Higher HBV DNA Levels Linked to Increased Risk of Liver Cirrhosis in People with Chronic Hepatitis B

Over years or decades, chronic hepatitis B virus (HBV) infection can lead to the development of advanced liver disease, including cirrhosis and hepatocellular carcinoma.

Some previous research has shown that serum HBV DNA levels directly correlate with progression to cirrhosis in chronic hepatitis B patients, but previous studies have been limited by the fact that HBV DNA was only measured at the time of enrollment.

In a study presented at the Digestive Disease Week 2008 conference last month in San Diego, researchers investigated the relationship between HBV DNA levels and progression to cirrhosis over a longer follow-up period.

The study included 239 chronic hepatitis B patients confirmed by liver biopsy between 2001 and 2007 at the Zhong Shan Hospital of Fudan University in Shanghai, China.

Participants were followed for a mean period of 32 months (range 5 to 77 months). HBV DNA was measured at study entry and at the follow-up endpoint. Other blood tests including HBV serum markers (antibodies and antigen), hemoglobin, white blood cell and platelet counts, total bilirubin, albumin, prothrombin time, and the liver enzymes ALT, AST, GGT, and alkaline phosphatase were measured at study entry.

Liver inflammation grade and fibrosis stage were determined using Scheuer's
classification. The clinical endpoint was cirrhosis, which was diagnosed by ultrasound, computerized tomography (CT) scans, and clinical features.

Results

• Compared to patients without cirrhosis, the group that progressed to cirrhosis was on average older and had higher serum HBV DNA levels at the endpoint.

• Kaplan-Meier analysis showed that higher HBV DNA level at the endpoint was significantly associated with increased risk of cirrhosis progression (P = 0.021).

• However, there was no significant difference in cirrhosis progression related to baseline HBV DNA level at study entry (P = 0.531).

• Cox regression indicated that the following were independent risk factors for cirrhosis:

• HBV DNA level at the endpoint (relative risk [RR] 2.034; P = 0.002);
• Fibrosis stage (RR 1.609; P = 0.049);
• Hepatitis B "e" antigen (HBeAg) positive status (RR 0.097; P = 0.008);
• Alkaline phosphatase level (RR 1.011; P = 0.020).

Conclusions

"Progression to cirrhosis in chronic hepatitis B patients is correlated strongly with fluctuation of HBV DNA levels," the investigators concluded. "Sustained high level of viral replication is an independent risk factor for cirrhosis."

6/06/08

Reference
J Wang and L Liu. Correlation between HBV DNA level and progression to cirrhosis in patients with chronic hepatitis B. Digestive Disease Week (DDW) 2008. San Diego, CA. May 17-22, 2008. Abstract M1925.