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Immunofluorescence to Monitor the Cellular Uptake of Human Lactoferrin and its Associated Antiviral Activity Against the Hepatitis C Virus
Published on: October 1, 2015
IMMUNOHISTOCHEMICAL ASSESSMENT OF LYMPHATIC VESSELS IN HUMAN LIVERS WITH CHRONIC HEPATITIS C - RELATION TO
Aline Kawassaki Assato1, Ana Paula Beltrame Farina Pasinato2, Cinthya Dos Santos Cirqueira3
1Faculdade de Medicina da Universidade de São Paulo, Departamento de Patologia, Laboratório de Investigação Médica em Patologia Hepática, LIM14, São Paulo, SP, Brasil.
Insights
Hepatitis C virus (HCV) infection leads to increased lymphatic vessels in the liver, particularly with advanced fibrosis and cirrhosis. This study used immunohistochemistry to visualize and quantify these changes in liver biopsies.
Area of Science:
- Hepatology
- Immunohistochemistry
- Vascular Biology
Background:
- Hepatitis C virus (HCV) infection poses a significant global health burden, potentially leading to severe liver disease like cirrhosis and hepatocellular carcinoma.
- Despite advancements in antiviral treatments, ongoing monitoring is crucial for patients with prior HCV infections due to residual liver damage.
Purpose of the Study:
- To investigate the immunohistochemical characteristics of lymphatic sprouts and mature lymphatic vasculature in the context of liver injury from HCV and fatty liver disease.
- To correlate lymphatic vascularity with histological features of liver damage, including staging, activity, and specific HCV genotypes.
Main Methods:
- Analysis of 72 liver biopsies from patients with chronic hepatitis C.
- Morphological assessment of liver injury (staging and activity) and immunohistochemical staining using D2-40 anti-podoplanin antibody.
- Quantification of histological variables and assessment of associations with HCV genotypes (1 and 3).
Main Results:
- Increased portal lymphatic sprouts and mature lymphatic vessels were observed with advancing liver disease, peaking in cirrhosis.
- Lymphatic vessel proliferation correlated with the degree of portal/septal inflammatory infiltrate.
- Fatty liver disease was more prevalent in patients with HCV genotype 3; no significant associations were found between lymphatic vessels and necro-inflammatory activity or HCV genotypes.
Conclusions:
- Immunohistochemistry with D2-40 effectively visualizes and quantifies lymphatic sprouts and vessels in HCV-related liver disease.
- Increased lymphatic vascularity is strongly associated with liver fibrosis progression, reaching its maximum in cirrhosis.
- No significant correlation was found between lymphatic vessel proliferation and the degree of necro-inflammatory activity within the liver parenchyma or at the interface.
Background:
Viral hepatitis C is a significant public health challenge. The disease may remain clinically silent in both acute and chronic forms, and chronic infections may progress to advanced disease such as cirrhosis and hepatocellular carcinoma, requiring costly treatment, compromising the patient's quality of life and even leading to death. For this reason, it is one of the most frequent indications for liver transplantation. Although treatment with direct-acting antivirals represents remarkable progress, many patients are still infected and even those who cleared the viral infection must be followed due to their previous hepatic lesions, especially regarding the disturbances of lobular architecture and the sanguineal and lymphatic vessels.
Objective:
To assess immunohistochemical aspects of lymphatic sprouts and mature lymphatic vascularity with histological variables of liver injury attributable to hepatitis C virus (HCV) and fatty disease.
Methods:
The present study included 72 liver biopsies of cases with chronic hepatitis C. Morphologic changes reflecting "staging" and "activity" were analyzed. Immunohistochemical reactions were performed with monoclonal antibody D2-40 anti-podoplanin. Major histological variables were also semiquantified so as to enable the search for possible associations among histological and Immunohistochemical criteria, as well as with genotypes 1 and 3 of HCV.
Results:
Histological findings showed that the different degrees of strutural changes were well represented in this casuistic. Intralobular/parenchymal necro-inflammatory activity was predominantly mild to moderate. Most cases did not show major evidences of fatty disease, which was found significantly higher in cases infected with HCV genotype 3. The amount of portal lymphatic sprouts increased along with the progression of structural changes, maximal at cirrhosis. Portal lymphatic sprouts as well as portal mature lymphatic vessels also showed an increase parallel to the increase in the degree of portal/septal inflammatory infiltrate. In the present study, no significant association was found between the proportion of portal lymphatic sprouts or portal mature lymphatic vessels and the degree of periportal/periseptal activity. No significant relations were detected between lymphatic sprouts/mature vessels and periportal or parenchymal inflammatory activity, nor with infections due to HCV genotype 1 or 3.
Conclusion:
Visualization and semiquantitation of sprouts and mature lymphatic vessels were clearly yielded by Immunohistochemical staining with monoclonal antibody D2-40. The amount of lymphatics was increased along fibrogenic process, significantly related to progression of liver disease and maximal at cirrhosis. No significant relations were detected with necro-inflammatory activity at interface or in the parenchyma.
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