Katharina Willuweit

Successful treatment of chronic hepatitis C virus infection with sofosbuvir and ledipasvir in renal transplant recipients

Background Treatment of chronic hepatitis C virus (HCV) infection after renal allograft transplantation has been an obstacle because of contraindications associated with IFN-based therapies. Direct-acting antiviral agents are highly efficient treatment options that do not require IFN and may not require ribavirin. Therefore, we assessed the efficacy and safety of sofosbuvir and ledipasvir in renal transplant patients with chronic HCV infection. Methods Fifteen renal allograft recipients with therapy-naive HCV genotype (GT) 1a, 1b, or 4 were treated with the combination of sofosbuvir and ledipasvir without ribavirin for 8 or 12 weeks. Clinical data were retrospectively analyzed for viral kinetics and for renal and liver function parameters. Patients were closely monitored for trough levels of immunosuppressive agents, laboratory values, and potential adverse effects. Results Ten patients (66%) exhibited a rapid virologic response within 4 weeks (HCV GT1a, n = 4; HCV GT1b, n = 6). The other 5 patients exhibited a virologic response within 8 (HCV GT 1b, n = 4) or 12 weeks (HCV GT4, n = 1). One hundred percent of patients exhibited sustained virologic response at week 12 after the end of treatment. Clinical measures of liver function improved substantially for all patients. Adverse events were scarce; renal transplant function and proteinuria remained stable. Importantly, dose adjustments for tacrolimus were necessary for maintaining sufficient trough levels. Conclusions The described regimen appears to be safe and effective for patients after renal transplant and is a promising treatment regimen for eradicating HCV in this patient population.

Liver transplantation from HCV RNA-positive donors in the era of interferon-free HCV therapeutics: a re-examination of the situation.

Although the availability of donor organs is limited, liver grafts from HCV-positive donors remained yet an obstacle, primarily because of limited therapeutic options for HCV reinfection and lower rates of graft and patient survival. However, new interferon-free regimens containing direct-acting antiviral agents have fewer adverse effects and better effectiveness, making HCV treatment feasible early after transplant. In 2014, we successfully used sofosbuvir and ribavirin to treat a patient with HCV genotype 3 cirrhosis who was listed for liver transplantation. Because the patients hepatocellular carcinoma score was outside the Milan criteria, an allograft from a donor with HCV genotype 3 was accepted as rescue treatment. Patient characteristics, laboratory results, and the course of disease and treatment were documented from March 2014 to May 2015. HCV reinfection was successfully treated with sofosbuvir and ribavirin early after transplant, with no adverse effects. Viral load was below detectable levels 4 weeks after start of treatment. Liver values returned to normal, and the FibroScan score improved. Sustained virologic response was documented 12 weeks after treatment. With interferon-free regimens for HCV infection, expanding the donor pool by including HCV-positive organs is an interesting option that could substantially decrease waiting times and mortality rates for patients listed for transplant. This review comprehends and discusses available data, challenges and chances for using HCV-positive donor organs in the advent of new HCV therapeutic options.

Immunosuppression with mTOR inhibitors prevents the development of donor-specific antibodies after liver transplant

Donor‐specific antibodies (DSAs) are an important cause of complications after solid organ transplant. Risk factors and, thus, strategies for preventing DSA development are not well defined.

Liver Maximum Capacity: A Novel Test to Accurately Diagnose Different Stages of Liver Fibrosis

Aim: To assess the diagnostic accuracy of liver maximum capacity (LiMAx®) test compared to transient elastography (TE) and serum biomarkers for the noninvasive detection of different stages of liver fibrosis and cirrhosis. Patients and Methods: We retrospectively correlated LiMAx®, TE, aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio (AAR), AST-to-platelet ratio index (APRI), and fibrosis-4 (FIB-4) score with histological specimens in 102 patients with chronic liver disease (CLD) who underwent liver biopsy (either percutaneously or via mini-laparoscopy) at the University Clinic of Essen between 10/2016 and 12/2017. Results: Median LiMAx® values showed a tendency to decrease in accordance with increasing histological degree of fibrosis based on the Desmet scoring system (F0: 446.5 [381.0–592.5] µg/h/kg, F1: 405.0 [343.0–547.0] µg/h/kg, F2: 337.0 [250.0–394.0] µg/h/kg, F3: 281.0 [262.0–364.0] µg/h/kg, and F4: 181.5 [130.0–256.5] µg/h/kg. Furthermore, LiMAx® was superior to TE, FIB-4, AAR, and APRI in detecting different stages of fibrosis, while Spearman’s rank correlation test showed a statistically significant association of –0.68, 0.62, 0.61, 0.46, and 0.42, respectively. However, the combination of TE and LiMAx® had the highest diagnostic accuracy in detecting liver cirrhosis (sensitivity 88.9%, specificity 84.6%, Youden index 0.735). Conclusion: Enzymatic liver function measured by LiMAx® showed strong correlation with histology in patients with CLD irrespective of its underlying etiology and was superior to TE and serum biomarkers, possibly making it useful as a novel and noninvasive tool for the determination of hepatic disease severity.

Diagnostics and treatment of a severe humoral rejection after liver transplantation: donor-specific antibodies as a still underestimated cause of graft failure.

BACKGROUND Donor-specific antibodies (DSAs) are increasingly being considered a cause of complications after liver transplant (LT). However, neither monitoring of DSAs nor the appropriate therapeutic procedures for humoral graft damage are yet standardized. Here we report a case of DSA-positive humoral rejection after LT that was successfully treated with plasmapheresis and immunoglobulins. METHODS Human leukocyte antigen (HLA)-specific DSAs were detected by Luminex bead assay. Patient characteristics, laboratory values, and data about the patients general condition were documented from April 2013 to June 2015. CASE REPORT Eighteen months after LT, a 54-year-old man experienced severe hepatopathy with rapidly increasing transaminase activity and total bilirubin levels. Histologic findings were inconclusive, demonstrating chronic cholestasis and minimal positive staining for C4 d. However, an analysis for anti-HLA antibodies detected DSAs against HLA class II molecules with high mean fluorescence intensity. The patient underwent 8 courses of plasmapheresis, resulting in sustained amelioration of his condition and decreases in bilirubin levels and transaminase activity. CONCLUSION De novo DSAs can be responsible for graft failure after LT. Thus, procedures aimed at detecting DSAs are recommended, and regular monitoring of DSAs after LT is important for individualized risk management. Plasmapheresis is an efficient therapeutic procedure for DSA-associated graft failure.