The proapoptotic molecule TNF‐related apoptosis‐inducing ligand (TRAIL) has earned attention because of its ability to induce apoptosis in liver cancer cells without damaging normal liver cells. It may play an important role in preventing the development and outgrowth of hepatocellular carcinoma (HCC). TRAIL expression was investigated in a large series of human HCCs. We analyzed liver tissue from 108 patients undergoing partial liver resection (PLR) or liver transplantation (LT) because of either HCC or other indications. TRAIL expression was correlated with the cause of liver disease, demographic and clinical variables and pathologic properties. Our analysis found that in 66% of HCCs TRAIL expression was significantly lower than in the surrounding non‐cancerous liver tissue (p ≤ 0.012). Separation by cause of disease showed that HCC TRAIL mRNA expression was lower in almost all groups than in non‐cancerous tissue but most significantly lower in NASH‐associated liver tumors. Interestingly, low HCC TRAIL expression was found to correlate with tumor size (p ≤ 0.007) and stage, as well as with tumor recurrence after resection and poor survival rates. The results of this study suggest that low TRAIL mRNA levels may be both a dominant feature in HCC development and growth and a predictor of tumor recurrence and poorer survival rates.

To estimate protection from cytomegalovirus (CMV) replication after solid organ transplantation, CMV serology has been considered insufficient and thus CMV immunity is increasingly assessed by cellular in vitro methods. We compared two commercially available IFN-γ ELISpot assays (T-Track CMV and T-SPOT.CMV) and an IFN-γ ELISA (QuantiFERON-CMV). Currently, there is no study comparing these three assays. The assays were performed in 56 liver transplant recipients at the end of antiviral prophylaxis and one month thereafter. In CMV high- or intermediate-risk patients the two ELISpot assays showed significant correlation (p < 0.0001, r > 0.6) but the correlation of the ELISpot assays with QuantiFERON-CMV was weaker. Results of both ELISpot assays were similarly predictive of protection from CMV-DNAemia ≥500 copies/mL [CMV pp65 T-SPOT.CMV at the end of prophylaxis: area under curve (AUC) = 0.744, cut-off 142 spot forming units (SFU), sensitivity set to 100%, specificity 46%; CMV IE-1 T-Track CMV at month 1: AUC = 0.762, cut-off 3.5 SFU, sensitivity set to 100%, specificity 59%]. The QuantiFERON-CMV assay was inferior, reaching a specificity of 23% when setting the sensitivity to 100%. In conclusion, both CMV-specific ELISpot assays appear suitable to assess protection from CMV infection/reactivation in liver transplant recipients.

Background: Transplanting kidneys from deceased donors with hepatitis C virus (HCV) viremia has been controversial for some time. Direct‐acting antiviral agents have been shown to be highly effective in treating HCV infection. We report our experience with transplanting kidneys from HCV‐positive donors with detectable viremia into HCV‐negative recipients, followed by early treatment with a sofosbuvir‐based antiviral regimen.Methods: Data were collected from seven HCV‐negative recipients receiving kidneys from five deceased HCV‐viremic donors. Before transplantation, all intentional transplanted recipients had given informed consent regarding the acceptance of an HCV‐viremic kidney. Recipients were closely monitored after transplant with measurements of HCV viremia, liver and renal function, and trough levels of immunosuppressive drugs.Results: Four donors were infected with HCV genotype 1; the other with HCV genotype 3a. HCV viremia was detectable in all seven renal transplant recipients within 3 days after transplant. After determination of HCV genotype, antiviral treatment with a sofosbuvir‐based regimen (sofosbuvir/ledipasvir, n = 4; sofosbuvir/velpatasvir, n = 3) was initiated within a median of 7 days after transplantation and was continued for 8 to 12 weeks. For all recipients, viral load was below the level of detection at the end of treatment, and all exhibited a sustained virologic response 12 weeks later. All recipients exhibited normal liver enzyme activity at the end of treatment. Renal allograft function and trough levels of tacrolimus remained stable.Conclusions: Early administration of a sofosbuvir‐based regimen to HCV‐negative recipients of kidneys from HCV‐viremic donors is feasible and safe. The definition of an optimal therapeutic approach warrants further investigation.

Optimizing therapy of post‐transplant HCV recurrence remains important, especially in advanced liver disease. We evaluated daclatasvir (DCV) plus sofosbuvir (SOF), with or without ribavirin (RBV), in patients with post‐liver transplant recurrence in a real‐world European cohort at high risk of decompensation or death within 12 months. Recommended treatment was DCV 60 mg plus SOF 400 mg once daily for 24 weeks; RBV use/shorter treatment duration was at physicians’ discretion. Patients (N = 87) were 70% male, 93% white, and mostly infected with HCV genotypes 1b (48%), 1a (32%), or 3 (9%); 37 (43%) had cirrhosis (16 decompensated), five had fibrosing cholestatic hepatitis. Sustained virologic response at post‐treatment week 12 (SVR12) was 94% (80/85) in a modified intention‐to‐treat analysis: 95% (58/61) without RBV and 92% (22/24) with RBV, with no virologic failures. SVR12 was 100% (80/80) in an as‐observed analysis excluding five nonvirologic failures. Four patients (5%) discontinued therapy for adverse events (AEs); 16 (18%) experienced serious AEs. One patient died on treatment and five during follow‐up. Most AEs were associated with advanced liver disease and unrelated to therapy. No clinically significant drug–drug interactions were observed. DCV + SOF ± RBV was well tolerated and achieved high SVR12 (94%) in patients with post‐transplant HCV recurrence, including patients with severe liver disease.