Characterization of Individuals With Hepatitis B Virus-Related Cirrhosis in a Large Integrated Health Care Organization, 2008-2019.

CONTEXT: Chronic hepatitis B (CHB), caused by hepatitis B virus (HBV), is a risk factor for cirrhosis. The management of HBV-related cirrhosis is challenging, with guidelines recommending treatment initiation and regular monitoring for those affected. OBJECTIVE: Our study characterized Kaiser Permanente Southern California patients with HBV-related cirrhosis and assessed whether they received recommended laboratory testing and imaging monitoring. DESIGN: Retrospective cohort study. SETTING AND PARTICIPANTS: We identified KPSC members aged ≥18 years with CHB (defined by 2, consecutive positive hepatitis B surface antigens ≥6 months apart) from 2008 to 2019. Of these patients, we further identified patients with potential HBV-related cirrhosis through ICD-10 code diagnosis, adjudicated via chart review. MAIN OUTCOME MEASURES: Age, race/ethnicity, laboratory tests (eg, alanine aminotransferase [ALT]), and hepatocellular carcinoma (HCC) screening (based on standard screening recommendations via imaging) were described in those with HBV-related cirrhosis versus those without. RESULTS: Among patients with CHB, we identified 65 patients with HBV-related cirrhosis over ~8 years. Diabetes was the most common comorbidity and was approximately 3 times more prevalent among patients with cirrhosis compared to patients without cirrhosis (21.5% vs. 7.1%). Of the 65 patients with cirrhosis, 72.3% (N = 47) received treatment. Generally, we observed that liver function tests (eg, ALT) were completed frequently in this population, with patients completing a median of 10 (6, 16) tests/year. All patients with cirrhosis had ≥1 ALT completed over the study period, and almost all cirrhotic patients (N = 64; 98.5%) had ≥1 HBV DNA test. However, the proportion of yearly imaging visits completed varied across the study years, between 64.0% in 2012 and 87.5% in 2009; overall, 35% (N = 23) completed annual imaging. CONCLUSIONS: Our findings suggest that among patients with HBV-related cirrhosis, at the patient-level, completed imaging orders for HCC screening were sub-optimal. However, we observed adequate disease management practices through frequent liver function tests, linkage to specialty care, image ordering, and shared EHR between KPSC providers.

On-treatment risks of cirrhosis and hepatocellular carcinoma among a large cohort of predominantly non-Asian patients with non-cirrhotic chronic hepatitis B.

Background & Aims: The vast majority of studies evaluating differences in on-treatment risks of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB) have been conducted in Asia. Data on the course of CHB on antiviral therapy among predominantly non-Asian populations is less well described. We aimed to evaluate overall risks of cirrhosis and HCC and the influence of baseline factors on this risk among a predominantly non-Asian cohort of patients with CHB in the US. Methods: Using longitudinal data from the national Veterans Affairs database, we evaluated the incidence of cirrhosis or HCC among adults with non-cirrhotic CHB on continuous antiviral therapy. Cumulative incidence functions and adjusted Cox proportional hazards models employed competing risks methods and evaluated overall risk and predictors of developing cirrhosis or HCC while on treatment. Results: Among 2,496 patients with non-cirrhotic CHB (39.1% African American, 38.4% non-Hispanic White, 18.8% Asian, mean age 58.0 ± 13.4 years), the overall incidences of cirrhosis and HCC were 3.99 per 100 person-years (95% CI 3.66-4.35) and 0.43 per 100 person-years (95% CI 0.33-0.54), respectively. The highest incidences of cirrhosis and HCC were observed in non-Hispanic White patients (5.74 and 0.52 per 100 person-years, respectively), which were significantly higher than in Asian patients (1.93 and 0.17 per 100 person-years, respectively, p <0.0001). On multivariate regression, only baseline FIB-4 score was consistently associated with long-term risk of cirrhosis or HCC. Conclusions: Using a longitudinal cohort of predominantly non-Asian Veterans with non-cirrhotic CHB on antiviral therapy (an understudied population), we provide important epidemiological data to describe long-term risks of cirrhosis and HCC. Impact and implications: In one of the largest studies to date of a predominantly non-Asian cohort of patients with non-cirrhotic chronic hepatitis B, we provide important epidemiological data describing the long-term risks of cirrhosis and hepatocellular carcinoma among patients on antiviral therapies. Among this understudied population, the overall incidence of cirrhosis was 3.99 per 100-person-years (95% CI 3.66-4.35) and of HCC was 0.43 per 100-person-years (95% CI 0.33-0.54). These data also emphasize the importance of continued monitoring and HCC surveillance among CHB patients who are maintained on antiviral therapies.

Global trends and the impact of chronic hepatitis B and C on disability-adjusted life years.

BACKGROUND AND AIMS: Advances in hepatitis B virus (HBV) and hepatitis C virus (HCV) therapies have improved morbidity and mortality, but global disparities in viral hepatitis outcomes remain. We evaluate global trends in the impact of HBV and HCV on disability-adjusted life years (DALYs). METHODS: Using data from the 2010-2019 Global Burden of Diseases Study (GBD), overall all-cause DALYs for patients with acute HBV or HCV, HBV- or HCV-related cirrhosis, and HBV- or HCV-related hepatocellular carcinoma (HCC) was calculated as the sum of years of life lost because of premature death and years lived with disability. DALYs were presented as age-standardized rates per 100 000 population stratified by age and sex. RESULTS: From 2010 to 2019, the overall global impact of HBV on DALYs per 100 000 decreased from 27.6 to 20.9 for acute HBV and 168.6 to 129.8 for HBV-related cirrhosis but remained stable for HBV-related HCC. The impact of HCV on DALYs per 100 000 decreased from 5.23 to 3.3 for acute HCV, 159.2 to 146.2 for HCV-related cirrhosis, and 37.5 to 34.9 for HCV-related HCC. We observed significant differences in the impact of HBV and HCV on DALYs when stratified by world regions. CONCLUSION: Decreases in HBV and HCV DALYs from 2010 to 2019 were observed. Disparities in DALY improvements across world regions suggest unequal access to viral hepatitis care and treatment. Achieving goals of viral hepatitis elimination will require enhanced prevention efforts and funding for high-burden regions and regions that have not had substantial reductions in DALYs because of HBV and HCV.

Screening Practices for Latent Tuberculosis Infection in Clinical Trials Evaluating Treatments for Chronic Hepatitis B Virus Infection.

Latent tuberculosis infection (LTBI) prevalence among adults with chronic hepatitis B (CHB) is two times higher than LTBI prevalence in the general adult population. Although newer CHB treatments evaluated in clinical trials modulate the immune system and potentially increase LTBI reactivation risk, it is unknown whether CHB clinical trials are screening for LTBI. We describe LTBI screening practices in CHB clinical trials. We utilized the ClinicalTrials.gov website to identify clinical trials that evaluated CHB treatments. CHB treatments were categorized according to LTBI reactivation risk as unknown, low, moderate, and high-risk. Tuberculosis burden among countries in which CHB clinical trials were conducted were defined using World Health Organization definitions. Of 651 CHB clinical trials identified, 452 (69%) were included in the final cohort, among which 337 (75%), 108 (24%), and 7 (1%) evaluated CHB medications with a low, unknown, and moderate LTBI reactivation risk, respectively. A total of 330 (73.0%) CHB clinical trials reviewed were conducted in high TB burden countries. Three (0.6%) CHB trials reviewed screened for LTBI; one each among CHB treatments with low, moderate, and high LTBI reactivation risk. Although nearly 75% of all CHB clinical trials were conducted in high TB burden countries and 25% of trials evaluated CHB treatments with an unknown LTBI reactivation risk, less than 1% of trials screened for LTBI. Consideration should be given to screen for LTBI among CHB clinical trials given high prevalence of co-infection and potential for increased LTBI reactivation risk with CHB treatments evaluated.

Global incidence and mortality of hepatitis B and hepatitis C acute infections, cirrhosis and hepatocellular carcinoma from 2010 to 2019.

Hepatitis B virus (HBV) and hepatitis C virus (HCV) contribute to significant healthcare burden globally. We aim to provide an updated and comprehensive analysis of global trends in the incidence and mortality of HBV and HCV related acute infections, cirrhosis and hepatocellular carcinoma (HCC). Estimates of annual cause-specific disease incidence and mortality for HBV and HCV were analysed using the 2010-2019 Global Burden of Diseases, Injuries and Risk Factors Study database. Three distinct disease states were evaluated: acute infections, cirrhosis and HCC. Age-standardized disease incidence and mortality were presented per 100,000 population and stratified by age, sex, year and 21 world regions. From 2010 to 2019, overall incidence of acute HBV declined by 19.3% (95% CI 4.1-32.0, p < .05) and HBV cirrhosis declined by 15.0% (95% CI 9.8-20.7, p < .05). Incidence of HCV cirrhosis increased by 5.6% (95% CI 0.3-10.2, p < .05) and HCV HCC remained stable. Incidence of acute HCV declined until 2015, after which it began increasing. From 2010 to 2019, overall mortality for HBV cirrhosis and HCV cirrhosis declined, whereas mortality for acute infections and HCC remained stable. Major differences in HBV and HCV incidence and mortality trends were observed when stratified by world regions. In conclusion, while our analyses of global trends in HBV and HCV incidence and mortality demonstrate encouraging trends, disparities in disease epidemiology were observed across world regions. These observations will identify regions and populations where greater focus and resources are needed to continue progressing towards viral hepatitis elimination.

Prevalence of Latent Tuberculosis Infection Among Persons with Chronic Hepatitis B Virus Infection: A Systematic Review and Meta-Analysis.

BACKGROUND: Tuberculosis (TB) and chronic hepatitis B virus infection (HBV) can be prevented through latent tuberculosis infection (LTBI) treatment and HBV vaccination, respectively. Prevalence of LTBI and HBV are six- and ninefold higher among non-US-born compared to US-born persons, respectively. Few studies have described the prevalence of LTBI-HBV co-infection. AIMS: In this study, we estimated LTBI prevalence among persons with chronic HBV. METHODS: We conducted a systematic review and meta-analysis using PubMed from inception through September 1, 2019, and identified and reviewed studies that provided data regarding LTBI prevalence among adults with chronic HBV. Pooled LTBI prevalence among adults with HBV was calculated using a random-effects meta-analysis model. RESULTS: A total of 1,205 articles were identified by systematic review of the published literature. Six studies were included in the meta-analysis; five studies were conducted in North America, and one was in China. LTBI prevalence among adults with chronic HBV was estimated to be 34.25% (95% confidence interval: 17.88-50.62%). CONCLUSION: LTBI prevalence among adults with chronic HBV was two times higher than the LTBI prevalence among all non-US-born persons. The high LTBI prevalence and increased risk of hepatotoxicity with TB medications among persons with chronic HBV may warrant consideration of routine screening for HBV among persons who are tested for LTBI. Reducing morbidity and mortality associated with TB and chronic HBV may require healthcare systems and public health to ensure that persons at risk of both infections are screened and treated for LTBI and chronic HBV.

Clonally related Burkholderia contaminans among ventilated patients without cystic fibrosis.

We investigated a cluster of 10 Burkholderia cepacia complex-positive cultures among ventilated patients and those with a tracheostomy in an acute care hospital. Isolates from 5 patients had outbreak-strain-related Burkholderia contaminans. Isolates of B. cepacia complex unrelated to the outbreak strain were cultured from a sink drain. The investigation identified practices that might have led to contamination of patient respiratory care supplies with tap water, which might have contributed to the cluster.

Epidemiology of community-associated Clostridium difficile infection, 2009 through 2011.

IMPORTANCE: Clostridium difficile infection (CDI) has been increasingly reported among healthy individuals in the community. Recent data suggest that community-associated CDI represents one-third of all C difficile cases. The epidemiology and potential sources of C difficile in the community are not fully understood. OBJECTIVES: To determine epidemiological and clinical characteristics of community-associated CDI and to explore potential sources of C difficile acquisition in the community. DESIGN AND SETTING: Active population-based and laboratory-based CDI surveillance in 8 US states. PARTICIPANTS: Medical records were reviewed and interviews performed to assess outpatient, household, and food exposures among patients with community-associated CDI (ie, toxin or molecular assay positive for C difficile and no overnight stay in a health care facility within 12 weeks). Molecular characterization of C difficile isolates was performed. Outpatient health care exposure in the prior 12 weeks among patients with community-associated CDI was a priori categorized into the following 3 levels: no exposure, low-level exposure (ie, outpatient visit with physician or dentist), or high-level exposure (ie, surgery, dialysis, emergency or urgent care visit, inpatient care with no overnight stay, or health care personnel with direct patient care). MAIN OUTCOMES AND MEASURES: Prevalence of outpatient health care exposure among patients with community-associated CDI and identification of potential sources of C difficile by level of outpatient health care exposure. RESULTS: Of 984 patients with community-associated CDI, 353 (35.9%) did not receive antibiotics, 177 (18.0%) had no outpatient health care exposure, and 400 (40.7%) had low-level outpatient health care exposure. Thirty-one percent of patients without antibiotic exposure received proton pump inhibitors. Patients having CDI with no or low-level outpatient health care exposure were more likely to be exposed to infants younger than 1 year (P = .04) and to household members with active CDI (P = .05) compared with those having high-level outpatient health care exposure. No association between food exposure or animal exposure and level of outpatient health care exposure was observed. North American pulsed-field gel electrophoresis (NAP) 1 was the most common (21.7%) strain isolated; NAP7 and NAP8 were uncommon (6.7%). CONCLUSIONS AND RELEVANCE: Most patients with community-associated CDI had recent outpatient health care exposure, and up to 36% would not be prevented by reduction of antibiotic use only. Our data support evaluation of additional strategies, including further examination of C difficile transmission in outpatient and household settings and reduction of proton pump inhibitor use.

Epidemiologic and clinical features among patients hospitalized in Wisconsin with 2009 H1N1 influenza A virus infections, April to August 2009.

BACKGROUND: During April 15 through July 23, 2009, Wisconsin reported the most confirmed and probable cases of 2009 influenza A (H1N1) virus (2009 H1N1) infection in the United States. Preliminary reports suggest that 2009 H1N1 infection disproportionately affected minority populations. METHODS: Prospective surveillance among all acute care hospitals in Wisconsin to detect patients hospitalized at least 24 hours with confirmed 2009 H1N1 infection during April 23 through August 15, 2009. RESULTS: During the study interval, 252 patients were hospitalized and 11 (4%) died. Statewide hospitalization rates by age, sex, and race/ethnicity categories were highest among patients aged <1 year (21.6/100,000), females (4.9/100,000), and African Americans (36.3/100,000). The median age was 28 years: Hispanics (median age=16 years) and African Americans (24 years) were younger than non-Hispanic whites (37 years) and Asians (38 years). African Americans were more likely to have a hematologic condition and be morbidly obese (BMI > or = 40 kg/m2), and less likely to be admitted to an intensive care unit compared to other race/ethnicity groups (P<0.05). Hispanics and non-Hispanic whites were more likely to have cancer, be non-morbidly obese (BMI 30-39.9 kg/m2 or BMI percentile > or = 95%), and be hospitalized for >5 days compared to African Americans and Asians (P<0.05). There were no significant racial/ethnic differences in time from illness onset to admission or receipt of antiviral therapy, need for mechanical ventilation, acute respiratory distress syndrome, or death. CONCLUSIONS: The first wave of the 2009 H1N1 pandemic in Wisconsin disproportionately affected hospitalized patients who were African Americans, Asians, and Hispanics compared to non-Hispanic whites. Preventive measures focused on these populations may reduce morbidity associated with 2009 H1N1 infection.