Significance of pSmad2/3 and Smad4 in hepatitis C virus-related liver fibrosis and hepatocellular carcinoma

Hepatitis C virus (HCV) is one of the most epidemic viral infections in the world. Three-quarters of individuals infected with HCV become chronic. As a consequence of persistent inflammation, a considerable percentage of chronic patients progress to liver fibrosis, cirrhosis, and finally hepatocellular carcinoma. Cytokines, which are particularly produced from T-helper cells, play a crucial role in immune protection against HCV and the progression of the disease as well. In this study, the role of interleukins IL-33, IL-17, and IL-25 in HCV patients and progression of disease from chronicity to hepatocellular carcinoma will be characterized in order to use them as biomarkers of disease progression. The serum levels of the tested interleukins were measured in patients suffering from chronic hepatitis C (CHC), hepatocellular carcinoma (HCC), and healthy controls (C), and their levels were correlated to the degree of liver fibrosis, liver fibrosis markers and viral load. In contrast to the IL-25 serum level, which increased in patients suffering from HCC only, the serum levels of both IL-33 and IL-17 increased significantly in those patients suffering from CHC and HCC. In addition, IL-33 serum level was found to increase by liver fibrosis progression and viral load, in contrast to both IL-17 and IL-25. Current results indicate a significant role of IL-33 in liver inflammation and fibrosis progress in CHC, whereas IL-17 and IL-25 may be used as biomarkers for the development of hepatocellular carcinoma.

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Post-treatment Mac-2-Binding Protein is a Useful Predictor of Hepatocellular Carcinoma Development after Hepatitis C Virus Eradication

10.21203/rs.3.rs-276843/v1 ◽

2021 ◽

Author(s):

Shunsuke Sato ◽

Hironori Tsuzura ◽

Yuji Kita ◽

Yuji Ikeda ◽

Daishi Kabemura ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Hepatitis C Virus ◽

Hepatitis C ◽

Liver Fibrosis ◽

Binding Protein ◽

Virologic Response ◽

Virus Eradication ◽

Direct Acting Antiviral ◽

Noninvasive Biomarker ◽

Direct Acting

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.

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Clinical and epidemiological overview of liver fibrosis and hepatocellular carcinoma in patients infected with the hepatitis C virus

Research Society and Development ◽

10.33448/rsd-v9i7.4645 ◽

2020 ◽

Vol 9 (7) ◽

pp. e688974645

Author(s):

Joao Victor Cordeiro Farias ◽

Isabela Cristina Cordeiro Farias ◽

Penelopy Rodrigues Macedo ◽

Patrícia Muniz Mendes Freire de Moura

Keyword(s):

Hepatocellular Carcinoma ◽

Hepatitis C Virus ◽

Hepatitis C ◽

Liver Fibrosis ◽

Chronic Infection ◽

Detection Methods ◽

Enzyme Linked Immunosorbent Assay ◽

Hcv Rna ◽

Medical Centers ◽

Direct Acting

About 2.4 million people die each year worldwide as a result of chronic infection with the hepatitis C virus (HCV). HCV is a worldwide problem, more than 170 million people are infected with the virus worldwide, corresponding to about 3% of the population. Some common signs for patients chronically infected with HCV are: increased liver enzyme activity and chronic liver diseases, such as fibrosis, cirrhosis, and hepatocellular carcinoma. The present study consists of a literature review, of a qualitative nature which aims to approach the main clinical and epidemiological aspects of the chronic infection caused by the HCV. HCV detection is carried out by screening for antibodies by enzyme-linked immunosorbent assay (ELISA) and screening for HCV-RNA through polymerase chain reaction (PCR). The current detection methods are not viable for all medical centers and outpatient clinics, making it necessary to develop new detection methods, since the technological apparatus for screening HCV-RNA, as well as ELISA, is a distant reality for the vast majority of the global health system. The development of direct-acting antivirals (DAAs) increased the viral response, reaching up to 92.7% success rate. It is necessary to monitor post-treatment patients, as well as to treat patients who are still affected by the virus worldwide, to ensure that there is no progression of liver fibrosis in cirrhosis, nor the development of HCC. Additionally, vigilance should be maintained for possible mutations and the emergence of viral resistance to DAAs.

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