Summary Background Virologic and safety outcomes of ombitasvir/paritaprevir/ritonavir ± dasabuvir ± ribavirin (OBV/PTV/r ± DSV ± RBV) therapy have shown high sustained virologic response (SVR) rates and good tolerability in most patient populations in pre‐registration studies. Aim To confirm these clinical trial findings in the treatment of genotype 1 and 4 hepatitis C under real‐world conditions. Methods Patients enrolled for treatment with OBV/PTV/r ± DSV ± RBV based on therapeutic guidelines were included, and the regimen was administered according to product characteristics. Clinical and laboratory data, including virologic response, were collected at baseline, end of treatment (EOT) and 12 weeks after EOT. Results A total of 209 patients with chronic hepatitis C were enrolled, most were genotype 1b‐infected (84.2%) and 119 (56.9%) had liver cirrhosis. Among these, 150 (71.7%) had failed previous anti‐viral therapies and 84 (40.2%) were null‐responders. At 12 weeks after EOT, SVR was achieved by 207 (99.0%) patients, ranging from 96.4% to 100.0% across subgroups. All Child–Pugh B and post‐orthotopic liver transplantation patients achieved SVR. Adverse events occurred in 151 (72.2%) patients and were mostly mild and associated with the use of RBV. Serious adverse events, including hepatic decompensation, renal insufficiency, anaemia, hepatotoxicity and diarrhoea, were reported in eight (3.8%) patients. In five (2.4%) patients, adverse events led to treatment discontinuation. On‐treatment decompensation was experienced by seven (3.3%) patients. Conclusions The results of our study confirm previous findings. They demonstrate excellent effectiveness and a good safety profile of OBV/PTV/r± DSV±RBV in HCV genotype 1‐infected patients treated in the real‐world setting.

Molecular diagnosis of rejection is emerging in kidney, heart, and lung transplant biopsies and could offer insights for liver transplant biopsies. We measured gene expression by microarrays in 235 liver transplant biopsies from 10 centers. Unsupervised archetypal analysis based on expression of previously annotated rejection-related transcripts identified 4 groups: normal "R1 normal " (N = 129), T cell-mediated rejection (TCMR) "R2 TCMR " (N = 37), early injury "R3 injury " (N = 61), and fibrosis "R4 late " (N = 8). Groups differed in median time posttransplant, for example, R3 injury 99 days vs R4 late 3117 days. R2 TCMR biopsies expressed typical TCMR-related transcripts, for example, intense IFNG-induced effects. R3 injury displayed increased expression of parenchymal injury transcripts (eg, hypoxia-inducible factor EGLN1). R4 late biopsies showed immunoglobulin transcripts and injury-related transcripts. R2 TCMR correlated with histologic rejection although with many discrepancies, and R4 late with fibrosis. R2 TCMR , R3 injury , and R4 late correlated with liver function abnormalities. Supervised classifiers trained on histologic rejection showed less agreement with histology than unsupervised R2 TCMR scores. No confirmed cases of clinical antibody-mediated rejection (ABMR) were present in the population, and strategies that previously revealed ABMR in kidney and heart transplants failed to reveal a liver ABMR phenotype. In conclusion, | 2157 MADILL-THOMSEN ET AL. 1 | INTRODUC TI ON Diagnosis of rejection in liver transplantation remains an important issue in clinical management. 1-4 The current standard-of-care (SOC) for liver biopsy diagnoses is histology, generally following Banff guidelines. 5 Histology is based on pattern recognition by experts, and assessments differ between observers. 6-11 Reported kappa values for pathology related to T cell-mediated rejection (TCMR) are low to moderate (0.15-0.62 12) especially when comorbidities are present, 7 leaving an unmet need for improvement in precision. Moreover, the diagnosis and prevalence of antibody-mediated rejection (ABMR) in liver transplants remain controversial. 5,13-15 Liver transplants present unique challenges because of their tolerogenic properties, inviting clinicians to consider reducing immunosuppression. 16-20 However, this practice requires a precise and accurate system for diagnosing rejection. 21-25 Liver function test abnormalities are associated with rejection but cannot distinguish TCMR from other diseases such as steatohepatitis. 26,27 Molecular measurement of gene expression using microarrays coupled with machine learning has the potential to improve the assessment of transplant biopsies by overcoming the limitations of conventional diagnostics. 28 We previously developed the Molecular Microscope ® Diagnostic System (MMDx) for kidney, 29-32 heart, 33,34 and lung transplants. 35-37 A number of factors argue that MMDx testing is more accurate than histology 29 : for example, use of continuous quantitative measurements, 29 low samplin...

The results confirm the negative association between chronic HCV and DQB1*0301 and identify two novel genetic associations. In particular, the DRB1*0701-DQA1*0201-DQB1*02 haplotype is associated with both chronic infection and response to alpha-interferon. Interestingly, the same haplotype is reportedly associated with non-response to hepatitis B vaccination.

The aim of the EpiTer-2 study was to analyse patient characteristics and their medication for HCV infection in Poland at the beginning of the interferon-free era. Analysis of data of HCV infected patients treated during the initial period of availability of interferon-free regimens in Poland, who started therapy after 1 July 2015 and had available an efficacy evaluation report before 30 June 2017 was undertaken. A total of 2879 patients with chronic hepatitis C were entered, including 46% with liver cirrhosis. The most common was genotype 1b (86.8%). The study population was gender balanced, the majority of patients were overweight or obese and 69% presented comorbidities, with the highest prevalence that for hypertension. More than half of patients were retreated due to failure of previous therapy with pegylated interferon and ribavirin. Almost two-third of patients received current therapy with ombitasvir/paritaprevir/ritonavir±dasabuvir (OPrD) ±ribavirin. Other patients received mostly sofosbuvir-based regimens including combination with ledipasvir and pegylated interferon and ribavirin for genotype 3-infected patients. Efficacy of treatment in the whole study population measured as intent-to-treat analysis was 95%. The most frequent regimen, administered for patients infected with genotype 1b, was 12 weeks of OPrD, resulting in an SVR rate of 98%. At least one adverse event was reported in 38% of patients, and the death rate was 0.8%. In conclusion, data from the EpiTer-2 study confirmed the excellent efficacy and safety profile of the real-world experience with recently introduced therapeutic options for genotype 1 HCV infection, but demonstrated weakness of the current therapeutic programme regarding genotype 3 infections.

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