372 results on '"Van Natta, Mark L."'
Search Results
2. Fibrosis Progression Rate in Biopsy-Proven Nonalcoholic Fatty Liver Disease Among People With Diabetes Versus People Without Diabetes: A Multicenter Study
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Huang, Daniel Q, Wilson, Laura A, Behling, Cynthia, Kleiner, David E, Kowdley, Kris V, Dasarathy, Srinivasan, Amangurbanova, Maral, Terrault, Norah A, Diehl, Anna Mae, Chalasani, Naga, Neuschwander-Tetri, Brent A, Sanyal, Arun J, Tonascia, James, Loomba, Rohit, Allende, Daniela, Bellar, Annette, Dasarathy, Jaividhya, Welch, Nicole, Yerrapothu, Rahul, Bashir, Mustafa, Guy, Cynthia, Kopping, Mariko, Piercy, Dawn, Suzuki, Ayako, Tawadrou, Naglaa, Cruz, Mandy, Cummings, Oscar W, Garrison, Lisa, Gawrieh, Samer, Samala, Niharika, Vuppalanchi, Raj, Carpenter, Danielle, Cattoor, Theresa, Freebersyser, Janet, Angkanaworakul, Pannapat, Berihun, Achashman, Buysse, Andrew, Dorrian, Theresa, Gulati, Breanna, Liu, Kevin, Misic, Sandra, Sohal, Adam, Vuong, Joseph, Ajmera, Veeral, Madamba, Egbert, Middleton, Michael S, Richards, Lisa, Singh, Seema, Sirlin, Claude, Gill, Ryan, Hameed, Bilal, Awe, Remilekun, Olvera, Daisy, Terrault, Norah, Yuan, Liyun, Yeh, Matthew, Albhaisi, Somaya, Asgharpour, Amon, Boyett, Sherry, Contos, Melissa J, Luketic, Velimir AC, Schlosser, Jolene, Siddiqui, Mohammad S, Adamo, Peggy, Belt, Patricia, Clark, Jeanne M, DeSanto, Jennifer M, Meinert, Jill, Miriel, Laura, Mitchell, Emily P, Shade, Carrie, Smith, Jacqueline, Smith, Michael, Sternberg, Alice, Van Natta, Mark L, Wagoner, Annette, Woreta, Tinsay, and Yates, Katherine P
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Biomedical and Clinical Sciences ,Clinical Sciences ,Hepatitis ,Liver Disease ,Digestive Diseases ,Chronic Liver Disease and Cirrhosis ,Clinical Research ,Diabetes ,Obesity ,Metabolic and endocrine ,Good Health and Well Being ,Adult ,Humans ,Female ,Male ,Non-alcoholic Fatty Liver Disease ,Diabetes Mellitus ,Type 2 ,Cohort Studies ,Liver Cirrhosis ,Biopsy ,Nonalcoholic Steatohepatitis ,NAFLD ,Cirrhosis ,Type 2 Diabetes Mellitus ,NASH Clinical Research Network ,Neurosciences ,Paediatrics and Reproductive Medicine ,Gastroenterology & Hepatology ,Clinical sciences ,Nutrition and dietetics - Abstract
Background & aimsThere are limited data regarding fibrosis progression in biopsy-proven nonalcoholic fatty liver disease (NAFLD) in people with type 2 diabetes mellitus (T2DM) compared with people without T2DM. We assessed the time to fibrosis progression in people with T2DM compared with people without T2DM in a large, multicenter, study of people with NAFLD who had paired liver biopsies.MethodsThis study included 447 adult participants (64% were female) with NAFLD who had paired liver biopsies more than 1 year apart. Liver histology was systematically assessed by a central pathology committee blinded to clinical data. The primary outcome was the cumulative incidence of a ≥1-stage increase in fibrosis in participants with T2DM compared with participants without T2DM.ResultsThe mean (SD) age and body mass index (calculated as weight in kilograms divided by the square of the height in meters) were 50.9 (11.5) years and 34.7 (6.3), respectively. The median time between biopsies was 3.3 years (interquartile range, 1.8-6.1 years). Participants with T2DM had a significantly higher cumulative incidence of fibrosis progression at 4 years (24% vs 20%), 8 years (60% vs 50%), and 12 years (93% vs 76%) (P = .005). Using a multivariable Cox proportional hazards model adjusted for multiple confounders, T2DM remained an independent predictor of fibrosis progression (adjusted hazard ratio, 1.69; 95% CI, 1.17-2.43; P = .005). The cumulative incidence of fibrosis regression by ≥1 stage was similar in participants with T2DM compared with participants without T2DM (P = .24).ConclusionsIn this large, multicenter cohort study of well-characterized participants with NAFLD and paired liver biopsies, we found that fibrosis progressed faster in participants with T2DM compared with participants without T2DM. These data have important implications for clinical practice and trial design.
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- 2023
3. Incidence of Type 2 Diabetes in Children With Nonalcoholic Fatty Liver Disease
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Newton, Kimberly P, Wilson, Laura A, Crimmins, Nancy A, Fishbein, Mark H, Molleston, Jean P, Xanthakos, Stavra A, Behling, Cynthia, Schwimmer, Jeffrey B, Network, Nonalcoholic Steatohepatitis Clinical Research, Garner, Donna, Hertel, Paula, Lawson, Alicia, Pham, Yen, Triggs, Nicole, Bramlage, Kristin, Carr, April, McNeill, Meghan, Mouzaki, Marialena, Xanthakos, Stavra, Alazraki, Adina, Cleeton, Rebecca, Cordero, Maria, Karpen, Saul, Vos, Miriam, Carr, Laura, Cummings, Oscar W, Harlow, Kathryn, Klipsch, Ann, Morlan, Wendy, Ragozzino, Emily, Sawyers, Cindy, Anthony, Angela, Cattoor, Theresa, Freebersyser, Janet, Jain, Ajay K, Torretta, Susan, Durelle, Janis, Goyal, Nidhi P, Ugalde-Nicalo, Patricia, Wang, Andrew, Blondet, Niviann, Cooper, Kara, Otto, Randolph, Yeh, Matthew, Young, Melissa, Kleiner, David E, Doo, Edward C, Hall, Sherry, Hoofnagle, Jay H, Sherker, Averell H, Torrance, Rebecca, Robuck, Patricia R, Adamo, Peggy, Belt, Patricia, Clark, Jeanne M, Meinert, Jill, Miriel, Laura, Shade, Carrie, Sharkey, Emily P, Smith, Jacqueline, Smith, Michael, Sternberg, Alice, Tonascia, ScM James, Van Natta, Mark L, Wagoner, Annette, Woreta, Tinsay, Yates, Katherine P, Dodge, John, Donithan, Michele, and Isaacson, Milana
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Biomedical and Clinical Sciences ,Clinical Sciences ,Pediatric ,Prevention ,Digestive Diseases ,Nutrition ,Clinical Research ,Chronic Liver Disease and Cirrhosis ,Hepatitis ,Diabetes ,Liver Disease ,Aetiology ,2.1 Biological and endogenous factors ,Metabolic and endocrine ,Male ,Humans ,Female ,Child ,Non-alcoholic Fatty Liver Disease ,Diabetes Mellitus ,Type 2 ,Incidence ,Liver ,Risk Factors ,Obesity ,Gender ,Hispanic ,Steatohepatitis ,Nonalcoholic Steatohepatitis Clinical Research Network ,Gastroenterology & Hepatology ,Clinical sciences - Abstract
Background & aimsType 2 diabetes (T2D) is a growing problem in children. Children with NAFLD are at potentially high risk for developing T2D; however, the incidence of T2D in this population is unknown. This study aimed to determine the incidence of T2D in children with NAFLD and identify associated risk factors.MethodsChildren with NAFLD enrolled in the Nonalcoholic Steatohepatitis Clinical Research Network were followed longitudinally. Incidence of T2D was determined by using clinical history and fasting laboratory values. Cumulative incidence curves were developed for time to T2D. A Cox regression multivariable model was constructed using best subsets Akaike's Information Criteria selection.ResultsThis study included 892 children with NAFLD and with a mean age of 12.8 years (2.7) followed for 3.8 years (2.3) with a total 3234 person-years at risk. The incidence rate of T2D was 3000 new cases per 100,000 person-years at risk. At baseline, 63 children had T2D, and during follow-up, an additional 97 children developed incident T2D, resulting in a period prevalence of 16.8%. Incident T2D was significantly higher in females versus males (hazard ratio [HR], 1.8 [1.0-2.8]), associated with BMI z-score (HR, 1.8 [1.0-3.0]), and more severe liver histology including steatosis grade (HR, 1.3 [1.0-1.7]), and fibrosis stage (HR, 1.3 [1.0-1.5]).ConclusionsChildren with NAFLD are at high risk for existing and incident T2D. In addition to known risk factors for T2D (female and BMI z-score), severity of liver histology at the time of NAFLD diagnosis was independently associated with T2D development. Targeted strategies to prevent T2D in children with NAFLD are needed.
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- 2023
4. Randomized placebo‐controlled trial of losartan for pediatric NAFLD
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Vos, Miriam B, Van Natta, Mark L, Blondet, Niviann M, Dasarathy, Srinivasan, Fishbein, Mark, Hertel, Paula, Jain, Ajay K, Karpen, Saul J, Lavine, Joel E, Mohammad, Saeed, Miriel, Laura A, Molleston, Jean P, Mouzaki, Marialena, Sanyal, Arun, Sharkey, Emily P, Schwimmer, Jeffrey B, Tonascia, James, Wilson, Laura A, Xanthakos, Stavra A, and Network, NASH Clinical Research
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Biomedical and Clinical Sciences ,Clinical Sciences ,Pediatric ,Digestive Diseases ,Clinical Research ,Prevention ,Hepatitis ,Liver Disease ,Clinical Trials and Supportive Activities ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,Adolescent ,Angiotensin Receptor Antagonists ,Blood Pressure ,Child ,Double-Blind Method ,Female ,Humans ,Hypertension ,Losartan ,Male ,Non-alcoholic Fatty Liver Disease ,Treatment Outcome ,NASH Clinical Research Network ,Medical Biochemistry and Metabolomics ,Immunology ,Gastroenterology & Hepatology ,Clinical sciences - Abstract
Background and aimsTo date, no pharmacotherapy exists for pediatric NAFLD. Losartan, an angiotensin II receptor blocker, has been proposed as a treatment due to its antifibrotic effects.Approach and resultsThe Nonalcoholic Steatohepatitis Clinical Research Network conducted a multicenter, double-masked, placebo-controlled, randomized clinical trial in children with histologically confirmed NAFLD at 10 sites (September 2018 to April 2020). Inclusion criteria were age 8-17 years, histologic NAFLD activity score ≥ 3, and serum alanine aminotransferase (ALT) ≥ 50 U/l. Children received 100 mg of losartan or placebo orally once daily for 24 weeks. The primary outcome was change in ALT levels from baseline to 24 weeks, and the preset sample size was n = 110. Treatment effects were assessed using linear regression of change in treatment group adjusted for baseline value. Eighty-three participants (81% male, 80% Hispanic) were randomized to losartan (n = 43) or placebo (n = 40). During an enrollment pause, necessitated by the 2019 coronavirus pandemic, an unplanned interim analysis showed low probability (7%) of significant group difference. The Data and Safety Monitoring Board recommended early study termination. Baseline characteristics were similar between groups. The 24-week change in ALT did not differ significantly between losartan versus placebo groups (adjusted mean difference: 1.1 U/l; 95% CI = -30.6, 32.7; p = 0.95), although alkaline phosphatase decreased significantly in the losartan group (adjusted mean difference: -23.4 U/l; 95% CI = -41.5, -5.3; p = 0.01). Systolic blood pressure decreased in the losartan group but increased in placebo (adjusted mean difference: -7.5 mm Hg; 95% CI = -12.2, -2.8; p = 0.002). Compliance by pill counts and numbers and types of adverse events did not differ by group.ConclusionsLosartan did not significantly reduce ALT in children with NAFLD when compared with placebo.
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- 2022
5. Comparison of clinical prediction rules for ruling out cirrhosis in nonalcoholic fatty liver disease (NAFLD)
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Brandman, Danielle, Boyle, Marie, McPherson, Stuart, Van Natta, Mark L, Sanyal, Arun J, Kowdley, Kris, Neuschwander‐Tetri, Brent, Chalasani, Naga, Abdelmalek, Manal F, Terrault, Norah A, McCullough, Art, Bettencourt, Ricki, Caussy, Cyrielle, Kleiner, David E, Behling, Cynthia, Tonascia, James, Anstee, Quentin M, Loomba, Rohit, and Network, Members of the Nonalcoholic Steatohepatitis Clinical Research
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Biomedical and Clinical Sciences ,Clinical Sciences ,Digestive Diseases ,Hepatitis ,Liver Disease ,Chronic Liver Disease and Cirrhosis ,Detection ,screening and diagnosis ,4.2 Evaluation of markers and technologies ,Oral and gastrointestinal ,Good Health and Well Being ,Adult ,Biopsy ,Clinical Decision Rules ,Cross-Sectional Studies ,Female ,Fibrosis ,Humans ,Liver ,Liver Cirrhosis ,Non-alcoholic Fatty Liver Disease ,cirrhosis ,nonalcoholic fatty liver disease ,noninvasive assessment ,Members of the Nonalcoholic Steatohepatitis Clinical Research Network ,Pharmacology and Pharmaceutical Sciences ,Gastroenterology & Hepatology ,Clinical sciences ,Pharmacology and pharmaceutical sciences - Abstract
Background and aimsPatients with nonalcoholic fatty liver disease (NAFLD) cirrhosis benefit from referral to subspecialty care. While several clinical prediction rules exist to identify advanced fibrosis, the cutoff for excluding cirrhosis due to NAFLD is unclear. This analysis compared clinical prediction rules for excluding biopsy-proven cirrhosis in NAFLD.MethodsAdult patients were enrolled in the NASH Clinical Research Network (US) and the Newcastle Cohort (UK). Clinical and laboratory data were collected at enrolment, and a liver biopsy was taken within 1 year of enrolment. Optimal cutoffs for each score (eg, FIB-4) to exclude cirrhosis were derived from the US cohort, and sensitivity, specificity, positive predictive value, negative predictive value and AUROC were calculated. The cutoffs were evaluated in the UK cohort.Results147/1483 (10%) patients in the US cohort had cirrhosis. All prediction rules had similarly high NPV (0.95-0.97). FIB-4 and NAFLD fibrosis scores were the most accurate in characterising patients as having cirrhosis (AUROC 0.84-0.86). 59/494 (12%) patients in the UK cohort had cirrhosis. Prediction rules had high NPV (0.92-0.96), and FIB-4 and NAFLD fibrosis score the most accurate in the prediction of cirrhosis in the UK cohort (AUROC 0.87-0.89).ConclusionsThis cross-sectional analysis of large, multicentre international datasets shows that current clinical prediction rules perform well in excluding cirrhosis with appropriately chosen cutoffs. These clinical prediction rules can be used in primary care to identify patients, particularly those who are white, female, and
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- 2022
6. Validation of the accuracy of the FAST™ score for detecting patients with at-risk nonalcoholic steatohepatitis (NASH) in a North American cohort and comparison to other non-invasive algorithms
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Woreta, Tinsay A, Van Natta, Mark L, Lazo, Mariana, Krishnan, Arunkumar, Neuschwander-Tetri, Brent A, Loomba, Rohit, Diehl, Anna Mae, Abdelmalek, Manal F, Chalasani, Naga, Gawrieh, Samer, Dasarathy, Srinivasan, Vuppalanchi, Raj, Siddiqui, Mohammad S, Kowdley, Kris V, McCullough, Arthur, Terrault, Norah A, Behling, Cynthia, Kleiner, David E, Fishbein, Mark, Hertel, Paula, Wilson, Laura A, Mitchell, Emily P, Miriel, Laura A, Clark, Jeanne M, Tonascia, James, and Sanyal, Arun J
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Biomedical and Clinical Sciences ,Clinical Sciences ,Digestive Diseases ,Liver Disease ,Chronic Liver Disease and Cirrhosis ,Women's Health ,Obesity ,Hepatitis ,Clinical Research ,4.2 Evaluation of markers and technologies ,Oral and gastrointestinal ,Adult ,Algorithms ,Biopsy ,Cohort Studies ,Female ,Fibrosis ,Humans ,Liver ,Liver Cirrhosis ,Male ,Middle Aged ,Non-alcoholic Fatty Liver Disease ,Severity of Illness Index ,NASH Clinical Research Network ,General Science & Technology - Abstract
Background and aimsManagement of patients with NASH who are at elevated risk of progressing to complications of cirrhosis (at-risk NASH) would be enhanced by an accurate, noninvasive diagnostic test. The new FAST™ score, a combination of FibroScan® parameters liver stiffness measurement (LSM) and controlled attenuation parameter (CAP) and aspartate aminotransferase (AST), has shown good diagnostic accuracy for at-risk NASH (area-under-the-Receiver-Operating-Characteristic [AUROC] = 0.80) in European cohorts. We aimed to validate the FAST™ score in a North American cohort and show how its diagnostic accuracy might vary by patient mix. We also compared the diagnostic performance of FAST™ to other non-invasive algorithms for the diagnosis of at-risk NASH.MethodsWe studied adults with biopsy-proven non-alcoholic fatty liver disease (NAFLD) from the multicenter NASH Clinical Research Network (CRN) Adult Database 2 (DB2) cohort study. At-risk-NASH was histologically defined as definite NASH with a NAFLD Activity Score (NAS) ≥ 4 with at least 1 point in each category and a fibrosis stage ≥ 2. We used the Echosens® formula for FAST™ from LSM (kPa), CAP (dB/m), and AST (U/L), and the FAST™-based Rule-Out (FAST™ ≤ 0.35, sensitivity = 90%) and Rule-In (FAST™ ≥ 0.67, specificity = 90%) zones. We determined the following diagnostic performance measures: AUROC, sensitivity (Se), specificity (Sp), positive predictive value (PPV), and negative predictive value (NPV); these were calculated for the total sample and by subgroups of patients and by FibroScan® exam features. We also compared the at-risk NASH diagnostic performance of FAST™ to other non-invasive algorithms: NAFLD fibrosis score (NFS), Fibrosis-4 (FIB-4) index, and AST to platelet ratio index (APRI).ResultsThe NASH CRN population of 585 patients was 62% female, 79% white, 14% Hispanic, and 73% obese; the mean age was 51 years. The mean (SD) AST and ALT were 50 (37) U/L and 66 (45) U/L, respectively. 214 (37%) had at-risk NASH. The AUROC of FAST™ for at-risk NASH in the NASH CRN study population was 0.81 (95% CI: 0.77, 0.84. Using FAST™-based cut-offs, 35% of patients were ruled-out with corresponding NPV = 0.90 and 27% of patients were ruled-in with corresponding PPV = 0.69. The diagnostic accuracy of FAST™ was higher in non-whites vs. whites (AUROC: 0.91 vs 0.78; p = 0.001), and in patients with a normal BMI vs. BMI > 35 kg/m2 (AUROC: 0.94 vs 0.78, p = 0.008). No differences were observed by other patient characteristics or FibroScan® exam features. The FAST™ score had higher diagnostic accuracy than other non-invasive algorithms for the diagnosis of at-risk NASH (AUROC for NFS, FIB-4, and APRI 0.67, 0.73, 0.74, respectively).ConclusionWe validated the FAST™ score for the diagnosis of at-risk NASH in a large, multi-racial population in North America, with a prevalence of at-risk NASH of 37%. Diagnostic performance varies by subgroups of NASH patients defined by race and obesity. FAST™ performed better than other non-invasive algorithms for the diagnosis of at-risk NASH.
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- 2022
7. Prospective Study of Outcomes in Adults with Nonalcoholic Fatty Liver Disease
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Sanyal, Arun J, Van Natta, Mark L, Clark, Jeanne, Neuschwander-Tetri, Brent A, Diehl, AnnaMae, Dasarathy, Srinivasan, Loomba, Rohit, Chalasani, Naga, Kowdley, Kris, Hameed, Bilal, Wilson, Laura A, Yates, Katherine P, Belt, Patricia, Lazo, Mariana, Kleiner, David E, Behling, Cynthia, and Tonascia, James
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Chronic Liver Disease and Cirrhosis ,Clinical Research ,Liver Disease ,Digestive Diseases ,Good Health and Well Being ,Adult ,Biopsy ,Carcinoma ,Hepatocellular ,Female ,Gastrointestinal Hemorrhage ,Humans ,Incidence ,Liver ,Liver Cirrhosis ,Liver Neoplasms ,Male ,Middle Aged ,Non-alcoholic Fatty Liver Disease ,Prognosis ,Prospective Studies ,Severity of Illness Index ,NASH Clinical Research Network ,Medical and Health Sciences ,General & Internal Medicine - Abstract
BackgroundThe prognoses with respect to mortality and hepatic and nonhepatic outcomes across the histologic spectrum of nonalcoholic fatty liver disease (NAFLD) are not well defined.MethodsWe prospectively followed a multicenter patient population that included the full histologic spectrum of NAFLD. The incidences of death and other outcomes were compared across baseline histologic characteristics.ResultsA total of 1773 adults with NAFLD were followed for a median of 4 years. All-cause mortality increased with increasing fibrosis stages (0.32 deaths per 100 person-years for stage F0 to F2 [no, mild, or moderate fibrosis], 0.89 deaths per 100 persons-years for stage F3 [bridging fibrosis], and 1.76 deaths per 100 person-years for stage F4 [cirrhosis]). The incidence of liver-related complications per 100 person-years increased with fibrosis stage (F0 to F2 vs. F3 vs. F4) as follows: variceal hemorrhage (0.00 vs. 0.06 vs. 0.70), ascites (0.04 vs. 0.52 vs. 1.20), encephalopathy (0.02 vs. 0.75 vs. 2.39), and hepatocellular cancer (0.04 vs. 0.34 vs. 0.14). As compared with patients with stage F0 to F2 fibrosis, patients with stage F4 fibrosis also had a higher incidence of type 2 diabetes (7.53 vs. 4.45 events per 100 person-years) and a decrease of more than 40% in the estimated glomerular filtration rate (2.98 vs. 0.97 events per 100 person-years). The incidence of cardiac events and nonhepatic cancers were similar across fibrosis stages. After adjustment for age, sex, race, diabetes status, and baseline histologic severity, the incidence of any hepatic decompensation event (variceal hemorrhage, ascites, or encephalopathy) was associated with increased all-cause mortality (adjusted hazard ratio, 6.8; 95% confidence interval, 2.2 to 21.3).ConclusionsIn this prospective study involving patients with NAFLD, fibrosis stages F3 and F4 were associated with increased risks of liver-related complications and death. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; NAFLD DB2 ClinicalTrials.gov number, NCT01030484.).
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- 2021
8. Fibrosis Progression Rate in Biopsy-Proven Nonalcoholic Fatty Liver Disease Among People With Diabetes Versus People Without Diabetes: A Multicenter Study
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Allende, Daniela, Bellar, Annette, Dasarathy, Jaividhya, Dasarathy, Srinivasan, Welch, Nicole, Yerrapothu, Rahul, Bashir, Mustafa, Diehl, Anna Mae, Guy, Cynthia, Kopping, Mariko, Piercy, Dawn, Suzuki, Ayako, Tawadrou, Naglaa, Chalasani, Naga, Cruz, Mandy, Cummings, Oscar W., Garrison, Lisa, Gawrieh, Samer, Samala, Niharika, Vuppalanchi, Raj, Carpenter, Danielle, Cattoor, Theresa, Freebersyser, Janet, Neuschwander-Tetri, Brent A., Angkanaworakul, Pannapat, Berihun, Achashman, Buysse, Andrew, Dorrian, Theresa, Gulati, Breanna, Kowdley, Kris V., Liu, Kevin, Misic, Sandra, Sohal, Adam, Vuong, Joseph, Ajmera, Veeral, Behling, Cynthia, Loomba, Rohit, Madamba, Egbert, Middleton, Michael S., Richards, Lisa, Singh, Seema, Sirlin, Claude, Gill, Ryan, Hameed, Bilal, Awe, Remilekun, Olvera, Daisy, Terrault, Norah, Yuan, Liyun, Yeh, Matthew, Albhaisi, Somaya, Asgharpour, Amon, Boyett, Sherry, Contos, Melissa J., Luketic, Velimir A.C., Sanyal, Arun J., Schlosser, Jolene, Siddiqui, Mohammad S., Kleiner, David E., Adamo, Peggy, Belt, Patricia, Clark, Jeanne M., DeSanto, Jennifer M., Meinert, Jill, Miriel, Laura, Mitchell, Emily P., Shade, Carrie, Smith, Jacqueline, Smith, Michael, Sternberg, Alice, Tonascia, James, Van Natta, Mark L., Wagoner, Annette, Wilson, Laura A., Woreta, Tinsay, Yates, Katherine P., Huang, Daniel Q., Amangurbanova, Maral, and Terrault, Norah A.
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- 2023
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9. Incidence of Type 2 Diabetes in Children With Nonalcoholic Fatty Liver Disease
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Garner, Donna, Hertel, Paula, Lawson, Alicia, Pham, Yen, Triggs, Nicole, Bramlage, Kristin, Carr, April, McNeill, Meghan, Mouzaki, Marialena, Xanthakos, Stavra, Alazraki, Adina, Cleeton, Rebecca, Cordero, Maria, Karpen, Saul, Vos, Miriam, Carr, Laura, Cummings, Oscar W., Harlow, Kathryn, Klipsch, Ann, Molleston, Jean P., Morlan, Wendy, Ragozzino, Emily, Sawyers, Cindy, Anthony, Angela, Fishbein, Mark H., Cattoor, Theresa, Freebersyser, Janet, Jain, Ajay K., Torretta, Susan, Behling, Cynthia, Durelle, Janis, Goyal, Nidhi P., Newton, Kimberly P., Schwimmer, Jeffrey B., Ugalde-Nicalo, Patricia, Wang, Andrew, Blondet, Niviann, Cooper, Kara, Otto, Randolph, Yeh, Matthew, Young, Melissa, Kleiner, David E., Doo, Edward C., Hall, Sherry, Hoofnagle, Jay H., Sherker, Averell H., Torrance, Rebecca, Robuck, Patricia R., Adamo, Peggy, Belt, Patricia, Clark, Jeanne M., Meinert, Jill, Miriel, Laura, Shade, Carrie, Sharkey, Emily P., Smith, Jacqueline, Smith, Michael, Sternberg, Alice, Tonascia, ScM; James, Van Natta, Mark L., Wagoner, Annette, Wilson, Laura A., Woreta, Tinsay, Yates, Katherine P., Dodge, John, Donithan, Michele, Isaacson, Milana, Crimmins, Nancy A., and Xanthakos, Stavra A.
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- 2023
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10. Impact of obeticholic acid on the lipoprotein profile in patients with non-alcoholic steatohepatitis
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Siddiqui, Mohammad Shadab, Van Natta, Mark L, Connelly, Margery A, Vuppalanchi, Raj, Neuschwander-Tetri, Brent A, Tonascia, James, Guy, Cynthia, Loomba, Rohit, Dasarathy, Srinivasan, Wattacheril, Julia, Chalasani, Naga, Sanyal, Arun J, and CRN, for the NASH
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Biomedical and Clinical Sciences ,Clinical Sciences ,Atherosclerosis ,Hepatitis ,Clinical Trials and Supportive Activities ,Cardiovascular ,Chronic Liver Disease and Cirrhosis ,Liver Disease ,Clinical Research ,Digestive Diseases ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Good Health and Well Being ,Adult ,Biopsy ,Chenodeoxycholic Acid ,Drug Therapy ,Combination ,Female ,Humans ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,Lipoproteins ,HDL ,Lipoproteins ,LDL ,Lipoproteins ,VLDL ,Liver ,Male ,Middle Aged ,Non-alcoholic Fatty Liver Disease ,Receptors ,Cytoplasmic and Nuclear ,Treatment Outcome ,Nonalcoholic steatohepatitis ,NASH ,Very low-density lipoprotein ,Low-density lipoprotein ,High-density lipoprotein ,Lipoproteins ,Cholesterol ,OCA ,NASH CRN ,Public Health and Health Services ,Gastroenterology & Hepatology ,Clinical sciences - Abstract
Background & aimsObeticholic acid (OCA), a farnesoid X receptor agonist, increases total and low-density lipoprotein cholesterol (LDL-C) in patients with non-alcoholic steatohepatitis. In the present study, we aimed to evaluate the impact of OCA therapy on lipoprotein sub-particles.MethodThis study included 196 patients (99 OCA group and 97 placebo group) who were enrolled in the FLINT trial and had samples available for lipid analysis and liver biopsies at enrollment and end-of-treatment (EOT) at 72 weeks. Very low-density lipoprotein (VLDL), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) particles were evaluated at baseline, 12 and 72 weeks after randomization, and 24 weeks following EOT.ResultsBaseline lipoprotein profiles were similar among OCA and placebo groups. OCA did not affect total VLDL particle concentrations, but OCA vs. placebo treatment was associated with decreased large VLDL particle concentration at 12 weeks (baseline-adjusted mean: 6.8 vs. 8.9 nmol/L; p = 0.002), mirrored by an increase in less atherogenic, small VLDL particle concentration (33.9 vs. 28.0 nmol/L; p = 0.02). After 12 weeks, total LDL particle concentration was higher in the OCA group than the placebo group (1,667 vs. 1,329 nmol/L; p
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- 2020
11. Progress in Gastroparesis - A Narrative Review of the Work of the Gastroparesis Clinical Research Consortium
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Pasricha, Pankaj J., Grover, Madhusudan, Yates, Katherine P., Abell, Thomas L., Koch, Kenneth L., McCallum, Richard W., Sarosiek, Irene, Bernard, Cheryl E., Kuo, Braden, Bulat, Robert, Shulman, Robert J., Chumpitazi, Bruno P., Tonascia, James, Miriel, Laura A., Wilson, Laura A., Van Natta, Mark L., Mitchell, Emily, Hamilton, Frank, Farrugia, Gianrico, and Parkman, Henry P.
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- 2022
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12. Diagnostic Accuracy of Noninvasive Fibrosis Models to Detect Change in Fibrosis Stage
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Siddiqui, Mohammad Shadab, Yamada, Goro, Vuppalanchi, Raj, Van Natta, Mark, Loomba, Rohit, Guy, Cynthia, Brandman, Danielle, Tonascia, James, Chalasani, Naga, Neuschwander-Tetri, Brent, Sanyal, Arun J, Allende, Daniela, Dasarathy, Srinivasan, McCullough, Arthur J, Penumatsa, Revathi, Dasarathy, Jaividhya, Lavine, Joel E, Abdelmalek, Manal F, Bashir, Mustafa, Buie, Stephanie, Diehl, Anna Mae, Kigongo, Christopher, Kopping, Mariko, Malik, David, Piercy, Dawn, Cummings, Oscar W, Gawrieh, Samer, Ragozzino, Linda, Sandrasegaran, Kumar, Brunt, Elizabeth M, Cattoor, Theresa, Carpenter, Danielle, Freebersyser, Janet, King, Debra, Lai, Jinping, Neuschwander-Tetri, Brent A, Siegner, Joan, Stewart, Susan, Torretta, Susan, Wriston, Kristina, Gonzalez, Maria Cardona, Davila, Jodie, Jhaveri, Manan, Kowdley, Kris V, Mukhtar, Nizar, Ness, Erik, Poitevin, Michelle, Quist, Brook, Soo, Sherilynn, Ang, Brandon, Behling, Cynthia, Bhatt, Archana, Middleton, Michael S, Sirlin, Claude, Akhter, Maheen F, Bass, Nathan M, Gill, Ryan, Hameed, Bilal, Maher, Jacqueline, Terrault, Norah, Ungermann, Ashley, Yeh, Matthew, Boyett, Sherry, Contos, Melissa J, Kirwin, Sherri, Luketic, Velimir AC, Puri, Puneet, Schlosser, Jolene, Siddiqui, Mohammad S, Yost-Schomer, Leslie, Fowler, Kathryn, Kleiner, David E, Doo, Edward C, Hall, Sherry, Hoofnagle, Jay H, Lee, Jessica J, Robuck, Patricia R, Sherker, Averell H, Torrance, Rebecca, Belt, Patricia, Clark, Jeanne M, Dodge, John, Donithan, Michele, Hallinan, Erin, Isaacson, Milana, Lazo, Mariana, Meinert, Jill, Miriel, Laura, Smith, Jacqueline, Smith, Michael, Sternberg, Alice, and Van Natta, Mark L
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Clinical Research ,Chronic Liver Disease and Cirrhosis ,Liver Disease ,Digestive Diseases ,Detection ,screening and diagnosis ,4.2 Evaluation of markers and technologies ,Good Health and Well Being ,Adult ,Alanine Transaminase ,Aspartate Aminotransferases ,Biopsy ,Disease Progression ,Female ,Humans ,Liver ,Liver Cirrhosis ,Male ,Middle Aged ,Non-alcoholic Fatty Liver Disease ,Platelet Count ,Predictive Value of Tests ,Retrospective Studies ,Sensitivity and Specificity ,Severity of Illness Index ,Nonalcoholic Steatohepatitis ,Diagnostic ,Prognostic ,Scoring System Comparison ,NASH Clinical Research Network ,Clinical Sciences ,Gastroenterology & Hepatology - Abstract
Background & aimsNoninvasive methods are needed to determine disease stage in patients with nonalcoholic fatty liver disease (NAFLD). We evaluated the diagnostic performance of several widely available fibrosis models for the assessment of hepatic fibrosis in patients with NAFLD.MethodsWe performed a retrospective analysis of data from individuals enrolled in the NIDDK NASH Clinical Research Network, from 2004 through 2018. Using biopsy as the reference standard, we determined the diagnostic performance of the aspartate aminotransferase (AST):platelet ratio (APRI), FIB-4, ratio of AST:alanine aminotransferase (ALT) and the NAFLD fibrosis score (NFS) in a cross-sectional study of 1904 subjects. The ability of these models to detect changes in fibrosis stage was assessed in a longitudinal data set of 292 subjects with 2 biopsies and accompanying laboratory data. Outcomes were detection of fibrosis of any stage (stages 0-4), detection of moderate fibrosis (stages 0-1 vs 2-4), and detection of advanced fibrosis (stages 0-2 vs 3-4). Diagnostic performance was evaluated using the C-statistic, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) analyses.ResultsIn the cross-sectional study, FIB-4 and NFS outperformed other non-invasive models for detecting advanced fibrosis; the C-statistics were 0.80 for FIB-4 and 0.78 for NFS. In the longitudinal study, 216 patients had non-advanced fibrosis at baseline and 35 patients progressed to advanced fibrosis after median follow up of 2.6 years. After we adjusted for fibrosis stage and model score at initial biopsy, change in APRI, FIB-4, and NFS were significantly associated with change in fibrosis. A unit change in APRI, FIB-4, or NFS was associated with changes in fibrosis stage of 0.33 (95% CI, 0.20-0.45; P < .001), 0.26 (95% CI, 0.15-0.37; P < .001), and 0.19 (95% CI, 0.07-0.31; P = .002), respectively. The cross-validated C-statistic for detecting progression to advanced fibrosis for APRI was 0.82 (95% CI, 0.74-0.89), for FIB-4 was 0.81 (95% CI, 0.73-0.81), and for NFS was 0.80 (95% CI, 0.71-0.88).ConclusionsIn a combined analysis of data from 2 large studies, we found that FIB-4, APRI, and NFS can detect advanced fibrosis and fibrosis progression in patients with NAFLD.
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- 2019
13. Association of Systemic Inflammation With Retinal Vascular Caliber in Patients With AIDS
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Jabs, Douglas A, Van Natta, Mark L, Trang, Garrett, Jones, Norman, Milush, Jeffrey M, Cheu, Ryan, Klatt, Nichole R, Pak, Jeong Won, Danis, Ronald P, and Hunt, Peter W
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Eye Disease and Disorders of Vision ,Clinical Research ,Aging ,Cardiovascular ,Acquired Immunodeficiency Syndrome ,Adult ,Age Factors ,Arterioles ,Biomarkers ,Cardiovascular Diseases ,Female ,Humans ,Inflammation ,Linear Models ,Male ,Middle Aged ,Retinal Artery ,Retinal Vein ,Retinal Vessels ,Risk Factors ,Venules ,retinal vascular caliber ,inflammation ,AIDS ,Biological Sciences ,Medical and Health Sciences ,Ophthalmology & Optometry - Abstract
PurposeTo evaluate relationships among retinal vascular caliber and biomarkers of systemic inflammation in patients with AIDS.MethodsA total of 454 participants with AIDS had retinal vascular caliber (central retinal artery equivalent and central retinal vein equivalent) determined from enrollment retinal photographs by reading center graders masked to clinical and biomarker information. Cryopreserved plasma specimens were assayed for inflammatory biomarkers, including C-reactive protein (CRP), IL-6, interferon-γ inducible protein (IP)-10, kynurenine/tryptophan (KT) ratio, and intestinal fatty acid binding protein (I-FABP).ResultsIn the simple linear regression of retinal vascular caliber on plasma biomarkers, elevated CRP, IL-6, and IP-10 were associated with retinal venular dilation, and elevated KT ratio with retinal arteriolar narrowing. In the multiple linear regression, including baseline characteristics and plasma biomarkers, AMD was associated with dilation of retinal arterioles (mean difference: 9.1 μm; 95% confidence interval [CI] 5.2, 12.9; P < 0.001) and venules (mean difference, 10.9 μm; 95% CI, 5.3, 16.6; P < 0.001), as was black race (P < 0.001). Hyperlipidemia was associated with retinal venular narrowing (mean difference, -7.5 μm; 95% CI, -13.7, -1.2; P = 0.02); cardiovascular disease with arteriolar narrowing (mean difference, -5.2 μm; 95% CI, -10.3, -0.1; P = 0.05); age with arteriolar narrowing (slope, -0.26 μm/year; 95% CI, -0.46, -0.06; P = 0.009); and IL-6 with venular dilation (slope, 5.3 μm/standard deviation log10[plasma IL-6 concentration]; 95% CI, 2.7, 8.0; P < 0.001).ConclusionsThese data suggest that retinal vascular caliber is associated with age, race, AMD, hyperlipidemia, cardiovascular disease, and selected biomarkers of systemic inflammation.
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- 2019
14. Hepatic R2* is more strongly associated with proton density fat fraction than histologic liver iron scores in patients with nonalcoholic fatty liver disease
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Bashir, Mustafa R, Wolfson, Tanya, Gamst, Anthony C, Fowler, Kathryn J, Ohliger, Michael, Shah, Shetal N, Alazraki, Adina, Trout, Andrew T, Behling, Cynthia, Allende, Daniela S, Loomba, Rohit, Sanyal, Arun, Schwimmer, Jeffrey, Lavine, Joel E, Shen, Wei, Tonascia, James, Van Natta, Mark L, Mamidipalli, Adrija, Hooker, Jonathan, Kowdley, Kris V, Middleton, Michael S, Sirlin, Claude B, and Network, on behalf of the NASH Clinical Research
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Biomedical and Clinical Sciences ,Clinical Sciences ,Liver Disease ,Digestive Diseases ,Chronic Liver Disease and Cirrhosis ,Aetiology ,2.1 Biological and endogenous factors ,Oral and gastrointestinal ,Adipose Tissue ,Adolescent ,Adult ,Aged ,Child ,Cross-Sectional Studies ,Female ,Humans ,Iron ,Liver ,Magnetic Resonance Imaging ,Male ,Middle Aged ,Non-alcoholic Fatty Liver Disease ,Prospective Studies ,Protons ,Retrospective Studies ,Young Adult ,nonalcoholic steatohepatitis ,NASH ,nonalcoholic fatty liver disease ,NAFLD ,proton density fat fraction ,PDFF ,R2* ,hepatic steatosis ,NASH Clinical Research Network ,Physical Sciences ,Engineering ,Medical and Health Sciences ,Nuclear Medicine & Medical Imaging ,Clinical sciences - Abstract
BackgroundThe liver R2* value is widely used as a measure of liver iron but may be confounded by the presence of hepatic steatosis and other covariates.PurposeTo identify the most influential covariates for liver R2* values in patients with nonalcoholic fatty liver disease (NAFLD).Study typeRetrospective analysis of prospectively acquired data.PopulationBaseline data from 204 subjects enrolled in NAFLD/NASH (nonalcoholic steatohepatitis) treatment trials.Field strength1.5T and 3T; chemical-shift encoded multiecho gradient echo.AssessmentCorrelation between liver proton density fat fraction and R2*; assessment for demographic, metabolic, laboratory, MRI-derived, and histological covariates of liver R2*.Statistical testsPearson's and Spearman's correlations; univariate analysis; gradient boosting machines (GBM) multivariable machine-learning method.ResultsHepatic proton density fat fraction (PDFF) was the most strongly correlated covariate for R2* at both 1.5T (r = 0.652, P
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- 2019
15. Vibration-Controlled Transient Elastography to Assess Fibrosis and Steatosis in Patients With Nonalcoholic Fatty Liver Disease
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Siddiqui, Mohammad S, Vuppalanchi, Raj, Van Natta, Mark L, Hallinan, Erin, Kowdley, Kris V, Abdelmalek, Manal, Neuschwander-Tetri, Brent A, Loomba, Rohit, Dasarathy, Srinivasan, Brandman, Danielle, Doo, Edward, Tonascia, James A, Kleiner, David E, Chalasani, Naga, Sanyal, Arun J, and Network, NASH Clinical Research
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Biomedical and Clinical Sciences ,Clinical Sciences ,Chronic Liver Disease and Cirrhosis ,Digestive Diseases ,Clinical Research ,Liver Disease ,4.2 Evaluation of markers and technologies ,Detection ,screening and diagnosis ,Oral and gastrointestinal ,Good Health and Well Being ,Adolescent ,Adult ,Aged ,Aged ,80 and over ,Elasticity Imaging Techniques ,Fatty Liver ,Female ,Humans ,Liver Cirrhosis ,Male ,Middle Aged ,Non-alcoholic Fatty Liver Disease ,Prospective Studies ,ROC Curve ,Severity of Illness Index ,Young Adult ,NAFLD ,Fibroscan ,VCTE ,Vibration Controlled Transient Elastography ,Controlled Attenuation Parameter ,Fibrosis ,Steatosis ,NASH Clinical Research Network ,Gastroenterology & Hepatology ,Clinical sciences - Abstract
Background & aimsVibration-controlled transient elastography (VCTE), which measures liver stiffness, has become an important tool for evaluating patients with nonalcoholic fatty liver disease (NAFLD). We aimed to determine the diagnostic accuracy of VCTE in detection of NAFLD in a multicenter cohort of patients.MethodsWe performed a prospective study of 393 adults with NAFLD who underwent VCTE within 1 year of liver histology analysis (median time, 49 d; interquartile range, 25-78 d), from July 1, 2014, through July 31, 2017. Liver stiffness measurement (LSM) cut-off values for pairwise fibrosis stage and controlled attenuation parameter cut-off values for pairwise steatosis grade were determined using cross-validated area under the receiver operating characteristics curve (AUROC) analyses. Diagnostic statistics were computed at a sensitivity fixed at 90% and a specificity fixed at 90%.ResultsLSM identified patients with advanced fibrosis with an AUROC of 0.83 (95% CI, 0.79- 0.87) and patients with cirrhosis with an AUROC of 0.93 (95% CI, 0.90-0.97). At a fixed sensitivity, a cut-off LSM of 6.5 kPa excluded advanced fibrosis with a negative predictive value of 0.91, and a cut-off LSM of 12.1 kPa excluded cirrhosis with a negative predictive value of 0.99. At a fixed specificity, LSM identified patients with advanced fibrosis with a positive predictive value of 0.71 and patients with cirrhosis with a positive predictive value of 0.41. Controlled attenuation parameter analysis detected steatosis with an AUROC of 0.76 (95% CI, 0.64-0.87). In contrast, the VCTE was less accurate in distinguishing lower fibrosis stages, higher steatosis grades, or the presence of NASH.ConclusionsIn a prospective study of adults with NAFLD, we found VCTE to accurately distinguish advanced vs earlier stages of fibrosis, using liver histology as the reference standard.
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- 2019
16. Diagnostic accuracy of magnetic resonance imaging hepatic proton density fat fraction in pediatric nonalcoholic fatty liver disease
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Middleton, Michael S, Van Natta, Mark L, Heba, Elhamy R, Alazraki, Adina, Trout, Andrew T, Masand, Prakash, Brunt, Elizabeth M, Kleiner, David E, Doo, Edward, Tonascia, James, Lavine, Joel E, Shen, Wei, Hamilton, Gavin, Schwimmer, Jeffrey B, Sirlin, Claude B, and Network, for the NASH Clinical Research
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Biomedical and Clinical Sciences ,Clinical Sciences ,Clinical Research ,Digestive Diseases ,Biomedical Imaging ,Chronic Liver Disease and Cirrhosis ,Liver Disease ,Oral and gastrointestinal ,Adolescent ,Child ,Cross-Sectional Studies ,Cysteamine ,Cystine Depleting Agents ,Double-Blind Method ,Female ,Humans ,Liver ,Magnetic Resonance Imaging ,Male ,Non-alcoholic Fatty Liver Disease ,Prospective Studies ,Protons ,Sensitivity and Specificity ,NASH Clinical Research Network ,Medical Biochemistry and Metabolomics ,Immunology ,Gastroenterology & Hepatology ,Clinical sciences - Abstract
We assessed the performance of magnetic resonance imaging (MRI) proton density fat fraction (PDFF) in children to stratify hepatic steatosis grade before and after treatment in the Cysteamine Bitartrate Delayed-Release for the Treatment of Nonalcoholic Fatty Liver Disease in Children (CyNCh) trial, using centrally scored histology as reference. Participants had multiecho 1.5 Tesla (T) or 3T MRI on scanners from three manufacturers. Of 169 enrolled children, 110 (65%) and 83 (49%) had MRI and liver biopsy at baseline and at end of treatment (EOT; 52 weeks), respectively. At baseline, 17% (19 of 110), 28% (31 of 110), and 55% (60 of 110) of liver biopsies showed grades 1, 2, and 3 histological steatosis; corresponding PDFF (mean ± SD) values were 10.9 ± 4.1%, 18.4 ± 6.2%, and 25.7 ± 9.7%, respectively. PDFF classified grade 1 versus 2-3 and 1-2 versus 3 steatosis with areas under receiving operator characteristic curves (AUROCs) of 0.87 (95% confidence interval [CI], 0.80, 0.94) and 0.79 (0.70, 0.87), respectively. PDFF cutoffs at 90% specificity were 17.5% for grades 2-3 steatosis and 23.3% for grade 3 steatosis. At EOT, 47% (39 of 83), 41% (34 of 83), and 12% (10 of 83) of biopsies showed improved, unchanged, and worsened steatosis grade, respectively, with corresponding PDFF (mean ± SD) changes of -7.8 ± 6.3%, -1.2 ± 7.8%, and 4.9 ± 5.0%, respectively. PDFF change classified steatosis grade improvement and worsening with AUROCs (95% CIs) of 0.76 (0.66, 0.87) and 0.83 (0.73, 0.92), respectively. PDFF change cut-off values at 90% specificity were -11.0% and +5.5% for improvement and worsening.ConclusionMRI-estimated PDFF has high diagnostic accuracy to both classify and predict histological steatosis grade and change in histological steatosis grade in children with NAFLD. (Hepatology 2018;67:858-872).
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- 2018
17. Association of Retinal Vascular Caliber and Age-Related Macular Degeneration in Patients With the Acquired Immunodeficiency Syndrome
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Jabs, Douglas A, Van Natta, Mark L, Pak, Jeong Won, Danis, Ronald P, and Hunt, Peter W
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Neurodegenerative ,Macular Degeneration ,Prevention ,Eye Disease and Disorders of Vision ,HIV/AIDS ,Clinical Research ,Neurosciences ,Aging ,Eye ,Acquired Immunodeficiency Syndrome ,Adult ,Arterioles ,Cohort Studies ,Female ,Humans ,Male ,Middle Aged ,Photography ,Prospective Studies ,Retinal Artery ,Retinal Vein ,Risk Factors ,Venules ,acquired immunodeficiency syndrome ,age-related macular degeneration ,retinal vascular caliber ,Biological Sciences ,Medical and Health Sciences ,Ophthalmology & Optometry - Abstract
PurposeTo evaluate the relationship between retinal vascular caliber and AMD in patients with AIDS.MethodsParticipants enrolled in the Longitudinal Study of the Ocular Complications of AIDS had retinal photographs taken at enrollment. Retinal vascular caliber (central retinal artery equivalent [CRAE] and central retinal vein equivalent [CRVE]) and intermediate-stage AMD were determined from these retinal photographs. Photographs were evaluated by graders at a centralized reading center, using the Age-Related Eye Disease Study grading system for AMD and semiautomated techniques for evaluating retinal vascular caliber.ResultsOf the 1171 participants evaluated, 110 (9.4%) had AMD and 1061 (90.6%) did not. Compared with participants without AMD, participants with AMD had larger mean CRAEs (151 ± 16 μm versus 147 ± 16 μm; P = 0.009) and mean CRVEs (228 ± 24 μm versus 223 ± 25 μm; P = 0.02). The unadjusted differences were: CRAE, 4.3 μm (95% confidence interval [CI] 1.1-7.5; P = 0.009) and CRVE, 5.5 μm (95% CI 0.7-10.3; P = 0.02). After adjustment for age, race/ethnicity, sex, human immunodeficiency syndrome (HIV) transmission category, smoking, enrollment and nadir CD4+ T cells, and enrollment and maximum HIV load, the differences between patients with and without AMD were as follows: CRAE, 5.4 μm (95% CI 2.3-8.5; P = 0.001) and CRVE, 6.0 μm (95% CI 1.4-10.6; P = 0.01).ConclusionsIn patients with AIDS, AMD is associated with greater retinal arteriolar and venular calibers, suggesting a role for shared pathogenic mechanisms, such as persistent systemic inflammation.
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- 2018
18. Performance characteristics of vibration‐controlled transient elastography for evaluation of nonalcoholic fatty liver disease
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Vuppalanchi, Raj, Siddiqui, Mohammad S, Van Natta, Mark L, Hallinan, Erin, Brandman, Danielle, Kowdley, Kris, Neuschwander‐Tetri, Brent A, Loomba, Rohit, Dasarathy, Srinivas, Abdelmalek, Manal, Doo, Edward, Tonascia, James A, Kleiner, David E, Sanyal, Arun J, Chalasani, Naga, and Network, for the NASH Clinical Research
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Biomedical and Clinical Sciences ,Clinical Sciences ,Liver Disease ,Digestive Diseases ,Chronic Liver Disease and Cirrhosis ,Good Health and Well Being ,Adult ,Aged ,Biopsy ,Needle ,Body Mass Index ,Databases ,Factual ,Elasticity Imaging Techniques ,Female ,Humans ,Immunohistochemistry ,Logistic Models ,Male ,Middle Aged ,Multivariate Analysis ,Non-alcoholic Fatty Liver Disease ,Obesity ,Observer Variation ,Retrospective Studies ,Risk Assessment ,Severity of Illness Index ,Task Performance and Analysis ,Vibration ,NASH Clinical Research Network ,Medical Biochemistry and Metabolomics ,Immunology ,Gastroenterology & Hepatology ,Clinical sciences - Abstract
Vibration-controlled transient elastography estimates liver stiffness measurement (LSM) and controlled attenuation parameter (CAP), which are noninvasive assessments of hepatic fibrosis and steatosis, respectively. However, prior vibration-controlled transient elastography studies reported high failure rates in patients with nonalcoholic fatty liver disease. We examined the performance characteristics of the FibroScan 502 Touch with two probes, medium (M+) and extra large (XL+), in patients with nonalcoholic fatty liver disease in a multicenter setting. A total of 1,696 exams were attempted in 992 patients (body mass index, 33.6 ± 6.5 kg/m2 ) with histologically confirmed nonalcoholic fatty liver disease. Simultaneous assessment of LSM and CAP was performed using the FibroScan 502 Touch with an automatic probe selection tool. Testing was conducted twice in patients by either a single operator (87%) or two operators (13%). Failure was defined as the inability to obtain a valid examination. An examination was considered unreliable if LSM interquartile range/median was >30%. Significant disagreement between two readings was defined as >95% limits of agreement between two readings. A total of 1,641 examinations yielded valid results with a failure rate of 3.2% (55/1,696). The proportion of unreliable scans for LSM was 3.9%. The proportion of unreliable scans with operator experience in the top quartile (≥59 procedures) was significantly lower than that in the lower three quarters combined (1.6% versus 4.7%, P = 0.02 by Fisher's exact test). The significant disagreement between first and second readings for LSM and CAP when obtained back to back was 18% and 11%, respectively.ConclusionVibration-controlled transient elastography for estimation of LSM and CAP can be successfully deployed in a multicenter setting with low failure (3.2%) and high reliability (>95%) rates and high reproducibility. (Hepatology 2018;67:134-144).
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- 2018
19. Agreement Between Magnetic Resonance Imaging Proton Density Fat Fraction Measurements and Pathologist-Assigned Steatosis Grades of Liver Biopsies From Adults With Nonalcoholic Steatohepatitis
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Middleton, Michael S, Heba, Elhamy R, Hooker, Catherine A, Bashir, Mustafa R, Fowler, Kathryn J, Sandrasegaran, Kumar, Brunt, Elizabeth M, Kleiner, David E, Doo, Edward, Van Natta, Mark L, Lavine, Joel E, Neuschwander-Tetri, Brent A, Sanyal, Arun, Loomba, Rohit, Sirlin, Claude B, and Network, NASH Clinical Research
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Biomedical and Clinical Sciences ,Clinical Sciences ,Liver Disease ,Digestive Diseases ,Clinical Trials and Supportive Activities ,Biomedical Imaging ,Hepatitis ,Clinical Research ,Chronic Liver Disease and Cirrhosis ,Adiposity ,Adult ,Area Under Curve ,Biopsy ,Chenodeoxycholic Acid ,Female ,Humans ,Liver ,Magnetic Resonance Imaging ,Male ,Middle Aged ,Non-alcoholic Fatty Liver Disease ,ROC Curve ,Single-Blind Method ,FLINT ,NAFLD ,Direct Comparison ,Non-Invasive ,NASH Clinical Research Network ,Neurosciences ,Paediatrics and Reproductive Medicine ,Gastroenterology & Hepatology ,Clinical sciences ,Nutrition and dietetics - Abstract
Background & aimsWe assessed the diagnostic performance of magnetic resonance imaging (MRI) proton density fat fraction (PDFF) in grading hepatic steatosis and change in hepatic steatosis in adults with nonalcoholic steatohepatitis (NASH) in a multi-center study, using central histology as reference.MethodsWe collected data from 113 adults with NASH participating in a multi-center, randomized, double-masked, placebo-controlled, phase 2b trial to compare the efficacy cross-sectionally and longitudinally of obeticholic acid vs placebo. Hepatic steatosis was assessed at baseline and after 72 weeks of obeticholic acid or placebo by liver biopsy and MRI (scanners from different manufacturers, at 1.5T or 3T). We compared steatosis estimates by PDFF vs histology. Histologic steatosis grade was scored in consensus by a pathology committee. Cross-validated receiver operating characteristic (ROC) analyses were performed.ResultsAt baseline, 34% of subjects had steatosis grade 0 or 1, 39% had steatosis grade 2, and 27% had steatosis grade 3; corresponding mean PDFF values were 9.8%±3.7%, 18.1%±4.3%, and 30.1%±8.1%. PDFF classified steatosis grade 0-1 vs 2-3 with an area under the ROC curve (AUROC) of 0.95 (95% CI, 0.91-0.98), and grade 0-2 vs grade 3 steatosis with an AUROC of 0.96 (95% CI, 0.93-0.99). PDFF cut-off values at 90% specificity were 16.3% for grades 2-3 and 21.7% for grade 3, with corresponding sensitivities of 83% and 84%. After 72 weeks' of obeticholic vs placebo, 42% of subjects had a reduced steatosis grade (mean reduction in PDFF from baseline of 7.4%±8.7%), 49% had no change in steatosis grade (mean increase in PDFF from baseline of 0.3%±6.3%), and 9% had an increased steatosis grade (mean increase in PDFF from baseline of 7.7%±6.0%). PDFF change identified subjects with reduced steatosis grade with an AUROC of 0.81 (95% CI, 0.71-0.91) and increased steatosis grade with an AUROC of 0.81 (95% CI, 0.63-0.99). A PDFF reduction of 5.15% identified subjects with reduced steatosis grade with 90% specificity and 58% sensitivity, whereas a PDFF increase of 5.6% identified those with increased steatosis grade with 90% specificity and 57% sensitivity.ConclusionsBased on data from a phase 2 randomized controlled trial of adults with NASH, PDFF estimated by MRI scanners of different field strength and at different sites, accurately classifies grades and changes in hepatic steatosis when histologic analysis of biopsies is used as a reference.
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- 2017
20. Incidence of Intermediate-stage Age-related Macular Degeneration in Patients With Acquired Immunodeficiency Syndrome
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Jabs, Douglas A, Van Natta, Mark L, Pak, Jeong Won, Danis, Ronald P, and Hunt, Peter W
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Biomedical and Clinical Sciences ,Ophthalmology and Optometry ,Neurodegenerative ,Prevention ,Macular Degeneration ,Clinical Research ,HIV/AIDS ,Eye Disease and Disorders of Vision ,Aging ,2.4 Surveillance and distribution ,Aetiology ,2.1 Biological and endogenous factors ,Eye ,Good Health and Well Being ,Acquired Immunodeficiency Syndrome ,Adult ,Disease Progression ,Female ,Follow-Up Studies ,HIV ,Humans ,Male ,Prospective Studies ,Risk Assessment ,Risk Factors ,Severity of Illness Index ,United States ,Clinical Sciences ,Opthalmology and Optometry ,Public Health and Health Services ,Ophthalmology & Optometry ,Ophthalmology and optometry - Abstract
PurposeTo evaluate the incidence of intermediate-stage age-related macular degeneration (AMD) in patients with acquired immunodeficiency syndrome (AIDS).DesignCohort study.MethodsPatients enrolled in the Longitudinal Study of the Ocular Complications of AIDS (LSOCA) underwent 5- and 10-year follow-up retinal photographs. Intermediate-stage AMD (AREDS stage 3) was determined from these photographs by graders at a centralized Reading Center, using the Age-Related Eye Disease Study-2 grading system. The incidence of AMD in LSOCA was compared with that in the Multi-Ethnic Study of Atherosclerosis (MESA), a Human Immunodeficiency Virus (HIV)-uninfected cohort, which used a similar photographic methodology.ResultsThe incidence of AMD in LSOCA was 0.65/100 person-years (PY). In a multivariate analysis the only significant risk factor for AMD in LSOCA was smoking; the relative risk vs never-smokers was 3.4 for former smokers (95% confidence interval [CI] 1.3, 9.5; P = .02) and 3.3 for current smokers (95% CI 1.1, 9.7; P = .03). Compared with the MESA cohort, the race/ethnicity- and sex-adjusted risk of AMD in LSOCA was 1.75 (95% CI 1.16, 2.64; P = .008), despite the fact that the mean age of the MESA cohort was 17 years greater than the LSOCA cohort (61 ± 9 years vs 44 ± 8 years).ConclusionsPatients with AIDS have a 1.75-fold increased race- and sex-adjusted incidence of intermediate-stage AMD compared with that found in an HIV-uninfected cohort. This increased incidence is consistent with the increased incidence of other age-related diseases in antiretroviral-treated, immune-restored, HIV-infected persons when compared with HIV-uninfected persons.
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- 2017
21. In Children With Nonalcoholic Fatty Liver Disease, Cysteamine Bitartrate Delayed Release Improves Liver Enzymes but Does Not Reduce Disease Activity Scores
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Schwimmer, Jeffrey B, Lavine, Joel E, Wilson, Laura A, Neuschwander-Tetri, Brent A, Xanthakos, Stavra A, Kohli, Rohit, Barlow, Sarah E, Vos, Miriam B, Karpen, Saul J, Molleston, Jean P, Whitington, Peter F, Rosenthal, Philip, Jain, Ajay K, Murray, Karen F, Brunt, Elizabeth M, Kleiner, David E, Van Natta, Mark L, Clark, Jeanne M, Tonascia, James, Doo, Edward, Abrams, Stephanie H, Barlow, Sarah, Himes, Ryan, Krisnamurthy, Rajesh, Maldonado, Leanel, Mahabir, Rory, Bernstein, Kimberlee, Bramlage, Kristin, Cecil, Kim, DeVore, Stephanie, Lake, Kathleen, Podberesky, Daniel, Towbin, Alex, Xanthakos, Stavra, Behr, Gerald, Lefkowitch, Jay H, Mencin, Ali, Reynoso, Elena, Alazraki, Adina, Cleeton, Rebecca, Karpen, Saul, Munos, Jessica Cruz, Raviele, Nicholas, Vos, Miriam, Bozic, Molly, Cummings, Oscar W, Klipsch, Ann, Munson, Sarah, Sandrasegaran, Kumar, Subbarao, Girish, Kafka, Kimberly, Scheimann, Ann, Amsden, Katie, Fishbein, Mark H, Kirwan, Elizabeth, Mohammad, Saeed, Rigsby, Cynthia, Sharda, Lisa, Derdoy, Jose, Jain, Ajay, King, Debra, Osmack, Pat, Siegner, Joan, Stewart, Susan, Torretta, Susan, Wriston, Kristina, Baker, Susan S, Zhu, Lixin, Africa, Jonathon, Angeles, Jorge, Arroyo, Sandra, Awai, Hannah, Behling, Cynthia, Bross, Craig, Durelle, Janis, Middleton, Michael, Newton, Kimberly, Paiz, Melissa, Sanford, Jennifer, Sirlin, Claude, Ugalde-Nicalo, Patricia, Villarreal, Mariana Dominguez, Aouizerat, Bradley, Courtier, Jesse, Ferrell, Linda D, Fleck, Shannon, Gill, Ryan, Langlois, Camille, Perito, Emily Rothbaum, Tsai, Patrika, Cooper, Kara, Horslen, Simon, and Hsu, Evelyn
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Biomedical and Clinical Sciences ,Clinical Sciences ,Clinical Trials and Supportive Activities ,Chronic Liver Disease and Cirrhosis ,Clinical Research ,Hepatitis ,Liver Disease ,Digestive Diseases ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,Oral and gastrointestinal ,Adolescent ,Alanine Transaminase ,Aspartate Aminotransferases ,Biopsy ,Body Weight ,Child ,Cysteamine ,Cystine Depleting Agents ,Delayed-Action Preparations ,Double-Blind Method ,Female ,Humans ,Intention to Treat Analysis ,Liver ,Liver Cirrhosis ,Male ,Non-alcoholic Fatty Liver Disease ,Severity of Illness Index ,Pediatrics ,ALT ,AST ,Obesity ,NASH CRN ,Neurosciences ,Paediatrics and Reproductive Medicine ,Gastroenterology & Hepatology ,Clinical sciences ,Nutrition and dietetics - Abstract
Background & aimsNo treatment for nonalcoholic fatty liver disease (NAFLD) has been approved by regulatory agencies. We performed a randomized controlled trial to determine whether 52 weeks of cysteamine bitartrate delayed release (CBDR) reduces the severity of liver disease in children with NAFLD.MethodsWe performed a double-masked trial of 169 children with NAFLD activity scores of 4 or higher at 10 centers. From June 2012 to January 2014, the patients were assigned randomly to receive CBDR or placebo twice daily (300 mg for patients weighing ≤65 kg, 375 mg for patients weighing >65 to 80 kg, and 450 mg for patients weighing >80 kg) for 52 weeks. The primary outcome from the intention-to-treat analysis was improvement in liver histology over 52 weeks, defined as a decrease in the NAFLD activity score of 2 points or more without worsening fibrosis; patients without biopsy specimens from week 52 (17 in the CBDR group and 6 in the placebo group) were considered nonresponders. We calculated the relative risks (RR) of improvement using a stratified Cochran-Mantel-Haenszel analysis.ResultsThere was no significant difference between groups in the primary outcome (28% of children in the CBDR group vs 22% in the placebo group; RR, 1.3; 95% confidence interval [CI], 0.8-2.1; P = .34). However, children receiving CBDR had significant changes in prespecified secondary outcomes: reduced mean levels of alanine aminotransferase (reduction, 53 ± 88 U/L vs 8 ± 77 U/L in the placebo group; P = .02) and aspartate aminotransferase (reduction, 31 ± 52 vs 4 ± 36 U/L in the placebo group; P = .008), and a larger proportion had reduced lobular inflammation (36% in the CBDR group vs 21% in the placebo group; RR, 1.8; 95% CI, 1.1-2.9; P = .03). In a post hoc analysis of children weighing 65 kg or less, those taking CBDR had a 4-fold better chance of histologic improvement (observed in 50% of children in the CBDR group vs 13% in the placebo group; RR, 4.0; 95% CI, 1.3-12.3; P = .005).ConclusionsIn a randomized trial, we found that 1 year of CBDR did not reduce overall histologic markers of NAFLD compared with placebo in children. Children receiving CBDR, however, had significant reductions in serum aminotransferase levels and lobular inflammation. ClinicalTrials.gov no: NCT01529268.
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- 2016
22. Factors Predicting Visual Acuity Outcome in Intermediate, Posterior, and Panuveitis: The Multicenter Uveitis Steroid Treatment (MUST) Trial
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Kempen, John H, Van Natta, Mark L, Altaweel, Michael M, Dunn, James P, Jabs, Douglas A, Lightman, Susan L, Thorne, Jennifer E, Holbrook, Janet T, Jaffe, Glenn J, Branchaud, Brenda, Hahn, Paul, Koreen, Larry, Lad, Eleonora M, Lin, Phoebe, Martel, Joseph Nissim, Serrano, Neha, Skalak, Cindy, Vajzovic, Lejla, Baer, Claxton, Bryant, Joyce, Chavala, Sai, Cusick, Michael, Day, Shelley, Dayani, Pouya, Ehlers, Justis, Kesen, Muge, Lee, Annie, Melamud, Alex, Qureshi, Jawad A, Scott, Adrienne Williams, See, Robert F, Shuler, Robert K, Wood, Megan, Yeh, Steven, Fernandes, Alcides, Gibbs, Deborah, Leef, Donna, Martin, Daniel F, Srivastava, Sunil, Begum, Hosne, Boring, Jeff, Brotherson, Kristen L, Burkholder, Bryn, Butler, Nicholas J, Cain, Dennis, Cook, Mary A, Emmert, David, Graul, Janis R, Herring, Mark, Laing, Ashley, Leung, Theresa G, Mahon, Michael C, Moradi, Ahmafreza, Nwankwo, Antonia, Ostheimer, Trucian L, Reed, Terry, Arnold, Ellen, Barnabie, Patricia M, Belair, Marie-Lynn, Bolton, Stephen G, Brodine, Joseph B, Brown, Diane M, Brune, Lisa M, Galor, Anat, Gan, Theresa, Jacobowitz, Adam, Kapoor, Meera, Kedhar, Sanjay, Kim, Stephen, Leder, Henry A, Livingston, Alison G, Morton, Yavette, Nolan, Kisten, Peters, George B, Soto, Priscilla, Stevenson, Ricardo, Tarver-Carr, Michelle, Wang, Yue, Foster, C Stephen, Anesi, Stephen D, Bruner, Linda, Ceron, Olga, Hinkle, David M, Persons, Nancy, Wentworth, Bailey, Acevedo, Sarah, Anzaar, Fahd, Cesca, Tom, Contero, Angelica, Fitzpatrick, Kayleigh, Goronga, Faith, Johnson, Jyothir, Lebron, Karina Q, Marvell, Danielle, Morgan, Chandra, Patel, Nita, Pinto, Jennifer, Siddique, Sana S, and Sprague, Janet
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Clinical Trials and Supportive Activities ,Clinical Research ,Eye Disease and Disorders of Vision ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,Eye ,Aged ,Drug Implants ,Female ,Follow-Up Studies ,Glucocorticoids ,Humans ,Male ,Middle Aged ,Panuveitis ,Time Factors ,Tomography ,Optical Coherence ,Treatment Outcome ,Visual Acuity ,Multicenter Uveitis Steroid Treatment (MUST) Trial Research Group ,Clinical Sciences ,Opthalmology and Optometry ,Public Health and Health Services ,Ophthalmology & Optometry - Abstract
PurposeTo identify factors associated with best-corrected visual acuity (BCVA) presentation and 2-year outcome in 479 intermediate, posterior, and panuveitic eyes.DesignCohort study using randomized controlled trial data.MethodsMulticenter Uveitis Steroid Treatment (MUST) Trial masked BCVA measurements at baseline and at 2 years follow-up used gold-standard methods. Twenty-three clinical centers documented characteristics per protocol, which were evaluated as potential predictive factors for baseline BCVA and 2-year change in BCVA.ResultsBaseline factors significantly associated with reduced BCVA included age ≥50 vs 10 vs grade 0; cataract; macular thickening; and exudative retinal detachment. Over 2 years, eyes better than 20/50 and 20/50 or worse at baseline improved, on average, by 1 letter (P = .52) and 10 letters (P < .001), respectively. Both treatment groups and all sites of uveitis improved similarly. Factors associated with improved BCVA included resolution of active AC cells, resolution of macular thickening, and cataract surgery in an initially cataractous eye. Factors associated with worsening BCVA included longer duration of uveitis (6-10 or >10 vs
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- 2015
23. APOL1 variant alleles associate with reduced risk for opportunistic infections in HIV infection
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An, Ping, Sezgin, Efe, Kirk, Gregory D., Duggal, Priya, Binns-Roemer, Elizabeth, Nelson, George, Limou, Sophie, Van Natta, Mark L., Jabs, Douglas A., Estrella, Michelle, Kopp, Jeffrey B., and Winkler, Cheryl A.
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- 2021
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24. Association of elevated plasma inflammatory biomarker levels with age-related macular degeneration but not cataract in persons with AIDS
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Jabs, Douglas A., Van Natta, Mark L., Schneider, Michael F., Pak, Jeong Won, Trang, Garrett, Jones, Norman G., Milush, Jeffrey, and Hunt, Peter W.
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- 2022
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25. Farnesoid X nuclear receptor ligand obeticholic acid for non-cirrhotic, non-alcoholic steatohepatitis (FLINT): a multicentre, randomised, placebo-controlled trial
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Neuschwander-Tetri, Brent A, Loomba, Rohit, Sanyal, Arun J, Lavine, Joel E, Van Natta, Mark L, Abdelmalek, Manal F, Chalasani, Naga, Dasarathy, Srinivasan, Diehl, Anna Mae, Hameed, Bilal, Kowdley, Kris V, McCullough, Arthur, Terrault, Norah, Clark, Jeanne M, Tonascia, James, Brunt, Elizabeth M, Kleiner, David E, Doo, Edward, and Network, for the NASH Clinical Research
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Biomedical and Clinical Sciences ,Clinical Sciences ,Clinical Research ,Diabetes ,Liver Disease ,Chronic Liver Disease and Cirrhosis ,Clinical Trials and Supportive Activities ,Digestive Diseases ,Hepatitis ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,Oral and gastrointestinal ,Administration ,Oral ,Chenodeoxycholic Acid ,Cholesterol ,HDL ,Cholesterol ,LDL ,Double-Blind Method ,Female ,Humans ,Liver ,Liver Cirrhosis ,Male ,Middle Aged ,Non-alcoholic Fatty Liver Disease ,Receptors ,Cytoplasmic and Nuclear ,Treatment Outcome ,Weight Loss ,NASH Clinical Research Network ,Medical and Health Sciences ,General & Internal Medicine ,Biomedical and clinical sciences ,Health sciences - Abstract
BackgroundThe bile acid derivative 6-ethylchenodeoxycholic acid (obeticholic acid) is a potent activator of the farnesoid X nuclear receptor that reduces liver fat and fibrosis in animal models of fatty liver disease. We assessed the efficacy of obeticholic acid in adult patients with non-alcoholic steatohepatitis.MethodsWe did a multicentre, double-blind, placebo-controlled, parallel group, randomised clinical trial at medical centres in the USA in patients with non-cirrhotic, non-alcoholic steatohepatitis to assess treatment with obeticholic acid given orally (25 mg daily) or placebo for 72 weeks. Patients were randomly assigned 1:1 using a computer-generated, centrally administered procedure, stratified by clinical centre and diabetes status. The primary outcome measure was improvement in centrally scored liver histology defined as a decrease in non-alcoholic fatty liver disease activity score by at least 2 points without worsening of fibrosis from baseline to the end of treatment. A planned interim analysis of change in alanine aminotransferase at 24 weeks undertaken before end-of-treatment (72 weeks) biopsies supported the decision to continue the trial (relative change in alanine aminotransferase -24%, 95% CI -45 to -3). A planned interim analysis of the primary outcome showed improved efficacy of obeticholic acid (p=0·0024) and supported a decision not to do end-of-treatment biopsies and end treatment early in 64 patients, but to continue the trial to obtain the 24-week post-treatment measures. Analyses were done by intention-to-treat. This trial was registered with ClinicalTrials.gov, number NCT01265498.FindingsBetween March 16, 2011, and Dec 3, 2012, 141 patients were randomly assigned to receive obeticholic acid and 142 to placebo. 50 (45%) of 110 patients in the obeticholic acid group who were meant to have biopsies at baseline and 72 weeks had improved liver histology compared with 23 (21%) of 109 such patients in the placebo group (relative risk 1·9, 95% CI 1·3 to 2·8; p=0·0002). 33 (23%) of 141 patients in the obeticholic acid developed pruritus compared with nine (6%) of 142 in the placebo group.InterpretationObeticholic acid improved the histological features of non-alcoholic steatohepatitis, but its long-term benefits and safety need further clarification.FundingNational Institute of Diabetes and Digestive and Kidney Diseases, Intercept Pharmaceuticals.
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- 2015
26. Gut Epithelial Barrier Dysfunction and Innate Immune Activation Predict Mortality in Treated HIV Infection
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Hunt, Peter W, Sinclair, Elizabeth, Rodriguez, Benigno, Shive, Carey, Clagett, Brian, Funderburg, Nicholas, Robinson, Janet, Huang, Yong, Epling, Lorrie, Martin, Jeffrey N, Deeks, Steven G, Meinert, Curtis L, Van Natta, Mark L, Jabs, Douglas A, and Lederman, Michael M
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Medical Microbiology ,Biomedical and Clinical Sciences ,Immunology ,HIV/AIDS ,Infectious Diseases ,Sexually Transmitted Infections ,Aetiology ,2.1 Biological and endogenous factors ,Infection ,Inflammatory and immune system ,Good Health and Well Being ,Adult ,Blood Coagulation ,Case-Control Studies ,Female ,HIV Infections ,Humans ,Immunity ,Innate ,Inflammation ,Intestinal Mucosa ,Lymphocyte Activation ,Male ,Middle Aged ,T-Lymphocytes ,HIV ,gut epithelial cell barrier ,intestinal fatty acid binding protein ,zonulin-1 ,sCD14 ,IL-6 ,D-dimer ,hsCRP ,cytomegalovirus ,CD57 ,CD28 ,CD38 ,HLA-DR ,T-cell activation ,mortality ,antiretroviral therapy ,immune activation ,Biological Sciences ,Medical and Health Sciences ,Microbiology ,Biological sciences ,Biomedical and clinical sciences ,Health sciences - Abstract
BackgroundWhile inflammation predicts mortality in treated human immunodeficiency virus (HIV) infection, the prognostic significance of gut barrier dysfunction and phenotypic T-cell markers remains unclear.MethodsWe assessed immunologic predictors of mortality in a case-control study within the Longitudinal Study of the Ocular Complications of AIDS (LSOCA), using conditional logistic regression. Sixty-four case patients who died within 12 months of treatment-mediated viral suppression were each matched to 2 control individuals (total number of controls, 128) by duration of antiretroviral therapy-mediated viral suppression, nadir CD4(+) T-cell count, age, sex, and prior cytomegalovirus (CMV) retinitis. A similar secondary analysis was conducted in the SCOPE cohort, which had participants with less advanced immunodeficiency.ResultsPlasma gut epithelial barrier integrity markers (intestinal fatty acid binding protein and zonulin-1 levels), soluble CD14 level, kynurenine/tryptophan ratio, soluble tumor necrosis factor receptor 1 level, high-sensitivity C-reactive protein level, and D-dimer level all strongly predicted mortality, even after adjustment for proximal CD4(+) T-cell count (all P ≤ .001). A higher percentage of CD38(+)HLA-DR(+) cells in the CD8(+) T-cell population was a predictor of mortality before (P = .031) but not after (P = .10) adjustment for proximal CD4(+) T-cell count. Frequencies of senescent (defined as CD28(-)CD57(+) cells), exhausted (defined as PD1(+) cells), naive, and CMV-specific T cells did not predict mortality.ConclusionsGut epithelial barrier dysfunction, innate immune activation, inflammation, and coagulation-but not T-cell activation, senescence, and exhaustion-independently predict mortality in individuals with treated HIV infection with a history of AIDS and are viable targets for interventions.
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- 2014
27. Diagnostic Accuracy of Noninvasive Fibrosis Models to Detect Change in Fibrosis Stage
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Allende, Daniela, Dasarathy, Srinivasan, McCullough, Arthur J., Penumatsa, Revathi, Dasarathy, Jaividhya, Lavine, Joel E., Abdelmalek, Manal F., Bashir, Mustafa, Buie, Stephanie, Diehl, Anna Mae, Guy, Cynthia, Kigongo, Christopher, Kopping, Mariko, Malik, David, Piercy, Dawn, Chalasani, Naga, Cummings, Oscar W., Gawrieh, Samer, Ragozzino, Linda, Sandrasegaran, Kumar, Vuppalanchi, Raj, Brunt, Elizabeth M., Cattoor, Theresa, Carpenter, Danielle, Freebersyser, Janet, King, Debra, Lai, Jinping, Neuschwander-Tetri, Brent A., Siegner, Joan, Stewart, Susan, Torretta, Susan, Wriston, Kristina, Gonzalez, Maria Cardona, Davila, Jodie, Jhaveri, Manan, Kowdley, Kris V., Mukhtar, Nizar, Ness, Erik, Poitevin, Michelle, Quist, Brook, Soo, Sherilynn, Ang, Brandon, Behling, Cynthia, Bhatt, Archana, Loomba, Rohit, Middleton, Michael S., Sirlin, Claude, Akhter, Maheen F., Bass, Nathan M., Brandman, Danielle, Gill, Ryan, Hameed, Bilal, Maher, Jacqueline, Terrault, Norah, Ungermann, Ashley, Yeh, Matthew, Boyett, Sherry, Contos, Melissa J., Kirwin, Sherri, Luketic, Velimir A.C., Puri, Puneet, Sanyal, Arun J., Schlosser, Jolene, Siddiqui, Mohammad S., Yost-Schomer, Leslie, Fowler, Kathryn, Kleiner, David E., Doo, Edward C., Hall, Sherry, Hoofnagle, Jay H., Lee, Jessica J., Robuck, Patricia R., Sherker, Averell H., Torrance, Rebecca, Belt, Patricia, Clark, Jeanne M., Dodge, John, Donithan, Michele, Hallinan, Erin, Isaacson, Milana, Lazo, Mariana, Meinert, Jill, Miriel, Laura, Smith, Jacqueline, Smith, Michael, Sternberg, Alice, Tonascia, James, Van Natta, Mark L., Wagoner, Annette, Wilson, Laura A., Yamada, Goro, Yates, Katherine, Siddiqui, Mohammad Shadab, Van Natta, Mark, and Neuschwander-Tetri, Brent
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- 2019
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28. Ethnic, Racial, and Sex Differences in Etiology, Symptoms, Treatment, and Symptom Outcomes of Patients With Gastroparesis
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Parkman, Henry P., Yamada, Goro, Van Natta, Mark L., Yates, Katherine, Hasler, William L., Sarosiek, Irene, Grover, Madhusudan, Schey, Ron, Abell, Thomas L., Koch, Kenneth L., Kuo, Braden, Clarke, John, Farrugia, Gianrico, Nguyen, Linda, Snape, William J., Miriel, Laura, Tonascia, James, Hamilton, Frank, Pasricha, Pankaj J., and McCallum, Richard W.
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- 2019
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29. HIV-infected individuals with low CD4/CD8 ratio despite effective antiretroviral therapy exhibit altered T cell subsets, heightened CD8+ T cell activation, and increased risk of non-AIDS morbidity and mortality.
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Serrano-Villar, Sergio, Sainz, Talia, Lee, Sulggi A, Hunt, Peter W, Sinclair, Elizabeth, Shacklett, Barbara L, Ferre, April L, Hayes, Timothy L, Somsouk, Ma, Hsue, Priscilla Y, Van Natta, Mark L, Meinert, Curtis L, Lederman, Michael M, Hatano, Hiroyu, Jain, Vivek, Huang, Yong, Hecht, Frederick M, Martin, Jeffrey N, McCune, Joseph M, Moreno, Santiago, and Deeks, Steven G
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T-Lymphocyte Subsets ,CD8-Positive T-Lymphocytes ,Humans ,HIV-1 ,HIV Infections ,Anti-HIV Agents ,Lymphocyte Count ,CD4-CD8 Ratio ,Treatment Outcome ,Antiretroviral Therapy ,Highly Active ,Morbidity ,Mortality ,Risk Factors ,Case-Control Studies ,Cohort Studies ,Lymphocyte Activation ,Adult ,Female ,Male ,Virology ,Microbiology ,Immunology ,Medical Microbiology - Abstract
A low CD4/CD8 ratio in elderly HIV-uninfected adults is associated with increased morbidity and mortality. A subset of HIV-infected adults receiving effective antiretroviral therapy (ART) fails to normalize this ratio, even after they achieve normal CD4+ T cell counts. The immunologic and clinical characteristics of this clinical phenotype remain undefined. Using data from four distinct clinical cohorts and three clinical trials, we show that a low CD4/CD8 ratio in HIV-infected adults during otherwise effective ART (after CD4 count recovery above 500 cells/mm3) is associated with a number of immunological abnormalities, including a skewed T cell phenotype from naïve toward terminally differentiated CD8+ T cells, higher levels of CD8+ T cell activation (HLADR+CD38+) and senescence (CD28- and CD57+CD28-), and higher kynurenine/tryptophan ratio. Changes in the peripheral CD4/CD8 ratio are also reflective of changes in gut mucosa, but not in lymph nodes. In a longitudinal study, individuals who initiated ART within six months of infection had greater CD4/CD8 ratio increase compared to later initiators (>2 years). After controlling for age, gender, ART duration, nadir and CD4 count, the CD4/CD8 ratio predicted increased risk of morbidity and mortality. Hence, a persistently low CD4/CD8 ratio during otherwise effective ART is associated with increased innate and adaptive immune activation, an immunosenescent phenotype, and higher risk of morbidity/mortality. This ratio may prove useful in monitoring response to ART and could identify a unique subset of individuals needed of novel therapeutic interventions.
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- 2014
30. Factors Predicting Visual Acuity Outcome in Intermediate, Posterior, and Panuveitis: The Multicenter Uveitis Steroid Treatment (MUST) Trial
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Jaffe, Glenn J., Branchaud, Brenda, Hahn, Paul, Koreen, Larry, Lad, Eleonora (Nora) M., Lin, Phoebe, Martel, Joseph Nissim, Serrano, Neha (Shah), Skalak, Cindy, Vajzovic, Lejla, Baer, Claxton, Bryant, Joyce, Chavala, Sai, Cusick, Michael, Day, Shelley, Dayani, Pouya, Ehlers, Justis, Kesen, Muge, Lee, Annie, Melamud, Alex, Qureshi, Jawad A., Scott, Adrienne Williams, See, Robert F., Shuler, Robert K., Wood, Megan, Yeh, Steven, Fernandes, Alcides, Gibbs, Deborah, Leef, Donna, Martin, Daniel F., Srivastava, Sunil, Dunn, James P., Begum, Hosne, Boring, Jeff, Brotherson, Kristen L., Burkholder, Bryn, Butler, Nicholas J., Cain, Dennis, Cook, Mary A., Emmert, David, Graul, Janis R., Herring, Mark, Laing, Ashley, Leung, Theresa G., Mahon, Michael C., Moradi, Ahmafreza, Nwankwo, Antonia, Ostheimer, Trucian L., Reed, Terry, Arnold, Ellen, Barnabie, Patricia M., Belair, Marie-Lynn, Bolton, Stephen G., Brodine, Joseph B., Brown, Diane M., Brune, Lisa M., Galor, Anat, Gan, Theresa, Jacobowitz, Adam, Kapoor, Meera, Kedhar, Sanjay, Kim, Stephen, Leder, Henry A., Livingston, Alison G., Morton, Yavette, Nolan, Kisten, Peters, George B., Soto, Priscilla, Stevenson, Ricardo, Tarver-Carr, Michelle, Wang, Yue, Foster, C. Stephen, Anesi, Stephen D., Bruner, Linda, Ceron, Olga, Hinkle, David M., Persons, Nancy, Wentworth, Bailey, Acevedo, Sarah, Anzaar, Fahd, Cesca, Tom, Contero, Angelica, Fitzpatrick, Kayleigh, Goronga, Faith, Johnson, Jyothir, Lebron, Karina Q., Marvell, Danielle, Morgan, Chandra, Patel, Nita, Pinto, Jennifer, Siddique, Sana S., Sprague, Janet, Yilmaz, Taygan, Sen, H. Nida, Bono, Michael, Cunningham, Denise, Hayes, Darryl, Koutsandreas, Dessie, Nussenblatt, Robert B., Sherry, Patti R., Short, Gregory L., Smith, Wendy, Temple, Alana, Bamji, Allison, Coleman, Hanna, Davuluri, Geetaniali, Faia, Lisa, Gottlieb, Chloe, Jirawuthiworavong, Guy V., Lew, Julie C., Mercer, Richard, Obiyor, Dominic, Perry, Cheryl H., Potapova, Natalia, Weichel, Eric, Wroblewski, Keith J., Latkany, Paul A., Coonan, Corinne, Honda, Andrea, Lorenzo-Latkany, Monica, Masini, Robert, Morell, Susan, Nguyen, Angela, Badamo, Jason, Boyd, Kenneth M., Enos, Matthew, Gallardo, Jenny, Jarczynski, Jacek, Lee, Ji Yun, McGrosky, Mirjana, Nour, Ann, Sanchez, Meredith, Steinberg, Kate, Stawell, Richard J., Breayley, Lisa, D'Sylva, Carly, Glatz, Elizabeth, Hodgson, Lauren, Lim, Lyndell, Ling, Cecilia, McIntosh, Rachel, Morrison (Ewing), Julie, Newton, Andrew, Sanmugasundram, Sutha, Smallwood, Richard, Zamir, Ehud, Hunt, Nicola, Jones, Lisa, Koukouras, Ignatios, Williams, Suzanne, Merrill, Pauline T., Carns, Danielle, Richine, Len, Voskuil-Marre, Denise L., Woo, Kisung, Gaynes, Bruce, Giannoulis, Christina, Hulvey, Pam, Kernbauer, Elaine, Khan, Heena S., Levine, Sarah J., Toennessen, Scott, Tonner, Eileen, Wang, Robert C., Aguado, Hank, Arceneaux, Sally, Duignan, Karen, Fish, Gary E., Hesse, Nick, Jaramillo, Diana, Mackens, Michael, Arnwine, Jean, Callanan, David, Cummings, Kimberly, Gray, Keith, Howden, Susie, Mutz, Karin, Sanchez, Brenda, Lightman, Susan, Ismetova, Filis, Prytherch, Ashley, Seguin-Greenstein, Sophie, Tomkins, Oren, Bar, Asat, Edwards, Kate, Joshi, Lavanish, Moraji, Jiten, Samy, Ahmed, Stubbs, Timothy, Taylor, Simon, Towler, Hamish, Tronnberg, Rebecca, Holland, Gary N., Almanzor, Robert D., Castellanos, Jose, Hubschman, Jean Pierre, Johiro, Ann K., Kukuyev, Alla, Levinson, Ralph D., McCannel, Colin A., Ransome, Susan S., Gonzales, Christine R., Gupta, Anurag, Kalyani, Partho S., Kapamajian, Michael A., Kappel, Peter J., Arcinue, Cheryl, Chuang, Janne, Barteselli, Giulio, Currie, Glenn, Mendoza, Veronica, Powell, Debbie, Clark, Tom, Cochran, Denine E., Freeman, William R., Hedaya, Joshua, Kemper, Tiara, Kozak, Igor, LeMoine, Jacqueline M., Loughran, Megan E., Magana, Luzandra, Mojana, Francesca, Morrison, Victoria, Nguyen, Vivian, Oster, Stephen F., Acharya, Nisha, Clay, David, Lee, Salena, Lew, Mary, Margolis, Todd P., Stewart, Jay, Wong, Ira G., Brown, Debra, Khouri, Claire M., Goldstein, Debra A., Birnbaum, Andrea, Degillio, Andrea, Rosa, Gemma De la, Ramirez, Carmen, Simjanowski, Evica, Skelly, Mariner, Castro-Malek, Anna L., Crooke, Catherine E., Huntley, Melody, Nash, Katrina, Niec, Marcia, Pyatetsky, Dimitry, Ramirez, Misel, Rozenbajgier, Zuzanna, Tessler, Howard H., Davis, Janet L., Albini, Thomas A., Chin, Marie, Castaño, Daniela, Elizondo, Ariana, Ho, Macy, Kovach, Jaclyn L., Lin, Richard C-S., Mandelcorn, Efrem, Nguyen, Jackie K-D., Pacini, Aura, Pineda, Susan, Pinto, David A., Rebimbas, Jose, Stepien, Kimberly E., Teran, Claudia, Elner, Susan G., Bernard, Hillary, Fournier, Linda, Godsey, Lindsay, Goings, Linda, Hackel, Richard, Hesselgrave, Moella, Jayasundera, K. Thiran, Prusak, Robert, Titus, Pamela, Bergeron, Melissa, Blosser, Reneé, Brown, Rebecca, Chrisman-McClure, Carrie, Gothrup, Julie R., Saxe, Stephen J., Sizemore, Deanna, Kempen, John H., Berger, James, Drossner, Sheri, DuPont, Joan C., Maguire, Albert M., Petner, Janice, Engelhard, Stephanie, Hopkins, Tim, Lo, Jonathan, McCall, Dawn, McRay, Monique, Salvo, Rebecca, Will, Daniel, Xu, Wei, Windsor, Elizabeth, Weeney, Laurel, Pavan, Peter R., Albritton, Ken, Leto, JoAnn, Madow, Brian, Mayor, Lori, Pautler, Scott E., Saxon, Wyatt, Soto, Judy, Goldstein, Burton, Klukoff, Amy, Lambright, Lucy, McDonald, Kim, Ortiz, Maria, Scymanky, Susan, Szalay, Dee Dee, Rao, Narsing, Davis, Tamara, Douglass, Jackie, Linton, Judith, Padilla, Margaret, Ramos, Sylvia, Rao, Narsing A., Aguirre, Alexia, Chong, Lawrence, Cisneros, Lupe, Corona, Elizabeth, Eliott, Dean, Fawzi, Amani, Garcia, Jesse, Khurana, Rahul, Lim, Jennifer, Mead, Rachel, Tsai, Julie H., Vitale, Albert, Bernstein, Paul S., Carlstrom, Bonnie, Gilman, James, Hanseen, Sandra, Morris, Paula, Ramirez, Diana, Wegner, Kimberley, Sheppard, John D., Anthony, Brianne, Casper, Amber, Felix-Kent, Lisa, Fernandez, Jeanette, Johnson, Tari, Scoper, Stephen V., Cole, R. Denise, Crawford, Nancy, Franklin, Lisa, Hamelin, Krista, Martin, Jen, Marx, Rebecca, Schultz, Gregory, Webb, Joseph, Yeager, Pamela, Kim, Rosa Y., Benz, Matthew S., Brown, David M., Chen, Eric, Fish, Richard H., Kegley, Eric, Shawver, Laura, Wong, Tien P., De La Garza, Rebecca, Friday (Hay), Shayla, Rao, P. Kumar, Adcock, Eve, Apte, Rajendra S., Baladenski, Amy, Curtis, Rhonda, Gould, Sarah, Hebden, Amanda, Kambarian, Jamie, Meyer, Charla, Pistorius, Sam, Quinn, Melanie, Rathert, Greg, Blinder, Kevin J., Hartz, Ashley, Light, Pam, Shah, Gaurav K., VanGelder, Russell, Jabs, Douglas A., Altaweel, Michael M., Holbrook, Janet T., Kurinij, Natalie, Brown, Diane, Prusakowski, Nancy, Thorne, Jennifer E., Hubbard, Larry, Wittes, Janet, Barlow, William E., Hochberg, Marc, Lyon, Alice T., Palestine, Alan G., Simon, Lee S., Rosenbaum, James T., Smith, Harmon, Davis, Janet, Thorne, Jennifer, Acharya, Nisha R., Vitale, Albert T., Boring, Jeffrey A., Alexander, Judith, Ng, Wai Ping, Friedman, David S., Adler, Anna, Burke, Alyce, Katz, Joanne, Reed, Susan, Ansari, Husam, Cohen, Nicholas, Modak, Sanjukta, Sugar, Elizabeth A., Burke, Alyce E., Drye, Lea T., Van Natta, Mark L., Frick, Kevin, Katz, JoAnn, Louis, Thomas A., Shade, David, Pascual, Karen, Slutsky-Sanon, Jill S., Allen, Amanda, Glomp, Colby, Hilal, Yasmin, Nieves, Melissa A., Stevens, Maria, Abreu, Francis, Casper, Anne Shanklin, Ewing, Cathleen, Hart, Adante, Lears, Andrea, Li, Shirley, Meinert, Jill, Morrison, Vinnette, Nowakowski, Deborah, Reyes, Girlie, Shade, Dave M., Smith, Jacqueline, Steuernagle, Karen, Van Natta, Mark, Venugopal, Vidya, Yu, Tsung, Chen, Paul, Collins, Karen, Dodge, John, Frick, Kevin D., Jackson, Rosetta, Jimenez, Christian, Landers, Ariel, Livingston, Hope, Meinert, Curtis L., Rayapudi, Sobharani, Shen, Weijiang, Shiflett, Charles, Smith, Rochelle, Tieman, Ada, Tonascia, James A., Zheng, Richard, Allan, James, Benz, Wendy K., Domalpally, Amitha, Johnson, Kristine A., Myers, Dawn J., Won Pak, Jeong, Reimers, James L., Chambers, Geoffrey, Christianson, Debra J., Fleischli, Margaret A., Freund, Jacquelyn, Gama, Vonnie, Gangaputra, Sapna, Glander, Kathleen E., Goulding, Anne, Hafford, Dennis, Harris, Susan E., Hubbard, Larry D., Joyce, Jeffrey M., Kruse, Christina N., Nagle, Lauren, Padden-Lechten, Gwyn E., Pohlman, Alyson, Remm, Amy, Shaw, Ruth A., Sivesind, Peggy, Thayer, Dennis, Treichel, Erika, Warren, Kelly J., Watson, Sheila M., Webster, Mary K., White, James K., Wilhelmson, Tara, Zhang, Grace, and Lightman, Susan L.
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- 2015
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31. Airway Obstruction Worsens in Young Adults with Asthma Who Become Obese
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Williams, Paul, Lasley, Mary V., Chinn, Tamara, Hinatsu, Michele, Furukawa, Clifton T., Altman, Leonard C., Virant, Frank S., Kennedy, Michael S., Tilles, Stephen, Becker, Jonathan W., Bierman, C. Warren, Crawford, Dan, DuHamel, Thomas, Eliassen, Heather, Hammond, Babi, MacLaren, Miranda, Minotti, Dominick A., Reagan, Chris, Shapiro, Gail, Sharpe, Marian, Tatum, Ashley, White, Grace, Wighton, Timothy G., Fuhlbrigge, Anne, Plunkett, Anne, Madden, Nancy, Anderson, Susan, Boehnert, Mark, Feins, Anita, Gentile, Amanda, Kandror, Natalia, MacAulay, Kelly, Sampong, Ernestina, Weiss, Scott, Torda, Walter, Tata, Martha, Babigian, Sally, Barrant, Peter, Benson, Linda, Caicedo, Jose, Calder, Tatum, Darcy, Christine, DeFilippo, Anthony, Dorsainvil, Cindy, Erickson, Julie, Fulton, Phoebe, Grace, Mary, Gilbert, Jennifer, Greineder, Dirk, Haynes, Stephanie, Higham, Margaret, Jakubowski, Deborah, Kelleher, Susan, Koslof, Jay, Mandel, Dana, Martin, Patricia, Martinez, Agnes, McAuliffe, Jean, Nakamoto, Erika, Pacella, Paola, Parks, Paula, Sagarin, Johanna, Seligsohn, Kay, Swords, Susan, Syring, Meghan, Traylor, June, Van Horn, Melissa, Wells, Carolyn, Whitman, Ann, Grasemann, Hartmut, Miki, Melody, Solomon, Melinda, Subbarao, Padmaja, MacLusky, Ian, Reisman, Joe, Levison, Henry, Hall, Anita, Benedet, Yola, Carpenter, Susan, Chay, Jennifer, Collinson, Michelle, Finlayson-Kulchin, Jane, Gore, Kenneth, Hipolito, Nina, Holmes, Noreen, Hoorntje, Erica, Klassen, Sharon, Quenneville, Joseé, Sananes, Renée, Wasson, Christine, Wilson, Margaret, Adkinson, N. Franklin, Jr., Bull, Deborah, Philips, Stephanie, Eggleston, Peyton, Huss, Karen, Plotnick, Leslie, Pulsifer, Margaret, Rand, Cynthia, Aylward, Elizabeth, Bollers, Nancy, Pessaro, Kathy, Wheeler, Barbara, Szefler, Stanley, Covar, Ronina, Nelson, Harold S., Bender, Bruce, Liu, Andrew, Sundström, D., Phillips, Melanie, White, Michael P., Gleason, Melanie, Brelsford, Kristin, Bridges, Jessyca, Ciacco, Jody, Eltz, Michael, Feeley, Jeryl, Flynn, Michael, Junk-Blanchard, Tara, Hassell, Joseph, Hefner, Marcia, Hendrickson, Caroline, Hettleman, Daniel, Irvin, Charles G., Kamada, Alan, Krawiec, Marzena, Larsen, Gary, Nimmagadda, Sai, Sandoval, Kendra, Sheridan, Jessica, Spahn, Joseph, Spears, Gayle, Washington, Trella, Willcutt, Eric, Cardona, Ivan, Carel, Kirstin, Doshi, Jayna, Hendershot, Rich, Jacobs, Jeffrey, Jain, Neal, Kang, June-ku Brian, Kruzick, Tracy, Leo, Harvey, Macomber, Beth, Malka, Jonathan, Mjaanes, Chris, Prpich, John, Stewart, Lora, Song, Ben, Tamesis, Grace, Zeiger, Robert S., Friedman, Noah, Mellon, Michael H., Schatz, Michael, Long, Terrie, Macaraeg, Travis, Christensen, Sandra, Easton, James G., Feinberg, M., Galbreath, Linda L., Gulczynski, Jennifer, Harden, Kathleen, Hansen, Ellen, Jalowayski, Al, Jenson, Elaine, Lincoln, Alan, Kaufman, Jennie, King, Shirley, Lopez, Brian, Magiari-Ene, Michaela, Mostafa, Kathleen, Moscona, Avraham, Nelle, Catherine A., Powers, Jennifer, Rodriguez, Elsa, Rodriguez, Eva, Sandoval, Karen, Wilson, Nevin W., Raissy, Hengameh H., Jacobs, Aaron, Kelly, H. William, Spicher, Mary, Batson, Christina, Harkings, Michelle, McCallum, Katie, Annett, Robert, Archibeque, Teresa, Bashir, Naim, Bereket, H. Selda, Braun, Marisa, Bush, Carrie, Bush, Shannon C., Clayton, Michael, Colon-Semidey, Angel, Devault, Sara, Esparham, Anna, Grad, Roni, Hunt, David, Larsson, Jeanne, McClelland, Sandra, McWilliams, Bennie, Montoya, Elisha, Moreshead, Margaret, Murphy, Shirley, Ortega, Barbara, Weers, David, Zayas, Jose, Strunk, Robert C., Bacharier, Leonard, Rodgers, Denise, Albers, Ellen, Belle, Gregg, Bloomberg, Gordon R., Buchanan, W. Patrick, Caesar, Mary, Corry, James M., DeMuth, Karen, Dolinsky, Marisa, Fisher, Edwin B., Gaioni, Stephen J., Glynn, Emily, Heckman, Bernadette D., Kemp, Debra, Kertz, Lila, Lawhon, Claire, Morgan, Valerie, Moseid, Cynthia, Oliver-Welker, Tina, Richardson, Diana, Ryan, Elizabeth, Sagal, Sharon, Smith, Thomas F., Sylvia, Susan, Turner, Carl, White, Deborah K., Tonascia, James, Belt, Patricia, Collins, Karen, Collison, Betty, Dodge, John, Donithan, Michele, Ewing, Cathleen, Jackson, Rosetta, May, Patrick, Meinert, Jill, Reyes, Girlie, Smith, Michael, Sternberg, Alice L., Van Natta, Mark L., Wagoner, Annette, Wilson, Laura, Wise, Robert, Yates, Katherine, Taggart, Virginia, Eggers, Lois, Kiley, James, Moore, Howard, Zheng, Gang, Albert, Paul, Hurd, Suzanne, Parker, Sydney, Randall, Pamela, Wu, Margaret, Cloutier, Michelle, Connett, John, Cuttler, Leona, Gilliland, Frank, Davis, Clarence E., Eigen, Howard, Evans, David, Kattan, Meyer, Menendez, Rogelio, Simons, F. Estelle R., Leikin, Sanford, Strunk, Robert, Adkinson, N. Franklin, Cherniack, Reuben, DuHamel, Thomas R., Meinert, Curtis L., Shapiro, Gail G., Zeiger, Robert, Colvin, Ryan, Bacharier, Leonard B., Forno, Erick, Arbelaez, Ana Maria, and Tantisira, Kelan G.
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- 2015
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32. Prevalence of Intermediate-Stage Age-Related Macular Degeneration in Patients With Acquired Immunodeficiency Syndrome
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Jabs, Douglas A., Van Natta, Mark L., Sezgin, Efe, Pak, Jeong Won, and Danis, Ronald
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- 2015
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33. Postprandial symptoms in patients with symptoms of gastroparesis: roles of gastric emptying and accommodation
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Parkman, Henry P., primary, Van Natta, Mark L., additional, Maurer, Alan H., additional, Koch, Kenneth L., additional, Grover, Madhusudan, additional, Malik, Zubair, additional, Sarosiek, Irene, additional, Abell, Thomas L., additional, Bulat, Robert, additional, Kuo, Braden, additional, Shulman, Robert J., additional, Farrugia, Gianrico, additional, Miriel, Laura, additional, Tonascia, James, additional, Hamilton, Frank, additional, Pasricha, Pankaj J., additional, and McCallum, Richard W., additional
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- 2022
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34. Evaluation of Hepatitis C Virus as a Risk Factor for HIV-Associated Neuroretinal Disorder
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Branch, Andrea D., Drye, Lea T., Van Natta, Mark L., Sezgin, Efe, Fishman, Sarah L., Dieterich, Douglas T., Meinert, Curtis L., and Jabs, Douglas A.
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- 2013
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35. Letter: non‐invasive prediction models to exclude cirrhosis in NAFLD —not everyone fits the mould. Authors' reply
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Brandman, Danielle, primary, Boyle, Marie, additional, McPherson, Stuart, additional, Van Natta, Mark L., additional, Sanyal, Arun J., additional, Kowdley, Kris, additional, Neuschwander‐Tetri, Brent, additional, Chalasani, Naga, additional, Abdelmalek, Manal F., additional, Terrault, Norah A., additional, McCullough, Art, additional, Bettencourt, Ricki, additional, Caussy, Cyrielle, additional, Kleiner, David E., additional, Behling, Cynthia, additional, Tonascia, James, additional, Anstee, Quentin M., additional, and Loomba, Rohit, additional
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- 2022
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36. The nonalcoholic steatohepatitis extended hepatocyte ballooning score: histologic classification and clinical significance.
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Gill, Ryan M., Allende, Daniela, Belt, Patricia H., Behling, Cynthia A., Cummings, Oscar W., Guy, Cynthia D., Carpenter, Daniela, Neuschwander-Tetri, Brent A., Sanyal, Arun J., Tonascia, James, Van Natta, Mark L., Wilson, Laura A., Yamada, Goro, Yeh, Matthew, and Kleiner, David E.
- Subjects
NON-alcoholic fatty liver disease ,FATTY liver ,BODY mass index ,MEDICAL research ,METABOLIC syndrome ,LIVER biopsy - Abstract
Background and Aims: The NAFLD activity score was developed to measure histologic changes in NAFLD during therapeutic trials. Hepatocyte ballooning (HB) is the most specific feature in steatohepatitis diagnosis, yet the impact of variations in HB has not been incorporated. Approach and Results: Liver biopsies from patients enrolled in the NASH Clinical Research Network with an initial diagnosis of NASH or NAFL (n =1688) were evaluated to distinguish classic hepatocyte ballooning (cHB) from smaller, nonclassic hepatocyte ballooning (nHB), and also to designate severe ballooning and assign an extended hepatocyte ballooning (eB) score [0 points, no ballooning (NB); 1 point, few or many nHB; 2 points, few cHB; 3 points, many cHB; 4 points, severe cHB] to the biopsy assessment. The eB score was reproducible among NASH CRN liver pathologists (weighted kappa 0.76) and was significantly associated with older age (mean 52.1 y, cHB; 48.5 y, nHB, p< 0.001), gender (72.3% female, cHB; 54.5% female, nHB, p < 0.001), diabetes (49.8% diabetes, cHB; 28.2% diabetes, nHB, p <0.001), metabolic syndrome (68.5% metabolic syndrome, nHB; 50.2% metabolic syndrome, NB, p <0.001), and body mass index [33.2, 34.2, 35 mean body mass index (kg/m2); NB, nHB, and cHB, respectively, p <0.05]. Finally, fibrosis stage, as a marker of disease severity, was significantly correlated with the eB score (p< 0.001). Conclusions: The eB score allows for a reproducible and more precise delineation of the range of ballooned hepatocyte morphology and corresponds with both clinical features of NASH and fibrosis stage. [ABSTRACT FROM AUTHOR]
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- 2023
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37. Mortality in Hepatitis C Virus—Infected Patients With a Diagnosis of AIDS in the Era of Combination Antiretroviral Therapy
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Studies of the Ocular Complications of AIDS Research Group, Branch, Andrea D., Van Natta, Mark L., Vachon, Marie-Louise, Dieterich, Douglas T., Meinert, Curtis L., and Jabs, Douglas A.
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- 2012
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38. Multicohort Genomewide Association Study Reveals a New Signal of Protection Against HIV-1 Acquisition
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Limou, Sophie, Delaneau, Olivier, van Manen, Daniëlle, An, Ping, Sezgin, Efe, Le Clerc, Sigrid, Coulonges, Cédric, Troyer, Jennifer L., Veldink, Jan H., van den Berg, Leonard H., Spadoni, Jean-Louis, Taing, Lieng, Labib, Taoufik, Montes, Matthieu, Delfraissy, Jean-François, Schachter, François, O'Brien, Stephen J., Buchbinder, Susan, van Natta, Mark L., Jabs, Douglas A., Froguel, Philippe, Schuitemaker, Hanneke, Winkler, Cheryl A., and Zagury, Jean-François
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- 2012
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39. Retinal Vessel Caliber Among People With Acquired Immunodeficiency Syndrome: Relationships With Disease-Associated Factors and Mortality
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Gangaputra, Sapna, Kalyani, Partho S., Fawzi, Amani A., Van Natta, Mark L., Hubbard, Larry D., Danis, Ronald P., Thorne, Jennifer E., and Holland, Gary N.
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- 2012
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40. Retinal Vessel Caliber Among People With Acquired Immunodeficiency Syndrome: Relationships With Visual Function
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Kalyani, Partho S., Fawzi, Amani A., Gangaputra, Sapna, van Natta, Mark L., Hubbard, Larry D., Danis, Ronald P., Thorne, Jennifer E., and Holland, Gary N.
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- 2012
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41. Excess Mortality in Patients with AIDS in the Era of Highly Active Antiretroviral Therapy: Temporal Changes and Risk Factors
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Puhan, Milo A., Van Natta, Mark L., Palella, Frank J., Addessi, Adrienne, and Meinert, Curtis
- Published
- 2010
42. Association of Host Genetic Risk Factors With the Course of Cytomegalovirus Retinitis in Patients Infected With Human Immunodeficiency Virus
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Sezgin, Efe, van Natta, Mark L., Ahuja, Alka, Lyon, Alice, Srivastava, Sunil, Troyer, Jennifer L., O'Brien, Stephen J., and Jabs, Douglas A.
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- 2011
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43. Evaluation of the United States Public Health Service Guidelines for Discontinuation of Anticytomegalovirus Therapy After Immune Recovery in Patients With Cytomegalovirus Retinitis
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Holbrook, Janet T., Colvin, Ryan, van Natta, Mark L., Thorne, Jennifer E., Bardsley, Mark, and Jabs, Douglas A.
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- 2011
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44. Association of elevated plasma inflammatory biomarker levels with age-related macular degeneration but not cataract in persons with AIDS
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Jabs, Douglas A., primary, Van Natta, Mark L., additional, Schneider, Michael F., additional, Pak, Jeong Won, additional, Trang, Garrett, additional, Jones, Norman G., additional, Milush, Jeffrey, additional, and Hunt, Peter W., additional
- Published
- 2021
- Full Text
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45. Factors Associated with Persistence of Severe Asthma from Late Adolescence to Early Adulthood
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Izadi, Neema, primary, Baraghoshi, David, additional, Curran-Everett, Douglas, additional, Zeiger, Robert S., additional, Szefler, Stanley J., additional, Covar, Ronina A., additional, Williams, Paul, additional, Lasley, Mary V., additional, Chinn, Tamara, additional, Hinatsu, Michele, additional, Furukawa, Clifton T., additional, Altman, Leonard C., additional, Virant, Frank S., additional, Kennedy, Michael S., additional, Tilles, Stephen, additional, Becker, Jonathan W., additional, Bierman, C. Warren, additional, Crawford, Dan, additional, DuHamel, Thomas, additional, Eliassen, Heather, additional, Hammond, Babi, additional, MacLaren, Miranda, additional, Minotti, Dominick A., additional, Reagan, Chris, additional, Shapiro, Gail, additional, Sharpe, Marian, additional, Tatum, Ashley, additional, White, Grace, additional, Wighton, Timothy G., additional, Fuhlbrigge, Anne, additional, Plunkett, Anne, additional, Madden, Nancy, additional, Anderson, Susan, additional, Boehnert, Mark, additional, Feins, Anita, additional, Gentile, Amanda, additional, Kandror, Natalia, additional, MacAulay, Kelly, additional, Sampong, Ernestina, additional, Weiss, Scott, additional, Torda, Walter, additional, Tata, Martha, additional, Babigian, Sally, additional, Barrant, Peter, additional, Benson, Linda, additional, Caicedo, Jose, additional, Calder, Tatum, additional, Darcy, Christine, additional, DeFilippo, Anthony, additional, Dorsainvil, Cindy, additional, Erickson, Julie, additional, Fulton, Phoebe, additional, Grace, Mary, additional, Gilbert, Jennifer, additional, Greineder, Dirk, additional, Haynes, Stephanie, additional, Higham, Margaret, additional, Jakubowski, Deborah, additional, Kelleher, Susan, additional, Koslof, Jay, additional, Mandel, Dana, additional, Martin, Patricia, additional, Martinez, Agnes, additional, McAuliffe, Jean, additional, Nakamoto, Erika, additional, Pacella, Paola, additional, Parks, Paula, additional, Sagarin, Johanna, additional, Seligsohn, Kay, additional, Swords, Susan, additional, Syring, Meghan, additional, Traylor, June, additional, Van Horn, Melissa, additional, Wells, Carolyn, additional, Whitman, Ann, additional, Grasemann, Hartmut, additional, Miki, Melody, additional, Solomon, Melinda, additional, Subbarao, Padmaja, additional, MacLusky, Ian, additional, Reisman, Joe, additional, Levison, Henry, additional, Hall, Anita, additional, Benedet, Yola, additional, Carpenter, Susan, additional, Chay, Jennifer, additional, Collinson, Michelle, additional, Finlayson-Kulchin, Jane, additional, Gore, Kenneth, additional, Hipolito, Nina, additional, Holmes, Noreen, additional, Hoorntje, Erica, additional, Klassen, Sharon, additional, Quenneville, Joseé, additional, Sananes, Renée, additional, Wasson, Christine, additional, Wilson, Margaret, additional, Adkinson, N. Franklin, additional, Bull, Deborah, additional, Philips, Stephanie, additional, Eggleston, Peyton, additional, Huss, Karen, additional, Plotnick, Leslie, additional, Pulsifer, Margaret, additional, Rand, Cynthia, additional, Aylward, Elizabeth, additional, Bollers, Nancy, additional, Pessaro, Kathy, additional, Wheeler, Barbara, additional, Nelson, Harold S., additional, Bender, Bruce, additional, Liu, Andrew, additional, Sundström, D., additional, Phillips, Melanie, additional, White, Michael P., additional, Gleason, Melanie, additional, Brelsford, Kristin, additional, Bridges, Jessyca, additional, Ciacco, Jody, additional, Eltz, Michael, additional, Feeley, Jeryl, additional, Flynn, Michael, additional, Junk-Blanchard, Tara, additional, Hassell, Joseph, additional, Hefner, Marcia, additional, Hendrickson, Caroline, additional, Hettleman, Daniel, additional, Irvin, Charles G., additional, Kamada, Alan, additional, Krawiec, Marzena, additional, Larsen, Gary, additional, Nimmagadda, Sai, additional, Sandoval, Kendra, additional, Sheridan, Jessica, additional, Spahn, Joseph, additional, Spears, Gayle, additional, Washington, Trella, additional, Willcutt, Eric, additional, Carel, Kirstin, additional, Doshi, Jayna, additional, Hendershot, Rich, additional, Jacobs, Jeffrey, additional, Jain, Neal, additional, Kang, June-ku Brian, additional, Kruzick, Tracy, additional, Leo, Harvey, additional, Macomber, Beth, additional, Malka, Jonathan, additional, Mjaanes, Chris, additional, Prpich, John, additional, Stewart, Lora, additional, Song, Ben, additional, Tamesis, Grace, additional, Friedman, Noah, additional, Mellon, Michael H., additional, Schatz, Michael, additional, Long, Terrie, additional, Macaraeg, Travis, additional, Christensen, Sandra, additional, Easton, James G., additional, Feinberg, M., additional, Galbreath, Linda L., additional, Gulczynski, Jennifer, additional, Harden, Kathleen, additional, Hansen, Ellen, additional, Jalowayski, Al, additional, Jenson, Elaine, additional, Lincoln, Alan, additional, Kaufman, Jennie, additional, King, Shirley, additional, Lopez, Brian, additional, Magiari-Ene, Michaela, additional, Mostafa, Kathleen, additional, Moscona, Avraham, additional, Nelle, Catherine A., additional, Powers, Jennifer, additional, Rodriguez, Elsa, additional, Rodriguez, Eva, additional, Sandoval, Karen, additional, Wilson, Nevin W., additional, Raissy, Hengameh H., additional, Jacobs, Aaron, additional, Kelly, H. William, additional, Spicher, Mary, additional, Batson, Christina, additional, Harkings, Michelle, additional, McCallum, Katie, additional, Annett, Robert, additional, Archibeque, Teresa, additional, Bashir, Naim, additional, Bereket, H. Selda, additional, Braun, Marisa, additional, Bush, Carrie, additional, Bush, Shannon C., additional, Clayton, Michael, additional, Colon-Semidey, Angel, additional, Devault, Sara, additional, Esparham, Anna, additional, Grad, Roni, additional, Hunt, David, additional, Larsson, Jeanne, additional, McClelland, Sandra, additional, McWilliams, Bennie, additional, Montoya, Elisha, additional, Moreshead, Margaret, additional, Murphy, Shirley, additional, Ortega, Barbara, additional, Weers, David, additional, Zayas, Jose, additional, Strunk, Robert C., additional, Bacharier, Leonard, additional, Rodgers, Denise, additional, Albers, Ellen, additional, Belle, Gregg, additional, Bloomberg, Gordon R., additional, Buchanan, W. Patrick, additional, Caesar, Mary, additional, Corry, James M., additional, DeMuth, Karen, additional, Dolinsky, Marisa, additional, Fisher, Edwin B., additional, Gaioni, Stephen J., additional, Glynn, Emily, additional, Heckman, Bernadette D., additional, Kemp, Debra, additional, Kertz, Lila, additional, Lawhon, Claire, additional, Morgan, Valerie, additional, Moseid, Cynthia, additional, Oliver-Welker, Tina, additional, Richardson, Diana, additional, Ryan, Elizabeth, additional, Sagal, Sharon, additional, Smith, Thomas F., additional, Sylvia, Susan, additional, Turner, Carl, additional, White, Deborah K., additional, Tonascia, James, additional, Belt, Patricia, additional, Collins, Karen, additional, Collison, Betty, additional, Dodge, John, additional, Donithan, Michele, additional, Ewing, Cathleen, additional, Jackson, Rosetta, additional, May, Patrick, additional, Meinert, Jill, additional, Reyes, Girlie, additional, Smith, Michael, additional, Sternberg, Alice L., additional, Van Natta, Mark L., additional, Wagoner, Annette, additional, Wilson, Laura, additional, Wise, Robert, additional, Yates, Katherine, additional, Taggart, Virginia, additional, Eggers, Lois, additional, Kiley, James, additional, Moore, Howard, additional, Zheng, Gang, additional, Albert, Paul, additional, Hurd, Suzanne, additional, Parker, Sydney, additional, Randall, Pamela, additional, Wu, Margaret, additional, Cloutier, Michelle, additional, Connett, John, additional, Cuttler, Leona, additional, Gilliland, Frank, additional, Davis, Clarence E., additional, Eigen, Howard, additional, Evans, David, additional, Kattan, Meyer, additional, Menendez, Rogelio, additional, Simons, F. Estelle R., additional, Leikin, Sanford, additional, Strunk, Robert, additional, Cherniack, Reuben, additional, DuHamel, Thomas R., additional, Meinert, Curtis L., additional, Shapiro, Gail G., additional, and Zeiger, Robert, additional
- Published
- 2021
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46. Patterns of Growth and Decline in Lung Function in Persistent Childhood Asthma
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McGeachie, Michael J., Yates, Katherine P., Zhou, Xiaobo, Guo, Feng, Sternberg, Alice L., Van Natta, Mark L., Wise, Robert A., Szefler, Stanley J., Sharma, Sunita, Kho, Alvin T., Cho, Michael H., Croteau-Chonka, Damien C., Castaldi, Peter J., Jain, Gaurav, Sanyal, Amartya, Zhan, Ye, Lajoie, Bryan R., Dekker, Job, Stamatoyannopoulos, John, Covar, Ronina A., Zeiger, Robert S., Adkinson, N. Franklin, Williams, Paul V., Kelly, H. William, Grasemann, Hartmut, Vonk, Judith M., Koppelman, Gerard H., Postma, Dirkje S., Raby, Benjamin A., Houston, Isaac, Lu, Quan, Fuhlbrigge, Anne L., Tantisira, Kelan G., Silverman, Edwin K., Tonascia, James, Weiss, Scott T., and Strunk, Robert C.
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- 2016
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47. Association Between Abnormal Contrast Sensitivity and Mortality Among People With Acquired Immunodeficiency Syndrome
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Holland, Gary N., Kappel, Peter J., Van Natta, Mark L., Palella, Frank J., Lyon, Alice T., Shah, Kayur H., Pavan, Peter R., and Jabs, Douglas A.
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- 2010
- Full Text
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48. Effects of Liver Biopsy Sample Length and Number of Readings on Sampling Variability in Nonalcoholic Fatty Liver Disease
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Vuppalanchi, Raj, Ünalp, Aynur, Van Natta, Mark L., Cummings, Oscar W., Sandrasegaran, Kumar E., Hameed, Tariq, Tonascia, James, and Chalasani, Naga
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- 2009
- Full Text
- View/download PDF
49. Sa394 SYMPTOM CHANGES DURING GASTRIC EMPTYING SCINTIGRAPHY AND WATER LOAD SATIETY TEST IN PATIENTS WITH SYMPTOMS OF GASTROPARESIS: ROLES OF IMPAIRED ACCOMMODATION AND VISCERAL HYPERSENSITIVITY.
- Author
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Parkman, Henry P., primary, Van Natta, Mark L., additional, Maurer, Alan H., additional, Koch, Kenneth L., additional, Grover, Madhusudan, additional, Malik, Zubair A., additional, Sarosiek, Irene, additional, Abell, Thomas, additional, Kuo, Braden, additional, Shulman, Robert J., additional, Farrugia, Gianrico, additional, Miriel, Laura A., additional, Tonascia, James, additional, Hamilton, Frank A., additional, Pasricha, Pankaj J., additional, and McCallum, Richard W., additional
- Published
- 2021
- Full Text
- View/download PDF
50. Vision Function in HIV-Infected Individuals without Retinitis: Report of the Studies of Ocular Complications of AIDS Research Group
- Author
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Freeman, William R., Van Natta, Mark L., Jabs, Douglas, Sample, Pamela A., Sadun, Alfredo A., Thorne, Jennifer, Shah, Kayur H., and Holland, Gary N.
- Published
- 2008
- Full Text
- View/download PDF
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