Viral Dominance in HBV/HCV Dual Infection

SUMMARY
Asian ethnicity is a significant independent predictor of HBV-dominant disease in people with HBV/HCV dual infection. With undetectable HBV viral load, HCV dominance is more common in non-Asians.

By James Learned

As much of 20% of the world's population has hepatitis B virus (HBV) and hepatitis C virus (HCV) dual infection. In recent years, the number of immigrants in the U.S. from Asia and the Pacific region, where HBV is endemic, has increased to about 14 million. The number of people with dual infection may be both underreported and increasing. As testing becomes more widespread and more dual infections are identified, it will be even more necessary to understand how best to care for and treat people with both viral infections.

HBV/HCV dual infection can lead to more serious liver disease -- including fulminant hepatitis, advanced cirrhosis, and hepatocellular carcinoma (HCC) -- than either HBV or HCV monoinfection. Additionally, people with dual infection are less likely to respond to interferon-based treatment. The interaction between HBV and HCV in dual infection seems to be one of "reciprocal inhibition," with each virus preventing or decreasing the ability of the other to replicate. HCV is usually the dominant virus, yet some studies suggest that HBV can be the dominant virus under certain circumstances.

As described in the June 2011 issue of Hepatology, Long Nguyen and colleagues conducted a 15-year retrospective study to identify clinical, viral, and demographic factors (including ethnicity) of people with HBV/HCV dual infection compared to people with HBV monoinfection, in order to determine characteristics that influence viral dominance.

The researchers drew upon chart reviews of patients who received medical care at 2 sites in California between January 1994 and March 2009. A total of 115 patients with HBV/HCV dual infection were identified, all of whose medical charts had serial HBV DNA, HCV RNA, and alanine aminotransferase (ALT) test results. The control group was made up of 115 HBV-monoinfected individuals chosen randomly and matched with the dual-infected group by age, sex, study site, and ethnicity (Asian vs non-Asian, either self-identified or as identified by their provider). HBV monoinfected patients were diagnosed based on positive serum hepatitis B surface antigen (HBsAg).

The dual infection and HBV monoinfection groups were evenly matched -- 68% men and 83% Asian people in both. The groups were also evenly matched at the time of presentation in terms of body mass index, hepatitis B "e" antigen (HBeAg) or antibodies to HBeAg, median follow-up duration (38 months vs 33 months), family history of either hepatitis B or C, family history of HCC, preexisting HCC, HBV genotype, and the presence of HBV viral mutations.

Results

Dual-infected patients most often presented with evidence of HBV/HCV infection at baseline (88%), with HBV DNA and HCV RNA and/or HBsAg and HCV antibodies.

The remaining 12% were infected with the second virus at least 3 months following diagnosis of the first viral infection.

Among these patients, 8% had HBV before acquiring HCV, and the other 4% had HCV before HBV.

Among dual-infected Asian patients, 14% had negative viral load results for both HBV and HCV.

Among dual-infected non-Asian patients, 25% had negative viral load results for both viruses.

HBV-dominant infection was found in 38% of Asian patients compared to only 10% of non-Asian patients, a significant difference:

	Of the 38% of Asian patients with HBV-dominant infection, 83% had complete dominance as defined by negative HCV RNA and detectable HBV DNA.
	The remaining 17% had partial HBV dominance (detectable HBV and HCV viral loads, with the HBV DNA level being higher than that of HCV RNA).

All non-Asian patients with HBV-dominant disease had complete HBV dominance.

HCV dominance was found in 48% of Asian patients and 65% of non-Asian patients:

Of this group, 70% of Asian patients had undetectable HBV viral load and positive HCV RNA.

	The remaining 30% had detectable viral loads for both HBV and HCV.
	Similar results were seen in non-Asian patients with HCV dominance.

Among dual-infected patients, Asian ethnicity predicted HBV dominance after adjusting for sex, age, and baseline ALT elevation.

Among dual-infected patients, both female sex and baseline ALT elevation independently predicted HCV dominance after adjusting for age and ethnicity.

People with HBV monoinfection were significantly more likely to receive HBV treatment than their counterparts with dual infection (43% versus 24%).

28% of people with dual infection received HCV treatment.

At baseline, HBV monoinfected patients had lower median ALT levels than patients with dual infection.

	ALT levels remained lower among HBV monoinfected patients during follow-up compared to those with dual infection.
	During follow-up, 64% of people with HBV monoinfection had at least one elevated ALT result compared to 75% of those with dual infection.

"The results demonstrate that Asian ethnicity can be a predictor for HBV-dominant dual infection, and female sex and baseline ALT level can predict HCV-dominant disease, with non-Asian ethnicity trending toward significance," the researchers wrote.

They continued, "The findings of the current study support the literature that suggests dual-infected patients often have a disease course characterized by dominance of one virus over the other." However, they noted that patients with dual infection did not have higher rates of liver disease or HCC compared to patients with HBV monoinfection, in contrast to some prior studies.

The authors noted certain limitations of their study. The median follow-up period was short (38 months for the HBV monoinfection group and 33 months for the dual infection group), making comparisons between the groups in terms of end-stage liver disease and HCC beyond the study's scope. Furthermore, the study compared patients with HBV/HCV dual infection to patients with HBV monoinfection, but not HCV monoinfection.

The investigators concluded that their findings "…suggest that ethnicity may predict for the dual infection viral dominance profile -- specifically, that Asian ethnicity is an independent predictor for HBV-dominated dual infection."

Investigator affiliations: Stanford University, School of Medicine, Stanford, CA; Pacific Health Foundation, San Jose, CA; San Jose Gastroenterology, San Jose, CA; and Division of Gastroenterology and Hepatology, Stanford University Medical Center, Stanford, CA.

7/5/11

Reference
LH Nguyen, S Ko, SS Wong, et al. Ethnic Differences in Viral Dominance Patterns in Patients with Hepatitis B Virus and Hepatitis C Virus Dual Infection. Hepatology 53(6): 1839-1845 (abstract) June 2011.