Table I.
Summary of Parameters Included in NAFLD SimPops
| Parameter Name in NAFLDsym | Data Source for Distribution |
|---|---|
| Vmax for aHSC proliferation | Assumed standard deviation of ± 20% and parameter range of 2.5 times the S.D. and validated with data from Abdeen 2009, El Gendi 2012, Washington 2000 |
| ATP decrement necrosis Vmax | Assumed standard deviation of ± 20% and parameter range of 2.5 times the S.D. and validated with outcome data |
| Basal fasting glucose | Browning 2004, Maximos 2015, Copaci 2015, Dudekula 2014, Wong 2013, Stepnova 2010, Tanaka 2013, Zein 2012 |
| Basal plasma triglycerides concentration | Yki-Jarvinen 2014, Maximos 2015 |
| Basal value of mito ETC flux | Perez-Carreras 2003 |
| Rate constant for FFA release from Peripheral storage | Based on relationship between fat mass and adipose fatty acid release described by Mittendorfer 2009 |
| Basal liver triglycerides | Yki-Jarvinen 2014, Maximos 2015, Browning 2004 |
| Body Mass | Yki-Jarvinen 2014, Maximos 2015, Browning 2005 |
| Caspase-mediated apoptosis scaling constant | Bantel 2001 |
| Liver macrophage CCL3 production Vmax | Assumed standard deviation of ± 20% and parameter range of 2.5 times the S.D. and validated with data from DuPlessis 2015, DuPlessis 2016 |
| CL activated HSC apoptosis scalar | El-Gendi 2012, Abdeen 2012, Carpino 2004 (to provide steady state aHSC in accordance with the effects of the CL_aHSC crowding_scalar on aHSC proliferation) |
| CL activated HSC crowding scalar | El-Gendi 2012, Abdeen 2012, Carpino 2004 |
| CL fibrosis hepatocyte displacement scalar | Carpino 2004, D’Ambrosio 2012 |
| Collagen 1 baseline formation rate | Decaris 2017, Masugi 2018 |
| Collagen 1 formation rate | Decaris 2017, Masugi 2018 |
| Collagen 3 baseline formation rate | Decaris 2017, Masugi 2018 |
| Collagen 3 formation rate | Decaris 2017, Masugi 2018 |
| Extracellular vesicle release from apoptotic cells | Povero 2016 |
| Maximum LSEC HGF production rate per liver LSEC | Assumed standard deviation of ± 20% and parameter range of 2.5 times the S.D. and validated with outcome data |
| Maximum macrophage HGF production rate per macrophage | Dominguez-Perez 2016, Balaban 2006, Agrawal 2013 |
| Maximum neutrophil HGF production rate per liver neutrophil | Dominguez-Perez 2016, Balaban 2006, Agrawal 2013 |
| HGF mediated regeneration Vmax | Assumed standard deviation of ± 20% and parameter range of 2.5 times the S.D. and validated with outcome data |
| Vmax for HSC activation | Assumed standard deviation of ± 20% and parameter range of 2.5 times the S.D. and validated with data from Abdeen 2009, El Gendi 2012, Washington 2000 |
| Rate constant for DNL precursor production | Lambert 2014, Donnely 2005, Lee 2015, Diraison 2003 |
| Rate constant for lactate contribution to DNL | Lambert 2014, Donnely 2005, Lee 2015, Diraison 2003 |
| Conversion of mature to labile collagen rate constant | Arima 2004, D’Ambrosio 2012 |
| Rate constant for hepatic Chylo-TG uptake | Tushuizen 2010, McQuaid 2011 |
| Rate constant for hepatic glucose uptake | McMahon 1989, Cersosimo 2011 |
| Rate constant for hepatic VLDL-TG uptake | Yki-Jarvinen 2014, Maximos 2015, Mittendorfer 2003, Sane 1988, Beil 1982 |
| Km for FFA2DAG | Required to have appropriate dynamics with TG Lipolysis mechanism activated |
| Km for triglyceride lipolysis | Variability in this parameter provides variability in the liver TG-ALT relationship described by Yki-Jarvinen 2014, Maximos 2015, Browning 2004 |
| Rate constant for Chylo-TG uptake by peripheral tissues | Tushuizen 2010, McQuaid 2011 |
| Rate constant for VLDL-TG uptake by peripheral tissues | Yki-Jarvinen 2014, Maximos 2015, Mittendorfer 2003, Sane 1988, Beil 1982 |
| Vmax for LOX | Assumed standard deviation of ± 20% and parameter range of 2.5 times the S.D. and validated with data from Mesarwi 2015 |
| ML fibrosis hepatocyte displacement scalar | Carpino 2004, D’Ambrosio 2012 |
| Vmax for MMP | Assumed standard deviation of ± 20% and parameter range of 2.5 times the S.D |
| Vmax for MMP (fragments) | Assumed standard deviation of ± 20% and parameter range of 2.5 times the S.D |
| PP fibrosis hepatocyte displacement scalar | Carpino 2004, D’Ambrosio 2012 |
| Half-life for plasma Pro-C3 | Assumed standard deviation of ± 50% and parameter range of 2.5 times the S.D. and validated with data reported by Levin 2017 (abstract) |
| Procollagen 1 production rate | Decaris 2017, Masugi 2018 |
| Procollagen 1 baseline production rate | Decaris 2017, Masugi 2018 |
| Procollagen 3 production rate | Decaris 2017, Masugi 2018 |
| Procollagen 3 baseline production rate | Decaris 2017, Masugi 2018 |
| Scaling coeff. representing reserve mitochondria function | Perez-Carreras 2003 |
| Liver RNS/ROS baseline clearance Vmax | Hardwick 2010, Videla 2004, Tanaka 2013 |
| Serum adiponectin initial value | Adiels 2006 |
| Prior (weight) for liver TG % to steatosis Grade 0 model | Randomized distribution of histologic steatosis to provide variability between the four grades |
| Prior (weight) for liver TG % to steatosis Grade 1 model | Randomized distribution of histologic steatosis to provide variability between the four grades |
| Prior (weight) for liver TG % to steatosis Grade 2 model | Randomized distribution of histologic steatosis to provide variability between the four grades |
| Prior (weight) for liver TG % to steatosis Grade 3 model | Randomized distribution of histologic steatosis to provide variability between the four grades |
| Triglyceride lipolysis switch | Required to ensure TG Lipolysis mechanism activated |
| Liver macrophage TGF-beta production Vmax | Assumed standard deviation of ± 20% and parameter range of 2.5 times the S.D. and validated with data from Das 2011 |
| Maximum inhibition of MMP by TIMPs | Assumed standard deviation of ± 20% and parameter range of 2.5 times the S.D |
| Liver macrophage TIMP production Vmax | Ando 2018, Miele 2009 |
| Liver macrophage TNF-alpha production Vmax | Assumed standard deviation of ± 20% and parameter range of 2.5 times the S.D. and validated with data from Das 2011, Zahran 2013, Hui 2004, Paredes-Turrubiarte 2016 |
| Vmax for FFA2DAG | Required to ensure appropriate hepatocyte fatty acid and DAG dynamics |
| VLDL-triglyceride secretion rate Vmax | Fabbrini 2008, Adiels 2006 |