HBVDNA水平的确有关系（2005.4.22）

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HBV DNA Plasma Levels Do Matter?br>

By Marina Nunez, MD, PhD

In an oral HBV session Dr Chen from the National Taiwan University presented results from the R.E.V.E.A.L.-HBV study which assessed the impact of HBV DNA levels on the development of hepatocellular carcinoma (HCC) [1].

The objectives of the study were:

1) To elucidate the independent effect of serum HBV DNA levels after adjusting by HBeAg serostatus and ALT levels on the development of HCC

?/span>2) To determine if HBV DNA levels increased the risk of developing HCC across biological gradients

3) To investigate if the decrease in HBV DNA levels over time has an impact on the incidence of HCC.

After interviewing 89,293 individuals from 30 to 65 years of age, 3,851 subjects with positive HBsAg were included in the study (43,993 person-years of follow-up). HBeAg was positive in 15% of the subjects.

The risk of developing HCC was strongly associated with higher HBV-DNA levels after adjustment for gender, age, habits of cigarette smoking, and alcohol consumption, anti-HCV antibodies, HBeAg and ALT levels (p<0.0001). Patients with ?/span> 106 copies/mL of serum HBV DNA had the highest incidence of HCC.

The RR after adjusting for HBeAg serostatus were 2.5 for HBV DNA levels 104-105 copies/mL and 6.4 for levels > 105 copies/mL, both compared to < 104 copies/mL.

Among people with ALT within normal limits, those with HBV DNA levels > 105 copies/mL had a 10.2-fold higher risk of developing HCC compared to those with undetectable HBV DNA.

Individuals with persistently elevated HBV DNA levels had higher risk of developing HCC compared to those who cleared the virus on repeat samples (RRadj: 6.4).

The authors concluded that the increase in incidence of HCC correlated with the increase in HBV DNA levels across gradients in persons with chronic hepatitis B, regardless of HBeAg serostatus, ALT levels and HCV coinfection. Moreover, reduction of HBV DNA levels over time was protective against the development of HCC. Asked by the audience, Dr Chen added that patients with HBV genotype C had both, higher levels of HBV DNA and higher incidence of HCC.

As summarized in table 1, several posters addressing the issue of the influence of HBV DNA levels on several clinical end-points in patients with chronic hepatitis B were presented at this meeting [2-7]. Several abstracts concern to data from the Asian study.?

These data suggest that effective suppression of HBV replication to very low levels may reduce progression of chronic hepatitis B to cirrhosis and prevent the development of HCC.?

Table 1. Abstracts presented at EASL 2005 meeting addressing the impact of HBV DNA levels on several clinical end-points in patients with chronic hepatitis B.

Abstract

End-point

N

Specific findings

# 476

Cirrhosis

3,774

?/span>105 vs. ?/span>103 cops/mL: RRadj: 8.6 in HBeAg+?and 4.9 in HBeAg-negative pts

i# 489

Cirrhosis

102

HBV-DNA levels correlated with severity of liver histology (p=0.04) in patients infected by HBV-D

# 496

Cirrhosis

3,774

Risk started to increase at 104 level (RRadj 2.4); RR 9.3 at >106 cops/mL.

# 497

Cirrhosis

3,851

?/span>105 vs. ?/span>103 cops/mL: RRadj: 6.1 in patients with normal ALT and 10.1 in those with abnormal ALT.

# 538

Decomp. Cir*

3,851

RRadj 7 for patients with HBV DNA levels >106 copies/mL.

# 477

Mortality

2,354

Increased mortality risk related to HCC and CLD across viral load categories

# 35

HCC

3,851

(See text above)

*Decompensated cirrhosis.

CLD: chronic liver disease.

HCC: hepatocellular carcinoma.

1. C J Chen and others. Elevated serum level of hepatitis B virus DNA is an independent risk factor for hepatocellular carcinoma: a long-term follow-up study in Taiwan. Abstract 35. 40th EASL. April 13-17, 2005. Paris, France.

2. C J Chen, and others. Viral load is a strong predictor of liver cirrhosis risk in people chronically infected with hepatitis B virus regardless of hepatitis B e antigen status. Abstract 476. 40th EASL. April 13-17, 2005. Paris, France.

3. G Germanidis, and others. What does the hepatitis B virus DNA level tell us in HBeAg-negative patients infected with HBV genotype D? Abstract 489. 40th EASL. April 13-17, 2005. Paris, France.

4. U H Iloeje, and others. Serum hepatitis B virus DNA level predicts the incidence of liver cirrhosis in persons chronically infected with HBV. Abstract 496. 40th EASL. April 13-17, 2005. Paris, France.

5. U H Iloeje, and others Viral load not serum ALT is the primary predictor of progression to cirrhosis in persons chronically infected with HBV: results from a long-term prospective study. Abstract 497. 40th EASL. April 13-17, 2005. Paris, France.

6. H I Yang, and others. Progression to decompensated cirrhosis in chronic hepatitis B virus infected persons is strongly associated with baseline viral load. Abstract 538. 40th EASL. April 13-17, 2005. Paris, France.

7. G Chen, and others. Viral load as a predictor of mortality from hepatocellular carcinoma and chronic liver disease in chronic hepatitis B infection. Abstract 477. 40th EASL. April 13-17, 2005. Paris, France.