ABSTRACT
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.
Subject(s)
Coinfection , HIV Infections , Hepatitis B, Chronic , Hepatitis B , Adult , Humans , Hepatitis B virus/genetics , Hepatitis B e Antigens , Hepatitis B, Chronic/complications , Hepatitis B, Chronic/drug therapy , Hepatitis B Surface Antigens , Coinfection/drug therapy , Cohort Studies , Viremia/drug therapy , HIV , DNA, Viral/genetics , Hepatitis B Core Antigens , Biomarkers , RNA , Antiviral Agents/therapeutic use , HIV Infections/complications , HIV Infections/drug therapyABSTRACT
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.
Subject(s)
Hepatitis B, Chronic , Hepatitis B , Adult , Humans , Hepatitis B virus/genetics , Hepatitis B Surface Antigens , Hepatitis B e Antigens , Hepatitis B, Chronic/diagnosis , Hepatitis B, Chronic/drug therapy , Cohort Studies , RNA , DNA, Viral , Hepatitis B Core Antigens , Hepatitis B/drug therapy , Antiviral Agents/therapeutic use , BiomarkersABSTRACT
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.
Subject(s)
Coinfection , HIV Infections , Hepatitis B , Humans , Adult , Male , Middle Aged , Female , Tenofovir/adverse effects , HIV Infections/complications , HIV Infections/drug therapy , Hepatitis B virus , Cohort Studies , Prospective Studies , Coinfection/drug therapy , Prevalence , Hepatitis B/epidemiology , Hepatitis B/drug therapy , Kidney/physiology , Bone RemodelingABSTRACT
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.
Subject(s)
Hepatitis B, Chronic , Adult , Male , Humans , Aged , Female , Hepatitis B virus/genetics , Hepatitis B e Antigens , Cohort Studies , Cross-Sectional Studies , Hepatitis B Surface Antigens , Alanine Transaminase , DNA, Viral , Immune ToleranceABSTRACT
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).
Subject(s)
Hepatitis B, Chronic , Hepatitis B , Adult , Humans , Hepatitis B, Chronic/drug therapy , Hepatitis B Surface Antigens/genetics , Hepatitis B e Antigens , DNA, Viral , Antigens, Surface/therapeutic use , RNA/therapeutic use , Hepatitis B/drug therapy , Hepatitis B virus/genetics , Hepatitis B Core Antigens , DNA, Circular/therapeutic use , Biomarkers , Antiviral Agents/therapeutic useABSTRACT
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.
Subject(s)
Coinfection , HIV Infections , Hepatitis B Core Antigens , Hepatitis B virus , Hepatitis B, Chronic , Virus Replication , Adult , Humans , Middle Aged , Antiviral Agents/therapeutic use , Biomarkers/blood , Coinfection/diagnosis , DNA, Viral , Hepatitis B Core Antigens/blood , Hepatitis B e Antigens/blood , Hepatitis B Surface Antigens/blood , Hepatitis B virus/isolation & purification , Hepatitis B virus/physiology , Hepatitis B, Chronic/complications , Hepatitis B, Chronic/diagnosis , HIV Infections/complications , HIV Infections/drug therapy , Prospective Studies , RNA, Viral/bloodABSTRACT
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.
Subject(s)
Gastric Bypass , Obesity, Morbid , Urinary Incontinence , Humans , Gastric Bypass/adverse effects , Gastrectomy/adverse effects , Obesity, Morbid/surgery , Urinary Incontinence/etiology , Urinary Incontinence/surgeryABSTRACT
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.
ABSTRACT
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.
Subject(s)
Gastric Bypass , Adult , Cohort Studies , Female , Gastrectomy/methods , Gastric Bypass/methods , Humans , Male , Middle Aged , Pain , Treatment OutcomeABSTRACT
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.
Subject(s)
Gastric Bypass , Obesity, Morbid , Adult , Body Mass Index , C-Reactive Protein , Female , Follow-Up Studies , Humans , Male , Middle Aged , Obesity, Morbid/complications , Obesity, Morbid/surgery , Prospective Studies , Retrospective Studies , Treatment Outcome , Weight LossABSTRACT
OBJECTIVE: To examine associations of objectively-measured physical activity (PA) with changes in weight after roux-en-Y gastric bypass (RYGB) over 7 years. BACKGROUND: The contribution of free-living PA to surgery-induced weight loss and subsequent weight regain is not well understood. METHODS: Participants of a multi-center prospective cohort study of bariatric surgery were followed annually ≥7 years. Of 807 participants who underwent RYGB and were given an activity monitor, 649 (80%) had sufficient data for this report (78% female; median age 47 years; median body mass index 46âkg/m2). Mean daily steps, hours/day in SB and minutes/week in moderate-to-vigorous physical activity (MVPA) were determined at each assessment. Mixed models tested associations between PA measures and weight outcomes, controlling for sociodemographics, health status, and eating behaviors. RESULTS: Across follow-up, mean pre to postsurgery changes in PA were small, and mean postsurgery PA level was below PA recommendations for health (eg, 101 MVPA min/week 7 years postsurgery versus the ≥150 MVPA min/week recommendation). There was a dose-response association between more steps, less SB and more MVPA with greater weight loss. Steps and SB, but not MVPA, were also associated with weight regain. For example, participants in the highest versus lowest steps quartile lost 2.9% (95% confidence interval, 1.8-4.1) more of their presurgery weight and regained 5.4% (95% confidence interval, 2.4-8.3) less of their maximum weight lost across follow-up. CONCLUSIONS: Despite only small increases in objectively-measured PA level after RYGB, PA level was independently associated with weight outcomes of bariatric surgery throughout 7 years of follow-up. REPRINTS: Reprints will not be available from the authors.
Subject(s)
Gastric Bypass , Obesity, Morbid , Body Mass Index , Exercise , Female , Humans , Male , Middle Aged , Obesity, Morbid/surgery , Prospective Studies , Weight Gain , Weight Loss/physiologyABSTRACT
OBJECTIVE: To examine associations of objectively-measured free-living physical activity (PA) with changes in depressive symptoms and mental and physical health-related quality of life (HRQoL) over 7 years after Roux-en-Y gastric bypass surgery (RYGB). BACKGROUND: The contributions of PA to improvements in mental and physical health after RYGB, independent of weight loss, are unclear. METHODS: Adults undergoing RYGB in a US multi-center cohort study wore an activity monitor and completed the Beck depression inventory (BDI) and 36-Item Short Form Health Survey (SF-36) annually ≤7 years (N = 646; 78% female, median age 47 years, median body mass index 46kg/m 2 ). Linear mixed models estimated associations of quartiles of steps, sedentary behavior (SB), and moderate-to-vigorous intensity physical activity (MVPA), respectively, with pre-to-post-surgery changes in the BDI and SF-36 mental component summary and physical component summary scores, respectively, over 1-7 years post-surgery, with adjustment for sex, age, race, pre-surgerybody mass index, the respective pre-surgery score, treatment for depression (time-varying) and pre-to-post-surgery weight change (time-varying). RESULTS: There were dose-response associations between steps, SB (inverse) and MVPA quartiles, respectively, with improvements in each score. Across follow-up, mean improvements in the BDI, Mental Component Summary and physical component summary scores, were 1.9 [95% confidence interval (CI), 1.0-2.8], 3.1 (95% CI, 1.5-4.7), and 4.0 (95% CI, 2.7-5.4) points higher, respectively, in the highest versus lowest steps quartile. CONCLUSION: Among adults who underwent RYGB, multiple objective PA measures were associated with decreases in depressive symptoms and improvements in mental and physical HRQoL throughout 7 years, independent of weight loss, indicating PA is a modifiable behavior to augment outcomes.
Subject(s)
Gastric Bypass , Obesity, Morbid , Adult , Female , Humans , Middle Aged , Male , Quality of Life , Depression/etiology , Obesity, Morbid/surgery , Cohort Studies , Prospective Studies , Exercise/physiology , Weight Loss/physiologyABSTRACT
BACKGROUND: There are limited data on noninvasive methods to identify hepatic steatosis in coexisting hepatitis B virus (HBV) infection. AIMS: To evaluate the diagnostic performance of noninvasive serum-based scores to detect steatosis using two distinct chronic HBV cohorts with liver histology evaluation. METHODS: Chronic HBV cohorts with untreated HBV mono-infection (N = 302) and with treated HBV-HIV (N = 92) were included. Liver histology was scored centrally. Four serum-based scores were calculated: hepatic steatosis index (HSI), nonalcoholic fatty liver disease Liver Fat Score (NAFLD-LFS), visceral adiposity index (VAI), and triglyceride glucose (TyG) index. Optimal cutoffs (highest sensitivity + specificity) to detect ≥ 5% HS, stratified by cohort, were evaluated. RESULTS: HBV-HIV (vs. HBV mono-infected) patients were older (median 50 vs. 43 years), and a higher proportion were male (92% vs. 60%), were black (51% vs. 8%), had the metabolic syndrome (41% vs. 25%), and suppressed HBV DNA (< 1000 IU/mL; 82% vs. 9%). Applying optimal cutoffs, the area under the receiver operator curve for detecting ≥ 5% steatosis in HBV-only and HBV-HIV, respectively, was 0.69 and 0.61 for HSI, 0.70 and 0.76 for NAFLD-LFS, 0.68 and 0.64 for TyG, and 0.68 and 0.69 for VAI. The accuracy of optimal cutoffs ranged from 61% (NAFLD-LFS) to 67% (TyG) among HBV-only and 56% (HSI) to 76% (NAFLD-LFS) among HBV-HIV. Negative predictive values were higher than positive predictive values for all scores in both groups. CONCLUSION: The relative utility of scores to identify steatosis in chronic HBV differs by co-infection/anti-HBV medication status. However, even with population-specific cutoffs, several common serum-based scores have only moderate utility. ClinicalTrials.gov NCT01924455.
Subject(s)
Anti-HIV Agents/therapeutic use , Antiviral Agents/therapeutic use , HIV Infections/blood , Hepatitis B, Chronic/blood , Non-alcoholic Fatty Liver Disease/blood , Obesity/blood , Adult , Alanine Transaminase/blood , Aspartate Aminotransferases/blood , Coinfection , DNA, Viral/blood , Diabetes Mellitus/blood , Diabetes Mellitus/epidemiology , Female , HIV Infections/drug therapy , HIV Infections/epidemiology , HIV Infections/pathology , Hepatitis B, Chronic/drug therapy , Hepatitis B, Chronic/epidemiology , Hepatitis B, Chronic/pathology , Humans , Intra-Abdominal Fat , Male , Metabolic Syndrome/blood , Metabolic Syndrome/epidemiology , Metabolic Syndrome/pathology , Middle Aged , Non-alcoholic Fatty Liver Disease/epidemiology , Non-alcoholic Fatty Liver Disease/pathology , Obesity/epidemiology , Obesity/pathology , Severity of Illness Index , Triglycerides/blood , Viral Load , Waist CircumferenceABSTRACT
BACKGROUND: Fatty liver disease (FLD) and hepatitis B virus (HBV) infection occur commonly in human immunodeficiency virus (HIV). FLD resolution is associated with improvement in lipoproteins in HIV-uninfected patients. We evaluated changes in FLD in an HBV/HIV-coinfected cohort. METHODS: One hundred eight HBV/HIV-coinfected adults with baseline liver biopsies were followed every 24 weeks (median, 166 weeks) and 60 had follow-up biopsies. Baseline FLD categories (none, ≥5% steatosis, steatohepatitis), their change, and relationships with clinical and lipid/lipoprotein parameters were explored using multivariable modeling. RESULTS: Median age was 50 years, and 93% were male. At baseline 30% had FLD. With control for lipid-lowering medications and body mass index, low-density lipoprotein (LDL) cholesterol (LDL-C), LDL particle concentration (LDL-P), and apolipoprotein B (apoB) decreased and adiponectin increased over time (all P < .05); On follow-up (vs baseline), there was no significant difference in FLD category (P = .85); 60% remained without FLD, 17% had unchanged, 12% worsening, and 12% improved FLD. Baseline low-density lipoproteins (LDL-C, LDL-P, small LDL-P) and apoB appeared highest in those with unchanged FLD status (all P < .05). No associations between changes in FLD across follow-up (worsening/improvement vs unchanged) and lipid/lipoproteins changes were identified. CONCLUSIONS: In this cohort, there was no significant change in FLD prevalence over a relatively short timeframe. Baseline atherogenic lipids appeared highest in those with persistent steatosis or steatohepatitis, suggesting potentially increased cardiovascular risk in this group, but an independent relationship between individual-level change in FLD status and lipid/lipoprotein levels across follow-up was not observed.
Subject(s)
Coinfection , Fatty Liver , HIV Infections , Hepatitis B , Adult , Apolipoproteins B , Cholesterol, LDL , Fatty Liver/complications , Female , HIV , HIV Infections/complications , HIV Infections/drug therapy , Hepatitis B/complications , Hepatitis B virus , Humans , Lipoproteins , Male , Middle AgedABSTRACT
BACKGROUND AND AIMS: Histological and clinical outcomes in HBV-HIV coinfection in the era of combination antiretroviral therapy (cART) are poorly defined. APPROACH AND RESULTS: Adult patients co-infected with HBV-HIV from eight North American sites were enrolled in this National Institutes of Health (NIH)-funded prospective observational study (n = 139). Demographic, clinical, serological, and virological data were collected at entry and every 24 weeks for ≤ 192 weeks. Paired liver biopsies were obtained at study entry and at ≥ 3 years of follow-up. Biopsies were assessed by a central pathology committee using the modified Ishak scoring system. Clinical outcome rate and changes in histology are reported. Among participants with follow-up data (n = 114), median age was 49 years, 91% were male, 51% were non-Hispanic Black, and 13% had at-risk alcohol use, with a median infection of 20 years. At entry, 95% were on anti-HBV cART. Median CD4 count was 562 cells/mm3 and 93% had HIV < 400 copies/mL. HBeAg was positive in 61%, and HBV DNA was below the limit of quantification (< 20 IU/mL) in 61% and < 1,000 IU/mL in 80%. Clinical events were uncommon across follow-up: one hepatic decompensation, two HCC, no liver transplants, and one HBV-related deaths, with a composite endpoint rate of 0.61/100 person-years. Incident cirrhosis (n = 1), alanine aminotransferase flare (n = 2), and HBeAg loss (n = 13) rates were 0.40, 0.65, and 6.86 per 100 person-years, respectively. No participants had HBsAg loss. Paired biopsy (n = 62; median 3.6 years apart) revealed minimal improvement in Histologic Activity Index (median [interquartile range]: 3 [2-4] to 3 [1-3]; P = 0.02) and no significant change in fibrosis score (1 [1-2] to 1 [0-3]; P = 0.58). CONCLUSIONS: In a North American cohort of adults with HBV-HIV on cART with virological suppression, clinical outcomes and worsening histological disease were uncommon.
Subject(s)
Antiviral Agents/therapeutic use , HIV Infections/drug therapy , Hepatitis B, Chronic/drug therapy , Adolescent , Adult , Aged , Alanine Transaminase/blood , Coinfection , Drug Therapy, Combination , Female , Guanine/analogs & derivatives , Guanine/therapeutic use , HIV Infections/complications , Hepatitis B Surface Antigens/blood , Hepatitis B e Antigens/blood , Hepatitis B, Chronic/blood , Hepatitis B, Chronic/complications , Hepatitis B, Chronic/pathology , Humans , Lamivudine/therapeutic use , Liver/pathology , Male , Middle Aged , North America , Prospective Studies , Reverse Transcriptase Inhibitors/therapeutic use , Tenofovir/therapeutic use , Treatment Outcome , Young AdultABSTRACT
BACKGROUND: Change in short-term (i.e., 10-year) and lifetime risk of cardiovascular disease (CVD) following Roux-en-Y gastric bypass (RYGB) has significant heterogeneity. OBJECTIVE: To identify predictors of change in CVD risk and cardiovascular events following RYGB. METHODS: Between 2006-2009, 1625 adults without a history of CVD enrolled in a prospective cohort study and underwent RYGB at 1 of 10 U.S. hospitals. Participants were followed annually for a maximum of 7 years. Associations between presurgery characteristics (anthropometric, sociodemographic, physical and mental health, alcohol/drug use, eating behaviors) and 1) pre to postsurgery change in 10 year and lifetime atherosclerotic CVD (ASCVD) risk scores, respectively, and 2) having a CVD event (nonfatal myocardial infarction, stroke, ischemic heart disease, congestive heart failure, angina, percutaneous coronary intervention, coronary artery bypass grafting, or CVD-attributed death) as repeated measures (yr 1-7) were evaluated. SETTING: Observational cohort study at ten hospitals throughout the United States. RESULTS: Presurgery factors independently associated with decreases in both 10-year and lifetime risk scores 1-7 years post-RYGB were higher CVD risk score, female sex, higher household income, and normal kidney function. Additionally, Black race and having diabetes were independently associated with decreases in 10-year risk, while not having diabetes and a higher (better) composite mental health score were independently related to decreases in lifetime risk. A lower (worse) presurgery composite physical health score was associated with a higher CVD event risk (RR = 1.68, per 10 points). CONCLUSION: This study identified multiple presurgery factors that characterize patients who may have more cardiovascular benefit from RYGB, and patients who might require additional support to improve their cardiovascular health.
Subject(s)
Cardiovascular Diseases , Gastric Bypass , Obesity, Morbid , Adult , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/etiology , Cohort Studies , Female , Gastric Bypass/adverse effects , Humans , Obesity, Morbid/complications , Obesity, Morbid/surgery , Prospective Studies , United States/epidemiologyABSTRACT
BACKGROUND: Long-term changes in cardiovascular disease (CVD) risk after bariatric surgery are not well characterized. OBJECTIVE: To report sex-specific changes in CVD risk after Roux-en-Y gastric bypass surgery (RYGB). SETTING: Observational cohort study at ten hospitals throughout the United States. METHODS: Between 2006 and 2009, 1770 adults enrolled in a prospective cohort study underwent RYGB at 1 of 10 U.S. hospitals. Research assessments were conducted presurgery and annually postsurgery over 7 years. Sex specific-predicted 10-year and lifetime CVD risk were calculated using the Framingham10-year and lifetime risk scores, Framingham-body mass index, and atherosclerotic CVD scoring algorithms among participants with no history of CVD. Of 1566 eligible participants, 1234 (75.9%) with CVD risk determination pre- and postsurgery were included (1013 females, 221 males). RESULTS: Based on the Framingham10-year and lifetime risk scores, the percentage of females with predicted high (>20%) 10-year CVD risk declined from presurgery (6.5% [95% confidence interval: 6.7-7.5]) to 1 year postsurgery (1.0% [95% confidence interval: .8-1.2]; P < .001), then increased 1 to 7 years postsurgery (to 2.8% [95% confidence interval: 1.6-3.3]; P = .003), but was lower 7 years postsurgery versus presurgery (P < .001). Time trends for percentage of high-risk participants and mean CVD risk scores were similar for both sexes and other evaluated CVD risk scores. For example, among males mean lifetime atherosclerotic CVD score declined from presurgery to 1 year postsurgery, then increased 1 to 7 years postsurgery. However, there was a net decline from presurgery (P < .001). CONCLUSION: Among both females and males, predicted 10-year and lifetime CVD risk was substantially lower 7 years post RYGB than presurgery, suggesting RYGB surgery can lead to sustained improvements in short- and long-term CVD risk.
Subject(s)
Bariatric Surgery , Cardiovascular Diseases , Gastric Bypass , Obesity, Morbid , Adult , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/etiology , Cohort Studies , Female , Gastric Bypass/adverse effects , Humans , Male , Obesity, Morbid/surgery , Prospective Studies , United States/epidemiologyABSTRACT
Published estimates of weight regain (WR) after bariatric surgery vary greatly. Understanding the sources of variability in the literature and clarifying the magnitude of WR after Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) are critical for informing expectations and planning interventions. A literature search through January 2019 yielded 15 English-language studies that reported WR in at least 30 participants, not selected based on weight loss or WR, at least 3 years after primary RYGB (n = 11) or SG (n = 5). Median follow-up was 5.0 (range, 3.2-10.0) years. Median sample size was 62 (range, 33-464). Samples represented a median of 54.3% (range, 10.7%-100%) of eligible participants. Nadir weight was determined by serial research assessments (n = 1), medical records (n = 7), participant recall (n = 4), or an undisclosed method (n = 4). Three continuous and 8 binary WR measures (the latter, based on various thresholds for clinically meaningful WR) were reported. To enable comparison across studies, the percentage difference in WR in each study versus a reference sample (n = 1433 RYGB), matched on time since surgery and WR measure, was calculated. Median WR in the reference sample increased from 8.2 (25th-75th percentile: 0-19.5) to 23.8 (25th-75th percentile: 9.0-33.9) percent of maximum weight lost, 3 to 6 years post RYGB surgery. Studies of RYGB versus SG, with larger versus smaller samples, with higher versus lower participation rates, that determined nadir weight via participant recall versus medical records, and reported continuous versus binary WR measures tended to have WR values closer to the reference sample and each other. Variation in WR estimates was explained by heterogeneity in WR measures, timing of assessment, surgical procedure, and study design characteristics. The best estimate of WR after RYGB likely comes from the large reference sample. WR after SG versus RYGB appears higher. However, additional high-quality studies with uniform reporting of WR by surgical procedure are needed.
Subject(s)
Bariatric Surgery , Gastric Bypass , Obesity, Morbid , Gastrectomy , Humans , Obesity, Morbid/surgery , Retrospective Studies , Weight Gain , Weight LossABSTRACT
OBJECTIVE: To identify patient behaviors and characteristics related to weight regain after Roux-en-Y gastric bypass surgery (RYGB). BACKGROUND: There is considerable variation in the magnitude of weight regain after RYGB, highlighting the importance of patient-level factors. METHODS: A prospective cohort study of adults who underwent bariatric surgery in 6 US cities between 2006 and 2009 included presurgery, and 6-month and annual assessments for up to 7 years. Of 1573 eligible participants, 1278 (81%) with adequate follow-up were included (80% female, median age 46 years, median body mass index 46âkg/m). Percentage of maximum weight lost was calculated each year after weight nadir. RESULTS: Weight was measured a median of 8 (25th-75th percentile, 7-8) times over a median of 6.6 (25th-75th percentile, 5.9-7.0) years. ß coefficients, that is, the mean weight regain, compared with the reference, and 95% confidence interval, are reported. Postsurgery behaviors independently associated with weight regain were: sedentary time [2.9% (1.2-4.7), for highest vs lowest quartile], eating fast food [0.5% (0.2-0.7) per meal/wk], eating when feeling full [2.9% (1.2-4.5)], eating continuously [1.6% (0.1-3.1)], binge eating and loss-of-control eating [8.0% (5.1-11.0) for binge eating; 1.6 (-0.1 to 3.3) for loss of control, vs neither], and weighing oneself Subject(s)
Gastric Bypass
, Health Behavior
, Weight Gain
, Adult
, Aged
, Cohort Studies
, Female
, Humans
, Male
, Middle Aged
, Prospective Studies
, Time Factors
, Young Adult