Metabolic comorbidities and male sex influence steatosis in chronic hepatitis C after viral eradication by direct-acting antiviral therapy (DAAs): Evaluation by the controlled attenuation parameter (CAP)

Cespiati, Annalisa; Petta, Salvatore; Lombardi, Rosa; Marco, V. Di; Calvaruso, V.; Bertelli, C.; Pisano, Giuseppina; Fatta, E.; Sigon, Giordano; Iuculano, F.; Crapanzano, L.; Gibilaro, Gerlando; Francione, Paolo; Craxı̀, Antonio

doi:10.1016/j.dld.2020.11.001

Cited by 11 publications

(20 citation statements)

References 44 publications

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“…Given the mechanism of steatosis differs between HCV-GT3 and other genotypes, additional information in HCV-GT1 is necessary. Moreover, data regarding the change of steatosis following successful DAAs in HCV-GT1 were not consistent with conflicting findings among previous studies [ 12 – 18 ].…”

Section: Discussioncontrasting

confidence: 71%

“…Although reducing in fibrosis is feasible after SVR, it is unclear whether HCV clearance might induce steatosis improvement. In this context, some studies demonstrated a reduction in liver steatosis after SVR [ 12 – 14 ], while other reports showed a tendency towards continuing or increased steatosis from baseline [ 15 – 18 ]. These conflicting results emphasize the need for further studies with a longer duration of follow-up that could identify factors predictive of steatosis change in patients achieved SVR.…”

Section: Introductionmentioning

confidence: 99%

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Improvement of liver fibrosis, but not steatosis, after HCV eradication as assessment by MR-based imaging: Role of metabolic derangement and host genetic variants

et al. 2022

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Significant liver fibrosis regression occurs after hepatitis C virus (HCV) therapy. However, the impact of direct-acting antivirals (DAAs) on steatosis is less clear. This study was aimed at evaluating serial fibrosis and steatosis alterations in patients with HCV genotype 1, who achieved sustained virological response (SVR). We enrolled 55 HCV mono-infected and 28 HCV/HIV co-infected patients receiving elbasvir/grazoprevir from a clinical trial. Fibrosis and steatosis were assessed at baseline, follow-up week-24 (FUw24) and week-72 (FUw72) by magnetic resonance elastography (MRE) and proton density fat fraction (PDFF), respectively. Patatin-like phospholipase domain-containing protein 3 (PNPLA3) rs738409, transmembrane six superfamily member 2 (TM6SF2) rs58542926 and membrane bound O-acyltransferase domain-containing 7 (MBOAT7) rs641738 polymorphisms were determined by allelic discrimination. Overall, mean MRE decreased significantly from baseline to FUw24 and FUw72. At FUw72, patients with baseline F2-F4 had higher rate of ≥30% MRE decline compared with individuals with baseline F0-F1 (30.2%vs.3.3%, P = 0.004). In multivariate analysis, significant fibrosis was associated with MRE reduction. The prevalence of steatosis (PDFF≥5.2%) at baseline was 21.7%. Compared to baseline, there were 17 (20.5%) patients with decreased PDFF values at FUw72 (<30%), while 23 (27.7%) patients had increased PDFF values (≥30%). Regarding the overall cohort, mean PDFF significantly increased from baseline to FUw72, and displayed positive correlation with body mass index (BMI) alteration. In multivariate analysis, the presence of diabetes, PNPLA3 CG+GG genotypes and increased BMI at FUw72 were significantly associated with progressive steatosis after SVR. Other genetic variants were not related to fibrosis and steatosis alteration. This study concluded that HCV eradication was associated with fibrosis improvement. However, progressive steatosis was observed in a proportion of patients, particularly among individuals with metabolic derangement and PNPLA3 variants. The combined clinical parameters and host genetic factors might allow a better individualized strategy in this sub-group of patients to alleviate progressive steatosis after HCV cure.

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Section: Discussioncontrasting

confidence: 71%

Section: Introductionmentioning

confidence: 99%

Improvement of liver fibrosis, but not steatosis, after HCV eradication as assessment by MR-based imaging: Role of metabolic derangement and host genetic variants

et al. 2022

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“…In an Italian multicentric cohort of 794 patients with HCV infection, the prevalence of steatosis (defined at a CAP value of 248 dB/m or higher) before starting DAA treatment was 46%. At 6 months after SVR, de novo steatosis developed in 29% of cases, whereas resolution was observed in 30% of cases, and both were associated with the presence of metabolic comorbidities [ 50 ].…”

Section: Monitoring Changes In Liver Fat Content Over Timementioning

confidence: 99%

Quantitative assessment of liver steatosis using ultrasound controlled attenuation parameter (Echosens)

Ferraioli

2021

J Med Ultrasonics

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Controlled attenuation parameter (CAP) is the algorithm available on the FibroScan system (Echosens, France) for quantification of liver steatosis. It assesses the ultrasound beam attenuation, which is directly related to liver fat content. The inter-observer reproducibility of the technique is high, with a reported concordance correlation coefficient of 0.82. Specific quality criteria for CAP measurements are not clearly defined yet, and there are conflicting results in the literature. Using liver biopsy as the reference standard, several studies have assessed the CAP performance in grading liver steatosis, and have reported that values are not affected by liver fibrosis. The cutoff for detection of liver steatosis reported in the literature ranges from 222 decibels per meter (dB/m) in a cohort of patients with chronic hepatitis C to 294 dB/m in a meta-analysis of nonalcoholic fatty liver disease (NAFLD) patients. CAP has been used as a tool to noninvasively evaluate the prevalence of NAFLD in groups at risk or in the general population; however, it should be underscored that different CAP cutoffs for steatosis detection (S > 0) were used in different studies, and this limits the robustness of the findings. CAP, alone or combined with other noninvasive indices or biomarkers, has been proposed as a tool for assessing nonalcoholic steatohepatitis or as a noninvasive predictor of prognosis in patients with chronic liver disease. CAP is easy to perform and has become a point-of-care technique. However, there is a large overlap of values between consecutive grades of liver steatosis, and cutoffs are not clearly defined.

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“…Alternatively, a moderate post-cure increase was noted only in patients with mild fibrosis [ 70 ]. This partial recovery of circulating lipids is accompanied by increasing steatosis in patients with or without co-existing predisposing factors, through unclear mechanisms [ 72 , 73 ]. Although we did not determine the concentration of lipids and cholesterol in our samples, the HCV-dictated ANGPTL-3 levels remaining after viral eradication could be causally involved, at least in part, in shaping specific lipid species and steatosis after treatment.…”

Section: Discussionmentioning

confidence: 99%

Differential Expression of the Host Lipid Regulators ANGPTL-3 and ANGPTL-4 in HCV Infection and Treatment

Valiakou

Eliadis

Karamichali

et al. 2021

IJMS

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Host lipid metabolism reprogramming is essential for hepatitis C virus (HCV) infection and progression to severe liver disease. Direct-acting antivirals (DAAs) achieve a sustained virological response (SVR) in most patients, but virus eradication does not always protect against hepatocellular carcinoma (HCC). Angiopoietin-like protein-3 (ANGPTL-3) and angiopoietin-like protein-4 (ANGPTL-4) regulate the clearance of plasma lipids by inhibiting cellular lipase activity and possess emerging roles in tumourigenesis. We used ELISA and RT-qPCR to investigate ANGPTL-3 and ANGPTL-4 expression in HCV patients with characterised fibrosis throughout the natural history of hepatitis C and in long-term HCV infection in vitro, before and after DAA treatment. ANGPTL-3 was decreased in patients with advanced fibrosis compared to other disease stages, while ANGPTL-4 was progressively increased from acute infection to cirrhosis and HCC, peaking at the advanced fibrosis stage. Only ANGPTL-3 mRNA was down-regulated during early infection in vitro, although both ANGPTLs were increased later. DAA treatment did not alter ANGPTL-3 levels in advanced fibrosis/cirrhosis and in HCV infection in vitro, in contrast to ANGPTL-4. The association between ANGPTLs and fibrosis in HCV infection was underlined by an inverse correlation between the levels of ANGPTLs and serum transforming growth factor- β (TGF-β). Collectively, we demonstrate the pivotal role of advanced fibrosis in defining the expression fate of ANGPTLs in HCV infection and after treatment and propose a role for ANGPTL-3 as a contributor to post-treatment deregulation of lipid metabolism that could predispose certain individuals to HCC development.

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Metabolic comorbidities and male sex influence steatosis in chronic hepatitis C after viral eradication by direct-acting antiviral therapy (DAAs): Evaluation by the controlled attenuation parameter (CAP)

Cited by 11 publications

References 44 publications

Improvement of liver fibrosis, but not steatosis, after HCV eradication as assessment by MR-based imaging: Role of metabolic derangement and host genetic variants

Improvement of liver fibrosis, but not steatosis, after HCV eradication as assessment by MR-based imaging: Role of metabolic derangement and host genetic variants

Quantitative assessment of liver steatosis using ultrasound controlled attenuation parameter (Echosens)

Differential Expression of the Host Lipid Regulators ANGPTL-3 and ANGPTL-4 in HCV Infection and Treatment

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