DOES DUAL INFECTION BY HEPATITIS-B AND HEPATITIS-C VIRUSES PLAY AN IMPORTANT ROLE IN THE PATHOGENESIS OF HEPATOCELLULAR-CARCINOMA IN JAPAN

BACKGROUND. There are contradictory data concerning the synergistic ef fect of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection on the progression from chronic hepatitis to hepatocellular carcinoma (HCC). METHODS. To clarify the role of coinfection with HBV and HCV in the progression and pathogenesis of HCC, viral and clinicopathologic features were studied in 368 consecutive HCC patients at the Universit y of Tokyo from 1991-1995. RESULTS. Approximately 83% of patients (305 patients) were seropositive for the HCV antibody (''C-viral'') and ap proximately 10% (37 patients) were positive for the hepatitis B surfac e antigen (''B-viral''). Positivity for both (dual infection) was foun d in only 2% of patients, and negativity for both in 5%. The incidence of dual infection in HCC patients was similar to that in 549 patients with chronic hepatitis (1%) and 119 patients with cirrhosis (1%). Of the six HCC patients with dual infection, five patients were positive for the HBV early antigen and HBV DNA was less than measurable, wherea s HCV RNA was detected and ranged from 10(3)-10(6) copies/50 mu L of s erum by competitive reverse transcriptase-polymerase chain reaction, a nd the clinical features resembled those of ''C-viral'' HCC. The remai ning patient was early antigen positive and had HBV DNA by slot blot a nalysis, but the serum HCV RNA level was less than measurable. These d ata indicate that mutually exclusive viral replication occurred in pat ients with persistent coinfection. To further clarify further the poss ible involvement of I-IBV infection in ''C-viral'' HCC, HBV core antib ody (HBcAb) was tested in 192 patients and was found to be positive in 111 and negative in 81. The serum HCV RNA level and clinicopathologic features (such as age and the severity of liver disease) were similar among the ''C-viral'' HCC patients irrespective of the presence or ab sence of HBcAb. CONCLUSIONS. Based on these results, coinfection was f ound to be much less prevalent than generally is claimed, and even in a few HCC patients with the coinfection the mutually exclusive viral r eplication was noted, suggesting that coinfection plays little if any role in the development of HCC. (C) 1997 American Cancer Society.