Factors Associated with Progression to Cirrhosis and Liver Cancer

It is clear that a proportion of patients with chronic hepatitis B virus (HBV) infection eventually develop cirrhosis and/or hepatocellular carcinoma (HCC), but the factors that predict liver disease progression are not well understood.

Predictors of Cirrhosis

One study presented at the Digestive Disease Week 2006 conference investigated the relationship between clinical and pathological features and the development of cirrhosis in patients with chronic hepatitis B.

Researchers collected data and liver biopsy results for consecutive chronic hepatitis B patients hospitalized at Zhongshan Hospital in Shanghai from May 1993 through January 2004; those receiving HBV treatment were excluded. Follow-up continued through June 2004

Results

A total of 434 patients met the inclusion criteria, 52 of whom were lost to follow-up. Of the remaining 382 individuals, 315 were men, the mean age was 34 years, and 262 were HBeAg-positive. After an average follow-up period of 89 weeks (range 20-260), 75 patients (19.6%) developed compensated cirrhosis, for an annual occurrence rate of 0.95%. Of these, 32 (8.4%) progressed to decompensated cirrhosis, for an annual occurrence rate of 0.39%.

By HBeAg status, 22.5% of HBeAg-negative patients developed compensated cirrhosis, compared with 18.3% of HBeAg-positive patients; for decompensated cirrhosis, the corresponding rates were 11.61% and 6.87%. There was no statistically significant difference between the HBeAg-negative and HBeAg-positive subjects in terms of liver disease grade or stage.

The study also found that histological stage at the time of hospitalization was an independent predictive factor for development of compensated and decompensated cirrhosis. However, a multivariate analysis showed that histological grade, serum albumin level, ALT and AST, alpha-fetoprotein (AFP), and prothrombin time were not associated with development of cirrhosis.

Conclusion

The researchers concluded that fibrosis stage at the time of presentation was strongly associated with the development of compensated and decompensated cirrhosis. But neither inflammatory grade nor HBeAg-negative status was predictive of cirrhosis.

Occult HBV and HCC

A second study looked at the relationship between occult HBV infection¾defined as the detection of HBV DNA in serum or liver tissue of HBV surface antigen (HBsAg)-negative patients¾and the development of HCC. Patients with occult HBV who have HBV core antibodies (anti-HBc) may also have HBV surface antibodies (anti-HBs); such individuals show evidence for immunoclearance of HBsAg, while patients who lack anti-HBs are often regarded as low-grade viremic HBV carriers.

HCC is uncommon in patients with occult HBV infection; when it does occur, HBV DNA typically can be detected in the liver and tumor tissues. In this study, researchers attempted to determine whether presence of anti-HBsAb was related to the extent of HBV integration into tumor and non-tumor tissue.

The study included 11 consecutive HBsAg-negative, anti-HBc-positive patients with HCC who underwent surgical resection at Singapore General Hospital. Subjects were classified as either anti-HBs-positive or anti-HBs-negative. PCR testing was performed to detect HBV “S” and “X” genomes in serum and tumor and non-tumor tissue.

Results

The HBV “S” genome was detected in 83% of tumor tissue and 100% of non-tumor tissue samples from anti-HBs-positive patients, compared with 80% and 60%, respectively, from anti-HBs-negative subjects. The “X” genome was detected in 50% of tumor tissue and 100% of non-tumor tissue samples from anti-HBs-positive patients, and 100% and 60%, respectively, from anti-HBs-negative subjects. The “X” genome was not detected in serum from any of the patients, and the “S” genome was detected in serum from just one anti-HBs-positive patient.

Conclusion

The researchers concluded that despite the presence or lack of anti-HBs, HBV genomic integration occurred to a similar extent in host liver tissue of patients with HCC. This suggests that the pathogenesis of HCC is similar in patients with occult HBV whether they are anti-HbsAb-positive or -negative. As such, strategies to prevent the development of HCC should be similar regardless of anti-HBs status.

6/06/06

References

J. Wang, H. Wang, C. Zhu. The relationship between clinical/pathological features and development of cirrhosis in 382 Chinese patients with chronic hepatitis B. Abstract T1856. Digestive Disease Week 2006 (DDW 2006). May 20-25, 2006. Los Angeles, CA.

C. Tan, J. Chang, G. Lim, and others. Occult hepatitis B virus infection with and without anti-HBs antibodies¾implications in the development of hepatocellular carcinoma C. Abstract T1862. DDW 2006. May 20-25, 2006. Los Angeles, CA.