scholarly journals The Effect of Hepatitis C Virologic Clearance on Cardiovascular Disease Biomarkers in Human Immunodeficiency Virus/Hepatitis C Virus Coinfection

2014 ◽  
Vol 1 (3) ◽  
Author(s):  
Kara W. Chew ◽  
Lei Hua ◽  
Debika Bhattacharya ◽  
Adeel A. Butt ◽  
Lorelei Bornfleth ◽  
...  

Abstract Background.  Successful hepatitis C virus (HCV) treatment may reduce cardiovascular disease (CVD) risk and improve levels of CVD biomarkers produced outside the liver (nonhepatic biomarkers). Methods.  Stored serum or plasma from before and 24 weeks after end of HCV treatment (EOT) from human immunodeficiency virus (HIV)/HCV-coinfected subjects who received up to 72 weeks of peginterferon/ribavirin, 27 with and 27 without sustained virologic response (SVR) matched by race, ethnicity and sex, were tested for nonhepatic (soluble intercellular adhesion molecule-1 [sICAM-1], soluble P-selectin [sP-selectin], interleukin [IL]-6, d-dimer, and lipoprotein-associated phospholipase A2 [Lp-PLA2]) and hepatic (cholesterol and high-sensitivity C-reactive protein) CVD and macrophage activation markers (soluble CD163 [sCD163] and soluble CD14). Changes in biomarkers and their association with SVR were examined by t tests or Wilcoxon tests and regression models. Results.  Of the 54 subjects, 30 were white, 24 were black, and 44 were male. Pretreatment levels of nonhepatic biomarkers were high: sICAM-1 overall median, 439.2 ng/mL (interquartile range [IQR], 365.6–592.8]; sP-selectin, 146.7 ng/mL (IQR, 94.1–209.9), and IL-6, 2.32 pg/mL (IQR, 1.61–3.49). Thirty-seven of 52 (71%) subjects had Lp-PLA2 >235 ng/mL. Sustained virologic response was associated with decrease in sICAM-1 (P = .033) and sCD163 (P = .042); this result was attenuated after controlling for changes in the alanine aminotransferase level. At 24 weeks after EOT, 17 (63%) SVRs had Lp-PLA2 >235 ng/mL vs 25 (93%) non-SVRs (P = .021). Conclusions.  Hepatitis C virus clearance may reduce hepatic and, subsequently, systemic inflammation and CVD risk in HIV/HCV coinfection.

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S562-S563
Author(s):  
Poonam Mathur ◽  
Roman Kaplan ◽  
Amanda Theppote ◽  
Shyam Kottilil ◽  
Eleanor Wilson

Abstract Background Sustained virologic response (SVR) after hepatitis C virus (HCV) treatment with either Interferon (IFN)-based or IFN-free regimens with direct-acting antivirals (DAAs) has been shown to reduce cardiovascular disease (CVD) events in majority white populations stratified by ASCVD score. However, the effect of IFN-free therapy on lipid profiles after SVR, as an indirect measure of CVD risk, is unknown in Black patients. Methods We evaluated HCV-infected Veterans from the Baltimore VA who were treated with DAAs between 2015-2019. We performed a retrospective analysis comparing lipid profile changes following SVR among those with early stage (F0-F2) fibrosis and advanced liver disease (ALD, F3-F4 fibrosis) using two-tailed paired t-tests. Independent t-tests were used to assess differences in lipid profiles based on fibrosis stage in patients with HIV and Type II Diabetes Mellitus (DM2). Results Of those treated for HCV (n=1,528), 96% (n=1,474) achieved SVR. Demographics are shown in Table 1. Most patients were Black males (75%) and a minority (2.7%) received statin therapy during treatment (Table 1). Of 1,094 patients for whom data was available, an increase in total cholesterol (TC) and LDL (p< 0.01 for both) was seen an average of 17 months after SVR, regardless of fibrosis stage (Figure 1). A significant decrease in triglyceride levels (p=0.04) was also seen in the ALD group after SVR (Figure 1). Mean pre-treatment HCV RNA level was comparable between fibrosis groups (F0-F2: 6.35 logs, F3-F4: 6.37 logs, p=0.46). There were 101 and 436 patients with HIV and DM2, respectively, for whom pre-treatment liver fibrosis data was available. In both groups, there were significant increases in LDL (p=0.008 (HIV), p=0.003 (DM2)) among patients with ALD following SVR. Table 1. Baseline characteristics of treated HCV-infected persons who achieved SVR. Figure 1. Mean lipid profile parameters before and after HCV treatment for patients who achieved SVR. TC was measured a mean of 8.1 months (228 days, SD 333 days) before treatment and 17.4 months (488 days, SD 196 days) after SVR. LDL was measured a mean of 8 months (224 days, SD 284 days) before treatment and 17.5 months (492 days, SD 201 days) after SVR. *=differences in means using paired t-test were statistically significant with p<0.05. HCV= Hepatitis C Virus, SVR= Sustained Virologic Response TC=Total Cholesterol, HDL= High Density Lipoprotein, LDL= Lipoprotein, TG= Triglycerides. Conclusion In a cohort of mostly Black HCV-infected Veterans, significant increases in TC, driven by increases in LDL, were seen after SVR regardless of fibrosis stage. In addition, patients with ALD and HIV or DM2, who have an inherently higher risk of CVD, had increased LDL levels, suggesting that these patients should be screened and treated for HCV prior to development of ALD. Correlates such as the ASCVD score should be considered in the timing of HCV treatment, in order to reduce the long-term risk of CVD. Disclosures Shyam Kottilil, MD PhD, Arbutus Pharmaceuticals (Grant/Research Support)Gilead Sciences (Grant/Research Support)Merck Inc (Grant/Research Support, Advisor or Review Panel member)


2017 ◽  
Vol 4 (2) ◽  
Author(s):  
Giovanni Guaraldi ◽  
Roberto Rossotti ◽  
Gabriella Verucchi ◽  
Marcello Tavio ◽  
Luisa Pasulo ◽  
...  

Abstract This retrospective study reports the data of sofosbuvir-based anti-hepatitis C virus treatment in 24 candidates and 24 recipients of liver transplantation coinfected with human immunodeficiency virus. Sustained virologic response was cumulatively 85% (90% and 100% in those treated with optimal schedules pre- and posttransplant, respectively).


Author(s):  
Nadine Kronfli ◽  
Jim Young ◽  
Shouao Wang ◽  
Joseph Cox ◽  
Sharon Walmsley ◽  
...  

Abstract Background Noninvasive markers of liver fibrosis such as aspartate aminotransferase-to-platelet ratio (APRI) and transient elastography (TE) have largely replaced liver biopsy for staging hepatitis C virus (HCV). As there is little longitudinal data, we compared changes in these markers before and after sustained virologic response (SVR) in human immunodeficiency virus (HIV)-HCV coinfected patients. Methods Participants from the Canadian Coinfection Cohort study who achieved SVR after a first treatment with either interferon/ribavirin or direct acting antivirals (DAAs), with at least 1 pre- and posttreatment fibrosis measure were selected. Changes in APRI or TE (DAA era only) were modeled using a generalized additive mixed model, assuming a gamma distribution and adjusting for sex, age at HCV acquisition, duration of HCV infection, and time-dependent body mass index, binge drinking, and detectable HIV RNA. Results Of 1981 patients, 151 achieved SVR with interferon and 553 with DAAs; 94 and 382 met inclusion criteria, respectively. In the DAA era, APRI increased (0.03 units/year; 95% credible interval (CrI): −.05, .12) before, declined dramatically during, and then changed minimally (−0.03 units/year; 95% CrI: −.06, .01) after treatment. TE values, however, increased (0.74 kPa/year; 95% CrI: .36, 1.14) before treatment, changed little by the end of treatment, and then declined (−0.55 kPa/year; 95% CrI: −.80, −.31) after SVR. Conclusions TE should be the preferred noninvasive tool for monitoring fibrosis regression following cure. Future studies should assess the risk of liver-related outcomes such as hepatocellular carcinoma according to trajectories of fibrosis regression measured using TE to determine if and when it will become safe to discontinue screening.


2020 ◽  
Vol 7 (4) ◽  
Author(s):  
Ruth O Adekunle ◽  
Kathryn DeSilva ◽  
Emily J Cartwright

Abstract Background Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) coinfection is associated with accelerated progression to cirrhosis, end-stage liver disease, and liver-associated death. It is fortunate that curative direct-acting antivirals for the treatment of HCV are widely available in the VA healthcare system. We attempted to identify, evaluate, and treat all HIV/HCV-coinfected persons at the Atlanta VA Healthcare System. Methods Human immunodeficiency virus/HCV-coinfected persons at Atlanta VA between 2015 and 2018 were identified using the HIV Atlanta Veterans Affairs Cohort Study and Hepatitis C VA Clinical Case Registry. Retrospective reviews of each electronic medical record were conducted by the hepatitis C clinical team for validation. The primary end point was achieving sustained virologic response. Results One hundred thirty-eight veterans with HIV and hepatitis C viremia were identified. One hundred twenty-five (90%) were evaluated for treatment and 113 (91%) were initiated on direct-acting antiviral therapy. Median age at initiation of treatment was 60 years and the majority were black race (90%). Genotype 1a was most common (70%) and 41% had compensated cirrhosis. One hundred eight completed treatment and 96% achieved sustained virologic response. Six veterans had virologic relapse; 4 had treatment-emergent resistance mutations in the NS5a gene. Mean CD4 was 580 cells/mm3 with HIV viral suppression in 82% of the cohort. In those not treated, unstable housing (25%), active substance use (31%), and psychiatric conditions (42%) were identified barriers to care. Conclusions Through a concerted, systematic effort, over 80% of HIV/hepatitis C persons in the Atlanta VA have been initiated on treatment for hepatitis C, 96% of which have been cured.


2019 ◽  
Vol 30 (7) ◽  
pp. 689-695 ◽  
Author(s):  
Jennifer O Lam ◽  
Leo B Hurley ◽  
Scott Chamberland ◽  
Jamila H Champsi ◽  
Laura C Gittleman ◽  
...  

U.S. guidelines recommend that patients coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) be prioritized for HCV treatment with direct-acting antiviral agents (DAAs), but the high cost of DAAs may contribute to disparities in treatment uptake and outcomes. We evaluated DAA initiation and effectiveness in HIV/HCV-coinfected patients in a U.S.-based healthcare system during October 2014–December 2017. Of 462 HIV/HCV-coinfected patients, 276 initiated DAAs (70% cumulative proportion treated over three years). Lower likelihood of DAA initiation was observed among patients with Medicare (government-sponsored insurance) versus commercial insurance (adjusted rate ratio [aRR] = 0.62, 95% CI = 0.46–0.84), patients with drug abuse diagnoses (aRR = 0.72, 95% CI = 0.54–0.97), patients with CD4 cell count <200 cells/µl versus ≥500 (aRR = 0.45, 95% CI = 0.23–0.91), and patients without prior HCV treatment (aRR = 0.68, 95% CI = 0.48–0.97). There were no significant differences in DAA initiation by age, gender, race/ethnicity, socioeconomic status, HIV transmission risk, alcohol use, smoking, fibrosis level, HIV RNA levels, antiretroviral therapy use, hepatitis B infection, or number of outpatient visits. Ninety-five percent of patients achieved sustained virologic response (SVR). We found little evidence of sociodemographic disparities in DAA initiation among HIV/HCV-coinfected patients, and SVR rates were high. Efforts are needed to increase DAA uptake among coinfected Medicare enrollees, patients with drug abuse diagnoses, patients with low CD4 cell count, and patients receiving first-time HCV treatment.


2017 ◽  
Vol 4 (1) ◽  
Author(s):  
Tanyaporn Wansom ◽  
Oluwaseun Falade-Nwulia ◽  
Catherine G. Sutcliffe ◽  
Shruti H. Mehta ◽  
Richard D. Moore ◽  
...  

Abstract Background Hepatitis C is a major cause of mortality among human immunodeficiency virus (HIV)-infected patients, yet hepatitis C virus (HCV) treatment uptake has historically been low. Although the removal of interferon removes a major barrier to HCV treatment uptake, oral therapies alone may not fully eliminate barriers in this population. Methods Within the Johns Hopkins Hospital HIV cohort, a nested case-control study was conducted to identify cases, defined as patients initiating HCV treatment between January 1996 and 2013, and controls, which were selected using incidence density sampling (3:1 ratio). Controls were matched to cases on date of enrollment. Conditional logistic regression was used to evaluate factors associated with HCV treatment initiation. Results Among 208 treated cases and 624 untreated controls, the presence of advanced fibrosis (odds ratio [OR], 2.23; 95% confidence interval [CI], 1.26–3.95), recent active drug use (OR, 0.36; 95% CI, 0.19–0.69), and non-black race (OR, 2.01; 95% CI, 1.26–3.20) were independently associated with initiation of HCV therapy. An increasing proportion of missed visits was also independently associated with lower odds of HCV treatment (25%–49% missed visits [OR, 0.49; 95% CI, 0.27–0.91] and ≥50% missed visits [OR, 0.24; 95% CI, 0.12–0.48]). Conclusions Interferon-free treatments may not be sufficient to fully overcome barriers to HCV care in HIV-infected patients. Interventions to increase engagement in care for HIV and substance use are needed to expand HCV treatment uptake.


2003 ◽  
Vol 188 (10) ◽  
pp. 1498-1507 ◽  
Author(s):  
Francesca J. Torriani ◽  
Ruy M. Ribeiro ◽  
Tari L. Gilbert ◽  
Uschi M. Schrenk ◽  
Marietta Clauson ◽  
...  

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