Update on the association of hepatitis B with intrahepatic cholangiocarcinoma: Is there new evidence?

Abstract

Intrahepatic cholangiocarcinoma (iCCA) is a subgroup of cholangiocarcinoma that accounts for about 10%-20% of the total cases. Infection with hepatitis B virus (HBV) is one of the most important predisposing factors leading to the formation of iCCA. It has been recently estimated based on abundant epidemiological data that the association between HBV infection and iCCA is strong with an odds ratio of about 4.5. The HBV-associated mechanisms that lead to iCCA are under intense investigation. The diagnosis of iCCA in the context of chronic liver disease is challenging and often requires histological confirmation to distinguish from hepatocellular carcinoma. It is currently unclear whether antiviral treatment for HBV can decrease the incidence of iCCA. In terms of management, surgical resection remains the mainstay of treatment. There is a need for effective treatment modalities beyond resection in both first- and second-line treatment. In this review, we summarize the epidemiological evidence that links the two entities, discuss the pathogenesis of HBV-associated iCCA, and present the available data on the diagnosis and management of this cancer.

HBcAb positivity increases the risk of postoperative complications after extended hemihepatectomy for hilar cholangiocarcinoma

“…Numerous studies demonstrated that HBV infection was closely associated with hepatocellular carcinoma (HCC) and CCA. 26 , 27 , 28 , 29 , 30 Although the exact effect of HBV on tumorigenesis is unknown, integration of HBV DNA into the host genome induces genomic instability and direct insertion mutations of multiple cancer‐related genes, which have been proven to be an essential risk factor for carcinogenesis. 28 , 30 As we all know, both hepatocytes and cholangiocytes have the same progenitor cells.…”

“… 31 In addition, inflammatory changes caused by the continuous presence of the virus involve multiple signaling pathways leading to malignant transformation. 29 HBcAb positivity reflects prior HBV infection, which has recently attracted attention as a risk factor for liver carcinogenesis. 32 , 33 , 34 A previous meta‐analysis suggested that HBcAb positivity increased the risk of cholangiocarcinoma.…”

“…Therefore, HBV is likely to induce HCC and CCA through similar mechanisms 31 . In addition, inflammatory changes caused by the continuous presence of the virus involve multiple signaling pathways leading to malignant transformation 29 . HBcAb positivity reflects prior HBV infection, which has recently attracted attention as a risk factor for liver carcinogenesis 32–34 .…”

Immune Microenvironment and Immunotherapeutic Management in Virus-Associated Digestive System Tumors

“…Chronic inflammatory state is considered crucial for iCCA development regardless of the etiopathogenic mechanism that induces it. This state favors carcinogenesis via promoting genetic and epigenetic aberrations [ 42 , 43 ]. Carcinogenesis is facilitated by the overregulation of several growth factors and cytokines that promote increased cell multiplication, as well as angiogenesis.…”

MRI for Hepatitis B‐Associated Intrahepatic Cholangiocarcinoma: A Multicenter Comparative Study

“…[3][4][5] Viral hepatitis may involve multiple pathways acting through diverse mechanisms in an environment conducive of proliferation and oncogene mutations leading to malignant transformation, and may act as an oncogene and promote oncogenicity per se. 4 Moreover, HBV infection has recently been suggested as a favorable prognostic factor for iCCA, relating to better survival. [6][7][8][9] However, compared to iCCAs without HBV infection, diagnosis of iCCA is challenging in HBV-infected patients due to the overlapping clinical manifestations and imaging patterns, especially with patients suffering from HCC.…”