Evaluation of a pilot emergency department linkage to care program for patients previously diagnosed with Hepatitis C.

There is a significant number of Emergency Department (ED) patients with known chronic hepatitis C virus (HCV) infection who have not been treated with directly acting antivirals. We implemented a pilot ED-based linkage-to-care program to address this need and evaluated the impact of the program using the HCV Care Continuum metrics. Between March 2015 and May 2016, dedicated patient care navigators identified HCV RNA-positive patients in an urban ED and offered expedited appointments with the on-site viral hepatitis clinic. Patient demographics and care continuum outcomes were abstracted from the EMR and analysed to determine significant factors influencing linkage-to-care (LTC) and treatment initiation rates. The ED linkage-to-care program achieved a 43% linkage-to-care rate (165/384), 22% treatment rate (84/384) and 16% sustained virologic response rate (63/384). Significant associations were found between linkage-to-care and increasing age (OR = 1.03), Medicare insurance (OR = 2.21) and having a primary care physician (PCP) (OR = 4.03). For patients who were linked, the odds of initiating treatment were also positively significantly associated with increasing age (OR = 1.04) and having a PCP (OR = 2.77). For patients who initiated treatment, the odds of sustained virologic response were marginally associated with having a PCP (OR = 4.92).Our ED linkage-to-care program utilized care coordination to successfully link nearly half of approached HCV RNA-positive patients to care. This design can be feasibly replicated by other EDs given limited non-clinical training required for linkage-to-care staff. Adoption of similar programs in other EDs may improve the rates of LTC and treatment initiation for previously diagnosed HCV patients.

Nonadherence to Ledipasvir/Sofosbuvir Did Not Predict Sustained Virologic Response in a Randomized Controlled Trial of Human Immunodeficiency Virus/Hepatitis C Virus Coinfected Persons Who Use Drugs.

BACKGROUND: Eliminating hepatitis C virus (HCV) will require effective treatment delivery to persons with substance use disorders (SUDs). We evaluated the relationship between ledipasvir/sofosbuvir treatment persistence (receiving 84 tablets), adherence, and sustained virologic response (SVR) in persons with human immunodeficiency virus (HIV)/HCV coinfection. METHODS: Of the 144 participants with HIV/HCV and SUDs, 110 initiated a 12-week treatment course under 1 of 3 conditions (usual care, peer mentors, and cash incentives). We used self-report, pharmacy pill counts, and expected date of refill to examine adherence. Persistent participants were categorized as high adherence (taking ≥90% of doses) or low adherence (taking <90% of doses). RESULTS: Most participants persisted on treatment after initiation (n = 105), with 95% (n = 100) achieving SVR. One third (34%) of participants had moderate/heavy alcohol use by the biomarker phosphatidylethanol ([Peth] ≥50 ng/mL), and 44% had urine toxicology positive for cocaine or heroin at enrollment. The proportion of persons with high adherence was 72% (n = 76), and the proportion of persons with low adherence was 28%. Although low adherence was associated with moderate/heavy alcohol use by PEth (relative risk = 2.77; 95% confidence interval, 1.50-5.12), SVR did not vary according to adherence (P = .702), and most participants (97%) with low adherence achieved SVR. CONCLUSIONS: Treatment persistence led to high SVR rates among persons with HIV/HCV, despite imperfect adherence and SUDs.

Sharing the cure: Building primary care and public health infrastructure to improve the hepatitis C care continuum in Maryland.

In 2014, trained healthcare provider capacity was insufficient to deliver care to an estimated 70 000 persons in Maryland with chronic hepatitis C virus (HCV) infection. The goal of Maryland Community Based Programs to Test and Cure Hepatitis C, a public health implementation project, was to improve HCV treatment access by expanding the workforce. Sharing the Cure (STC) was a package of services deployed 10/1/14-9/30/18 that included enhanced information technology and public health infrastructure, primary care provider training and practice transformation. Nine primary care sites enrolled. HCV clinical outcomes were documented among individuals who presented for care at sites and met criteria for HCV testing including risk factor or birth cohort (born between 1945 and 1965) based testing. Fifty-three providers completed the STC training. STC providers identified 3237 HCV antibody-positive patients of which 2624 (81%) were RNA+. Of those HCV RNA+, 1739 (66%) were staged, 932 (36%) were prescribed treatment, 838 (32%) started treatment, 721 (27%) completed treatment and 543 (21%) achieved cure. Among 1739 patients staged, 693 (40%) patients had a liver fibrosis assessment score < F2, rendering them ineligible for treatment under Maryland Medicaid guidelines. HCV RNA testing among HCV antibody-positive people increased from 40% (baseline) to 95% among STC providers. Of 554 patients with virologic data reported, 543 (98%) achieved cure. Primary care practices can effectively serve as HCV treatment centers to expand treatment access. However, criteria by insurance providers in Maryland were a major barrier to treatment.

Unreported alcohol use was common but did not impact hepatitis C cure in HIV-infected persons who use drugs.

We investigated the prevalence and impact of heavy alcohol use on the hepatitis C virus (HCV) care continuum amongst HIV/HCV co-infected persons who use drugs. In the CHAMPS study, 144 HIV/HCV co-infected persons were randomized to contingent cash incentives, peer mentors and usual care to evaluate the impact on HCV care. Alcohol use was ascertained using the 10-item AUDIT (hazardous: male ≥8, female ≥4) and phosphatidylethanol (PEth) (heavy: ≥50 ng/mL), an alcohol biomarker. Log binomial regression was used to evaluate the association between heavy alcohol use and failure to initiate treatment and to achieve sustained virologic response (SVR). Of the 135 participants with PEth data, median age was 55 years, 59% were male, 92% were Black, 91% reported a history of drug use, and 97% were on antiretroviral therapy. Hazardous drinking was reported on AUDIT by 28% of participants, and 35% had heavy alcohol use by PEth. Of the 47 individuals with a PEth ≥50 ng/mL, 23 (49%) reported no or minimal alcohol use by AUDIT. HCV treatment was initiated in 103 of 135 participants, and SVR was achieved in 92%. PEth ≥50 ng/mL (Relative Risk [RR] 0.72, 95% CI 0.35-1.48) was not significantly associated with failure to initiate HCV treatment or failure to achieve SVR (RR 0.85, 95% CI 0.46-1.57).In conclusion, alcohol use was common and frequently not detected by self-report. However, heavy alcohol use, even when measured objectively, was not associated with failure to initiate HCV treatment or to achieve cure.

Relationship of liver disease stage and antiviral therapy with liver-related events and death in adults coinfected with HIV/HCV.

CONTEXT: Human immunodeficiency virus (HIV) accelerates hepatitis C virus (HCV) disease progression; however, the effect of liver disease stage and antiviral therapy on the risk of clinical outcomes is incompletely understood. OBJECTIVE: To determine the incidence of end-stage liver disease (ESLD), hepatocellular carcinoma (HCC), or death according to baseline hepatic fibrosis and antiviral treatment for HIV/HCV coinfected individuals. DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort of 638 coinfected adults (80% black, 66% men) receiving care at the Johns Hopkins HIV clinic and receiving a liver biopsy and who were prospectively monitored for clinical events between July 1993 and August 2011 (median follow-up, 5.82 years; interquartile range, 3.42-8.85 years). Histological specimens were scored for hepatic fibrosis stage according to the METAVIR scoring system. MAIN OUTCOME MEASURE: Incidence of composite outcome of ESLD, HCC, or death. RESULTS: Patients experienced a graded increased risk in incidence of clinical outcomes based on baseline hepatic fibrosis stage (classification range, F0-F4): F0, 23.63 (95% CI, 16.80-33.24); F1, 36.33 (95% CI, 28.03-47.10); F2, 53.40 (95% CI, 33.65-84.76); F3, 56.14 (95% CI, 31.09-101.38); and F4, 79.43 (95% CI, 55.86-112.95) per 1000 person-years (P < .001). In multivariable negative binomial regression, fibrosis stages F2 through F4 and antiretroviral therapy were independently associated with composite ESLD, HCC, or all-cause mortality after adjustment for demographic characteristics, injection drug use, and CD4 cell count. Compared with F0, the incidence rate ratio (RR) for F2 was 2.31 (95% CI, 1.23-4.34; P = .009); F3, 3.18 (95% CI, 1.47-6.88; P = .003); and F4, 3.57 (95% CI, 2.06-6.19; P < .001). Human immunodeficiency virus treatment was associated with fewer clinical events (incidence RR, 0.27; 95% CI, 0.19-0.38; P < .001). For the 226 patients who underwent HCV treatment, the incidence of clinical events did not significantly differ between treatment nonresponders and untreated patients (incidence RR, 1.27; 95% CI, 0.86-1.86; P = .23). In contrast, no events were observed in the 51 patients with sustained virologic response (n = 36) and relapse (n = 15), including 19 with significant fibrosis. CONCLUSION: In this cohort of patients with HIV/HCV coinfection, hepatic fibrosis stage was independently associated with a composite outcome of ESLD, HCC, or death.

A Randomized Controlled Trial of Cash Incentives or Peer Support to Increase HCV Treatment for Persons With HIV Who Use Drugs: The CHAMPS Study.

BACKGROUND: Despite access to direct-acting antivirals, barriers to a hepatitis C virus (HCV) cure persist, especially among persons living with human immunodeficiency virus (HIV) (PLWH) who use drugs. Interventions such as peer mentors or cash incentives may improve the care continuum. METHODS: The CHAMPS (Chronic HepAtitis C Management to ImProve OutcomeS) study randomized 144 PLWH, recruited from an outpatient clinic, with substance use disorders into three treatment groups: usual care (UC) (n = 36), UC plus cash incentives (n = 54), and UC plus peer mentors (n = 54) to evaluate HCV treatment uptake and cure. All participants received 12-weeks of ledipasvir/sofosbuvir (LDV/SOF). Trained peer mentors had well-controlled HIV and HCV. Cash incentives were contingent on visit attendance (maximum $220). The primary endpoint was HCV treatment initiation; secondary endpoints included sustained virologic response (SVR) and HCV reinfection. RESULTS: The majority of participants were male (61%), Black (93%), and unemployed (85%). Depression and active drug and alcohol use were common. Overall, 110 of 144 (76%) participants initiated LDV/SOF. Although treatment initiation rates were higher in PLWH randomized to peers (83%, 45 of 54) or cash (76%, 41 of 54) compared to UC (67%, 24 of 36), these differences were not statistically significant (P = .11). Most PLWH who initiated treatment achieved SVR (100 of 110, 91%). LDV/SOF was well tolerated; peers and cash had no effect on drug and alcohol use during therapy. One individual from the cash cohort experienced HCV reinfection. CONCLUSION: After removal of system barriers, one-third of PLWH in UC did not initiate HCV treatment. Among those who initiated, SVR rates were high. Research involving PLWH who use drugs should focus on overcoming barriers to treatment initiation. CLINICAL TRIAL INFORMATION: The registration data for the trial are in the ClinicalTrials.gov database, number NCT02402218.

Rapid fibrosis progression among HIV/hepatitis C virus-co-infected adults.

OBJECTIVES: To define the incidence of fibrosis progression among hepatitis C virus (HCV)/HIV-co-infected adults, to assess whether HCV or HIV treatment alters the risk of progression, and to determine the utility of liver biopsy to predict future disease. DESIGN: This prospective cohort evaluated 184 HIV/HCV-co-infected individuals who had at least two liver biopsies (median interval 2.9 years). METHODS: Biopsies were scored according to the Ishak modified histological activity index scoring system by a single pathologist blind to biopsy sequence. Significant fibrosis progression was defined as an increase of at least two Ishak fibrosis units between the first and second liver biopsy. Logistic regression analysis was used to assess determinants of fibrosis progression. RESULTS: A total of 174 non-cirrhotic patients were eligible; the majority were African-American men undergoing HIV treatment. On initial biopsy, no or minimal fibrosis was identified in 136 patients (77%). Significant fibrosis progression occurred in 41 patients (24%). Measures of HIV disease and its treatment before and after initial biopsy were not significantly different in progressors and non-progressors. Fibrosis progression was not associated with HCV treatment, which was received by 37 patients (21%) but only three sustained HCV-RNA suppression. In adjusted analysis, only an elevated serum aspartate aminotransferase level between biopsies was associated with progression (odd ratio 3.4, 95% confidence interval 1.4-7.9). CONCLUSION: Over a 3-year interval, significant fibrosis progression can occur in co-infected individuals even if minimal disease was detected on initial biopsy. In this context, factors other than treatment for HIV or HCV modify the risk of fibrosis progression.

Candida esophagitis in a human immunodeficiency virus-1-positive elite controller with hepatitis C virus cirrhosis.

We describe a case of Candida esophagitis in a human immunodeficiency virus elite controller with a preserved CD4 count, a population in which opportunistic infections are almost never seen. The patient has hepatitis C virus coinfection and compensated cirrhosis, suggesting a possible multifactorial etiology of immune dysregulation.

The effect of antiretroviral therapy on liver disease among adults with HIV and hepatitis C coinfection.

In the era of antiretroviral therapy (ART), liver disease has emerged as an important cause of death among persons with human immunodeficiency virus (HIV)/hepatitis C virus (HCV) coinfection. The objective of this study was to estimate the burden of liver disease and evaluate determinants of liver fibrosis and necroinflammatory activity among HIV/HCV coinfected patients receiving ART. We studied 112 randomly selected and 98 referred HCV-infected patients undergoing care in the Johns Hopkins University HIV clinic. Liver disease was characterized clinically and histologically. Of the 210 individuals studied--64% of whom had received ART within 2 years of liver disease assessment--33% had no fibrosis (F0), and 26% had bridging fibrosis or cirrhosis (> or =F3). The median necroinflammatory activity score was 3 (range, 0-9 of 18). ART was not associated with fibrosis; however, significantly less hepatic necroinflammatory activity was observed among persons who had received highly active antiretroviral therapy longer (P = .02) and more effectively (defined by HIV RNA suppression; P < .01). Twelve percent of individuals had previous ART-associated liver enzyme elevations (grades 3-4), but liver fibrosis was not more severe if the liver enzyme elevation resolved. On the other hand, liver fibrosis was more severe in persons with persistent liver enzyme elevations (grades 1-4). In conclusion, despite widespread exposure to ART and documented instances of ART-related hepatitis, we found no evidence that ART caused serious histological liver disease. Recognition of bridging fibrosis and cirrhosis in some but not most patients underscores the importance of identifying and treating liver disease in HIV/HCV coinfected persons.