Liver transplantation for alcohol-associated hepatitis.

PURPOSE OF REVIEW: Early liver transplantation is emerging as a treatment option for severe alcohol-associated hepatitis refractory to pharmacotherapies. This review outlines the current status of transplantation for alcohol-associated hepatitis and the treatment of alcohol use disorder after liver transplantation. RECENT FINDINGS: Rates of early liver transplantation for alcohol-associated hepatitis are increasing with significant heterogeneity in practices across the Unites States. Recent studies have demonstrated a substantial survival benefit in patients transplanted for alcohol-associated hepatitis with improved outcomes in early vs. late transplantation, first vs. prior hepatic decompensation, and posttransplant abstinence/delayed relapse vs. early return to alcohol use. Several prediction algorithms have been developed to ascertain patients' risk of alcohol relapse and aid in candidate selection, though data on treatment of alcohol use disorders in transplant recipients remains limited. SUMMARY: Although controversial, early liver transplantation for severe alcohol-associated hepatitis has shown to be a lifesaving intervention. Additional research is needed to evaluate its long-term outcomes, optimize candidate selection, and understand treatment of alcohol use disorder posttransplant.

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

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

Early Readmission Predicts Increased Mortality in Cirrhosis Patients After Clostridium difficile Infection.

GOALS: We sought to determine the impact of Clostridium difficile infections (CDI) in cirrhosis by evaluating trends and outcomes of early readmission and mortality. BACKGROUND: The incidence of CDI in cirrhotics is increasing. STUDY: We analyzed the Nationwide Readmissions Database (2011 to 2014) for hospitalized patients with CDI and differentiated them by presence of cirrhosis. Baseline characteristics, surgical rates, and outcomes were collected. The primary outcomes of interest included readmission and mortality rates. RESULTS: Of 366,283 patients hospitalized with CDI, 12,274 (3.4%) had cirrhosis, of which 7741 (63.1%) were decompensated. Among patients with CDI, 30-day readmission rates (33% vs. 24%), index admission mortality (5% vs. 2.5%), and calendar-year mortality (9% vs. 4%) were higher in patients with cirrhosis compared with those without cirrhosis. Recurrent CDI (rCDI) (46%) and cirrhosis-related complications (34.6%) were the most common reasons for readmission. Patients with decompensated cirrhosis were more likely to be readmitted within 30-days than those with compensated cirrhosis [odds ratio (OR), 1.19; 95% confidence interval (CI), 1.03-1.36]. Multivariable analyses revealed that among patients with cirrhosis, index colectomy (OR, 6.50; 95% CI, 1.61-26.24) and decompensation (OR, 3.61; 95% CI, 2.49-5.23) predicted index admission mortality. In addition, 30-day readmission (OR, 3.71; 95% CI, 2.95-4.67) and decompensated cirrhosis (OR, 1.49; 95% CI, 1.17-1.89) independently predicted calendar-year mortality. CONCLUSIONS: One-third of CDI patients with cirrhosis were readmitted within 30-days, most commonly because of rCDI. The mortality associated with CDI in patients with cirrhosis is high, with decompensation and 30-day readmission heralding a poor prognosis. Reducing rCDI-related readmissions may potentially improve these outcomes.

Simplified Readability Metric Drives Improvement of Radiology Reports: an Experiment on Ultrasound Reports at a Pediatric Hospital.

Highly complex medical documents, including ultrasound reports, are greatly mismatched with patient literacy levels. While improving radiology reports for readability is a longstanding concern, few articles objectively measure the effectiveness of physician training for readability improvement. We hypothesized that writing styles may be evaluated using an objective two-dimensional measure and writing training could improve the writing styles of radiologists. To test it, a simplified "grade vs. length" readability metric is developed based on results from factor analysis of ten readability metrics applied to more than 500,000 radiology reports. To test the short-term effectiveness of a writing workshop, we measured the writing style improvement before and after the training. Statistically significant writing style improvement occurred as a result of the training. Although the degree of improvement varied for different measures, it is evident that targeted training could provide potential benefits to improve readability due to our statistically significant results. The simplified grade vs. length metric enables future clinical decision support systems to quantitatively guide physicians to improve writing styles through writing workshops.

Induction Immunosuppression Does Not Worsen Tumor Recurrence After Liver Transplantation for Hepatocellular Carcinoma.

BACKGROUND: Prior studies are inconsistent regarding the impact of antibody induction therapy on outcomes after liver transplantation (LT) for hepatocellular carcinoma (HCC). METHODS: Adults transplanted with HCC exception priority were identified from February 27, 2002, to March 31, 2019, using the United Network for Organ Sharing database. Time-to-event analyses evaluated the association of antibody induction therapy (none, nondepleting induction [NDI], depleting induction [DI]) with overall post-LT patient survival and HCC recurrence. Separate multivariable models adjusted for tumor characteristics on either last exception or on explant. The interaction of induction and maintenance regimen at LT discharge was investigated. RESULTS: Among 22 535 LTs for HCC, 17 688 (78.48%) received no antibody induction, 2984 (13.24%) NDI, and 1863 (8.27%) DI. Minimal differences in patient and tumor characteristics were noted between induction groups, and there was significant center variability in practices. NDI was associated with improved survival, particularly when combined with a calcineurin inhibitor (CNI) and antimetabolite (hazard ratio [HR] 0.73 versus no induction plus 3-drug therapy in the last exception model [ P < 0.001]; HR 0.64 in the explant model [ P = 0.011]). The combination of DI with CNI alone was also protective (HR 0.43; P = 0.003). Neither NDI nor DI was associated with tumor recurrence (all P > 0.1). However, increased HCC recurrence was observed with no induction plus CNI monotherapy (HR 1.47, P = 0.019; versus no induction plus 3-drug therapy). CONCLUSIONS: In conclusion, induction immunosuppression was not associated with worse post-LT outcomes in patients transplanted with HCC exception priority. An improvement in survival was possibly observed with NDI.

Cost-effectiveness of direct-acting antivirals for chronic hepatitis C virus in the United States from a payer perspective.

BACKGROUND: Direct-acting antivirals (DAAs) have been a breakthrough therapeutic innovation in the treatment of chronic hepatitis C virus (HCV) with significantly improved efficacy, safety, and tolerability. OBJECTIVE: To evaluate the cost-effectiveness of treating patients with HCV with DAAs compared with pre-DAAs or no treatment over a lifetime horizon from the perspective of the US Veterans Affairs (VA) health care system. METHODS: A hybrid decision-tree and Markov model simulated the health outcomes of a cohort of 142,147 patients with HCV with an average age of 63 years. Demographic data, treatment rates and distribution, treatment efficacy by subpopulation, and health state costs were sourced from VA data. Treatment costs and utility values were sourced from publicly available databases and prior publications for older regimens. RESULTS: Over a lifetime horizon, the use of DAAs results in a significant reduction in advanced liver disease events compared with pre-DAA and no treatment. Total cost savings of $7 and $9 billion over a lifetime horizon (50 years) were predicted for patients who received DAA treatments compared with patients treated with pre-DAA treatments and those who were untreated, respectively. Cost savings were achieved quickly after treatment, with DAAs being inexpensive when compared with both the pre-DAA and untreated scenarios within 5 years. The DAA intervention dominated (ie, more effective and less costly) for both the pre-DAA and untreated strategies on both a per-patient and cohort basis. CONCLUSIONS: The use of DAA-based treatments in patients with HCV in the VA system significantly reduced long-term HCV-related morbidity and mortality, while providing cost savings within only 5 years of treatment. DISCLOSURES: This work was supported by Gilead Inc. Health Economic Outcomes Research group, grant number GS-US-18-HCV003. Drs Yehoshua and Kaushik are employees of Gilead in the Health Economic Outcome Research group. These individuals reviewed the manuscript but did not contribute to input or output of the Markov model. Maple Health Group (Dr El-Moustaid, Ms Raad, and Dr Smith) are consultants hired by Gilead for Markov modeling expertise. The model used in this study was previously published and peer reviewed. Data inputted into the model related to patient demographic, treatment outcomes, clinical outcomes, and costs were completely independent in derivation by Drs Kaplan, Serper, and Durkin and were not influenced by the funding sponsor. Dr Kaplan reports grants from Gilead Inc. during the conduct of the study and grants from Gilead Inc., other from Glycotest Inc., other from AstraZeneca, other from Exact Sciences, and other from Bayer outside the submitted work.

T2 Hepatocellular Carcinoma Exception Policies That Prolong Waiting Time Improve the Use of Evidence-based Treatment Practices.

BACKGROUND: A United Network for Organ Sharing policy change in 2015 created a 6-mo delay in the receipt of T2 hepatocellular carcinoma exception points. It was hypothesized that the policy changed locoregional therapy (LRT) practices and explant findings because of longer expected waiting time. METHODS: Patients transplanted with a first T2 hepatocellular carcinoma exception application between January 1, 2010 and December 31, 2014 (prepolicy; N = 6562), and those between August 10, 2015 and December 2, 2019 (postpolicy; N = 2345), were descriptively compared using data from United Network for Organ Sharing. RESULTS: Median time from first application to transplantation was more homogenous across the US postpolicy, due to greater absolute increases in Regions 3, 6, 10, and 11 (>120 d). During waitlisting, postpolicy candidates received more LRT overall (P < 0.001), with more notable increases in previously short-wait regions. Postpolicy explants were overall more likely to have ≥1 tumor with complete necrosis (23.9 versus 18.4%; P < 0.001) and less likely have ≥1 tumor with no necrosis (32.6% versus 38.5%; P < 0.001). Significant geographic variability in explant treatment response was observed prepolicy with recipients in previously short-wait regions having more frequent tumor viability at transplant. Postpolicy, there were no differences in the prevalence of recipients with ≥1 tumor with 100% or 0% necrosis across regions (P = 0.9 and 0.2, respectively). CONCLUSIONS: The 2015 T2 exception policy has led to reduced geographic variability in the use of pretransplant LRT and in less frequent tumor viability on explant for recipients in previously short-waiting times.

Unavailability of Endoscopic Retrograde Cholangiography Adversely Impacts Hospital Outcomes of Acute Biliary Pancreatitis: A National Survey and Propensity-Matched Analysis.

OBJECTIVES: There is a paucity of literature assessing the impact of endoscopic retrograde cholangiopancreatography (ERCP) availability at hospitals and the management of acute biliary pancreatitis (ABP). Thus, we sought to evaluate the impact of ERCP availability on the clinical outcomes of ABP. METHODS: The Nationwide Inpatient Sample (2004-2013) was reviewed to identify adult inpatients (≥18 years) with ABP. Clinical outcomes (mortality, severe acute pancreatitis, and health care resource utilization) between hospitals that perform ERCP versus hospitals that do not perform ERCP were compared using multivariate and propensity score-matched analyses. RESULTS: A majority of the non-ERCP hospitals were rural (73%) in location. Multivariate analysis demonstrated that the lack of ERCP availability was independently associated with increased mortality from ABP (odds ratio, 1.83; 95% confidence interval, 1.16-2.88). A propensity score-matched cohort analysis confirmed a significant increase in mortality from ABP in non-ERCP hospitals (1.1% vs 0.53%; odds ratio, 2.08; 95% confidence interval, 1.05-4.15, P = 0.037) compared with ERCP hospitals. CONCLUSIONS: This national survey reveals increased mortality for patients with ABP admitted to hospitals lacking ERCP services. While there is a need to increase ERCP availability in rural areas, optimizing strategies for early transfer of patients with ABP to hospitals with ERCP availability can potentially offset these limitations.

Advanced diagnostics for pancreatic cysts: Confocal endomicroscopy and molecular analysis.

Technological advances and the widespread use of medical imaging have led to an increase in the identification of pancreatic cysts in patients who undergo cross-sectional imaging. Current methods for the diagnosis and risk-stratification of pancreatic cysts are suboptimal, resulting in both unnecessary surgical resection and overlooked cases of neoplasia. Accurate diagnosis is crucial for guiding how a pancreatic cyst is managed, whether with surveillance for low-risk lesions or surgical resection for high-risk lesions. This review aims to summarize the current literature on confocal endomicroscopy and cyst fluid molecular analysis for the evaluation of pancreatic cysts. These recent technologies are promising adjuncts to existing approaches with the potential to improve diagnostic accuracy and ultimately patient outcomes.

Weight Loss Surgery Reduces Healthcare Resource Utilization and All-Cause Inpatient Mortality in Morbid Obesity: a Propensity-Matched Analysis.

AIMS: There is a lack of population studies evaluating the impact of bariatric surgery (BRS) on all-cause inpatient mortality. We sought to determine the impact of prior BRS on all-cause mortality and healthcare utilization in hospitalized patients. METHODS: We analyzed the National Inpatient Sample database from 2007 to 2013. Participants were adult (≥ 18 years) inpatients admitted with a diagnosis of morbid obesity or a history of BRS. Propensity score-matched analyses were performed to compare mortality and healthcare resource utilization (hospital length of stay and cost). RESULTS: There were 9,044,103 patient admissions with morbid obesity and 1,066,779 with prior BRS. A propensity score-matched cohort analysis demonstrated that prior BRS was associated with decreased mortality (OR = 0.58; 95% CI [0.54, 0.63]), shorter length of stay (0.59 days; P < 0.001), and lower hospital costs ($2152; P < 0.001) compared to morbid obesity. A subgroup of propensity score-matched analysis among patients with high-risk of mortality (leading ten causes of mortality in morbid obesity) revealed a consistently significant reduction in odds of mortality for patients with prior BRS (OR = 0.82; 95% CI [0.72, 0.92]). CONCLUSION AND RELEVANCE: Hospitalized patients with a history of BRS have lower all-cause mortality and healthcare resource utilization compared to those who are morbidly obese. These observations support the continued application of BRS as an effective and resource-conscious treatment for morbid obesity.