Persistent Hepatitis B Viral Replication Affects Recurrence of Hepatocellular Carcinoma After Curative Resection

[Guest guest]

FULL TEXT: http://www.medscape.com/viewarticle/575629?src=mp & spon=43 & uac=31238BR

From Liver International

Persistent Hepatitis B Viral Replication Affects Recurrence of Hepatocellular

Carcinoma After Curative Resection

Posted 06/27/2008

Beom Kyung Kim; Jun Yong Park; Do Young Kim; Ja Kyung Kim; Kyung Sik Kim; Jin

Sub Choi; Byung Soo Moon; Kwang Hyub Han; Chae Yoon Chon; Young Myoung Moon;

Sang Hoon Ahn

Abstract and Introduction

Abstract

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, á-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.

Introduction

Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related

deaths worldwide, with an annual incidence of approximately one million

cases.[1-3] Aetiologically, the majority of HCC develops in chronic hepatitis B

virus (HBV) carriers.[4] 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.[4,5] 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.[6-9] 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.[9-11]

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%.[12,13] Many

studies have examined the risk factors for recurrence after resection,

identifying tumour number, size, vascular invasion and Edmondson grade as

significant prognostic factors.[3,14,15] 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.[16] 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.

_________________________________________________________________

Need to know now? Get instant answers with Windows Live Messenger.

http://www.windowslive.com/messenger/connect_your_way.html?ocid=TXT_TAGLM_WL_mes\

senger_072008