Jama Darling - Academia.edu (original) (raw)

Papers by Jama Darling

Research paper thumbnail of Impact of Pruritus on Quality of Life and Current Treatment Patterns in Patients with Primary Biliary Cholangitis

Digestive Diseases and Sciences

Research paper thumbnail of Hepatitis C

Research paper thumbnail of Membranoproliferative Glomerulonephritis, Type II Cryoglobulinemia and Triple Therapy for Hepatitis C: A Case Series and Review of the Literature

Digestive Diseases and Sciences, Mar 16, 2014

Research paper thumbnail of Liver disease symptoms are associated with higher risk of adverse clinical outcomes: A longitudinal study of North American adults with chronic Hepatitis B

GastroHep, 2021

Symptoms of chronic hepatitis B (CHB) are not well characterised.

Research paper thumbnail of A Pragmatic, Randomized Controlled Trial of Oral Antivirals for the Treatment of Chronic Hepatitis C: The PRIORITIZE Study

Hepatology, 2021

BACKGROUND & AIMS Multiple direct-acting antiviral (DAA) regimens are available to treat hepa... more BACKGROUND & AIMS Multiple direct-acting antiviral (DAA) regimens are available to treat hepatitis C virus (HCV), genotype 1 infection. However, comparative effectiveness from randomized controlled trials of DAA regimens is unavailable. Approach & Results We conducted a pragmatic randomized controlled trial (NCT02786537) to compare the effectiveness of DAAs for HCV genotype 1a or 1b on viral response, safety, tolerability, and medication non-adherence. Adults with compensated liver disease, HCV genotype 1, not pregnant or breast feeding, and with health insurance likely to cover ledipasvir/sofosbuvir (LDV/SOF) were recruited from 34 U.S. viral hepatitis clinics. Participants were randomized (± ribavirin) to ledipasvir/sofosbuvir (LDV/SOF), elbasvir/grazoprevir (EBR/GZR), and paritaprevir/ritonavir/ombitasvir+dasabuvir (PrOD, treatment arm stopped early). Primary outcomes included sustained viral response at 12 weeks (SVR12), clinician-recorded adverse events, patient-reported symptoms, and medication non-adherence. Between June 2016 and March 2018, 1609 participants were randomized. Among 1128 participants who received ≥ 1 dose of EBR/GZR or LDV/SOF (± ribavirin), SVR12 were 95.2% [95% CI, 92.8 to 97.6] and 97.4% [95% CI, 95.5 to 99.2] respectively, with a difference estimate of 2.2% [ -0.5, 4.7%], falling within the 'equivalence' interval [-5, 5%]. While most (56%) participants experienced adverse events, few were serious (4.2%) or severe (1.8%). In the absence of ribavirin, discontinuations due to adverse events were rare. Patient-reported symptoms and medication non-adherence were similar. Study limitations were drop-out due to insurance denial and lost to follow-up after treatment, limiting the ability to measure SVR12. CONCLUSIONS This pragmatic trial demonstrated high SVR12 for participants treated with EBR/GZR and LDV/SOF with few adverse effects. Overall, the two regimens were equivalent in effectiveness. The results support current HCV guidelines that do not distinguish between ribavirin-free EBR/GZR or LDV/SOF.

Research paper thumbnail of Clinical significance of quantitative e antigen in a cohort of hepatitis B virus‐infected children and adults in North America

Journal of Viral Hepatitis, 2021

Background: In chronic hepatitis B (CHB) viral infection, e antigen positivity (HBeAg+) is associ... more Background: In chronic hepatitis B (CHB) viral infection, e antigen positivity (HBeAg+) is associated with high levels of viral replication and infectivity. Furthermore, HBeAg‐positive CHB is associated with a liver disease spectrum ranging from none to severe. Aim: To assess whether the level of circulating HBeAg is associated with different clinical presentations of HBeAg‐positive CHB. Methods: A cross‐sectional analysis was conducted among HBV mono‐infected participants enrolled in Hepatitis B Research Network (HBRN) cohorts to explore clinical and virological associations with quantitative HBeAg (qHBeAg). Results: Among 763 HBeAg+ participants (56% female; 85% Asian; median age 26 years), multivariable median regression modelling significantly associated qHBeAg with liver injury (inverse qHBeAg association with ALT p<.001 and APRI p<.001), and with both race and age (p=0.01). Among Asians, qHBeAg was inversely related to age; a relationship less clear among Blacks and Whites. Among Asians also, median qHBeAg levels were higher among those infected with HBV genotype C versus B (p<0.001), suggesting causal virologic differences. Across all races, median qHBeAg was higher in women (p=.01). Independent of sex, age, race and HBV genotype, qHBeAg was higher in participants with predominant wild‐type versus basal core promoter and/or precore ‘stop’ viral variants (p<0.001). Conclusion: Lower qHBeAg was observed among HBRN participants with the greatest degree of liver injury independent of demographics and HBV genotype. These data support longitudinal studies to examine the role of qHBeAg in modulating the host immune response and predicting the outcomes of chronic HBV infection.

Research paper thumbnail of Second International Guidelines for the Diagnosis and Management of Hereditary Hemorrhagic Telangiectasia

Annals of Internal Medicine, 2020

Research paper thumbnail of medLow Incidence of Adverse Outcomes in Adults with Chronic Hepatitis B Virus Infection in the Era of Antiviral Therapy

Research paper thumbnail of 519 a Quality Improvement Initiative Results in Improved Rates of Timely Post-Variceal Bleeding Surveillance Endoscopy

Research paper thumbnail of A Quality Improvement Initiative Results in Improved Rates of Timely Postvariceal Bleeding Surveillance Endoscopy

The American Journal of Gastroenterology, 2020

Research paper thumbnail of Quality Improvement Initiative to Improve Receipt of Timely Surveillance Endoscopy After Variceal Bleeding

American Journal of Gastroenterology, 2019

Research paper thumbnail of Treatment Status of Hepatocellular Carcinoma Does Not Influence Rates of Sustained Virologic Response: An HCV‐TARGET Analysis

Hepatology Communications, 2019

Research paper thumbnail of THU-182-The PRIORITIZE study: A pragmatic, randomized study of oral regimens for hepatitis C-transforming decision-making for patients, providers, and stakeholders

Journal of Hepatology, 2019

Research paper thumbnail of Age, race and viral genotype are associated with the prevalence of Hepatitis B e antigen in children and adults with chronic Hepatitis B

Journal of Viral Hepatitis, 2019

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

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

Clinical Gastroenterology and Hepatology, 2019

Research paper thumbnail of Su1428 Daclatasvir and Sofosbuvir Therapy for Patients with Decompensated Cirrhosis or Post-Liver Transplant HCV Recurrence and Advanced Fibrosis or Cirrhosis: United States Multicenter Treatment Protocol

Research paper thumbnail of Effectiveness and safety of sofosbuvir plus ribavirin for the treatment of HCV genotype 2 infection: results of the real-world, clinical practice HCV-TARGET study

Research paper thumbnail of Effectiveness of Simeprevir plus Sofosbuvir, With or Without Ribavirin, in Real-World Patients with HCV Genotype 1 Infection

Gastroenterology, Jan 21, 2015

The interferon-free regimen of simeprevir plus sofosbuvir was recommended by professional guideli... more The interferon-free regimen of simeprevir plus sofosbuvir was recommended by professional guidelines for certain patients with hepatitis C virus (HCV) genotype 1 infection based on the findings of a phase 2 trial. We aimed to evaluate the safety and efficacy of this regimen in clinical practice settings in North America. We collected demographic, clinical, and virologic data, as well as reports of adverse outcomes, from sequential participants in HCV-TARGET-a prospective, observational cohort study of patients undergoing HCV treatment in routine clinical care settings. From January through October 2014, 836 patients with HCV genotype 1 infection began 12 weeks of treatment with simeprevir plus sofosbuvir (treatment duration of up to 16 weeks); 169 of these patients received ribavirin. Most patients were male (61%), Caucasian (76%), or black (13%); 59% had cirrhosis. Most had failed prior treatment with peginterferon and ribavirin without (46%) or with telaprevir or boceprevir (12%)....

Research paper thumbnail of High MIG (CXCL9) plasma levels favors response to peginterferon and ribavirin in HCV-infected patients regardless of DPP4 activity

Liver International, 2015

Research paper thumbnail of Expression of metalloproteinases in pigmented villonodular synovitis

Research paper thumbnail of Impact of Pruritus on Quality of Life and Current Treatment Patterns in Patients with Primary Biliary Cholangitis

Digestive Diseases and Sciences

Research paper thumbnail of Hepatitis C

Research paper thumbnail of Membranoproliferative Glomerulonephritis, Type II Cryoglobulinemia and Triple Therapy for Hepatitis C: A Case Series and Review of the Literature

Digestive Diseases and Sciences, Mar 16, 2014

Research paper thumbnail of Liver disease symptoms are associated with higher risk of adverse clinical outcomes: A longitudinal study of North American adults with chronic Hepatitis B

GastroHep, 2021

Symptoms of chronic hepatitis B (CHB) are not well characterised.

Research paper thumbnail of A Pragmatic, Randomized Controlled Trial of Oral Antivirals for the Treatment of Chronic Hepatitis C: The PRIORITIZE Study

Hepatology, 2021

BACKGROUND & AIMS Multiple direct-acting antiviral (DAA) regimens are available to treat hepa... more BACKGROUND & AIMS Multiple direct-acting antiviral (DAA) regimens are available to treat hepatitis C virus (HCV), genotype 1 infection. However, comparative effectiveness from randomized controlled trials of DAA regimens is unavailable. Approach & Results We conducted a pragmatic randomized controlled trial (NCT02786537) to compare the effectiveness of DAAs for HCV genotype 1a or 1b on viral response, safety, tolerability, and medication non-adherence. Adults with compensated liver disease, HCV genotype 1, not pregnant or breast feeding, and with health insurance likely to cover ledipasvir/sofosbuvir (LDV/SOF) were recruited from 34 U.S. viral hepatitis clinics. Participants were randomized (± ribavirin) to ledipasvir/sofosbuvir (LDV/SOF), elbasvir/grazoprevir (EBR/GZR), and paritaprevir/ritonavir/ombitasvir+dasabuvir (PrOD, treatment arm stopped early). Primary outcomes included sustained viral response at 12 weeks (SVR12), clinician-recorded adverse events, patient-reported symptoms, and medication non-adherence. Between June 2016 and March 2018, 1609 participants were randomized. Among 1128 participants who received ≥ 1 dose of EBR/GZR or LDV/SOF (± ribavirin), SVR12 were 95.2% [95% CI, 92.8 to 97.6] and 97.4% [95% CI, 95.5 to 99.2] respectively, with a difference estimate of 2.2% [ -0.5, 4.7%], falling within the 'equivalence' interval [-5, 5%]. While most (56%) participants experienced adverse events, few were serious (4.2%) or severe (1.8%). In the absence of ribavirin, discontinuations due to adverse events were rare. Patient-reported symptoms and medication non-adherence were similar. Study limitations were drop-out due to insurance denial and lost to follow-up after treatment, limiting the ability to measure SVR12. CONCLUSIONS This pragmatic trial demonstrated high SVR12 for participants treated with EBR/GZR and LDV/SOF with few adverse effects. Overall, the two regimens were equivalent in effectiveness. The results support current HCV guidelines that do not distinguish between ribavirin-free EBR/GZR or LDV/SOF.

Research paper thumbnail of Clinical significance of quantitative e antigen in a cohort of hepatitis B virus‐infected children and adults in North America

Journal of Viral Hepatitis, 2021

Background: In chronic hepatitis B (CHB) viral infection, e antigen positivity (HBeAg+) is associ... more Background: In chronic hepatitis B (CHB) viral infection, e antigen positivity (HBeAg+) is associated with high levels of viral replication and infectivity. Furthermore, HBeAg‐positive CHB is associated with a liver disease spectrum ranging from none to severe. Aim: To assess whether the level of circulating HBeAg is associated with different clinical presentations of HBeAg‐positive CHB. Methods: A cross‐sectional analysis was conducted among HBV mono‐infected participants enrolled in Hepatitis B Research Network (HBRN) cohorts to explore clinical and virological associations with quantitative HBeAg (qHBeAg). Results: Among 763 HBeAg+ participants (56% female; 85% Asian; median age 26 years), multivariable median regression modelling significantly associated qHBeAg with liver injury (inverse qHBeAg association with ALT p<.001 and APRI p<.001), and with both race and age (p=0.01). Among Asians, qHBeAg was inversely related to age; a relationship less clear among Blacks and Whites. Among Asians also, median qHBeAg levels were higher among those infected with HBV genotype C versus B (p<0.001), suggesting causal virologic differences. Across all races, median qHBeAg was higher in women (p=.01). Independent of sex, age, race and HBV genotype, qHBeAg was higher in participants with predominant wild‐type versus basal core promoter and/or precore ‘stop’ viral variants (p<0.001). Conclusion: Lower qHBeAg was observed among HBRN participants with the greatest degree of liver injury independent of demographics and HBV genotype. These data support longitudinal studies to examine the role of qHBeAg in modulating the host immune response and predicting the outcomes of chronic HBV infection.

Research paper thumbnail of Second International Guidelines for the Diagnosis and Management of Hereditary Hemorrhagic Telangiectasia

Annals of Internal Medicine, 2020

Research paper thumbnail of medLow Incidence of Adverse Outcomes in Adults with Chronic Hepatitis B Virus Infection in the Era of Antiviral Therapy

Research paper thumbnail of 519 a Quality Improvement Initiative Results in Improved Rates of Timely Post-Variceal Bleeding Surveillance Endoscopy

Research paper thumbnail of A Quality Improvement Initiative Results in Improved Rates of Timely Postvariceal Bleeding Surveillance Endoscopy

The American Journal of Gastroenterology, 2020

Research paper thumbnail of Quality Improvement Initiative to Improve Receipt of Timely Surveillance Endoscopy After Variceal Bleeding

American Journal of Gastroenterology, 2019

Research paper thumbnail of Treatment Status of Hepatocellular Carcinoma Does Not Influence Rates of Sustained Virologic Response: An HCV‐TARGET Analysis

Hepatology Communications, 2019

Research paper thumbnail of THU-182-The PRIORITIZE study: A pragmatic, randomized study of oral regimens for hepatitis C-transforming decision-making for patients, providers, and stakeholders

Journal of Hepatology, 2019

Research paper thumbnail of Age, race and viral genotype are associated with the prevalence of Hepatitis B e antigen in children and adults with chronic Hepatitis B

Journal of Viral Hepatitis, 2019

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

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

Clinical Gastroenterology and Hepatology, 2019

Research paper thumbnail of Su1428 Daclatasvir and Sofosbuvir Therapy for Patients with Decompensated Cirrhosis or Post-Liver Transplant HCV Recurrence and Advanced Fibrosis or Cirrhosis: United States Multicenter Treatment Protocol

Research paper thumbnail of Effectiveness and safety of sofosbuvir plus ribavirin for the treatment of HCV genotype 2 infection: results of the real-world, clinical practice HCV-TARGET study

Research paper thumbnail of Effectiveness of Simeprevir plus Sofosbuvir, With or Without Ribavirin, in Real-World Patients with HCV Genotype 1 Infection

Gastroenterology, Jan 21, 2015

The interferon-free regimen of simeprevir plus sofosbuvir was recommended by professional guideli... more The interferon-free regimen of simeprevir plus sofosbuvir was recommended by professional guidelines for certain patients with hepatitis C virus (HCV) genotype 1 infection based on the findings of a phase 2 trial. We aimed to evaluate the safety and efficacy of this regimen in clinical practice settings in North America. We collected demographic, clinical, and virologic data, as well as reports of adverse outcomes, from sequential participants in HCV-TARGET-a prospective, observational cohort study of patients undergoing HCV treatment in routine clinical care settings. From January through October 2014, 836 patients with HCV genotype 1 infection began 12 weeks of treatment with simeprevir plus sofosbuvir (treatment duration of up to 16 weeks); 169 of these patients received ribavirin. Most patients were male (61%), Caucasian (76%), or black (13%); 59% had cirrhosis. Most had failed prior treatment with peginterferon and ribavirin without (46%) or with telaprevir or boceprevir (12%)....

Research paper thumbnail of High MIG (CXCL9) plasma levels favors response to peginterferon and ribavirin in HCV-infected patients regardless of DPP4 activity

Liver International, 2015

Research paper thumbnail of Expression of metalloproteinases in pigmented villonodular synovitis