Chronic hepatitis B, C, and D virus infections contribute significantly to the morbidity and mortality of immunocompromised individuals. To contextualize discussion of these infections in immunocompromised patients, this paper provides an overview of aspects of infection in normal hosts. It then describes differences in disease, diagnostic testing, and therapeutic management observed in immunocompromised patients.

Chronic hepatitis B virus (HBV) infection could cause severe liver disease including cirrhosis, hepatocellular carcinoma, and end-stage liver failure in HIV-positive individuals. The available data from clinical studies suggest that HIV infection modulates the HBV-specific T cell response. However, the virological and molecular aspects of HIV-HBV coinfection are currently poorly understood due to the lack of appropriate model systems. In this study, the effect of HIV infection on the life cycle of HBV was explored using an in vitro model system. The present data show that the extracellular and intracellular hepatitis B surface antigen (HBsAg) and e antigen (HBeAg) decrease significantly in HepG2 cells cotransfected with HIV NL4-3 and pHBV1.3 as compared to those cells transfected only with pHBV1.3. Moreover, a significant decrease in HBV DNA and mRNA expression was also observed in the cotransfected cells. HIV Rev protein, an RNA-bound regulatory protein, could significantly decrease the expression levels of extracellular and intracellular HBsAg and HBeAg by mediating the expression of HBV mRNA in cells cotransfected with plasmids containing HIV-1 Rev and pHBV1.3. Further experiments demonstrate that HIV Rev manipulated neither the promoters of HBV nor the nuclear export of HBV mRNA. These results from the in vitro model system might provide clues to further understand the rapid progression of liver disease in HIV-HBV-coinfected patients.

HIV and hepatitis B virus (HBV) share transmission routes, and coinfection is associated with higher morbidity and mortality. To date, no Canadian studies have examined HIV-HBV coinfection.

To examine the prevalence and correlates of HIV and HBV coinfections in Northern Alberta.

The present study was a retrospective database review of all HIV-infected (HIV+) individuals in Northern Alberta from 1982 to 2010 and a chart review of HBV surface antigen-positive individuals for whom charts were available (46.2%).

Of 2844 HIV+ patients, 2579 (90.7%) had been tested for HBV surface antigen, and 143 (5.5%) of these were HBV coinfected. Coinfected males were primarily Caucasian (70.8%), and coinfected females were primarily black (56.4%) or Aboriginal (31.3%). Coinfected individuals were more likely to be male (88.1% versus 71.3%; P<0.001) and to have died (34.3% versus 17.9%; P<0.001).

The prevalence of coinfection with HBV in HIV-infected patients in Northern Alberta is lower than reported in other developed nations. The pattern of coinfections in Northern Alberta likely follows immigration trends. Recognition and management may be improving with time; however, further research and additional strategies are required to enhance the prevention, identification and management of HBV infection in HIV-infected individuals.

Prevalence and risk factors for isolated antibody to hepatitis B core antigen (anti-HBc) and occult hepatitis B virus (HBV) infection are not well known in human immunodeficiency virus type 1 (HIV-1)-infected pregnant women. It is unclear if women with occult infections are at risk of transmitting HBV to their infants.

HIV-1-infected and HBV surface antigen (HBsAg)-negative pregnant women were tested for antibody to HBsAg (anti-HBs) and anti-HBc using enzyme immunoassay. Women with isolated anti-HBc were assessed for occult HBV infection, defined as HBV DNA levels >15 IU/mL, using the Abbott RealTime HBV DNA assay. Infants born to women with isolated anti-HBc and detectable HBV DNA were tested at 4 months of age for HBV DNA. Logistic regression analysis was used to identify factors associated with isolated anti-HBc and occult HBV infection.

Among 1812 HIV-infected pregnant women, 1682 were HBsAg negative. Fourteen percent (95% confidence interval [CI], 12%-15%) of HBsAg-negative women had an isolated anti-HBc that was independently associated with low CD4 count, age >35 years, birth in northern Thailand, and positive anti-hepatitis C virus serology. Occult HBV infection was identified in 24% (95% CI, 18%-30%) of women with isolated anti-HBc, representing 2.6% (95% CI, 1.9%-3.5%) of HIV-1-infected pregnant women, and was inversely associated with HIV RNA levels. None of the women with isolated anti-HBc and occult HBV infection transmitted HBV to their infants.

HIV-1-infected pregnant women with isolated anti-HBc and occult HBV infection have very low HBV DNA levels and are thus at very low risk to transmit HBV to their infants.

In regions that are hyperendemic for chronic hepatitis B virus (HBV) infection, prevalence of and risk factors associated with isolated anti-hepatitis B core antibody (anti-HBc) in HIV-positive patients are less well described. HIV-positive patients who were tested for hepatitis B surface antigen (HBsAg), anti-hepatitis B surface antibody (anti-HBs) and anti-HBc at designated hospitals for HIV care in Taiwan were included for analysis. HBV DNA was detected by real-time polymerase chain reaction in patients with and without isolated anti-HBc. Of 2351 HIV-positive patients, 450 (19.1%) were HBsAg positive, 411 (17.5%) were anti-HBc positive alone and 963 (41.0%) for both anti-HBs and anti-HBc. Compared with patients who were positive for both anti-HBs and anti-HBc, patients with isolated anti-HBc were older, less likely to have anti-hepatitis C virus antibody (anti-HCV), had lower CD4 lymphocyte counts and higher plasma HIV RNA loads. Older age (adjusted odds ratio, 1.029; 95% confidence interval, 1.015-1.043) and CD4 <100 cells/microL (adjusted odds ratio, 1.524; 95% confidence interval, 1.025-2.265) were independently associated with isolated anti-HBc by logistic regression, while presence of anti-HCV and injecting drug use were not. HBV DNA was detectable in 8.3% of 277 patients with isolated anti-HBc and 14.3% of 56 patients with both anti-HBs and anti-HBc (P = 0.160). In a country hyperendemic for HBV infection, HIV-positive patients at older age and with CD4 <100 cells/microL were more likely to have isolated anti-HBc, suggesting that compromised immunity plays a role in the presence of this marker.

Hepatitis B-specific memory B cell (HSMBC) frequencies were measured following hepatitis B vaccination in 15 HIV uninfected and 12 HIV infected adolescents. HSMBC were detected at significantly lower frequencies in HIV infected than in HIV uninfected individuals. The detection of HBsAb >10mIU/ml at study week 28 was strongly associated with the detection of HSMBC and a direct correlation between HBsAb titers and HSMBC frequencies was observed. In HIV uninfected individuals, antibody titers >1000mIU/ml were associated with higher HSMC frequencies. Lower HSMBC frequencies, reduced memory B cell (MBC) proliferation, and altered B cell phenotypes were measured in viremic HIV infected individuals compared with aviremic HIV infected or HIV uninfected individuals.

HBV infection may reactivate in the setting of immunosuppression, although the frequency and consequences of HBV reactivation are not well known. We report 6 patients who experienced loss of serologic markers of hepatitis B immunity and reappearance of HBsAg in the serum as a result of a variety of acquired immune deficiencies.

Between 2000 and 2005, six patients with reactivation of hepatitis B were seen in consultation by the Liver Diseases Branch at the Clinical Center, National Institutes of Health. The course and outcome of these 6 patients were reviewed.

All 6 patients developed reappearance of HBsAg and evidence of active liver disease after stem cell transplantation (n = 4), immunosuppressive therapy (n = 1), or change in human immunodeficiency virus antiretroviral regimen (n = 1), despite having antibody to HBsAg (anti-HBs) or antibody to hepatitis B core antigen (anti-HBc) without HBsAg before. All 6 patients developed chronic hepatitis B, 2 patients transmitted hepatitis B to their spouses, and 1 patient developed cirrhosis. The diagnosis of hepatitis B reactivation was frequently missed or delayed and often required interruption of the therapy for the underlying condition. None of the patients received antiviral prophylaxis against HBV reactivation.

Serologic evidence of recovery from hepatitis B infection does not preclude its reactivation after immunosuppression. Screening for serologic evidence of hepatitis B and prophylaxis of those with positive results by using nucleoside analogue antiviral therapy should be provided to individuals in whom immunosuppressive therapy is planned.

Isolated antibody to hepatitis B core antigen (anti-HBc) is a common serologic finding in persons infected with human immunodeficiency virus (HIV), but the outcome and clinical significance are uncertain.

We performed repeated hepatitis B virus (HBV) serologic tests on women who participated in the Women's Interagency HIV Study and who had isolated anti-HBc at study entry.

Repeated serologic tests were performed for 322 women (282 HIV-infected and 40 HIV-uninfected) at a median of 7.5 years after study entry. Seventy-one percent of women retained isolated anti-HBc serologic status, 20% acquired antibody to hepatitis B surface antigen (anti-HBs), and 2% acquired hepatitis B surface antigen (HBsAg). In unadjusted analysis, increasing age, injection drug use, and hepatitis C viremia were negatively associated with acquisition of anti-HBs. For HIV-infected women, predictors of acquisition of anti-HBs were an increase in CD4 cell count and the use of highly active antiretroviral therapy (HAART). Receipt of drugs with activity against HBV and self-reported HBV vaccination did not predict anti-HBs acquisition. In the multivariable regression model, HAART use remained a significant predictor of anti-HBs acquisition, whereas women with hepatitis C viremia were more likely to retain isolated anti-HBc serologic status.

Isolated anti-HBc status remained stable over time for the majority of women, especially women with chronic hepatitis C virus infection. Development of anti-HBs was predicted by HAART use and an increase in CD4 cell count. We conclude that a proportion of HIV-infected women with isolated anti-HBc have prior natural HBV infection with anti-HBs that is at an undetectable level because of immune dysfunction. Isolated anti-HBc in the presence of chronic hepatitis C virus infection may be attributable to a different phenomenon, such as dysfunctional antibody production.

Coinfection with human immunodeficiency virus-1 (HIV) and hepatitis B virus (HBV) is common; worldwide, an estimated 10% of HIV-infected persons have chronic hepatitis B. Because the incidence of traditional acquired immunodeficiency syndrome-related opportunistic infections has decreased with successful anti-HIV therapy, liver disease has emerged as a leading cause of morbidity and mortality in HIV-infected individuals. HIV infection negatively impacts all phases of the natural history of hepatitis B leading to increased rates of persistent infection, higher HBV DNA levels, lower rates of hepatitis B e antigen loss, increased cirrhosis and liver-related mortality, and increased risk of hepatocellular carcinoma at lower CD4+ T cell counts. The management of hepatitis B in HIV infection is complicated by the dual activity of several nucleoside analogs, the more rapid development of lamivudine-resistant HBV in patients who are HIV-positive, and the paucity of studies in this population. Until further research emerges on the optimal treatment for this population, data from HBV monoinfected persons will need to be extrapolated to the HIV-HBV coinfected population. Further research is also needed to determine the mechanism(s) for the increased liver disease progression and optimal treatment goals.

To investigate the maintenance of long-term memory B cells specific for hepatitis B surface antigen (HBsAg), purified blood B cells were polyclonally stimulated and cells secreting antibodies directed to HBsAg (HBs-SC) enumerated by ELISpot. HBs-SC were found in 18/20 HIV-1-infected patients with either natural or vaccinal immunity to hepatitis B virus, including six subjects with serum anti-hepatitis B surface antibody levels less than 10 mIU/ml. A lower number of HBs-SC was found in HBsAg-vaccinated patients compared with vaccinated controls.

Evolution of serological markers of hepatitis B virus (HBV) carriage or infection has rarely been investigated among human immunodeficiency virus (HIV)-infected patients receiving highly active antiretroviral therapy (HAART).

During the period 1997-2002, a total of 633 HIV-infected patients were tested for HBV serological markers at baseline, including hepatitis B surface antigen (HBsAg), antibody to HBsAg (anti-HBs ), antibody to hepatitis B core antigen (anti-HBc), hepatitis C virus (HCV) antibody (anti-HCV) antibody, HCV RNA level, and HBV DNA level, all of which were retested at least 1 year apart. Medical records were reviewed to identify clinical characteristics associated with evolution of these serological markers.

After a median duration of follow-up for 4.96 years, 161 patients (25.4%) had changes in HBV serological markers. Of 119 patients (18.8%) who tested positive for HBsAg at baseline, 6 (5.0%) developed anti-HBs, and 9 (7.6%) developed isolated anti-HBc. Of 270 patients (42.7%) who tested positive for anti-HBs, 18 (6.7%) lost anti-HBs. Of 179 patients (28.3%) in whom isolated anti-HBc had been detected, 73 (40.8%) developed anti-HBs, 18 (10.1%) lost all HBV markers, and 7 (3.9%) developed HBsAg. Of 65 patients (10.2%) who tested negative for all HBV markers, 13 (20%) developed anti-HBs, 13 (20%) developed isolated anti-HBc, and 4 (6.2%) developed HBsAg, indicating a high risk of HBV exposure. Patients in whom anti-HBc was detected at baseline were more likely to have acquired immunodeficiency syndrome (P=.008). Multivariate analysis revealed that an increase in the CD4 cell count after the commencement of HAART was significantly associated with persistence or subsequent development of anti-HBs in patients with anti-HBs or anti-HBc at baseline, respectively.

Periodic measurements of HBV serological markers in HIV-infected patients are recommended, because new HBV infections and changes of HBV serological markers are not uncommon in patients with improved immunity after commencement of HAART.

The outcome of chronic hepatitis B and the efficacy of interferon alfa (IFN-alpha) remain controversial in human immunodeficiency virus (HIV)-positive patients. We analyzed the influence of HIV coinfection on the response to IFN-alpha therapy, long-term virologic status, progression to cirrhosis, and mortality.

This was a retrospective follow-up cohort study of 141 consecutive hepatitis B e antigen-positive patients (69 HIV positive) followed up for 45 months.

The short-term response to IFN-alpha therapy was not significantly different in HIV-positive and HIV-negative patients (28% vs. 51%; P = 0.06) but was poorer in cases of low CD4 cell count (P = 0.038). The hepatitis B virus (HBV) reactivation rate was higher in HIV-positive patients (P = 0.033) and was associated with low CD4 cell count. The risk of cirrhosis was higher in HIV-positive patients with a CD4 cell count <200/mm(3) (relative risk [RR], 4.57; P = 0.007), in IFN-alpha-untreated patients (RR, 2.63; P = 0.041), in patients older than 33 years (RR, 4.59; P = 0.008), and in cases of high necroinflammatory score at baseline (RR, 1.27; P = 0.010). Cirrhosis-related death was more frequent in HIV-positive patients with low CD4 cell count at baseline (P = 0.041), in alcohol consumers (P = 0.001), in IFN-alpha-untreated patients (P = 0.052), and in patients with high histology activity index at baseline (P = 0.005).

HIV coinfection was associated with poorer response to IFN-alpha therapy, more frequent HBV reactivations, and increased incidence of cirrhosis and cirrhosis-related death in cases of low CD4 count. IFN-alpha therapy decreased the incidence of HBV cirrhosis regardless of HIV status or serologic response.

Hepatitis B virus (HBV) and human immunodeficiency virus (HIV) share common routes of transmission. Therefore, markers of either active or past HBV infection are present in many HIV-infected patients, particularly in intravenous drug users (IDUs). The aim of this study was to analyze the serological pattern of past HBV infection (presence or absence of anti-HBs) and the course of past HBV infection (changes in anti-HBs status, and HBV reactivation) in two cohorts of IDUs with and without HIV infection.

HBV serum markers were studied in 388 HIV-positive and 197 HIV-negative IDUs. Among them, 263 HIV-positive and 50 HIV-negative patients with past HBV infection (serum HBsAg negative and anti-HBc positive, with or without anti-HBs) were followed-up for a median of 21 and 13 months, respectively, to detect changes in anti-HBs status and HBV reactivation.

The prevalence of HBV infection (either active or past) was higher in HIV-positive than in HIV-negative cases (90% vs 62%, p < 0.001), even when stratified by years of drug use. Most cases (92% of HIV-positive and 89% of HIV-negative) had markers of past infection. Among those patients with past HBV infection, 60% of HIV-positive and 72% of HIV-negative presented serum anti-HBs (p = 0.03). The incidence of anti-HBs loss was 1.8 cases/100 person-year in HIV-positive, and 1.8 cases/100 person-year in HIV-negative patients (RR 1.0, 95% CI 0.1-94, p = NS). Incidence of anti-HBs development was 17.6 cases/100 person-year in HIV-positive and 25.6 cases/100 person-year in HIV-negative IDUs (RR, 1.5, 95% CI, 0.6-3.5, p = NS). Only one HIV-positive patient with markers of past HBV infection developed an active infection (0.2 events/100 person-year).

HBV infection (either active or past) is particularly frequent in HIV-positive IDUs. Most cases have markers of past infection. Isolated detection of anti-HBc (absence of anti-HBs) is more common in HIV-positive than in HIV-negative IDUs. Despite their progressive immunosuppression, both anti-HBs loss and HBV reactivation are rare in HIV-infected IDUs.

In HIV-infected patients, who have recovered completely from an acute hepatitis B infection and become anti-HBs positive, hepatitis B infection may be reactivated after progression to AIDS.

We present the case of a homosexual male patient with AIDS who developed clinical and serological reactivation of hepatitis B with detectable HBV-DNA 18 years after complete recovery from acute hepatitis B infection. Prior to reactivation, antiretroviral triple therapy including lamivudine was changed to therapy without lamivudine. After reintroduction of lamivudine in the triple therapy, HBV-DNA became undetectable and the patient lost HBsAg and again developed anti-HBs antibodies.

The hepatitis B in this patient can be explained best by reactivation of persistent HBV infection, possibly because of transient decline in antibodies against HBs-antigen due to a reduction in CD4+ lymphocyte numbers and B cell dysfunction. This observation points to the clinical relevance of HBV persistence in serum and blood cells of anti-HBs-positive subjects for many years after recovery from acute hepatitis B infection. The possible role of lamivudine withdrawal which immediately preceded HBV breakthrough in our patient is noteworthy. Regular monitoring of markers of HBV infection, including HBV-DNA, in patients with AIDS appears justified after discontinuation of lamivudine.

Sera of 1980 homo- and bisexual men who visited the Landesinstitut für Tropenmedizin Berlin (West) between April 1983 and December 1987 were tested for HIV antibodies; 24.3% were positive. Of HIV-antibody-positive men, 78.9% reported both active and passive anal intercourse, 58.8%, rectal enemas, and 53.3%, use of butyl nitrite. There was a sexual partner with known positive HIV-antibody status or AIDS in 33.9%, and in 32.4% there was a history of sexual activity in the USA. In the year before the test, 18.8% had had more than 50 partners. All these behavioral characteristics were found to be significantly correlated to HIV antibodies. We noted a substantial reduction of high-risk behavior from 1983 to 1987. The most important behavioral factor for HIV infection in 1983 and 1984 was sexual activity in the USA, and from 1984 to 1987, the numbers of lifetime partners. Persons infected with HIV were significantly more often carriers of antibodies against HAV, HBV, CMV, EBV, and syphilis. Prevalence of antibodies against HIV, HAV, HBV, and syphilis increased with age, duration of homosexual practice, and the number of partners. Overall crude prevalence rates of HIV antibodies, anti-HBc, anti-HAV, and antibodies to syphilis declined during the observation period. Clinical findings such as fever, oral lesions, and lymphadenopathy syndrome (LAS) were found to be highly indicative of HIV infection. Lower hemoglobin values, a reduced white cell count, and hyperimmunoglobulinemia were significantly more frequent in subjects with HIV antibodies.