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Prevalence and Predictors of Hepatic Steatosis in Patients with HIV/HCV Coinfection and the Impact of HCV Eradication
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Download the PDF here
Download the PDF here
Download the PDF here
"Notably, a significant increase in CAP (from 225 ± 52.9 to 235 ± 50.7 dB/m; p = 0.047) was observed after HCV eradication.....Among all 247 HIV/HCV-coinfected patients, HS was prevalent in 31%, mean age was 43.3 years, 75% were male"
from Jules: previous studies find fatty liver in HIV+ associated early old nuke use, metabolic disorders, hypertension, diabetes, elected lipids, belly fat, obesity. Fatty liver is not well understood & not on the radar with HIV clinicians. Elevated ALTs, ASTs could be a signal but many with normal liver enzymes could also have fatty liver. The result of fibrosis and advancing liver disease is the outcome of concern.
"NAFLD is an umbrella term that comprises a continuum of liver conditions varying in severity of injury and resulting fibrosis.....highly variable natural history of NAFLD reflects the diverse but convergent impacts of the environment, the microbiome, metabolism, comorbidities and genetic risk factors......Presence of metabolic syndrome (MetS) in an individual is the strongest risk factor for NAFLD and NASH (Box 2). MetS is variably defined, but typically includes increased waist circumference (i.e., obesity), hyperglycemia, dyslipidemia and systemic hypertension (HTN)18. .......Among the features of MetS, diabetes mellitus has the clearest biologic link to the progression of NAFLD, and up to 75% of individuals with type 2 diabetes have NAFLD, those with NAFLD and diabetes are also at increased risk of developing liver-related complications..."
By using the CAP as a noninvasive tool for HS assessment, we found that nearly one-third of HIV/HCV presenting at our center are affected by HS-with similar prevalence being reported in previous reports.14 The use of PI-containing ART and the duration of HIV infection were found to increase the risk of HS in HIV/HCV patients. Further, we observed an increase of CAP after DAA-induced HCV eradication and an increase in TCHOL levels-indicating an expressed impact of HCV on hepatic lipid metabolism.....Mean age was 43.3 years, the majority were Caucasian (96%; 238/247) and male (75%; 185/247), 55% (135/247) had a "people who inject drugs" (PWID) background, while 30% (73/247) were categorized as "men who have sex with men" (MSM)......Ultimately, it remains to be established if HIV patients with elevated CAP values and LDL levels after HCV eradication are at higher risk of HS and its associated metabolic and cardiovascular events.
CAP value ≥248 dB/m defined HS and all CAP values were adapted to compensate for body mass index (BMI) and diabetes mellitus. Among all 247 HIV/HCV-coinfected patients, HS was prevalent in 31%, mean age was 43.3 years, 75% were male, the main ethnicity was Caucasian (96%), and mean BMI was 23.33 kg/m2. Independent risk factors for HS were BMI, years exposed to HIV, PNPLA3 G-alleles, and protease inhibitor (PI) intake. Notably, a significant increase in CAP (from 225 ± 52.9 to 235 ± 50.7 dB/m; p = 0.047) was observed after HCV eradication
However, variability is also a concern in CAP measurements. While there are insufficient data on the intra- and interobserver agreement of individual CAP measurements, our personal experience is that CAP measurements well correlate with steatosis and are accurate if quality criteria for LSM are fulfilled (as in our study). Still, we cannot completely exclude that CAP variability impacted on the results.
Still, a cutoff for a "clinically meaningful" change in CAP that corresponds to clinical outcomes has not yet been established. A recently published study suggested that a change of more than 38 dB/m in CAP would indicate a >1% change in magnetic resonance imaging-estimated proton density fat fraction (PDFF).54 However, in general, CAP had a poor performance for predicting changes in PDFF and the study was not designed to assess the clinical impact of this absolute change in CAP. Thus, our results derived from the follow-up cohort are limited by the unknown clinical significance of the measured dynamics in CAP.
PREDICTORS- Higher BMI was associated with the presence of HS (22.6 ± 3.79 vs. 24.9 ± 4.3 kg/m2; p < 0.001). Moreover, HOMA-IR was slightly increased [2.32 (3.69) vs. 3.32 (2.17); p = 0.047] in individuals with HS, while plasma lipids did not significantly differ (Fig. 2A). Most patients with PWID as the suspected route of HCV transmission had HS (71% vs. 47%; p < 0.001), whereas opioid substitution therapy, DM, arterial hypertension, and ethnicity were not associated with HS (Supplementary Table S1). While HS was absent in all three Asian patients, the number of subjects with non-Caucasian race (African American N = 4, Hispanic N = 2, Asian N = 3) seemed too small to accurately detect differences in HS prevalence and dynamics according to race in our prediction models. Further, protease inhibitor (PI) intake, as part of ART, was more frequent among patients with HS [39% (29/74) vs. 11% (18/167); p < 0.001] (Fig. 2B).
NATAP Dedicated Fatty Liver site
EASL: MR elastography based fibrosis correlates with clinical liver events in patients with non-alcoholic fatty liver disease: A multi-center study - (05/08/19)
Mechanisms of NAFLD development and therapeutic strategies - (07/18/17)
EASL: HIV-infected individuals at high risk of non-alcoholic fatty liver disease (NAFLD) and progressive liver disease- ILC 2019: Latest studies confirm increasing burden of NAFLD in people with HIV infection as viral hepatitis prevalence and associated mortality decline - (04/12/19)
CROI: FATTY LIVER DISEASE: A GROWING CONCERN - - (04/12/17) a plenary talk by noted fatty liver expert Rohit Loomba from UCSD
CROI: Changes in Liver Fibrosis and Steatosis in HIV Mono-Infected patients over 24 months - 50% have fatty liver at average age of 46 - (03/28/17)...- AZT, ddI, d4T - caused fatty liver. HIV itself causes fatty liver, which was found in this study, and unsuppressed viral load & low nadir CD4 contribute to fatty liver. The metabolic syndrome caused by HIV which persists depute suppressed HIV & high CD4s I am sure contributes to fatty liver. Again, diet & exercise are important, but more important is to pay greater attention to this health hazard particularly as HIV patient population ages. There are no really reliable biomarkers so more research is needed. But fatty liver, hepatic steatosis can cause severe liver disease & fibrosis, this needs more attention in HIV because we still do not have much data on the contribution of each ART & class, ARTs used in this modern era.
CROI: LIVER STEATOSIS AND FIBROSIS IN AT-RISK EUROPEAN HIV-MONOINFECTED PATIENTS - 64% with steatosis among those who had elevated LFTs and/or metabolic syndrome and/or lipodystrophy - (03/28/17)
EASL: LIFESTYLE FOR THE TREATMENT OF NON-ALCOHOLIC FATTY LIVER DISEASE - (04/30/19)
EASL: APPLICATION OF GUIDELINES FOR FATTY LIVER IN TWO PROSPECTIVE COHORTS OF HIV+ PATIENTS: 32% have NAFLD; among those without NAFLD 18% with elevated ALT - (04/22/19)
EASL: The Increasing Importance of Non-alcoholic Fatty Liver Disease (NAFLD) in Patients with Human Immunodeficiency Virus (HIV) - (04/18/19)
Fatty Liver in HIV - (07/18/17)
AGE: More than 40% of HIV group has hepatic steatosis, regardless of age - Mark Mascolini (09/19/18)
EASL: Liver enzymes cut offs in patients with advanced non-alcoholic fatty liver disease: A multi-center study - (05/07/19)
EASL: Insulin resistance is a cause of steatosis and fibrosis progression in chronic hepatitis C - (05/07/19)
EASL: LIFESTYLE FOR THE TREATMENT OF NON-ALCOHOLIC FATTY LIVER DISEASE - (04/30/19)
EASL: Food, Obesity and Non-Alcoholic Fatty Liver Disease (NAFLD) - (04/30/19)
EASL: A diet based on high-heat-treated foods promotes risk factors for diabetes mellitus and cardiovascular diseases - (04/23/19)
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Prevalence and Predictors of Hepatic Steatosis in Patients with HIV/HCV Coinfection and the Impact of HCV Eradication
Published Online:6 May 2019 - AIDS PATIENT CARE and STDs
Volume 33, Number 5, 2019 - David Chromy, MD,1,2 Mattias Mandorfer, MD,1,2 Theresa Bucsics, MD,1,2 Philipp Schwabl, MD,1,2
David Bauer, MD,1,2 Bernhard Scheiner, MD,1,2 Caroline Schmidbauer, MD,1,2 Gerold Felician Lang, MD,2,3
Thomas Szekeres, MD,4 Peter Ferenci, MD,1 Michael Trauner, MD,1 and Thomas Reiberger, MD1,2
Abstract
Human immunodeficiency virus (HIV)-induced metabolic abnormalities and antiretroviral therapy (ART), genetic factors, most importantly the rs738409 C > G p.I148M variant in the patatin-like phospholipase domain containing 3 (PNPLA3)-gene, as well as hepatitis C virus (HCV) coinfection may all cause hepatic steatosis (HS). However, recent studies suggest a protective effect of HCV infection on HS. Thus, we evaluated HS prior and after HCV eradication in an HIV/HCV-coinfected cohort at the Medical University of Vienna between January 2014 and June 2017. Two hundred forty-seven patients underwent liver stiffness measurement and controlled attenuation parameter (CAP)-based steatosis assessment. A subcohort of 138 patients also had follow-up CAP measurement after HCV eradication by direct-acting antivirals (DAAs). A CAP value ≥248 dB/m defined HS and all CAP values were adapted to compensate for body mass index (BMI) and diabetes mellitus. Among all 247 HIV/HCV-coinfected patients, HS was prevalent in 31%, mean age was 43.3 years, 75% were male, the main ethnicity was Caucasian (96%), and mean BMI was 23.33 kg/m2. Independent risk factors for HS were BMI, years exposed to HIV, PNPLA3 G-alleles, and protease inhibitor (PI) intake. Notably, a significant increase in CAP (from 225 ± 52.9 to 235 ± 50.7 dB/m; p = 0.047) was observed after HCV eradication, whereas patients on PI-containing ART experienced a significant decrease in CAP. Overall, one-third of HIV/HCV-coinfected patients are affected by HS with PI-based ART and PNPLA3 impacting on HS prevalence. While HCV eradication by DAAs increased HS, as assessed by CAP, future studies should account for metabolic syndrome and evaluate whether changes in CAP-based steatosis assessments correspond to a clinically relevant outcome.
Introduction
Hepatitis C virus (HCV)-related liver disease is a major contributor to morbidity and mortality in individuals infected with human immunodeficiency virus (HIV).1 Due to shared routes of transmission, HIV/HCV coinfection is common2 and has been associated with a more rapid progression toward severe liver disease, compared with HCV monoinfection.3 Several HIV-related factors such as drug-induced liver injury by antiretroviral therapy (ART) or immunological dysregulation might accelerate liver fibrosis progression and increase the risks for cirrhosis and hepatocellular carcinoma in HIV/HCV.4,5 Thus, non-AIDS-related mortality remains significantly increased among individuals infected with HIV, even in the era of modern ART.6
Prior studies have suggested a link between hepatic steatosis (HS) and liver fibrosis progression in HCV-infected patients,7 as well as an association with higher body mass index (BMI), diabetes mellitus (DM), older age, HCV genotype (GT) 3, hepatic inflammation,8 and a G-allele [rs738409(G)] in patatin-like phospholipase domain containing 3 (PNPLA3)-gene.9 Notably, HS seems to be more prevalent in HIV/HCV coinfected than in HCV monoinfected patients,10 with concomitant ART playing a potential pathogenic role. Prior studies described a higher prevalence of HS among HIV patients exposed to ART for more than 4 years or if certain nucleoside analogs were used.10,11 In addition, early ART regimens have been found to promote metabolic abnormalities (i.e., insulin resistance),12 which are linked to HS in HIV/HCV.13 However, recent studies surprisingly found a protective effect of non-GT-3-HCV infection for HS and a faster progression of HS and liver fibrosis in HIV+ individuals without HCV coinfection.14,15
These discrepant data on HS in HIV/HCV-coinfected patients may be explained by different methods and devices used for the assessment of HS. While liver biopsy is still regarded the diagnostic gold standard for diagnosis of HS, noninvasive magnetic resonance imaging- or ultrasound-based techniques are increasingly being used for HS evaluation. Controlled attenuation parameter (CAP), implemented in a transient elastography (TE) device, is now one of the most commonly used methods.16 It is well-validated in HCV-infected patients, who undergo CAP and liver stiffness measurement (LSM) in a single examination.16 A recent meta-analysis based on individual patient data presented optimized CAP cutoffs for HS quantification and provided important information on the influence of covariates (i.e., DM, BMI) on CAP results.17
The impact of HCV eradication on HS was assessed in studies using interferon (IFN)-based therapies.18,19 Despite the use of individualized treatment strategies and the addition of first-generation direct-acting antivirals (DAAs),20 sustained virological response (SVR) rates remained insufficient. Since IFN-free DAA regimens21,22 and systematic screening strategies have been implemented,23 HCV can now be effectively treated in HIV-coinfected patients. Current challenges in treating HCV in HIV-positive patients encompass insurance and pricing barriers, as well as the treating physician's education.24
In our study, we aimed to investigate the prevalence and predictors of HS, determined by CAP cutoffs according to Karlas et al.,17 in HCV-viremic HIV-coinfected "all-comers." Further, we aimed to assess the impact of HCV eradication with IFN-free DAA regimens on HS as well as on plasma lipids.
Results
Patient characteristics
Three hundred three patients with HIV/HCV coinfection visited our outpatient ward since 2014. After exclusion of patients with negative HCV-RNA and patients without available CAP value measurements, 247 patients were included in the prevalence cohort (Fig. 1) with 31% (76/247) having HS as defined by CAP value ≥248 dB/m. A second TE, including CAP following HCV eradication with IFN-free treatment, was available in 138 patients who were included in the follow-up cohort.
Mean age was 43.3 years, the majority were Caucasian (96%; 238/247) and male (75%; 185/247), 55% (135/247) had a "people who inject drugs" (PWID) background, while 30% (73/247) were categorized as "men who have sex with men" (MSM). Mean BMI in the prevalence cohort was 23.3 kg/m2. Only 3% (8/247) had diabetes and 9% (22/247) were diagnosed with arterial hypertension. Steatogenic PNPLA3 GTs were present in 4% (rs738409 G/G, 9/213) and 44% (rs738409 G/C, 94/213), respectively. The median time since HIV diagnosis was 11.3 years and the majority of patients were on ART (98%; 243/247). Eighty-two percent (199/243) showed suppressed HIV viremia (HIV-RNA <50 copies/mL). HCV-GT-1a was most frequent (49%; 120/245) followed by HCV-GT-3 (23%; 56/245). Liver fibrosis stage F0/1 and cirrhosis (F4) were observed in 49% (114/247) and 13% (33/247), respectively.
Predictors for HS in HIV/HCV-coinfected patients
Higher BMI was associated with the presence of HS (22.6 ± 3.79 vs. 24.9 ± 4.3 kg/m2; p < 0.001). Moreover, HOMA-IR was slightly increased [2.32 (3.69) vs. 3.32 (2.17); p = 0.047] in individuals with HS, while plasma lipids did not significantly differ (Fig. 2A). Most patients with PWID as the suspected route of HCV transmission had HS (71% vs. 47%; p < 0.001), whereas opioid substitution therapy, DM, arterial hypertension, and ethnicity were not associated with HS (Supplementary Table S1). While HS was absent in all three Asian patients, the number of subjects with non-Caucasian race (African American N = 4, Hispanic N = 2, Asian N = 3) seemed too small to accurately detect differences in HS prevalence and dynamics according to race in our prediction models. Further, protease inhibitor (PI) intake, as part of ART, was more frequent among patients with HS [39% (29/74) vs. 11% (18/167); p < 0.001] (Fig. 2B).
Importantly, on multivariate analysis, longer duration of HIV infection [per year; adjusted odds ratio (aOR): 1.04 (1.01-1.07); p = 0.006], BMI {per unit; aOR: 1.18 [95% confidence intervals (95-CI) 1.09-1.28; p < 0.001], PNPLA3 [per "G" allele; aOR: 2.30 (95-CI 1.28-4.13); p = 0.006]}, and PI intake [aOR: 4.23 (95-CI 1.97-9.08); p < 0.001] remained independent risk factors for HS. Notably, HCV-GT-3 was not significantly associated with an increased risk for HS [OR: 1.39 (95-CI 0.74-2.61); p = 0.309].
Impact of HCV eradication
One hundred thirty-eight patients underwent paired CAP measurements and laboratory assessment. While the BMI did not significantly change (23.8 ± 4.36 vs. 24.1 ± 4.64 kg/m2; p = 0.113), higher CAP values (225 ± 52.9 vs. 235 ± 50.7; p = 0.047) were observed after HCV eradication (Fig. 3). In contrast, SVR resulted in significant decreases of AST (p < 0.001), ALT (p < 0.001), gamma-glutamyl transpeptidase (GGT; p < 0.001) levels, as well as of liver stiffness (p < 0.001) (Table 2). Moreover, a low-density lipoprotein (LDL)-driven rise in total cholesterol (TCHOL; p < 0.001) was documented. Achieving SVR after HCV treatment was associated with an increase in the proportion of patients with HIV suppression [100% (128/128) vs. 85% (115/136) at BL; p < 0.001]. In addition, the CD4+ T lymphocyte count increased (p < 0.001).
Predictors for changes of HS after HCV eradication
Patients with an increase in ΔCAP >10% of BL were more often MSM [51% (25/49) vs. 26% (23/89); p = 0.013] and had higher LDL values at BL (101 ± 32.1 vs. 82.1 ± 33.7 mg/dL; p = 0.005). Notably, higher BL HCV-RNA was associated with increasing ΔCAP >10% (7.17 ± 9.56 vs. 6.13 ± 0.79 log IU/mL; p < 0.001), while HCV-GT or DAA regimen had no impact on HS (Table 2). Individuals on PI-containing ART more frequently had no change in HS [34% (30/87) vs. 8% in non-PI-ART users (4/49); p = 0.001]. Interestingly, while the mean CAP increased in the overall follow-up cohort, it decreased significantly from BL to follow-up among patients receiving a PI-containing ART (253 ± 56.5 vs. 231 ± 60.8 dB/m; p = 0.040). Importantly, the discontinuation of PI-ART regimens due to potential drug/drug interactions (DDI) with HCV regimens prior/during DAA treatment was not associated with a change in ΔCAP >10% of BL (p = 0.926).
In logistic regression models (Supplementary Table S2), independent factors not associated with change in CAP were PI-containing ART before DAA initiation [aOR: 4.75 (95-CI 1.32-17.14); p = 0.017] and high HCV-RNA [per log IU; aOR: 1.77 (95-CI 1.14-2.74); p = 0.011], while elevated BL LDL levels were indicative for HS progression [per 10 IU; aOR: 1.18 (95-CI 1.02-1.35); p = 0.022].
Discussion
By using the CAP as a noninvasive tool for HS assessment, we found that nearly one-third of HIV/HCV presenting at our center are affected by HS-with similar prevalence being reported in previous reports.14 The use of PI-containing ART and the duration of HIV infection were found to increase the risk of HS in HIV/HCV patients. Further, we observed an increase of CAP after DAA-induced HCV eradication and an increase in TCHOL levels-indicating an expressed impact of HCV on hepatic lipid metabolism.
The capabilities of CAP for detecting increased fat content have been shown earlier29 and while the limited reliability of the assessment in patients with high BMI has been discussed previously,30 sufficient corrective algorithms and the XL-probe have been introduced to overcome this potential limitation.17,31 Both methods were applied in our study to compensate for high BMI. Moreover, since alcohol intake could be another confounder, we have rigorously interviewed patients about any alcohol use during the study period and thus are confident that our patients did not have harmful alcohol intake during the treatment period.
Previous data have shown a significant impact of SVR to IFN-based therapy on HS improvement in patients with HCV-GT3 monoinfection, strongly suggesting a direct steatogenic effect of HCV-GT3.18,19 However, since treatment response to IFN-based regimens was low and dependent on multiple other host factors,32 IFN-associated SVR might introduce a potential bias. As IFN-free DAA-based regimens result in SVR rates >95%,22,33,34 these patient cohorts are not preselected by treatment response and changes in HS can be assessed with a low risk of bias. Further, histological HS assessment involves a considerable risk of severe complications35 and thus is often limited to patients with evidence of ongoing liver disease. Accordingly, liver biopsy-based studies are prone to selection bias in addition to the commonly observed sample variability due to irregularities in liver parenchyma.36 However, variability is also a concern in CAP measurements. While there are insufficient data on the intra- and interobserver agreement of individual CAP measurements, our personal experience is that CAP measurements well correlate with steatosis and are accurate if quality criteria for LSM are fulfilled (as in our study). Still, we cannot completely exclude that CAP variability impacted on the results.
Several independent risk factors for HS could be identified in our prevalence cohort. As previously reported,37 HS was linked to increased BMI, HOMA-IR index, and the presence of a PNPLA3-G allele. Only 3% of our cohort was diagnosed with DM, which is in line with the previously reported prevalence of DM among HIV/HCV.38 Due to type 2 error, the low prevalence of DM may have contributed to the lack of a significant association between DM and HS. Moreover, the low prevalence of DM indicates a low frequency of metabolic syndrome, which could explain why hypertension, high TCHOL levels, and low high-density lipoprotein levels as metabolic syndrome determinants39 were not predictive for HS. Since waist circumference as a critical diagnostic component for metabolic syndrome was not available, a diagnosis of metabolic syndrome could not be accurately established and thus was not included in the prediction models. However, PI-based ART was associated with the highest aOR for the presence of HS. Two studies, one conducted by Macias et al. in 201440 including 505 HIV+ (including a subgroup of 159 HCV-coinfected patients) individuals and the other by Vuille-Lessard et al. in 201641 including 300 HIV+ individuals, found no significant association between PI-containing ART and HS measured by CAP. Interestingly, while we observed an overall increase in CAP after HCV eradication, patients receiving a PI-containing ART had a significant decrease in CAP after HCV eradication. Moreover, the observed effect was independent of PI discontinuation, which was required in some of the patients to circumvent DDI with HCV-DAAs. Thus, our data suggest a steatogenic effect of PI-containing ART only in the presence of HCV. However, since CAP values were the highest among patients with PI intake at BL, our observation might be affected by the statistical phenomenon referred to as "regression to the mean."42 It occurs frequently when the mean of a specific parameter of a cohort diverges extremely from the expected value.
At a subsequent measurement, it will tend to be closer to the average. Taken together, this effect may augment the high statistical significance observed for CAP regression after HCV eradication in patients on a PI.
Further, switching from a PI-containing ART to an non-nucleoside reverse-transcriptase inhibitor (NNRTI) or integrase inhibitor (INSTI) plus nucleos(t)idic reverse-transcriptase inhibitor [N(t)RTI] backbone leads to decreases in triglycerides, TCHOL, and LDL in HIV-monoinfected patients.43,44 In addition, PI intake modulates the impact of alcohol consumption on hepatic fibrogenesis.45 HCV itself, however, also impacts hepatic lipid metabolism and transport: HCV circulates as highly lipidated particles and takes advantage of the LDL receptor and the Niemann Pick C1-Like 1 protein as entry factors.46 Once it has entered the hepatocytes, it induces the sterol response element binding protein (SREBP).46 Consecutively, HCV promotes the expression of fatty acid synthase along with HMG-co-A reductase while simultaneously inhibiting cholesterol secretion.47 Hence, decreased levels of LDL and further TCHOL have been described in HCV patients.48 Moreover, causality is confirmed by the increase of serum LDL after HCV eradication49-which was also observed in our follow-up cohort. In addition, we found significant increases in CAP after HCV eradication, a subsequent effect of HCV eradication that was previously reported for HIV-negative patients.50 This may be also due to a "return-to-health effect,"51 which might be associated with increased appetite and a psychogenic "de-depression" after HCV eradication.52,53 However, BMI did not significantly change between BL and follow-up-which suggests that a "return-to-health effect" may not be a major determinant of increasing CAP after HCV eradication in our cohort. Still, a cutoff for a "clinically meaningful" change in CAP that corresponds to clinical outcomes has not yet been established. A recently published study suggested that a change of more than 38 dB/m in CAP would indicate a >1% change in magnetic resonance imaging-estimated proton density fat fraction (PDFF).54 However, in general, CAP had a poor performance for predicting changes in PDFF and the study was not designed to assess the clinical impact of this absolute change in CAP. Thus, our results derived from the follow-up cohort are limited by the unknown clinical significance of the measured dynamics in CAP.
In conclusion, HS can be found in about one-third of HIV/HCV-coinfected patients. Next to host factors such as BMI and PNPLA3 risk alleles, the duration of HIV infection and exposure to PI-containing ART are independent risk factors for HS in HIV/HCV patients. Importantly, HCV eradication by DAA-based therapy seems to increase CAP values-in parallel to increases in cholesterol, that is, in LDL plasma levels. Interestingly, elevated BL LDL and the use of non-PI-ART regimens were associated with increases in CAP values after HCV eradication. Ultimately, it remains to be established if HIV patients with elevated CAP values and LDL levels after HCV eradication are at higher risk of HS and its associated metabolic and cardiovascular events.
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