Leveraging opportunities for treatment/user simplicity (LOTUS): Navigating the current treatment landscape for achieving hepatitis C virus elimination among persons who inject drugs.

All-oral, direct-acting antivirals can cure hepatitis C virus (HCV) in almost all infected individuals; yet, many individuals with chronic HCV are not treated, and the incidence of acute HCV is increasing in some countries, including the United States. Strains on healthcare resources during the COVID-19 pandemic negatively impacted the progress toward the World Health Organization goal to eliminate HCV by 2030, especially among persons who inject drugs (PWID). Here, we present a holistic conceptual framework termed LOTUS (Leveraging Opportunities for Treatment/User Simplicity), designed to integrate the current HCV practice landscape and invigorate HCV treatment programs in the setting of endemic COVID-19: (A) treatment as prevention (especially among PWID), (B) recognition that HCV cure may be achieved with variable adherence with evidence supporting some forgiveness for missed doses, (C) treatment of all persons with active HCV infection (viremic), regardless of acuity, (D) minimal monitoring (MinMon) during treatment, and (E) rapid test and treat (TnT). The objective of this article is to review the current literature supporting each LOTUS petal; identify remaining gaps in knowledge or data; define the remaining barriers facing healthcare providers; and review evidence-based strategies for overcoming key barriers.

Impact of hepatitis C cure on risk of mortality and morbidity in people with HIV after antiretroviral therapy initiation.

OBJECTIVE: Hepatitis C virus (HCV) co-infection is associated with increased morbidity and mortality in people with HIV (PWH). Sustained virological response (SVR) decreases the risk of HCV-associated morbidity. We compared mortality, risk of AIDS-defining events, and non-AIDS nonliver (NANL) cancers between HCV-co-infected PWH who reached SVR and mono-infected PWH. DESIGN: Adult PWH from 21 cohorts in Europe and North America that collected HCV treatment data were eligible if they were HCV-free at the time of ART initiation. METHODS: Up to 10 mono-infected PWH were matched (on age, sex, date of ART start, HIV acquisition route, and being followed at the time of SVR) to each HCV-co-infected PWH who reached SVR. Cox models were used to estimate relative hazards (hazard ratio) of all-cause mortality, AIDS-defining events, and NANL cancers after adjustment. RESULTS: Among 62 495 PWH, 2756 acquired HCV, of whom 649 reached SVR. For 582 of these, at least one mono-infected PWH could be matched, producing a total of 5062 mono-infected PWH. The estimated hazard ratios comparing HCV-co-infected PWH who reached SVR with mono-infected PWH were 0.29 [95% confidence interval (CI) 0.12-0.73] for mortality, 0.85 [0.42-1.74] for AIDS-defining events, and 1.21 [0.86-1.72] for NANL cancer. CONCLUSION: PWH who reached SVR a short time after HCV acquisition were not at higher risk of overall mortality compared with mono-infected PWH. However, the apparent higher risk of NANL cancers in HCV-co-infected PWH who reached SVR after a DAA-based treatment compared with mono-infected PWH, though compatible with a null association, suggests a need for monitoring of those events following SVR.

Sexual Transmission of Viral Hepatitis.

Ongoing sexual transmission presents a significant barrier to viral hepatitis control. Endemic transmission of hepatitis A virus continues through communities of men with male sex partners, despite vaccine availability. Increased incidence of hepatitis B virus from 2014-2018 prompted expanded vaccination guidelines, but uptake and physician awareness remain poor. Hepatitis C virus while strongly associated with injection drug use, is also transmitted by high-risk sexual contact. Despite universal screening recommendations and curative treatment, incidence continues to increase. Even with safe and highly effective vaccinations or treatments, sexual transmission of viral hepatitides must be addressed to achieve disease elimination.

Hepatitis C coinfection and extrahepatic cancer incidence among people living with HIV.

OBJECTIVES: We assessed the incidence of extrahepatic cancer among people with HIV/HCV coinfection and the potential impact of direct-acting antivirals (DAAs) on extrahepatic cancer risk among people with HIV/HCV coinfection. DESIGN: Our study cohort included adults who initiated HIV care at a CNICS site in the US during 1995-2017, excluding those with previous cancer and without HCV testing. METHODS: We used Cox regression to estimate hazard ratios for extrahepatic cancer incidence among patients with HIV/HCV coinfection compared with those with HIV monoinfection. Standardized morbidity ratio (SMR) weights were used to create a 'pseudopopulation' in which all patients were treated with antiretroviral therapy (ART), and to compare extrahepatic cancer incidence among patients with untreated HIV/HCV coinfection with the incidence that would have been observed if they had been successfully treated for HCV. RESULTS: Of 18 422 adults, 1775 (10%) had HCV RNA and 10 899 (59%) were on ART at baseline. Incidence rates of any extrahepatic cancer among patients with HIV/HCV coinfection and HIV monoinfection were 1027 and 771 per 100 000 person-years, respectively. In SMR-weighted analyses, the risk of any extrahepatic cancer among patients with untreated HCV coinfection at baseline was similar to the risk if they had been successfully treated for HCV. Patients with untreated HCV coinfection at baseline had higher incidence of kidney, lung and inflammation-related cancers than if their HCV had been successfully treated, but these associations were not statistically significant. CONCLUSIONS: We did not find evidence that treating HCV coinfection with DAAs would reduce the incidence of extrahepatic cancers among people with HIV receiving ART.

Treatment and prevention of viral hepatitis in pregnancy.

Viral hepatitis in pregnancy may be caused by many types of viruses that cause systemic infection or target hepatocytes in their pathogenesis. Because viral hepatitis during pregnancy may represent acute or chronic infection or the reactivation of a prior infection, a high clinical suspicion, medical history review, and awareness of risk factors for the acquisition of infection are important management principles. The route of infection varies widely and ranges from fecal-oral transmission for the hepatitis A and E viruses to vertical transmission for hepatitis B, blood-borne transmission for hepatitis C, and sexual transmission for the herpes simplex virus. For this reason, the exposure details about travel, food preferences, drug use, and sexual contacts are important to elicit. Although routine prenatal screening is recommended for chronic viral hepatitis caused by hepatitis B and C, most other causes of viral hepatitis in pregnancy are detected in the setting of compatible signs and symptoms (fatigue, abdominal discomfort, jaundice, scleral icterus) or incidentally noted transaminitis on routine labs. Serologic testing is helpful for diagnosis with molecular testing as indicated to guide the management of hepatitis B and C. Preventive vaccines for hepatitis A and B with established safety of use in pregnancy are recommended for women who are at risk of acquisition. Postexposure prophylaxis for hepatitis A is a single dose of immunoglobulin and vaccination can be used if immunoglobulin G is not available. Antiviral therapy with tenofovir disoproxil fumarate is recommended as prophylaxis in pregnant women with active hepatitis B and an elevated viral load (>200,000 IU/mL) during the third trimester to prevent vertical transmission. The neonate exposed to hepatitis B at birth should receive immunoglobulin G and a monovalent birth dose vaccine within 12 hours, followed by completion of the 3-dosage vaccine series. The prevalence of hepatitis C in women of reproductive age has increased in the United States, and the role of antiviral therapy during pregnancy is of great interest. Cesarean delivery is not currently recommended for the sole purpose of reducing vertical transmission risk in pregnant women with viral hepatitis. Breastfeeding is recommended in women with hepatitis A, B, and C. New and promising prevention and treatment options for hepatitis B and C are under investigation. Investigators and regulatory authorities should ensure that these clinical trials for promising antivirals and vaccines are designed to include pregnant and lactating women.

Updated Pathway to Micro-elimination of Hepatitis C Virus in the Hemodialysis Population.

Chronic hepatitis C virus (HCV) infection continues to be transmitted to hemodialysis (HD) patients within HD facilities globally. The goal of the World Health Organization to micro-eliminate HCV infection from the HD population by the year 2030 is not on target to be achieved. Obstacles to eliminate HCV in HD settings remain daunting due to a complex system created by a confluence of guidelines, legislation, regulation, and economics. HCV prevalence remains high and seroconversion continues among the HD patient population globally as a result of the HD procedure. Preventive strategies that effectively prevent HCV transmission, treatment-as-prevention, and rapid referral to treatment balanced with kidney transplant candidacy should be added to the current universal precautions approach. A safer system must be designed before HCV transmission can be halted and eliminated from the HD population.

Direct Acting Antivirals in Hepatitis C-Infected Kidney Transplant Recipients: Associations with Long-term Graft Failure and Patient Mortality.

BACKGROUND: Direct-acting antiviral (DAA) therapy among hepatitis C virus (HCV)-infected kidney transplant recipients is associated with short-term improvement in protein/creatinine (P/C) ratios, but how HCV cure affects long-term graft outcomes remains unknown. METHODS: This is a retrospective follow-up study of 59 HCV-infected patients who underwent kidney transplant at the University of Alabama at Birmingham between 2007-2015 who were followed until the end of 2017. We examined the association of DAA-induced HCV cure with graft failure or death by survival analyses (Kaplan-Meier, Cox regression). RESULTS: Mean age was 55 years, 73% were African American, and 68% were male. Median baseline creatinine was 1.4 mg/dL, P/C ratio was 0.5, and estimated glomerular filtration rate (eGFR) was 59 mL/min. Of those who received DAA, 24 (83%) achieved cure. The remaining 5 DAA patients (17%) did not have documented evidence of sustained virologic response (SVR). Overall, 19 (32%) patients experienced graft failure or death; with lower incidence in treated patients than untreated (4 vs 15 events; 2.6 vs 10.3 per 100 person-years [cHR 0.19, 95% CI: 0.06-0.66]). When adjusted for age, sex, race, and proteinuria, the association remained strong and invariant across time-varying (aHR 0.30, 95% CI: 0.08-1.10), time-averaged (aHR 0.28, 95% CI: 0.07-1.07), and time-varying-cumulative (aHR 0.32, 95% CI: 0.08-1.21) proteinuria metrics. CONCLUSIONS: DAAs therapy was associated with improved graft survival and reduced mortality. While not statistically significant, the association was strong, and these single-center findings warrant larger studies to demonstrate the benefits of HCV treatment in this population.

Hepatitis C Among High-Risk Alabamians: Disease Burden and Screening Effectiveness.

BACKGROUND: The effectiveness of hepatitis C testing and linkage-to-care (LTC) is poorly characterized in low-resource jurisdictions facing gaps in harm reduction, including illegality of syringe exchange services. Effectiveness of a community-based test/LTC program was evaluated in Alabama. METHODS: In 2016-2018, shelters, drug treatment centers (DTCs), AIDS organizations, and Federally Qualified Health Centers (FQHCs) engaged in screening/LTC. A coordinator navigated individuals to confirm viremia and link to substance use treatment or primary care with hepatitis C prescribers. RESULTS: Point-of-care (POC) tested 4293 individuals (10% [427] antibody-positive, 71% [299/419] RNA performed, 80% [241/299] viremia confirmed) and 93% linked to care (225/241). Electronic medical record (EMR)-based reflex strategy screened 4654 (15% [679] antibody positive, 99% [670/679] RNA performed, 64% [433/679] viremia confirmed) and 85% linked to care (368/433). We observed higher odds of RNA confirmation in EMR-based reflex versus POC (OR, 2.07; P < .0001) and higher odds of LTC in EMR-based reflex versus POC (OR, 1.51; P < .0001). Overall, 53% individuals tested were nonbaby boomers. CONCLUSIONS: In Alabama, screening at high-risk settings identified significant hepatitis C burden and reflex testing outperformed point-of-care linkage indicators. Colocating testing in DTCs and treatment in FQHCs provided key LTC venues to at-risk younger groups.

High Prevalence of Hepatitis C Infection Among Adult Patients at Four Urban Emergency Departments - Birmingham, Oakland, Baltimore, and Boston, 2015-2017.

Identifying persons with hepatitis C virus (HCV) infection has become an urgent public health challenge because of increasing HCV-related morbidity and mortality, low rates of awareness among infected persons, and the advent of curative therapies (1). Since 2012, CDC has recommended testing of all persons born during 1945-1965 (baby boomers) for identification of chronic HCV infection (1); urban emergency departments (EDs) are well positioned venues for detecting HCV infection among these persons. The United States has witnessed an unprecedented opioid overdose epidemic since 2013 that derives primarily from commonly injected illicit opioids (e.g., heroin and fentanyl) (2). This injection drug use behavior has led to an increase in HCV infections among persons who inject drugs and heightened concern about increases in human immunodeficiency virus (HIV) and HCV infection within communities disproportionately affected by the opioid crisis (3,4). However, targeted strategies for identifying HCV infection among persons who inject drugs is challenging (5,6). During 2015-2016, EDs at the University of Alabama at Birmingham; Highland Hospital, Oakland, California; Johns Hopkins Hospital, Baltimore, Maryland; and Boston University Medical Center, Massachusetts, adopted opt-out (i.e., patients can implicitly accept or explicitly decline testing), universal hepatitis C screening for all adult patients. ED staff members offered HCV antibody (anti-HCV) screening to patients who were unaware of their status.* During similar observation periods at each site, ED staff members tested 14,252 patients and identified an overall 9.2% prevalence of positive results for anti-HCV among the adult patient population. Among the 1945-1965 birth cohort, prevalence of positive results for anti-HCV (13.9%) was significantly higher among non-Hispanic blacks (blacks) (16.0%) than among non-Hispanic whites (whites) (12.2%) (p<0.001). Among persons born after 1965, overall prevalence of positive results for anti-HCV was 6.7% and was significantly higher among whites (15.3%) than among blacks (3.2%) (p<0.001). These findings highlight age-associated differences in racial/ethnic prevalences and the potential for ED venues and opt-out, universal testing strategies to improve HCV infection awareness and surveillance for hard-to-reach populations. This opt-out, universal testing approach is supported by new recommendations for hepatitis C screening at least once in a lifetime for all adults aged ≥18 years, except in settings where the prevalence of positive results for HCV infection is <0.1% (7).

Predictors of linkage to care for a nontargeted emergency department hepatitis C screening program.

OBJECTIVE: We implemented a nontargeted, opt-out HCV testing and linkage to care (LTC) program in an academic tertiary care emergency department (ED). Despite research showing the critical role of ED-based HCV testing programs, predictors of LTC have not been defined for patients identified through the nontargeted ED testing strategy. In order to optimize health outcomes for patients with HCV, we sought to identify predictors of LTC failure. METHODS: This was a retrospective cohort study of adult patients who were tested for HCV in the ED between August 2015 and September 2018 and were confirmed to have chronic HCV infection through RNA testing. We used logistic regression to assess the relationship between candidate predictors and the primary outcome, LTC failure, which was defined as a patient not being seen by an HCV treating provider after discharge from the ED. RESULTS: Of 53,297 patients tested, 1,674 (3.1%) had HCV on confirmatory testing, and 355 (21%) linked to care. Predictors of LTC failure included younger age (OR 0.96, 95% CI 0.95-0.97), white race (OR 1.65, 95% CI 1.23-2.22), homelessness (OR 1.91, 95% CI 1.19-3.08), substance use (OR 1.77, 95% CI 1.34-2.34), and comorbid psychiatric illness (OR 2.16, 95% CI 1.59-2.94). Patients with significant medical comorbidities (OR 0.57, 95% CI 0.41-0.78) or HIV co-infection (OR 0.11, 95% CI 0.03-0.46) were less likely to experience LTC failure. CONCLUSIONS: One in five HCV-infected patients identified by ED-based nontargeted testing successfully linked to an HCV treating provider. Predictors of LTC failure may guide the development of targeted interventions to improve LTC success.

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 Men's Health: Research, Practice, and Policy Implications, which is sponsored by the National Institutes of Health.

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%). Posttreatment 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.

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.

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.

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

UNLABELLED: 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.

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/mm(3) (aOR = 0.69, 95% CI: 0.53-0.92). CONCLUSION: Poor retention in HIV care is strongly associated with suboptimal hepatitis B vaccination.

National estimates of healthcare utilization by individuals with hepatitis C virus infection in the United States.

BACKGROUND: Hepatitis C virus (HCV) infection is a major public health problem in the United States. Although prior studies have evaluated the HCV-related healthcare burden, these studies examined a single treatment setting and did not account for the growing "baby boomer" population (individuals born during 1945-1965). METHODS: Data from the National Ambulatory Medical Care Survey, the National Hospital Ambulatory Medical Care Survey, and the Nationwide Inpatient Sample were analyzed. We sought to characterize healthcare utilization by individuals infected with HCV in the United States, examining adult (≥18 years) outpatient, emergency department (ED), and inpatient visits among individuals with HCV diagnosis for the period 2001-2010. Key subgroups included persons born before 1945 (older), between 1945 and 1965 (baby boomer), and after 1965 (younger). RESULTS: Individuals with HCV infection were responsible for >2.3 million outpatient, 73 000 ED, and 475 000 inpatient visits annually. Persons in the baby boomer cohort accounted for 72.5%, 67.6%, and 70.7% of care episodes in these settings, respectively. Whereas the number of outpatient visits remained stable during the study period, inpatient admissions among HCV-infected baby boomers increased by >60%. Inpatient stays totaled 2.8 million days and cost >$15 billion annually. Nonwhites, uninsured individuals, and individuals receiving publicly funded health insurance were disproportionately affected in all healthcare settings. CONCLUSIONS: Individuals with HCV infection are large users of outpatient, ED, and inpatient health services. Resource use is highest and increasing in the baby boomer generation. These observations illuminate the public health burden of HCV infection in the United States.

When to start antiretroviral therapy: as soon as possible.

BACKGROUND: The 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. DISCUSSION: In 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. SUMMARY: From 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.