Hepatocellular carcinoma among patients with chronic hepatitis B in the indeterminate phase.

Hepatitis B virus (HBV) infection is a dynamic disease where patients progress through several stages defined by HBV e-antigen (HBeAg) status, HBV-DNA levels and transaminase elevations, with antiviral therapy indicated only in specific stages. However, some patients cannot be classified into one of the stages and are said to fall into an 'indeterminate phase' or 'grey zone'. Exact definitions of the indeterminate phase vary from guideline to guideline as a result of different cut-off values for biomarker measurements. Data suggest that as many as 50% of HBV patients may be in an indeterminate phase and may not rapidly transition out of this phase. Clinical data that suggest these patients are at increased risk of hepatocellular carcinoma (HCC) are complemented by molecular evidence of integrations of HBV-DNA into the host genome, chromosomal translocations and immune activation despite liver enzymes that may suggest lack of inflammation. Antiviral therapy reduces these hepatocarcinogenic mechanisms and is reflected in a reduction of fibrosis and HCC risk. We review key data on patients in the indeterminate phase, with emphasis on HCC as an outcome. We take a holistic approach and link new biological data with clinical observations as well as examine the potential role of antiviral therapy in reducing HCC risk among patients in the indeterminate phase. With the availability of safe and effective oral antivirals, consideration must be given as to how much residual risk of HCC should be tolerated among patients in the indeterminate phase.

Abnormal Colorectal Cancer Test Follow-Up: A Quality Improvement Initiative at a Federally Qualified Health Center.

INTRODUCTION/OBJECTIVES: Colonoscopy completion rates after an abnormal fecal immunochemical test (FIT) are suboptimal, resulting in missed opportunities for early detection and prevention of colorectal cancer. Patient navigation and structured follow-up may improve colonoscopy completion, but implementation of these strategies is not widespread. METHODS: We conducted a quality improvement study using a Plan-Do-Study-Act (PDSA) Model to increase colonoscopy completion after abnormal FIT in a large federally qualified health center serving a diverse and low-income population. Intervention components included patient navigation, and a checklist to promote completion of key steps required for abnormal FIT follow-up. Primary outcome was proportion of patients achieving colonoscopy completion within 6 months of abnormal FIT, assessed at baseline for 156 patients pre-intervention, and compared to 208 patients during the intervention period from April 2017 to December 2019. Drop offs at each step in the follow-up process were assessed. RESULTS: Colonoscopy completion improved from 21% among 156 patients with abnormal FIT pre-intervention, to 38% among 208 patients with abnormal FIT during the intervention (P < .001; absolute increase: 17%, 95% CI: 6.9%-25.2%). Among the 130 non-completers during the intervention period, lack of completion was attributable to absence of colonoscopy referral for 7.7%; inability to schedule a pre-colonoscopy specialist visit for 71.5%; failure to complete a pre-colonoscopy visit for 2.3%; the absence of colonoscopy scheduling for 9.2%; failure to show for a scheduled colonoscopy for 9.2%. CONCLUSIONS: Patient navigation and structured follow-up appear to improve colonoscopy completion after abnormal FIT. Additional strategies are needed to achieve optimal rates of completion.

A technology-enabled multi-disciplinary team-based care model for the management of Long COVID and other fatiguing illnesses within a federally qualified health center: protocol for a two-arm, single-blind, pragmatic, quality improvement professional cluster randomized controlled trial.

BACKGROUND: The clinical burden of Long COVID, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and other post-infectious fatiguing illnesses (PIFI) is increasing. There is a critical need to advance understanding of the effectiveness and sustainability of innovative approaches to clinical care of patients having these conditions. METHODS: We aim to assess the effectiveness of a Long COVID and Fatiguing Illness Recovery Program (LC&FIRP) in a two-arm, single-blind, pragmatic, quality improvement, professional cluster, randomized controlled trial in which 20 consenting clinicians across primary care clinics in a Federally Qualified Health Center system in San Diego, CA, will be randomized at a ratio of 1:1 to either participate in (1) weekly multi-disciplinary team-based case consultation and peer-to-peer sharing of emerging best practices (i.e., teleECHO (Extension for Community Healthcare Outcomes)) with monthly interactive webinars and quarterly short courses or (2) monthly interactive webinars and quarterly short courses alone (a control group); 856 patients will be assigned to participating clinicians (42 patients per clinician). Patient outcomes will be evaluated according to the study arm of their respective clinicians. Quantitative and qualitative outcomes will be measured at 3- and 6-months post-baseline for clinicians and every 3-months post assignment to a participating clinician for patients. The primary patient outcome is change in physical function measured using the Patient-Reported Outcomes Measurement Information System (PROMIS)-29. Analyses of differences in outcomes at both the patient and clinician levels will include a linear mixed model to compare change in outcomes from baseline to each post-baseline assessment between the randomized study arms. A concurrent prospective cohort study will compare the LC&FIRP patient population to the population enrolled in a university health system. Longitudinal data analysis approaches will allow us to examine differences in outcomes between cohorts. DISCUSSION: We hypothesize that weekly teleECHO sessions with monthly interactive webinars and quarterly short courses will significantly improve clinician- and patient-level outcomes compared to the control group. This study will provide much needed evidence on the effectiveness of a technology-enabled multi-disciplinary team-based care model for the management of Long COVID, ME/CFS, and other PIFI within a federally qualified health center. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05167227 . Registered on December 22, 2021.

Comparing Latino Community Members' and Clinical Staff's Perspectives on Barriers and Facilitators to Colorectal Cancer Screening.

Latinos in the United States have low rates of colorectal cancer (CRC) screening even though CRC is the third leading cause of cancer death among Latinos. This qualitative study aimed to understand and compare the perspectives of clinical staff (CS) and Latino community members (LCMs) in an urban Southern California community regarding barriers and facilitators of CRC screening. Through purposive sampling, 39 LCMs (mean age: 59.4 years, 79.5% female) were recruited to participate in one of five focus groups, and 17 CS (mean age: 38.8 years, 64.7% female) were recruited to participate in semi-structured in-depth interviews, along with a demographic survey. Interviews and focus group recordings were transcribed verbatim, translated, and analyzed using direct content analysis. Demographic data were summarized using descriptive statistics. Findings suggest that CS and LCMs have both similar and opposing perspectives with regard to barriers and facilitators of CRC screening. Themes discussed included attitudes towards CRC screening, CRC knowledge, access to resources, commitments and responsibilities, social support, vicarious learning, patient-provider communication, trust, and social relationships. Study findings can be used to guide interventions and policies to improve access to CRC screening among LCMs.

Effectiveness of a Decentralized Hub and Spoke Model for the Treatment of Hepatitis C Virus in a Federally Qualified Health Center.

Hepatitis C virus (HCV) is a major cause of cirrhosis, liver cancer, and mortality in the United States. We assessed the effectiveness of decentralized HCV treatment delivered by nurse practitioners (NPs), primary care physicians (PMDs), or an infectious disease physician (ID MD) using direct-acting antivirals in a Federally Qualified Health Center (FQHC) in urban San Diego, CA. We conducted a cross-sectional analysis of 1,261 patients who received treatment from six NPs, 10 PMDs, and one ID MD practicing in 10 clinics between January 2014 and January 2020. Care was delivered based on the Extension for Community Healthcare Outcomes (Project ECHO) model with one hub and nine spokes. HCV was deemed cured if a patient had a sustained virologic response (SVR) after 12 weeks of treatment (SVR12). We evaluated differences in the prevalence of cure between provider types and hub or spoke status using Poisson regression. Patients were 34% Latino, 16% black, 63% were aged >50 years, and 59% were homeless; 53% had advanced fibrosis, 69% had genotype 1, and 5% were coinfected with human immunodeficiency virus. A total of 943 patients achieved SVR12 (96% per protocol and 73% intention to treat). Even after adjustment for demographics, resources, and disease characteristics, the prevalence of cure did not differ between the ID MD and PMDs (prevalence ratio [PR], 1.00; 95% confidence interval [CI], 0.95-1.04) or NPs (PR, 1.01; 95% CI, 0.96-1.05). Similarly, there were no differences between the hub and spokes (PR, 1.01; 95% CI, 0.98-1.04). Conclusion: Among a low-income and majority homeless cohort of patients at urban FQHC clinics, HCV treatment administered by nonspecialist providers was not inferior to that provided by a specialist.

A Promotor-Led Pilot Study to Increase Colorectal Cancer Screening in Latinos: The Juntos Contra El Cáncer Program.

Background. Latinos have lower colorectal cancer (CRC) screening rates compared to other racial/ethnic groups in the United States, despite an overall increase in CRC screening over the past 10 years. To address this disparity, we implemented a promotor-led intervention to increase CRC screening test adherence in community-based settings, connecting community members with a partnering federally qualified health center. Purpose. To evaluate the Juntos Contra el Cáncer/Together Against Cancer (JUNTOS) intervention, by assessing pre-post changes in (1) CRC screening test adherence and (2) CRC knowledge and perceived barriers to CRC screening. We also assessed the feasibility and acceptability of program activities. Method. JUNTOS was a group-based intervention, delivered by promotores (community health workers), to promote CRC screening test adherence among Latino adults. The intervention consisted of a culturally tailored 2½-hour interactive workshop followed by an appointment scheduling assistance from a promotor. Workshop participants were Latino adults (males and females) aged 50 to 75 years who were not up-to-date with CRC screening guidelines. We conducted interviews before and 6 to 9 months after the workshop to assess program outcomes. Results. Of the 177 participants included, 118 reported completing the CRC screening test (66.7%) by 6 to 9 months postintervention. We observed baseline to 6- to 9-month increase in CRC knowledge and lower perceived barriers to obtaining CRC screening. Furthermore, the intervention was found to be feasible and acceptable. Conclusion. Results suggest that JUNTOS can be feasibly implemented in partnership with a federally qualified health center. The current study supports group-based CRC interventions in community and clinic settings.

Optimal Threshold of Controlled Attenuation Parameter for Detection of HIV-Associated NAFLD With Magnetic Resonance Imaging as the Reference Standard.

BACKGROUND: Controlled attenuation parameter (CAP) is an ultrasound-based point-of-care method to quantify liver fat; however, the optimal threshold for CAP to detect pathologic liver fat among persons living with human immunodeficiency virus (HIV; PLWH) is unknown. Therefore, we aimed to identify the diagnostic accuracy and optimal threshold of CAP for the detection of liver-fat among PLWH with magnetic resonance imaging proton-density fat fraction (MRI-PDFF) as the reference standard. METHODS: Patients from a prospective single-center cohort of PLWH at risk for HIV-associated nonalcoholic fatty liver disease (NAFLD) who underwent contemporaneous MRI-PDFF and CAP assessment were included. Subjects with other forms of liver disease including viral hepatitis and excessive alcohol intake were excluded. Receiver operatic characteristic (ROC) curve analysis were performed to identify the optimal threshold for the detection of HIV-associated NAFLD (liver fat ≥ 5%). RESULTS: Seventy PLWH (90% men) at risk for NAFLD were included. The mean (± standard deviation) age and body mass index were 48.6 (±10.2) years and 30 (± 5.3) kg/m2, respectively. The prevalence of HIV-associated NAFLD (MRI-PDFF ≥ 5%) was 80%. The M and XL probes were used for 56% and 44% of patients, respectively. The area under the ROC curve of CAP for the detection of MRI-PDFF ≥ 5% was 0.82 (0.69-0.95) at the cut-point of 285 dB/m. The positive predictive value of CAP ≥ 285 dB/m was 93.2% in this cohort with sensitivity of 73% and specificity of 78.6%. CONCLUSIONS: The optimal cut-point of CAP to correctly identify HIV-associated NAFLD was 285 dB/m, is similar to previously published cut-point for primary NAFLD and may be incorporated into routine care to identify patients at risk of HIV-associated NAFLD.

Diagnostic colonoscopy completion after abnormal fecal immunochemical testing and quality of tests used at 8 Federally Qualified Health Centers in Southern California: Opportunities for improving screening outcomes.

BACKGROUND: The effectiveness of colorectal cancer screening with fecal immunochemical tests (FITs) of stool blood depends on high rates of colonoscopy follow-up for abnormal FITs and the use of high-quality tests. This study characterized colonoscopy referral and completion among patients with abnormal FITs and the types of FITs implemented in a sample of Southern California Federally Qualified Health Centers (FQHCs). METHODS: FQHCs in San Diego, Imperial, and Los Angeles Counties were invited to define a cohort of ≥150 consecutive patients with abnormal FITs in 2015-2016 and to provide data on sex, insurance status, diagnostic colonoscopy referrals and completion within 6 months of abnormal FITs, and the types (brands) of FITs implemented. The primary outcomes were the proportions with colonoscopy referrals and completion for all patients at each FQHC and in aggregate. RESULTS: Eight FQHCs provided data for 1229 patients with abnormal FITs; 46% were male, and 20% were uninsured. Among patients with abnormal FITs, 89% (1091 of 1229; 95% confidence interval [CI], 0.87-0.91) had a colonoscopy referral, and 44% (539 of 1229; 95% CI, 0.41-0.47) had colonoscopy completion. Across FQHCs, the range for colonoscopy referral was 73% to 96%, and the range for completion was 18% to 57%. Six of the 8 FQHCs (75%) reported FIT brands with limited data to support their effectiveness. CONCLUSIONS: In a sample of Southern California FQHCs, diagnostic colonoscopy completion after abnormal FITs was substantially below the nationally recommended benchmark to achieve 80% completion, and the use of FIT brands with limited data to support their effectiveness was high. These findings suggest a need for policies and multilevel interventions to promote diagnostic colonoscopy among individuals with abnormal FITs and the use of higher quality FITs.

MRI Assessment of Treatment Response in HIV-associated NAFLD: A Randomized Trial of a Stearoyl-Coenzyme-A-Desaturase-1 Inhibitor (ARRIVE Trial).

Aramchol, an oral stearoyl-coenzyme-A-desaturase-1 inhibitor, has been shown to reduce hepatic fat content in patients with primary nonalcoholic fatty liver disease (NAFLD); however, its effect in patients with human immunodeficiency virus (HIV)-associated NAFLD is unknown. The aramchol for HIV-associated NAFLD and lipodystrophy (ARRIVE) trial was a double-blind, randomized, investigator-initiated, placebo-controlled trial to test the efficacy of 12 weeks of treatment with aramchol versus placebo in HIV-associated NAFLD. Fifty patients with HIV-associated NAFLD, defined by magnetic resonance imaging (MRI)-proton density fat fraction (PDFF) ≥5%, were randomized to receive either aramchol 600 mg daily (n = 25) or placebo (n = 25) for 12 weeks. The primary endpoint was a change in hepatic fat as measured by MRI-PDFF in colocalized regions of interest. Secondary endpoints included changes in liver stiffness using magnetic resonance elastography (MRE) and vibration-controlled transient elastography (VCTE), and exploratory endpoints included changes in total-body fat and muscle depots on dual-energy X-ray absorptiometry (DXA), whole-body MRI, and cardiac MRI. The mean (± standard deviation) of age and body mass index were 48.2 ± 10.3 years and 30.7 ± 4.6 kg/m2 , respectively. There was no difference in the reduction in mean MRI-PDFF between the aramchol group at -1.3% (baseline MRI-PDFF 15.6% versus end-of-treatment MRI-PDFF 14.4%, P = 0.24) and the placebo group at -1.4% (baseline MRI-PDFF 13.3% versus end-of-treatment MRI-PDFF 11.9%, P = 0.26). There was no difference in the relative decline in mean MRI-PDFF between the aramchol and placebo groups (6.8% versus 1.1%, P = 0.68). There were no differences in MRE-derived and VCTE-derived liver stiffness and whole-body (fat and muscle) composition analysis by MRI or DXA. Compared to baseline, end-of-treatment aminotransferases were lower in the aramchol group but not in the placebo arm. There were no significant adverse events. Conclusion: Aramchol, over a 12-week period, did not reduce hepatic fat or change body fat and muscle composition by using MRI-based assessment in patients with HIV-associated NAFLD (clinicaltrials.gov ID:NCT02684591).

Project ECHO: a model for complex, chronic care in the Pacific Northwest region of the United States.

The Pacific Northwest of the US is a large, sparsely populated region. A telehealth programme called Project ECHO (Extension for Community Health Outcomes) was tested in this region in 2009. Weekly videoconferences were held in the areas of hepatitis C, chronic pain, integrated addictions and psychiatry, and HIV/AIDS. Rural clinicians presented cases to a panel of experts at an academic medical centre and received management advice and access to best practices. During the trial, more than 900 clinicians participated, and more than 700 patient cases were presented. At the end of June 2012, a total of 23 videoconference clinics for hepatitis C had been held, 16 clinics in addiction and psychiatry, 97 in chronic pain and 13 in HIV/AIDS. The Project ECHO model improves access to health care. It may provide a way to bring specialist care to rural areas in developing countries.

The uncertain significance of anti-glomerular basement membrane antibody among HIV-infected persons with kidney disease.

Glomerular lesions that complicate patients with human immunodeficiency virus (HIV) infection include HIV-associated nephropathy, membranous glomerulopathy, and immune-complex glomerulonephritides. This case series presents 3 patients with clinically significant renal disease and positive test results for anti-glomerular basement membrane (anti-GBM) antigen. Characteristic histological findings that would suggest anti-GBM antibodies have a significant role in the pathological state of each patient's kidney disease were absent. In addition, each patient recovered without specific treatment for anti-GBM disease. This case series suggests that anti-GBM antibodies likely are related to the B-cell expansion previously described in patients with HIV infection. We propose that clinicians interpret results of anti-GBM antibody tests carefully for patients with HIV infection, considering biopsy before empiric therapy, particularly in a clinical presentation that is atypical for Goodpasture disease.