By Liz Highleyman

Due to overlapping transmission routes, many people have been exposed to both hepatitis B virus (HBV) and hepatitis C virus (HCV), and a smaller proportion are chronically infected with both viruses, especially in regions such as Asia where HBV is endemic. Estimates suggest that up to 10% of people with HCV may also have HBV, while perhaps 20% of people with HBV are coinfected with HCV. However, treatment of hepatitis C in HBV-HCV coinfected individuals has not been well studied.

Treatment is complicated by the fact that HCV and HBV appear to inhibit each other's replication (though not all studied have observed this interaction). Therefore, treatment that fully suppresses HCV could potentially allow HBV to re-emerge, or vice versa.

As reported in the February 2009 Gastroenterology, C.J. Liu from the National Taiwan University College of Medicine and colleagues conducted a study of 321 Taiwanese patients with active HCV infection, half of whom (n = 161) were also hepatitis B surface antigen (HBsAg) positive. In addition, 6.3% of the HCV "monoinfected" patients had occult or hidden HBV infection, defined as detectable serum HBV DNA despite the absence of HBsAg.

Participants with HCV genotype 1 were treated with 180 mcg/week pegylated interferon alfa-2a (Pegasys) plus 1000-1200 mg/day weight-adjusted ribavirin for 48 weeks, while those with genotype 2 or 3 received the same pegylated interferon dose plus 800 mg/day ribavirin for 24 weeks -- the standard regimens for patients with chronic hepatitis C alone. For people with chronic hepatitis B alone, conventional or pegylated interferon without ribavirin (and with or without anti-HBV nucleoside/nucleotide analogs) is among the approved therapies.

Sustained virological response (SVR) was determined 24 weeks after the end of treatment, defined as HCV RNA < 25 IU/mL.

Results

24 weeks after completion of therapy, genotype 1 HBV-HCV coinfected patients had an SVR rate of 72.2%, which was not significantly different from the rate of 77.3% for genotype 1 patients with HCV alone.

HBV-HCV coinfected participants with HCV genotype 2 or 3 had an SVR rate of 82.8%, similar to the 84.0% rate observed for HCV monoinfected patients with these genotypes.

Coinfected patients with detectable HBV DNA before treatment were less likely to achieve HCV clearance than those with detectable HBsAg but undetectable HBV viremia.

About 24% of coinfected patients who experienced SVR had persistent elevated ALT, and 76% of these individuals were found to have detectable serum HBV DNA after treatment.

More than one-third (36.3%) of the 77 participants who had undetectable serum HBV DNA before interferon-based treatment eventually developed detectable HBV viremia during the observation period.

However, the researchers stated, this was not accompanied by significant clinical symptoms of liver inflammation or injury.

Conversely, 11.2% of the initially HBV-HCV coinfected patients demonstrated HBsAg clearance after hepatitis C treatment.

In addition, all participants with occult HBV achieved undetectable HBV DNA during interferon treatment.

Overall, treatment was safe, with no unexpected safety issues and adverse events consistent with those such typically associated with interferon-based therapy.

Based on these findings, the study authors stated, "Combination therapy with peginterferon alfa-2a and ribavirin is equally effective in patients with HCV monoinfection and in those with dual chronic HCV-HBV infection."

"The treatment recommendations regarding therapy duration according to genotype in HCV monoinfected patients appear to be applicable also for this patient group," they added.

In a discussion of their findings, the researchers noted that the SVR rates for genotype 1 patients in this study were higher than the rates typically seen in previous studies of mostly Caucasian patients, but is in keeping with rates observed in prior Taiwanese studies. The higher SVR rate in this study, they suggested, might be due to lower pretreatment HCV viral load and lower mean body weight.

"Although our study showed that peginterferon alfa-2a plus ribavirin is effective in eradicating hepatitis C in patients chronically infected with both HBV and HCV," the researchers continued, "it remains to be determined whether this regimen also is suitable for dually infected patients who are positive for HBeAg and have a higher hepatitis B viral load."

In an accompanying editorial entitled "Releasing the Enemy Within," Stuart Gordona of Henry Ford Hospital in Detroit and Kenneth Sherman from the University of Cincinnati College of Medicine discussed the reciprocal inhibitory relationship between of HBV and HCV and its implications for HBV-HCV coinfected individuals.

The authors offered more questions than answers, demonstrating the need for further research in this area: "Will these results translate to the non-Asian, higher body mass index population? Are the results applicable to the HBeAg positive (or HBV-dominant) coinfected cohort? Should we be checking HBV DNA levels [in] our HCV monoinfected patients? …Should oral nucleoside/nucleotide analogs be added preemptively to obviate HBV reactivation?"

Finally, they asked, "as we enter a new HCV antiviral era that may include triple therapy regimens (interferon, ribavirin, and HCV protease or polymerase inhibitors), how will these new agents interact with HBV in the coinfected population?"

National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei, Taiwan; Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Chang Gung Memorial Hospital-Kaohsiung, Kaohsiung, Taiwan; Changhua Christian Hospital, Changhua, Taiwan; Taipei City Hospital, Ren-Ai Branch, Taipei, Taiwan; Chi Mei Medical Center, Tainan, Taiwan; Tri-Service General Hospital, Taipei, Taiwan; Chia-Yi Chang Gung Memorial Hospital, Chiayi Hsien, Taiwan; Cathay General Hospital, Taipei, Taiwan.

4/10/09

References

CJ Liu, WL Chuang, CM Lee, and others. Peginterferon Alfa-2a Plus Ribavirin for the Treatment of Dual Chronic Infection With Hepatitis B and C Viruses. Gastroenterology 136(2): 496-504. February 2009. (Abstract).

SC Gordona and KE Sherman. Treatment of HBV/HCV Coinfection: Releasing the Enemy Within. Gastroenterology 136(2): 393-396. February 2009.