Long-term Follow-up of Hepatitis C Patients Who Achieved Sustained Virologic Response in the Pragmatic PRIORITIZE Study.

Multiple real-world studies have confirmed the safety and efficacy of hepatitis C (HCV) direct-acting antivirals (DAAs); however, few studies have provided data on long-term outcomes of patients without cirrhosis after achieving sustained virologic response (SVR).1-3 The aims of this analysis were to describe, among individuals in the PRIORITIZE Study achieving SVR: (1) the frequency of laboratory testing and imaging during long-term follow-up (LTFU), (2) changes in liver tests, (3) occurrence of hepatic decompensation or hepatocellular carcinoma (HCC) and deaths, and (4) durability of SVR.

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.

A Pragmatic, Randomized Controlled Trial of Oral Antivirals for the Treatment of Chronic Hepatitis C: The PRIORITIZE Study.

BACKGROUND AND AIMS: Multiple direct-acting antiviral (DAA) regimens are available to treat HCV genotype 1 infection. However, comparative effectiveness from randomized controlled trials of DAA regimens is unavailable. APPROACH AND RESULTS: We conducted a pragmatic randomized controlled trial (NCT02786537) to compare the effectiveness of DAAs for HCV genotype 1a or 1b on viral response, safety, tolerability, and medication nonadherence. Adults with compensated liver disease, HCV genotype 1, not pregnant or breastfeeding, and with health insurance likely to cover ledipasvir/sofosbuvir (LDV/SOF) were recruited from 34 US viral hepatitis clinics. Participants were randomized (± ribavirin) to LDV/SOF, elbasvir/grazoprevir (EBR/GZR), and paritaprevir/ritonavir/ombitasvir+dasabuvir (PrOD; treatment arm stopped early). Primary outcomes included sustained viral response at 12 weeks (SVR12), clinician-recorded adverse events, patient-reported symptoms, and medication nonadherence. Between June 2016 and March 2018, 1,609 participants were randomized. Among 1,128 participants who received ≥1 dose of EBR/GZR or LDV/SOF (± ribavirin), SVR12 was 95.2% (95% CI, 92.8%-97.6%) and 97.4% (95% CI, 95.5%-99.2%), respectively, with a difference estimate of 2.2% (-0.5% to 4.7%), falling within the "equivalence" interval (-5% to 5%). While most (56%) participants experienced adverse events, few were serious (4.2%) or severe (1.8%). In the absence of ribavirin, discontinuations due to adverse events were rare. Patient-reported symptoms and medication nonadherence were similar. Study limitations were dropout due to insurance denial and loss to follow-up after treatment, limiting the ability to measure SVR12. CONCLUSIONS: This pragmatic trial demonstrated high SVR12 for participants treated with EBR/GZR and LDV/SOF with few adverse effects. Overall, the two regimens were equivalent in effectiveness. The results support current HCV guidelines that do not distinguish between ribavirin-free EBR/GZR and LDV/SOF.

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.

High hepatitis C cure rates among black and nonblack human immunodeficiency virus-infected adults in an urban center.

Hepatitis C virus (HCV) cure rates have been similar in patients with and without human immunodeficiency virus (HIV) coinfection; however, in the ION-4 study, black patients treated with ledipasvir/sofosbuvir (LDV/SOF) were significantly less likely to achieve cure (90%) compared to nonblack patients (99%). There are limited real-world data on the effectiveness of oral direct-acting antivirals (DAAs) in predominantly minority HIV/HCV coinfected populations. We analyzed HCV treatment outcomes among 255 HCV coinfected patients initiating DAAs between February 2014 and March 2016 in an urban clinic in Baltimore, Maryland. To facilitate adherence, patients received standardized HIV nurse/pharmacist support, which included nurse visits and telephone calls. Median age was 43 years, 88% were black, 73% male, 69% had a history of injection drug use, 45% a history of hazardous alcohol use, and 57% a comorbid psychiatric diagnosis. Median CD4 count was 577 (interquartile range, 397-820) cells/mm3 ; most (97%) were on antiretroviral therapy, had HIV RNA <20 copies/mL (87%), and were infected with HCV genotype 1 (98%). Over 60% had significant fibrosis (Fibrosis-4 Index score 1.45-3.25 [44%] and >3.25 [17%, cirrhosis]) and 30% were HCV treatment experienced. The majority of patients received LDV/SOF with or without ribavirin (91%) and were treated for 12 weeks. Overall, the sustained virological response rate was 97% (95% confidence interval [CI], 93-98) and did not vary by race (black, 96% [95% CI, 93-98]; nonblack, 97%, [95% CI, 83-99]), history of injection drug use, alcohol use, or psychiatric diagnosis. CONCLUSION: HCV treatment was highly effective among HIV-infected patients who received care within an integrated nurse/pharmacist adherence support program. These results suggest that race and psychosocial comorbidity may not be barriers to HCV elimination. (Hepatology 2017;66:1402-1412).

Efficacy and Safety of Ledipasvir/Sofosbuvir for the Treatment of Chronic Hepatitis C in Persons With Sickle Cell Disease.

Patients with sickle cell disease are at high risk for chronic hepatitis C infection. Prior treatment has been limited due to the use of ribavirin causing hemolytic anemia and interferon causing cytopenias. We demonstrate the safety and efficacy of fixed-dose combination ledipasvir and sofosbuvir for 12 weeks in this population.

Reinfection incidence and risk among people treated for recent hepatitis C virus infection.

OBJECTIVE: Reinfection poses a challenge to hepatitis C virus (HCV) elimination. This analysis assessed incidence of, and factors associated with reinfection among people treated for recent HCV (duration of infection <12 months). METHODS: Participants treated for recent HCV (primary infection or reinfection) in an international randomized trial were followed at 3-monthly intervals for up to 2 years to assess for reinfection. Reinfection incidence was calculated using person-time of observation. Factors associated with HCV reinfection were assessed using Cox proportional hazards regression analysis. RESULTS: Of 222 participants treated for recent HCV, 196 (62% primary infection, 38% reinfection) were included in the cohort at risk for reinfection, of whom 87% identified as gay or bisexual men, 71% had HIV and 20% injected drugs in the month prior to enrolment. During 198 person-years of follow-up, 28 cases of HCV reinfection were identified among 27 participants, for an incidence of 14.2 per 100 person-years [95% confidence interval (CI) 9.8-20.5]. Reinfection was associated with prior HCV reinfection [adjusted hazards ratio (aHR) 2.42; 95% CI 1.08-5.38], injection drug use posttreatment (aHR 2.53; 95% CI 1.14-5.59), condomless anal intercourse with casual male partners (aHR 3.32; 95% CI 1.14-9.65) and geographic region (United Kingdom, aHR 0.21; 95% CI 0.06-0.75). Among gay and bisexual men (GBM), reinfection was also associated with sexualized drug use involving injecting posttreatment (aHR 2.97; 95% CI 1.10-8.02). CONCLUSION: High reinfection incidence following treatment for recent HCV among people with ongoing sexual and drug use risk behaviour highlights the need for posttreatment surveillance, rapid retreatment of reinfection and targeted harm reduction strategies.

An unusual etiology of infective endocarditis: Enterobacter cloacae.

Gram-negative microorganisms are rarely implicated in causing infective endocarditis (IE). Although the traditionally identified risk factor for Gram-negative endocarditis has been intravenous drug abuse, recent studies have revealed that healthcare contact and the presence of prosthetic cardiac devices are primary risk factors for IE secondary to non-HACEK Gram-negative bacteria. We present a case of Enterobacter endocarditis in a patient with no prior history of valvular heart disease, implanted endovascular device, or intravenous drug abuse. The patient was treated successfully with carbapenem monotherapy. We have reviewed 43 cases of Enterobacter endocarditis reported in the literature to date. Clinical summary and management of IE secondary to Enterobacter based on all the published cases is outlined.

Depression in patients with nonalcoholic fatty liver disease and chronic viral hepatitis B and C.

BACKGROUND: Patients with chronic liver disease (CLD) and depression may be at a higher risk for various complications, including impaired quality of life and more advanced liver disease. The purpose of this study was to determine the prevalence of depression in CLD patients (non-alcoholic fatty liver disease (NAFLD), Hepatitis B (HBV), and Hepatitis C (HCV)) and to identify potential clinical and laboratory correlates of depression in these patients. METHODS: We used a database of CLD patients that contains extensive clinical (including self-reported depression) and laboratory data for each patient. We compared the prevalence of depression in patients with HBV, HCV, and NAFLD. We also used regression models to find independent predictors of depression in these patients. RESULTS: Of 878 CLD patients, 207 (23.6%) had a diagnosis of depression (NAFLD 27.2%, HCV 29.8%, and HBV 3.7%). Examination of predictors of depression differed by the type of chronic liver disease. For NAFLD, independent predictors of depression were the presence of hypertension, smoking, history of lung disease, being female, and non-African-American. For HBV patients, the only independent predictor of depression was excessive alcohol consumption (defined as >10 g/d), while for HCV patients, independent predictors were being female and non-Asian, presence of fatigue, and excessive alcohol intake. CONCLUSIONS: This study demonstrates that individuals with NAFLD and HCV have a higher prevalence of depression than HBV patients and the rates of depression reported for the general population. The most consistent correlates of depression status in CLD patients are being female and excessive alcohol consumption.

Hepatitis C Elimination in People With HIV Is Contingent on Closing Gaps in the HIV Continuum.

BACKGROUND: Bolstered by the high efficacy of hepatitis C virus (HCV) treatment, the World Health Organization has called for HCV elimination by 2030. People with HIV (PWH) have been identified as a population in which elimination should be prioritized. METHODS: We examined progress in HCV elimination through the HCV care continuum among patients infected with HIV/HCV receiving HIV care at Johns Hopkins Hospital in Baltimore, Maryland, United States. Patients with HIV care visits in at least 2 consecutive years were followed through December 15, 2018, for referral to HCV care, treatment initiation, and cure. RESULTS: Among 593 HIV/HCV-coinfected individuals, 547 (92%) were referred for HCV care, 517 (87%) were evaluated for HCV treatment, 457 (77%) were prescribed HCV treatment, 426 (72%) initiated treatment, and 370 (62%) achieved HCV cure. In multivariable analysis, advanced liver disease (hazard ratio [HR], 1.48; 95% confidence interval [CI], 1.17-1.88) remained significantly positively associated with HCV treatment initiation. Conversely, being insured by state Medicaid (HR, 0.75; 95% CI, 0.61-0.92), having an HIV RNA >400 copies/mL (HR, 0.29; 95% CI, 0.18-0.49), and having missed 1%-24% (HR, 0.72; 95% CI, 0.54-0.97), 25%-49% (HR, 0.66; 95% CI, 0.49-0.89), and ≥50% of HIV care visits (HR, 0.39; 95% CI, 0.25-0.60) were significantly negatively associated with HCV treatment initiation. CONCLUSIONS: HCV infection can be eliminated in PWH. However, HCV elimination requires unrestricted access to HCV treatment and improved methods of retaining people in medical care.

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.

Disparities in activity level and nutrition between patients with chronic hepatitis C and blood donors.

OBJECTIVE: To compare physical activity levels and dietary choices of patients who have chronic hepatitis C (CHC) with those of blood donors (BDs). DESIGN: A prospective survey. SETTING: A liver disease treatment center and a blood donor center from a nonprofit health system. PATIENTS: A total of 149 subjects (93 with CHC and 56 BDs) participated. Subjects were 18 years or older and agreed to participate; those with CHC had no evidence of cirrhosis. METHODS: All subjects provided basic clinical information and completed a nutrition survey, which contained questions about dietary choices and their frequency, and the Human Activity Profile, which measured maximum effort (Maximum Activity Score; MAS) and daily activity (Adjusted Activity Score; AAS). MAIN OUTCOMES MEASUREMENTS: MAS and AAS scales and 13 indices on the nutrition survey. Independent samples t-tests, Pearson correlations, and multiple stepwise regression analyses were performed. RESULTS: No significant differences were found between BDs and patients with CHC in terms of age, gender, race, body mass index, hyperlipidemia, hypertension, or diabetes mellitus. Mean body mass index was 27.5, 17.8% had hyperlipidemia, and 9.6% had diabetes. BDs reported significantly more exercise per week (mean: patients with CHC = 193.6 minutes/week and BDs = 280.4 minutes/week; P = .039) and had a significantly greater MAS (mean: patients with CHC = 77.2 and BDs = 87.4, P = .0001) and AAS (mean: patients with CHC = 72.58 and BDs = 83.8, P = .0001). Stepwise multiple regression analysis proposed 2 models predicting AAS: the presence of CHC (R = .445; R(2) = .198; adjusted R(2) = .184); and the presence of CHC and presence of hypertension (R = .537; R(2) = .289; adjusted R(2) = .263). BDs consumed significantly more alcohol and starchy foods than did patients with CHC (P = .0001 and P = .031, respectively), which may be explained by the compliance of patients with CHC to their hepatologist's recommendations regarding the minimization of alcohol consumption. CONCLUSIONS: Persons with CHC participate in less activity and less vigorous physical activity than do BDs and consume less starch and alcohol. These data about activity level and dietary intake in patients with CHC are novel; few data on these topics have been published previously. Low level of activity adds a substantial risk to this overweight CHC population, many of whom have multiple components of metabolic syndrome.