Pseudomonas aeruginosa Bacteremic Patients Exhibit Nonprotective Antibody Titers Against Therapeutic Antibody Targets PcrV and Psl Exopolysaccharide.

BACKGROUND: The type 3 secretion protein PcrV and Psl exopolysaccharide are promising therapeutic antibody targets against Pseudomonas aeruginosa. We examined P. aeruginosa bloodstream infection (BSI) isolates for the ability to express PcrV and Psl and evaluated corresponding patient serum for active titers to these targets. METHODS: We identified 114 patients with acute P. aeruginosa BSI; 56 cases were accompanied by acute sera. Serum was evaluated for PcrV- and Psl-specific immunoglobulin G (IgG) and for cytotoxicity and opsonophagocytosis. Isolates were evaluated for susceptibility to antibiotics, expression of PcrV and Psl, and susceptibility to the anti-PcrV/Psl bispecific antibody and clinical candidate MEDI3902. RESULTS: In-hospital mortality for patients with P. aeruginosa BSI was 39%. A total of 26% of isolates were resistant to ≥3 antibiotic classes. Although PcrV and/or Psl were detected in 99% of isolates, a majority of patients lacked active titers to PcrV (100%) and Psl (98%). In addition, MEDI3902 was active against all tested isolates. CONCLUSIONS: A vast majority of P. aeruginosa BSI isolates express PcrV and Psl; however, patient sera most often lacked IgG and functionally active responses to these targets. These results suggest that therapies directed at PcrV and Psl could be a promising approach for combating P. aeruginosa bloodstream infections.

Reproducibility of hepatic fat fraction measurement by magnetic resonance imaging.

PURPOSE: To evaluate the reproducibility of magnetic resonance imaging (MRI)-determined hepatic fat fraction (%) across imaging sites with different magnet types and field strength. Reproducibility among MRI platforms is unclear, even though evaluating hepatic fat fractions (FFs) using MRI-based methods is accurate against MR spectroscopy. MATERIALS AND METHODS: Overweight subjects were recruited to undergo eight MRI examinations at five imaging centers with a range of magnet manufacturers and field strengths (1.5 and 3 T). FFs were estimated in liver and in fat-emulsion phantoms using three methods: 1) dual-echo images without correction (nominally out-of-phase [OP] and in-phase [IP]); 2) dual-dual-echo images (two sequences) with T2* correction (nominally OP/IP and IP/IP); and 3) six-echo images with spectral model and T2* correction, at sequential alternating OP and IP echo times (Methods 1, 2, and 3, respectively). RESULTS: Ten subjects were recruited. For Methods 1, 2, and 3, respectively, hepatic FF ranged from -2.5 to 27.0, 1.9 to 29.6, and 1.3 to 34.4%. Intraclass correlation coefficients were 0.85, 0.89, and 0.91 for each method, and within-subject coefficients of variation were 18.5, 9.9, and 10.3%, respectively. Mean phantom FFs derived by Methods 2 and 3 were comparable to the known FF for each phantom. Method 1 underestimated phantom FF. CONCLUSION: Methods 2 and 3 accurately assess FF. Strong reproducibility across magnet type and strength render them suitable for use in multicenter trials and longitudinal assessments.

Willingness to undergo a repeat liver biopsy among HIV/hepatitis C virus-coinfected and hepatitis C virus-monoinfected patients.

BACKGROUND: Guidelines for chronic hepatitis C virus (HCV) management have recommended that a liver biopsy be repeated at 3-year intervals for HIV/HCV-coinfected patients and 5-year intervals for those with HCV monoinfection to assess fibrosis progression. However, it is unclear if patients are willing to repeat this procedure. OBJECTIVE: To determine the prevalence and factors, particularly HIV coinfection, associated with willingness to repeat a liver biopsy. METHODS: A questionnaire was administered to 235 HCV-infected patients (113 with HIV coinfection) between January 2008 and June 2011 who previously underwent liver biopsy. The main outcome was self-reported willingness to repeat the biopsy. The questionnaire collected data on other hypothesized determinants of willingness to repeat the biopsy. These were evaluated by logistic regression. RESULTS: Among 235 subjects who completed the questionnaire, 32 (14%) reported unwillingness to repeat the biopsy, most commonly because of a perception that it was unimportant for care [13(41%)], concerns regarding pain [12(38%)], and a poor experience with the prior biopsy [7(21%)]. Considering biopsy to be safe [odds ratio (OR), 4.45; 95% CI, 1.50-13.27], important (OR, 4.87; 95% CI, 1.83-12.95), and knowing a person who underwent liver biopsy (OR, 3.45; 95% CI, 1.16-10.23) were associated with willingness to repeat the biopsy. HIV was not associated with willingness to repeat the biopsy (OR, 1.42; 95% CI, 0.67-3.03). CONCLUSIONS: Eighty-six percent of chronic HCV-infected patients were willing to repeat a liver biopsy. HIV was not associated with unwillingness. In patients in whom a repeat liver biopsy is indicated, education on the utility and safety of the biopsy is important to its acceptance.

Distribution of hepatitis C virus genotypes in a diverse US integrated health care population.

Hepatitis C virus (HCV) genotypes influence response to therapy, and recently approved direct-acting antivirals are genotype-specific. Genotype distribution information can help to guide antiviral development and elucidate infection patterns. HCV genotype distributions were studied in a diverse cross-section of patients in the Northern California Kaiser Permanente health plan. Associations between genotype and race/ethnicity, age, and sex were assessed with multivariate logistic regression models. The 10,256 patients studied were median age 56 years, 62% male, 55% White non-Hispanic. Overall, 70% were genotype 1, 16% genotype 2, 12% genotype 3, 1% genotype 4, <1% genotype 5, and 1% genotype 6. Blacks (OR 4.5 [3.8-5.5]) and Asians (OR 1.2 [1.0-1.4]) were more likely to have genotype 1 than 2/3 versus non-Hispanic Whites. Women less likely had genotype 1 versus 2/3 than did men (OR 0.86 [0.78-0.94]). Versus non-Hispanic Whites, Asians (OR 0.38 [0.31-0.46]) and Blacks (OR 0.73 [0.63-0.84]) were less likely genotype1a than 1b; Hispanics (OR 1.3 [1.1-1.5]) and Native Americans (OR 1.9 [1.2-2.8]) more likely had genotype 1a than 1b. Patients age ≥65 years less likely had genotype 1a than 1b versus those age 45-64 (OR 0.34 [0.29-0.41]). The predominance of genotype 1 among all groups studied reinforces the need for new therapies targeting this genotype. Racial/ethnic variations in HCV genotype and subtype distribution must be considered in formulating new agents and novel strategies to successfully treat the diversity of hepatitis C patients.

Test-retest repeatability of MR elastography for noninvasive liver fibrosis assessment in hepatitis C.

PURPOSE: To conduct a rigorous evaluation of the repeatability of liver stiffness assessed by MR elastography (MRE) in healthy and hepatitis-C-infected subjects. MATERIALS AND METHODS: A biopsy-correlated repeatability study using four-slice MRE was conducted in five healthy and four HCV-infected subjects. Subjects were scanned twice on day 1 and after 7-14 days. Each slice was acquired during a 14-s breath-hold with a commercially available acquisition technique (MR-Touch, GE Healthcare). Results were analyzed by two independent analysts. RESULTS: The intraclass correlation coefficient (ICC) was 0.85 (90% confidence interval [CI]: 0.71 to 0.98) for the between-scan average of maximum stiffness within each slice and 0.88 (90% CI: 0.78 to 0.99) for the average of mean stiffness within each slice for the primary analyst. For both analysts, the average of the mean liver stiffness within each slice was highly reproducible with ICC of 0.93 and 0.94. Within-subject coefficients of variation ranged from 6.07% to 10.78% for HCV+ and healthy subjects. CONCLUSION: MRE is a highly reproducible modality for assessing liver stiffness in HCV patients and healthy subjects and can discriminate between moderate fibrosis and healthy liver. MRE is a promising modality for noninvasive assessment of liver fibrosis (CLINICALTRIALS.GOV IDENTIFIER: NCT00896233).

STK11 (LKB1) mutations in metastatic NSCLC: Prognostic value in the real world.

BACKGROUND: Mutations in STK11 (STK11m) and frequently co-occurring KRAS mutations (KRASm/STK11m) are associated with poor survival in metastatic NSCLC (mNSCLC) immuno-oncology trials. There are limited data regarding the prognostic significance of these mutations in a real-world setting. METHODS: This retrospective cohort study analyzed de-identified electronic medical records from the Flatiron Clinico-Genomic database to identify patients with mNSCLC who had initiated first-line immunotherapy (IO; alone or in combination) or chemotherapy under routine care between January 1, 2013 and June 30, 2017. The primary objectives were to assess the prevalence of STK11m and KRASm/STK11m and to determine associations of these mutations with overall and progression-free survival (OS, PFS). RESULTS: Of 2407 patients with mNSCLC, STK11m and KRASm/STK11m were present in 13.6% and 6.5% of patients, respectively. Worse OS outcomes were observed in patients with STK11m versus STK11wt mNSCLC receiving IO (first-line, HR [95% CI], 1.4 [0.9-2.3; p = 0.1]; second-line [subset of first-line cohort], HR, 1.6 [1.3-2.0; p = 0.0002]) or chemotherapy (first-line, HR, 1.4 [1.2-1.6; p < 0.0001]); PFS outcomes showed similar trends. KRASm/STK11m double mutations were associated with worse OS and PFS outcomes versus KRASwt/STK11wt with IO and chemotherapy, similar to the single mutation (STK11m vs STK11wt) findings. CONCLUSIONS: This large observational genomic study among patients receiving routine care highlights the negative prognostic impact of STK11m in patients with mNSCLC treated with IO or chemotherapy. These results complement previous clinical trial data and provide further evidence in the real world of a patient population that would benefit from new treatment options.

Fine-Needle Aspiration for the Evaluation of Hepatic Pharmacokinetics of Vaniprevir: A Randomized Trial in Patients With Hepatitis C Virus Infection.

Fine-needle aspiration (FNA) for serial hepatic sampling may be an efficient and less invasive alternative to core needle biopsy (CNB), the current standard for liver tissue sampling. In this randomized, open-label trial in 31 participants with hepatitis C virus genotype 1 infection (NCT01678131/Merck protocol PN048), we evaluated the feasibility of using FNA to obtain human liver tissue samples appropriate for measuring hepatic pharmacokinetics (PK), using vaniprevir as a tool compound. The primary end point was successful retrieval of liver tissue specimens with measurable vaniprevir concentrations at two of three specified FNA time points. Twenty-nine patients met the primary end point and, therefore, were included in the PK analyses. Hepatic vaniprevir concentrations obtained with FNA were consistent with known vaniprevir PK properties. The shape of liver FNA and CNB concentration-time profiles were comparable. In conclusion, FNA may be effective for serial tissue sampling to assess hepatic drug exposure in patients with liver disease.

Hepatitis E virus antibodies in patients with chronic liver disease.

In the United States, the seroprevalence rate for hepatitis E virus (HEV) is approximately 20%. This study examined HEV seroprevalence in persons with and without chronic liver disease. Our data indicate that HEV seropositivity is high in patients with chronic liver disease and that HEV seroprevalence increases significantly with age.

Improving noninvasive methods of assessing liver fibrosis in patients with hepatitis C virus/human immunodeficiency virus co-infection.

BACKGROUND & AIMS: Liver fibrosis is a significant concern for patients with hepatitis C virus/human immunodeficiency virus co-infection. Fibrosis staging by biopsy is accurate, but costly and invasive. Several fibrosis prediction models using noninvasive biomarkers have been developed but are suboptimal in co-infected patients. We compared results from different staging models and ordinal regression with biopsy data. METHODS: Data from the Adult Acquired Immune Deficiency Syndrome Clinical Trials Group protocol A5178 were used to evaluate 5 models of fibrosis staging; areas under receiver-operator characteristic curves (AUROC) were assessed. Individual covariates were assessed with univariable regression and then entered into an ordinal logistic regression model from which a stage-wise index was developed. RESULTS: Data from 173 patients were evaluated; 85% were on antiretroviral therapy, 31.2% had severe fibrosis (F3/F4), and 14% had cirrhosis (F4). Differences in CD4+ cell and platelets counts and international normalized ratio values were observed between those with and without F3/F4. Among existing models, the FIB-4 index ([age x AST])/[platelet count x (ALT)(1/2)]) performed best, with 88% specificity for F4 and greater than 86% negative predictive values for F3/F4, although AUROC values were low (0.56 +/- 0.03 for F3/F4). By using patients' demographic, clinical, and laboratory data, the ordinal regression model outperformed others, with an AUROC of 0.85 (standard error, 0.03) for predicting stage F3/F4 and 0.89 (standard error, 0.05) for stage 3 alone. CONCLUSIONS: Current noninvasive methods of fibrosis assessment have poor discriminatory capacity in hepatitis C virus/human immunodeficiency virus co-infected patients. Ordinal regression analysis outperformed other noninvasive fibrosis prediction models. Longitudinal studies with paired biopsies will assist in refining the Ordinal Regression Index.

Cytokine expression during chronic versus occult hepatitis B virus infection in HIV co-infected individuals.

Chronic hepatitis B virus infection is characterized by persistent detectable levels of hepatitis B surface antigen (HBsAg) and HBV DNA in the serum. In contrast, HBsAg is not detectable during occult HBV infection, despite the presence of HBV DNA. An altered host immune response could play a role in the development of occult HBV infection; however, potential differences in immune responses among chronic and occult HBV-infected patients have not been evaluated in vivo. In the current study, we evaluated serum levels of regulatory, apoptotic, and fibrotic/anti-fibrotic cytokines/markers as indicators of immune responses in 25 chronic and 12 occult HBV-infected patients. More than half of the patients in both chronic and occult HBV infection groups had IL-2, IL-4, IL-13, and IFN-gamma levels below detectable limits. In contrast, most patients had detectable levels of IL-8, IL-10, IP-10, sFas, sFasL, and TGF-beta1. Of these, only sFas was significantly different between the two groups, with lower levels observed during occult compared to chronic HBV infection (p=0.01). As a surrogate marker of apoptotic inhibition, decreased sFas during occult HBV infection suggests that apoptosis occurs at different rates in occult compared to chronic HBV infection and therefore, may contribute to persistence of occult HBV infection.

Anterior and posterior cruciate ligaments at different patient ages: MR imaging findings.

PURPOSE: To retrospectively compile normative data on the anterior cruciate ligament (ACL) and the posterior cruciate ligament (PCL) in children and young adults. MATERIALS AND METHODS: This HIPAA-compliant study was approved by the institutional review board. The requirement for informed patient consent was waived. Knee MR imaging examinations (n = 324) were performed in 168 female and 156 male patients (age range, 1-20 years) at 1.5 and 3.0 T, and the image findings were retrospectively evaluated by two blinded radiologists separately. One radiologist reviewed all images twice at two sessions, and the other reviewed a random subset of half the images during one session. Discordant assessments were resolved by consensus. The sagittal and coronal ACL-tibial angles, Blumensaat line-ACL angle, angle of inclination of the intercondylar roof, ACL-tibial insertion site, and PCL angle and horizontal component-to-vertical component ratio were measured. The associations between these values and patient age, patient sex, and physeal patency were assessed. Linear and fractional polynomial regression models were used to evaluate the relationships between measurements. RESULTS: ACL-tibial angles became significantly larger (P < .001) with increasing age during skeletal growth and approached adult values after physeal fusion. The Blumensaat line-ACL angle was constant after age 2 years. The inclination of intercondylar roof angle became significantly smaller (P < .001) with increasing age. The ACL-tibial insertion site was constant at the junction of the anterior and middle thirds of the tibial anteroposterior diameter and was not age dependent. The PCL angle became significantly larger (P < .001) with advancing age and in children who had fused as opposed to open physes. The horizontal component-to-vertical component PCL ratio became significantly smaller with advancing age (P < .001). CONCLUSION: During growth, angulation of the ACL is age dependent. The angle and morphologic changes of the PCL are age dependent throughout skeletal maturation.

Cure Strategies for Hepatitis B Virus: The Promise of Immunotherapy.

Chronic hepatitits B virus remains a public health challenge, infecting more than 240 million people globally and causing 600,000 deaths per year from end-stage liver disease and/or hepatocellular carcinoma. Current antiviral therapeutic agents are highly effective at blocking viral replication, but discontinuation of therapy prior to loss of hepatitis B surface antigen generally leads to relapse. New modalities that target host factors of viral persistence such as immune response pathway inhibition hold promise. Other experimental approaches may target virally related persistence factors, including covalently closed circular DNA. All these approaches will require creative new means of assessing proof of biology and proof of mechanism, particularly in the relevant compartment of liver tissue. Furthermore, it is likely to require combinations of modalities in defined patient populations to achieve optimal response. A precompetitive consortium approach may enable companies, regulators, and academic researchers to share best practices and evaluate preclinical and clinical pathways for these novel approaches.

Hyperbilirubinemia is not a major contributing factor to altered bone mineral density in patients with chronic liver disease.

Reduced bone density is commonly encountered in patients with chronic liver disease. Prior studies have shown that unconjugated bilirubin inhibits osteoblast activity and function in vitro and in animal models of bone mineralization. To determine whether hyperbilirubinemia promotes the development of hepatic osteodystrophy, bone mineral density (BMD) was measured by dual energy X-ray absorptiometry in a cohort of 86 consecutive patients with chronic liver disease referred for liver transplant evaluation. The mean age of the study population was 52 years (range, 22-73), in which 52% were female and 90% were white. Average bone density values were significantly lower than expected for age, race, and sex, with Z-scores for the femoral neck and spine of -0.50 (95% confidence interval [CI] -0.63 to -0.37; p=0.0003) and -0.69 (95% CI -0.85 to -0.52; p=0.0001), respectively. Sixty-one subjects (71%) exhibited reduced BMD (T-score of femoral neck or spine

Clinical trials of treatment for hepatitis C virus infection in HIV-infected patients: past, present, and future.

Coinfection with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) type 1 is common. Rates of liver-related morbidity and mortality have been increasing in the coinfected population, and treatment for HCV infection in this group remains a challenge. The HCV-monoinfected population, especially patients infected with HCV genotype 2 or 3, has benefited dramatically from the advent of treatment with pegylated interferon plus ribavirin; rates of sustained virological response approach 55%. Coinfected patients lag behind, with rates of sustained virological response ranging between 26% and 40%; rates of sustained virological response are even lower among patients infected with HCV genotype 1. It is encouraging, however, that therapies known to be safe for treating monoinfected patients have been proven to be generally safe and well tolerated in patients coinfected with HIV and HCV, as well. Future therapies, some of which are currently in development, will likely include new targets, such as helicase and polymerase. It is hoped that, as more-effective agents are discovered, the disparity in treatment response will diminish.

Outcomes among patients with end-stage liver disease who are coinfected with HIV and hepatitis C virus.

In at-risk populations, shared routes of transmission lead to high rates of concordance between infection with human immunodeficiency virus (HIV) type 1 and hepatitis C virus (HCV). In the era of highly active antiretroviral therapy (HAART), end-stage liver disease (ESLD) has emerged as a leading cause of mortality in coinfected patients. HAART-related toxicities have been implicated, especially when given to patients with viral hepatitis. Rates of response to treatment for HCV infection in coinfected patients continue to lag behind those in monoinfected patients, even with the advent of pegylated interferons. Liver transplantation has been approached with caution in this population because of concern about the sequelae of immunosuppression and HAART-related hepatotoxicity, and results have been conflicting. Clinical and serological markers of ESLD in coinfected patients, management of cirrhosis, and the appropriateness of transplantation are discussed.

Liver injury and changes in hepatitis C Virus (HCV) RNA load associated with protease inhibitor-based antiretroviral therapy for treatment-naive HCV-HIV-coinfected patients: lopinavir-ritonavir versus nelfinavir.

BACKGROUND: Highly active antiretroviral therapy (HAART) initiation in patients coinfected with human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV) has been associated with transaminase and HCV viral load flares. Previous studies have included highly variable antiretroviral regimens. We compared effects of 2 protease inhibitor-based regimens on alanine aminotransferase (ALT) levels and HCV loads in HCV-HIV-coinfected patients initiating HAART. METHODS: Seventy HIV-infected patients with positive baseline results of HCV enzyme-linked immunosorbant assay from a treatment trial comparing lopinavir-ritonavir with nelfinavir were evaluated during a 48-week period. HCV and HIV titers were analyzed at baseline, at weeks 24 and 48 of treatment, and during flares in the ALT level of >5 times the upper limit of normal. RESULTS: A total of 57 of 70 patients tested positive for HCV RNA at baseline. HCV titers for patients in lopinavir-ritonavir and nelfinavir groups, respectively, were as follows: baseline, 6.07 and 6.22 log IU/mL; week 24 of treatment, 6.68 and 6.48 log IU/mL; and week 48 of treatment, 6.32 and 6.44 log IU/mL. Of patients with a CD4+ cell count of <100 cells/mm3 at baseline, 5 of 11 in the nelfinavir group and 0 of 10 in the lopinavir-ritonavir group had an increase in the HCV load of >0.5 log IU/mL from baseline to week 48. The mean ALT level increased by 45 U/L at 24 weeks and 18 U/L at 48 weeks in the nelfinavir group but decreased by 18 U/L at 24 weeks and 7 U/L at 48 weeks in the lopinavir-ritonavir group. Eight patients in the nelfinavir group and 2 patients in the lopinavir-ritonavir group had grade 3 or 4 flares in the ALT level. CONCLUSIONS: HAART initiation is associated with increased HCV loads and ALT levels. A low baseline CD4+ cell count is associated with persistent increases in the HCV RNA load in nelfinavir-treated patients. These results warrant careful interpretation of abnormalities in the ALT load after HAART initiation in HCV-HIV-coinfected patients to prevent premature discontinuation of treatment.

Epidemiology of Hepatitis C Virus: A Battle on New Frontiers.

The hepatitis C virus (HCV) is a leading cause of liver-related morbidity and mortality in the United States and other parts of the world. The epidemiology of the disease is highly variable between and within countries, and strategies to deal with HCV identification and treatment must be tailored to the geographic location and the political and economic environment of the region. Although great strides have been made in improving HCV transmission risk in blood supply products, new challenges related to changing patterns of disease incidence continue to require fresh evaluation and new approaches to disease prevention.

Highly active antiretroviral therapy in patients infected with human immunodeficiency virus increases CD40 ligand expression and IL-12 production in cells ex vivo.

Highly active anti-retroviral therapy (HAART) restores CD4(+) T-cell numbers in the periphery; however, its efficacy in restoring functional immunity is not fully elucidated. Here we evaluated longitudinal changes in the expression of several key markers of T-cell activation, namely CD40 ligand (CD154), OX40 (CD134), or CD69, after anti-CD3/CD28 activation, as well as levels of IL-12 production after Staphylococcus aureus Cowan stimulation in 28 HIV-infected adult patients. Patients were followed up to 12 mo post-HAART initiation. Viral burdens and CD4 cell counts were measured at the same time points. A control group of 15 HIV-uninfected adult subjects was included for comparison. Significant increases in CD40L and OX40 expression, but not of CD69 expression, were observed over time in the overall patient population, and more particularly in patients with baseline CD4 counts lower than or equal to 200 cells/µL, or those with baseline viral loads lower than or equal to 10(5) RNA copies/mL. Similar increases were seen for IL-12 production. Viral loads were inversely associated with CD40L expression or IL-12 production in a mixed linear model analysis, while CD4 counts were directly associated. CD40L expression and IL-12 production were significantly correlated. In conclusion, HAART-mediated control of viral replication led to partial restoration of CD40L upregulation/expression, and to increased IL-12 production, but the magnitude of the response depended on the baseline characteristics of the treated patients.

The prevalence and significance of 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 co-amplify 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.