Evaluation of Impact of Serial Hepatitis B Virus DNA Levels on Development of Hepatocellular Carcinoma

Abstract

We aimed to investigate the impact of hepatitis B virus (HBV) DNA on the development of hepatocellular carcinoma (HCC). We conducted a case/control study based on 506 chronic HBV patients followed up since 1997. Forty-one patients developed HCC, and each of them was age and gender matched with two simultaneously recruited controls without HCC. HBV DNA was measured at the initial visit, at yearly intervals, and at the last visit. Patient age at the time of HCC development was 55 ؎ 9 years. Forty-nine (40%) patients experienced antiviral treatment. The median time from diagnosis to the development of HCC was 17 months, and the control patients were followed for 92 months. At the trough level (defined as lowest level among all studied visits), more (27 patients; 66%) HCC patients had HBV DNA levels of >10,000 copies/ml than the controls (17 patients; 21%). The area under the receiver operating characteristic curve of the trough log HBV DNA level for HCC was 0.79 (95% confidence interval [CI], 0.69 to 0.89). Trough log HBV DNA (odds ratio, 11.4; 95% CI, 3.6 to 37.6; P < 0.0001) and liver cirrhosis (odds ratio, 11.4; 95% CI, 3.6 to 36.2; P < 0.0001) levels were independently associated with HCC after an adjustment for age, gender, antiviral treatment, and HBV genotype. The difference in the trough HBV DNA level was more obvious among untreated patients (5.7 ؎ 1.4 log copies/ml in HCC patients versus 3.2 ؎ 1.3 log copies/ml in control patients; P < 0.0001) than among those who had received antiviral treatment (3.0 ؎ 1.4 log copies/ml in HCC patients versus 2.5 ؎ 0.9 log copies/ml in control patients; P ‫؍‬ 0.38). A high trough HBV DNA level was associated with a higher risk of HCC. Whether antiviral treatment could prevent HCC was uncertain.

Impact of Serial Hepatitis B Virus DNA on Hepatocellular Carcinoma Development in Patients with Liver Cirrhosis

“…However, our retrospective study had too small a number to suggest the usefulness of antiviral treatment in liver cirrhosis for preventing the HCC. This is the consistent with the recent report by Chan et al [19] .…”

“…In that study [19] , among patients with antiviral treatment, the differences in trough HBV DNA levels between the HCC and control patients were less obvious, although among patients without antiviral treatment, HCC patients had significantly higher trough HBV DNA levels than the control patients. They were not able to match the cirrhosis status and treatment status, although the importance of the trough HBV DNA level remained significant after adjustment for the treatment factor.…”

Potential risk factors for the reactivation of the replication of hepatitis B and C viruses after transcatheter arterial chemoembolization of hepatocellular carcinoma

“…Increase of HBV DNA viral loads can initiate host immune response and also cause elevation of ALT levels [23,24]. HBV reactivation after chemotherapy or immunosuppressive therapy might follow the two steps.…”

Molecular mechanisms of transcriptional regulation by Poly(ADP-ribose) polymerase 1

“…Repair related PARP1 activity is suppressed to ensure efficient virus replica tion, while PARP1 binding to the ACTTCAAA sequence of the virus genome provides a signal for transcriptional activation of virus genes [105]. This may trigger expression of the oncogenic properties of HBV, especially when virus DNA accumulates to a high level [118][119][120]. PARP1 increases the efficien cies of virus DNA replication and transcription, while PARP1 dependent ADP ribosylation is inhibited and repair activity is consequently decreased in the infected host cell.…”