Abstract

Objective and BackgroundThe roles of chronic hepatitis B virus (HBV) co-infection (CI) in carcinogenesis of hepatitis C virus (HCV)-associated hepatocellular carcinoma (HCC) remained controversial. To gain new insights into this issue, we investigated the postoperative prognostic value of HBVCI in HCV-associated HCC.MethodsA study cohort of 115 liver tissues obtained from the noncancerous parts of surgically removed HCV-associated HCCs were subjected to virological analysis in a tertiary care setting. Assayed factors included clinicopathological variables, tissue amounts of viral genomes, genotypic characterization of viruses, as well as the presence of overt (serum HBsAg positive) or occult (serum HBsAg negative but tissue HBV-DNA positive) HBVCI. Cox proportional hazard model was used to estimate postoperative survivals.ResultsOf the 115 patients, overt and occult HBVCIs were detected in 35 and 16 patients, respectively. Multivariate analysis revealed that tumor size >3 cm (adjusted hazard ratio (AHR), 2.079 [95% confidence interval, 1.149∼3.761]), alpha-fetoprotein >8 ng/mL (AHR, 5.976 [2.007∼17.794]) albumin <4 g/dL(AHR, 2.539 [1.399∼4.606]), ALT >50 U/L (AHR,1.086 [1.006∼1.172]), presence of occult HBVCI (AHR, 2.708 [1.317∼5.566]), and absence of overt HBVCI (AHR, 2.216 [1.15∼4.269]) were independently associated with unfavorable disease-free survival. Patients with occult HBVCI had a shorter disease-free (P = 0.002), a shorter overall survival (P = 0.026), a higher bilirubin level (P = 0.003) and a higher prevalence of precore G1896A mutation (P = 0.006) compared with those with overt HBVCI.ConclusionOccult and overt HBVCI served as independent predictors for postoperative survival in HCV-associated HCC.

Highlights

  • Hepatocellular carcinoma (HCC) accounts for .90% of primary liver malignancies and ranks the fifth most common solid cancer and the third leading cause of cancer-related death worldwide [1]

  • About three-quarters of HCCs are attributed to chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections [2]

  • HCV infection is the most important risk factor for HCC in Hispanics and African Americans, whereas HBV infection is the dominant risk in Asians [4]

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Summary

Introduction

Hepatocellular carcinoma (HCC) accounts for .90% of primary liver malignancies and ranks the fifth most common solid cancer and the third leading cause of cancer-related death worldwide [1]. About three-quarters of HCCs are attributed to chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections [2]. Chronic HCV infection was found in .30% of HCC patients and the prevalence of HBV decreased to about 70% [6]. A high prevalence of occult HBV co-infection (HBVCI) has been found in patients with chronic HCV infection [12]. In Japan, a hyperendemic area for HCV infection, the prevalence of occult HBVCI in patients infected with HCV ranged from 37 to 95% [13] comparing with 0 to 20% in patients of a control population [14]

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