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BACKGROUND & AIMS: Acute kidney injury (AKI) frequently complicates the course of hospitalized patients with cirrhosis and negatively affects their prognosis. How AKI response influences the timing of liver transplantation (LT) remains unclear. We sought to assess the impact of AKI response to treatment on survival and LT rates in cirrhosis patients awaiting LT. APPROACH & RESULTS: This was a retrospective multicenter study of cirrhosis patients waitlisted for LT and hospitalized with AKI in 2019. The exposure was AKI response versus no response during hospitalization. Outcomes were 90-day overall and transplant-free survival, and rates of LT with time to transplant. We adjusted for age, sex, race, cirrhosis etiology, site, and MELD-Na score. Among the 317 patients in this study, 170 had AKI response (53.6%), and 147 had no response (46.4%). Compared to non-responders, responders had better 90-day overall survival (89.4% vs. 76.2%, adjusted sHR for mortality 0.34, p=0.001), and transplant-free survival (63.5% vs. 25.2%, aHR for probability of death or transplant 0.35, p<0.001). The LT rate was lower in responders (45.9% vs. 61.2%, adjusted sHR 0.55, p=0.005). 79% of transplants in responders occurred after discharge, at a median of 103 days, while 62% of transplants in non-responders occurred during hospitalization, with the remainder occurring post-discharge at a median of 58 days. CONCLUSIONS: In patients with cirrhosis waitlisted for LT who are hospitalized with AKI, AKI response to therapy is associated with improved 90-day survival, despite a reduced LT rate and longer time to LT.
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It is unclear what impact Affordable Care Act (ACA) Medicaid expansion has had on the liver transplantation (LT) waitlist. We aimed to assess associations between ACA Medicaid expansion and LT waitlist outcomes. The United Network for Organ Sharing Standard Transplant Analysis and Research (UNOS STAR) database was queried for patients listed for LT between January 1, 2009, and December 31, 2018. Our primary outcome was waitlist mortality and our secondary outcomes included Medicaid use on the LT waitlist and transplant rate. States were divided into groups based on their expansion status and the study period was divided into 2 time intervals-pre-expansion and post-expansion. Difference-in-difference (DiD) models were created to assess the impacts of expansion on each of the outcomes and for racial/ethnic and sex groups. In total, 56,414 patients from expansion states and 32,447 patients from nonexpansion states were included. Three-year waitlist mortality decreased at a similar rate in both cohorts [DiD estimate: 0.1, (95% CI, -1.1, -1.4), p = 0.838], but Medicaid use increased [DiD estimate: +7.7, (95% CI, 6.7, 8.7), p < 0.001] to a greater degree in expansion states after expansion than nonexpansion states. Between the 2 time intervals, Medicaid use on the LT waitlist increased from 19.4% to 26.1% in expansion states but decreased from 13.4% to 12.1% in nonexpansion states. In patients on Medicaid, there was a slight increase in the 3-year transplant rate associated with Medicaid expansion [DiD estimate +5.0, (95% CI, 1.8, 8.3), p = 0.002], which may in part be explained by differences in patient characteristics. Medicaid expansion was associated with increased Medicaid use on the LT waitlist without worsening overall waitlist mortality or transplant rate, suggesting that lenient and widespread public health insurance may increase access to the LT waitlist without adversely affecting outcomes.
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Transplante de Fígado , Medicaid , Estados Unidos/epidemiologia , Humanos , Patient Protection and Affordable Care Act , Transplante de Fígado/efeitos adversos , Listas de Espera , Acessibilidade aos Serviços de Saúde , Cobertura do SeguroRESUMO
Currently, one-year survival following liver transplantation (LT) exceeds 90% in large international registries, and LT is considered definitive treatment for patients with end-stage liver disease and liver cancer. Recurrence of disease, including hepatocellular carcinoma (HCC), significantly hampers post-LT outcomes. An optimal approach to immunosuppression (IS), including safe weaning, may benefit patients by mitigating the effect on recurrent diseases, as well as reducing adverse events associated with over-/under-IS, including chronic kidney disease (CKD). Prediction of these outcome measures-disease recurrence, CKD, and immune status-has long been based on relatively inaccurate clinical models. To address the utility of new biomarkers in predicting these outcomes in the post-LT setting, the European Society of Organ Transplantation (ESOT) and International Liver Transplant Society (ILTS) convened a working group of experts to review literature pertaining to primary disease recurrence, development of CKD, and safe weaning of IS. Summaries of evidence were presented to the group of panelists and juries to develop guidelines, which were discussed and voted in-person at the Consensus Conference in Prague November 2022. The consensus findings and recommendations of the Liver Working Group on new biomarkers in LT, clinical applicability, and future needs are presented in this article.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Transplante de Fígado , Transplante de Órgãos , Insuficiência Renal Crônica , Humanos , Biomarcadores , Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/cirurgiaRESUMO
BACKGROUND: Hospital admissions for patients with cirrhosis continue to increase. In New York City, 25% to 30% of hospitalized cirrhotics are readmitted within 30 days. Rehospitalization is associated with increased mortality, poor quality of life, and financial burden to patients, hospitals, and payers. Preventable readmissions are partially accounted for by a well-documented quality gap between evidence-based guidelines for cirrhosis management and real-world adherence to these recommendations. METHODS: We performed a prospective cohort study that compared outcomes among cirrhotic patients admitted to 4 internal medicine teams over a 6-month period. An electronic medical record (EMR) note template that outlined best-practice measures for cirrhotics was developed. Inpatient providers on 2 teams were instructed to include it in daily progress notes and discharge summaries. The recommended practices included diagnostic paracentesis and diuretics for ascites, rifaximin, and lactulose for hepatic encephalopathy, beta blockers for esophageal varices, and antibiotic prophylaxis for spontaneous bacterial peritonitis. The remaining 2 teams continued the standard of care for cirrhotic patients. The primary outcome was 30-day readmissions. Secondary outcomes included in-hospital mortality, 30-day mortality, length of stay, and adherence to best-practice guidelines. RESULTS: Over a 6-month period, 108 cirrhotic patients were admitted, 83 in the interventional group and 25 in the control group. MELD-Na scores on admission did not differ between the groups (20.1 vs. 21.1, P =0.56). Thirty-day readmissions were not significantly different between the interventional and control groups (19.3% vs. 24%, P =0.61). However, 30-day mortality was significantly lower in the interventional group (8.4% vs. 28%, P =0.01). There was no difference between the 2 groups in in-hospital mortality (4.8% vs. 0%, P =0.27), 90-day mortality (15.7% vs. 28.0%, P =0.17) or length of stay (10.2 vs. 12.6 d, P =0.34). Adherence to best-practice metrics was similar between the groups, except for rates of diagnostic paracentesis, which were higher in the interventional group (98% vs. 80%, P =0.01). CONCLUSION: Implementation of an EMR note template with cirrhosis best practices was associated with lower 30-day mortality and higher rates of diagnostic paracentesis among admitted patients with cirrhosis. These findings suggest that the integration of best-practice measures into the EMR may improve outcomes in hospitalized cirrhotic patients. Larger studies are required to validate these findings.
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Registros Eletrônicos de Saúde , Qualidade de Vida , Humanos , Estudos Prospectivos , Hospitalização , Cirrose Hepática/diagnóstico , Cirrose Hepática/terapia , Cirrose Hepática/complicaçõesRESUMO
Although sex and racial disparities for liver transplantation (LT) are known, it is unclear if disparities exist for patients with alcohol-associated liver disease (ALD). We aimed to compare sex and racial/ethnic differences in mortality, LT listing, and LT rates in patients with and without ALD. We analyzed patients who were listed for LT and/or died of end-stage liver disease (ESLD) between 2014 and 2018 using the United Network for Organ Sharing Standard Transplant Analysis and Research and Centers for Disease Control and Prevention Wide-ranging OnLine Data for Epidemiologic Research databases, respectively. Patients with ALD were compared with non-ALD patients. Our primary outcome was the ratio of listings for LT to deaths from ESLD-listing-to-death ratio (LDR)-a previously derived metric to assess access to the waiting list. Differences between sex and race/ethnicity were analyzed with chi-square tests and multivariable linear regression. There were 65,588 deaths and 16,133 listings for ALD compared with 75,020 deaths and 40,194 listings for non-ALD. LDR was lower for ALD (0.25 vs. 0.54; p < 0.001). Black patients had the lowest LDR in both ALD and non-ALD (0.13 and 0.39 for Black patients vs. 0.26 and 0.54 for White patients; p < 0.001). Women with ALD had a lower LDR (0.21 vs. 0.26; p < 0.001), whereas women without ALD had higher LDR than men (0.69 vs. 0.47; p < 0.001). There were significant negative interactions between women and ALD in LDR and the transplant-to-death ratio. Multivariable analysis and a sensitivity analysis, with more liberal definitions of ALD and non-ALD, confirmed these findings. Patients with ALD have lower access to LT. Among those with ALD, female and Black patients have the lowest access. New initiatives are needed to eliminate these inequities.
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Doença Hepática Terminal , Hepatopatias Alcoólicas , Transplante de Fígado , Masculino , Humanos , Feminino , Estudos Retrospectivos , Etnicidade , Listas de EsperaRESUMO
INTRODUCTION: Although there are well-documented challenges in access to living donor liver transplant (LDLT) among recipients, it is unclear whether living liver donors (LLDs) face similar challenges. METHODS: We analyzed the UNOS Standard Transplant Analysis and Research database, including LLDs ≥ 18 years in the United States from 1/1998 to 12/2018. We compared sociodemographic characteristics (age, gender, race/ethnicity, education level, employment status, BMI, and relationship to recipient) of LLDs across three eras-pre-MELD (1998-2002), MELD (2003-2013), and post-direct acting antivirals (DAA) (2014-2018). We also described sociodemographic characteristics of living donor recipients and waitlisted patients. Chi-squared and one-way analysis of variance (ANOVA) were used to compare categorical and continuous variables, respectively. RESULTS: From 1998 to 2018, 4756 LDLTs and 99 765 DDLTs were performed. Across the three eras, LLD age did not change significantly (P = .3), but donors were generally young (mean age 37 ± 11). While men comprised most LLDs in the pre-MELD era (55.2%), women surpassed them in the post-DAA era (52.9%), P < .001. In total, White donors comprised 81.5% of total LLDs, while Black and Asian donors were a small minority of total donors (3.7% and 2.5%, respectively). Most donors had at least a college education and were employed. Educational attainment and employment did not significantly change over the study period. CONCLUSION: During the last 20 years, LLDs have remained White, employed, highly educated, and young with increasing numbers of women LLDs. The relative lack of change in the characteristics of donors is likely attributable largely to socioeconomic factors, which should be assessed in future investigation.
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Hepatite C Crônica , Transplante de Fígado , Adulto , Antivirais , Feminino , Humanos , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Estados UnidosRESUMO
Approximately 20% of patients with symptomatic syndrome-associated coronavirus-2 (SARS-CoV-2) infection have gastrointestinal bleeding and/or diarrhea. Most are managed without endoscopic evaluation because the risk of practitioner infection outweighs the value of biopsy analysis unless symptoms are life-threatening. As a result, much of what is known about the gastrointestinal manifestations of coronavirus disease-2019 (COVID-19) has been gleaned from surgical and autopsy cases that suffer from extensive ischemic injury and/or poor preservation. There are no detailed reports describing any other gastrointestinal effects of SARS-CoV-2 even though >3,000,000 people have died from COVID-19 worldwide. The purpose of this study is to report the intestinal findings related to SARS-CoV-2 infection by way of a small case series including one with evidence of direct viral cytopathic effect and 2 with secondary injury attributed to viral infection. Infection can be confirmed by immunohistochemical stains directed against SARS-CoV-2 spike protein, in situ hybridization for spike protein-encoding RNA, and ultrastructural visualization of viruses within the epithelium. It induces cytoplasmic blebs and tufted epithelial cells without inflammation and may not cause symptoms. In contrast, SARS-CoV-2 infection can cause gastrointestinal symptoms after the virus is no longer detected, reflecting systemic activation of cytokine and complement cascades rather than direct viral injury. Reversible mucosal ischemia features microvascular injury with hemorrhage, small vessel thrombosis, and platelet-rich thrombi. Systemic cytokine elaboration and dysbiosis likely explain epithelial cell injury that accompanies diarrheal symptoms. These observations are consistent with clinical and in vitro data and contribute to our understanding of the protean manifestations of COVID-19.
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COVID-19/patologia , Enteropatias/patologia , Enteropatias/virologia , Intestinos/patologia , Intestinos/virologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/metabolismo , Biópsia , COVID-19/diagnóstico , COVID-19/imunologia , Citocinas/metabolismo , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/imunologia , Hemorragia Gastrointestinal/patologia , Hemorragia Gastrointestinal/virologia , Humanos , Enteropatias/diagnóstico , Enteropatias/imunologia , Intestinos/imunologia , Isquemia/diagnóstico , Isquemia/imunologia , Isquemia/patologia , Isquemia/virologia , Masculino , Trombose/diagnóstico , Trombose/imunologia , Trombose/patologia , Trombose/virologiaRESUMO
Abstinence in patients with alcohol-associated liver disease (ALD) reduces mortality. Most predictors of relapse are not quantifiable, preventing objective analysis of relapse risk and targeted intervention to improve clinical outcomes. We prospectively enrolled patients with ALD from November 2016 to December 2019 and administered a survey with two previously published scales to assess insight into alcohol-use disorder (Hanil Alcohol Insight Scale [HAIS]) and social support (Community Assessment Inventory Scale [CAIS]). Relapse was assessed using surveys and metabolite testing. Unadjusted and prespecified adjusted regression analyses identified predictors of relapse. We enrolled 81% of eligible patients (n = 136), of whom 58 had follow-up data available at the time of analysis. Over a median follow-up of 1 year (interquartile range: 0.5-1.4), 10 patients relapsed (17%). Patients who relapsed were more likely to continue drinking despite either a diagnosis of liver disease or a decompensating event, and were less likely to have been transplanted (all P < 0.05). In unadjusted regression, the HAIS and the "support inside the home" subcategory of the CAIS were predictive of relapse, with odds ratio (OR) = 0.84 (95% confidence interval 0.72-0.97) and 0.85 (0.74-0.97). In adjusted regression, the HAIS was no longer significant, with adjusted OR = 0.70 (0.49-1.00, P = 0.05), whereas the "support inside the home' subcategory of CAIS remained significant, with adjusted OR = 0.69 (0.51-0.92, P = 0.01). Conclusions: Risk factors for relapse in patients with ALD were identified and quantified prospectively, suggesting opportunities to objectively identify patients at risk for relapse as well as to intervene to prevent relapse.
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The burden of Clostridioides difficile infection (CDI) has greatly increased. We evaluated the risks for CDI transmission to community members after hospitalized patients are discharged. We conducted a systematic literature review in MEDLINE/PubMed, EMBASE, CINAHL plus EBSCO, Web of Science, Cochrane Library, and gray literature during January 2000âFebruary 2019 and identified 4,798 citations were identified. We eliminated 4,554 citations through title and abstract screening; 217 additional citations did not meet full criteria. We reviewed texts for the 27 remaining articles qualitatively for internal/external validity. A few identified studies describing risks to community members lacked accurate risk measurement or preventative strategies. Primary data are needed to assess efficacy of and inform current expertise-driven CDI prevention practices. Raising awareness among providers and researchers, conducting clinical and health services research, linking up integrated monitoring and evaluation processes at hospitals and outpatient settings, and developing and integrating CDI surveillance systems are warranted.
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Clostridioides difficile , Infecções por Clostridium , Infecção Hospitalar , Transição para Assistência do Adulto , Clostridioides , Atenção à Saúde , HumanosRESUMO
The Affordable Care Act expanded Medicaid around the same time that direct-acting antivirals became widely available for the treatment of hepatitis C virus (HCV). However, there is significant variation in Medicaid HCV treatment eligibility criteria between states. We explored the combined effects of Medicaid expansion and leniency of HCV coverage under Medicaid on liver outcomes. We assessed state-level end-stage liver disease (ESLD) mortality rates, listings for liver transplantation (LT), and listing-to-death ratios (LDRs) for adults aged 25 to 64 years using data from United Network for Organ Sharing and Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research. States were divided into 4 nonoverlapping groups based on expansion status on January 1, 2014 (expansion versus nonexpansion) and leniency of Medicaid HCV coverage (lenient versus restrictive coverage). Joinpoint regression analysis evaluated the significant changes in slope over time (joinpoints) during the pre-expansion (2009-2013) and postexpansion (2014-2018) time periods. We found significant changes in the annual percent change for population-adjusted ESLD deaths between 2014 and 2015 in all cohorts except for the nonexpansion/restrictive cohort, in which deaths increased at the same annual percent change from 2009 to 2018 (annual percent change of +2.5%; 95% confidence interval [CI], 1.8-3.3]). In the expansion/lenient coverage cohort, deaths increased at an annual percent change of +2.6% (95% CI, 1.8-3.5) until 2014 and then tended to decrease at an annual percent change of -0.4% (95% CI, -1.5 to 0.8). LT listings tended to decrease over time for all cohorts. For LDRs, only the expansion/lenient and expansion/restrictive cohorts had statistically significant joinpoints. Improvements in ESLD mortality and LDRs were associated with both Medicaid expansion and leniency of HCV coverage under Medicaid. These findings suggest the importance of implementing more lenient and widespread public health insurance to improve liver disease outcomes, including mortality.
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Doença Hepática Terminal , Hepatite C Crônica , Hepatite C , Transplante de Fígado , Adulto , Antivirais , Doença Hepática Terminal/diagnóstico , Doença Hepática Terminal/cirurgia , Hepacivirus , Hepatite C/tratamento farmacológico , Hepatite C/epidemiologia , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/epidemiologia , Humanos , Cobertura do Seguro , Medicaid , Pessoa de Meia-Idade , Patient Protection and Affordable Care Act , Estados Unidos/epidemiologiaRESUMO
BACKGROUND AND AIMS: The Model for End-Stage Liver Disease score may have eliminated racial disparities on the waitlist for liver transplantation (LT), but disparities prior to waitlist placement have not been adequately quantified. We aimed to analyze differences in patients who are listed for LT, undergo transplantation, and die from end-stage liver disease (ESLD), stratified by state and race/ethnicity. APPROACH AND RESULTS: We analyzed two databases retrospectively, the Center for Disease Control Wide-ranging Online Data for Epidemiologic Research (CDC WONDER) and the United Network for Organ Sharing (UNOS) databases, from 2014 to 2018. We included patients aged 25-64 years who had a primary cause of death of ESLD and were listed for transplant in the CDC WONDER or UNOS database. Our primary outcome was the ratio of listing for LT to death from ESLD-listing to death ratio (LDR). Our secondary outcome was the transplant to listing and transplant to death ratios. Chi-squared and multivariable linear regression evaluated for differences between races/ethnicities. There were 135,367 patients who died of ESLD, 54,734 patients who were listed for transplant, and 26,571 who underwent transplant. Patients were mostly male and White. The national LDR was 0.40, significantly lowest in Black patients (0.30), P < 0.001. The national transplant to listing ratio was 0.48, highest in Black patients (0.53), P < 0.01. The national transplant to death ratio was 0.20, lowest in Black patients (0.16), P < 0.001. States that had an above-mean LDR had a lower transplant to listing ratio but a higher transplant to death ratio. Multivariable analysis confirmed that Black race is significantly associated with a lower LDR and transplant to death ratio. CONCLUSIONS: Black patients face a disparity in access to LT due to low listing rates for transplant relative to deaths from ESLD.