Relationship between hepatocyte proliferation and hepatitis delta virus replication in neoplastic and non‐neoplastic liver tissues

Abstract

We studied the relationship between hepatocyte proliferation and hepatitis delta virus (HDV) replication at the single cell level. The proliferating cell nuclear antigen (PCNA) (by immunohistochemistry) and the HDV RNA (by in situ hybridization) were stained in neoplastic and non-neoplastic liver tissues of 19 patients with chronic HDV infection, including four cases of cirrhosis with superimposed hepatocellular carcinoma (HCC). As controls, we assessed the hepatocyte proliferation of liver tissues from 16 patients with chronic hepatitis B and on three normal livers. The hepatocyte PCNA labelling index of HDV-infected tissues was comparable with that seen in chronic hepatitis B-infected livers but was significantly higher than that observed in normal livers. Although cirrhotic tissues had lower hepatocyte proliferating fractions than non-cirrhotic tissues, the difference was not statistically significant. The hepatocyte proliferation rate did not correlate with the level of intrahepatic HDV replication or with the histological activity. In double-labelling experiments, PCNA and HDV RNA staining did not co-localize, with the exception of two of three cirrhotic tissues associated with HCC, where the association between the two markers was statistically significant. This co-localization was not observed, however, in the adjacent tumorous tissues. In patients with chronic HDV infection the hepatocyte proliferation was increased with respect to normal liver tissue, but was comparable with that observed in patients with chronic hepatitis B virus infection and did not correlate with the level of HDV replication or the histological activity. In the cirrhotic tissue of patients with HCC (but not in the tumour counterpart), HDV RNA may occasionally co-localize with the marker of hepatocyte proliferation. Whether this association between viral replication and cell division is related to liver carcinogenesis remains to be established.

IFN-alpha prevents the growth of pre-neoplastic lesions and inhibits the development of hepatocellular carcinoma in the rat

“…Hepatocellular carcinoma (HCC) is one of the most common cancers in the world. In hepatitis B virus (HBV) or hepatitis C virus (HCV) carriers, persistent virus infection seems to be associated with hepatocarcinogenesis (1,2). Interferon (IFN)alpha can eradicate the hepatitis virus and is clinically useful for treating persistent hepatitis.…”

Different responses of rat liver adenosine metabolizing enzymes during in vivo and in vitro treatment with interferon‐α2b

“…Persistent hepatitis B or hepatitis C infection seems to be associated with an accelerated progression towards hepatocellular carcinoma, perhaps because of stimulated hepatic proliferation [1,2]. Several studies have documented that interferon-α2b (IFN-α2b) possesses an antiproliferative effect in both normal and malignant liver cells.…”

Hepatocellular Carcinoma. Recent Advances in Diagnosis and Treatment

“…Впервые измерение АФП-L3 для диагностирования ГЦК было предложено Taketa и соавторами в 1990 году [12]. Чувствительность и специфичность АФП-L3 при уровне интерпретации маркера 15% варьирует от 75% до 96,9% и от 90 до 92% соответственно [11,22]. По сравнению с АФП показатель АФП-L3 обладает более высокой специ фичностью, но схожей чувствительностью.…”