Abstract
Hepatitis B virus infection is a well-known risk factor for intrahepatic cholangiocarcinoma. However, its prognostic impact has rarely been investigated in advanced intrahepatic cholangiocarcinoma. Between April 2010 and May 2015, 296 patients with unresectable or metastatic intrahepatic cholangiocarcinoma who received gemcitabine plus cisplatin (GemCis) were categorized into a hepatitis B virus group (n=62; 21%) and a non-hepatitis B virus group (n=234; 79%). Clinicopathological features and survival outcomes were retrospectively reviewed and analyzed. The median age of patients was 59 years (range, 27-78). The median overall survival with first-line GemCis was 9.4 months (95% CI 8.4, 10.4). Compared to the non-hepatitis B virus group, the hepatitis B virus group was younger (median age, 57 vs. 61 years, P = 0.001), mainly male (74% vs. 57%, P = 0.02), and had lower frequency of elevated cancer antigen (CA) 19-9 (34% vs. 59%, P = 0.001) and alkaline phosphatase (43% vs. 61%, P = 0.01). In a univariate analysis, the hepatitis B virus infection showed a marginal relationship with poor overall survival compared to the non-hepatitis B virus infection (median, 8.3 vs. 10.0 months; P=0.13). A multivariate analysis of potential prognostic factors revealed a significant association with poor overall survival in the hepatitis B virus group (hazard ratio (HR) =1.50, P = 0.02). Initial metastatic disease (vs. recurrent/unresectable disease; HR=1.50), metastatic sites ⩾ 2 (vs. 0-1; HR=1.51), Eastern Cooperative Oncology Group performance status ⩾ 2 (vs. 0-1; HR=1.93), elevated total bilirubin (vs. normal; HR=1.83), and low albumin (vs. normal; HR=1.52) were significantly related to an unfavorable overall survival. This study suggests that the hepatitis B virus infection may be associated with distinctive clinicopathological characteristics and poor outcome in advanced intrahepatic cholangiocarcinoma treated with GemCis.
Highlights
Intrahepatic cholangiocarcinoma (ICC) is the second most common hepatic malignancy following hepatocellular carcinoma (HCC), and accounts for approximately 10% of all liver cancers.[1]
The mechanism of the development of ICC by chronic hepatitis B infection is unclear, patients with hepatitis B virus (HBV)-associated ICC have been reported to have different clinicopathological characteristics and survival outcomes compared to patients without HBV infection
Because many ICC patients present with advanced disease at the time of initial diagnosis, and have a high recurrence rate even after curative resection, evaluating the impact of HBV infection on the clinical outcomes of patients with gemcitabine plus cisplatin (GemCis), the standard first-line chemotherapy for unresectable or metastatic cholangiocarcinoma, is important.[6,7]
Summary
Intrahepatic cholangiocarcinoma (ICC) is the second most common hepatic malignancy following hepatocellular carcinoma (HCC), and accounts for approximately 10% of all liver cancers.[1]. Various risk factors of ICC have been identified, including hepatolithiasis, primary sclerosing cholangitis, primary biliary cirrhosis, choledochal cysts, and hepatic parasite infections.[3] Recently, hepatitis B virus (HBV)—a widely known cause of liver cirrhosis and HCC—has been recently found to be associated with the development of ICC in HBV epidemic areas.[4,5] the mechanism of the development of ICC by chronic hepatitis B infection is unclear, patients with HBV-associated ICC have been reported to have different clinicopathological characteristics and survival outcomes compared to patients without HBV infection Such previous studies were mainly performed in patients with early resectable ICC. We retrospectively analyzed patients with advanced ICC who received first-line GemCis to compare clinicopathological features and clinical outcomes according to HBV infection
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