Safety and yield of percutaneous liver biopsy in adults and children with chronic hepatitis B: Results from a prospective, multicenter study.

BACKGROUND: Prospective data regarding the safety and yield of liver biopsy in both adults and children with chronic hepatitis B are limited. The aim of this study is to report safety, yield, and complication rates among adults and children with chronic hepatitis B undergoing percutaneous liver biopsy. METHODS: Data on the indication for procedural characteristics and complication rate for liver biopsies performed as part of the Hepatitis B Research Network were prospectively recorded on a study case report form and analyzed in aggregate. RESULTS: Among 2506 adult and pediatric subjects enrolled in the Hepatitis B Research Network between 2011 and 2018, 465 (19%) underwent 491 liver biopsies for clinical or research reasons. Adequate liver tissue was obtained in 98% of the procedures. In total, there were 32 complications reported for 24 biopsies: 23 biopsies with 30 complications in adults and 1 biopsy with 2 complications in children. Pain (n=19) and vasovagal reaction (n=6) were the most common complications. There were 7 serious adverse events, including an arterioportal venous fistula, a pneumothorax, 4 cases of bleeding, and severe pain with no associated condition. There were no deaths. CONCLUSIONS: These data demonstrate that percutaneous liver biopsy is associated with a high yield of tissue (98%) and a rate of serious complications of 1.4% in both children and adults with chronic HBV. These results support the focused use of liver biopsy in the evaluation of novel treatments in development for chronic hepatitis B.

Racial Disparities in Treatment Initiation and Outcomes of Chronic Hepatitis B Virus Infection in North America.

Importance: Disparities in treatment initiation may affect outcomes, but data on racially diverse populations with chronic hepatitis B virus (HBV) infection are limited. Objective: To examine whether HBV treatment initiation and outcomes differ among racial groups. Design, Setting, and Participants: From January 14, 2011, to January 28, 2018, hepatitis B surface antigen-positive adults (age ≥18 years) not receiving anti-HBV therapy were enrolled and followed up at weeks 12, 24, and every 24 weeks thereafter in a multicenter longitudinal cohort study (Hepatitis B Research Network [HBRN] adult cohort study) conducted in North America. The last study visit and data collection were completed January 28, 2019. Data were analyzed from August 27, 2021, to August 25, 2022. All HBRN participants were included unless they had acute HBV, HIV, hepatitis C or D, less than 24-weeks of follow-up after enrollment, initiated treatment at or immediately after enrollment, or had unknown race. Exposures: Participants had clinical and laboratory assessments and could receive anti-HBV treatment after enrollment. Main Outcomes and Measures: Hepatitis B virus treatment initiation and major adverse liver outcomes (hepatic decompensation, hepatocellular carcinoma, liver transplant, and death). Results: Of 1550 participants, 193 (12%) were African American or Black, 1157 (75%) were Asian, 157 (10%) were White, and 43 (3%) were other races; 789 (51%) were women, and the median age was 41.2 (IQR, 32.9-51.6) years. Sociodemographic and virologic parameters differed between groups. During 5727 person-years of follow-up, 504 participants initiated treatment, with incidences of 4.8 per 100 person-years in African American or Black individuals, 9.9 per 100 person-years in Asian individuals, 6.6 per 100 person-years in White individuals, and 7.9 per 100 person-years in those of other races (P < .001). A lower proportion (14%) of African American or Black participants met treatment criteria compared with Asian (22%) and White (27%) individuals (P = .01). The cumulative probabilities of treatment initiation after meeting the criteria were not significantly different among racial groups (African American or Black, 0.45; Asian, 0.38; White, 0.40 at 48 weeks and African American or Black, 0.45; Asian, 0.51; White, 0.51 at 72 weeks; P = .68). The incidence of major adverse liver outcomes was 0.1 per 100 person-years and did not differ by race. Conclusions and Relevance: In this observational study of chronic HBV, African American or Black participants were less likely than individuals of other races to meet treatment criteria, but among those who did, HBV treatment receipt did not differ significantly by race or socioeconomic factors. Not all eligible participants initiated treatment, but adverse liver outcomes were rare. These findings may not be generalizable to patients with chronic HBV receiving care in other settings.

Associations Between Physical Activity and Changes in Weight Across 7 Years After Roux-en-Y Gastric Bypass Surgery: A Multicenter Prospective Cohort Study.

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 46 kg/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.

Changes in Smoking Behavior Before and After Gastric Bypass: A 7-year Study.

OBJECTIVE: To evaluate smoking history and change in smoking behavior, from 1 year before through 7 years after Roux-en-Y gastric bypass (RYGB) surgery, and to identify risk factors for post-surgery smoking. BACKGROUND: Smoking behavior in the context of bariatric surgery is poorly described. METHODS: Adults undergoing RYGB surgery entered a prospective cohort study between 2006 and 2009 and were followed up to 7 years until ≤2015. Participants (N = 1770; 80% female, median age 45 years, median body mass index 47 kg/m2) self-reported smoking history pre-surgery, and current smoking behavior annually. RESULTS: Almost half of participants (45.2%) reported a pre-surgery history of smoking. Modeled prevalence of current smoking decreased in the year before surgery from 13.7% [95% confidence interval (CI) = 12.1-15.4] to 2.2% (95% CI = 1.5-2.9) at surgery, then increased to 9.6% (95% CI = 8.1-11.2) 1-year post-surgery and continued to increase to 14.0% (95% CI = 11.8-16.0) 7-years post-surgery. Among smokers, mean packs/day was 0.60 (95% CI = 0.44-0.77) at surgery, 0.70 (95% CI = 0.62-0.78) 1-year post-surgery and 0.77 (95% CI = 0.68-0.88) 7-years post-surgery. At 7-years, smoking was reported by 61.7% (95% CI = 51.9-70.8) of participants who smoked 1-year pre-surgery (n = 221), 12.3% (95% CI = 8.5-15.7) of participants who formerly smoked but quit >1 year pre-surgery (n = 507), and 3.8% (95% CI = 2.1-4.9) of participants who reported no smoking history (n = 887). Along with smoking history (ie, less time since smoked), younger age, household income <$25,000, being married or living as married, and illicit drug use were independently associated with increased risk of post-surgery smoking. CONCLUSION: Although most adults who smoked 1-year before RYGB quit pre-surgery, smoking prevalence rebounded across 7-years, primarily due to relapse.

Associations Between Physical Activity and Changes in Depressive Symptoms and Health-related Quality of Life Across 7 Years After Roux-en-Y Gastric Bypass Surgery: A Multicenter Prospective Cohort Study.

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.

Low Incidence of Adverse Outcomes in Adults With Chronic Hepatitis B Virus Infection in the Era of Antiviral Therapy.

BACKGROUND AND AIMS: Outcomes of persons with chronic hepatitis B virus (HBV) infection in the era of antiviral therapy (AVT) are not well characterized. We determined the incidence and factors associated with clinical outcomes in a multiethnic, North American cohort of adults with chronic HBV infection, who were not on AVT at enrollment. APPROACH AND RESULTS: Adults with chronic HBV infection, not receiving AVT, and without a history of decompensation, HCC, or liver transplantation (LT), were prospectively followed. Participants with known human immunodeficiency virus (HIV), hepatitis C virus, or hepatitis D virus (HDV) coinfection were excluded. During follow-up, treatment could be initiated per standard of care. Clinical outcomes included: incident cirrhosis, decompensation, HCC, OLT, and HBV-related death. Among 1,418 participants analyzed, 51.5% were women, median age was 41.1 years, 75% were Asian, 10% White, 13% Black, 24% HBeAg(+), and 1.5% cirrhosis at baseline. During the study, 274 started treatment, 83 had an alanine aminotransferase flare, 118 of 330 initially HBeAg(+) became HBeAg(-), and 90 of 1,329 became HBsAg(-). After 6,641 person-years follow-up, 8 participants (4 of 21 with baseline cirrhosis) had 12 clinical outcomes (2 decompensation, 5 HCC, 2 OLT, and 3 HBV-related deaths) and 19 of 1,397 had incident cirrhosis. Twenty-one of 26 participants had first outcome before treatment, none had become HBsAg(-), whereas 5/9 HBeAg(+) had become HBeAg(-) at time of first outcome. Cumulative percentage of clinical outcomes was 16% at year 4 in participants with baseline cirrhosis and 2% (including incident cirrhosis) at year 7 in those without. CONCLUSIONS: Incidence of adverse outcomes was low in this closely monitored, large cohort of North American adults with predominantly inactive, chronic HBV without cirrhosis. Our data highlight the benefits of HBsAg loss and the importance of early diagnosis and treatment to prevent cirrhosis and other complications of chronic HBV infection.

Patient Behaviors and Characteristics Related to Weight Regain After Roux-en-Y Gastric Bypass: A Multicenter Prospective Cohort Study.

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 46 kg/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

Mortality after bariatric surgery: findings from a 7-year multicenter cohort study.

BACKGROUND: Patients having bariatric surgery have lower mortality compared with those with similar body mass index who do not undergo surgery. It is unclear whether mortality post-bariatric surgery is similar to the general population. The benefit of bariatric surgery would be highlighted should people previously at high risk for premature death have comparable, or better, mortality as the general population. OBJECTIVE: To compare mortality after bariatric surgery to the general U.S. population of the same age, sex, and race. SETTING: The Longitudinal Assessment of Bariatric Surgery-2 (LABS-2) prospective cohort of 2458 adults who underwent bariatric surgery at 10 U.S. hospitals between 2006 and 2009. METHODS: Deaths were identified via LABS-2 follow-up and the National Death Index. Standardized mortality ratios (SMR) of post-bariatric surgery mortality observed in LABS-2 versus age-, sex-, race-, and year-adjusted expected mortality in the general U.S. population were calculated and compared with 1, which results when the number of observed and expected deaths are equal. RESULTS: LABS-2 median follow-up was 6.6 (interquartile range: 5.9-7.0) years postsurgery. Seventy-six deaths were observed over 15,616 person-years (PY) of observation (4.9 deaths/1000 PY). The rate expected in the general U.S. population with the same age, sex, race, and year distribution was 4.8 deaths per 1000 PY (SMR = 1.02, 95% confidence interval [CI]: .80-1.27). There were no significant differences between observed and expected mortality by surgical procedure. Compared with expected mortality in the general U.S. population, people 35-44 years old at time of surgery had significantly more deaths (SMR = 2.06, 95% CI: 1.22-3.25), while people at least 55 years of age had significantly fewer (SMR = .63, 95% CI: .42-.92). Significantly more deaths than expected occurred in the perioperative period and 5-7 years after surgery. CONCLUSIONS: Mortality within 7 years of bariatric surgery is comparable to the general U.S. population, which is likely to have better survival than people with severe obesity. However, more deaths than expected were identified 5-7 years after surgery.

Silymarin in non-cirrhotics with non-alcoholic steatohepatitis: A randomized, double-blind, placebo controlled trial.

The botanical product silymarin, an extract of milk thistle, is commonly used by patients to treat chronic liver disease and may be a treatment for NASH due to its antioxidant properties. We aimed to assess the safety and efficacy of higher than customary doses of silymarin in non-cirrhotic patients with NASH. This exploratory randomized double-blind placebo controlled multicenter Phase II trial tested a proprietary standardized silymarin preparation (Legalon®, Rottapharm|Madaus, Mylan) and was conducted at 5 medical centers in the United States. Eligible adult patients had liver biopsy within 12 months showing NASH without cirrhosis with NAFLD Activity Score (NAS) ≥4 per site pathologist's assessment. Participants were randomized to Legalon® 420 mg, 700 mg, or placebo t.i.d. for 48 weeks. The primary endpoint was histological improvement ≥2 points in NAS. Of 116 patients screened, 78 were randomized. There were no significant differences in adverse events among the treatment groups. After 48-50 weeks, 4/27 (15%) in the 700 mg dose, 5/26 (19%) participants randomized to 420 mg, and 3/25 (12%) of placebo recipients reached the primary endpoint (p = 0.79) among all randomized participants, indicating no benefit from silymarin in the intention to treat analysis Review by a central pathologist demonstrated that a substantial number of participants (49, 63%) did not meet histological entry criteria and that fibrosis stage improved most in the placebo treated group, although not significantly different from other groups. Silymarin (Legalon®) at the higher than customary doses tested in this study is safe and well tolerated. The effect of silymarin in patients with NASH remains inconclusive due to the substantial number of patients who entered the study but did not meet entry histological criteria, the lack of a statistically significant improvement in NAS of silymarin treated patients, and the unanticipated effect of placebo on fibrosis indicate the need for additional clinical trials. Trial Registration: clinicaltrials.gov, Identifier: NCT00680407.

Proximal Roux-en-Y gastric bypass: Addressing the myth of limb length.

BACKGROUND: Some studies suggest that changes in weight or metabolic outcomes are affected by the lengths of the gastrointestinal limbs in the Roux-en-Y gastric bypass. METHODS: Participants (N = 1,770) underwent primary Roux-en-Y gastric bypass and were followed ≤7 years in the Longitudinal Assessment of Bariatric Surgery-2, a multicenter US cohort study. Alimentary limb and biliopancreatic limb lengths were measured according to research protocol; common channel was measured in a subsample (N = 547). Aimentary limb, biliopancreatic limb, and common channel ratio to total small bowel length were calculated. RESULTS: Median presurgery body mass index was 46 (25th-75th percentile: 43-51) kg/m2. Medians (25th-75th percentiles) for alimentary limb length were 125 cm (100-150), for biliopancreatic limb length were 50 cm (50-60), and common channel length were 410 cm (322-520). Statistics for ratios to the small bowel length were 0.23 (0.18-0.27) for alimentary limb, 0.09 (0.07-0.10) for biliopancreatic limb, and 0.69 (0.63-0.73) for common length. There were no significant associations between alimentary limb, biliopancreatic limb, common channel, alimentary limb ratio, biliopancreatic limb ratio or common channel ratio, and either weight loss or improvement in cardiometabolic outcomes. CONCLUSION: The common channel length in Roux-en-Y gastric bypass is highly variable between individuals. None of the limb lengths in this study, nor alimentary limb, biliopancreatic limb, or common channel ratios, seem to be related to weight loss or metabolic improvements >7 years.

Hepatic Encephalopathy in Children With Acute Liver Failure: Utility of Serum Neuromarkers.

BACKGROUND: Pediatric acute liver failure (PALF) is a public heath burden, often requiring prolonged hospitalization and liver transplantation. Hepatic encephalopathy (HE) is a complication of PALF with limited diagnostic tools to predict outcomes. Serum neurological markers (neuron-specific enolase, S100ß, and myelin basic protein) can be elevated in traumatic or ischemic brain injury. We hypothesized that these neuromarkers would be associated with the development of HE in PALF. METHODS: PALF study participants enrolled between May 2012 and December 2014 by 12 participating centers were the subjects of this analysis. Daily HE assessments were determined by study investigators. Neurological and inflammatory markers were measured using enzyme-linked immunosorbent assay and MILLIPLEX techniques, respectively. To model encephalopathy, these markers were log2 transformed and individually examined for association with HE using a generalized linear mixed model with a logit link and random intercept. RESULTS: Eighty-two children had neurological and inflammatory marker levels and HE assessments recorded, with the majority having assessments for 3 days during their illness. An indeterminate diagnosis (29%) was most common and the median age was 2.9 years. Significant associations were observed for HE with S100ß (odds ratio 1.16, 95% confidence interval [1.03-1.29], P = 0.04) and IL-6 (odds ratio 1.24 [1.11-1.38], P = 0.006). CONCLUSIONS: Serum S100ß and IL-6 are associated with HE in children with PALF. Measuring these markers may assist in assessing neurological injury in PALF, impacting clinical decisions.

Age, race and viral genotype are associated with the prevalence of hepatitis B e antigen in children and adults with chronic hepatitis B.

Hepatitis B e antigen (HBeAg) is an important serological marker of hepatitis B virus (HBV) infection and is associated with higher levels of viraemia, increased risk of infectivity to others and increased risk of hepatocellular carcinoma. We analysed HBeAg status in a large cohort of adults and children enrolled in Cohort Studies of the Hepatitis B Research Network, long-term natural history studies of chronic HBV infection. A cross-sectional analysis examined factors associated with HBeAg positivity, including demographic and virologic data, across the age spectrum. Among 2241 enrolled participants who met criteria for this analysis, 825 (37%) were seropositive for HBeAg. The prevalence of HBeAg was lower in those with older age, ranging from 85% among those up to 10 years of age to only 12% among those older than 50 years. In addition to age, both race and HBV genotype were independently associated with HBeAg positivity. There was a significant interaction between age and race; the prevalence of HBeAg was significantly higher among Asians > 10-30 years old vs Whites or Blacks who were >10 to 30 years old and those infected with HBV genotype C. Conversely, the presence of the basal core promoter and precore variants was associated with significantly lower prevalence of HBeAg, even when adjusted for age, race and genotype. These data will provide a better understanding of factors associated with seropositivity for HBeAg and may lead to better strategies for preventing HBV infection and broader indications for antiviral therapy.

A longitudinal examination of suicide-related thoughts and behaviors among bariatric surgery patients.

BACKGROUND: Past research suggests self-harm/suicidality are more common among adults who have undergone bariatric surgery than the general population. OBJECTIVES: To compare prevalence of self-harm/suicidal ideation over time and identify presurgery risk factors for postsurgery self-harm/suicidal ideation. SETTING: The Longitudinal Assessment of Bariatric Surgery-2 is a cohort study with presurgery and annual postsurgery assessments conducted at 10 U.S. hospitals. METHODS: Adults with severe obesity undergoing bariatric surgery between March 2006 and April 2009 (n = 2458). Five-year follow-up is reported. Self-reported history of suicidality assessed retrospectively via the Suicide Behavior Questionnaire-Revised (SBQ-R) and self-reported self-harm/suicidal ideation assessed prospectively via the Beck Depression Inventory-Version 1 (BDI-1). RESULTS: The SBQ-R was completed by 1540 participants; 2217 completed the BDI-1 pre- and postsurgery. Over 75% of participants were female, with a median age of 46 years and body mass index of 45.9 kg/m2. Approximately one fourth of participants (395/1534) reported a presurgery history of suicidal thoughts or behavior (SBQ-R). The prevalence of self-harm/suicidal ideation (BDI-1) was 5.3% (95% confidence interval [CI], 3.7-6.8) presurgery and 3.8% (95% CI, 2.5-5.1) at year 1 postsurgery (P = .06). Prevalence increased over time postsurgery to 6.6% (95% CI, 4.6-8.6) at year 5 (P = .001) but was not significantly different than presurgery (P = .12). CONCLUSIONS: A large cohort of adults with severe obesity who underwent bariatric surgery had a prevalence of self-harm/suicidal ideation that may have decreased in the first postoperative year but increased over time to presurgery levels, suggesting screening for self-harm/suicidality is warranted throughout long-term postoperative care. Several risk factors were identified that may help with enhanced monitoring.

Association Between Severe Serum Alanine Aminotransferase Flares and Hepatitis B e Antigen Seroconversion and HBV DNA Decrease in Untreated Patients With Chronic HBV Infection.

BACKGROUND & AIMS: The incidence and outcomes of alanine aminotransferase (ALT) flares during the natural history of chronic HBV infection has not been determined in a large, racially heterogeneous group of patients in North America. METHODS: We collected data from the Hepatitis B Research Network-an observational cohort study of untreated adults with chronic HBV infection enrolled at 21 sites in the United States and Canada. Clinical and laboratory data were collected from 1587 participants (49.9% male, 73.7% Asian, 35.2% genotype B infection, mean age of 42.6 years) at enrollment, at weeks 12 and 24, and every 24 weeks thereafter for a planned 5 years of follow up (from January 2011 through May 2016). Participants were excluded if they had a history of hepatic decompensation, hepatocellular carcinoma, solid organ or bone marrow transplantation, chronic immune suppression, or antiviral therapy within 6 months before enrollment. Levels of ALT were measured in serum samples and flares were defined as at least 10 times the upper limit of normal (300 U/L in males and 200 U/L in females). RESULTS: ALT flares occurred in 102 participants (6%), with 31 flares (30%) occurring at baseline. The 4-year cumulative incidence of ALT flares was 5.7%. The median peak level of ALT was 450 U/L (25th-75th percentile, 330 U/L to 747 U/L) with a maximum of 2578 U/L. In multivariable analysis, factors associated with the occurrence of an ALT flares were: male sex (odds ratio [OR], 3.02; P=.0007), higher baseline HBV DNA values (OR per log10, 1.41; P<.0001), at risk alcohol use (OR, 2.27 vs none or moderate; P=.02), and higher FIB-4 values (OR, 1.85 per log2; P<.0001). Older age was associated with lower odds of an ALT flare (OR, 0.63 per 10 years; P=.004). Rate of decrease in level of HBV DNA by 1 log10 or more (59 vs 23 per 100 person-years for HB e antigen (HBeAg)-positive vs HBeAg-negative patients; P=.003) and HBeAg loss (47 vs 15 per 100 person-years; P=.002) were higher in patients with an ALT flare than in patients without, but the rate of HBsAg loss was similar (4 vs 2 per 100 person-years; P=.26). No hepatic decompensation, liver transplants, or deaths were observed in participants with ALT flares. CONCLUSION: In a large racially heterogeneous cohort of adults with chronic HBV infection, the cumulative incidence of severe ALT flares was low and associated with greater decreases in HBV DNA and loss of HBeAg, but not with loss of HBsAg.

Entecavir and Peginterferon Alfa-2a in Adults With Hepatitis B e Antigen-Positive Immune-Tolerant Chronic Hepatitis B Virus Infection.

Monotherapy with interferon or nucleoside analog is generally not recommended during the immune-tolerant (IT) phase of chronic hepatitis B virus (HBV) infection. Recognition that high HBV DNA levels are associated with hepatocellular carcinoma has increased interest in treating HBV in the IT phase. Small pediatric studies reported efficacy with combination nucleoside analog and interferon therapy. The aim of this study was to evaluate the safety and efficacy of the combination of entecavir and peginterferon in adults in the IT phase of chronic HBV infection. Hepatitis B e antigen (HBeAg)-positive adults with HBV DNA > 107 IU/mL and alanine aminotransferase (ALT) ≤ 1.5 times the upper limit of normal (ULN) (male: ≤ 45, female: ≤ 30 U/L) received entecavir 0.5 mg daily for 8 weeks followed by the addition of peginterferon alfa-2a 180 µg/week to entecavir for an additional 40 weeks. The primary endpoint was HBeAg loss and HBV DNA ≤ 1,000 IU/mL 48 weeks after end of treatment (EOT). Among 28 participants from 11 sites, the median age was 37.2 (range: 22-61) years, 54% were male, and 96% were Asian. Nearly all were infected with genotype C (64%) or B (32%). Median baseline HBV DNA was 8.2 log10 IU/mL, and ALT was 0.9 times the ULN. Although one (4%) participant cleared HBeAg, none met the primary endpoint of both HBeAg loss AND HBV DNA ≤ 1,000 IU/mL 48 weeks post-EOT. ALT elevations > 5 times the ULN occurred in eight (29%) participants, and none were associated with icterus. Forty-eight weeks posttreatment, HBV DNA rebounded to baseline levels in all participants, including the participant who lost HBeAg, and ALT values returned to near baseline levels in all but four participants. Conclusion: A lead-in strategy of 8 weeks of entecavir followed by combination peginterferon and entecavir therapy for 40 weeks had limited efficacy in adults in the IT phase of chronic HBV infection and cannot be recommended.

Association of Obesity Subtypes in the Longitudinal Assessment of Bariatric Surgery Study and 3-Year Postoperative Weight Change.

OBJECTIVE: The study objective was to empirically identify subgroups of patients with obesity and investigate their association with postoperative weight change. METHODS: A longitudinal analysis of 2,458 adults in the Longitudinal Assessment of Bariatric Surgery (LABS) study was used. Baseline data were used to identify subgroups. The outcome was 3-year weight change after bariatric surgery. RESULTS: We identified four classes (subtypes) of obesity, which could be characterized as diabetes with low rates of high-density lipoprotein (Class 1), disordered eating (Class 2), mixed (Class 3), and extreme obesity with early onset (Class 4). Approximately 98% of participants in Class 1 had diabetes compared with < 40% in the other classes. There were high rates of binge eating in Class 2, and more than 92% of those in this class reported eating when not hungry. Class 4 was characterized by a higher BMI at baseline. Adults in Class 4 lost an average of 25.0% (males) and 30.3% (females) of their baseline weight over 3 years. In contrast with participants in Class 1, those in Classes 2 and 3 had significantly larger 3-year weight losses than their peers in Class 4. CONCLUSIONS: Obesity is a heterogeneous disease. Bariatric surgery may be most beneficial for adults with disordered eating.

Comparison of the Performance of Common Measures of Weight Regain After Bariatric Surgery for Association With Clinical Outcomes.

Importance: Estimates of weight regain following bariatric surgery vary widely. Objective: To describe weight regain after reaching nadir weight following Roux-en-Y gastric bypass (RYGB) surgery and compare weight regain measures for association with outcomes. Design, Setting, and Participants: Prospective cohort study of 2458 adults who underwent bariatric surgery at 10 hospitals in 6 US cities between March 2006 and April 2009. Assessments were conducted within 30 days' presurgery, at 6 months' postsurgery, and then annually until January 2015. Of the 1703 participants who underwent RYGB surgery, 1406 (83%) were followed up for 5 years or longer and had 5 or more weight measurements (excluding those who died or underwent surgical reversal). Exposures: Weight regain assessed by 5 continuous measures (weight in kilograms, body mass index [BMI], percentage of presurgery weight, percentage of nadir weight, and percentage of maximum weight lost) and 8 dichotomous measures (per established thresholds) were compared in relation to clinical outcomes based on statistical significance, magnitude of association, and model fit. Main Outcomes and Measures: Progression of diabetes, hyperlipidemia, and hypertension and declines in physical and mental health-related quality of life and satisfaction with surgery. Results: Among the 1406 participants who underwent RYGB surgery, the median age was 47 years (25th-75th percentile, 38-55 years) and the median BMI was 46.3 (25th-75th percentile, 42.3-51.8) prior to surgery. Most participants were female (80.3%) and white (85.6%). The median follow-up was 6.6 years (25th-75th percentile, 5.9-7.0 years). The median percentage of maximum weight loss was 37.4% (25th-75th percentile, 31.6%-43.3%) of presurgery weight and occurred a median of 2.0 years after RYGB surgery (25th-75th percentile, 1.0-3.2 years). The rate of weight regain was highest during the first year after reaching nadir weight, but weight regain continued to increase throughout follow-up (range, a median of 9.5% of maximum weight lost [25th-75th percentile, 4.7%-17.2%] to 26.8% of maximum weight lost [25th-75th percentile, 16.7%-41.5%] 1 to 5 years after reaching nadir weight). The percentage of participants who regained weight depended on threshold (eg, 5 years after nadir weight, 43.6% regained ≥5 BMI points; 50.2% regained ≥15% of nadir weight; and 67.3% regained ≥20% of maximum weight lost). Compared with other continuous weight regain measures, the percentage of maximum weight lost had the strongest association and best model fit for all outcomes except hyperlipidemia, which had a slightly stronger association with BMI. Of the dichotomous measures, 20% or greater of maximum weight lost performed better or similarly with most of the outcomes, and was the second best measure for hyperlipidemia (after ≥10 kg of weight) and hypertension (after ≥10% of maximum weight lost). Conclusions and Relevance: Among a large cohort of adults who underwent RYGB surgery, weight regain quantified as percentage of maximum weight lost performed better for association with most clinical outcomes than the alternatives examined. These findings may inform standardizing the measurement of weight regain in studies of bariatric surgery.

Long-term weight change and health outcomes for sleeve gastrectomy (SG) and matched Roux-en-Y gastric bypass (RYGB) participants in the Longitudinal Assessment of Bariatric Surgery (LABS) study.

BACKGROUND: Data from a US multicenter longitudinal study of bariatric surgery were used to compare weight change (primary outcome) and comorbidities (secondary outcome) in patients who underwent sleeve gastrectomy versus Roux-en-Y gastric bypass. METHODS: This study includes participants who underwent sleeve gastrectomy and matched participants who underwent Roux-en-Y gastric bypass from the Longitudinal Assessment of Bariatric Surgery-2 (LABS-2) study. Adults undergoing initial bariatric surgical procedures between 2006 and 2009 were enrolled. Participants who underwent sleeve gastrectomy were high-risk or superobese and intended to have a second-stage procedure. Mixed models were used to evaluate percent weight change from baseline through 7 years, and diabetes, dyslipidemia, and hypertension prevalence through 5 years. RESULTS: Fifty-seven of 59 participants who underwent sleeve gastrectomy were matched one to one. Most were female (68%) and white (81%), and had a median age of 49 (37-56) years and median body mass index of 56.4 (35.5-76.8) kg/m2 presurgery. Weight loss was significantly less 1 to 7 years after sleeve gastrectomy versus matched Roux-en-Y gastric bypass (eg, year 7 mean weight loss was 23.6% vs 30.4%, respectively; P = .001). For both surgical groups, prevalence of diabetes, low high-density lipoprotein, and hypertension were significantly (P < .05) lower 5 years postsurgery versus baseline. CONCLUSION: Higher-risk or super-obese participants after sleeve gastrectomy lost less weight than did matched Roux-en-Y gastric bypass counterparts throughout 7 years. Both groups exhibited improvements in comorbidities from presurgery through 5 years.

Seven-Year Weight Trajectories and Health Outcomes in the Longitudinal Assessment of Bariatric Surgery (LABS) Study.

Importance: More information is needed about the durability of weight loss and health improvements after bariatric surgical procedures. Objective: To examine long-term weight change and health status following Roux-en-Y gastric bypass (RYGB) and laparoscopic adjustable gastric banding (LAGB). Design, Setting, and Participants: The Longitudinal Assessment of Bariatric Surgery (LABS) study is a multicenter observational cohort study at 10 US hospitals in 6 geographically diverse clinical centers. Adults undergoing bariatric surgical procedures as part of clinical care between 2006 and 2009 were recruited and followed up until January 31, 2015. Participants completed presurgery, 6-month, and annual research assessments for up to 7 years. Main Outcome and Measures: Percentage of weight change from baseline, diabetes, dyslipidemia, and hypertension, determined by physical measures, laboratory testing, and medication use. Results: Of 2348 participants, 1738 underwent RYGB (74%) and 610 underwent LAGB (26%). For RYBG, the median age was 45 years (range, 19-75 years), the median body mass index (calculated as weight in kilograms divided by height in meters squared) was 47 (range, 34-81), 1389 participants (80%) were women, and 257 participants (15%) were nonwhite. For LAGB, the median age was 48 years (range, 18-78), the body mass index was 44 (range, 33-87), 465 participants (76%) were women, and 63 participants (10%) were nonwhite. Follow-up weights were obtained in 1300 of 1569 (83%) eligible for a year-7 visit. Seven years following RYGB, mean weight loss was 38.2 kg (95% CI, 36.9-39.5), or 28.4% (95% CI, 27.6-29.2) of baseline weight; between years 3 and 7 mean weight regain was 3.9% (95% CI, 3.4-4.4) of baseline weight. Seven years after LAGB, mean weight loss was 18.8 kg (95% CI, 16.3-21.3) or 14.9% (95% CI, 13.1-16.7), with 1.4% (95% CI, 0.4-2.4) regain. Six distinct weight change trajectory patterns for RYGB and 7 for LAGB were identified. Most participants followed trajectories in which weight regain from 3 to 7 years was small relative to year-3 weight loss, but patterns were variable. Compared with baseline, dyslipidemia prevalence was lower 7 years following both procedures; diabetes and hypertension prevalence were lower following RYGB only. Among those with diabetes at baseline (488 of 1723 with RYGB [28%]; 175 of 604 with LAGB [29%]), the proportion in remission at 1, 3, 5, and 7 years were 71.2% (95% CI, 67.0-75.4), 69.4% (95% CI, 65.0-73.8), 64.6% (95% CI, 60.0-69.2), and 60.2% (95% CI, 54.7-65.6), respectively, for RYGB and 30.7% (95% CI, 22.8-38.7), 29.3% (95% CI, 21.6-37.1), 29.2% (95% CI, 21.0-37.4), and 20.3% (95% CI, 9.7-30.9) for LAGB. The incidence of diabetes at all follow-up assessments was less than 1.5% for RYGB. Bariatric reoperations occurred in 14 RYGB and 160 LAGB participants. Conclusions and Relevance: Following bariatric surgery, different weight loss patterns were observed, but most participants maintained much of their weight loss with variable fluctuations over the long term. There was some decline in diabetes remission over time, but the incidence of new cases is low following RYGB. Trial Registration: clinicaltrials.gov Identifier: NCT00465829.