Person:
Afdhal, Nezam

Profile Picture

Email Address

AA Acceptance Date

Birth Date

Research Projects

Organizational Units

Job Title

Last Name

Afdhal

First Name

Nezam

Name

Afdhal, Nezam
Author's Publications: search.filters.isAuthorOfPublication.55104176-715c-45a0-a8e3-106f221816ef

Search Results

Now showing 1 - 2 of 2
  • Thumbnail Image
    Publication
    The ASK1 inhibitor selonsertib in patients with nonalcoholic steatohepatitis: A randomized, phase 2 trial
    (John Wiley and Sons Inc., 2017) Loomba, Rohit; Lawitz, Eric; Mantry, Parvez S.; Jayakumar, Saumya; Caldwell, Stephen H.; Arnold, Hays; Diehl, Anna Mae; Djedjos, C. Stephen; Han, Ling; Myers, Robert P.; Subramanian, G. Mani; McHutchison, John G.; Goodman, Zachary D.; Afdhal, Nezam; Charlton, Michael R.
    Inhibition of apoptosis signal–regulating kinase 1, a serine/threonine kinase, leads to improvement in inflammation and fibrosis in animal models of nonalcoholic steatohepatitis. We evaluated the safety and efficacy of selonsertib, a selective inhibitor of apoptosis signal–regulating kinase 1, alone or in combination with simtuzumab, in patients with nonalcoholic steatohepatitis and stage 2 or 3 liver fibrosis. In this multicenter phase 2 trial, 72 patients were randomized to receive 24 weeks of open‐label treatment with either 6 or 18 mg of selonsertib orally once daily with or without once‐weekly injections of 125 mg of simtuzumab or simtuzumab alone. The effect of treatment was assessed by paired pretreatment and posttreatment liver biopsies, magnetic resonance elastography, magnetic resonance imaging–estimated proton density fat fraction, quantitative collagen content, and noninvasive markers of liver injury. Due to the lack of effect of simtuzumab on histology or selonsertib pharmacokinetics, selonsertib groups with and without simtuzumab were pooled. After 24 weeks of treatment, the proportion of patients with a one or more stage reduction in fibrosis in the 18‐mg selonsertib group was 13 of 30 (43%; 95% confidence interval, 26‐63); in the 6‐mg selonsertib group, 8 of 27 (30%; 95% confidence interval, 14‐50); and in the simtuzumab‐alone group, 2 of 10 (20%; 95% confidence interval, 3‐56). Improvement in fibrosis was associated with reductions in liver stiffness on magnetic resonance elastography, collagen content and lobular inflammation on liver biopsy, as well as improvements in serum biomarkers of apoptosis and necrosis. There were no significant differences in adverse events between the treatment groups. Conclusion: These findings suggest that selonsertib may reduce liver fibrosis in patients with nonalcoholic steatohepatitis and stage 2‐3 fibrosis. (Hepatology 2018;67:549‐559).
  • Thumbnail Image
    Publication
    Cost-Effectiveness Analysis: Risk Stratification of Nonalcoholic Fatty Liver Disease (NAFLD) by the Primary Care Physician Using the NAFLD Fibrosis Score
    (Public Library of Science, 2016) Tapper, Elliot; Hunink, M. G. Myriam; Afdhal, Nezam; Lai, Michelle; Sengupta, Neil
    Background: The complications of Nonalcoholic Fatty Liver Disease (NAFLD) are dependent on the presence of advanced fibrosis. Given the high prevalence of NAFLD in the US, the optimal evaluation of NAFLD likely involves triage by a primary care physician (PCP) with advanced disease managed by gastroenterologists. Methods: We compared the cost-effectiveness of fibrosis risk-assessment strategies in a cohort of 10,000 simulated American patients with NAFLD performed in either PCP or referral clinics using a decision analytical microsimulation state-transition model. The strategies included use of vibration-controlled transient elastography (VCTE), the NAFLD fibrosis score (NFS), combination testing with NFS and VCTE, and liver biopsy (usual care by a specialist only). NFS and VCTE performance was obtained from a prospective cohort of 164 patients with NAFLD. Outcomes included cost per quality adjusted life year (QALY) and correct classification of fibrosis. Results: Risk-stratification by the PCP using the NFS alone costs $5,985 per QALY while usual care costs $7,229/QALY. In the microsimulation, at a willingness-to-pay threshold of $100,000, the NFS alone in PCP clinic was the most cost-effective strategy in 94.2% of samples, followed by combination NFS/VCTE in the PCP clinic (5.6%) and usual care in 0.2%. The NFS based strategies yield the best biopsy-correct classification ratios (3.5) while the NFS/VCTE and usual care strategies yield more correct-classifications of advanced fibrosis at the cost of 3 and 37 additional biopsies per classification. Conclusion: Risk-stratification of patients with NAFLD primary care clinic is a cost-effective strategy that should be formally explored in clinical practice.