To the Editor:

We read with great interest the article by Bini et al.,1 who reported a study of hepatitis B virus (HBV) infection among 1257 patients with chronic hepatitis C virus (HCV) infection in the United States. They concluded that younger age, Asian race, injection drug use, and a greater number of lifetime sexual partners are risk factors for HBV-HCV dual infection. An interesting and clinically important finding is the marked difference in the severity of liver disease. Compared with patients monoinfected with HCV, patients dually infected with HBV and HCV have higher alanine aminotransferase levels and necroinflammatory scores, more advanced fibrosis, and faster fibrosis progression rates. In particular, patients with dual infection have a greater severity of hepatic steatosis, which has never been evaluated in this population before.

To further elucidate the association between HBV-HCV dual infection and hepatic steatosis, we conducted a study enrolling 100 consecutive dually infected patients [59 males and 41 females, 52.5 ± 11.3 years old, with 31% positive for HBV DNA by the COBAS Amplicor HBV monitor (Roche Diagnostics, Branchburg, NJ) and 100% positive for HCV RNA by Amplicor (Roche Diagnostics)] and 100 age-matched, sex-matched, and body mass index (BMI)–matched individuals with chronic hepatitis C in Taiwan, in which both viruses are endemic.2-4 Patients with HBV-HCV dual infection and patients with HCV monoinfection were similar with respect to the ratio of diabetes mellitus, HCV genotype, alanine aminotransferase levels, and necroinflammatory scores, although patients with dual infection had more advanced fibrosis scores (F3 and F4; P = 0.041) and lower platelet counts (P = 0.045) than those with HCV monoinfection. Based on the Metavir classification system,5 the prevalence of hepatic steatosis was comparable between the two groups; however, dually infected patients had a higher severity of steatosis (grade 2 or 3) than those infected with HCV alone (P = 0.025; Fig. 1). Among dually infected patients, factors associated with the presence of steatosis by multivariate analysis were advanced fibrosis [odds ratio (OR) = 3.703, 95% confidence interval (CI) = 1.527-9.009, P = 0.004] and BMI (OR = 1.191, 95% CI = 1.037-1.368, P = 0.014). Likewise, independent variables associated with advanced fibrosis were the platelet count (104/μL; OR = 0.818, 95% CI = 0.725-0.923, P = 0.001), grade 2 or 3 steatosis (OR = 6.695, 95% CI = 1.911-23.45, P = 0.003), and higher necroinflammatory scores (OR = 2.880, 95% CI = 1.084-7.647, P = 0.034).

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Figure 1. Steatosis grade in the 100 patients dually infected with HBV and HCV and in the 100 age-matched, sex-matched, and BMI-matched patients monoinfected with HCV. Grade 2 or 3 steatosis was more frequently found in dually infected patients versus those infected with HCV alone (P = 0.025).

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Hepatic steatosis, a frequent histological feature of chronic HCV infection, has been recognized as a cofactor influencing the presence and progression of fibrosis.6, 7 In contrast, the association between HBV infection and hepatic steatosis is controversial.8, 9 In this case-control study, our data, in keeping with the findings of Bini et al.,1 confirm that patients dually infected with HBV and HCV have more severe steatosis than those with HCV monoinfection. Furthermore, multivariate analysis has shown that steatosis in HBV-HCV dual infection correlates independently with advanced fibrosis and BMI; however, the latter association was not found by Bini et al. The reasons for this difference are likely the small number of dually infected subjects in their study and differences in the patient characteristics. In our study, most of the dually infected patients had lower serum HBV loads because HBV is usually acquired perinatally or in early infancy and is inhibited by a subsequent HCV superinfection.2-4 Further investigation will be required to elucidate the contribution of steatosis to fibrogenesis in patients with HBV-HCV dual infection.


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  • 1
    Bini EJ, Perumalswami PV. Hepatitis B virus infection among American patients with chronic hepatitis C virus infection: prevalence, racial/ethnic differences, and viral interactions. HEPATOLOGY 2010; 51: 759-766.
  • 2
    Liaw YF. Role of hepatitis C virus in dual and triple hepatitis virus infection. HEPATOLOGY 1995; 22: 1101-1108.
  • 3
    Hung CH, Lee CM, Lu SN, Wang JH, Tung HD, Chen CH, et al. Combination therapy with interferon-alpha and ribavirin in patients with dual hepatitis B and hepatitis C virus infection. J Gastroenterol Hepatol 2005; 20: 727-732.
  • 4
    Liu CJ, Chuang WL, Lee CM, Yu ML, Lu SN, Wu SS, et al. Peginterferon alfa-2a plus ribavirin for the treatment of dual chronic infection with hepatitis B and C viruses. Gastroenterology 2009; 136: 496-504.
  • 5
    French METAVIR Cooperative Study Group. Intraobserver and interobserver variations in liver biopsy interpretation in patients with chronic hepatitis C. HEPATOLOGY 1994; 20: 15-20.
  • 6
    Adinolfi LE, Gambardella M, Andreana A, Tripodi MF, Utili R, Ruggiero G. Steatosis accelerates the progression of liver damage of chronic hepatitis C patients and correlates with specific HCV genotype and visceral obesity. HEPATOLOGY 2001; 33: 1358-1364.
  • 7
    Hung CH, Kuo FY, Wang JH, Lu SN, Hu TH, Chen CH, et al. Impact of steatosis on long-term histological outcome in chronic hepatitis C after antiviral therapy. Antivir Ther 2006; 11: 483-489.
  • 8
    Gordon A, McLean CA, Pedersen JS, Bailey MJ, Roberts SK. Hepatic steatosis in chronic hepatitis B and C: predictors, distribution and effect on fibrosis. J Hepatol 2005; 43: 38-44.
  • 9
    Tai DI, Lin SM, Sheen IS, Chu CM, Lin DY, Liaw YF. Long-term outcome of hepatitis B e antigen-negative hepatitis B surface antigen carriers in relation to changes of alanine aminotransferase levels over time. HEPATOLOGY 2009; 49: 1859-1867.

Chao-Hung Hung M.D.*, Chuan-Mo Lee M.D.*, Sheng-Nan Lu M.D., M.P.H., Ph.D.*, Jing-Houng Wang M.D.*, Chien-Hung Chen M.D., Ph.D.*, Tsung-Hui Hu M.D., Ph.D.*, * Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung Memorial Hospital–Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan.