Abdul-Badi Abou-Samra

Effect of addition of statins to antiviral therapy in hepatitis C virus-infected persons: Results from ERCHIVES.

3‐hydroxy‐3‐methylglutaryl coenzyme A reductase inhibitors (statins) have been variably noted to affect hepatitis C virus (HCV) treatment response, fibrosis progression, and hepatocellular carcinoma (HCC) incidence, with some having a more potent effect than others. We sought to determine the impact of adding statins to antiviral therapy upon sustained virological response (SVR) rates, fibrosis progression, and HCC development among HCV‐infected persons using the Electronically Retrieved Cohort of HCV Infected Veterans (ERCHIVES), an established, longitudinal, national cohort of HCV‐infected veterans. Within ERCHIVES, we identified those who received HCV treatment and a follow‐up of >24 months after treatment completion. We excluded those with human immunodeficiency virus coinfection, hepatitis B surface antigen positivity, cirrhosis, and HCC at baseline. Our main outcomes were liver fibrosis progression measured by FIB‐4 scores, SVR rates, and incident HCC (iHCC). Among 7,248 eligible subjects, 46% received statin therapy. Statin use was significantly associated with attaining SVR (39.2% vs. 33.3%; P < 0.01), decreased cirrhosis development (17.3% vs. 25.2%; P < 0.001), and decreased iHCC (1.2% vs. 2.6%; P < 0.01). Statins remained significantly associated with increased odds of SVR (odds ratio = 1.44; 95% confidence interval [CI] = 1.29, 1.61), but lower fibrosis progression rate, lower risk of progression to cirrhosis (hazard ratio [HR] = 0.56; 95% CI = −0.50, 0.63), and of incident HCC (HR = 0.51; 95% CI = 0.34, 0.76) after adjusting for other relevant clinical factors. Conclusions: Statin use was associated with improved virological response (VR) rates to antiviral therapy and decreased progression of liver fibrosis and incidence of HCC among a large cohort of HCV‐positive Veterans. These data support the use of statins in patients with HCV. (Hepatology 2015) Hepatology 2015;62:365–374

The short‐term incidence of hepatocellular carcinoma is not increased after hepatitis C treatment with direct‐acting antivirals: An ERCHIVES study

Recent studies have reported higher rates of hepatocellular carcinoma (HCC) in individuals treated with direct‐acting antivirals (DAAs). However, making definitive conclusions has been challenging because of the heterogeneous populations and methodologies of these reports. We investigated whether DAA use is associated with higher rates of incident HCC compared to treatment with interferon (IFN)‐based regimens. We performed a retrospective, population‐based cohort study using the Electronically Retrieved Cohort of HCV Infected Veterans (ERCHIVES) database. In a cohort of 17,836 persons, sustained virological response (SVR) was achieved by 66.6% and 96.2% of the IFN and DAA groups, respectively. Among all treated persons, risk of HCC was not higher in the DAA group compared to the IFN group (hazard ratio, 1.07; 95% confidence interval, 0.55, 2.08). Among persons with cirrhosis who achieved SVR, neither the HCC incidence rate nor HCC‐free survival were significantly different in the DAA group compared to the IFN group (21.2 vs. 22.8 per 1,000 person‐years; P = 0.78 and log‐rank P = 0.17, respectively). Untreated persons with cirrhosis had a significantly higher HCC incidence rate (45.3 per 1,000 person‐years) compared to those treated with either IFN or DAAs (P = 0.03). Both groups of treated persons had significantly lower probability of HCC development compared to untreated persons (log‐rank, P = 0.0004). Conclusion: DAA treatment is not associated with a higher risk of HCC in persons with cirrhosis with chronic HCV infection in the short term. Previously reported higher rates of HCC associated with DAA treatment may be explained by both the presence of relatively fewer baseline HCC risk factors in persons treated with IFN as well as selection bias, given that DAA regimens were used to treat persons at higher risk for developing HCC. (Hepatology 2018;67:2244‐2253).

Effect of Paritaprevir/Ritonavir/Ombitasvir/Dasabuvir and Ledipasvir/Sofosbuvir Regimens on Survival Compared With Untreated Hepatitis C Virus–Infected Persons: Results From ERCHIVES

Background Interferon-based regimens are associated with a substantial survival benefit for persons infected with hepatitis C virus (HCV). Survival data with direct-acting antiviral agents are not available. We conducted this study to quantify the effect of paritaprevir/ritonavir, ombitasvir, dasabuvir (PrOD) and ledipasvir/sofosbuvir (LDV/SOF) regimens upon mortality. Methods In the Electronically Retrieved Cohort of HCV Infected Veterans (ERCHIVES), a well-established national cohort of HCV-infected Veterans, we identified HCV-infected persons initiated on PrOD or LDV/SOF, excluding those with human immunodeficiency virus, hepatitis B surface antigen positivity, hepatocellular carcinoma, or missing HCV RNA or FIB-4 scores. For each case, we identified a propensity score-matched control never initiated on treatment. Primary outcome was survival. Outcomes were assessed using frequency of events, Kaplan-Meier curves, and Cox proportional hazards regression analyses. Results We identified 1473 persons on PrOD, 5497 on LDV/SOF, and 6970 propensity score-matched untreated persons. Treated persons were more likely to be obese and have cirrhosis, but less likely to have stage 3-5 chronic kidney disease (CKD), alcohol or drug abuse or dependence diagnosis, and anemia. The proportion of persons who died was higher in the untreated group compared with either treatment group (PrOD, 0.3%; LDV/SOF, 1.4%; untreated controls, 2.5%; P < .001). A significantly larger percentage of treated patients survived to 18 months of follow-up, compared with untreated controls (P < .001). In multivariable Cox regression analysis, treatment with either regimen (hazard ratio [HR], 0.43; 95% confidence interval [CI], .33-.57) and attainment of sustained virologic response (SVR) were associated with significantly lower mortality (HR, 0.57; 95% CI, .33-.99). Conclusions Treatment with PrOD or LDV/SOF and SVR are associated with a significant mortality benefit, apparent within the first 18 months of treatment.

Antibiotic prescription patterns for upper respiratory tract infections in the outpatient Qatari population in the private sector

BACKGROUND Antibiotics are often inappropriately prescribed for upper respiratory tract infections (URTIs) in developed countries. Data on the proportion of inappropriate prescriptions are lacking from the Middle East and other developing countries. METHODS Health insurance claims for all antibiotics prescribed for URTIs in the private sector in the State of Qatar between May 2014 and December 2015 were retrieved. During the study period, health insurance was limited to Qatari nationals. Topical antibiotics were excluded. Data on the prescribers specialty, as listed with the licensing authority, were also retrieved. Diagnoses were classified as appropriate or inappropriate based on the likelihood of a bacterial etiology that may warrant antibiotic use. RESULTS A total of 75 733 claims were made during the study period. Of these, 41 556 (55%) were for an appropriate indication, while 34 177 (45%) were for an inappropriate indication. The most common antibiotic classes prescribed were cephalosporins (43% of claims; 44% inappropriate), penicillins (28% of claims; 44% inappropriate), macrolides (19% of claims; 52% inappropriate), and fluoroquinolones (9% of claims; 40% inappropriate). Nearly 5% of antibiotics were prescribed in intravenous formulations. The most common prescribers were General/Family Practice physicians (53% of claims; 50% inappropriate), followed by Pediatrics (18.6% of claims; 36% inappropriate) and Internal Medicine (14.1% of claims; 44% inappropriate). CONCLUSIONS There is a high rate of inappropriate antibiotic prescription for acute URTIs in the private health care sector in the State of Qatar. Further studies are needed to determine the population-based rates across the country. Interventions to decrease inappropriate use in such settings are urgently needed.

Hepatitis B reactivation and outcomes in persons treated with directly acting antiviral agents against hepatitis C virus: results from ERCHIVES.

Higher risk of hepatitis B reactivation (HBV‐r) has been reported in patients with hepatitis C treated with newer directly acting antiviral agents (DAAs).

Risk of Acute Myocardial Infarction Among Hepatitis C Virus (HCV)-Positive and HCV-Negative Men at Various Lipid Levels: Results From ERCHIVES

Background Risk of acute myocardial infarction (AMI) among hepatitis C virus (HCV)-positive versus HCV-negative persons with similar lipid levels is unknown. We determined incident AMI rates among HCV-positive and HCV-negative men among various lipid strata. Methods We created a propensity score matched (PSM) cohort and a low cardiovascular disease (CVD) risk cohort. Primary outcome was incident AMI rates by HCV status in each lipid strata using National Cholesterol Program guidelines for lipid strata. Results We identified 85863 HCV-positive and HCV-negative men in the PSM population. The incidence rates/1000 patient-years (95% confidence interval [CI]) for AMI among total cholesterol (TC) 200-239 stratum were 5.3 (4.89, 5.71) for HCV-positive versus 4.71 (4.42, 5) for HCV-negative men (P = .02) and for TC >240 mg/dL were 7.38 (6.49, 8.26) versus 6.17 (5.64, 6.71) (P = .02). For low-density lipoprotein cholesterol (LDL) of 130-159 mg/dL, AMI rates were 5.44 (4.97, 5.91) for HCV-positive and 4.81 (4.48, 5.14) for HCV-negative men (P = .03). The rise in risk with increasing lipid levels was greater in younger HCV-positive than in HCV-negative men (e.g., TC > 240 mg/dL: age >50 HR 1.38 [HCV-positive] and 1.12 [HCV-negative]; age ≤50 HR 1.6 [HCV-positive] and 1.29 [HCV-negative]), and more profoundly altered in HCV-positive men by lipid lowering therapy (change in HR with lipid-lowering therapy for TC >240 mg/dL from 1.82 to 1.19 [HCV-positive] from 1.48 to 1.03 [HCV-negative]). Conclusions HCV-positive men have a higher risk of AMI than HCV-negative men at higher TC/LDL levels; this risk is more pronounced at a younger age. Lipid lowering therapy significantly reduces this risk, with more profound reduction among HCV-positive versus HCV-negative men at similar lipid levels.

Prevalence of newly detected diabetes in pregnancy in Qatar, using universal screening

Background Diabetes first detected during pregnancy is currently divided into gestational diabetes mellitus (GDM) and diabetes mellitus (DM)- most of which are type 2 DM (T2DM). This study aims to define the prevalence and outcomes of diabetes first detected in pregnancy based on 75-gram oral glucose tolerance test (OGTT)using the recent WHO/IADPSG guidelines in a high-risk population. Methods This is a retrospective study that included all patients who underwent a 75 g (OGTT) between Jan 2016 and Apr 2016 and excluded patients with known pre-conception diabetes. Results The overall prevalence of newly detected diabetes in pregnancy among the 2000 patients who fulfilled the inclusion/exclusion criteria was 24.0% (95% CI 22.1–25.9) of which T2DM was 2.5% (95% CI 1.9–3.3), and GDM was 21.5% (95% CI 19.7–23.3). The prevalence of newly detected diabetes in pregnancy was similar among the different ethnic groups. The T2DM group was older (mean age in years was 34 ±5.7 vs 31.7±5.7 vs 29.7 ±5.7, p<0.001); and has a higher mean BMI (32.4±6.4 kg/m2 vs 31.7±6.2 kg/m2 vs 29.7± 6.2 kg/m2, p< 0.01) than the GDM and the non-DM groups, respectively. The frequency of pre-eclampsia, pre-term delivery, Caesarean-section, macrosomia, LGA and neonatal ICU admissions were significantly higher in the T2DM group compared to GDM and non-DM groups. Conclusion Diabetes first detected in pregnancy is equally prevalent among the various ethnic groups residing in Qatar. Newly detected T2DM carries a higher risk of poor pregnancy outcomes; stressing the importance of proper classification of cases of newly detected diabetes in pregnancy.

HCV treatment initiation in persons with chronic kidney disease in the directly acting antiviral agents era: Results from ERCHIVES

Newer direct acting antiviral agents against HCV (DAAs) are safe and efficacious in persons with chronic kidney disease (CKD). Whether approval of newer DAAs has resulted in more persons with CKD initiating HCV treatment remains unknown.

HCV Treatment Initiation in Patients with Chronic Kidney Disease: Results from ERCHIVES

Abstract Background Newer directing antiviral agents against HCV (DAAs) are safe and efficacious in persons with chronic kidney disease (CKD). Whether availability of these newer DAAs has resulted in more persons with CKD initiating HCV treatment remains unknown. Methods We identified HCV+ persons in ERCHIVES. We excluded HIV+ and HBsAg+ and those with missing HCV RNA and eGFR data. We determined the CKD stage according to National Kidney Foundation criteria. We determined the number of persons initiated on any of the approved DAA-regimen (defined as >14 days of DAA prescription). Logistic regression analyses was used to determine factors associated with treatment initiation. Results Among 76,513 evaluable persons, 21.1% initiated DAA treatment. Initiation rates differed significantly by CKD stage: 21.1% (15,136/68,469) for eGFR>90mL/minute/1.73m2 and CKD stage-2; 14.0% 9853/6,086) for CKD stage 3; and 7.6% (148/1,958) for CKD stage-4/5. Those with CKD stage-3 were 35% less likely and those with CKD stage-4/5 were 65% less likely to initiate treatment with a DAA compared with those with baseline eGFR>90mL/minute/1.73m2. Those with Body Mass Index (BMI)>30 were more likely to initiate treatment (OR 1.24, 95% CI 1.19,1.29). Treatment initiation was less likely in HCV genotype 2 or 3 and those with diabetes (OR 0.82, 95% CI 0.78,0.86), cardiovascular disease (OR 0.73, 95% CI 0.68,0.78), alcohol abuse or dependence (OR 0.75, 95% CI 0.72,0.78) or cirrhosis (OR 0.85, 95% CI 0.80,0.89) at baseline. Conclusion Persons with more advanced CKD are less likely to receive treatment for HCV. Strategies are needed to improve treatment rates in the HCV/CKD population. Disclosures A. Butt, Merck: Investigator, Grant recipient. A. Puenpatom, Merck: Employee, Salary. J. M. Arduino, Merck: Employee, Salary. R. Kumar, Merck: Employee, Salary

Effectiveness and Safety of Sofosbuvir/Ledipasvir and Paritaprevir/ritonavir / Ombitasvir + Dasabuvir in Patients with Chronic Kidney Diseases: Results from ERCHIVES

Abstract Background Chronic kidney disease (CKD) was a relative contraindication to HCV treatment in the interferon/ribavirin era due to poor tolerability and lower efficacy. Our aim was to determine the effectiveness treatment completion, and safety of sofosbuvir/ledipasvir (SOF/LDV) and paritaprevir/ritonavir/ombitasvir/dasabuvir (PrOD) regimens in persons with CKD. Methods We identified all persons started on a SOF/LDV or PrOD regimen in ERCHIVES before 30 April 2016. We excluded those with missing HCV genotype, or eGFR values. We determined treatment completion, sustained virologic response (SVR) rates and proportion of persons with worseningrenal function or developing grade 3/4 anemia. Results We identified 9,837 persons on SOF/LDV, 3,826 on SOF/LDV+RBV, 1,017 on PrOD and 2,944 on PrOD+RBV. Genotype 1a was the predominant genotype for SOF/LDV+RBV (77.3% no RBV; 70.0% with RBV) and PrOD+RBV (79.5%) groups, while only 4.3% of PrOD with no RBV group were genotype 1a. Among treated patients, the prevalence of patients with stage 4–5 CKD was 0.8% (SOF/LDV + RBV), 1.1% (SOF/LDVno RBV), 2.2% (PrOD +RBV) and 5.4% (PrOD no RBV). Among 13,663 total persons on SOF/LDV, 67.8% completed treatment while the treatment completion rate of those on PrOD was 74.0% (N = 2,932/3,961) (Table 1). The overall SVR rates of persons on SOF/LDV or PrOD regimens were 96.3%. A drop in treatment completion rates was seen in CKD stage 4–5 and those on PrOD+RBV, but the impact of RBV on SVR was unclear. While about one-third of the persons with a CKD stage 1–2 experienced a >10 mL/minute/1,73m2, about 15% decline among those with CKD stage 3. The incidence of grade3/4 anemia by CKD stages increased significantly across the treatment groups. Grade 3/4 anemia ranged from 9.7% (SOF/LDV) to 21.8% (PrOD) among patients with CKD stage 4–5 (Table 2). Conclusion SVR rates among persons treated with SOF/LDV or PrOD were high in the CKD population despite 22% not completing the treatment regimen. Incidence of grade3/4 anemia increased significantly in CKD stage 4–5 across the treatment groups. Disclosures A. Butt, Merck: Investigator, Grant recipient.A. Puenpatom, Merck: Employee, Salary. J. M. Arduino, Merck: Employee, Salary. R. Kumar, Merck: Employee, Salary