Liver steatosis and dyslipidemia after HCV eradication by direct acting antiviral agents are synergistic risks of atherosclerosis

Kawagishi, Naoki; Suda, Goki; Nakamura, Akinobu; Kimura, Megumi; Maehara, Osamu; Suzuki, Kazuharu; Nakamura, Akihisa; Ohara, Masatsugu; Izumi, Takeshi; Umemura, Machiko; Nakai, Masato; Sho, Takuya; Natsuizaka, Mitsuteru; Morikawa, Kenichi; Ogawa, Koji; Kudo, Yusuke; Nishida, Mutsumi; Miyoshi, Hideaki; Sakamoto, Naoya

doi:10.1371/journal.pone.0209615

Cited by 37 publications

(54 citation statements)

References 45 publications

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“…In this study, we suggest a link between the low physical quality of life after DAA-SVR and an increasing rate of obesity and hypercholesterolemia in those patients. Our findings are consistent with other research: treatment with DAAs reduces liver stiffness, but is associated with an increase in hepatic steatosis [24][25][26] . Nevertheless the treatment itself might not have a negative impact on glucose metabolism [26][27][28] .…”

Section: Discussionsupporting

confidence: 93%

“…Nevertheless the treatment itself might not have a negative impact on glucose metabolism [26][27][28] . There are also strong data showing an increase in total cholesterol and LDL levels 24,26,29 , which we could not confirm, probably due to the small test group. The post-treatment increase in CAP and LDL was highest among patients with low pre-treatment steatosis 25 and did not affect individuals with the highest initial levels of LDL 24 .…”

Section: Discussioncontrasting

confidence: 63%

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Impact of chronic HCV treatment on quality of life of patients with metabolic disorders in context of immunological disturbances

Kierepa¹,

Witkowska²,

Kaczmarek

et al. 2020

Sci Rep

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Chronic viral hepatitis C (CHC) and its complications have a negative effect on patient's quality of life. We evaluated the impact of a successful interferon-free treatment on the quality of life of patients with obesity and metabolic disorders in the context of immunological disturbances. Twenty overweight or obese (BMi > 25) patients with CHC were tested before the therapy and after a successful treatment regimen. After the therapy, patient's emotional well-being improved (p = 0.02), while physical wellbeing remained unchanged. There was a decrease of patient's liver fibrosis and an increase of steatosis along with body mass. Among HCV-infected individuals, the expression of toll-like receptor 3 (TLR3) on lymphocytes was higher than in the control group (p = 0.03), but it decreased (p = 0.001) after the treatment. There was also a decrease of the intensity of immunofluorescence of FoxP3+ after the treatment (p = 0.04). Our study showed an improvement in mental aspects of patient's quality of life after the treatment. Unfortunately, probably due to rapid immunological changes, patient's BMI, serum cholesterol levels and hepatic steatosis have a tendency to increase and may lead to cardiovascular and other complications, like hepatocellular carcinoma. Chronic viral hepatitis C (CHC) affects about 150 million people worldwide, resulting in the deaths of roughly 700 000 persons a year 1. Long-lasting presence of HCV in a human body causes variety of incremental disorders, of which liver cirrhosis and hepatocellular carcinoma are the most serious. Moreover, due to immunological alterations, CHC may cause several extrahepatic manifestations. It also increases the risk of metabolic disorders 2. All of the above vitally affect the patient's health-related quality of life (HRQOL) 3-5. Liver cirrhosis and its common complications like encephalopathy, ascites or low body mass index, have a significant negative impact on a patient's quality of life 4,5. Approximately one in five outpatients with cirrhosis have low HRQOL, even considering the high proportion of non-hospitalized individuals without signs of hepatic decompensation 5. The coexistence of encephalopathy and depression suggests a possible pathophysiological link between them 4. Of note, the development of cirrhosis among patients chronically infected with HCV is often proceeded by a low muscle-skeletal mass, whereas malnutrition, a significant complication in end-stage liver disease, substantially affects HRQOL 6 and is associated with reduced survival 7. A meta-analysis of 102 studies has shown that the presence of extra-hepatic manifestations, with depression the most common amongst them (25%), affects health-related quality-of-life and has a negative impact on overall mental and physical health 3. CHC is bound to increase the risk of developing metabolic diseases, especially type 2 diabetes (with prevalence of up to 15% among HCV-infected patients) 3 , liver steatosis and hypercholesterolemia. Moreover, factors commonly resulting from co-existent depression, l...

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Section: Discussionsupporting

confidence: 93%

Section: Discussioncontrasting

confidence: 63%

Impact of chronic HCV treatment on quality of life of patients with metabolic disorders in context of immunological disturbances

Kierepa¹,

Witkowska²,

Kaczmarek

et al. 2020

Sci Rep

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show abstract

“…Nevertheless, 77.1% experienced a slight improvement in FAST score, with an influence on the decline of liver stiffness measurement (LSM), but not controlled attenuation parameter (CAP). This finding was consistent with a recent Japanese report 5 ; however, we need to keep in mind that the longitudinal CAP score differs by HCV genotype, race/ethnicity and region. Increase in weight and skeletal muscle after HCV cure has been suggested in small studies 6,7 …”

supporting

confidence: 92%

Editorial: FAST score‐ a new predictive marker for HCC after SVR—author's reply

Ogawa

2020

Aliment Pharmacol Ther

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“…FibroScan 502 (Echosens) was utilized for LSM and controlled attenuation parameter (CAP) evaluation with the M‐probe and XL‐probe. As described previously, each patient was placed in the supine position with the right hand at the most abducted position during the procedure . At least 10 valid measurements were obtained, and effective measurements were defined as those >60% with an interquartile range of <30%.…”

Section: Methodsmentioning

confidence: 99%

High serum angiopoietin‐2 level predicts non‐regression of liver stiffness measurement‐based liver fibrosis stage after direct‐acting antiviral therapy for hepatitis C

Kawagishi

Suda

Kimura

et al. 2020

Hepatology Research

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Aim Factors associated with improvement of liver fibrosis after successful hepatitis C virus (HCV) eradication by interferon (IFN)‐free direct‐acting antiviral agents (DAAs) have been not clarified well. Angiopoietin‐2 (Ang2) is reported to be associated with vascular leak and inflammation observed in patients with advanced liver fibrosis. Methods In this retrospective study, patients treated with IFN‐free DAAs who underwent transient elastography before and at 24‐weeks post‐treatment and achieved sustained viral response were enrolled. Baseline serum Ang2 was measured, and its relationship with other clinical factors was analyzed. Liver fibrosis stage was defined based on liver stiffness according to a previous report. Predictive factors for regression of liver fibrosis stage after DAA therapy were evaluated. Results Overall, 116 patients were analyzed. Baseline serum Ang2 levels were significantly associated with liver stiffness, spleen index, and liver stiffness‐based liver fibrosis stage. Moreover, 75% of patients experienced regression of liver fibrosis stage after DAA therapy. Multivariate analysis revealed that advanced liver fibrosis stage and Ang2 levels were significantly associated with regression of liver fibrosis stage after DAA therapy. In patients with advanced liver fibrosis (F3/4), baseline Ang2 level alone could predict regression of liver fibrosis stage. A baseline Ang2 cut‐off value (354 pg/ML) could predict regression of liver fibrosis stage after DAA therapy with high accuracy (sensitivity 0.882, specificity 0.733). Conclusions Evaluation of serum Ang2 levels before DAA therapy is important. Our results provide a novel mechanistic insight into non‐regression of liver stiffness after DAA therapy. Long‐term and larger studies are required.

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Liver steatosis and dyslipidemia after HCV eradication by direct acting antiviral agents are synergistic risks of atherosclerosis

Cited by 37 publications

References 45 publications

Impact of chronic HCV treatment on quality of life of patients with metabolic disorders in context of immunological disturbances

Impact of chronic HCV treatment on quality of life of patients with metabolic disorders in context of immunological disturbances

Editorial: FAST score‐ a new predictive marker for HCC after SVR—author's reply

High serum angiopoietin‐2 level predicts non‐regression of liver stiffness measurement‐based liver fibrosis stage after direct‐acting antiviral therapy for hepatitis C

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