in predicting important outcomes in UGIH. STUDY A prospective cohort study in 2 tertiary referral centers and 1 community teaching hospital. Adults with UGIH were included. The AIMS65 score and GBRS were calculated for each patient. The primary outcome was inpatient mortality. Secondary outcomes were 30-day mortality, in-hospital rebleeding, 30-day rebleeding, length of stay, and a composite endpoint of in-hospital mortality, transfusions, or need for intervention (endoscopic, radiologic, or surgical treatment). The area under the receiver operating characteristic curve (AUROC) was calculated for each score and outcome. RESULTS A total of 298 patients were enrolled. The AIMS65 score was superior to the GBRS in predicting in-hospital mortality (AUROC, 0.85 vs. 0.66; P

Background & Aims Guidelines do not recommend transplanting hepatitis C virus (HCV)-infected livers into HCV-uninfected recipients. Direct-acting antivirals (DAAs) can be used to treat donor-derived HCV infection. However, the added cost of DAA therapy is a barrier. We evaluated the cost effectiveness of transplanting HCV-positive livers into HCV-negative patients with preemptive DAA therapy. Methods A previously validated Markov-based mathematical model was adapted to simulate a virtual trial of HCV-negative patients on the liver transplant waitlist. The model compared long-term clinical and economic outcomes in patients willing to accept only HCV-negative livers vs those willing to accept any liver (HCV negative or HCV positive). Recipients of HCV-positive livers received 12 weeks of preemptive DAA therapy. The model incorporated data from the United Network for Organ Sharing and published sources. Results For patients with a model for end-stage liver disease (MELD) score ≥ 22, accepting any liver vs waiting for only HCV-negative livers was cost effective, with incremental cost-effectiveness ratios ranging from $56,100 to $91,700/quality-adjusted life-year. For patients with a MELD score of 28 (the median MELD score of patients undergoing transplantation in the United States), accepting any liver was cost effective at an incremental cost-effectiveness ratio of $62,600/quality-adjusted life year. In patients with low MELD scores, which may not accurately reflect disease severity, accepting any liver was cost effective, irrespective of MELD score. Conclusions Using a Markov-based mathematical model, we found transplanting HCV-positive livers into HCV-negative patients with preemptive DAA therapy to be a cost-effective strategy that could improve health outcomes.

Purpose Donor availability has continued to be a major issue limiting the number of cardiac transplantations in the United States. Given this shortage, it is necessary to consider strategies aimed at increasing the donor pool. We sought to evaluate the expanded use of hepatitis C virus (HCV) donor hearts, and characterize early allograft function in HCV-negative patients receiving pre-emptive anti-viral therapy following receipt of an HCV-infected donor heart. Methods Patients who underwent heart transplantation with HCV-positive donors at our institution between November 2017 and October 2018 were studied. Invasive hemodynamic and echocardiographic data were collected from routine scheduled post-transplant procedures. Intensive care unit (ICU) time, time on inotropes and time until discharge were evaluated from the index hospitalization for heart transplantation and compared to data from our center in patients receiving non-HCV hearts between January 2016 and June 2018. Results In total, there have been 23 recipients of donor HCV-positive heart transplants. Cardiac allograft and patient survival has been 100% at a median of 114 (IQR 81-190) days post-transplant. The average time on inotropes was 4.7±3.3 days in recipients of donor HCV-positive heart transplants, average time spent in the ICU was 7.2±4 days in the study group compared with 7.8±7.8 days in patients receiving non-HCV hearts and the average time to discharge was 19 ± 9 days in the study group compared with 21±22 days in patients receiving non-HCV hearts (both p>0.05). Among 80 echocardiograms done on or after post-operative day 2 in recipients of HCV-positive donor hearts, the ejection fraction (EF) was 65±9% with a single value falling below 50% (45%) that normalized 6 days later. One and 8-week hemodynamic values, respectively, were as follows: right atrial pressure of 7±5 and 5±3 mmHg, mean pulmonary arterial pressure of 20±7 and 20±6 mmHg, mean pulmonary capillary wedge pressure of 14±6 and 11±5 mmHg, and cardiac index of 2.8±0.8 and 2.9±0.4 L/min/m2. Conclusion In this single-center prospective study, patients who received preemptive direct-acting antiviral therapy following receipt of an HCV-positive donor heart demonstrated preserved early allograft function post-transplant.

Purpose Due to the shortage of donor hearts in the United States, it is essential we continuously evaluate strategies aimed at increasing donor organ availability. Our institution sought to expand the cardiac donor pool by utilizing hepatitis C virus (HCV) positive donor hearts. In a single center retrospective study, we examined the quality of HCV-positive donor hearts as compared to HCV-negative donor hearts. Methods Between October 2015 and October 2018, 111 cardiac transplants occurred at our center. 23 of these organs came from HCV-positive donors. Baseline donor characteristics were examined for all cardiac transplants and donor quality between HCV-positive and HCV-negative donors compared. Results Twenty-three (20%) of patients received HCV-positive hearts. On average the HCV-positive donors were accepted by our program at lower match sequence numbers than HCV-negative donors (sequence 12±17 versus 64±103, p 0.05 for all comparisons) was seen between HCV-positive and HCV-negative donor hearts. Acceptance of HCV-positive donor hearts facilitated dual-organ transplantation with 3 (13%) patients receiving dual organs as compared to only 4 (4%) in the HCV-negative recipient group. All patients who received HCV-positive donor hearts were alive at the time of this analysis compared to 89% in the HCV-negative group. Conclusion In this single-center study, patients who underwent HCV-positive donor heart transplantation received hearts at lower sequence numbers with a trend toward lower donor age. Short-term outcomes with HCV-positive donor hearts are favorable. Acceptance of HCV-positive donor hearts represents a potential approach to safely expand the available donor pool.

BACKGROUND: The introduction of oral direct-acting antivirals (DAAs) has dramatically changed the landscape of HCV treatment. However, a small percentage of patients fail to achieve sustained virologic response (SVR). Understanding the number of people who fail on DAAs and require re-treatment is important for budget impact and disease burden projections. AIM: To quantify the number of HCV patients who fail to achieve SVR on oral DAAs (NS5A vs. non-NS5A) and require re-treatment. METHODS: We used a mathematical model to simulate clinical management of HCV in the United States, which included the implementation of HCV screening, treatment, and disease progression. We simulated different waves of DAA treatment and used real-world data to extract SVR rates and market shares of available therapies. RESULTS: Our model projected that the number of people living without viremia (i.e., cured) would increase from 0.70 million in 2014 to 1.78 million by 2020. Between 2014 and 2020, 1.50 million people would receive treatment with DAAs, of whom 124,000 (8.3%) are projected to fail to achieve SVR. Among those treatment failures, 66,600 (53.7%) patients would fail treatment with NS5A inhibitors and 69,600 (56.1%) would have cirrhosis. During the same period 34,200 people would progress to decompensated cirrhosis and 27,300 would develop hepatocellular carcinoma after failing to achieve SVR. CONCLUSIONS: Even in the era of highly-effective DAAs, a significant number of patients will fail to achieve SVR and will require re-treatment options. Timely and effective re-treatment is essential to prevent the long-term sequelae of HCV.

It is not standard practice to treat patients with acute hepatitis C virus (HCV) infection. However, as the incidence of HCV in the United States continues to rise, it may be time to re-evaluate acute HCV management in the era of direct-acting antiviral agents (DAAs). In this study a microsimulation model was developed to analyze the tradeoffs between initiating HCV therapy in the acute versus chronic phase of infection. By simulating the lifetime clinical course of patients with acute HCV infection, we were able to project long-term outcomes such as quality-adjusted life years (QALYs) and costs. We found that treating acute HCV versus deferring treatment until the chronic phase increased QALYs by 0.02 and increased costs by $483 in patients not at risk of transmitting HCV. The resulting incremental cost effectiveness ratio (ICER) was $19,991 per QALY, demonstrating that treatment of acute HCV was cost-effective using a willingness-to-pay threshold of $100,000 per QALY. In patients at risk of transmitting HCV, treating acute HCV became cost-saving, increasing QALYs by 0.03 and decreasing costs by $3655. Conclusion: Immediate treatment of acute HCV with DAAs can improve clinical outcomes and be highly cost-effective or cost-saving compared with deferring treatment until the chronic phase of infection. If future studies continue to demonstrate effective HCV cure with shorter 6 week treatment duration, then it may be time to revisit current HCV guidelines to incorporate recommendations that account for the clinical and economic benefits of treating acute HCV in the era of DAAs. This article is protected by copyright. All rights reserved.

Cirrhosis is a diffuse process affecting the hepatic parenchyma that results in fibrosis and scarring of the normal liver architecture. This chapter discusses cirrhosis classification schemes, reviews the causes of end-stage liver disease, and outlines the clinical features, approaches to diagnosis, treatment strategies, prognosis, and complications seen in patients with cirrhosis. Portal hypertension results from an increase in portal venous pressures. A potential complication of cirrhosis is the development of intrahepatic portal hypertension, the most common form of portal hypertension. Additional forms of prehepatic and posthepatic portal hypertension also exist and can occur in the absence of underling liver disease. The classification, clinical consequences, methods for measurement, evaluation, and approaches to management of patients with portal hypertension are discussed.

ObjectivesOral direct-acting antivirals (DAAs) for hepatitis C virus (HCV) have dramatically changed the treatment paradigm. Our aim was to project temporal trends in HCV diagnosis, treatment and disease burden in France, Germany, Italy, Spain and the UK.DesignA mathematical simulation model of natural history of HCV infection.ParticipantsHCV-infected patients defined based on country-specific age, fibrosis and genotype distributions.InterventionsHCV screening practice and availability of different waves of DAA treatment in each country.Outcome measuresTemporal trends in the number of patients who achieve sustained virological response (SVR), fail treatment (by drug regimen) and develop advanced sequelae from 2014 to 2030 in each country.ResultsWe projected that 1 324 000 individuals would receive treatment from 2014 to 2030 in the five European countries and 12 000–37 000 of them would fail to achieve SVR. By 2021, the number of individuals cured of HCV would supersede the number of actively infected individuals in France, Germany, Spain and the UK. Under status quo, the diagnosis rate would reach between 65% and 75% and treatment coverage between 65% and 74% by 2030 in these countries. The number of patients who fail treatment would decrease over time, with the majority of those who fail treatment having been exposed to non-structural protein 5A inhibitors.ConclusionsIn the era of DAAs, the number of people with HCV who achieved a cure will exceed the number of viraemic patients, but many patients will remain undiagnosed, untreated, fail multiple treatments and develop advanced sequelae. Scaling-up screening and treatment capacity, and timely and effective retreatment are needed to avail the full benefits of DAAs and to meet HCV elimination targets set by WHO.

Upper gastrointestinal bleeding (UGIB) is a substantial clinical and economic burden, with an estimated mortality rate between 3% and 15%. The initial management starts with hemodynamic assessment and resuscitation. Blood transfusions may be needed in patients with low hemoglobin levels or massive bleeding, and patients who are anticoagulated may require administration of fresh frozen plasma. Patients with significant bleeding should be started on a proton-pump inhibitor infusion, and if there is concern for variceal bleeding, an octreotide infusion. Patients with UGIB should be stratified into low-risk and high-risk categories using validated risk scores. The use of these risk scores can aid in separating low-risk patients who are suitable for outpatient management or early discharge following endoscopy from patients who are at increased risk for needing endoscopic intervention, rebleeding, and death. Upper endoscopy after adequate resuscitation is required for most patients and should be performed within 24 hours of presentation. Key to improving outcomes is appropriate initial management of patients presenting with UGIB.

Although interns are expected to be competent in handoff communication, it is currently unclear what level of exposure, participation, and comfort medical students have with handoffs prior to graduation.The aim of this study is to characterize passive and active involvement of third-year medical students in the major components of the handoff process.An anonymous voluntary retrospective cross-sectional survey administered in 2010.Rising fourth-year students at two large urban private medical schools.Participation and confidence in active and passive behaviors related to written signout and verbal handoffs during participants' third-year clerkships.Seventy percent of students (n = 204) responded. As third-year medical students, they reported frequent participation in handoffs, such as updating a written signout for a previously admitted patient (58 %). Students who reported frequent participation (at least weekly) in handoff tasks were more likely to report being confident in that task (e.g., giving verbal handoff 62 % vs. 19 %, p 0.001). Students at one site that did not have a handoff policy for medical students reported greater participation, more confidence, and less desire for training. Nearly all students believed they had witnessed an error in written signout (98 %) and almost two-thirds witnessed an error due to verbal handoffs (64 %).During their third year, many medical students are participating in handoffs, although reported rates differ across training environments. Medical schools should consider the appropriate level of competence for medical student participation in handoffs, and implement corresponding curricula and assessment tools to ensure that medical students are able to effectively conduct handoffs.

The purpose of this study was to evaluate the reliability of polyp measurements at CT colonography and the factors that affect the measurements.Fifty colonoscopically proven cases of polyps 6 mm in diameter or larger were analyzed by two observers who measured each polyp in supine and prone views. Manual measurements of 2D volume by summation of areas, 2D maximum diameter, and 3D maximum diameter and automated measurements of 3D maximum diameter and volume were recorded for each observer and were repeated for one of the observers. Intraobserver and interobserver agreement was calculated. Analysis was performed to determine the measurement parameter that correlated most with summation-of-areas volume. Supine and prone measurements as a surrogate for tracking change in polyp size over time were analyzed to determine the measurement parameter with the least variation.Maximum diameter measured manually on 3D images had the highest correlation with summation-of-areas volume. Manual summation-of-areas volume was found to have the least variation between supine and prone measurements.Linear polyp measurement in the 3D endoluminal view appears to be the most reliable parameter for use in the decision to excise a polyp according to current guidelines. In our study, manual calculation of volume with summation of areas was found to be the most reliable measurement parameter for observing polyp growth over serial examinations. High reliability of polyp measurements is essential for adequate assessment of change in polyp size over serial examinations because many patients with intermediate-size polyps are expected to choose surveillance.