{'fraction_non_alphanumeric': 0.030474989491382935, 'fraction_numerical': 0.015342580916351408, 'mean_word_length': 5.431081081081081, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
The importance of IL28B genotype in hepatitis C virus‐associated liver transplantation

Infection with hepatitis C virus (HCV) is a major global health problem affecting approximately 3% of all individuals worldwide (1). Most patients develop a chronic infection resulting in various levels of hepatic inflammation, fibrosis and – after years – in cirrhosis in a significant proportion of patients (1). Because of the rising age of HCV-infected individuals in the Western world, a dramatic increase in cases of HCVrelated cirrhosis and its complications, including hepatocellular carcinoma (HCC), is expected in the next decade (1). Obviously, this development may lead to a significantly rising number of patients requiring HCVrelated liver transplantation caused by end-stage liver disease or HCC, which certainly represents an enormous task in allocating and fair distributing liver grafts in many countries. Unfortunately, patient and graft survival are less favourable for HCV-related liver transplantation compared to liver transplantation caused by other diseases (2). The relatively poor prognosis of liver transplantation in HCV-infected patients can be mainly attributed to recurrent hepatitis C after liver transplantation, which is almost universal and which has a substantial impact on graft and overall survival (3). Therefore, prevention or treatment of HCV liver graft reinfection is of major importance. However, virological response rates to pegylated interferon-a (PEG-IFN-a) and ribavirin combination therapy after liver transplantation are even lower as compared to the non-transplant setting (3). Furthermore, antiviral treatment is associated with poor tolerability and frequent need for dose adjustments in liver transplanted patients. In nontransplanted patients, triple therapy comprising the HCV NS3-4A protease inhibitors telaprevir or boceprevir in combination with PEG-IFN-a and ribavirin is now the new standard treatment for patients infected with the difficult-to-cure HCV genotype 1, and numerous other directly acting antiviral agents are under development (4, 5). Recently completed phase III clinical trials have demonstrated superior efficacy of such triple therapy regimens in treatment-na€ıve and in treatment-experienced HCV genotype 1 patients compared to PEG-IFN-a and ribavirin alone (4, 5). In addition, recent data have clearly shown that SVR can be achieved by IFN-free combination therapies of DAA agents (and ribavirin) (5). However, it also became evident that such treatment regimens are less efficient in patients with advanced liver fibrosis or cirrhosis, and numerous drug–drug interactions seriously complicate the use of DAA agents in liver transplanted patients (5, 6). In view of these facts, the development of improved strategies to prevent and manage recurrent hepatitis C after liver transplantation still appears to be urgent. Recently, independent genome-wide association studies have yielded impressive results by identifying single nucleotide polymorphisms near the IL28B gene (encoding IFN-k3), which are strongly associated with spontaneous and treatment-induced clearance of HCV infection (7–10). These findings were subsequently confirmed and extended by numerous studies (11). Importantly, HCV genotype 1 patients with goodresponse IL28B genotype (e.g., rs12979860 CC vs. CT/ TT) achieve SVR rates after PEG-IFN-a/ribavirin therapy close to those which can be achieved in the ‘easy to treat’ HCV genotype 2 and 3 patients in general (11). Hence, it was obvious to assess the role of IL28B genetic variations in recurrent hepatitis C post liver transplantation as well. However, employing IL28B genotype in the management of recurrent hepatitis C is complicated by the genetic chimerism of transplanted patients, in whom liver donor and recipient IL28B genotypes frequently differ. Intriguingly, it was shown by several research groups that both, liver donor and recipient IL28B variations are associated with the outcome of IFN-a-based. In two of the first studies, both donor and recipient IL28B variations were strongly and independently associated with SVR after IFN-based therapy of recurrent hepatitis C, with minimal SVR rates in patients with donor and recipient poor-response IL28B genotype, intermediate SVR rates in patients with a good-response IL28B genotype of either the donor or the recipient and excellent SVR rates in patients with both donor and recipient goodresponse IL28B genotype (12, 13). However, other studies found a stronger effect of the IL28B donor genotype on treatment response (14, 15), whereas a single, but large study showed an almost exclusive effect of the recipient IL28B genotype (16). The reasons for these different associations remain unclear at