Understanding the Complex Patterns Observed during Hepatitis B Virus Therapy
Abstract
:1. Introduction
2. Materials and Methods
2.1. Mathematical Model
2.2. Monte Carlo Sampling
- MC.1
- The initial condition (2) exists and is stable, i.e., and .
- MC.2
- The components of initial condition (2) are bound by cells per ml, cells per mL, and virus per ml.
- MC.3
- The drug-dependent virus asymptotic removal condition (6) holds, i.e., . This condition guaranties that we are only examining drug therapy that is efficient in removing the hepatitis B virus.
- MC.4
- The total hepatocyte population is bound as follows cells per mL, for all t. This condition guarantees that the total liver cell population never decays below of the healthy hepatocyte concentration K [23].
3. Results
3.1. Parameter Regions for Bi-Phasic and Tri-Phasic Virus Dynamics
3.2. Relationship between Patterns and the Duration of Treatment
3.3. Liver Toxicity and the Role of Initial Conditions
4. Discussion
Supplementary Materials
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Figure 1 | K | p | c | ||||||
---|---|---|---|---|---|---|---|---|---|
(A) | 3 | 5 | 0.07 | 100 | 0.67 | 0.5 | 0.99934 | ||
(B) | 0.9 | 3.3 | 0.22 | 5 | 0.7 | 0.5 | 0.991 | ||
(C) | 0.8 | 2.9 | 0.25 | 1.4 | 0.18 | 0.2 | 0.9988 | ||
(D) | 0.5 | 7.2 | 0.06 | 164 | 1 | 0.5 | 0.997 |
Parameter | Description | Value | Reference |
---|---|---|---|
Infectivity rate | mL/(virions × d) | [22] | |
K | Hepatocyte-carrying capacity | cells/mL | [12] |
p | Viral production | 100 virions/(cell × d) | [22] |
c | Viral clearance | 0.67 | [21] |
Efficacy of therapy in blocking infection | 0.5 | [10] | |
Parameter | Description | Range | References |
Uninfected cell division rate | (0,4] | [12,22] | |
Infected cell division rate | (0,4] | [12] | |
Infected cells killing rate | [0.01,0.1] | [10,11,12,22] | |
Efficacy of therapy in blocking viral production | [0.2,1] | [10,12] |
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Carracedo Rodriguez, A.; Chung, M.; Ciupe, S.M. Understanding the Complex Patterns Observed during Hepatitis B Virus Therapy. Viruses 2017, 9, 117. https://doi.org/10.3390/v9050117
Carracedo Rodriguez A, Chung M, Ciupe SM. Understanding the Complex Patterns Observed during Hepatitis B Virus Therapy. Viruses. 2017; 9(5):117. https://doi.org/10.3390/v9050117
Chicago/Turabian StyleCarracedo Rodriguez, Andrea, Matthias Chung, and Stanca M. Ciupe. 2017. "Understanding the Complex Patterns Observed during Hepatitis B Virus Therapy" Viruses 9, no. 5: 117. https://doi.org/10.3390/v9050117
APA StyleCarracedo Rodriguez, A., Chung, M., & Ciupe, S. M. (2017). Understanding the Complex Patterns Observed during Hepatitis B Virus Therapy. Viruses, 9(5), 117. https://doi.org/10.3390/v9050117