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Mathematical and Computer Modelling of Dynamical Systems
Methods, Tools and Applications in Engineering and Related Sciences
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Research Article

Structural stability of the hepatitis C model with the proliferation of infected and uninfected hepatocytes

, , , ORCID Icon &
Pages 51-72 | Received 14 Nov 2023, Accepted 08 Jan 2024, Published online: 04 Feb 2024

ABSTRACT

The structural stability of the hepatitis C model with the proliferation of infected and uninfected hepatocytes is investigated in this paper. The model is clinically verified to accurately reflect the viral dynamics of hepatitis C. It is demonstrated that the limit transition from the hepatitis C model to the Riccati system coupled with the diffusive terms leads to the elimination of the quadratic terms. Such a novel effect leads to the introduction of the concept of the deformed order-1 solitary solutions. The generalized operator of differentiation is used to construct the deformed order-1 solitary solutions to the Riccati system coupled with the diffusive terms. Finally, it is demonstrated that the Riccati system coupled with the diffusive terms admits non-deformed order-1 solitary solutions, which proves the structural instability of the hepatitis C model with the proliferation of infected and uninfected hepatocytes.

1. Introduction

The hepatitis C virus (HCV) infection represents a significant global public health problem [Citation1]. One of the first mathematical models used to describe the kinetics of chronic HCV infection during treatment has been introduced more than two decades ago [Citation2]. This paradigmatic phenomenological model include

s three ordinary coupled differential equations representing the population of target cells, productively-infected cells, and virus cells. However, the model in [Citation2] is not able to explain some observed HCV kinetic profiles under treatment [Citation3]. The model in [Citation4] expands the HCV viral-dynamic model [Citation2] by incorporating density-dependent proliferation what make the model predictions to agree with experimental observations during acute infection, under antiviral therapy, and after the cessation of therapy. The mathematical properties of this model, including steady state and dynamical behaviour are thoroughly analysed in [Citation5].

A common feature of nonlinear dynamical systems is that solitary solutions represent a separatrix in the space of system parameters and initial conditions [Citation6]. Therefore, the existence of solitary solutions may help understand the global dynamics of the system.

Kink solitary solutions to the hepatitis C model in [Citation4] are derived in [Citation7]. It is demonstrated in [Citation7] that kink solutions can be in either linear or hyperbolic (inverse) relationship. If kink solutions are in the linear relationship, an infinitesimal perturbation of infected cell population results in an infinitesimal perturbation of uninfected cell population. However, if solutions are in the hyperbolic relationship, a small perturbation of the uninfected cell population can result in a large alteration of the infected cell population [Citation7].

From a mathematical point of view, the hepatitis C model in [Citation4] represents two nonlinear Riccati equations coupled with both multiplicative and diffusive terms [Citation7]. Solitary solutions to Riccati system coupled with only multiplicative terms have already been studied in [Citation8]. However, the dynamics of Riccati equations coupled with only diffusive terms remains unexplored territory.

Diffusively coupled models provide crucial insight into the dynamical behaviour of a wide range of biological and engineering systems. For example, synchronization of diffusively coupled models is a rich area of research [Citation9]. In particular, the derivation of conditions that rule out synchronization does facilitate the study of spatial pattern formation [Citation10,Citation11].

Therefore, the main objective of this paper directly follows from the previous discussion. The existence of solitary solutions to a system of Riccati equations coupled with diffusive terms is an open question, particularly important due to the connections with the Hepatitis C model with the proliferation of infected and uninfected hepatocytes.

While diffusively coupled models are significant in modelling HCV evolution, numerous studies also consider their stochastic counterparts. A stochastic model of the spread of infectious diseases in considered in [Citation12]. Numerous studies on stochastic models for the evolution of hepatitis B virus have been recently performed [Citation13–16]. The impact of such models and some of their unifying properties is discussed in [Citation17].

Another question of particular importance to the modelling of biological phenomena is boundedness of the solutions. This topic is discussed extensively in partial differential equation (PDE) models of biological systems, especially in parabolic PDEs. For example, unbounded solutions to a chemotaxis model are studied along with their blow-up criteria in [Citation18] and [Citation19].

The paper is structured as follows. Basic definitions are given in the Preliminaries section. The concept of the deformed order-1 solitary solutions is presented in section 3. The role of the deformation function is discussed in section 4. The structure and the simplification of the deformed system is derived in sections 5 and 6. Deformed order-1 solitary solutions are constructed in section 6. The structural stability of the hepatitis C model with the proliferation of infected and uninfected hepatocytes is discussed in section 7. Concluding remarks are given in the last section.

2. Preliminaries

2.1. The hepatitis C virus infection model

The hepatitis C virus infection model with the inclusion of the proliferation of infected and uninfected hepatocytes reads [Citation5]:

(1) dTdt=s0+r1T1T+ITmaxd1T(1η)βVT+qI,dIdt=r2I1T+ITmaxd2I+(1η)βVTqI,dVdt=(1ε)pIcV,(1)

where t is time, T(t) represents uninfected hepatocytes; I(t) represents infected cells; V(t) represents virus-free population. All other model parameters are constants: s and q represent the increase rate of uninfected hepatocytes through immigration and spontaneous cure by noncytolytic process respectively; r1 and r2 are parameters of the logistic proliferation of T and I respectively (logistic proliferation happens only if T<Tmax); d1 and d2 are death rates for uninfected hepatocytes and infected cells respectively; η is the infection reduction rate induced by the antiviral treatment; β is the rate of infection per free virus per hepatocyte; ε is the fraction of the viral production rate induced by the antiviral treatment; p is the free virus production rate per infected cell; c is the immune virus clearance rate.

It is demonstrated in [Citation5] that the range of rates of viral clearance is significantly faster compared to other parameters on the time scale. Furthermore, the viral dynamics closely follow the dynamics of infected after a short transient process, resulting in the following equality for V(t) [Citation5]:

(2) V(t)=1εVt0+εVt0expctt0.(2)

Then, (1) can be rearranged into the general form by the introduction of dimensionless state variables [Citation7]:

(3) dxdt=a0+a1x+a2x2+a3xy+a4y,dydt=b0+b1y+b2y2+b3xy+b4x.(3)

where ak,bkR; k=0,1,,4. From the mathematical point of view, system (3) does represent two Riccati differential equations with constant coefficients coupled with diffusive and multiplicative terms.

It is worthwhile to note that (3) represents a classical system for modelling HCV dynamics. These systems may have a variety of modifications, such as the application of a fractional-order derivative instead of classical derivation. The properties of such of such derivatives have been discussed in detail in [Citation20]. The value of their application to biological systems has been established in [Citation21] and a particular case concerning the hepatitis B virus (HBV) is considered in [Citation22].

2.2. Solitary solutions and their orders

The standard form of a solitary solution reads [Citation23]:

(4) xt=σk=1nexpηtt0xkk=1nexpηtt0tk,(4)

where nN is the order of the solitary solution; and σ, η, t0, xk, tkR are real parameters.

The first order solitary solution (at n=1) represents a sigmoid function describing the transition from one steady state to another steady state via a monotonous trajectory.

2.3. Riccati equation with constant coefficients

The Riccati equation with constant coefficients

(5) dxdt=a0+a1x+a2x2(5)

admits the first order solitary solution when parameters a0, a1, a2R are such that the roots of the polynomial a0+a1x+a2x2=a2xr1xr2 are real r1r2. Then, the first order solitary solution to 5 reads [Citation6]:

(6) x(t)=σexpηtt0x1expηtt0t1(6)

where σ=r2; η=a2r1r2; x1=r1r2ur2ur1; t1=ur2ur1; u denotes the initial condition xt0=u satisfying the system of inequalities r1ur2. The first order solitary solution is depicted in .

Figure 1. The first order solitary solution to (5) at a2=1,r1=12,r2=23 and the initial condition x(0)=13.

Figure 1. The first order solitary solution to (5) at a2=1,r1=12,r2=−23 and the initial condition x(0)=13.

2.4. A system of diffusively coupled Riccati equations

The paradigmatic model of two diffusively coupled dynamical systems reads [Citation9]:

(7) dxdt=Fx+εxyx;dydt=Gy+εyxy,(7)

where t is time; F and G are the functions that represent isolated chaotic dynamics of x and y; εx and εy are diffusive coupling parameters usually set as a positive constants.

Thus, the system of two diffusively coupled Riccati equations can be reduced to the following standard form:

(8) dxdt=a0+a1x+a2x2+εxy;dydt=b0+b1y+b2y2+εyx,(8)

where ak,bkR, k=1,2,3; a20; b20.

3. The concept of the deformed order–1 solitary solutions to (8)

Definition 3.1.

The order–1 solitary solutions to 8 read:

(9) x(t)=σxexpηtt0x1expηtt0t1;y(t)=σyexpηtt0y1expηtt0t1.(9)

Note that parameters η, t0, and t1 must be the same for both functions x(t) and y(t) in order to ensure the preservation of consistency between the coupled nonlinear differential equations [Citation7].

3.1. The existence of the order–1 solitary solutions to (8)

The existence of the order–1 solitary solutions to (8) follows directly from the properties of (3). The necessary condition for the existence of the order–1 solitary solutions to (3) is given by [Citation7]:

(10) a3=b2;b3=a2.(10)

The model (3) is mapped to (8) when both parameters a3 and b3 are set to zero (the multiplicative coupling is eliminated from (3)). However, in that case, the conditions for the existence of the order–1 solitary solutions (10) require that a2=0 and b2=0 which contradicts the definition of the Riccati Equationequations (5) (). Therefore, the following hypothesis is posed.

Figure 2. A schematic diagram illustrating the limit transition from the hepatitis C model to the degenerate riccati system with diffusive coupling.

Figure 2. A schematic diagram illustrating the limit transition from the hepatitis C model to the degenerate riccati system with diffusive coupling.

Hypothesis 3.1.

The limit transition from (3) to (8) suggests that order–1 solitary solutions to (8) do not exist.

3.2. The proposed architecture of the deformed order–1 solitary solutions

Definition 3.2.The deformed order–1 solitary solution reads:

(11) x(t)=σxφ(t)x1φ(t)t1;y(t)=σyφ(t)y1φ(t)t1,(11)
where the function φ(t) defines the unknown time deformation.

In other words, a hypothesis is posed that (8) admits the order–1 solitary solutions if only the time axis is deformed according to the deformation function φ(t).

Remark 1. For any pair of deformed order-1 solitary solutions (11), there exists parameters A,BR such that x(t) and y(t) are in a linear relationship Ax(t)+By(t)=1.

Proof. Using basic rearrangements, (11) yields:

(12) σyt1y1x(t)σxt1x1y(t)=σxσyx1y1.(12)

Dividing both sides by σxσyx1y1 yields:

(13) A=t1y1σxx1y1,B=t1x1σyy1x1,(13)

which proves the statement.

4. The role of the deformation function φ(t)

The proposed deformed order–1 solitary solution (11) may not satisfy (8). Note that (11) defines the non-deformed order–1 solitary solution (9) at φ(t)=expη(tt0). Therefore, (8) is extended in order to accommodate a larger class of solutions:

(14) f(t)dxdt=a0+a1x+a2x2+εxy,f(t)dydt=b0+b1y+b2y2+εyx,(14)

where f(t) is an unknown function representing this extension.

Definition 4.1. System (14) is called the extended system of (8).

Definition 4.2. The transformed time scale is defined as tˆ:=φ(t).

The variable substitution (t by tˆ) modifies the structure of (8). These changes are represented by the function fˆtˆ:

(15) fˆtˆdxˆdtˆ=a0+a1xˆ+a2xˆ2+εxyˆ,fˆtˆdyˆdtˆ=b0+b1yˆ+b2yˆ2+εyxˆ.(15)

Definition 4.3. System (15) is called the image system of (14).

Lemma 4.4. Functions fˆtˆ, tˆ=φ(t), and f(t) (if they exist) are related by the following differential equation:

(16) (t)dt=fˆ(φ(t))f(t).(16)

Proof. Consider the following solution to the extended system (14): x=x(t); y=y(t). Let us assume that the image system (15) exists. Then the solution to the image system (15) does satisfy the following identities:

(17) x(t)=xˆ(φ(t));y(t)=yˆ(φ(t)),(17)

if only the variable change function tˆ:=φ(t) exists. Then,

(18) dx(t)dt=dxˆtˆdtˆ|tˆ=φ(t)(t)dt;dy(t)dt=dyˆtˆdtˆ|tˆ=φ(t)(t)dt.(18)

The image system can be transformed into:

(19) fˆtˆdxˆdtˆ|tˆ=φ(t)=a0+a1xˆ+a2xˆ2+εxyˆ|tˆ=φ(t),fˆtˆdyˆdtˆ|tˆ=φ(t)=b0+b1yˆ+b2yˆ2+εyxˆ|tˆ=φ(t).(19)

Therefore,

(20) fˆ(φ(t))dx(t)dt/(t)dt=a0+a1x+a2x2+εxy,fˆ(φ(t))dy(t)dt/(t)dt=b0+b1y+b2y2+εyx.(20)

Comparing (14) and (20) yields the following identities:

(21) fˆ(φ(t))dx(t)dt/(t)dt=f(t)dx(t)dt;fˆ(φ(t))dy(t)dt/(t)dt=f(t)dy(t)dt,(21)

which concludes the proof.

Corollary 4.5 x(t)=xˆφ(t); y(t)=yˆφ(t).

Example 4.6. The Exp-function method for the Riccati equation.

The Exp-function method, which was proposed more than two decades ago in [Citation24], uses the exp-function variable substitution in order to transform the original differential equation to the image differential equation. Let us consider the Riccati equation with constant coefficients (5). The new variable tˆ is set in the form of the exponent:

(22) tˆ=expη(tt0)=φ(t).(22)

The change of variables transforms (5) into the image differential equation:

(23) ηtˆdxˆdtˆ=a0+a1xˆ+a2xˆ2.(23)

The solution to (23) can be constructed using operator techniques [Citation25] and expressed in the closed form:

(24) xtˆ=r2tˆx1tˆt1,(24)

where r2, x1, and t1 are defined in (6). Therefore, fˆtˆ=ηtˆ and f(t)=1. It follows from (22) that dt=ηexpη(tt0). On the other hand, according to (16):

(25) dt=fˆtˆf(t)=ηtˆ=ηexpη(tt0).(25)

Thus, the introduction of the deformation function φ(t) can be considered as the generalization of the Exp-function method where the function f(t) is not necessarily set to 1.

Example 4.7. The classical Exp-function method implies tˆ=exp(ηt). Then, functions fˆtˆ=ηtˆ, tˆ=exp(ηt) and f(t)=1 are related by (16). Thus, the image system (15) is given by:

(26) ηtˆdxˆdtˆ=a0+a1xˆ+a2xˆ2+εxyˆ,ηtˆdyˆdtˆ=b0+b1yˆ+b2yˆ2+εyxˆ,(26)

and xˆ=σxtˆx1tˆt1; yˆ=σytˆy1tˆt1 are the solutions to (26).

In other words, the original problem is split into two problems. The process of the construction of the solution to (14) is transformed into two consecutive problems (16) and (15).

5. The structure of the function fˆtˆ

As previously demonstrated, the deformed order–1 solitary solution to the image system (15) reads:

(27) xˆtˆ=σxtˆx1tˆt1,yˆtˆ=σytˆy1tˆt1.(27)

Thus,

(28) dxˆtˆdtˆ=σxx1t1(tˆt1)2,dyˆtˆdtˆ=σyy1t1(tˆt1)2.(28)

Inserting (27) and (28) into (15) yields a system of two identities:

(29) fˆtˆσx(x1t1)=a0(tˆt1)2+a1σx(tˆt1)(tˆx1)+a2σx2(tˆx1)2+εxσy(tˆy1)(tˆt1),fˆtˆσy(y1t1)=b0(tˆt1)2+b1σy(tˆt1)(tˆy1)+b2σy2(tˆy1)2+εyσx(tˆx1)(tˆt1).(29)

Definition 5.1. System (29) is called the balancing system of (15).

Taking tˆ equal to t1, x1, and y1 in the balancing system (29) yields the following systems of equations:

(30) fˆ(t1)σx(x1t1)=a2σx2(t1x1)2,fˆ(t1)σy(y1t1)=b2σy2(t1y1)2;(30)
(31) fˆ(x1)σx(x1t1)=a0(x1t1)2+εxσy(x1y1)(x1t1),fˆ(x1)σy(y1t1)=b0(x1t1)2+b1σy(x1y1)(x1t1)+b2σy2(x1y1)2;(31)
(32) fˆ(y1)σx(x1t1)=a0(y1t1)2+a1σx(y1x1)(y1t1)+a2σx2(y1x1)2,fˆ(y1)σy(y1t1)=b0(y1t1)2+εyσx(y1x1)(y1t1);(32)

Note that fˆ(t1), fˆ(x1), and fˆ(y1) are constants (the values of the function fˆtˆ at tˆ=t1, x1, and y1 accordingly).

In total, Riccati equations in (15) are comprised of eight unknowns (ak,bk,k=0,1,2 and εx,εy). Computer algebra helps to solve the system for six unknowns a0, a1, a2, b0, b1, and b2 from ((30), (31), (32)):

(33) a0=fˆ(x1)σx(x1y1)εxσyt1x1(33)
(34) a1=fˆ(x1)(t1y1)2σxfˆ(y1)(t1x1)2σx+fˆ(t1)(x1y1)2σx(t1x1)(t1y1)(x1y1)σx(t1y1)2(x1y1)εxσy(t1x1)(t1y1)(x1y1)σx(34)
(35) a2=fˆ(t1)(t1x1)σx(35)
(36) b0=fˆ(y1)σy(y1x1)εyσxt1y1(36)
(37) b1=fˆ(y1)(t1x1)2σyfˆ(x1)(t1y1)2σy+fˆ(t1)(y1x1)2σy(t1x1)(t1y1)(y1x1)σy(t1x1)2(y1x1)εyσx(t1x1)(t1y1)(y1x1)σy(37)
(38) b2=fˆ(t1)(t1y1)σy(38)

Inserting the expressions of a0, a1, a2, b0, b1, and b2 into any equality of the balancing system (29) yields the same expression of fˆtˆ:

(39) fˆtˆ=fˆ(x1)(t1y1)(tˆt1)(tˆy1)+fˆ(y1)(t1x1)(tˆt1)(tˆx1)(t1x1)(t1y1)(x1y1)+fˆ(t1)(x1y1)(tˆx1)(tˆy1)(t1x1)(t1y1)(x1y1).(39)

It is interesting to note that fˆtˆ is not dependant on εx,εy. Moreover, fˆtˆ is a second order polynomial with respect of tˆ:

(40) fˆtˆ=A0+A1tˆ+A2tˆ2,(40)

where

(41) A0=fˆ(x1)t1y1(t1y1)+fˆ(y1)t1x1(t1x1)+fˆ(t1)x1y1(x1y1)(t1x1)(t1y1)(x1y1),(41)
(42) A1=fˆ(x1)(t12y12)fˆ(y1)(t12x12)fˆ(t1)(x12y12)(t1x1)(t1y1)(x1y1),(42)
(43) A2=fˆ(x1)(t1y1)+fˆ(y1)(t1x1)+fˆ(t1)(x1y1)(t1x1)(t1y1)(x1y1).(43)

6. The simplification of the structure of the function fˆtˆ

The balancing system (29) reveals that the coefficient A2 in (40) is equal to zero if the following identities hold true:

(44) a0+a1σx+a2σx2+εxσy=0,b0+b1σy+b2σy2+εyσx=0.(44)

Let us assume that the parameters a0, a1, a2, b0, b1, b2, εx, and εy are given by the model of the system of two Riccati equations coupled with diffusive terms (8). Then, the parameters σx and σy can be computed via (44). In other words, a proper selection of σx and σy (the parameters of the deformed order–1 solitary solution) ensures that identities (44) hold true.

Lemma 6.1. Let the parameters a0, a1, a2, b0, b1, b2, εx, εy, t1 be fixed, and the parameters σx, σy, x1, x2 satisfy (44) in addition to the following system of identities:

(45) σy(y1t1)(a0t12+a1σxt1x1+a2σx2x12+εxσyy1t1)==σx(x1t1)(b0t12+b1σyt1y1+b2σy2y12+εyσxx1t1),σy(y1t1)(2a0t1+a1σx(t1+x1)+2a2σx2x1+εxσy(y1+t1))==σx(x1t1)(2b0t1+b1σy(t1+y1)+2b2σy2y1+εyσx(x1+t1)).(45)

Then, the structure of the function fˆtˆ is simplified to:

(46) fˆtˆ=A0+A1tˆ,(46)

and the deformed order1 solitary solution (27) satisfies the image system (15).

Proof. The proof follows directly from Lemma 4.4 and the balancing system (29).

Taking Lemma 6.1 into account, expressions (33)–(38) are simplified into:

(47) a0=A0σx+A1σxx1σyx1εx+σyy1εxx1t1;(47)
(48) a1=2A0σx+A1σxt1+A1σxx1σyt1εx+σyy1εxσxt1x1;(48)
(49) a2=A0+A1t1σxx1t1;(49)
(50) b0=A0σy+A1σyy1σxy1εy+σxx1εyy1t1;(50)
(51) b1=2A0σy+A1σyt1+A1σyy1σxt1εy+σxx1εyσyt1y1;(51)
(52) b2=A0+A1t1σyy1t1.(52)

Example 6.2. This example illustrates the inverse balancing technique used to reconstruct the extended system of two Riccati equations coupled with diffusive terms (14) from the deformed order–1 solitary solution (27).

Consider parameter values σx=74, σy=196, t1=2, x1=227, y1=5019. Thus,

(53) xˆtˆ=22+7tˆ8+4tˆ,yˆtˆ=50+19tˆ12+6tˆ.(53)

Let us choose fˆ(t1)=2, fˆx1=227, and fˆ(y1)=5019 which guarantees the identity fˆ(x1)(t1y1)+fˆ(y1)(t1x1)+fˆ(x1y1)=0. Therefore, by (43) A2=0 (A0=0, A1=1).

Now, εx=12 and εy=13 yield coefficients a0=26548, a1=4, a2=1, b0=22918, b1=7, b2=1.

Let us investigate two cases of function φ(t):

Case 1. Let φ(t)=t2. Then, fˆtˆ=tˆ and f(t)=t2. Finally,

(54) x(t)=22+7t28+4t2,y(t)=50+19t212+6t2(54)

is the analytical solution (see ) to:

(55) t2dx(t)dt=265484xx2+12y,t2dy(t)dt=229187y+y2+13x.(55)

Figure 3. Deformed order-1 solitary solutions x(t),y(t) (see eq. (54)) to (55).

Figure 3. Deformed order-1 solitary solutions x(t),y(t) (see eq. (54)) to (55).

Case 2. Let φ(t)=sin(t). Then, fˆtˆ=tˆ and f(t)=tan(t). Finally,

(56) x(t)=22+7sin(t)8+4sin(t),y(t)=50+19sin(t)12+6sin(t)(56)

is the analytical solution (see ) to:

(57) tan(t)dx(t)dt=265484xx2+12y,tan(t)dy(t)dt=229187y+y2+13x.(57)

Figure 4. Deformed order-1 solitary solutions x(t),y(t) (see eq. (56)) to (57).

Figure 4. Deformed order-1 solitary solutions x(t),y(t) (see eq. (56)) to (57).

7. The construction of deformed order-1 solitary solutions to (15)

7.1. The generalized operator of differentiation

The general solution to (15) is considered in the following form:

(58) xˆ0:=xˆ(tˆ,c,u,v),yˆ0:=yˆ(tˆ,c,u,v),(58)

where cR is the centre of the expansion of the solutions xˆ0 and yˆ0; u,vR are the initial conditions u=xˆ0(tˆ0,c,u,v) and v=yˆ0(tˆ0,c,u,v).

According to (46), the simplified structure of the function fˆtˆ is set to:

(59) fˆtˆ=κ(tˆν);(59)

where κ=A1 and ν=A0A1. Now, the generalized differential operator of (15) reads [Citation25]:

(60) Dcuv:=Dc+1κ(cν)(a0+a1u+a2u2+εxv)Du+(b0+b1v+b2v2+εyu)Dv(60)

where Dc:=∂c; Du:=∂u; Dv:=∂v. Then the general solution to (15) is given by:

(61) x0ˆ(tˆ,c,u,v)=j=0+(tˆc)jj!pj(c,u,v),y0ˆ(tˆ,c,u,v)=j=0+(tˆc)jj!qj(c,u,v),(61)

where

(62) pj(c,u,v):=Dcuvju,qj(c,u,v):=Dcuvjv.(62)

Solution (61) is the analytical solution to (15). However, the only solutions of interest to this study are those which can be expressed in closed form. The closed form solutions exist if the sequence of parameters pj(c,u,v) and qj(c,u,v) form linear recurrence sequences [8].

Lemma 7.1. The first roots of the characteristic polynomials of the linear recurrence sequences (62) are equal to 0.

Proof. The expression of the deformed order-1 solitary solutions in (27) can be rearranged as follows:

(63) xˆtˆ=σxtˆx1tˆt1=σx+σx(t1x1)tˆt1=σx+λ1j=0+(tˆt1)jj!j!ρxj,yˆtˆ=σytˆy1tˆt1=σy+σy(t1y1)tˆt1=σy+μ1j=0+(tˆt1)jj!j!ρyj,(63)

where λ1,μ1R, and the common ratios of the geometric progressions ρx and ρy are non-zero. Therefore, the roots of the characteristic polynomial of the linear recurrence sequence σx+λ1,λ1ρx,λ1ρx2, are 0 and ρx0. Analogously, the roots of the characteristic polynomial of the linear recurrence sequence σy+μ1,μ1ρy,μ1ρy2, are 0 and ρy0.

The structure of the deformed order-1 solitary solution (27) requires that the linear recurrence sequences have an order of 2:

(64) pj(c,u,v)=j!λ00j+λ1(ρx(c,u,v))j,qj(c,u,v)=j!μ00j+μ1(ρy(c,u,v))j,(64)

where λ0,λ1R; ρx and ρy are non-zero roots of the characteristic polynomials of the linear recurrence sequences (62).

Then, according to the basic properties of geometric progressions, the general solution to (15) reads:

(65) x0ˆ(tˆ,c,u,v)=λ0+λ1/(1ρx(c,u,v)(tˆc)),y0ˆ(tˆ,c,u,v)=μ0+μ1/(1ρy(c,u,v)(tˆc)).(65)

7.2. The Hankel determinants

Suppose that (64) hold true. Then, the following determinants of Hankel matrices are equal to zero at least for some values of the parameters c, u, and v:

(66) Hx(c,u,v)=detp11!p22!p22!p33!=0;Hy(c,u,v)=detq11!q22!q22!q33!=0.(66)

Note that higher-order Hankel determinants also vanish [Citation25]. Furthermore, full Hankel determinants p00!p11!p22!p11!p22!p33!p22!p33!p44! and q00!q11!q22!q11!q22!q33!q22!q33!q44! are not necessary to consider since the first root ρ0 of linear recurrence sequences (64) is zero (Lemma 7.1).

The expressions of pj(c,u,v) and qj(c,u,v); j=1,2,3 follow from 62. These expressions are listed in Appendix A.

Let us consider a hypothesis that the initial conditions u,v corresponding to order-1 solitary solutions are in the following linear relationship:

(67) L:u:=αxω+βx;v:=αyω+βy,(67)

where L denotes a line in the phase space of initial conditions; ω is the parameter generating the line; αx, αy, βx, βyR are parameters defining the orientation of line L.

Note that the Hankel determinants (66) can be expressed as fifth order polynomial with respect to ω:

(68) Hx(c,u,v)|u,vL=H˜x(ω,αx,αy,βx,βy)=j=05θj(x)ωj;Hy(c,u,v)|u,vL=H˜y(ω,αx,αy,βx,βy)=j=05θj(y)ωj,(68)

where the expressions of θj(x) and θj(y) are determined using computer algebra.

7.3. Conditions for the existence of deformed solitary solutions to 15

Coefficients θ5(x) and θ5(y) read:

(69) θ5(x)=4a2αx2αy(a2αxb2αy)2εx;θ5(y)=4b2αxαy2(a2αxb2αy)2εy.(69)

Equating θ5(x) and θ5(y) to zero yields the following relations:

(70) αx=b2αya2;αy=a2αxb2.(70)

Note that θ5(x) and θ5(y) may also vanish when a2,b2,αx,αy,εx,εy are set to zero, however, that would result in a special case of the considered system that is either uncoupled or linear. Because of this, these cases are no longer considered.

Solution to (70) reads:

(71) αx=b2;αy=a2.(71)

Relations (71) are applied in order to simplify the coefficients θ4(x) and θ4(y):

(72) θ4(x)=a22b22a12b22+4a0a2b222a2b1b2εx+a22εx22b22εxεy+b22κ2;(72)
(73) θ4(y)=a22b22b12a22+4b0b2a222b2a1a2εy+b22εy22a22εyεx+a22κ2.(73)

Setting θ4(x) to zero yields:

(74) κ2=a124a0a2+εx2a2b1b2a22εx+2b22εyb22.(74)

Analogously, setting θ4(y) to zero yields:

(75) κ2=b124b0b2+εy2b2a1a2b22εy+2a22εxa22.(75)

Identities (74) and (75) yield the following relation:

(76) 4a23b22a0+a12a22b222a1a2b23εya24εx2+2a23b1b2εx+4a22b0b23a22b12b22+b24εy2=0(76)

Relations (74)-(76) are applied to simplify the coefficients θ3(x) and θ3(y), resulting in:

(77) θ3(x)=εx2a22b2βx2b22a2βy+b2a2a1+a22εxb2a2b1εyb222;θ3(y)=εy2a22b2βx2b22a2βy+b2a2a1+a22εxb2a2b1εyb222.(77)

Note that due to the relation (70), coefficients θ3(x) and θ3(y) in (77) are proportional:

(78) θ3(y)=εyεxθ3(x).(78)

Thus, equating θ3(x) and θ3(y) to zero yields one equality instead of two:

(79) 2a2b22βy+b2a2b1+εyb22=2a22b2βx+a2b2a1+εxa22.(79)

Applying all the relations mentioned above yields θ2(x)=θ2(y)=θ1(x)\break=θ1(y)=θ0(x)=θ0(y)=0 and consequently Hx=Hy=0.

Note that the computations presented above demonstrate that the hypothesized relation between initial conditions u,v (67) yields order-1 solitary solutions.

7.4. Main theorem

Derivations provided up to this point can be summarized in the following Theorem:

Theorem 7.2. The image system of Riccati equations with diffusive coupling (15) and initial conditions xˆ(c)=u,yˆ(c)=v admits the kink solitary solution (27) if:

  1. Condition (76) holds true;

  2. Initial conditions u,v lie on the following line in the phase space:

    (80) a2a2βxb2βyu+b2b2βya2βxv=1,(80)

where βx,βy satisfy (79).

Proof.

  1. The proof is provided in Section 7.3: this condition is part of the sufficient condition for the Hankel determinants to become equal to zero.

  2. Equations (67) yield the following equality:

    (81) uβxαx=vβyαy.(81)

    Basic rearrangements result in the second point of Theorem.

Let the conditions (1) and (2) of Theorem 7.2 hold true. Then, according to Lemma 7.1, the first roots of the characteristic polynomials of the linear recurrence sequences (62) are equal to 0. The remaining non-zero roots ρx and ρy are computed using the following characteristic equations:

(82) p11!p22!1ρx=0;q11!q22!1ρy=0.(82)

Solving (82) yields:

(83) ρx=ρy=12κa2ca22(αyω+βy)b2κ+b1+b2εy.(83)

Parameters λ0, λ1, μ0, μ1 of the general solution (65) to (15) can be obtained by solving the following systems of linear equations (as seen from (64)):

(84) p0=1!(λ000+λ1ρx0)=λ0+λ1;p1=2!(λ001+λ1ρx1)=2λ1ρx;(84)
(85) q0=1!(μ000+μ1ρy0)=μ0+μ1;q1=2!(μ001+μ1ρy1)=2μ1ρy;(85)

Note that 00 is taken to be equal to 1 [Citation26].

Solutions to (84)–(85) are given as follows:

(86) λ0=a1b2+a2εx+κb22a2b2;λ1=uλ0;μ0=b1a2+b2εy+κa22b2a2;μ1=vμ0.(86)

Using Theorem 7.2, important conclusions are made about the original system of Riccati equations with diffusive coupling (14).

Corollary 7.3. The system of Riccati equations with diffusive coupling (14) and initial conditions x(t0)=u,y(t0)=v admits the deformed kink solitary solution (11) if:

  1. Condition (76) holds true;

  2. Initial conditions u,v lie on the line 80 where βx,βy satisfy (79);

  3. The independent variable substitution φ(t) reads:

    (87) φ(t)=ν+cνexpκt0tdτfτ,φ(t0)=c;(87)

Proof. Points 1 and 2 follow directly from Theorem 7.2. To prove point 3, note that by Lemma 4.4, the independent variable substitution φ(t) satisfies (16). Furthermore, fˆtˆ is given by (59). Combining these two equalities yields:

(88) dt=κφνf(t).(88)

Integration of the above equality with respect to t yields (87).

The relationship between the system of Riccati equations with diffusive coupling (14), the image system (15) and their respective solutions is depicted in .

Figure 5. Schematic summary of theorem 7.2 and corollary 7.3: the relationship between Riccati system with diffusive coupling, the image system and their kink solitary solutions.

Figure 5. Schematic summary of theorem 7.2 and corollary 7.3: the relationship between Riccati system with diffusive coupling, the image system and their kink solitary solutions.

8. The structural stability of (3)

Let us consider f(t)=1. Then, according to Lemma 4.4 the deformation function φ(t) reads:

(89) φ(t)=expt+ν.(89)

Inserting 89 into 11 yields:

(90) x(t)=σxexpt+νx1expt+νt1;y(t)=σyexpt+νy1expt+νt1,(90)

which are the non-deformed order–1 solitary solutions 9 to 8 (at η=1 and t0=0). In other words, Theorem 7.2 implies that Hypothesis 3.1 does not hold true.

This result is completely counter-intuitive. The transition from the hepatitis C virus infection model (3) to the model of two Riccati equations coupled with diffusive terms (8) can be executed only by erasing the multiplicative terms in (3). However, the necessary conditions for the existence of non-deformed order–1 solitary solutions to (3) require the identities (10) to hold true. But identities (10) eliminate the quadratic terms from (8). In other words, Riccati equations in (8) are reduced to linear differential equations. Therefore, the limiting transition in the hepatitis C virus infection model does not allow the existence of non-deformed order–1 solitary solutions to (8). However, Theorem 7.2 yields an opposite result. It is clear that non-deformed order-1 solitary solutions to (8) indeed exist.

Structural stability is a fundamental property of a dynamical system which means that the qualitative behaviour of the trajectories is unaffected by small perturbations [Citation27]. The limiting transition in (3) accompanied by the necessary and sufficient conditions for the existence of non-deformed order-1 solitary solutions does not produce correct results. In other words, the perturbation from (8) to (3) changes the existence of solitary solutions if executed by adding the multiplicative coupling terms (even with infinitesimal, but non-zero weight coefficients).

Corollary 8.1. The hepatitis C virus infection model 1 is structurally unstable with respect to the multiplicative coupling terms.

9. Concluding remarks

It is a common feature of nonlinear dynamical systems that a solitary solution form a separatrix in the space of system parameters and initial conditions [Citation6]. Therefore, the existence of solitary solutions may help to understand the global dynamics of the system [Citation28]. In particular, kink solitary solutions to the hepatitis C virus infection model can be either in a linear or in a hyperbolic relationship ([Citation7]). Thus, a large perturbation in the population of hepatitis infected cells does not necessarily lead to a large change in uninfected cells (if the relationship is hyperbolic) ([Citation7]).

However, the results of this paper imply that the situation with the order-1 solitary solutions to the hepatitis C virus infection model is even more complex. The limit transition from the hepatitis C virus infection model to the model of Riccati equations coupled with the diffusive terms does not destroy the existence of the order-1 solitary solutions. Furthermore, this controversy does not occur in the other limit transition from the hepatitis C virus infection model to the model of Riccati equations coupled with the multiplicative terms (setting a4 and b4 to zero in (3) does not destroy the structure of Riccati equations).

Apart from the biological relevance, this paper provides a significant contribution to the mathematical theory of solitary solutions to nonlinear differential equations. It appears that the role of diffusive and multiplicative coupling terms in the dynamics of nonlinear systems is very different not only from the point of view for the existence and the stability of equilibria, but also with respect to the existence of solitary solutions to the coupled equations. Further extension of the complexity of the coupled model to additional spatial dimensions (for example, coupled systems on heterogeneous graphs) and towards more complex nodal nonlinearity (beyond Riccati nomenclature) remains a definite objective of future research.

Disclosure statement

No potential conflict of interest was reported by the author(s).

References

  • L.B. Seeff and J.H. Hoofnagle. 2002. National institutes of health consensus development conference: Management of hepatitis C: 2002. Hepatology. 36 (5B): S1–S2. doi: 10.1053/jhep.2002.36992.
  • A.U. Neumann, N.P. Lam, H. Dahari, D.R. Gretch, T.E. Wiley, T.J. Layden, and A.S. Perelson. 1998. Hepatitis C viral dynamics in vivo and the antiviral efficacy of interferon-α therapy, Science. 282 (5386): 103–107. doi: 10.1126/science.282.5386.103.
  • H. Dahari, A. Lo, R.M. Ribeiro, and A.S. Perelson. 2007. Modeling hepatitis C virus dynamics: Liver regeneration and critical drug efficacy, J. Theor. Biol. 247 (2): 371–381. doi: 10.1016/j.jtbi.2007.03.006.
  • H. Dahari, R.M. Ribeiro, and A.S. Perelson. 2007. Triphasic decline of hepatitis C virus RNA during antiviral therapy, Hepatology 46 (1): 16–21. doi: 10.1002/hep.21657.
  • T.C. Reluga, H. Dahari, and A.S. Perelson. 2009. Analysis of hepatitis C virus infection models with hepatocyte homeostasis, SIAM J Appl Math 69 (4): 999–1023. doi: 10.1137/080714579.
  • T. Telksnys, Z. Navickas, I. Timofejeva, R. Marcinkevicius, and M. Ragulskis. 2019. Symmetry breaking in solitary solutions to the Hodgkin–Huxley model, Nonlinear Dyn 97 (1): 571–582. doi: 10.1007/s11071-019-04998-4.
  • T. Telksnys, Z. Navickas, M.A. Sanjuán, R. Marcinkevicius, and M. Ragulskis 2020. Kink solitary solutions to a hepatitis C evolution model, Discrete And Contin. Dynamical Syst.-B. 25 4427–4447.
  • Z. Navickas, R. Marcinkevicius, T. Telksnys, and M. Ragulskis. 2016. Existence of second order solitary solutions to Riccati differential equations coupled with a multiplicative term, Ima J. Appl. Math. 81 (6): 1163–1190. doi: 10.1093/imamat/hxw050.
  • J.K. Hale. 1997. Diffusive coupling, dissipation, and synchronization, J. Dyn. Differ. Equ. 9 (1): 1–52. doi: 10.1007/BF02219051.
  • M.C. Cross and P.C. Hohenberg. 1993. Pattern formation outside of equilibrium, Rev Mod Phys 65 (3): 851. doi: 10.1103/RevModPhys.65.851.
  • S.Y. Shafi, M. Arcak, M. Jovanović, and A.K. Packard 2013. Synchronization of diffusively-coupled limit cycle oscillators, Automatica 49 (12): 3613–3622. doi: 10.1016/j.automatica.2013.09.011.
  • A. Din. 2021. The stochastic bifurcation analysis and stochastic delayed optimal control for epidemic model with general incidence function, Chaos: An Interdiscip. J. Nonlinear Sci. 31 (12): doi: 10.1063/5.0063050
  • A. Din, Y. Li, A. Yusuf, J. Liu, and A.A. Aly. 2022. Impact of information intervention on stochastic hepatitis B model and its variable-order fractional network, Eur Phys J Spec Top 231 (10): 1859–1873. doi: 10.1140/epjs/s11734-022-00453-5.
  • A. Din, Y. Li, and A. Yusuf. 2021. Delayed hepatitis B epidemic model with stochastic analysis, Chaos Soliton. Fract. 146 110839. doi: 10.1016/j.chaos.2021.110839.
  • A. Din and Y. Li. 2021. Stationary distribution extinction and optimal control for the stochastic hepatitis B epidemic model with partial immunity, Phys. Scr. 96 (7): 074005. doi: 10.1088/1402-4896/abfacc.
  • A. Din and Y. Li. 2022. Mathematical analysis of a new nonlinear stochastic hepatitis B epidemic model with vaccination effect and a case study, Eur. Phys. J. Plus 137 (5): 1–24. doi: 10.1140/epjp/s13360-022-02748-x.
  • A. Din and Q.T. Ain. 2022. Stochastic optimal control analysis of a mathematical model: Theory and application to non-singular kernels, Fractal. Fract. 6 (5): 279 doi: 10.3390/fractalfract6050279.
  • A. Columbu, S. Frassu, and G. Viglialoro. 2023. Properties of given and detected unbounded solutions to a class of chemotaxis models, Stud. Appl. Math. 151 (4): 1349–1379. doi: 10.1111/sapm.12627.
  • T. Li, S. Frassu, and G. Viglialoro. 2023. Combining effects ensuring boundedness in an attraction–repulsion chemotaxis model with production and consumption, Z. Angew. Math. Phys. 74 (3): 109. doi: 10.1007/s00033-023-01976-0.
  • K. Hattaf. 2023. A new class of generalized fractal and fractal-fractional derivatives with non-singular kernels, Fractal. Fract. 7 (5): 395. doi: 10.3390/fractalfract7050395.
  • K. Hattaf. 2022. On the stability and numerical scheme of fractional differential equations with application to biology, Computation 10 (6): 97. doi: 10.3390/computation10060097.
  • A. Tridane, K. Hattaf, R. Yafia, and F.A. Rihan. 2016. Mathematical modeling of HBV with the antiviral therapy for the immunocompromised patients, Commun. Math. Biol. Neurosci 2016. Article–ID 20.
  • Scott A. 2006. Encyclopedia of Nonlinear Science. New York: Routledge.
  • J.H. He and X.H. Wu. 2006. Exp-function method for nonlinear wave equations, Chaos Soliton. Fract. 30 (3): 700–708. doi: 10.1016/j.chaos.2006.03.020.
  • Z. Navickas, L. Bikulciene, and M. Ragulskis. 2010. Generalization of Exp-function and other standard function methods, Appl. Math. Comput. 216 (8): 2380–2393. doi: 10.1016/j.amc.2010.03.083.
  • D.E. Knuth. 1992. Two notes on notation, Am. Math. Mon. 99 (5): 403–422. doi: 10.1080/00029890.1992.11995869.
  • Arnold V.I. 1988. Geometrical Methods in the Theory of Ordinary Differential Equations, Vol. 250. New York: Springer.
  • T. Nagatani. 2020. Migration difference in diffusively-coupled prey–predator system on heterogeneous graphs, Physica A 537 122705. doi: 10.1016/j.physa.2019.122705.

Appendix A.

Coefficients p1,p2,p3 and q1,q2,q3

(A1) p1=1κcνa0+a1u+a2u2+εxv;(A1)
(A2) q1=1κcνb0+b1v+b2v2+εyu;(A2)
(A3) p2=1κ2cν2(2u3a22a2κ3a1u2+2va2+εyεxκa1+2a0a2+a12u+va1+v2b2+κ+b1v+b0εxa0κa1);(A3)
(A4) q2=1κ2cν2(2v3b22b2κ3b1v2+2vb2+εxεyκb1+2b0b2+b12v+vb1+u2a2+κ+a1u+a0εyb0κb1);(A4)
(A5) p3=1κ3cν3(v2va2+εyεx2+8va22+3a2εyu2+2b2v2a2+2b16κ+8a1a2+2b2εyv+2b0a23εyκ23a113b1u+2b22v33κ13a1b1b2v2+4a0a2+a12+b13κa1+b123b1κ+2b2b0+2κ2v+εya03b0κ+b0a1+b1b0εx+6a2u2+a1u+a0×u2a22a2κa1u+13a0a2+13κa1κ12a1);(A5)
(A6) q3=1κ3cν3(u2vb2+εxεy2+8vb22+3b2εxv2+2a2u2b2+2a16κ+8b1b2+2a2εxu+2a0b23εxκ23b113a1v+2a22u33κ13b1a1a2u2+4b0b2+b12+a13κb1+a123a1κ+2a2a0+2κ2u+εxb03a0κ+a0b1+a1a0εy+6b2v2+b1v+b0×v2b22b2κb1v+13b0b2+13κb1κ12b1).(A6)