Hepatitis B virus (HBV) and hepatitis C virus

Prevalence and Predictors of Hepatitis B Virus Coinfection in a United States Cohort of Hepatitis C Virus-Infected Patients Gia L. Tyson, 1,2,3 Jennifer R. Kramer, 1,3 Zhigang Duan, 1,3 Jessica A. Davila, 1,3 Peter A. Richardson, 1,3 and Hashem B. El-Serag 1,2,3 There are sparse epidemiologic data on coinfection of hepatitis B (HBV) and hepatitis C (HCV) in the United States. Therefore, the aim of this study was to determine the prevalence and predictors of HBV coinfection in a large U.S. population of HCV patients. We used the National Veterans Affairs HCV Clinical Case Registry to identify patients tested for HCV during 1997-2005. Patients were categorized based on HCV exposure (any two 1HCV tests or one test with a diagnostic code), HCV infection (1RNA or genotype), HBV exposure (any 1HBV test, excluding 1HBsAb only), and HBV infection (1HBsAg, HBV DNA, or HBeAg). The prevalence of HBV exposure among patients with HCV exposure and that of HBV infection among patients with HCV infection were determined. Multivariate logistic regression evaluated potential demographic and clinical predictors of HBV coinfection. Among 168,239 patients with HCV exposure, 58,415 patients had HBV exposure for a prevalence of 34.7% (95% confidence interval [CI] 34.5-35.0). Among 102,971 patients with HCV infection, 1,431 patients had HBV coinfection for a prevalence of 1.4% (95% CI 1.3-1.5). Independent associations with HBV coinfection compared with HCV monoinfection were age 50 years, male sex, positive HIV status, history of hemophilia, sickle cell anemia or thalassemia, history of blood transfusion, cocaine and other drug use; there was decreased risk in patients of Hispanic ethnicity. Conclusion: This is the largest cohort study in the U.S. on the prevalence of HBV coinfection in HCV patients. Among veterans with HCV, exposure to HBV is common (35%), but HBV coinfection is relatively low (1.4%). Several possible risk factors were identified. (HEPATOLOGY 2013;58:538-545) Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are the most common causes of liver disease worldwide, affecting 350 million and 170 million people, respectively. 1-3 In the United States, HCV infection affects 2.7-3.2 million and HBV infection affects 800,000-1.4 million people. 1,4 It is estimated that 2%-10% of individuals with positive HCV antibodies also have HBV antibodies. 1,5,6 Reported risk factors of HBV HCV coinfection include older age, male sex, Asian ethnicity, injection drug use (IDU), a high number of sexual partners, and HIV infection, but not all of these risk factors have been consistently established. 1,6-11 Studies indicate that HBV HCV coinfection is associated with increased risk of worse clinical outcomes such as advanced fibrosis or cirrhosis, decompensation, hepatocellular carcinoma, and transplantation compared with HCV monoinfection. 1,3,5,7,8,12,13 Most information on the prevalence and predictors of HBV HCV coinfection comes from studies of Abbreviations: CCR, Clinical Case Registry; CPT, Current Procedural Terminology; HBcAb, hepatitis B core antibody; HBeAb, hepatitis Be antibody; HBeAg, hepatitis Be antigen; HBsAg, hepatitis B surface antigen; HBV, hepatitis B virus; HCV, hepatitis C virus; ICD-9, International Classification of Disease, 9th Revision; IDU, injection drug use; VA, Veterans Affairs. From the 1 Houston VA Health Services Research and Development Center of Excellence, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX; 2 Section of Gastroenterology and Hepatology, Baylor College of Medicine, Houston, TX; 3 Section of Health Services Research, Department of Medicine, Baylor College of Medicine, Houston, TX. Received May 31, 2012; accepted February 26, 2013. Partly funded by NIH grant T32 DK083266-01A1, NIH grant R01-CA-125487, NIH/National Institute of Diabetes and Digestive and Kidney Disease, Center Grant P30 DK56338 and the Houston Veterans Affairs Health Services Research and Development Center of Excellence HFP90-020 and MRP05-305. Disclaimer: The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs. 538

HEPATOLOGY, Vol. 58, No. 2, 2013 TYSON ET AL. 539 populations with chronic HBV infection 10-12,14,15 conducted primarily in Europe and Asia. 1,6-8,16,17 There is a paucity of data on the epidemiology of HBV coinfection in a U.S. population where chronic HCV infection is the more prevalent infection. 1,4 One of the few studies in the U.S. to address this topic was conducted between 1998 and 2004 among 1,257 HCVinfected patients in two New York hospitals, 1 but additional studies with a larger number of patients are needed. Awareness of the prevalence and predictors of HBV coinfection has implications for the screening and prevention of viral hepatitis. Furthermore, understanding the epidemiology of HBV coinfection is important given the potential for worse clinical outcomes in this cohort of patients. The Department of Veterans Affairs (VA) has the largest integrated healthcare system in the U.S. and it collects clinical data on a large number of patients within the system who have HCV. Therefore, we conducted a retrospective study using a national VA cohort of HCV-infected patients to determine the prevalence and predictors of HBV coinfection. Materials and Methods Data Source. The VA HCV Clinical Case Registry (CCR) was used to identify patients with positive HCV testing in the CCR during 1997-2005. Details on the CCR were published elsewhere. 18 The study protocol was approved by the Baylor College of Medicine Institutional Review Board and the Michael E. DeBakey Veterans Affairs Research and Development Committee. Study Variables. HCV exposure was defined as two positive HCV tests (antibody, RNA, or genotype) or one positive test combined with an International Classification of Disease, 9th Revision (ICD-9) code for HCV at any of the 128 VA healthcare facilities nationwide. HCV infection was defined as a positive HCV RNA or genotype. The HCV index date for these cases was defined as the first occurrence of a positive HCV test or HCV-related ICD-9 code. HBV exposure was defined as a positive test for hepatitis B core antibody (HBcAb), hepatitis B surface antigen (HBsAg), HBV DNA, hepatitis Be antigen (HBeAg), or hepatitis Be antibody (HBeAb) during 1997-2005. HBV coinfection was defined as a positive test for HBsAg, HBV DNA, or HBeAg within 1 year before or after the HCV index date. Other Variables. Potential predictors of HBV coinfection included demographic (age, sex, and race/ ethnicity) and clinical factors (HIV, diabetes, hemophilia, thalassemia, sickle cell anemia, dialysis, blood transfusions, organ transplantation, anxiety, posttraumatic stress disorder, bipolar/depression, psychosis and abuse of alcohol, cocaine, cannabis or other drugs). HIV, alcohol abuse, cocaine, and cannabis were defined by positive laboratory testing or ICD-9 code recorded any time prior to 1 year after the HCV index date. Hemophilia, thalassemia, and sickle cell anemia were defined by ICD-9 code recorded any time during the study period. Diabetes, dialysis, blood transfusion, organ transplantation, anxiety/posttraumatic stress disorder, bipolar/depression, psychosis, other drug abuse were defined by ICD-9 code that were recorded any time prior to 1 year after the HCV index date. Data Analysis. The prevalence estimate (and 95% confidence intervals [CIs]) of HBV exposure was calculated as the proportion of patients with HBV exposure among those with HCV exposure. We also determined the prevalence of HBV exposure among those with HCV infection. The prevalence estimate (and 95% CIs) of HBV coinfection was calculated as the proportion of patients with HBV coinfection among those with HCV infection. Patients were required to have at least one test determining HBV exposure or infection status to be included in the respective prevalence calculations. In addition to the definition of HBV coinfection described above, two sensitivity analyses were conducted of HBV coinfection prevalence in which HBV coinfection was defined as (1) positive test results for HBsAg, HBV DNA, or HBeAg at any time during the study period (1997-2005) as opposed to within 1 year of the HCV index date; and (2) the same HBV definitions as the primary analysis, but testing for HBV was not required to be included in the prevalence calculation. HBV vaccination in the study cohort was determined by the presence of Current Procedural Terminology (CPT) codes for HBV vaccine between Address reprint requests to: Gia L. Tyson, M.D., 2450 Holcombe Blvd. Suite 01Y, Houston, TX 77021. E-mail: gtyson@tulane.edu Copyright VC 2013 by the American Association for the Study of Liver Diseases. View this article online at wileyonlinelibrary.com. DOI 10.1002/hep.26400 Potential conflict of interest: Nothing to report.

540 TYSON ET AL. HEPATOLOGY, August 2013 Fig. 1. Prevalence of exposure to HBV among patients exposed to HCV. *Number of patients who tested positive for at least one of the HBV tests designated in the figure (this excludes HBsAb, which is associated with HBV vaccination). October 1 1996 and September 30 2006. The proportions of patients with HBV vaccination were calculated for the HCV exposure and HCV-infected cohorts. Annual rates of HBV vaccination, prevalence of HBV exposure, and HBV coinfection were calculated in the HCV infected cohort from 1997-2005. To identify independent predicators of HBV coinfection, a multivariate logistic regression model was used and odds ratios (ORs) with 95% CIs were estimated. The multivariate model included demographic (age, sex, race/ethnicity) and clinical predictors (HIV, hemophilia, thalassemia, sickle cell anemia, dialysis, blood transfusions, alcohol abuse, drug abuse, and Deyo comorbidity 19 index) chosen using a stepwise selection. Variables were included in the final model if P < 0.10. We compared several demographic and clinical factors between patients with HCV infection who received HBV testing and those who did not receive HBV testing. All statistical analyses were performed using SAS 9.1 (SAS Institute, Cary, NC). Results Prevalence of HBV Exposure and Coinfection. Between 1997 and 2005, there were 193,107 patients with exposure to HCV and of whom 168,239 patients (87.1%) were tested for HBV exposure. Of those tested, HBsAg was the only HBV testing in 21.5%, while 75.2% received some combination of HBV testing (HBsAg, HBcAb, HBV DNA, HBeAg, or HBeAb) (Fig. 1). Among 168,239 HCV-exposed patients with HBV testing, 58,415 tested positive, resulting in a 34.7% (95% CI 34.5-35.0) prevalence of HBV exposure (Fig. 1). Of the patients exposed to HCV, 137,283 patients (71.1%) were defined as having HCV infection by a positive HCV RNA or genotype. There were 102,971 patients (75.0%) with HCV infection who were tested for HBV infection within 1 year before or after the HCV index date. The prevalence of HBV exposure (any 1HBV test, excluding 1HBsAb only) among the cohort with HCV infection (1RNA or genotype) (n 5 102,971) was 36.6% (95% CI 36.3-36.9). In this cohort of HCV-infected patients 1,431 tested positive for HBV infection, resulting in a 1.4% (95% CI 1.3-1.5) prevalence of HBV coinfection among patients with HCV infection. Figure 2 presents the estimates of HBV testing and HBV coinfection. The demographics of the HCV infection cohort (n 5 102,971) were as follows: the mean age was 50.5 years (standard deviation 7.8 years), 97% males, 54% Caucasians, 32% African-Americans, 5% Hispanics, 0.2% Asians, 0.8% other, and 9% with missing race/ ethnicity (Table 1). Sensitivity analyses were conducted to determine if redefining the time period for HBV infection or eliminating the requirement for HBV testing would impact the prevalence of HBV coinfection. The prevalence of HBV coinfection from the sensitivity analyses ranged from 1.0%-1.7% (Table 2). The proportions of patients with HBV vaccination in the HCV-exposed cohort (defined by at least two 1HCV tests or one test with a diagnostic code) and in the HCV-infected cohort (defined by 1RNA or genotype) were 26.4% and 32.6%, respectively. Within the HCV-infected cohort the HBV vaccination rates

HEPATOLOGY, Vol. 58, No. 2, 2013 TYSON ET AL. 541 Fig. 2. Prevalence of HBV infection among patients with HCV infection. *Number of patients who tested positive for at least one of the HBV tests designated in the figure. increased slightly over time between 1997 and 2005, while at the same time the prevalence of HBV exposure (defined by any 1HBV test, excluding 1HBsAb only) and HBV coinfection (defined by a positive test for HBsAg, HBV DNA, or HBeAg within 1 year before or after the HCV index date) declined slightly (Table 3). Table 1. Characteristics of the HCV Infection Cohort of 102,971 Patients With a Positive HCV RNA or Genotype and Testing for HBV Infection Within 1 Year Before or After HCV Index Date Characteristics Number (%) Age 50 53,069 (51.5) 51-64 44,542 (43.3) 65 5,360 (5.2) Sex Female 2,873 (2.8) Male 100,098 (97.2) Race/Ethnicity Caucasian 55,404 (53.8) African-American 32,461 (31.5) Hispanic 4,604 (4.5) Asian 236 (0.2) Other 776 (0.8) Missing 9,490 (9.2) HIV1 6,397 (6.2) Hemophilia/SS/Thalassemia 362 (0.4) Blood Transfusions 3,306 (3.2) Drug Use Cocaine 25,823 (25.1) Other drugs 35,289 (34.3) Cannabis 15,383 (14.9) SS, sickle cell anemia. Predictors of HBV Coinfection. The prevalence of HBV coinfection significantly decreased, 1.6%, 1.2%, 0.8% with increasing age categories, 50, 51-64, 65, respectively (P < 0.0001). The prevalence of HBV coinfection was also significantly different among ethnicities (P < 0.01): Asians (2.1%), African-Americans (1.5%), Caucasians (1.4%), and Hispanics (1.0%). The final multivariate logistic regression model (Table 4) confirmed the age and ethnicity differences based on coinfection status. There was a trend of Asian ethnicity being associated with increased HBV coinfection, but this was not statistically significant (OR 1.64; 95% CI 0.67-3.99). Hispanic ethnicity was associated with a statistically significant decreased risk of HBV coinfection (OR 0.68; 95% CI 0.51-0.92). Risk for HBV coinfection decreased by 23% among those 51-64 years and by 50% among those 65 years compared to those 50years. There was a significantly increased risk of HBV coinfection associated with male sex, positive HIV status, a history of hemophilia, sickle cell anemia or thalassemia, history of blood transfusion, cocaine and other drug use (Table 4). The highest risk for HBV coinfection was in HIV-positive patients (more than 2-fold) and patients with a history of hemophilia, sickle cell anemia, or thalassemia (95% increased risk). Men were 76% more likely to have HBV coinfection than women. HBV testing was significantly more likely to occur in males than females (75.1 versus 71.5%, P < 0.0001), African-Americans, Hispanics, and Asians

542 TYSON ET AL. HEPATOLOGY, August 2013 Table 2. Prevalence of HBV Coinfection Among HCV-Infected Patients Prevalence of HBV (95% CI) HBV Coinfection Definition HBV Coinfection Tests HBV Testing Required * No HBV Testing Required Coinfection recorded at anytime during study period HBsAg1, HBV DNA1, or HBeAg1 2,027/119,323 2,027/137,283 1.7% (1.6-1.8) 1.5% (1.4-1.5) Coinfection recorded within 1 year before or after HCV index date HBsAg1, HBV DNA1, or HBeAg1 1,431/102,971 1,431/137,283 1.4% (1.3-1.5) 1.0% (1.0-1.1) HCV infection was defined as a positive HCV RNA or genotype. *Patients included in the calculation were required to have documented laboratory testing for HBsAg, HBV DNA, or HbeAg. compared to Caucasians (77.1 versus 74.2%, respectively, P < 0.0001). HBV testing was also significantly more likely to occur in the presence of the following conditions than their absence: HIV infection (81.8 versus 74.6%, P < 0.0001), dialysis (88.6 versus 74.9%, P < 0.0001), alcohol abuse (77.9 versus 72.6%, P < 0.0001), and cocaine abuse (79.1 versus 73.7%, P < 0.001). There was a minimal difference between patients with HBV testing and patients without testing regarding the presence of diabetes and hemophilia, thalassemia, or sickle cell anemia. Discussion This is the largest study in the U.S. to examine the prevalence and predictors of HBV coinfection in a cohort of patients with HCV. Approximately 35% of patients with exposure to HCV were also exposed to HBV in this study. Among HCV-infected patients, the prevalence of HBV coinfection defined by a positive test for HBsAg, HBV DNA, or HBeAg within 1 year before or after the HCV index date was 1.4%. The prevalence ranged from 1.0%-1.7% in the sensitivity analyses. The highest age-specific prevalence of HBV coinfection was 1.6% observed in the 50 age group, and the lowest prevalence was 0.8% in the 65 age Table 3. HBV Vaccination, HBV Exposure, and HBV Coinfection in the HCV-Infected Cohort (n 5 102,971) HCV Index Date HBV Vaccination (%) HBV Exposure Prevalence (%) HBV Coinfection Prevalence (%) 1997 28.8 46.6 2.5 1998 30.7 43.1 1.7 1999 32.0 41.5 1.7 2000 32.8 38.4 1.4 2001 33.5 35.5 1.2 2002 33.5 33.5 1.0 2003 33.9 32.8 1.0 2004 32.9 31.2 1.3 2005 34.0 27.9 1.1 HBV exposure defined as a positive test for HBcAb, HBsAg, HBV DNA,HBeAg, or HBeAb. HBV coinfection defined as a positive test for HBsAg, HBV DNA, or HBeAg within 1 year before or after the HCV index date. group. Asians had the highest prevalence (2.1%) of HBV coinfection and Hispanics had the lowest prevalence (1.0%). The independent predictors for HBV coinfection were male sex, positive HIV status, a history of hemophilia, sickle cell anemia or thalassemia, history of blood transfusion, cocaine and other drug use. The prevalence of HBV exposure among HCVinfected patients has been reported around 25% in a population-based study using the National Health and Nutrition Examination Survey data. 20 In hospital-based studies also using a U.S. cohort with HCV from New York and Detroit, the prevalence of HBV exposure has Table 4. Predictors of HBV Coinfection (n 5 1,431) Among HCV-Infected Patients (n 5 102,971) Predictors of HBV Coinfection Odds Ratio (95% CI) Age 50 51-64 0.77 (0.69-0.86) 65 0.50 (0.36-0.69) Sex Female Male 1.76 (1.17-2.64) Race/Ethnicity Caucasian African-American 1.02 (0.90-1.14) Hispanic 0.68 (0.51-0.92) Asian 1.64 (0.67-3.99) HIV1 Absent Present 2.03 (1.72-2.38) Hemophilia/SS/Thalassemia Absent Present 1.95 (1.04-3.68) Blood Transfusions Absent Present 1.63 (1.28-2.08) Drug use None Cocaine 1.23 (1.09-1.40) Other drug use 1.19 (1.03-1.39) Cannabis 1.33 (0.96-1.86) HBV coinfection defined as a positive test for HBsAg, HBV DNA, or HBeAg within 1 year before or after the HCV index date. HCV infection defined as a positive HCV RNA or genotype. SS, sickle cell anemia.

HEPATOLOGY, Vol. 58, No. 2, 2013 TYSON ET AL. 543 been reported around 60%. 1,21 The relatively high prevalence of exposure to HBV as found in our study (35%) and that reported in the literature (25%-60%) suggests a possible benefit of testing for HBV exposure among patients with exposure to HCV. This high prevalence may also warrant checking for HBsAb prior to vaccinating against HBV, as recommended by the American Association for the Study of Liver Diseases (AASLD), as a more cost-effective strategy given the likelihood of previous exposure to HBV. 21 The prevalence of HBV coinfection has been reported between 2%-10% in both U.S. and non-u.s. studies, 1,5-7,9 while the prevalence was only 1.4% in this study. Occult HBV infection (HBV DNA-positive and HBsAg-negative) was not captured in the definition used in our study for prevalence estimates and could have contributed to the relatively low prevalence. 5,6 Although it is possible that the prevalence of HBV coinfection among HCV cohorts is actually lower than previously reported, because another large study from Australia with 117,547 patients with viral hepatitis identified 2,604 patients to have both HBV and HCV, a prevalence of 2.2%. 7 HCV testing is likely to vary over time and among VA facilities; however, we are unable to account for changes in HCV or HBV testing in this study. It might be expected that with time newer and more sensitive tests would be used, resulting in an increased prevalence of HBV coinfection over time, but this was not observed. Based on our yearly prevalence estimates, HBV coinfection was more common in 1997, and steadily declined in subsequent years. The VA has guidelines for HBV screening and vaccination among HCV-positive patients. However, we previously reported using the VA CCR data that in an HCV-infected cohort HBV vaccination was performed in only 22%. 22 In the current study, the HBV vaccination rates among those with HCV exposure (any two 1HCV tests or one test with a diagnostic code) and HCV infection (1RNA or genotype) were 26.4% and 32.6%, respectively. While Table 3 suggests that the temporal increase in HBV vaccination rates correspond with decreases in the prevalence of exposure to HBV and HBV coinfection, the relatively low vaccination rate is not likely to explain this drop. The observed significant association between a history of hemophilia, sickle cell anemia, or thalassemia and a nearly 2-fold increased risk HBV coinfection has not previously been reported. One previous study has shown beta-thalassemia independent of unscreened blood consumption to be a risk factor for HCV infection, but HBV was not examined. 23 Additionally, there has been a suggestion of patients with thalassemia being at risk for HCV not related to blood transfusions, but the source of infections was not identified. 24,25 It is possible some risk factor(s) such as blood transfusions could not be completely accounted for in this study. While the observed association is strong, residual confounding may be present. The findings of this study confirm the associations of cocaine, other drug use, and ethnicity with HBV coinfection. 1,9,11,26 The finding that Asian ethnicity is likely associated with increased risk and Hispanic ethnicity associated with decreased risk of HBV coinfection is consistent with two smaller previous U.S. studies. 1,9 In these studies HBV coinfection was also associated with a higher prevalence or increased risk in IDU. 1,9 This study used cocaine and other drugs as surrogates for IDU since specific information on IDU was not available in the CCR. Both were associated with HBV coinfection, supporting the internal validity of this study, as IDU has been a consistent independent determinant of HBV coinfection. 1,11,26 The findings of this study that provide insight into inconsistent reports in the literature include the association of age, sex, and blood transfusions with HBV coinfection. In non-u.s. studies there has been no significant difference in age or blood transfusions based on coinfection status. 6,7 In another recent U.S. study by Bini and Perumalswami 1 from two New York hospitals, male sex and blood transfusions were not independently associated with HBV coinfection. In both our study and the Bini and Perumalswami 1 study, younger age (<50 years and <40 years, respectively) was associated with increased risk of HBV coinfection. The prevalence estimates and predictors of HBV coinfection in our study is limited by incomplete HBV and HCV testing in this VA cohort and the inability to differentiate between acute versus chronic HBV infection. However, our sensitivity analyses indicate that our prevalence estimates are robust to these assumptions. Although we presented the findings from the multivariate model evaluating predictors of HBV coinfection in the HCV-infected cohort who had HBV testing within 1 year of the HCV index date, we also conducted a multivariate model evaluating predictors of HBV coinfection detected at any time during the study period (n 5 119,323; HBV coinfection prevalence of 1.7%). The same significant predictors of HBV coinfection were identified in both models (data not shown). We cannot account for the demographic and clinical differences observed between patients tested for HBV and those not tested for HBV. It is possible that those less likely to be tested (i.e., older patients, females, non-hiv-infected patients) may have been more likely

544 TYSON ET AL. HEPATOLOGY, August 2013 to be HBV-infected, thus affecting our results about high-risk groups for coinfection (i.e., younger patients, male sex, HIV-infected patients). Yet the magnitude of the risk estimates and level of significance identified in the predictors of this study would suggest that the differences between patients tested for HBV and those not tested are unlikely to have affected the results. It is also possible that females may have been tested for HBV as part of obstetrical care provided outside of the VA, and this information would not be available in our dataset. The generalizability of the findings may be limited since most patients were male. Nevertheless, more than 2,500 women were assessed. The use of secondary data from the CCR limited the examination of other possible risk factors such as number of sexual partners, detailed information on viral loads for HBV or HCV, and timing of viral infections. Additionally, evaluation of other known risk factors of HBV infection, like country of origin, could not be examined in this study, because that information is not available in the CCR. However, it is unlikely that the country of origin would have played an important factor among a veterans population that is typically comprised of American-born individuals. 27 A major strength of this study is the use of the HCV CCR, which provided information on over 190,000 patients with HCV. The CCR is more than an administrative database with ICD-9 codes, but also contains laboratory data, which allowed for more accurate classification of patients and variables. The use of several definitions of HBV coinfection resulted in prevalence calculations within a relatively tight range (1.0%-1.7%), supporting the robustness of the findings. This large dataset allowed the identification of a sufficient number of coinfected patients to perform detailed analyses on predictors of HBV coinfection. The AASLD recommends screening of all persons with HCV for HBV infection. 28 Our study shows that most persons with exposure to HCV were indeed tested for HBV (87%). While we did not perform a formal cost-effectiveness analysis of HBV screening in the study population, the 1.4% yield of actual HBV coinfection and the 35% yield of past exposure may make the screening strategy worthwhile. The utility of the AASLD recommendation is in testing both HBsAg and HBsAb as the best screening strategy. Our study provides novel information on the prevalence of HBV exposure and coinfection among HCV patients in the U.S. Based on these findings, all patients with HCV exposure should be tested for HBV. Additionally, this study identified risk factors more frequent in patients with HBV coinfection than HCV monoinfection. These predictors of HBV coinfection can be used to target screening and prevention programs to those individuals who may be at greatest risk for coinfection. s 1. 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