All Patients With Advanced Fibrosis Should Continue to Be Screened for Hepatocellular Carcinoma After Sustained Virological Response of Hepatitis C Virus

Khan, Ruben; Velpari, Sugir; Koppe, Sean

doi:10.1002/cld.707

Cited by 4 publications

(3 citation statements)

References 7 publications

(8 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Conversely, a study of 106 hereditary hemochromatosis patients discovered a significant reduction in long-term HCC risk in patients with regression [ 24 ]. The risk for HCC in patients with fibrosis regression may vary depending on the underlying etiology [ 33 ].…”

Section: Discussionmentioning

confidence: 99%

Features of fibrosis regression abound in “non-cirrhotic” patients with resected hepatocellular carcinoma

et al. 2022

View full text Add to dashboard Cite

Cirrhosis is a major risk factor for developing hepatocellular carcinoma (HCC). However, many surgically resected HCCs are presumably non-cirrhotic. The dynamic nature of chronic liver disease leads to periods of hepatic repair and fibrosis regression. We hypothesize that most resected HCCs, including those from non-cirrhotic patients, exhibit features of fibrosis regression in their background liver, suggesting previously more advanced liver disease. We reviewed the histology of 37 HCC resections performed between 2005–2020, including 30 from non-cirrhotic patients. The non-neoplastic liver was evaluated for features of liver disease and of the hepatic repair complex (HRC). CD34 immunohistochemistry was performed as a marker of sinusoidal capillarization. CD34 staining was evaluated manually and also by a digital image classifier algorithm. Overall, 28 cases (76%) had a high number of fibrosis regression and hepatic repair features (≥4 out of 8 features). Amongst the 30 non-cirrhotic patients, 21 (70%) showed a high number of repair features. Relative CD34 expression was increased in cases with a high number (≥4) of HRC features versus a low number (≤3) of features (p = 0.019). High HRC cases were more likely to exhibit nodular circumferential CD34 staining (p = 0.019). Our findings suggest that most resected HCC from non-cirrhotic patients display features of fibrosis regression in their background liver. Thus many, if not most, HCC patients who are “non-cirrhotic” may in fact have regressed cirrhosis. This finding reinforces that patients with regressed cirrhosis continue to be at high risk for HCC.

show abstract

Section: Discussionmentioning

confidence: 99%

Features of fibrosis regression abound in “non-cirrhotic” patients with resected hepatocellular carcinoma

et al. 2022

View full text Add to dashboard Cite

show abstract

“…The F3 stage is known as the “bridging” step between complication-free liver disease and cirrhosis, the latter characterised by a deformed liver architecture, increased chances for HCC and severe systemic pathologies [ 57 , 58 ]. We chose to differentiate F3 patients from the other stages because although F3 patients tend to have better clinical outcomes and overall survival [ 57 ], many clinical researchers recommend that they should also be monitored for HCC development post-cure [ 19 , 59 ]. Additionally, there is still not enough information available about established HCV-mediated molecular mechanisms of tumourigenesis at this stage.…”

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

View full text Add to dashboard Cite

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.

show abstract

“…Following the achievement of SVR, fibrosis regression reached its plateau for about one year. In addition, the fibrosis regression does not prevent the development of HCC years after treatment as liver, although deprived of the pro-inflammatory viral trigger, still has a potentially carcinogenic persistence[ 70 , 71 ]. Therefore, because of the insufficient data regarding the decrease in HCC risk after SVR with DAAs, patients, especially those with severe fibrosis, should be committed to frequent HCC screening.…”

Section: Hepatocellular Carcinoma (Hcc) Post-daas and Relation To Fib...mentioning

confidence: 99%

Fibrosis regression following hepatitis C antiviral therapy

Elsharkawy¹,

Samir²,

El-Kassas³

2022

WJH

View full text Add to dashboard Cite

Hepatitis C virus (HCV) infection is one of the most common causes of liver pathology. It is a major etiological factor of continuous liver injury by triggering an uncontrolled inflammatory response, causing liver fibrosis and cirrhosis. Liver fibrosis is a dynamic process that can be reversible upon timely cessation of the injurious agent, which in cases of HCV is represented by the sustained virological response (SVR) following antiviral therapies. Direct-acting antiviral therapy has recently revolutionized HCV therapy and minimized complications. Liver fibrosis can be assessed with variable invasive and non-invasive methods, with certain limitations. Despite the broad validation of the diagnostic and prognostic value of non-invasive modalities of assessment of liver fibrosis in patients with HCV, the proper interpretation of liver stiffness measurement in patients after SVR remains unclear. It is also still a debate whether this regression is caused by the resolution of liver injury following treatment of HCV, rather than true fibrosis regression. Regression of liver fibrosis can possess a positive impact on patient's quality of life reducing the incidence of complications. However, fibrosis regression does not abolish the risk of developing hepatocellular carcinoma, which mandates regular screening of patients with advanced fibrosis.

show abstract

All Patients With Advanced Fibrosis Should Continue to Be Screened for Hepatocellular Carcinoma After Sustained Virological Response of Hepatitis C Virus

Abstract: http://aasldpubs.onlinelibrary.wiley.com/hub/journal/10.1002/(ISSN)2046-2484/video/12-5-reading-khan a video presentation of this article

Cited by 4 publications

References 7 publications

Features of fibrosis regression abound in “non-cirrhotic” patients with resected hepatocellular carcinoma

Features of fibrosis regression abound in “non-cirrhotic” patients with resected hepatocellular carcinoma

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

Fibrosis regression following hepatitis C antiviral therapy

Contact Info

Product

Resources

About