Change in Health-Related Quality of Life in Youth with Chronic Hepatitis B Living in North America: A 5-Year Cohort Study.

BACKGROUND: Greater hepatitis-related symptomology is associated with lower health-related quality-of-life (HRQoL) among untreated youth with chronic hepatitis B (CHB). How HRQoL changes over time in this population is unknown. METHODS: Children from 7 hepatology centers in North America positive for hepatitis B surface antigen, not taking anti-viral therapy, were enrolled in the Hepatitis B Research Network. A validated self-report HRQoL measure, the Child Health Questionnaire Child Report (CHQ-CF87), was completed annually by participants 10-17 years, with demographic variables, liver disease symptoms, and laboratory tests. Linear mixed-effects models were used to evaluate the 10 CHQ-CF87 subscale scores over 5 years among participants who completed the CHQ-CF87 at least twice. RESULTS: Participants (N = 174) completed the CHQ-CF87 a median of 4 times. Median age was 12 years (interquartile range: 10-14) at baseline; 60% were female, 79% Asian, and 47% adopted. The CHQ-CF87 subscale scores were high at baseline (median range: 75.4-100) and did not differ by time point, except for the Family Activities subscale (mean [95% CI]: 82.3 [79.8-84.8] at baseline; 90.8 [86.1-94.6] week 240). Most subscale scores lacked sufficient individual-level variability in change over time to evaluate predictors. Being White versus Asian predicted a more favorable change in Behavior (6.5 [95% CI: 2.0-11.0]). Older age predicted less favorable change in Mental Health (-0.8 [95% CI: -1.36 to -0.23] per year). Changes in liver enzymes and hepatitis B antigens, DNA, or symptom count were not related to changes in these subscale scores. CONCLUSION: HRQoL was generally good and consistent across 5 years in youth with CHB.

Human immunodeficiency virus coinfection differentially impacts hepatitis B virus viral markers based on hepatitis Be antigen status in patients with suppressed viremia.

Hepatitis B virus (HBV) RNA and hepatitis B core-related antigen (HBcrAg), reflecting transcriptional activity of covalently closed circular DNA, are gaining traction as important markers to assess viral activity. Whether their expression differs under viral suppression by HIV co-infection status is unknown. Among adults with chronic HBV on antiviral therapy, we sought to determine if the expression of HBV markers (specialized and well-established) differs between HBV-HIV co-infection vs. HBV mono-infection. We compared HBV marker levels among 105 participants in the Hepatitis B Research Network (HBRN) HBV-HIV Ancillary Study and 105 participants in the HBRN mono-infected Cohort Study, matched for HBeAg status and HBV DNA suppression on therapy. Among HBeAg+ participants (N = 58 per group), after adjusting for age, sex, race, ALT and HBV DNA, viral markers were higher (p < .05) in the HBV-HIV versus the HBV-only sample (HBeAg: 1.05 vs. 0.51 log10 IU/mL; HBsAg: 3.85 vs. 3.17 log10 IU/mL; HBV RNA: 5.60 vs. 3.70 log10 U/mL; HBcrAg: 6.59 vs. 5.51 log10 U/mL). Conversely, among HBeAg(-) participants (N = 47 per group), HBsAg (2.00 vs. 3.04 log10 IU/mL) and HBV RNA (1.87 vs. 2.66 log10 U/mL) were lower (p < .05) in HBV-HIV vs. HBV-only; HBcrAg levels were similar (4.14 vs. 3.64 log10 U/mL; p = .27). Among adults with chronic HBV with suppressed viremia on antiviral therapy, viral markers tracked with HIV co-infection status and associations differed inversely by HBeAg status. The greater sensitivity and specificity of HBV RNA compared to HBcrAg allows for better discrimination of transcriptional activity regardless of HBeAg status.

Maternal and Neonatal Outcomes of Pregnancy within 7 years after Roux-Y Gastric Bypass or Sleeve Gastrectomy Surgery.

PURPOSE: Few studies examine whether maternal and neonatal outcomes differ by time from metabolic and bariatric surgery (MBS) to conception. We describe maternal and neonatal outcomes among women with pregnancy after Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) overall and by whether conception occurred during the period when pregnancy is not recommended (< 18 months postoperative) versus later. MATERIALS AND METHODS: A prospective cohort study enrolled 135 US adult women (median age, 30 years, body mass index [BMI], 47.2 kg/m2) who underwent RYGB or SG (2006-2009) and subsequently reported ≥ 1 pregnancy within 7 years. Participants self-reported pregnancy-related information annually. Differences in prevalence of maternal and neonatal outcomes by postoperative conception timeframe (< 18 versus ≥ 18 months) were assessed. RESULTS: Thirty-one women reported ≥ 2 postoperative pregnancies. At time of postoperative conception (median 26 [IQR:22-52] months postoperative) median BMI was 31 (IQR:27-36) kg/m2. Excessive gestational weight gain (55%), cesarean section (42%) and preterm labor or rupture of membranes (40%) were the most common maternal outcomes. Forty percent of neonates had a composite outcome of still birth (1%), preterm birth (26%), small for gestational age (11%), or neonatal intensive care unit admission (8%). Prevalence of outcomes did not statistically significantly differ by timeframe. CONCLUSION: In US women who conceived ≤ 7 years following RYGB or SG, 40% of neonates had the composite neonatal outcome. The prevalence of maternal and neonatal outcomes post-MBS were not statistically significant by conception timeframe.

Use of HBV RNA and to predict change in serological status and disease activity in CHB.

BACKGROUND AND AIMS: Predicting changes in disease activity and serological endpoints is necessary for the management of patients with chronic hepatitis B (CHB). We examined whether HBV RNA and hepatitis B core-related antigen (HBcrAg), two specialized virological markers proposed to reflect the activity of covalently closed circular DNA, may improve the ability to predict not sustained inactive carrier phase, spontaneous alanine aminotransferase (ALT) flare, HBeAg loss, and HBsAg loss. APPROACH AND RESULTS: Among eligible participants enrolled in the North American Hepatitis B Research Network Adult Cohort Study, we evaluated demographic, clinical, and virologic characteristics, including HBV RNA and HBcrAg, to predict not sustained inactive carrier phase, ALT flare, HBeAg loss, and HBsAg loss through a series of Cox proportional hazard or logistic regression models, controlling for antiviral therapy use. Among the study population, 54/103 participants experienced not sustained inactive carrier phase, 41/1006 had a spontaneous ALT flare, 83/250 lost HBeAg, and 54/1127 lost HBsAg. HBV RNA or HBcrAg were predictive of all 4 events. However, their addition to models of the readily available host (age, sex, race/ethnicity), clinical (ALT, use of antiviral therapy), and viral factors (HBV DNA), which had acceptable-excellent accuracy (e.g., AUC = 0.72 for ALT flare, 0.92 for HBeAg loss, and 0.91 for HBsAg loss), provided only small improvements in predictive ability. CONCLUSION: Given the high predictive ability of readily available markers, HBcrAg and HBV RNA have a limited role in improving the prediction of key serologic and clinical events in patients with CHB.

SARS-CoV-2 control on a large urban college campus without mass testing.

OBJECTIVE: A small percentage of universities and colleges conducted mass SARS-CoV-2 testing. However, universal testing is resource-intensive, strains national testing capacity, and false negative tests can encourage unsafe behaviors. PARTICIPANTS: A large urban university campus. METHODS: Virus control centered on three pillars: mitigation, containment, and communication, with testing of symptomatic and a random subset of asymptomatic students. RESULTS: Random surveillance testing demonstrated a prevalence among asymptomatic students of 0.4% throughout the term. There were two surges in cases that were contained by enhanced mitigation and communication combined with targeted testing. Cumulative cases totaled 445 for the term, most resulting from unsafe undergraduate student behavior and among students living off-campus. A case rate of 232/10,000 undergraduates equaled or surpassed several peer institutions that conducted mass testing. CONCLUSIONS: An emphasis on behavioral mitigation and communication can control virus transmission on a large urban campus combined with a limited and targeted testing strategy.

A prospective cohort study of renal function and bone turnover in adults with hepatitis B virus (HBV)-HIV co-infection with high prevalence of tenofovir-based antiretroviral therapy use.

OBJECTIVE: Tenofovir disoproxil fumarate (TDF) is a common component of antiretroviral therapy in hepatitis B virus (HBV)-HIV co-infected adults but few studies have evaluated worsening renal function and bone turnover, known effects of TDF. METHODS: Adults from eight North American sites were enrolled in this cohort study. Research assessments were conducted at entry and every 24 weeks for ≤192 weeks. Bone markers were tested at baseline, week 96 and week 192 from stored serum. We evaluated changes in markers of renal function and bone turnover over time and potential contributing factors. RESULTS: A total of 115 patients were prospectively followed; median age 49 years, 91% male and 52% non-Hispanic Black. Duration of HIV was 20.5 years. TDF use ranged from 80% to 92% throughout follow-up. Estimated glomerular filtration rate (eGFR) (ml/min/1.73m2 ) decreased from 87.1 to 79.9 over 192 weeks (p < 0.001); however, the prevalence of eGFR <60 ml/min/1.73m2 did not appear to differ over time (always <16%; p = 0.43). From baseline to week 192, procollagen type I N-terminal propeptide (P1NP) (146.7 to 130.5 ng/ml; p = 0.001), osteocalcin (14.4 to 10.2 ng/ml; p < 0.001) and C-terminal telopeptides of type I collagen (CTX-1) (373 to 273 pg/ml; p < 0.001) decreased. Younger age, male sex and overweight/obesity versus normal weight predicted a decrease in eGRF. Black race, healthy weight versus underweight, advanced fibrosis, undetectable HBV DNA, and lower parathyroid hormone level predicted worsening bone turnover. CONCLUSION: In this HBV-HIV cohort with high prevalence of TDF use, several biomarkers of renal function and bone turnover indicated worsening status over approximately 4 years, highlighting the importance of clinical awareness in co-infected adults.

HBV transcription and translation persist despite viral suppression in HBV-HIV co-infected patients on antiretroviral therapy.

BACKGROUND AND AIMS: Liver injury may persist in patients with HBV receiving antiviral therapy who have ongoing transcription and translation. We sought to assess ongoing HBV transcription by serum HBV RNA, translation by serum hepatitis B core related antigen (HBcrAg), and their associations with hepatic HBsAg and HBcAg staining in patients coinfected with HBV and HIV. METHODS: This is a cross-sectional study of 110 adults coinfected with HBV and HIV who underwent clinical assessment and liver biopsy. Immunohistochemistry (IHC) was performed for HBsAg and HBcAg. Viral biomarkers included quantitative HBsAg, HBV RNA, and HBcrAg. RESULTS: Participants' median age was 49 years (male, 93%; Black, 51%; HBeAg+, 65%), with suppressed HBV DNA (79%) and undetectable HIV RNA (77%) on dually active antiretroviral therapy. Overall, HBV RNA and HBcrAg were quantifiable in 81% and 83%, respectively (96% and 100% in HBeAg+, respectively). HBcAg staining was detected in 60% and HBsAg in 79%. Higher HBV RNA was associated with higher HBcAg and HBsAg IHC grades (both p < 0.0001). The HBsAg membranous staining pattern was significantly associated with higher HBV-RNA and HBcrAg levels. CONCLUSION: HBcAg and HBsAg IHC staining persisted despite viral suppression, and IHC grades and staining patterns correlated with markers of transcription (HBV RNA) and translation (HBcrAg). These data indicate that apparent HBV suppression is associated with residual transcription and translation that could contribute to liver pathology. Additional antiviral strategies directed to HBV protein expression may be useful to ameliorate liver injury.

Characteristics of Older Patients With Immunotolerant Chronic Hepatitis B Virus Infection.

BACKGROUND & AIMS: Most patients in the immunotolerant (IT) phase of chronic hepatitis B (CHB) transition to the immune active (IA-hepatitis B surface antigen [HBeAg]+) phase by early adulthood. We examined characteristics of adults in the IT vs IA-HBeAg+ phase and rate of transition from IT to other phases of CHB, with a focus on those ≥40 years. METHODS: Demographic, clinical, and virologic characteristics of participants in the Hepatitis B Research Network adult cohort study with IT CHB (alanine aminotransferase ≤1.5 × upper limit of normal, hepatitis B virus DNA >107 IU/mL) were compared by age category, and to those with IA-HBeAg+ CHB in cross-sectional analysis. This study received institutional review board approval at all participating centers. RESULTS: Of 107 adult IT participants, 52 (48%) were <30, 33 (31%) were 30 to 39, and 22 (21%) were ≥40 years old (maximum, 71 years). Among IT groups, the proportion born in Asia and duration of CHB were greater in older IT groups, but virologic and liver disease characteristics were similar. Compared with IA-HBeAg+ participants (n = 192), IT participants were younger, fewer were men, more were Asian, and platelets, qHBsAg, and qHBeAg levels were higher. Similar differences were observed when comparisons were made with the ≥40 years IT group. Among IT participants, 60 (56%) transitioned during 206 person-years of follow-up. The phase transition rate per 100 person-years was highest in the <30 years group (33.0 [95% confidence interval [CI], 23.4-46.7]) vs the 30 to 39 years group (24.8 [95% CI, 15.6-39.4]) and ≥40 group (27.4 [95% CI, 14.8-50.9]), but 95% CIs overlapped. CONCLUSIONS: In a large North American population, over 50% of adults in the IT phase of CHB were ≥30 years and 20% were ≥40 years old, but older IT patients had similar characteristics and rates of transition as younger IT patients.

Hepatitis B RNA and Core-Related Antigen Provide Value Beyond DNA in Evaluating e But Not Surface Antigen Clearance.

In chronic hepatitis B virus (HBV) infection, hepatitis B e antigen (HBeAg) and hepatitis B surface antigen (HBsAg) clearance are important milestones toward immune control.1 A drop in HBV DNA is an established correlate of both HBeAg and HBsAg clearance.2 We evaluated changes in HBV RNA and hepatitis B core-related antigen (HBcrAg) levels, markers of transcriptional activity of covalently closed circular DNA (cccDNA),3,4 with HBeAg and HBsAg clearance, and compared them with changes in HBV DNA level among adult participants in the Hepatitis B Research Network (HBRN).

A Prospective Cohort Study of Novel Markers of Hepatitis B Virus Replication in Human Immunodeficiency Virus Coinfection.

BACKGROUND & AIMS: The contribution of the novel biomarkers, hepatitis B virus (HBV) RNA and HBV core-related antigen (HBcrAg), to characterization of HBV-human immunodeficiency virus (HIV) coinfection is unclear. We evaluated the longitudinal dynamics of HBV RNA and HBcrAg and their association with classical HBV serum biomarkers and liver histology and viral staining. METHODS: HBV-HIV co-infected adults from 8 North American centers entered a National Institutes of Health-funded prospective cohort study. Demographic, clinical, serological, and virological data were collected at entry and every 24 to 48 weeks for up to 192 weeks. Participants with HBV RNA and HBcrAg measured ≥2 times (N = 95) were evaluated; 56 had paired liver biopsies obtained at study entry and end of follow-up. RESULTS: Participants had a median age of 50 years; 97% were on combination anti-viral therapy. In hepatitis B e antigen (HBeAg)+ participants, there were significant declines in HBV RNA and HBcrAg over 192 weeks that tracked with declines in HBeAg, hepatitis B surface antigen, HBV DNA, and hepatitis B core antigen (HBcAg) hepatocyte staining grade (all P < .05). In HBeAg- participants, there were not significant declines in HBV RNA (P = .49) and HBcrAg (P = .63), despite modest reductions in hepatitis B surface antigen (P < .01) and HBV DNA (P = .03). HBV serum biomarkers were not significantly related to change in hepatic activity index, Ishak fibrosis score, or hepatocyte HBcAg loss (all P > .05). CONCLUSIONS: In HBV-HIV coinfected adults on suppressive dually active antiviral therapy, the use of novel HBV markers reveals continued improvement in suppression of HBV transcription and translation over time. The lack of further improvement in HBV serum biomarkers among HBeAg- patients suggests limits to the benefit of combination anti-viral therapy and provide rationale for additional agents with distinct mechanisms of action.

Seven-Year Durability of Improvements in Urinary Incontinence After Roux-en-Y Gastric Bypass and Sleeve Gastrectomy.

This cohort study evaluates the durability of improvements in urinary incontinence among women and men who underwent Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy.

Changes in Marital Status Following Roux-en-Y Gastric Bypass and Sleeve Gastrectomy: A US Multicenter Prospective Cohort Study.

Among a US cohort followed 5 years after Roux-en-Y gastric bypass or sleeve gastrectomy, cumulative incidence of marriage and separation/divorce were 18% among unmarried (N=614) and 13% among married (N=827) participants, respectively. Preoperative predictors of marriage included younger age, college degree, lower BMI and cohabitating or being separated (versus single). Objectives: To describe changes in marital status following Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG). Background: Spousal encouragement and finding a life partner are self-reported motivators for undergoing bariatric surgery. Methods: This study included 1441 US adults enrolled in a 6-center prospective cohort study who underwent RYGB or SG (2006-2009) and self-reported marital status preoperatively and annually postoperatively for ≤5 years. Time to change in marital status was analyzed with Kaplan-Meier estimates of cumulative incidence and Cox proportional-hazard models. Results: Preoperative, 57% of participants (79% female, median age 47 years, median body mass index [BMI] 47 kg/m2) were married, 5% cohabitating, 4% separated, 15% divorced, 2% widowed, and 17% always single. The 5-year cumulative incidence of marriage among unmarried participants (N = 614) was 18%. Cohabitating (hazard ratios [HR] = 5.25) or being separated (HR = 3.03) versus always single, younger age (HR = 1.69/10 years), having a college degree versus ≤high school (HR = 2.36), lower BMI (HR = 1.54/10kg/m2), and fewer depressive symptoms (HR = 1.47/10 Beck Depression Inventory points) preoperative independently predicted (P < 0.05) higher chance of marriage. The 5-year cumulative incidence of separation/divorce among married participants (N = 827) was 13%. Female sex (HR = 2.08), younger age (HR = 1.84/10 years), household income <$25,000 versus ≥$100,000 (HR = 2.48), smoking (HR = 1.76), and sexual desire ≥once/week versus never (HR = 2.12) preoperative independently predicted (P ≤ 0.05) separation/divorce. Conclusions: Among a cohort of US adults, the majority did not change marital status within 5 years following RYGB or SG. Cumulative incidence of marriage and separation/divorce was 18% among unmarried and 13% among married participants, respectively. Several preoperative predictors of marriage and separation/divorce were identified.

A 7-Year Study of the Durability of Improvements in Pain, Physical Function, and Work Productivity After Roux-en-Y Gastric Bypass and Sleeve Gastrectomy.

Importance: Bariatric surgical procedures are associated with clinically important improvements (CIIs) in pain and physical function. However, there are declines in initial improvement by the third postoperative year, and the long-term durability of improvements are not well-described. Objective: To evaluate the durability of improvements in pain and physical function through 7 years after Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG). Design, Setting, and Participants: This study is part of the Longitudinal Assessment of Bariatric Surgery-2 (LABS-2), a cohort study at 10 US hospitals. Adults with severe obesity (ie, body mass index of 35 or greater) undergoing bariatric surgery were assessed preoperatively (2006-2009) and followed up annually for as long as 7 years or until 2015. Of 1829 participants who underwent RYGB or SG in LABS-2, 338 were excluded from this study because they had a follow-up period of less than 5 years. Analysis of participants who underwent RYGB or SG and completed research assessments preoperatively and postoperatively for 5 to 7 years was conducted from March to April 2022. Main Outcomes and Measures: Preoperative-to-postoperative CIIs in pain and physical function scores from the 36-Item Short Form Health Survey and the Western Ontario McMaster Osteoarthritis Index, and 400-meter walk time, using previously established thresholds; and remission of mobility deficit, ie, inability to walk 400 meters in 7 minutes or less. Results: A total of 1491 individuals were included, with 1194 (80%) women; 59 (4%) Hispanic, 164 (11%) non-Hispanic Black, and 1205 (82%) non-Hispanic White individuals; a preoperative median (IQR) age of 47 (38-55) years; and a preoperative median (IQR) body mass index of 47 (42-52). Between 3 and 7 years after surgery, the percentage of participants with preoperative-to-postoperative CIIs in bodily pain decreased from 50% (95% CI, 48%-53%) to 43% (95% CI, 40%-46%), in physical function from 75% (95% CI, 73%-77%) to 64% (95% CI, 61%-68%), and in 400-meter walk time from 61% (95% CI, 56%-65%) to 50% (95% CI, 45%-55%). Among participants with a preoperative mobility deficit, remission decreased from 50% (95% CI, 42%-57%) to 41% (95% CI, 32%-49%), and among participants with severe knee or hip pain or disability, the percentage with CIIs in knee and hip pain and function decreased (eg, hip pain: from 77% [95% CI, 72%-82%] to 65% [95% CI, 58%-72%]; knee function: from 77% [95% CI, 73%-82%] to 72% [95% CI, 67%-77%]). Conclusions and Relevance: In this cohort study, despite decreases in preoperative-to-postoperative improvements across follow-up, CIIs in perceived bodily and joint-specific pain and in self-reported and objectively measured physical function ranged from 41% to 72%, depending on the measure and subgroup, 7 years after surgery, suggesting that RYGB and SG are commonly associated with long-term CIIs in pain and physical function.

Interrater reliability and internal consistency of the eating disorder examination in the longitudinal assessment of bariatric surgery study.

BACKGROUND: Psychometric studies of eating disorder measures within bariatric surgery populations are limited. OBJECTIVES: To examine the interrater reliability and internal consistency of the Eating Disorder Examination (EDE) among patients before and after bariatric surgery. SETTING: Three clinical centers of the Longitudinal Assessment of Bariatric Surgery Research Consortium. METHODS: The EDE-Bariatric Surgery Version was administered and audio-recorded by trained interviewers before and at annual assessments after bariatric surgery. Approximately 20% of interviews were randomly selected for rating by a second interviewer. Reliability of the original and brief EDE subscales was examined. RESULTS: Interrater reliability of the EDE subscales ranged from .86-.97 for the original subscales and .83-.95 for brief subscales before surgery, and .90-.98 for the original subscales and .92-.97 for brief subscales after bariatric surgery. Interrater agreement (based on kappa) was almost perfect for overeating and binge-eating behaviors and substantial for loss-of-control eating before surgery. Similar interrater agreements (based on kappa) were observed after surgery for subjective overeating and binge-eating episodes. Internal consistency of the subscale and global scores was variable, ranging from .41-.97. CONCLUSION: Findings provide support of the interrater reliability of the EDE, albeit with variable internal consistency, before and after bariatric surgery. Despite support for trained raters to reliably assess EDE constructs, variability in internal consistency suggests that further psychometric testing and rigorous scale development of disordered eating may be needed for the bariatric surgery population.

Change in C-reactive protein after Roux-en-Y gastric bypass through 7 years of follow-up.

BACKGROUND: Long-term change in CRP is not well characterized in the context of RYGB. OBJECTIVE: To report C-reactive protein (CRP) after Roux-en-Y gastric bypass surgery (RYGB). SETTING: Between 2006 and 2009 1770 adults enrolled in a prospective cohort study underwent Roux-en-Y gastric bypass (RYGB) at 1 of 10 U.S. hospitals. METHODS: Research assessments were conducted before surgery and annually postoperatively for up to 7 years. This study included those with high-sensitivity CRP assessed before surgery and 1 or more follow-up assessments (n = 1180). RESULTS: Before surgery, participants' median age was 46 years, and the median body mass index (BMI) was 46 kg/m2; 80% were female. Before surgery, mean (95% confidence interval [CI]) CRP was the highest of all time points (1.01 [.95-1.08] mg/L); it then decreased to a nadir of .18 (.15-.22) mg/L at 2 years postoperatively (P < .001). CRP was higher at 7 years (.26 [.22, .29] mg/L) than at 2 years postoperatively (P < .001) but remained lower at 7 years than preoperatively (P < .001). Additionally, only 3.2% (95% CI: 1.6%-4.8%) of participants had elevated CRP (>1 mg/dL) 7 years postoperatively versus 32.9% (95% CI: 30.2%-35.3%) preoperatively (P < .001). Several preoperative factors were associated with following a less favorable CRP trajectory over time, including higher preoperative CRP level, higher BMI, current smoking, and diabetes. CONCLUSION: The vast majority of adults who underwent RYGB experienced a sustained improvement in CRP throughout 7 years of follow-up with nonelevated values. However, those with higher preoperative CRP and BMI levels and diabetes and who smoke may benefit from additional testing and monitoring to ensure nonelevated inflammation after surgery.