Mac-2 binding protein glycosylation isomer as a novel predictive biomarker for patient survival after hepatitis C virus eradication by DAAs

2020 ◽  
Vol 55 (10) ◽  
pp. 990-999 ◽  
Author(s):  
Mina Nakagawa ◽  
◽  
Nobutoshi Nawa ◽  
Eiko Takeichi ◽  
Taro Shimizu ◽  
...  
2021 ◽  
Author(s):  
Shunsuke Sato ◽  
Hironori Tsuzura ◽  
Yuji Kita ◽  
Yuji Ikeda ◽  
Daishi Kabemura ◽  
...  

Abstract Background and aims: Recent advances of direct-acting antiviral drugs for hepatitis C virus (HCV) have dramatically improved the sustained virologic response (SVR) rate, but hepatocellular carcinoma (HCC) development not rarely occurs even in patients who achieve an SVR. Wisteria floribunda agglutinin-positive Mac-2-binding protein (WFA+-M2BP) was recently developed as a noninvasive biomarker of liver fibrosis. However, the association between the WFA+-M2BP level and HCC development after the achievement of an SVR is unclear. Methods: We examined the association between WFA+-M2BP and HCC development in 552 HCV patients who achieved an SVR (Interferon [IFN]-based therapy, n=228; IFN-free therapy, n=294). Results: Multivariate analysis revealed that a high WFA+-M2BP level at SVR week 24 after treatment (SVR24) (hazard ratio [HR]=1.215, P=0.020), low platelet counts (HR=0.876, P=0.037) and old age (HR=1.073, P=0.012) were independent risk factors for HCC development regardless of the treatment regimen. Receiver operator characteristics curve analysis revealed that an WFA+-M2BP level at SVR24 of ≥1.62 cut off index (COI) was the cut-off value for the prediction of HCC development (adjusted HR = 12.565, 95% CI 3.501-45.092, P<0.001). The 3- and 5-year cumulative incidences of HCC were 0.7% and 0.7% in patients with low WFA+-M2BP at SVR24 (<1.62 COI), and 4.8% and 12.4% in patients with high WFA+-M2BP (≥1.62 COI) were, respectively (P<0.001).Conclusion: The assessment of liver fibrosis using the WFA+-M2BP level at SVR24 is a useful predictor of HCC development after HCV eradication even in the IFN-free therapy era.


Healthcare ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 651
Author(s):  
Laura Huiban ◽  
Carol Stanciu ◽  
Cristina Maria Muzica ◽  
Tudor Cuciureanu ◽  
Stefan Chiriac ◽  
...  

(1) Background: The World Health Organization adopted a strategy for the Global Health Sector on Viral Hepatitis in 2016, with the main objective of eliminating hepatitis C virus (HCV) by 2030. In this work, we aimed to evaluate the prevalence of HCV infection and risk factors in a Romanian village using population-based screening as part of the global C virus eradication program. (2) Methods: We conducted a prospective study from March 2019 to February 2020, based on a strategy as part of a project designed to educate, screen, treat and eliminate HCV infection in all adults in a village located in Northeastern Romania. (3) Results: In total, 3507 subjects were invited to be screened by rapid diagnostic orientation tests (RDOT). Overall, 2945 (84%) subjects were tested, out of whom 78 (2.64%) were found to have positive HCV antibodies and were scheduled for further evaluation in a tertiary center of gastroenterology/hepatology in order to be linked to care. In total, 66 (85%) subjects presented for evaluation and 55 (83%) had detectable HCV RNA. Of these, 54 (98%) completed antiviral treatment and 53 (99%) obtained a sustained virological response. (4) Conclusions: The elimination of hepatitis C worldwide has a higher chance of success if micro-elimination strategies based on mass screening are adopted.


2020 ◽  
Vol 36 (11) ◽  
pp. 920-928 ◽  
Author(s):  
Chung‐Feng Huang ◽  
Chia‐Yen Dai ◽  
Ming‐Lun Yeh ◽  
Ching‐I Huang ◽  
Hsiang‐Chun Lee ◽  
...  

2015 ◽  
Vol 90 (6) ◽  
pp. 2794-2805 ◽  
Author(s):  
Giao V. Q. Tran ◽  
Trang T. D. Luong ◽  
Eun-Mee Park ◽  
Jong-Wook Kim ◽  
Jae-Woong Choi ◽  
...  

ABSTRACTHepatitis C virus (HCV) is a major cause of chronic liver disease and is highly dependent on cellular proteins for virus propagation. To identify the cellular factors involved in HCV propagation, we recently performed protein microarray assays using the HCV nonstructural 5A (NS5A) protein as a probe. Of 90 cellular protein candidates, we selected the soluble resistance-related calcium-binding protein (sorcin) for further characterization. Sorcin is a calcium-binding protein and is highly expressed in certain cancer cells. We verified that NS5A interacted with sorcin through domain I of NS5A, and phosphorylation of the threonine residue 155 of sorcin played a crucial role in protein interaction. Small interfering RNA (siRNA)-mediated knockdown of sorcin impaired HCV propagation. Silencing of sorcin expression resulted in a decrease of HCV assembly without affecting HCV RNA and protein levels. We further demonstrated that polo-like kinase 1 (PLK1)-mediated phosphorylation of sorcin was increased by NS5A. We showed that both phosphorylation and calcium-binding activity of sorcin were required for HCV propagation. These data indicate that HCV modulates sorcin activity via NS5A protein for its own propagation.IMPORTANCESorcin is a calcium-binding protein and regulates intracellular calcium homeostasis. HCV NS5A interacts with sorcin, and phosphorylation of sorcin is required for protein interaction. Gene silencing of sorcin impaired HCV propagation at the assembly step of the HCV life cycle. Sorcin is phosphorylated by PLK1 via protein interaction. We showed that sorcin interacted with both NS5A and PLK1, and PLK1-mediated phosphorylation of sorcin was increased by NS5A. Moreover, calcium-binding activity of sorcin played a crucial role in HCV propagation. These data provide evidence that HCV regulates host calcium metabolism for virus propagation, and thus manipulation of sorcin activity may represent a novel therapeutic target for HCV.


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