Chronic hepatitis C patients who are coinfected with occult hepatitis B virus face a high risk of progression toward cirrhosis, the development of hepatocellular carcinoma, and lower survival, an observational study demonstrated.
To evaluate the clinical evolution of chronic hepatitis C (CHC) patients according to their occult hepatitis B virus infection (OBI) status, 326 hepatitis B surface antigen–negative CHC patients who had undergone needle liver biopsy in the liver unit at the University of Messina (Italy) between 1991 and 2000 were tested for OBI by analysis of liver biopsy DNA extracts. More than half of the patients (65%) were male, and their median age was 52 years, researchers led by Dr. Giovanni Squadrito and Dr. Giovanni Raimondo of the University of Messina reported in an article in press from the Journal of Hepatology (2013 June 10).
None of them had received any antiviral therapy before liver biopsy was performed, none was infected with HIV, and none had evidence of alcoholic or autoimmune liver disease.
Of the 326 patients, 128 (39%) were OBI positive while the remaining 198 were OBI negative. A total of 94 patients (37 OBI positive and 57 OBI negative) were followed for a median of 11 years. Among these 94 patients, 79 underwent anti-HCV treatments and 26 achieved a sustained virologic response that occurred independently of their OBI status.
The researchers reported that 18 of the 94 patients (19%) developed hepatocellular carcinoma (HCC). Of these, 13 were among the 37 who were OBI positive and 5 were among the 57 who were OBI negative, a difference that was statistically significant (P less than .01). Among the 76 patients who did not develop HCC, 15 (20%) developed advanced forms of cirrhosis. Of these, 8 were among the 24 who were OBI positive and 7 were among the 52 who were OBI negative, a difference that was statistically significant (P less than .05).
During the follow-up period, 18 patients died (19%) and 2 underwent liver transplantation (2%). Of the 18 deaths, 14 occurred among HCC patients and 4, among patients with clear worsening of liver disease. The researchers found that the cumulative survival rate was significantly shorter among OBI-positive patients compared with OBI-negative patients (P = .003), while liver-related deaths occurred significantly more frequently in OBI-positive patients than in OBI-negative patients (P less than .01). In addition, nonresponse to anti-HCV therapy was significantly associated with lower survival (P = .02).
"The pro-oncogenic role of OBI is not surprising, considering that HBV is a major causative agent of liver cancer worldwide and the potential mechanisms whereby overt HBV might induce tumor formation are mostly maintained in the occult status," the researchers wrote. "In addition, when patients who developed HCC were excluded from the analysis, OBI still appears to play a negative role in the CHC outcome since it was significantly associated with the progression toward the severe deterioration and decompensation of the liver disease. Although this association is in accordance with the results of many cross-sectional studies performed in different areas of the world, how OBI may favor (or accelerate) the progression toward cirrhosis of CHC patients is far from being clearly understood."
The investigators noted that there is evidence "both in humans and in animal models that intrahepatic persistence of occult hepadnavirus genomes may produce a very mild but constant liver necroinflammation, and recent reports have shown an association between phases of a rise in ALT levels and reappearance of circulating HBV DNA in patients with chronic hepatitis C and combined occult HBV infection, thus suggesting an active role of transient reactivation of HBV replication in liver cell injury."
The study was supported by grants from the Associazione Italiana per la Ricerca sul Cancro. The researchers said they had no relevant financial disclosures.