Ricardo A. Franco

Unrecognized chronic hepatitis C virus infection among baby boomers in the emergency department

The Centers for Disease Control and Prevention and U.S. Preventive Services Task Force have highlighted public screening as an essential strategy for increasing hepatitis C virus (HCV) detection in persons born between 1945 and 1965 (“baby boomers”). Because earlier HCV screening efforts have not targeted emergency department (ED) baby boomer patients, we describe early experience with integrated opt‐out HCV antibody (Ab) screening of medically stable baby boomers presenting to an urban academic ED. We performed HCV Ab testing 24 hours per day and confirmed positive test results using polymerase chain reaction (PCR). The primary outcome was prevalence of unrecognized HCV infection. Among 2,325 unique HCV‐unaware baby boomers, 289 (12.7%) opted out of HCV screening. We performed HCV Ab tests on 1,529 individuals, of which 170 (11.1%) were reactive. Among Ab reactive cases, follow‐up PCR was performed on 150 (88.2%), of which 102 (68.0%) were confirmed RNA positive. HCV Ab reactivity was more likely in males compared to females (14.7% vs. 7.4%; P < 0.001), African Americans compared to whites (13.3% vs. 8.8%; P = 0.010), and underinsured/ uninsured patients compared to insured patients (16.8%/16.9% vs. 5.0%; P = 0.001). Linkage‐to‐care service activities were recorded for 100 of the 102 confirmed cases. Overall, 54 (54%) RNA‐positive individuals were successfully contacted by phone within five call‐back attempts. We confirmed initial follow‐up appointments for 38 (70.4%) RNA‐positive individuals successfully contacted, and 21 (55.3%) individuals with confirmed appointments attended their initial visit with a liver specialist; 3 (7.9%) are awaiting an upcoming scheduled appointment. Conclusion: We observed high prevalence of unrecognized chronic HCV infection in this series of baby boomers presenting to the ED, highlighting the ED as an important venue for high‐impact HCV screening and linkage to care. (Hepatology 2015;61:776–782)

When to start antiretroviral therapy: as soon as possible

BackgroundThe debate regarding ‘When to Start’ antiretroviral therapy has raged since the introduction of zidovudine in 1987. Based on the entry criteria for the original Burroughs Wellcome 002 study, the field has been anchored to CD4 cell counts as the prime metric to indicate treatment initiation for asymptomatic individuals infected with Human Immunodeficiency Virus. The pendulum has swung back and forth based mostly on the relative efficacy, toxicity and convenience of available regimens.DiscussionIn today’s world, several factors have converged that compel us to initiate therapy as soon as possible: 1) The biology of viral replication (1 to 10 billion viruses per day) strongly suggests that we should be starting early. 2) Resultant inflammation from unchecked replication is associated with earlier onset of multiple co-morbid conditions. 3) The medications available today are more efficacious and less toxic than years past. 4) Clinical trials have demonstrated benefits for all but the highest CD4 strata (>500 cells/μl). 5) Some cohort studies have demonstrated the clear benefit of antiretroviral therapy at any CD4 count and no cohort studies have demonstrated that early therapy is more detrimental than late therapy at the population level. 6) In addition to the demonstrated and inferred benefits to the individual patient, we now have evidence of a Public Health benefit from earlier intervention: treatment is prevention.SummaryFrom a practical, common sense perspective we are talking about life-long therapy. Whether we start at a CD4 count of 732 cells/μl or 493 cells/μl, the patient will be on therapy for over 40 to 50 years. There does not seem to be much benefit in waiting and there likely is significant long-term harm. Do not wait. Treat early.The counter-argument to this debate topic can be freely accessed here: http://www.biomedcentral.com/1741-7015/11/148.

Continuum of care for hepatitis C virus among patients diagnosed in the emergency department setting

Background. Urban emergency departments (EDs) seem to be able to detect new hepatitis C virus (HCV) infections at a high rate, but it is unknown the extent to which individuals screened in the ED can progress to treatment and cure. We evaluate the HCV Continuum of Care for patients identified with HCV in 2 urban EDs, and consider the results in the context of outcomes from ambulatory screening venues where 2%-10% of chronically infected patients are treated. Methods. This is a multicenter, retrospective cohort study of 2 ED HCV screening programs. Patients who screened HCV antibody reactive between 1 May and 31 October 2014 were followed for up to 18 months. The main outcome was the absolute number and proportion of eligible patients who completed each stage of the HCV Continuum of Care. Results. A total of 3704 ED patients were estimated to have undiagnosed HCV infection, and screening identified 532 (14.4%) HCV antibody-reactive patients. Of the 532 HCV antibody-reactive patients, 435 completed viral load testing (82%), of whom 301 (69%) were chronically infected. Of the 301 chronically infected patients, 158 had follow-up arranged (52%), of whom 97 attended their appointment (61%). Of these 97, 24 began treatment (25%), and 19 of these 24 achieved sustained virological response (79%). Conclusions. Urban EDs serve patients with poor access to preventive care services who have a high prevalence of HCV infection. Because ED patients identified with HCV infection can progress to treatment and cure with rates comparable to ambulatory care settings, implementation of ED HCV screening should be expanded.

Characterizing Failure to Establish Hepatitis C Care of Baby Boomers Diagnosed in the Emergency Department

Background. Emergency departments (EDs) are high-yield sites for hepatitis C virus (HCV) screening, but data regarding linkage to care (LTC) determinants are limited. Methods. Between September 2013 and June 2014, 4371 baby boomers unaware of their HCV status presented to the University of Alabama at Birmingham ED and underwent opt-out screening. A linkage coordinator facilitated referrals for positive cases. Demographic data, International Classification of Diseases, Ninth Revision codes, and clinic visits were collected, and patients were (retrospectively) followed up until February 2015. Linkage to care was defined as an HCV clinic visit within the hospital system. Results. Overall, 332 baby boomers had reactive HCV antibody and detectable plasma ribonucleic acid. The mean age was 57.3 years (standard deviation = 4.8); 70% were male and 61% were African Americans. Substance abuse (37%) and psychiatric diagnoses (30%) were prevalent; 9% were identified with cirrhosis. During a median follow-up of 433 days (interquartile range, 354–500), 117 (35%) linked to care and 48% needed inpatient care. In multivariable analysis, the odds of LTC failure were significantly higher for white males (adjusted odds ratio [aOR], 2.57; 95% confidence interval [CI], 1.03–6.38) and uninsured individuals (aOR, 5.16; 95% CI, 1.43–18.63) and lower for patients with cirrhosis (aOR, 0.36; 95% CI, 0.14–0.92) and access to primary care (aOR, 0.20; 95% CI, 0.10–0.41). Conclusions. In this cohort of baby boomers with newly diagnosed HCV in the ED, only 1 in 3 were linked to HCV care. Although awareness of HCV diagnosis remains important, intensive strategies to improve LTC and access to curative therapy for diagnosed individuals are needed.

Direct-acting Antivirals in Kidney Transplant Patients: Successful Hepatitis C Treatment and Short Term Reduction in Urinary Protein/Creatinine Ratios

Background: The role of Hepatitis C Virus (HCV) clearance in kidney graft survival is unknown. We examined short-term trends of protein/creatinine (P/C) ratios in HCV-infected kidney transplant recipients treated with direct-acting antivirals (DAAs). Methods: This is a retrospective study of 19 kidney transplant patients with HCV infection treated with DAAs at the University of Alabama at Birmingham between January 2013 and June 2016. Markers of glomerular damage were assessed using average urinary protein/creatinine (P/C) ratios measured pretreatment and posttreatment. Treatment efficacy was defined as sustained virologic response at 12 weeks post-HCV treatment (SVR12). Results: The median age of the 19 patients included was 59 years (Q1 = 58, Q3 = 64). Of these patients, 68% were African American, 32% were White and 63% were male. The median time between kidney transplant and initiation of DAA therapy was 2.25 years (Q1 = 0.79, Q3 = 3.79). Posttreatment P/C ratios (median = 0.127, Q1=0.090, Q3 = 0.220) were significantly lower (P = 0.01) than pretreatment ratios (median = 0.168, Q1 = 0.118, Q3 = 0.385). P/C ratios decreased in 14 of 19 patients (74%) with a median change of -0.072 (median percent change = -40%). Post-treatment estimated glomerular filtration rates (median = 58.9, Q1 = 48.9, Q3 = 72.3) were not significantly different (P = 0.82) than the pretreatment values (median = 57.0, Q1 = 48.8, Q3 = 67.8). All patients achieved SVR12. Conclusions: In this preliminary study, there was a statistically significant decrease in P/C ratios associated with HCV clearance, suggesting a potential role for DAAs in improving kidney graft survival. Larger cohort studies will be needed to assess the clinical and long-term benefits of DAAs in this population.

Emergency Department Screening for Hepatitis C Virus: Geographic Reach and Spatial Clustering in Central Alabama

Hepatitis C virus (HCV) infection is a growing problem, disproportionately affecting those born between 1945 and 1965. Here, we demonstrate the wide geographic reach and surveillance potential of emergency department-based screening and identify areas of elevated HCV infection in central Alabama that were socioeconomically disadvantaged compared with surrounding communities.

Racial and Geographic Disparities in Hepatocellular Carcinoma Outcomes

INTRODUCTION Hepatocellular carcinoma disproportionately affects minorities. Southern states have high proportions of black populations and prevalence of known risk factors. Further research is needed to understand the role of southern geography in hepatocellular carcinoma disparities. This paper examined racial disparities in hepatocellular carcinoma incidence, demographics, tumor characteristics, receipt of treatment, and all-cause mortality in southern and non-southern cancer registries. METHODS Surveillance Epidemiology and End Results data were probed in 2015 to identify 43,868 patients diagnosed with hepatocellular carcinoma from 2000 to 2012 (5,455 in southern registries [Atlanta, Louisiana, and Rural and Greater Georgia]). RESULTS Southern registries showed steeper increases of age-adjusted hepatocellular carcinoma incidence (from 2.89 to 5.29cases/100,000 people) versus non-southern areas (from 3.58 to 5.54cases/100,000 people). Blacks were over-concentrated in southern registries (32% vs 10%). Compared with whites, blacks were significantly younger at diagnosis, more likely diagnosed with metastasis, and less likely to receive surgical therapies in both registry groups. After adjustment, blacks had a significantly higher risk of all-cause mortality compared with whites in southern (hazard ratio=1.10, p=0.007) and non-southern areas (hazard ratio=1.08, p<0.001). For overall populations, southern registries had higher risk of all-cause mortality versus non-southern registries (hazard ratio=1.13, p<0.001). CONCLUSIONS Age-adjusted incidence rates of hepatocellular carcinoma are plateauing overall, but are still rising in southern areas. Race and geography had independent associations with all-cause mortality excess risk among patients with hepatocellular carcinoma. Further studies are needed to understand the root causes of potential mortality risk excess among overall populations with hepatocellular carcinoma living in the South. SUPPLEMENT INFORMATION This article is part of a supplement entitled African American Mens Health: Research, Practice, and Policy Implications, which is sponsored by the National Institutes of Health.

Acute disseminated encephalomyelitis presenting as a brainstem encephalitis

Acute disseminated encephalomyelitis (ADEM) is a disease characterized by inflammation and destruction of myelin. Acute hemorrhagic leukoencephalitis (AHLE) is a severe form of ADEM known for its particularly poor outcome. We present a case of a young Caucasian female who presented with drowsiness and slurred speech followed by rapid brainstem involvement resembling rhomboencephalitis. Despite multiple diagnostic tests and empiric therapy with immunosuppressants, immunoglobulins, and antimicrobials, she lost most brainstem reflexes within a few weeks and ultimately passed away. Magnetic resonance imaging (MRI) showed progression of lesions from the brainstem to eventually involve bilateral cerebral hemispheres. Autopsy and microscopic examination of the brain revealed several hemorrhagic lesions throughout the brain and rendered a diagnosis of AHLE. AHLE was initially described in 1941 and is thought to be autoimmune related, possibly related to cross reactivity between the immune system and CNS tissues like myelin. While a definitive inciting pathogen was not discovered, this case emphasizes the importance of considering AHLE in the differential diagnosis of patients with rapid loss of neurologic function and highlights an atypical presentation of ADEM/AHLE.

Impact of Poor Retention in HIV Medical Care on Hepatitis B Vaccination

Background: We identified factors associated with complete hepatitis B vaccination of patients with HIV. Methods: Retrospective analysis of patients undergoing HIV clinic orientation from 2000 to 2010. Vaccine-eligible patients had negative hepatitis B serologies at baseline. Receipt of at least 3 doses was defined as complete vaccination. Results: Of 1242 patients, 519 (42%) were completely vaccinated. Complete vaccination was positively associated with missing ≤25% of the visits during the first year of care (adjusted odds ratio [aOR] = 2.35, 95% confidence interval [CI]: 1.79-3.09), being naive to care (aOR = 1.50, 95% CI: 1.13-1.99), and living at the clinic’s county (aOR = 1.33, 95% CI: 1.02-1.75). Complete vaccination was negatively associated with failure to remain in care >2 years (aOR = 0.18, 95% CI: 0.13-0.24), history of intravenous drug use (aOR = 0.48, 95% CI: 0.27-0.87), and baseline CD4 count <200 cells/mm3 (aOR = 0.69, 95% CI: 0.53-0.92). Conclusion: Poor retention in HIV care is strongly associated with suboptimal hepatitis B vaccination.