Single-center experience with early liver transplantation for acute alcohol-related hepatitis-Limitations of the SALT score and directions for future study.

Alcohol-related liver disease (ALD) is the leading indication for liver transplantation worldwide. Since Mathurin et al. described their experience in providing early liver transplantation for patients with ALD in 2011, other centers have followed suit with generally favorable survival outcomes. This patient population poses a unique clinical challenge given the expedited nature of the evaluation and the lack of any significant sobriety period prior to transplantation. The SALT (Sustained Alcohol Use Post-Liver Transplant) score is a standardized psychometric tool increasingly used to help stratify the risk of relapse and guide listing decisions for these challenging clinical situations. In 2018, our center introduced a protocol for early liver transplantation for acute alcohol-related hepatitis (AAH). In this article, we offer a retrospective review of 26 patients transplanted between May 2018 and May 2021, including at least 1-year follow-up, and compare outcomes to initial SALT scores; we further identify additional factors that may impact post-transplant success. As transplant committees continue to weigh the ethical dilemma of denying lifesaving treatment against the obligation to remain stewards of a limited resource, we aim to contribute to a more nuanced understanding of risk regarding early transplantation for ALD.

Duration and cost-effectiveness of hepatocellular carcinoma surveillance in hepatitis C patients after viral eradication.

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.

Influence of donor and recipient hepatitis B virus infection on long-term outcomes after kidney transplantation.

BACKGROUND: 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. METHODS: 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: Our findings 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 GS different between donor and recipient HBsAg+ status. Finally, in 2019 kidney discard rates were 15% higher for HBsAg+ deceased donors compared to HBsAg- donors. CONCLUSIONS: 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.

Temporal trends and impact of willingness to accept organs from donors with hepatitis C virus.

Direct-acting antivirals (DAA) transformed hepatitis C virus (HCV) treatment in 2014; however, their impact on transplant candidates' willingness to accept (CWTA) organs from HCV+ donors remains uncertain. We retrospectively studied Organ Procurement and Transplantation Network data from 2008 to 2019, investigating CWTA different organs from HCV+ donors over time, using segmented multivariable logistic regression, and how that influenced wait-time and deceased-donor transplantation (DDTx) probability, using multivariable logistic or linear regression. We found that DAA availability was associated with a marked increase in CWTA in all organs from HCV+ donors except intestine. By December 2020, 40% of kidney, 33% of kidney-pancreas, 42% of pancreas, over 50% of liver, heart, lung, heart-lung, and 9% of intestine candidates waitlisted were CWTA an organ from HCV+ donors. Compared with pre-DAA, yearly CWTA kidney from HCV+ donors increased post-DAA 1.78 1.811.83 -fold, kidney-pancreas 2 .52 2.78 3.07 -fold, pancreas 3.15 3.69 4.43 -fold, liver 1.53 1.541.56 -fold, heart 1 .92 2.02 .08 -fold, and lung 2.00 2.12 .20 -fold. CWTA kidney and liver from HCV+ donors significantly increased DDTx probability post-DAA (1.98 2.042.1 -fold and 1.24 1.291.33 -fold, respectively) and shortened kidney candidates' wait-time78 90101 days (Mean with 95% CI). CWTA organs from HCV+ donors rose significantly with DAA availability, benefitting kidney and liver candidates with increased DDTx rates and shortened kidney candidates' wait time. Further long-term outcomes investigation and standardized organ from HCV+ donors' education could improve both provider and patient acceptance and utilization.

Model to Calculate Harms and Benefits of Early vs Delayed Liver Transplantation for Patients With Alcohol-Associated Hepatitis.

BACKGROUND & AIMS: Early 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. METHODS: We 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. RESULTS: Patients 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 (7.23 life years lost). Compared with delayed transplantation, early liver transplantation increased survival times in all simulated scenarios and combinations of Lille and MELD scores. CONCLUSIONS: In a modeling study of assumed carefully selected patients with AH, early vs delayed liver transplantation (6 months 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 increase in 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 the benefits of early transplantation. Strategies are needed to prevent and treat posttransplantation use of alcohol.

Computed Tomography Findings as a Novel Predictor of Alcohol-Associated Hepatitis Outcomes.

BACKGROUND: 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. AIMS: Our aim was to identify CT features that predict outcomes in AH. METHODS: 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. RESULTS: 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 < 0.0001), longer liver length (17.1 vs. 15.1 cm, P = 0.001), greater liver heterogeneity (moderate/severe: 21.3 vs. 8.2%, P = 0.007), and more likely to have splenomegaly (42.6 vs. 18.0%, P = 0.009) than those with mild AH. Univariate analysis revealed that ascites volume (OR 2.59 [1.35, 4.96], P = 0.004) predicted 90-day mortality. In multivariate analysis, degree of ascites predicted 90-day mortality when controlling for Maddrey DF (OR 2.36 [1.19, 4.69], P = 0.01) and trended toward significance when controlling for MELD score (OR 2.02 [0.95, 4.30], P = 0.07). CONCLUSION: CT findings in AH differentiate disease severity and predict 90-day mortality; therefore, the role of CT warrants further investigation as a tool in AH management.

Cost Effectiveness of Transplanting HCV-Infected Livers Into Uninfected Recipients With Preemptive Antiviral Therapy.

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.

Should we treat acute hepatitis C? A decision and cost-effectiveness analysis.

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 (DAA) agents. In this study, a microsimulation model was developed to analyze the trade-offs 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 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 $3,655. 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. (Hepatology 2018;67:837-846).

Transplanting hepatitis C virus-positive livers into hepatitis C virus-negative patients with preemptive antiviral treatment: A modeling study.

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).

Initial assessment and management of patients with nonvariceal upper gastrointestinal bleeding.

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.

Participation and experience of third-year medical students in handoffs: time to sign out?

BACKGROUND: 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. OBJECTIVE: 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. DESIGN: An anonymous voluntary retrospective cross-sectional survey administered in 2010. PARTICIPANTS: Rising fourth-year students at two large urban private medical schools. MAIN MEASURES: Participation and confidence in active and passive behaviors related to written signout and verbal handoffs during participants' third-year clerkships. KEY RESULTS: 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 %). CONCLUSIONS: 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.

Preferred language and disease severity predict evaluation for liver transplantation among patients admitted with alcohol-associated hepatitis.

BACKGROUND: Liver transplantation (LT) for alcohol-associated hepatitis (AH) is a relatively new practice and limited work exists surrounding the role social determinants of health may play in evaluation. This includes language that defines how patients interact with the healthcare system. We explored characteristics of patients with AH evaluated for LT within an integrated health system. METHODS: Using a system-wide registry, we identified admissions for AH from 1 January 2016 to 31 July 2021. A multivariable logistic regression model was developed to evaluate independent predictors of LT evaluation. RESULTS: Among 1723 patients with AH, 95 patients (5.5%) underwent evaluation for LT. Evaluated patients were more likely have English as their preferred language (95.8% vs 87.9%, P = 0.020), and had higher INR (2.0 vs 1.4, P < 0.001) and bilirubin (6.2 vs 2.9, P < 0.001). AH patients who underwent evaluation had a lower burden of mood and stress disorders (10.5% vs 19.2%, P < 0.05). Patients with English preferred language had a greater than three times adjusted odds of LT evaluation compared with all others when adjusting for clinical disease severity, insurance status, sex, and psychiatric comorbid conditions (OR, 3.20; 95% CI, 1.14-9.02). CONCLUSION: Patients with AH evaluated for LT were more likely to have English as their preferred language, more psychiatric comorbidities, and more severe liver disease. Despite adjustment for psychiatric comorbidities and disease severity, English preferred language remained the strongest predictor of evaluation. As programs expand LT for AH, it is vital to build equitable systems that account for the interaction between language and healthcare in transplantation.

Modern glucose-lowering drugs in liver transplant recipients: improvement in weight, glycemic control, and potentially allograft steatosis.

Introduction: Recurrent allograft steatosis occurs in one-third of transplanted livers. Antidiabetic agents like glucagon-like peptide-1 receptor agonists (GLP1RA) and sodium-glucose cotransporter type-2 (SGLT2) inhibitors are effective in the management of obesity and hepatic steatosis in the general population; however, there is limited evidence supporting their use in allograft steatosis. We aimed to evaluate their effects on steatosis, body weight, and glycemic control in liver transplant recipients at our institution. Methods: In this single-center retrospective cohort study of liver transplant recipients currently on a GLP1RA or SGLT2 inhibitor (transplanted 2015-2022), we compared clinical and radiological data before medication use and at follow-up. Differences were compared using Wilcoxon signed-rank test. Results: Thirty-seven liver transplant recipients were taking the agents. Diabetes was the most common indication (n = 33) followed by obesity (n = 4). Median follow up was 427 days (301,798). Among those with documented steatosis (n = 21), steatosis improved in 5, worsened in 4, remained unchanged in 1, and change could not be evaluated in 11 due to lack of comparable pre and post imaging. Average weight loss was 3.2 kg (p < 0.001) and BMI decreased by 1.2 kg/m2 (p < 0.001). Hemoglobin A1c decreased by 0.6 mmol/mol (p = 0.0014), insulin requirement reduced by 7 units/day (p = 0.02), and there was no change in additional antidiabetic medications. Discussion: GLP1RA and SGLT-2 inhibitors are tolerated in transplant patients and result in weight loss and better glycemic control. They are promising agents to treat recurrent or de-novo liver allograft steatosis, but further research is needed to evaluate long-term outcomes in liver transplant recipients.

Analysis of a Simulation Model to Estimate Long-term Outcomes in Patients with Nonalcoholic Fatty Liver Disease.

Importance: 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. Objective: 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. Design, Setting, and Participants: 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. Exposure: Simulated natural history of NAFLD. Main Outcomes and Measures: Main outcomes were life expectancy; all cause, liver-related, and non-liver-related mortality; and cumulative incidence of decompensated cirrhosis and/or HCC. Results: 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%). Conclusions and Relevance: 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.

Projected prevalence and mortality associated with alcohol-related liver disease in the USA, 2019-40: a modelling study.

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.

Liver transplantation with suprahepatic caval anastomosis including inferior vena cava stent.

Budd Chiari syndrome (BCS) results from hepatic outflow obstruction. Endovascular management to restore venous patency, including inferior vena cava (IVC) angioplasty with stenting, and transjugular intrahepatic shunt (TIPS) placement to decompress liver congestion, have become standard of care. Herein, we describe a patient with BCS requiring liver transplantation and the surgical technique of suprahepatic IVC anastomosis including thoracic extension of an IVC stent with a review of the relevant literature. A 29-year-old female with BCS due to polycythemia vera, who had been previously managed with TIPS and IVC stent placement, was taken for liver transplantation. Preoperative imaging confirmed stent extension into the thoracic IVC and the stent was unable to be removed intraoperatively. The thoracic IVC was clamped through the diaphragm at the level of the right atrium and the stent was left in place and incorporated within the suprahepatic anastomosis with good vascular outcome at one year follow up. Diligent preoperative preparation is essential with adequate imaging and cardiac surgical consultation in patients with malpositioned stents. Review of the literature shows four cases in which performing the suprahepatic anastomosis including an embedded stent is a viable alternative that allows for avoidance of a thoracotomy.

Transjugular Intrahepatic Portosystemic Shunt Placement for Portal Hypertension: Meta-Analysis of Safety and Efficacy of 8 mm vs. 10 mm Stents.

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.