Multidisciplinary teams, efficient communication, procedure services, and telehealth improve cirrhosis care: A qualitative study.

BACKGROUND: Cirrhosis care and outcomes are improved with access to subspecialty gastroenterology and hepatology care. In qualitative interviews, we investigated clinicians' perceptions of factors that optimize or impede cirrhosis care. METHODS: We conducted 24 telephone interviews with subspecialty clinicians at 7 Veterans Affairs medical centers with high- and low-complexity services. Purposive sampling stratified Veterans Affairs medical centers on timely post-hospitalization follow-up, a quality measure. We asked open-ended questions about facilitators and barriers of care coordination, access to appointments, procedures, transplantation, management of complications, keeping up to date with medical knowledge, and telehealth use. RESULTS: Key themes that facilitated care were structural: multidisciplinary teams, clinical dashboards, mechanisms for appointment tracking and reminders, and local or virtual access to transplant and liver cancer specialists through the "specialty care access network extension for community health care outcomes" program. Coordination and efficient communication between transplant and non-transplant specialists and between transplant and primary care facilitated timely care. Same-day access to laboratory, procedural, and clinical services is an indicator of high-quality care. Barriers included lack of on-site procedural services, clinician turnover, patient social needs related to transportation, costs, and patient forgetfulness due to HE. Telehealth enabled lower complexity sites to obtain recommendations for complex patient cases. Barriers to telehealth included lack of credit (eg, VA billing equivalent), inadequate staff, lack of audiovisual technology support, and patient and staff discomfort with technology. Telehealth was optimal for return visits, cases where physical examination was nonessential, and where distance and transportation precluded in-person care. Rapid telehealth uptake during the COVID-19 pandemic was a positive disruptor and facilitated use. CONCLUSIONS: We identify multi-level factors related to structure, staffing, technology, and care organization to optimize cirrhosis care delivery.

Attacking the public health crisis of hepatocellular carcinoma at its roots.

As the third most common cause of cancer-related death worldwide with significant mortality rates in the United States, hepatocellular carcinoma has strong association with cirrhosis and chronic hepatitis B virus (HBV) with a growing at-risk population from the rise in chronic liver disease from alcohol use and nonalcoholic fatty liver disease. Despite this, progress in identifying at-risk individuals and early detection of HCC in these populations have lagged behind treatment advances.The lack of consensus may undermine widespread adoption of surveillance programs, thus preventing HCC detection at a curable stage. This public policy corner piece focuses on opportunities for prevention of HCC by focusing on its principal risk factors: viral hepatitis, NAFLD, and alcohol-related liver disease, and three key action points to reverse the course of this public health crisis: 1) Awareness and education; 2) Screening and diagnosis, and 3) Partnerships and advocacy.

Ursodeoxycholic acid is associated with a reduction in SARS-CoV-2 infection and reduced severity of COVID-19 in patients with cirrhosis.

BACKGROUND AND AIMS: Studies have demonstrated that reducing farnesoid X receptor activity with ursodeoxycholic acid (UDCA) downregulates angiotensin-converting enzyme in human lung, intestinal and cholangiocytes organoids in vitro, in human lungs and livers perfused ex situ, reducing internalization of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into the host cell. This offers a potential novel target against coronavirus disease 2019 (COVID-19). The objective of our study was to compare the association between UDCA exposure and SARS-CoV-2 infection, as well as varying severities of COVID-19, in a large national cohort of participants with cirrhosis. METHODS: In this retrospective cohort study among participants with cirrhosis in the Veterans Outcomes and Costs Associated with Liver cohort, we compared participants with exposure to UDCA, with a propensity score (PS) matched group of participants without UDCA exposure, matched for clinical characteristics, and vaccination status. The outcomes included SARS-CoV-2 infection, symptomatic, at least moderate, severe, or critical COVID-19, and COVID-19-related death. RESULTS: We compared 1607 participants with cirrhosis who were on UDCA, with 1607 PS-matched controls. On multivariable logistic regression, UDCA exposure was associated with reduced odds of developing SARS-CoV-2 infection (adjusted odds ratio [aOR] 0.54, 95% confidence interval [CI] 0.41-0.71, p < 0.0001). Among patients who developed COVID-19, UDCA use was associated with reduced disease severity, including symptomatic COVID-19 (aOR 0.54, 95% CI 0.39-0.73, p < 0.0001), at least moderate COVID-19 (aOR 0.51, 95% CI 0.32-0.81, p = 0.005), and severe or critical COVID-19 (aOR 0.48, 95% CI 0.25-0.94, p = 0.03). CONCLUSIONS: In participants with cirrhosis, UDCA exposure was associated with both a decrease in SARS-CoV-2 infection, and reduction in symptomatic, at least moderate, and severe/critical COVID-19.

Patterns of Care Utilization and Hepatocellular Carcinoma Surveillance: Tracking Care Across the Pandemic.

INTRODUCTION: We studied longitudinal trends in mortality, outpatient, and inpatient care for cirrhosis in a national cohort in the first 2 years of the coronavirus disease-2019 pandemic. We evaluated trends in hepatocellular carcinoma (HCC) surveillance and factors associated with completion. METHODS: Within the national cirrhosis cohort in the Veterans Administration from 2020 to 2021, we captured mortality, outpatient primary care provider, gastroenterology/hepatology (GI/HEP) visits, and hospitalizations. HCC surveillance was computed as percentage of time up to date with surveillance every 6 months (PTUDS). Multivariable models for PTUDS were adjusted for patient demographics, clinical factors, and facility-level variables. RESULTS: The total cohort was 68,073; 28,678 were eligible for HCC surveillance. Outpatient primary care provider and GI/HEP appointment rates initially dropped from 30% to 7% with a rebound 1 year into the pandemic and steady subsequent use. Telemedicine monthly visit rates rose from less than 10% to a peak of 20% with a steady gradual decline. Nearly 70% of Veterans were up to date with HCC surveillance before the pandemic with an early pandemic nadir of approximately 50% and 60% PTUDS 2 years into the pandemic. In adjusted models, use of a population-based cirrhosis dashboard (ß 8.5, 95% CI 6.9-10.2) and GI/HEP visits both in-person (ß 3.2, 95% CI 2.9-3.6) and telemedicine (ß 2.1, 95% CI 1.9-2.4) were associated with a higher PTUDS. DISCUSSION: Outpatient utilization and HCC surveillance rates have rebounded but remain below at baseline. Population-based approaches and specialty care for cirrhosis were associated with a higher completion of HCC surveillance.

Comparison of infection-induced and vaccine-induced immunity against COVID-19 in patients with cirrhosis.

BACKGROUND AND AIMS: Immunity to SARS-CoV-2 can be infection or vaccine-induced. Cirrhosis is associated with vaccine hyporesponsiveness, but whether there is decreased immunity after SARS-CoV-2 infection in unvaccinated patients with cirrhosis is unknown. The objective of our study was to compare infection-induced and vaccine-induced immunity against COVID-19 among patients with cirrhosis. METHODS: This was a retrospective cohort study among US Veterans with cirrhosis between November 27, 2020, and November 16, 2021, comparing a vaccine-induced immunity group, defined as participants without a documented SARS-CoV-2 infection but fully vaccinated with two doses of an mRNA vaccine, and infection-associated immunity group, defined as unvaccinated participants who had a positive SARS-CoV-2 polymerase chain reaction (PCR). Both groups were propensity score matched for observed characteristics, including location, and the date of the immunity acquiring event, to control for the community prevalence of COVID-19 variants. The outcome was a positive SARS-CoV-2 PCR more than 60 days after previous infection in the infection-induced, or after full vaccination in the vaccine-induced immunity group. RESULTS: We compared 634 participants in the infection-induced immunity group with 27,131 participants in the vaccine-induced immunity group using inverse propensity of treatment weighting. Vaccine-induced immunity was associated with a reduced odds of developing SARS-CoV-2 infection (adjusted hazard ratio [aHR], 0.18; 95% confidence interval [CI], 0.16-0.20, p < 0.0001). On multivariable logistic regression, vaccine-induced immunity was associated with reduced odds of developing symptomatic (adjusted odds ratio [aOR], 0.36; 95% CI, 0.33-0.41, p < 0.0001), moderate/severe/critical (aOR, 0.27; 95% CI, 0.22-0.31, p < 0.0001), and severe or critical COVID-19 (aOR, 0.20; 95% CI, 0.16-0.26, p < 0.001), compared with infection-induced immunity. CONCLUSIONS: In participants with cirrhosis, vaccine-induced immunity is associated with reduced risk of developing COVID-19, compared with infection-induced immunity.

Third dose of COVID-19 mRNA vaccine appears to overcome vaccine hyporesponsiveness in patients with cirrhosis.

BACKGROUND & AIMS: Cirrhosis is associated with immune dysregulation and hyporesponsiveness to several vaccines including those against COVID-19. Our aim was to compare outcomes between patients with cirrhosis who received 3 doses of either the Pfizer BNT162b2 mRNA or Moderna mRNA-1273 vaccines to a propensity-matched control group of patients at similar risk of infection who received 2 doses. METHODS: This was a retrospective cohort study of patients with cirrhosis who received 2 or 3 doses of a COVID-19 mRNA vaccine at the Veterans Health Administration. Participants who received 3 doses of the vaccine (n = 13,041) were propensity score matched with 13,041 controls who received 2 doses, and studied between July 18, 2021 and February 11, 2022, when B.1.617.2 (delta) and B.1.1.529 (omicron) were the predominant variants. Outcomes were aggregated as all cases with COVID-19, symptomatic COVD-19, with at least moderate COVID-19, or severe or critical COVID-19. RESULTS: Receipt of the third dose of a COVID-19 mRNA vaccine was associated with an 80.7% reduction in COVID-19 (95% CI 39.2-89.1, p <0.001), an 80.4% reduction in symptomatic COVID-19, an 80% reduction in moderate, severe or critical COVID-19, (95% CI 34.5-87.6%, p = 0.005), a 100% reduction in severe or critical COVID-19 (95% CI 99.2-100.0, p = 0.01), and a 100% reduction in COVID-19-related death (95% CI 99.8-100.0, p = 0.007). The magnitude of reduction in COVID-19 was greater with the third dose of BNT 162b2 than mRNA-1273 and among participants with compensated rather than decompensated cirrhosis. CONCLUSIONS: Administration of a third dose of a COVID-19 mRNA vaccine was associated with a more significant reduction in COVID-19 in patients with cirrhosis than in the general population, suggesting that the third dose can overcome vaccine hyporesponsiveness in this population. LAY SUMMARY: Cirrhosis is associated with decreased responsiveness to several vaccines, including those against COVID-19. In this study of 26,082 participants with cirrhosis during the delta and omicron surge, receipt of the third dose of the vaccine was associated with an 80% reduction in COVID-19, a 100% reduction in severe/critical COVID-19, and a 100% reduction in COVID-19-related death. These findings support the importance of a third dose of mRNA vaccine among patients with cirrhosis.

Using Telemedicine to Facilitate Patient Communication and Treatment Decision-Making Following Multidisciplinary Tumor Board Review for Patients with Hepatocellular Carcinoma.

BACKGROUND AND AIMS: A rapid increase in the use of telemedicine for delivering healthcare has occurred since the onset of the Covid-19 pandemic. There is evidence for using telemedicine to facilitate cancer care delivery for patients with hepatocellular carcinoma (HCC). Examining how telemedicine can be used to communicate multidisciplinary tumor board (MTB) recommendations for HCC has not been studied. This study has two specific aims: (1) to evaluate the patient perspective of the MTB review process and identify best strategies for communicating treatment recommendations for HCC and (2) to pilot test a telemedicine intervention following MTB review to assess patient feasibility and satisfaction with using telemedicine to facilitate treatment decision-making and treatment referral. METHODS: We conducted a mixed-methods study. First, semi-structured qualitative interviews were conducted among patients diagnosed with HCC who were discussed in MTB review at one of three VA Medical Centers (VAMC). We collected information about the MTB process from the patient perspective and identified strategies for improving communication and delivery of care. Rapid qualitative analysis was used to inform intervention development. Using our qualitative data, a MTB telemedicine pilot intervention was developed and implemented to assess the feasibility of using this approach for patients with HCC. RESULTS: Almost all patients (94%) in the pilot study would recommend telemedicine to other patients with HCC, and half of the patients (50%) preferred telemedicine over in-person visits. Many patients (81%) found communication through telemedicine an acceptable platform to deliver difficult cancer information. Overall, patients felt they understood their treatment recommendations and found them clear and useful. Further, patients reported that they enjoyed being included in the decision-making process and appreciated being able to have family members easily join them for the telemedicine visit. CONCLUSIONS: Using telemedicine to communicate treatment recommendations following MTB review was found to be feasible and an acceptable alternative to an in-person visit for patient with HCC. Future studies could include expanding this approach for communicating MTB recommendations to patients with other types of cancers.

Palliative Care Always: Hepatology-Virtual Primary Palliative Care Training for Hepatologists.

Palliative care (PC) benefits patients with serious illness including end-stage liver disease (ESLD). As part of a cluster randomized trial, hepatologists were trained to deliver primary palliative care to patients with ESLD using an online course, Palliative Care Always: Hepatology (PCA:Hep). Here we present a multimethod formative evaluation (feasibility, knowledge acquisition, self-efficacy, and practice patterns) of PCA:Hep. Feasibility was measured by completion of coursework and achieving a course grade of >80%. Knowledge acquisition was measured through assessments before and throughout the course. Pre/post-course surveys were conducted to determine self-efficacy and practice patterns. The hepatologists (n = 39) enrolled in a 12-week online course and spent 1-3 hours on the course weekly. The course was determined to be feasible as 97% successfully completed the course and 100% passed. The course was acceptable to participants; 91.7 % reported a positive course experience and satisfaction with knowledge gained (91.6%). The pre/post knowledge assessment showed an improvement of 6.0% (pre 85.9% to post 91.9%, 95% CI [2.8, 9.2], P = 0.001). Self-efficacy increased significantly (P < 0.001) in psychological symptom management, hospice, and psychosocial support. A year after training, over 80% of the hepatologists reported integrating a variety of PC skills into routine patient care. Conclusion: PCA:Hep is feasible, acceptable, and improves learner knowledge and confidence in palliative care skills. This is a viable method to teach primary PC skills to specialists caring for patients with ESLD.

Postvaccination COVID-19 infection is associated with reduced mortality in patients with cirrhosis.

BACKGROUND AND AIMS: Patients develop breakthrough COVID-19 infection despite vaccination. The aim of this study was to identify outcomes in patients with cirrhosis who developed postvaccination COVID-19. METHODS: We performed a retrospective cohort study among US veterans with cirrhosis and postvaccination or unvaccinated COVID-19. Patients were considered fully vaccinated if COVID-19 was diagnosed 14 days after the second dose of either the Pfizer BNT162b2, the Moderna 1273-mRNA, or the single-dose Janssen Ad.26.COV2.S vaccines and partially vaccinated if COVID-19 was diagnosed 7 days after the first dose of any vaccine but prior to full vaccination. We investigated the association of postvaccination COVID-19 with mortality. RESULTS: We identified 3242 unvaccinated and 254 postvaccination COVID-19 patients with cirrhosis (82 after full and 172 after partial vaccination). In a multivariable analysis of a 1:2 propensity-matched cohort including vaccinated (n = 254) and unvaccinated (n = 508) participants, postvaccination COVID-19 was associated with reduced risk of death (adjusted HR [aHR], 0.21; 95% CI, 0.11-0.42). The reduction was observed after both full (aHR, 0.22; 95% CI, 0.08-0.63) and partial (aHR, 0.19; 95% CI, 0.07-0.54) vaccination, following the 1273-mRNA (aHR, 0.12; 95% CI 0.04-0.37) and BNT162b2 (aHR, 0.27; 95% CI, 0.10-0.71) vaccines and among patients with compensated (aHR, 0.19; 95% CI, 0.08-0.45) and decompensated (aHR, 0.27; 95% CI, 0.08-0.90) cirrhosis. Findings were consistent in a sensitivity analysis restricted to participants who developed COVID-19 after vaccine availability. CONCLUSIONS: Though patients with cirrhosis can develop breakthrough COVID-19 after full or partial vaccination, these infections are associated with reduced mortality.

Association of BNT162b2 mRNA and mRNA-1273 Vaccines With COVID-19 Infection and Hospitalization Among Patients With Cirrhosis.

Importance: Two mRNA-based vaccines against coronavirus disease 2019 (COVID-19) were found to be highly efficacious in phase 3 clinical trials in the US. However, patients with chronic illnesses, including cirrhosis, were excluded from clinical trials. Patients with cirrhosis have immune dysregulation that is associated with vaccine hyporesponsiveness. Objective: To study the association of receipt of the Pfizer BNT162b2 mRNA or the Moderna mRNA-1273 vaccines in patients with cirrhosis compared with a propensity-matched control group of patients at similar risk of infection and severe disease from COVID-19. Design, Setting, and Participants: We performed a retrospective cohort study of patients with cirrhosis who received at least 1 dose of a COVID-19 mRNA vaccine at the Veterans Health Administration. Patients who received at least 1 dose of the vaccine (n = 20 037) were propensity matched with 20 037 controls to assess the associations of vaccination with new COVID-19 infection and COVID-19 hospitalization and death. Exposures: Receipt of at least 1 dose of the BNT162b2 mRNA or the mRNA-1273 vaccines between December 18, 2020, and March 17, 2021. Main Outcomes and Measures: COVID-19 infection as documented by a positive result for COVID-19 by polymerase chain reaction, hospitalization, and death due to COVID-19 infection. Results: The median (interquartile range) age of the vaccinated individuals in the study cohort was 69.1 (8.4) years and 19 465 (97.2%) of the participants in each of the vaccinated and unvaccinated groups were male, consistent with a US veteran population. The mRNA-1273 vaccine was administered in 10 236 (51%) and the BNT162b2 mRNA in 9801 (49%) patients. Approximately 99.7% of patients who received the first dose of either vaccine with a follow-up of 42 days or more received a second dose. The number of COVID-19 infections in the vaccine recipients was similar to the control group in days 0 to 7, 7 to 14, 14 to 21, and 21 to 28 after the first dose. After 28 days, receipt of 1 dose of an mRNA vaccine was associated with a 64.8% reduction in COVID-19 infections and 100% protection against hospitalization or death due to COVID-19 infection. The association of reduced COVID-19 infections after the first dose was lower among patients with decompensated (50.3%) compared with compensated cirrhosis (66.8%). Receipt of a second dose was associated with a 78.6% reduction in COVID-19 infections and 100% reduction in COVID-19-related hospitalization or death after 7 days. Conclusions and Relevance: This cohort study of US veterans found that mRNA vaccine administration was associated with a delayed but modest reduction in COVID-19 infection but an excellent reduction in COVID-19-related hospitalization or death in patients with cirrhosis.

Patterns of COVID-19 testing and mortality by race and ethnicity among United States veterans: A nationwide cohort study.

BACKGROUND: There is growing concern that racial and ethnic minority communities around the world are experiencing a disproportionate burden of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19). We investigated racial and ethnic disparities in patterns of COVID-19 testing (i.e., who received testing and who tested positive) and subsequent mortality in the largest integrated healthcare system in the United States. METHODS AND FINDINGS: This retrospective cohort study included 5,834,543 individuals receiving care in the US Department of Veterans Affairs; most (91%) were men, 74% were non-Hispanic White (White), 19% were non-Hispanic Black (Black), and 7% were Hispanic. We evaluated associations between race/ethnicity and receipt of COVID-19 testing, a positive test result, and 30-day mortality, with multivariable adjustment for a wide range of demographic and clinical characteristics including comorbid conditions, health behaviors, medication history, site of care, and urban versus rural residence. Between February 8 and July 22, 2020, 254,595 individuals were tested for COVID-19, of whom 16,317 tested positive and 1,057 died. Black individuals were more likely to be tested (rate per 1,000 individuals: 60.0, 95% CI 59.6-60.5) than Hispanic (52.7, 95% CI 52.1-53.4) and White individuals (38.6, 95% CI 38.4-38.7). While individuals from minority backgrounds were more likely to test positive (Black versus White: odds ratio [OR] 1.93, 95% CI 1.85-2.01, p < 0.001; Hispanic versus White: OR 1.84, 95% CI 1.74-1.94, p < 0.001), 30-day mortality did not differ by race/ethnicity (Black versus White: OR 0.97, 95% CI 0.80-1.17, p = 0.74; Hispanic versus White: OR 0.99, 95% CI 0.73-1.34, p = 0.94). The disparity between Black and White individuals in testing positive for COVID-19 was stronger in the Midwest (OR 2.66, 95% CI 2.41-2.95, p < 0.001) than the West (OR 1.24, 95% CI 1.11-1.39, p < 0.001). The disparity in testing positive for COVID-19 between Hispanic and White individuals was consistent across region, calendar time, and outbreak pattern. Study limitations include underrepresentation of women and a lack of detailed information on social determinants of health. CONCLUSIONS: In this nationwide study, we found that Black and Hispanic individuals are experiencing an excess burden of SARS-CoV-2 infection not entirely explained by underlying medical conditions or where they live or receive care. There is an urgent need to proactively tailor strategies to contain and prevent further outbreaks in racial and ethnic minority communities.