Hepatitis B Viral Replication Affects Hepatocellular Carcinoma Recurrence
Hepatitis B Viral Replication Affects Hepatocellular Carcinoma Recurrence
Background: Elevated serum hepatitis B virus (HBV) DNA increases the development of hepatocellular carcinoma (HCC). Rather than instantaneous DNA level, the duration of persistent HBV replication is more important in carcinogenesis. Nevertheless, most investigators evaluated the DNA level at study entry. We assessed the effects of persistently detectable serum HBV DNA on HCC recurrence.
Patients and methods: We included 230 consecutive patients undergoing curative resection between 2000 and 2006. Patients who had antiviral therapy (at diagnosis or during follow-up), fluctuating DNA (cut-off value: 100 000 copies/ml) or recurrence within 12 months of resection were excluded. Ultimately, 157 were enrolled: 89 (non-viraemia group) had consistently negative DNA (<100 000 copies/ml), while 68 (viraemia group) had consistently positive DNA (> 100 000 copies/ml). Serum DNA level, biochemical tests, α-foetoprotein (AFP) and liver dynamic computed tomography were obtained every 3 months after surgery.
Results: There were no significant differences in age, gender, liver function, histology, AFP, tumour stages or follow-up duration between the two groups. During follow-up (median: 35 months), patients in the non-viraemia group had a lower 5-year cumulative recurrence rate (54.7%) than those in the viraemia group (72.9%; P = 0.043). In multivariate analysis, sustained viraemia (P = 0.041) increased recurrence independently.
Conclusions: Persistent viraemia increased recurrence independently after surgery. To prevent long-term recurrences, antiviral therapy should be initiated in those with detectable serum HBV DNA.
Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related deaths worldwide, with an annual incidence of approximately one million cases. Aetiologically, the majority of HCC develops in chronic hepatitis B virus (HBV) carriers. Individuals with chronic HBV infection have a 100-fold relative risk of developing HCC compared with non-carriers, and have increased incidences of liver cirrhosis and hepatic decompensation. Recently, an elevated serum HBV DNA level has been reported to be a strong predictor of the development of HCC and liver cirrhosis, regardless of the hepatitis B e antigen (HBeAg) status and serum alanine aminotransferase (ALT) level. In chronic HBV infection, in addition to an indirect mechanism induced by chronic necro-inflammatory processes, the high risk of HCC may also result from the oncogenic effects of HBV DNA. The X protein of HBV is said to contribute to carcinogenesis by activating proto-oncogenes, such as c-fos and c-jun, and inhibiting the p53 tumour suppressor gene.
Hepatic resection or transplantation is still the mainstay of treatment; however, the post-resection tumour recurrence rate remains high, with a cumulative 5-year tumour recurrence rate ranging from 40 to 80%. Many studies have examined the risk factors for recurrence after resection, identifying tumour number, size, vascular invasion and Edmondson grade as significant prognostic factors. Only a few studies have evaluated the viral replicative status of subjects as a predictor of recurrence, and these were limited in that most investigators evaluated the serum level of circulating virus measured at one time only (usually at the time of surgery) as a risk factor, and other factors for recurrence, including the occurrence of early recurrence from occult metastasis, the presence of acute exacerbation and the use of antiviral therapy, were not fully explained in their studies.
In fact, the duration of persistent HBV replication, that is, persistently detectable serum HBV DNA documented in serial examinations, rather than the instantaneous serum HBV DNA, is reported to better reflect the chronic liver damage resulting in liver cirrhosis and HCC. This is the first study to survey the natural course of patients with sustained viraemia documented in serial examinations after curative HCC resection and to validate its effects on recurrence.
We compared the long-term recurrence rate and survival outcomes according to the presence or the absence of sustained HBV viraemia after surgery.
Background: Elevated serum hepatitis B virus (HBV) DNA increases the development of hepatocellular carcinoma (HCC). Rather than instantaneous DNA level, the duration of persistent HBV replication is more important in carcinogenesis. Nevertheless, most investigators evaluated the DNA level at study entry. We assessed the effects of persistently detectable serum HBV DNA on HCC recurrence.
Patients and methods: We included 230 consecutive patients undergoing curative resection between 2000 and 2006. Patients who had antiviral therapy (at diagnosis or during follow-up), fluctuating DNA (cut-off value: 100 000 copies/ml) or recurrence within 12 months of resection were excluded. Ultimately, 157 were enrolled: 89 (non-viraemia group) had consistently negative DNA (<100 000 copies/ml), while 68 (viraemia group) had consistently positive DNA (> 100 000 copies/ml). Serum DNA level, biochemical tests, α-foetoprotein (AFP) and liver dynamic computed tomography were obtained every 3 months after surgery.
Results: There were no significant differences in age, gender, liver function, histology, AFP, tumour stages or follow-up duration between the two groups. During follow-up (median: 35 months), patients in the non-viraemia group had a lower 5-year cumulative recurrence rate (54.7%) than those in the viraemia group (72.9%; P = 0.043). In multivariate analysis, sustained viraemia (P = 0.041) increased recurrence independently.
Conclusions: Persistent viraemia increased recurrence independently after surgery. To prevent long-term recurrences, antiviral therapy should be initiated in those with detectable serum HBV DNA.
Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related deaths worldwide, with an annual incidence of approximately one million cases. Aetiologically, the majority of HCC develops in chronic hepatitis B virus (HBV) carriers. Individuals with chronic HBV infection have a 100-fold relative risk of developing HCC compared with non-carriers, and have increased incidences of liver cirrhosis and hepatic decompensation. Recently, an elevated serum HBV DNA level has been reported to be a strong predictor of the development of HCC and liver cirrhosis, regardless of the hepatitis B e antigen (HBeAg) status and serum alanine aminotransferase (ALT) level. In chronic HBV infection, in addition to an indirect mechanism induced by chronic necro-inflammatory processes, the high risk of HCC may also result from the oncogenic effects of HBV DNA. The X protein of HBV is said to contribute to carcinogenesis by activating proto-oncogenes, such as c-fos and c-jun, and inhibiting the p53 tumour suppressor gene.
Hepatic resection or transplantation is still the mainstay of treatment; however, the post-resection tumour recurrence rate remains high, with a cumulative 5-year tumour recurrence rate ranging from 40 to 80%. Many studies have examined the risk factors for recurrence after resection, identifying tumour number, size, vascular invasion and Edmondson grade as significant prognostic factors. Only a few studies have evaluated the viral replicative status of subjects as a predictor of recurrence, and these were limited in that most investigators evaluated the serum level of circulating virus measured at one time only (usually at the time of surgery) as a risk factor, and other factors for recurrence, including the occurrence of early recurrence from occult metastasis, the presence of acute exacerbation and the use of antiviral therapy, were not fully explained in their studies.
In fact, the duration of persistent HBV replication, that is, persistently detectable serum HBV DNA documented in serial examinations, rather than the instantaneous serum HBV DNA, is reported to better reflect the chronic liver damage resulting in liver cirrhosis and HCC. This is the first study to survey the natural course of patients with sustained viraemia documented in serial examinations after curative HCC resection and to validate its effects on recurrence.
We compared the long-term recurrence rate and survival outcomes according to the presence or the absence of sustained HBV viraemia after surgery.
Source...