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Increasing Serial HBV Viral Load & ALT Predicts HCC
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SERIAL MONITORING OF VIRAL LOAD AND SERUM ALANINE AMINOTRANFERASE LEVEL AND THE RISK OF HEPATOCELLULAR CARCINOMA (HCC): R.E.V.E.A.L.-HBV STUDY UPDATE
Reported by Jules Levin
43rd EASL Conference
April 23-27, 2008
Milan, Italy
C.J. Chen1,2, H.I. Yang1,2, J. Su3, C.L. Jen1,2, S.L. You1,2, C.F. Chen1,2, U.H. Iloeje4
1 Genomics Research Center, Academia Sinica, Taipei, Taiwan;
2 Graduate Institute Of Epidemiology, College Of Public Health, National Taiwan University, Taipei, Taiwan;
3 Global Epidemiology And Outcomes Research, Research And Development, Bristol-Myers Squibb Company, Wallingford, CT, USA;
4 Global Clinical Research, Research And Development, Bristol-Myers Squibb Company, Wallingford, CT, USA
PROGRAM ABSTRACT
Background and aims: Published data from the R.E.V.E.A.L.-HBV study showed that baseline viral load significantly predicted HCC risk. However, this analysis included subjects with baseline cirrhosis and did not evaluate the importance of serial HBV-DNA or serial ALT monitoring in predicting HCC risk. This analysis addresses HCC risk using the complete data on serial ALT and viral load.
Methods: This analysis included participants who were HBsAg-seropositive, anti-HCV- seronegative, and without liver cirrhosis at entry. All the follow-up blood samples available for all subjects with baseline HBV-DNA >=10-4th copies/mL (n=1,564) were tested, and for those <10-4th copies/mL (n=2,020) only baseline samples were used. Newly developed HCC was ascertained through data linkage with computerized profiles of the National Cancer Registry and Death Certification System in Taiwan and confirmed with established criteria. Time-dependent CoxÕs proportional hazard models were used to derive multivariable-adjusted hazards ratios (HRadj) which included entry and follow-up serum HBV-DNA levels as time-independent and time-dependent variables respectively.
Results:
3,584 subjects contributed 42,878 person-years of follow-up, with 131 new HCC cases accounting for a crude incidence rate of 305.5 per 100,000 person-years.
In the regression model adjusting for gender, age, cigarette smoking, alcohol consumption, and HBeAg status, HCC risk increased with increasing ALT and HBV-DNA levels (p for trend<0.001).
In a model integrating both baseline and follow-up HBV-DNA (same for serum ALT), the HRadj (95% CI) were
4.5 (1.3Ð15.2) for HBV-DNA levels of 300Ð9,999 copies/ml
3.6 (1.1Ð12.3) for HBV-DNA levels of 10,000-99,999 copies/ml
4.2 (1.2Ð14.5) for 100,000Ð999,999 c/ml
7.3 (2.3Ð23.5) >10-6th (1 million) copies/mL
(reference HBV-DNA <300 copies/mL)
The corresponding HRadj (95% CI) for serum ALT levels were 1.8 (1.2Ð2.8) and 3.8(2.3Ð6.5), respectively, for ALT 16Ð<45 and >=45 U/L (reference ALT <16 U/L).
Age, gender, HBeAg status, and alcohol consumption were also important predictors of HCC risk.
Conclusions: These results confirm that increasing HBV-DNA level remains a significant predictor of HCC after taking follow-up HBV-DNA and change in serum ALT into account. The persistence of high HBV load leads to the highest HCC risk. Long-term monitoring of HBV viral load is essential for the management of chronic hepatitis B.
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