Occult Hepatitis B Virus in a Prospective Cohort of HIV-Infected Patients
Occult Hepatitis B Virus in a Prospective Cohort of HIV-Infected Patients
Background: Occult hepatitis B virus (HBV) is defined as low-level HBV DNA without hepatitis B surface antigen (HBsAg). Prevalence estimates vary widely. We determined the prevalence of occult HBV at the University of Cincinnati Infectious Diseases Center (IDC).
Methods: Patients in the IDC HIV database (n = 3867) were randomly selected using a 25% sampling fraction. Samples were pooled for HBV nucleic acid extraction. Pools were tested for HBV DNA by a real-time polymerase chain reaction (PCR) assay to coamplify core/surface protein regions. The PCR assay was run on all individual samples from each DNA pool. DNA samples were tested for HBV serologic markers.
Results: A total of 909 patients without known HBV were selected. The mean CD4 count was 384 cells/mm. Forty-three patients were HBV DNA. Twelve of 43 were DNA/HBsAg (95% confidence interval for database: 0.58% to 1.90%). Five of 12 were negative for all serologic markers. Alanine aminotransferase, aspartate aminotransferase, and HBV DNA titers were elevated in HBsAg patients versus occult patients and versus HIV-monoinfected patients. No other significant differences were detected. No occult HBV patient was on treatment with anti-HBV activity.
Conclusions: Forty-three percent of those with HBV were not previously identified as HBV, indicating the need for ongoing screening in high-risk populations. Occult HBV may occur in persons with all negative serologic markers, representing a challenge for identification.
Coinfection with HIV and hepatitis B virus (HBV) is common because of shared blood-borne transmission routes such as injection drug use (IDU). Among those infected with HIV, rates of chronic HBV infection range from 7% to as high as 70% and markers of prior exposure may be found in 90%. Combined, these 2 viruses continue to constitute major public health threats, causing 3.7 million deaths each year. In the era of highly active antiretroviral therapy (HAART), prolonged survival of patients with HIV has facilitated the emergence of chronic liver disease, including viral hepatitis, as a leading cause of morbidity and mortality in several HIV-positive cohorts.
The classic chronic carrier state of HBV is characterized by persistent surface antigenemia (hepatitis B surface antigen [HBsAg]) and hepatitis B envelope antigen (HBeAg) for >6 months after infection and by antibodies directed against surface (anti-HBs) and core (anti-HBc) hepatitis B. In contrast, occult HBV has been defined as chronic low-level HBV replication in the absence of detectable HBsAg. The advent of sensitive polymerase chain reaction (PCR)-based assays has enabled detection of this low-level replication. Seropositivity for anti-HBc alone may serve as a surrogate for some cases of occult HBV infection. Other marker patterns have been observed in occult HBV infection, however.
Although the existence of occult HBV and the transmissibility of HBV via occult infection have been established in the literature, its prevalence and clinical significance remain unclear. It has been implicated in significant liver pathologic findings, raising the question of whether this phenomenon underlies some of the liver-related morbidity seen in HIV-positive cohorts. Successful antiretroviral therapy (ART) for HIV creates immune reconstitution that can result in immune-mediated liver injury in the setting of HBV infection. Occult HBV infection may be associated with elevation of liver enzymes that could be misclassified by physicians caring for these patients as HAART-associated liver toxicity. Furthermore, it is unknown if HBV treatment is indicated in these patients, which could have an impact on HIV clinical management.
Our objectives were to determine the prevalence of occult HBV in the HIV-infected population at the University of Cincinnati HIV clinical center and to characterize this cohort of occult HBV/HIV-coinfected subjects for associations between occult infection, transaminase elevations, and ART.
Abstract and Introduction
Abstract
Background: Occult hepatitis B virus (HBV) is defined as low-level HBV DNA without hepatitis B surface antigen (HBsAg). Prevalence estimates vary widely. We determined the prevalence of occult HBV at the University of Cincinnati Infectious Diseases Center (IDC).
Methods: Patients in the IDC HIV database (n = 3867) were randomly selected using a 25% sampling fraction. Samples were pooled for HBV nucleic acid extraction. Pools were tested for HBV DNA by a real-time polymerase chain reaction (PCR) assay to coamplify core/surface protein regions. The PCR assay was run on all individual samples from each DNA pool. DNA samples were tested for HBV serologic markers.
Results: A total of 909 patients without known HBV were selected. The mean CD4 count was 384 cells/mm. Forty-three patients were HBV DNA. Twelve of 43 were DNA/HBsAg (95% confidence interval for database: 0.58% to 1.90%). Five of 12 were negative for all serologic markers. Alanine aminotransferase, aspartate aminotransferase, and HBV DNA titers were elevated in HBsAg patients versus occult patients and versus HIV-monoinfected patients. No other significant differences were detected. No occult HBV patient was on treatment with anti-HBV activity.
Conclusions: Forty-three percent of those with HBV were not previously identified as HBV, indicating the need for ongoing screening in high-risk populations. Occult HBV may occur in persons with all negative serologic markers, representing a challenge for identification.
Introduction
Coinfection with HIV and hepatitis B virus (HBV) is common because of shared blood-borne transmission routes such as injection drug use (IDU). Among those infected with HIV, rates of chronic HBV infection range from 7% to as high as 70% and markers of prior exposure may be found in 90%. Combined, these 2 viruses continue to constitute major public health threats, causing 3.7 million deaths each year. In the era of highly active antiretroviral therapy (HAART), prolonged survival of patients with HIV has facilitated the emergence of chronic liver disease, including viral hepatitis, as a leading cause of morbidity and mortality in several HIV-positive cohorts.
The classic chronic carrier state of HBV is characterized by persistent surface antigenemia (hepatitis B surface antigen [HBsAg]) and hepatitis B envelope antigen (HBeAg) for >6 months after infection and by antibodies directed against surface (anti-HBs) and core (anti-HBc) hepatitis B. In contrast, occult HBV has been defined as chronic low-level HBV replication in the absence of detectable HBsAg. The advent of sensitive polymerase chain reaction (PCR)-based assays has enabled detection of this low-level replication. Seropositivity for anti-HBc alone may serve as a surrogate for some cases of occult HBV infection. Other marker patterns have been observed in occult HBV infection, however.
Although the existence of occult HBV and the transmissibility of HBV via occult infection have been established in the literature, its prevalence and clinical significance remain unclear. It has been implicated in significant liver pathologic findings, raising the question of whether this phenomenon underlies some of the liver-related morbidity seen in HIV-positive cohorts. Successful antiretroviral therapy (ART) for HIV creates immune reconstitution that can result in immune-mediated liver injury in the setting of HBV infection. Occult HBV infection may be associated with elevation of liver enzymes that could be misclassified by physicians caring for these patients as HAART-associated liver toxicity. Furthermore, it is unknown if HBV treatment is indicated in these patients, which could have an impact on HIV clinical management.
Our objectives were to determine the prevalence of occult HBV in the HIV-infected population at the University of Cincinnati HIV clinical center and to characterize this cohort of occult HBV/HIV-coinfected subjects for associations between occult infection, transaminase elevations, and ART.
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