Pragmatic strategies to address health disparities along the continuum of care in chronic liver disease.

Racial, ethnic, and socioeconomic disparities exist in the prevalence and natural history of chronic liver disease, access to care, and clinical outcomes. Solutions to improve health equity range widely, from digital health tools to policy changes. The current review outlines the disparities along the chronic liver disease health care continuum from screening and diagnosis to the management of cirrhosis and considerations of pre-liver and post-liver transplantation. Using a health equity research and implementation science framework, we offer pragmatic strategies to address barriers to implementing high-quality equitable care for patients with chronic liver disease.

Sexual and gender minority relevant policies in Canadian and United States organ and tissue donation and transplantation systems: An opportunity to improve equity and safety.

Current policies in organ and tissue donation and transplantation (OTDT) systems in Canada and the United States unnecessarily restrict access to donation for sexual and gender minorities (SGMs) and pose safety risks to transplant recipients. We compare SGM-relevant policies between the Canadian and United States systems. Policy domains include the risk assessment of living and deceased organ and tissue donors, physical examination considerations, viral testing recommendations, and informed consent and communication. Identified gaps between current evidence and existing OTDT policies along with differences in SGM-relevant policies between systems, represent an opportunity for improvement. Specific recommendations for OTDT system policy revisions to achieve these goals include the development of behavior-based, gender-neutral risk assessment criteria, a reduction in current SGM no-sexual contact period requirements pending development of inclusive criteria, and destigmatization of sexual contact with people living with human immunodeficiency virus. OTDT systems should avoid rectal examinations to screen for evidence of receptive anal sex without consent and mandate routine nucleic acid amplification test screening for all donors. Transplant recipients must receive enhanced risk-to-benefit discussions regarding decisions to accept or decline an offer of an organ classified as increased risk. These recommendations will expand the donor pool, enhance equity for SGM people, and improve safety and outcomes for transplant recipients.

Liver transplantation for people of minoritised sexual and gender identities in the USA.

The number of people who report to be of minoritised sexual or gender identities in the USA, including lesbian, gay, bisexual, transgender, queer, and other sexuality-diverse and gender-diverse identities, has been increasing in the past decade. This diverse and unique population continues to experience not only health disparities but also psychosocial, economic, and legal disparities in accessing and receiving health care, including liver transplantations. As liver transplantation is life-saving for people with end-stage liver disease, understanding the factors that can affect access to and quality of liver transplantation care in people of minoritised sexual and gender identities in the USA, including differential social supports, insurance coverage, and medical and psychiatric comorbidities, is crucial. Actions, such as collecting sexual orientation and gender identity data, implementing inclusive language, recognising implicit biases, building diverse teams, providing a safer environment, and supporting further research to understand the unique health challenges are needed to ensure equitable access to high-quality liver transplantation care for people of minoritised sexual and gender identities.

Transplanting hepatitis B surface antigen-positive livers in the United States: Outcomes and opportunities.

Livers from donors with positive hepatitis B surface antigens (HBsAg+) have been used to expand the donor pool; however, outcome data are limited. We aim to evaluate survival following liver transplant (LT) from HBsAg+ donors. Using the United Network for Organ Sharing registry, we identified HBsAg+ donors used for LT from 2009 to 2020. We used Kaplan-Meier survival and Cox proportional hazards regression to compare post-LT survival in hepatitis B virus-negative recipients who utilized HBsAg+ donors to propensity-matched cohorts who utilized other types of donors. From 2009-2020, 70 patients received HBsAg+ livers, and 58 of them did not carry a diagnosis of chronic hepatitis B virus. The 1- and 3-year post-LT survival for hepatitis B virus-negative patients who received livers from HBsAg+ donors were 96.6% and 91.4%, respectively, with no statistical differences compared with patients who received livers from hepatitis C virus viremic donors (96.5%/93.0%, P = .961/.427), donation after cardiac death donors (93.0%/86.0%, P = .651/.598), average-risk donors (89.5%/86.0%, P = 0.264/0.617), and a combination of extended-criteria donors, including donation after cardiac death, donor age over 70, and graft with greater than 30% steatosis (93.0%/91.2%, P = .621/.785). Recipients of HBsAg+ livers have similar post-LT survival compared with those receiving other types of grafts. Increasing the utilization of HBsAg+ livers could safely expand the donor pool.

Reduction in Racial and Ethnic Disparity in Survival Following Liver Transplant for Hepatocellular Carcinoma in the Direct-acting Antiviral Era.

BACKGROUND & AIMS: Black patients with hepatocellular cancer (HCC), often attributed to hepatitis C virus (HCV) infection, have suboptimal survival following liver transplant (LT). We evaluated the impact of direct-acting antiviral (DAA) availability on racial and ethnic disparities in wait list burden post-LT survival for candidates with HCC. METHODS: Using the United Network for Organ Sharing registry, we identified patients with HCC who were listed and/or underwent LT from 2009 to 2020. Based on date of LT, patients were categorized into 2 era-based cohorts: the pre-DAA era (LT between 2009 and 2011) and DAA era (LT between 2015 and 2017, with follow-up through 2020). Kaplan-Meier and Cox proportional hazards analyses were used to compare post-LT survival, stratified by era and race and ethnicity. RESULTS: Annual wait list additions for HCV-related HCC decreased significantly in White and Hispanic patients during the DAA era, with no change (P = .14) in Black patients. Black patients had lower 3-year survival than White patients in the pre-DAA era (70.6% vs 80.1%, respectively; P < .001) but comparable survival in the DAA era (82.1% vs 85.5%, respectively; P = .16). 0n multivariable analysis, Black patients in the pre-DAA era had a 53% higher risk (adjusted hazard ratio [HR], 1.53; 95% confidence interval [CI], 1.28-1.84), for mortality than White patients, but mortality was comparable in the DAA era (adjusted HR, 1.23; 95% CI, 0.99-1.52). In a stratified analysis in Black patients, HCV-related HCC carried more than a 2-fold higher risk of mortality in the pre-DAA era (adjusted HR, 2.86; 95% CI, 1.50-5.43), which was reduced in the DAA era (adjusted HR, 1.34; 95% CI, 0.78-2.30). CONCLUSIONS: With the availability of DAA therapy, racial disparities in post-LT survival have improved.

Improved Survival After Liver Transplantation for Patients With Human Immunodeficiency Virus (HIV) and HIV/Hepatitis C Virus Coinfection in the Integrase Strand Transfer Inhibitor and Direct-Acting Antiviral Eras.

BACKGROUND: People with human immunodeficiency virus (HIV) with and without hepatitis C virus (HCV) coinfection had poor outcomes after liver transplant (LT). Integrase strand transfer inhibitors (INSTIs) and direct-acting antivirals (DAAs) have changed the treatment landscape for HIV and HCV, respectively, but their impact on LT outcomes remains unclear. METHODS: This retrospective analysis of adults with HIV monoinfection (n = 246) and HIV/HCV coinfection (n = 286) who received LT compared mortality in patients with HIV who received LT before versus after approval of INSTIs and in patients with HIV/HCV coinfection who received LT before versus after approval of DAAs. In secondary analysis, we compared the outcomes in the different eras with those of propensity score-matched control cohorts of LT recipients without HIV or HCV infection. RESULTS: LT recipients with HIV monoinfection did not experience a significant improvement in survival between the pre-INSTI and INSTI recipients with HIV (adjusted hazard ratio [aHR], 0.70 [95% confidence interval {CI}, .36-1.34]). However, recipients with HIV/HCV coinfection in the DAA era had a 47% reduction (aHR, 0.53 [95% CI, .31-9.2] in 1-year mortality compared with coinfected recipients in the pre-DAA era. Compared to recipients without HIV or HCV, HIV-monoinfected recipients had higher mortality during the pre-INSTI era, but survival was comparable between groups during the INSTI era. HIV/HCV-coinfected recipients also experienced comparable survival during the DAA era compared to recipients without HCV or HIV. CONCLUSIONS: Post-LT survival for people with HIV monoinfection and HIV/HCV coinfection has improved with the introduction of INSTI and DAA therapy, suggesting that LT has become safer in these populations.

LR-3 and LR-4 Lesions Are More Likely to Be Hepatocellular Carcinoma in Transplant Patients with LR-5 or LR-TR Lesions.

BACKGROUND: Liver Imaging Reporting and Data System (LI-RADS) classifies liver nodules from LR-1 to LR-5 based on risk for hepatocellular carcinoma (HCC). It is challenging to know the nature of the LR-3 and LR-4 lesions. AIMS: To test our hypothesis that in patients with a definite HCC (LR-5) or treated HCC (LR-TR), a coexisting LR-3 or LR-4 lesion is more likely to represent HCC compared to patients without LR-5 or LR-TR lesions. METHODS: We conducted a retrospective study including all adult patients who received liver transplantation in our institution from 1/1/2014 to 3/3/2020 who had any LR-3 or LR-4 lesion on pre-transplant MRI. RESULTS: Seventy-eight patients were included in the final cohort (115 LR-3 and LR-4 lesions total). When accompanied by LR-5 or LR-TR lesions, 41% (28/69) of LR-3 lesions were HCC compared to 12% (3/25) when not accompanied by LR-5 LR-TR lesions. When accompanied by LR-5 or LR-TR lesions, 83% (10/12) of LR-4 lesions were HCC, versus 33% (3/9) when not accompanied by LR-5 or LR-TR lesions. In a multivariable analysis of all lesions, the presence of a LR-5 or LR-TR lesion was significantly associated with LR-3 or LR-4 lesions representing HCC (OR 6.4, p = 0.01). CONCLUSION: LR-3 and LR-4 lesions are more likely to be HCC in patients with LR-5 or LR-TR lesions. The presence of coexisting definite HCC may be a useful diagnostic feature to improve risk stratification of lesions without typical imaging features of HCC. This may also affect decision-making prior to liver transplant when HCC burden must be accurately determined.

Hepatitis B Virus-related Care Quality in Patients With Hepatitis B/Human Immunodeficiency Virus Coinfection Versus Hepatitis B Monoinfection: A National Cohort Study.

BACKGROUND: Guideline-adherent hepatitis B virus (HBV) care is critical for patients with HBV, particularly patients with HBV-human immunodeficiency virus (HIV) given increased risks of liver-related complications. However, a comprehensive assessment of HBV-related care in patients with HBV-HIV is lacking. METHODS: We retrospectively assessed adherence to HBV-related care guidelines in all patients with HBV-HIV and HBV monoinfection (HBV-M) in the national Veterans Health Administration healthcare system in 2019. RESULTS: We identified 1021 patients with HBV-HIV among 8323 veterans with chronic HBV. Adherence to HBV guidelines was similar or better in HBV-HIV versus HBV-M, including HBV treatment (97% vs 71%), biannual hepatocellular carcinoma (HCC) surveillance (55% vs 55%) for patients with cirrhosis, hepatitis A virus screening (69% vs 56%), hepatitis C virus screening (100% vs 99%), and on-therapy alanine aminotransferase monitoring (95% vs 96%). Compared with those seeing gastroenterology (GI) or infectious diseases (ID) providers, patients without specialty care were less likely to receive antiviral treatment (none, 39%; GI, 80%; ID, 84%) or HCC surveillance (none, 16%; GI, 66%; ID, 47%). These findings persisted in multivariable analysis. Compared with ID care alone, a higher proportion of patients with HBV-HIV seen dually by GI and ID received HCC surveillance (GI + ID 73% vs ID 31%) and on-therapy HBV-DNA monitoring (GI + ID, 82%; ID, 68%). CONCLUSIONS: Patients with HBV-HIV received similar or higher rates of guideline-adherent HBV-related care than patients with HBV-M. Patients with HBV-HIV under dual GI and ID care achieved higher quality care compared with ID care alone. Specialty care was independently associated with higher quality HBV care in patients with HBV-HIV and HBV-M.

Socioeconomic Status Is Associated with the Risk of Hepatic Encephalopathy after Transjugular Intrahepatic Portosystemic Shunt Creation.

PURPOSE: To determine whether socioeconomic status (SES) is associated with hepatic encephalopathy (HE) risk after transjugular intrahepatic portosystemic shunt (TIPS) creation. MATERIALS AND METHODS: This single-institution retrospective study included 368 patients (mean age = 56.7 years; n = 229 males) from 5 states who underwent TIPS creation. SES was estimated using the Agency for Healthcare Research and Quality SES index, a metric based on neighborhood housing, education, and income statistics. Episodes of new or worsening HE after TIPS creation, defined as hospitalization for HE or escalation in outpatient medical therapy, were identified from medical records. Multivariable ordinal regression, negative binomial regression, and competing risks survival analysis were used to identify factors associated with SES quartile, the number of episodes of new or worsening HE per unit time after TIPS creation, and mortality after TIPS creation, respectively. RESULTS: There were 83, 113, 99, and 73 patients in the lowest, second, third, and highest SES quartiles, respectively. In multivariable regression, only older age (ß = 0.04, confidence interval [CI] = 0.02-0.05; P < .001) and white, non-Hispanic ethnicity (ß = 0.64, CI = 0.07-1.21; P = .03) were associated with higher SES quartile. In multivariable regression, lower SES quartile (incidence rate ratio [IRR] = 0.80, CI = 0.68-0.94; P = .004), along with older age, male sex, higher model for end-stage liver disease score, nonalcoholic steatohepatitis, and proton pump inhibitor use were associated with higher rates of HE after TIPS creation. Ethnicity was not associated with the rate of HE after TIPS creation (IRR = 0.77, CI = 0.46-1.29; P = .28). In multivariable survival analysis, neither SES quartile nor ethnicity predicted mortality after creation of a TIPS. CONCLUSION: Lower SES is associated with higher rates of new or worsening HE after TIPS creation.

Proton pump inhibitor usage reduces sustained viral response rates for veterans with HIV/HCV coinfection on ledipasvir/sofosbuvir: a real-world study from a multicentre VA cohort.

Previous studies have reported an association of proton pump inhibitor (PPI) use and decreased sustained viral response rate (SVR) in patients taking ledipasvir/sofosbuvir (LDV/SOF). The relationship between PPI usage and SVR is less clear in patients with HIV/HCV coinfection, where concomitant antiretrovirals may result in more complex drug interactions. This retrospective study evaluates the effects of acid suppression medications (PPI or H2 -receptor antagonist [H2 B]) use and SVR rates in patients with HIV/HCV or HCV and taking LDV/SOF in a large multicentre veteran cohort. Patients in the Veterans Affairs Health Care System who received LDV/SOF ± ribavirin from 10/10/2014 to 12/31/2015 were included. The odds ratios (OR) of PPI or H2 B use for SVR were adjusted for clinical factors and with inverse probability of treatment weighting for non-random treatment selection for acid suppression medication use. There were 9703 veterans included in our final analysis. After adjustment of other clinical factors, PPI use is associated with a lower SVR in the overall cohort (95.0% vs. 96.1%, OR: 0.86, 95% CI: 0.74-0.99, p = .03, number needed to harm 90.9) and HIV/HCV coinfection subgroup (93.4% vs. 96.9%, OR: 0.47, 95% CI: 0.26-0.85, p = .01, number needed to harm 28.6). This present study reveals PPI use is associated with reduced SVR after LDV/SOF treatment, with a more significant impact in the subgroup of patients with HIV/HCV coinfection. Precautions need to be taken when using PPI and LDV/SOF in this group of patients.

Impact of exposure to patients with COVID-19 on residents and fellows: an international survey of 1420 trainees.

OBJECTIVES: To determine how self-reported level of exposure to patients with novel coronavirus 2019 (COVID-19) affected the perceived safety, training and well-being of residents and fellows. METHODS: We administered an anonymous, voluntary, web-based survey to a convenience sample of trainees worldwide. The survey was distributed by email and social media posts from April 20th to May 11th, 2020. Respondents were asked to estimate the number of patients with COVID-19 they cared for in March and April 2020 (0, 1-30, 31-60, >60). Survey questions addressed (1) safety and access to personal protective equipment (PPE), (2) training and professional development and (3) well-being and burnout. RESULTS: Surveys were completed by 1420 trainees (73% residents, 27% fellows), most commonly from the USA (n=670), China (n=150), Saudi Arabia (n=76) and Taiwan (n=75). Trainees who cared for a greater number of patients with COVID-19 were more likely to report limited access to PPE and COVID-19 testing and more likely to test positive for COVID-19. Compared with trainees who did not take care of patients with COVID-19 , those who took care of 1-30 patients (adjusted OR [AOR] 1.80, 95% CI 1.29 to 2.51), 31-60 patients (AOR 3.30, 95% CI 1.86 to 5.88) and >60 patients (AOR 4.03, 95% CI 2.12 to 7.63) were increasingly more likely to report burnout. Trainees were very concerned about the negative effects on training opportunities and professional development irrespective of the number of patients with COVID-19 they cared for. CONCLUSION: Exposure to patients with COVID-19 is significantly associated with higher burnout rates in physician trainees.

Predictors of Outcomes of COVID-19 in Patients With Chronic Liver Disease: US Multi-center Study.

BACKGROUND & AIMS: Chronic liver disease (CLD) represents a major global health burden. We undertook this study to identify the factors associated with adverse outcomes in patients with CLD who acquire the novel coronavirus-2019 (COVID-19). METHODS: We conducted a multi-center, observational cohort study across 21 institutions in the United States (US) of adult patients with CLD and laboratory-confirmed diagnosis of COVID-19 between March 1, 2020 and May 30, 2020. We performed survival analysis to identify independent predictors of all-cause mortality and COVID-19 related mortality, and multivariate logistic regression to determine the risk of severe COVID-19 in patients with CLD. RESULTS: Of the 978 patients in our cohort, 867 patients (mean age 56.9 ± 14.5 years, 55% male) met inclusion criteria. The overall all-cause mortality was 14.0% (n = 121), and 61.7% (n = 535) had severe COVID-19. Patients presenting with diarrhea or nausea/vomiting were more likely to have severe COVID-19. The liver-specific factors associated with independent risk of higher overall mortality were alcohol-related liver disease (ALD) (hazard ratio [HR] 2.42, 95% confidence interval [CI] 1.29-4.55), decompensated cirrhosis (HR 2.91 [1.70-5.00]) and hepatocellular carcinoma (HCC) (HR 3.31 [1.53-7.16]). Other factors were increasing age, diabetes, hypertension, chronic obstructive pulmonary disease and current smoker. Hispanic ethnicity (odds ratio [OR] 2.33 [1.47-3.70]) and decompensated cirrhosis (OR 2.50 [1.20-5.21]) were independently associated with risk for severe COVID-19. CONCLUSIONS: The risk factors which predict higher overall mortality among patients with CLD and COVID-19 are ALD, decompensated cirrhosis and HCC. Hispanic ethnicity and decompensated cirrhosis are associated with severe COVID-19. Our results will enable risk stratification and personalization of the management of patients with CLD and COVID-19. Clinicaltrials.gov number NCT04439084.