Considerations in Gender-Affirming Hormone Therapy in Transgender and Gender Diverse Patients Undergoing Liver Transplantation.

Liver transplantation is lifesaving for patients with end stage liver disease. Similar to the role of transplantation for patients with end stage liver disease, gender affirming hormone therapy (GAHT) can be lifesaving for transgender and gender diverse (TGGD) patients who experience gender dysphoria. However, management of such hormone therapy during the perioperative period is unknown and without clear guidelines. Profound strides can be made in improving care for TGGD patients through gender affirming care and appropriate management of GAHT in liver transplantation. In this article, we call for the transplant community to acknowledge the integral role of GAHT in the care of TGGD liver transplant candidates and recipients. We review the current literature and describe how the transplant community is ethically obligated to address this healthcare gap. We suggest tangible steps that clinicians may take to improve health outcomes for this minoritized patient population.

Fecal metabolite profiling identifies liver transplant recipients at risk for postoperative infection.

Metabolites produced by the intestinal microbiome modulate mucosal immune defenses and optimize epithelial barrier function. Intestinal dysbiosis, including loss of intestinal microbiome diversity and expansion of antibiotic-resistant pathobionts, is accompanied by changes in fecal metabolite concentrations and increased incidence of systemic infection. Laboratory tests that quantify intestinal dysbiosis, however, have yet to be incorporated into clinical practice. We quantified fecal metabolites in 107 patients undergoing liver transplantation (LT) and correlated these with fecal microbiome compositions, pathobiont expansion, and postoperative infections. Consistent with experimental studies implicating microbiome-derived metabolites with host-mediated antimicrobial defenses, reduced fecal concentrations of short- and branched-chain fatty acids, secondary bile acids, and tryptophan metabolites correlate with compositional microbiome dysbiosis in LT patients and the relative risk of postoperative infection. Our findings demonstrate that fecal metabolite profiling can identify LT patients at increased risk of postoperative infection and may provide guideposts for microbiome-targeted therapies.

Bifidobacteria metabolize lactulose to optimize gut metabolites and prevent systemic infection in patients with liver disease.

Progression of chronic liver disease is precipitated by hepatocyte loss, inflammation and fibrosis. This process results in the loss of critical hepatic functions, increasing morbidity and the risk of infection. Medical interventions that treat complications of hepatic failure, including antibiotic administration for systemic infections and lactulose treatment for hepatic encephalopathy, can impact gut microbiome composition and metabolite production. Here, using shotgun metagenomic sequencing and targeted metabolomic analyses on 847 faecal samples from 262 patients with acute or chronic liver disease, we demonstrate that patients hospitalized for liver disease have reduced microbiome diversity and a paucity of bioactive metabolites, including short-chain fatty acids and bile acid derivatives, that impact immune defences and epithelial barrier integrity. We find that patients treated with the orally administered but non-absorbable disaccharide lactulose have increased densities of intestinal bifidobacteria and reduced incidence of systemic infections and mortality. Bifidobacteria metabolize lactulose, produce high concentrations of acetate and acidify the gut lumen in humans and mice, which, in combination, can reduce the growth of antibiotic-resistant bacteria such as vancomycin-resistant Enterococcus faecium in vitro. Our studies suggest that lactulose and bifidobacteria serve as a synbiotic to reduce rates of infection in patients with severe liver disease.

Hepatitis C Guidance 2023 Update: AASLD-IDSA Recommendations for Testing, Managing, and Treating Hepatitis C Virus Infection.

The Infectious Diseases Society of America and the American Association for the Study of Liver Diseases have collaboratively developed evidence-based guidance regarding the diagnosis, management, and treatment of hepatitis C virus (HCV) infection since 2013. A panel of clinicians and investigators with extensive infectious diseases or hepatology expertise specific to HCV infection periodically review evidence from the field and update existing recommendations or introduce new recommendations as evidence warrants. This update focuses on changes to the guidance since the previous 2020 published update, including ongoing emphasis on recommended universal screening; management recommendations for incomplete treatment adherence; expanded eligibility for simplified chronic HCV infection treatment in adults with minimal monitoring; updated treatment and retreatment recommendations for children as young as 3 years old; management and treatment recommendations in the transplantation setting; and screening, treatment, and management recommendations for unique and key populations.

Dispensing of HIV and Hepatitis C Antivirals During COVID-19: An Interrupted Time-Series Analysis of U.S. National Data.

INTRODUCTION: Little is known about the potential changes in the dispensation of life-saving hepatitis C virus (HCV) and HIV antivirals after the initial U.S. outbreak of COVID-19. The objective of this study was to describe the immediate and 1-year impacts of the U.S. outbreak of COVID-19 on monthly dispensing of HIV and HCV antivirals, specifically direct-acting antivirals (DAA) to treat HCV, antiretroviral therapy (ART) to treat HIV, and pre-exposure prophylaxis (PrEP) to prevent HIV. METHODS: Authors used interrupted time-series analysis, examining IQVIA National Prescription Audit (includes 92% of U.S. retail pharmacies and 70% of U.S. mail order and long-term care pharmacies) for changes in monthly dispensed prescriptions, 2 years before and 1 year after the initial U.S. COVID-19 outbreak. Fitted linear segmented regression models were used to assess immediate level and slope changes, excluding data from April 2020 as a washout period. Authors stratified analyses by new/refill, age group, payer type, and delivery channel. RESULTS: After the initial outbreak, DAA prescription dispensing declined by almost one third. The COVID-19 outbreak was associated with an immediate-level decrease in total DAA prescriptions, followed by a slope increase in monthly dispensing. However, by April 2021, monthly DAA dispensing had not recovered to prepandemic levels. In contrast, ART and PrEP dispensing changed little over the same time period. CONCLUSIONS: U.S. dispensing of DAAs to treat HCV fell at the start of the U.S. COVID-19 outbreak and has yet to fully recover to prepandemic levels. Addressing barriers to care is crucial to reaching national HIV and hepatitis C elimination goals.

Mandatory Hepatology Education for Internal Medicine Residents: Long-Term Effects and Implications for Workforce Needs.

We previously created a mandatory, inpatient, hepatology resident curriculum that immediately improved comfort, knowledge, and career interest in chronic liver disease (CLD). The durability of these effects needs to be known to use this intervention to address the hepatologist shortage. Thus, we aimed to assess this curriculum's long-term outcomes on internal medicine (IM) residents' CLD comfort, knowledge, and career interest. From 2015 to 2019 at a single institution, one IM resident was always assigned to the rotation. Similar anonymous assessments were administered to incoming postgraduate year (PGY)-1 residents and graduating PGY-3 residents, including a historic control cohort that graduated in June 2015. At residency completion, the intervention cohort (n = 61) had significantly higher comfort (1, not at all comfortable/strongly disagree; 5, very comfortable/strongly agree) with both hepatology (e.g., hepatitis C, 2.5 vs. 3.3, P < 0.001) and common IM topics (e.g., heart failure, 3.6 vs. 4.8, P < 0.001) but not specialty topics lacking curricula (e.g., inflammatory bowel disease, 2.8 vs. 2.7, P = 0.54). Compared to the historic cohort (n = 27), the intervention cohort was more comfortable in several CLD topics (e.g., cirrhosis, 3.2 vs. 3.8; P = 0.005) and answered more questions correctly (65% vs. 55%; P = 0.04), but career interest was unchanged (1.9 vs. 1.8; P = 0.45). Many residents (33%) would consider a hepatology career if training were separated from gastroenterology. Conclusion: With the completion of a mandatory hepatology curriculum, residents' CLD comfort and knowledge durably improved and exceeded that of historic counterparts. Initial career interest was not sustained, perhaps due to prerequisite gastroenterology training. These findings suggest IM educational initiatives may better address hepatology workforce needs by generating comanagers than by recruiting trainees.

"Raising HOPE": Improved Outcomes for HIV/HCV-coinfected Liver Transplant Recipients in the Direct-acting Antiviral Era.

The 2013 HIV Organ Policy Equity Act has increased liver transplantation (LT) in HIV+ patients; however, transplant centers may remain reluctant to perform LT in HIV/hepatitis C virus (HCV)-coinfected patients due to inferior outcomes. We aimed to assess how direct-acting antivirals (DAAs) have impacted HIV+/HCV+-coinfected LT recipient outcomes. METHODS: national data including 70 125 adult LT recipients between 2008 and 2019 were analyzed. Kaplan-Meier survival analysis and Cox proportional hazards model were used to analyze outcomes. RESULTS: LT for HIV+ individuals increased in the DAA era from 28 in 2014 to 64 in 2019 (23 had HIV+/HCV+ coinfection). In the pre-DAA era, HIV+/HCV+-coinfected LT recipients had an increased risk of graft failure compared with HIV-/HCV--uninfected LT recipients (hazard ratio [HR], 1.85; P < 0.001). In contrast, there was no difference in graft failure between HIV+/HCV+-coinfected versus HIV-/HCV--uninfected LT recipients in the DAA era (HR, 1.24; P = 0.308). Among coinfected LT recipients in the DAA era, 1- and 3-y cumulative graft survivals were 88.6% and 81.7% compared with 76.3% and 58.0% in the pre-DAA era, respectively (P = 0.006). In Cox analysis, HCV coinfection was not associated with graft failure (HR, 1.00; 95% confidence interval, 0.53-1.89) among HIV+ LT recipients in the DAA era (n = 271). Black and Hispanic populations accounted for almost half of HIV+/HCV+ LTs in the DAA era. CONCLUSIONS: HIV+/HCV+-coinfected LT recipient outcomes have improved significantly in the DAA era. Our results should offer reassurance to transplant centers and encourage timely transplantation referral of HIV patients with decompensated cirrhosis, including patients coinfected with HCV.

Liver Transplantation of HCV-viremic Donors Into HCV-negative Recipients in the United States: Increasing Frequency With Profound Geographic Variation.

BACKGROUND: Direct-acting antiviral therapy made possible the novel practice of utilizing hepatitis C virus (HCV)-viremic (HCV RNA-positive) donors into HCV-negative recipients in the United States. Although initial reports of outcomes have been satisfactory, higher-quality longer-term outcomes remain to be elucidated. METHODS: National data were examined from the Organ Procurement and Transplantation Network on adult patients in the United States who underwent a primary, single organ, deceased donor liver transplant from January 1, 2016 to March 31, 2020. Outcomes of HCV-negative recipients (R-) who received an allograft from donors who were HCV RNA-positive (D HCV+) donors were compared with HCV RNA-negative (D HCV-) donors. RESULTS: There has been a 35-fold increase in D HCV+/R- liver transplants over the past 4 y in the United States, from 8 in 2016 to 280 in 2019. There was an almost 6-fold difference in this practice among UNOS geographic regions. Graft survival following D HCV+/R- liver transplantation was excellent, with 1-y rates being 91% and 90% and 2-y rates being 88.5% and 87% for D HCV+/R- and D HCV-/R-, respectively (P = 0.672). In multivariate analysis, adjusting for other donor and recipient attributes, D HCV+/R- was not associated with patient or graft survival. CONCLUSIONS: The practice of D HCV+/R- continues to increase without discernible impact on medium-term outcomes. Notable geographic variation exists, suggesting inconsistent perceptions about the impact of D HCV+/R- transplantation on outcomes. These results strengthen the perceived safety in utilizing HCV-viremic donor organs as a donor pool expansion strategy, not only in the United States, but also worldwide.

You Can't Have One Without the Other: Innovation and Ethical Dilemmas in Gastroenterology and Hepatology.

Medical innovation and ethical dilemmas are intertwined in gastroenterology and hepatology. This narrative review explores direct-acting antiviral (DAA) therapy for hepatitis C virus (HCV) as a touchstone example of how medical innovation breeds ethical dilemmas. A few quandaries-informed consent as well as informed deferral during the first wave of DAA approvals, sobriety restrictions from payors, and high DAA costs for patients-are addressed through the lens of the foundational principles of clinical medical ethics: autonomy, beneficence, non-maleficence, justice, and utility. By placing these issues within a medical ethics framework, we hope not only to focus on the solutions that the gastroenterology and hepatology community developed in the advent of DAA therapy, but to highlight an ethical paradigm that can be applied to similar dilemmas that will be faced as new therapies for other gastrointestinal diseases are approved.

Predictors of mortality and endoscopic intervention in patients with upper gastrointestinal bleeding in the intensive care unit.

BACKGROUND: The outcomes of patients undergoing esophagogastroduodenoscopy (EGD) in the intensive care unit (ICU) for upper gastrointestinal bleeding (UGIB) are not well described. Our aims were to determine predictors of 30-day mortality and endoscopic intervention, and assess the utility of existing clinical-prediction tools for UGIB in this population. METHODS: Patients hospitalized in an ICU between 2008 and 2015 who underwent EGD were identified using a validated, machine-learning algorithm. Logistic regression was used to determine factors associated with 30-day mortality and endoscopic intervention. Area under receiver-operating characteristics (AUROC) analysis was used to evaluate established UGIB scoring systems in predicting mortality and endoscopic intervention in patients who presented to the hospital with UGIB. RESULTS: A total of 606 patients underwent EGD for UGIB while admitted to an ICU. The median age of the cohort was 62 years and 55.9% were male. Multivariate analysis revealed that predictors associated with 30-day mortality included American Society of Anesthesiologists (ASA) class (odds ratio [OR] 4.1, 95% confidence interval [CI] 2.2-7.9), Charlson score (OR 1.2, 95% CI 1.0-1.3), and duration from hospital admission to EGD (OR 1.04, 95% CI 1.01-1.07). Rockall, Glasgow-Blatchford, and AIMS65 scores were poorly predictive of endoscopic intervention (AUROC: 0.521, 0.514, and 0.540, respectively) and in-hospital mortality (AUROC: 0.510, 0.568, and 0.506, respectively). CONCLUSIONS: Predictors associated with 30-day mortality include ASA classification, Charlson score, and duration in the hospital prior to EGD. Existing risk tools are poorly predictive of clinical outcomes, which highlights the need for a more accurate risk-stratification tool to predict the benefit of intervention within the ICU population.

Case Management and Capacity Building to Enhance Hepatitis C Treatment Uptake at Community Health Centers in a Large Urban Setting.

An estimated 4.1 million people in the United States are infected with hepatitis C virus (HCV). In 2014, the Hepatitis C Community Alliance to Test and Treat (HepCCATT) collaborative was formed to address hepatitis C in Chicago. From 2014 to 2017, the HepCCATT Case Management Program case managed 181 HCV-infected people and performed on-site capacity building at a 6-site community health center (CHC) that produced codified protocols, which were translated into a telehealth program to build capacity within CHCs to deliver hepatitis C care. HepCCATT's innovative approach to addressing multilevel barriers is a potential model for increasing access to hepatitis C care and treatment.