The novel coronavirus disease 2019 (COVID-19) pandemic laid bare long-standing racial and ethnic health inequities. At the height of the pandemic, the world watched a video of the murder of George Floyd, a 40-year-old Black man crushed under the knee of a police officer. The tragic juxtaposition of COVID-19 and George Floyd’s murder sparked widespread multicultural protests, an outcry for social and racial justice for all, in sickness and in health. It also led to a nationwide kneel-in that drew thousands of health care professionals. Some held signs asserting that racism is a public health crisis; that we must address the social determinants of health, defined as nonmedical factors that influence health outcomes; and that the medical establishment must prioritize equity, where everyone, regardless of background, has equal opportunity to attain optimal health.

Treatment adherence remains a potential barrier to achieving population-level hepatitis C virus (HCV) elimination by 2030. We aimed to understand barriers to and facilitators of HCV treatment adherence pre- and post-direct-acting antiviral (DAA) treatment. A cohort of US Veterans who were initiating DAA treatment completed pre- and post-treatment surveys assessing demographic information, psychological symptoms and perceived barriers to adherence. DAA adherence was assessed through self-report and pharmacy records. Sustained virologic response (SVR) was evaluated using the medical record. Mann-Whitney U , Fisher's exact tests, and logistic regression were employed to evaluate associations of patient characteristics and survey responses with adherence and SVR. Of 97 participants, the majority were male (98%), white (62%), low-income (less than 35 000/y; 82%), and had a history of self-reported prior substance use (93%). The most common anticipated adherence barrier prior to treatment was having side effects (21%). Over follow-up, 62% of participants missed doses and 84% achieved SVR. Decreased pain (OR 0.32, 95% CI 1.06-1.72), agreeing with ‘the medication will improve my health’ (OR 4, 95% CI 1.22-15.8) and disagreeing with being ‘worried about my liver disease getting worse’ (OR 0.2, 95% CI 0.05, 0.59) predicted successfully achieving SVR. After treatment, the most commonly reported barriers to adherence were being busy (13%) and being away from home (13%). Veterans reported non-significantly decreased substance use after treatment (38% vs 28%, P  = .18). In this population of Veterans with high rates of substance use, most participants missed doses but still achieved SVR. HCV treatment may also serve as an opportunity for substance use treatment.

BackgroundSignificant disparities in hepatitis C (HCV) treatment existed in the interferon treatment era, such that patients with mental health and substance use disorders were less likely to be treated. We aimed to evaluate whether these perceptions continue to influence HCV treatment decisions.MethodsWe e-mailed HCV providers a survey to assess their perceptions of barriers to HCV treatment adherence and initiation. We assessed the frequency of perceived barriers and willingness to initiate HCV treatment in patients with these barriers. We identified a group of providers more willing to treat patients with perceived barriers to adherence and determined the associated provider characteristics using Spearman's rho and Wilcoxon rank-sum tests.ResultsA total of 103 providers (29%) responded to the survey. The most commonly endorsed perceived barriers to adherence were homelessness (65%), ongoing drug (58%), and ongoing alcohol use (33%). However, 90%, 68%, and 90% of providers were still willing to treat patients with these comorbidities, respectively. Ongoing drug use was the most common reason providers were never or rarely willing to initiate HCV treatment. Providers who were less willing to initiate treatment more frequently endorsed patient-related determinants of adherence, while providers who were more willing to initiate treatment more frequently endorsed provider-based barriers to adherence (e.g., communication).ConclusionsMost responding providers were willing to initiate HCV treatment in all patients, despite the presence of perceived barriers to adherence or previous contraindications to interferon-based treatments. Ongoing substance use remains the most prominent influencer in the decision not to treat.

Despite the availability of direct acting antiviral medications (DAAs), there are ongoing concerns about adherence to hepatitis C virus (HCV) treatment. We sought to understand the barriers to and facilitators of DAA adherence in the Veteran population. Patients completed semi-structured interviews focused on barriers to and facilitators of HCV treatment adherence both pre- and post-DAA treatment. Adherence was assessed via provider pill count and self-report. Thematic analyses were conducted in the qualitative software program Atlas.ti in order to understand anticipated barriers to and facilitators of treatment adherence and completion. Charts were reviewed for clinical data and sustained virologic response (SVR12). Of 40 patients, 15 had cirrhosis and 10 had prior interferon-based treatment. Pre-treatment interviews revealed anticipated barriers to adherence such as side effects (n = 21) and forgetting pills (n = 11). Most patients (n = 27) reported following provider advice, and others had unique reasons not to (e.g., feeling like a “guinea pig”). Post-treatment interviews uncovered facilitators of treatment including wanting to cure HCV (n = 17), positive results (n = 18), and minimal side effects (n = 15). Three patients (8%) did not complete therapy (whom we further elaborate on) and 6 (15%) missed doses but completed treatment. SVR12 was achieved by all participants who completed therapy (93%). Patients who did not complete therapy or missed doses were all treatment naïve, mostly non-cirrhotic (8 of 9), and often anticipated concerns with forgetting their medications. This qualitative study uncovered several unanticipated determinants of HCV treatment completion and provides rationale for several targeted interventions such as incorporating structured positive reinforcement.

Background Provider perceptions regarding barriers to and facilitators of hepatitis C (HCV) treatment initiation and adherence have not been fully evaluated in the interferon-free treatment era. New treatments have provided opportunities for non-specialists to treat HCV, underscoring the importance of understanding primary care provider (PCP) and specialist perspectives. Methods Based on qualitative sampling principles, 12 PCPs and 12 hepatology providers (HPs) from the VA Pittsburgh Healthcare System completed audio-recorded semi-structured interviews. Qualitative analysts coded perceived barriers and facilitators from the interviews with 100% double coding. Codes were thematized and analyzed using Atlas.ti. Results Key barriers to treatment described by HPs and PCPs included patients’ substance use disorders, mental health, transportation availability, history of non-adherence, and concern about side effects. PCPs also focused on medication cost as a system-based barrier. The main facilitators of treatment initiation and adherence described by both HPs and PCPs were provider education and encouragement. HPs focused almost exclusively on provider-based facilitators, while PCPs noted patient-based facilitators including past adherence, media exposure to information about HCV medications, a desire to clear the virus, and positive feedback regarding treatment response. Conclusions Providers generally focused on perceived patient-level barriers to HCV treatment initiation and adherence, as well as provider-level facilitators; PCPs additionally noted patient preferences and system-level issues that guide decision making regarding treatment initiation. While HPs focused almost exclusively on provider-level facilitators, PCPs additionally focused on patient-level facilitators of treatment. These data provide novel insights and suggest focusing on patient, provider, and system-level strategies to further improve HCV treatment initiation and adherence.

Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome and a risk factor for both cardiovascular and hepatic related morbidity and mortality. The increasing prevalence of this disease requires novel therapeutic approaches to prevent disease progression. Farnesoid X receptors are bile acid receptors with roles in lipid, glucose, and energy homeostasis. Synthetic farnesoid X receptor (FXR) agonists have been developed to specifically target these receptors for therapeutic use in NAFLD patients. Here, we present a review of bile acid physiology and how agonism of FXR receptors has been examined in pre-clinical and clinical NAFLD. Early evidence suggests a potential role for synthetic FXR agonists in the management of NAFLD; however, additional studies are needed to clarify their effects on lipid and glucose parameters in humans.

A 24-year-old woman (53 kg) with a 5-year history of steroid-dependent ulcerative colitis with mild and extensive ulcerations presented to the gastroenterology clinic for symptom recurrence. She was given 100 mg/day (1.9 mg · kg−1 · day−1) azathioprine (AZA)5 for 1 month, after which the dose was increased to 125 mg/day (2.3 mg · kg−1 · day−1). Four months later, the patient was tapered off steroid therapy. Her symptoms persisted after 7 months of AZA therapy, however, and she experienced gastrointestinal side effects. The patient was switched to another thiopurine drug, 6-mercaptopurine (6-MP), at 75 mg/day (1.4 mg · kg−1 · day−1), which was well tolerated but similarly ineffective (8 stools daily). A brief course of steroid therapy rapidly produced a substantial but short-lived clinical improvement. To understand this patient's unresponsiveness to 2 thiopurine agents, we quantified thiopurine metabolites (1) 1 year after initiating AZA therapy. Intraerythrocyte concentrations of 6-thioguanine nucleotides (6-TGNs) were low (132 pmol/8 · 108 erythrocytes; therapeutic interval, 230–400 pmol/8 · 108 erythrocytes), and 6-methylmercaptopurine ribonucleotides (6-MMPRs) were very high (11 666 pmol/8 · 108 erythrocytes; therapeutic interval, <5800 pmol/8 · 108 erythrocytes). A second quantification of thiopurine metabolites 3 months later confirmed these results (6-TGNs, 127 pmol/8 · 108 erythrocytes; 6-MMPR, 26 304 pmol/8 · 108 erythrocytes). The patient had an unusual and extremely high thiopurine S -methyltransferase (TPMT) activity in erythrocytes [61.5 nmol · h−1 · (mL erythrocytes)−1; reference interval, 8.5–15 nmol · h−1 · (mL erythrocytes)−1]. The lack of clinical efficacy for 6-MP, together with the evidence of pharmacologic resistance, prompted discontinuation of 6-MP therapy. Thereafter, we administered the tumor necrosis factor-α (TNF-α) antagonist adalimumab, but we quickly replaced it with infliximab, which has a …

BACKGROUNDProton pump inhibitors (PPIs) are frequently prescribed for prophylaxis of nosocomial upper gastrointestinal tract bleeding. Some inpatients receiving PPIs may have no risk factors for nosocomial upper gastrointestinal tract bleeding, and PPIs may be continued unnecessarily at hospital discharge. We aimed to assess the effect of standardized guidelines on PPI prescribing practices.METHODSGuidelines for PPI use were implemented on the medical service at a tertiary center. We reviewed PPI use among inpatient admissions during the month before implementation of guidelines and then prospectively evaluated PPI use among admissions during the month after implementation of guidelines.RESULTSAmong an overall cohort of 942 patients, 48% were prescribed PPIs while inpatients, and 41% were prescribed PPIs at hospital discharge. Univariate predictors of inpatient PPI use included age, length of hospital stay, history of gastroesophageal reflux disease or upper gastrointestinal tract bleeding, and outpatient PPI, aspirin, or glucocorticoid use. Among patients not on an outpatient regimen of PPIs at admission, implementation of guidelines resulted in lower rates of inpatient PPI use (27% before vs 16% after, P = .001) and PPI prescription at discharge (16% before vs 10% after, P = .03).CONCLUSIONIntroduction of standardized guidelines resulted in lower rates of PPI use among a subset of inpatients and reduced the rate of PPI prescriptions at discharge.

BACKGROUND & AIMS: We aimed to identify the incidence and predictors of de novo gastroesophageal variceal formation and progression in a large cohort of patients with chronic hepatitis C and advanced fibrosis. METHODS: All participants in the Hepatitis C Antiviral Long-Term Treatment against Cirrhosis Trial were offered an endoscopy before treatment and again after 4 years. Patients with varices at baseline also had an endoscopy at 2 years. Baseline laboratory and clinical parameters were analyzed as predictors of de novo variceal formation and variceal progression. RESULTS: De novo varices developed in 157 of the 598 (26.2%) patients. Most of the new varices were small (76.4%) and only 1% of patients developed variceal hemorrhage. The likelihood of developing varices was associated with subject race (Hispanic Caucasian African American; P .0005), lower baseline levels of albumin (P .051), and higher levels of hyaluronic acid (P .001) with an area under the receiver operating characteristic curve .70. Among 210 patients with existing gastroesophageal varices, 74 (35.2%) had variceal progression or bleeding during follow-up. Patients with higher baseline ratios of serum aspartate/alanine aminotransferase (P .028) and lower platelet counts (P .0002) were at greatest risk of variceal progression (area under the receiver operating characteristic .72). Prolonged, low-dose peginterferon-2a therapy and -blockers did not influence the risk of developing new or enlarging varices. CONCLUSION: Development of varices in patients with chronic hepatitis C is associated with patient race/ethnicity and laboratory markers of disease severity. Prolonged low-dose peginterferon-2a therapy and -blockers do not reduce the risk of variceal development or progression.

OBJECTIVES:The objective of this study was to determine the incidence and risk factors associated with new-onset and worsening portal hypertensive gastropathy (PHG) in patients with chronic hepatitis C (CHC).METHODS:A total of 831 CHC patients with bridging fibrosis or cirrhosis at the time of entry were prospectively monitored for clinical and histological liver disease progression while receiving either low-dose peginterferon α2a or no antiviral therapy in the HALT-C (Hepatitis C Antiviral Long-term Treatment against Cirrhosis) trial. Upper endoscopy with grading of PHG was performed at baseline and at year 4 of the study. The presence and severity of PHG were determined using the NIEC (New Italian Endoscopy Conference) criteria, and worsening PHG was defined as a score increase of ≥1 point.RESULTS:During a median follow-up of 3.85 years, 50% of 514 subjects without PHG developed new-onset PHG, whereas 26% of 317 patients with baseline PHG had worsening PHG. Independent predictors of new-onset PHG included higher alkaline phosphatase and being diabetic, whereas predictors of worsening PHG were Caucasian race, lower albumin, as well as higher serum aspartate transaminase/alanine transaminase ratio and homeostatic model assessment levels. New-onset and worsening PHG were significantly associated with clinical and histological progression. They were also associated with new-onset and worsening gastroesophageal varices.CONCLUSIONS:New-onset and worsening PHG develop at a rate of 12.9% per year and 6.7% per year, respectively, in non-responder CHC patients with advanced fibrosis. If confirmed in other studies, endoscopic surveillance for PHG may need to be tailored to individual patient risk factors.

BACKGROUND & AIMS: We aimed to identify the incidence and predictors of de novo gastroesophageal variceal formation and progression in a large cohort of patients with chronic hepatitis C and advanced fibrosis. METHODS: All participants in the Hepatitis C Antiviral Long-Term Treatment against Cirrhosis Trial were offered an endoscopy before treatment and again after 4 years. Patients with varices at baseline also had an endoscopy at 2 years. Baseline laboratory and clinical parameters were analyzed as predictors of de novo variceal formation and variceal progression. RESULTS: De novo varices developed in 157 of the 598 (26.2%) patients. Most of the new varices were small (76.4%) and only 1% of patients developed variceal hemorrhage. The likelihood of developing varices was associated with subject race (Hispanic > Caucasian > African American; P = .0005), lower baseline levels of albumin (P = .051), and higher levels of hyaluronic acid (P < .001) with an area under the receiver operating characteristic curve = .70. Among 210 patients with existing gastroesophageal varices, 74 (35.2%) had variceal progression or bleeding during follow-up. Patients with higher baseline ratios of serum aspartate/alanine aminotransferase (P = .028) and lower platelet counts (P = .0002) were at greatest risk of variceal progression (area under the receiver operating characteristic = .72). Prolonged, low-dose peginterferon-alpha 2a therapy and beta-blockers did not influence the risk of developing new or enlarging varices. CONCLUSION: Development of varices in patients with chronic hepatitis C is associated with patient race/ethnicity and laboratory markers of disease severity. Prolonged low-dose peginterferon-alpha 2a therapy and beta-blockers do not reduce the risk of variceal development or progression.

Liver transplantation is a life-saving therapy for patients with end-stage liver disease (ESLD); however, donor livers are scarce. Several studies have demonstrated racial disparities in access to liver transplant as well as patient and graft survival after liver transplantation. These studies used data gathered before the model for end-stage liver disease (MELD) was used to determine priority for liver transplant. In this issue of the journal, Drs. Ananthakrishnan and Saeian examine survival after transplant in the MELD era by race and ethnicity, and show that the racial disparities in posttransplant outcomes persist despite MELD. This study provides further evidence that race, which is likely a proxy for a variety of biological and sociological factors, must be considered in any prognostic model for liver transplantation. The impact of race on liver transplantation outcomes should be evaluated further in a well-designed, multicentered, prospective study.

Chronic liver disease is the 12th leading cause of death in the United States and a significant cause of productivity loss and morbidity. Viral hepatitis is an important public health concern with a disproportionate impact on the African American community. As a result, African Americans have the greatest incidence of hepatocellular carcinoma, the most devastating consequence of chronic liver disease. Data suggest that African Americans are less likely than other ethnic/racial groups to receive vaccinations for hepatitis A and hepatitis B, to receive antiviral therapy for chronic hepatitis B and hepatitis C, and to respond to antiviral treatment for hepatitis C. This report reviews the current literature regarding acute and chronic viral infections among African Americans and makes recommendations for future public health and research initiatives to improve outcomes in this population.