**3.3 Viral factors**

210 Liver Transplantation – Basic Issues

age >50 years warm and cold ischemia long ischemia

genetics IL28B age older age gender male race black

genetics IL28B, TGF-β1 blood group mismatch histocompatibility mismatch

immunosuppression type, high levels ACR-episodes ACR-occurence

co-infection CMV

antiviral treatment non-response pre- and post-transplant

Liver graft has been quickly suspected to affect HCV-recurrence as a dominant location of pathologic events. Several studies detected a negative effect on HCV-recurrence regarding donor age, organ quality, histocompatibility matching, steatosis and iron concentration [30, 31]. Furthermore, transplant-related factors such as duration of organ harvesting, warm and cold ischemia time (transport and implantation) have been shown to contribute to HCVrelated post-transplant events and processes [21]. Genetic variance of growth factors and cytokines in donor is currently suspected to impact on the progression and treatment of

The development of fibrosis seems to be twice as fast in males compared to female recipients. In contrast to the controversially discussed role of recipient age, black race and male gender have been shown to negatively affect fibrosis progression [22]. Cytokines and growth factors are final effectors in the pathogenesis and may theoretically play a key role in fibrogenesis [1, 34]. Analogously to donor, genetic polymorphisms of recipient cytokines are being currently intensively investigated and seem so far to modulate the course of HCV-

recurrence and antiviral treatment success. This issue will be presented below.

viremia level early peak

genotype Ib HCV-related

Table 1. Variables related to the severity of HCV-recurrence

**3.1 Donor- and surgery-related factors** 

HCV-associated graft disease [32, 33].

**3.2 Host-related factors** 

ACR-treatment corticosteroids, OKT-3

organ quality steatosis, iron concentration

Variables

donor and surgery

host

immunology

The impact of viral properties on the course of HCV-associated graft disease has been assessed by several studies, obtaining partially controversial results. Progression of graft hepatitis-C seems to be accelerated in patients with HCV-genotype-Ib, high pre-transplant HCV-RNA-load and early post-transplant peak of viremia [29, 35-37]. Interestingly, HCVcore protein has been demonstrated to promote inflammation by the release of oxidative stress and to reinforce apoptosis and steatosis. During inflammation, activated hepatic stellate cells generate ECM-components and determine the rate of graft fibrosis progression. Furthermore, CMV-coinfection seems to reinforce fibrosis progression [25, 36].
