Occult, overt HBV coinfection predictive of outcomes from HCV-associated HCC

Chang M-L. PloS One. 2013;doi:10.1371/journal.pone.0064891.

  • July 16, 2013

Disease-free survival after surgical treatment of hepatitis C-associated hepatocellular carcinoma was significantly influenced by occult or overt hepatitis B coinfection in a recent study.

Researchers evaluated liver tissue from 115 patients with HCV-associated hepatocellular carcinoma (HCC) who underwent total surgical removal of tumors between July 1998 and August 2001 at Chang Gung Memorial Hospital in Linko, Taiwan. All tissue was collected from the noncancerous parts of the removed HCC.

Chau-Ting Yeh, MD, PhD

Chau-Ting Yeh

“Theoretically, occult HBV-infected patients can have negative serum HBV DNA and negative serum HBsAg, but positive liver tissue HBV DNA,” researcher Chau-Ting Yeh, MD, PhD, director of the Liver Research Center at the hospital, told Healio.com. “[However,] it is very difficult to identify such patients. Using surgically removed HCC tissue, we have an excellent opportunity to look into this issue.”

Overt hepatitis B coinfection (HBVCI) was observed in 35 patients, and occult coinfection was observed in 16 patients. These groups had similar HCV RNA levels or HCV genotype. Among 12 patients with positive anti-HCV but negative serum and tissue HCV RNA, nine patients had overt and one had occult HBVCI, suggesting that HBV repressed HCV replication, Yeh said.

Significant associations were observed between poor disease-free survival and occult HBV infection (adjusted HR=2.708; 95% CI, 1.317-5.566) and lack of overt HBVCI (aHR=2.216; 95% CI, 1.15-4.269), along with alpha-fetoprotein levels above 8 ng/mL (aHR=5.976; 95% CI, 2.007-17.794), albumin levels of 4 g/dL or lower (aHR=2.539; 95% CI, 1.399-4.606), ALT of greater than 50 U/L (aHR=1.086; 95% CI, 1.006-1.172) and tumors greater than 3 cm (aHR=2.079; 95% CI, 1.149-3.761).

Compared with patients with overt HBVCI , those with occult infection had shorter overall (P=.026) and disease-free survival (P=.002), higher bilirubin levels (P=.003) and were more likely to have precore G1896A mutations (P=.006.

“In HCV-associated hepatocellular carcinoma, patients with overt HBV coinfection had a better postoperative prognosis, whereas patients with occult HBV coinfection had a poorer postoperative prognosis,” Yeh said. “A significant proportion of patients had occult HBV infection, and these patients had a higher bilirubin level, suggesting a poorer functional reserve. This observation is consistent with the fact that such patients had a poorer postoperative outcome. Intriguingly, patients with overt HBV coinfection actually had a better postoperative outcome.”