Effectiveness of Ledipasvir/Sofosbuvir with/without Ribavarin in Liver Transplant Recipients with Hepatitis C.

Background and Aims: Recurrent infection of hepatitis C virus (HCV) in liver transplant (LT) recipients is universal and associated with significant morbidity and mortality. Methods: We retrospectively evaluated the safety and efficacy of ledipasvir/sofosbuvir with and without ribavirin in LT recipients with recurrent genotype 1 hepatitis C. Results: Eighty-five LT recipients were treated for recurrent HCV with ledipasvir/sofosbuvirwith and without ribavirin for 12 or 24 weeks. The mean (± standard deviation [SD]) time from LT to treatment initiation was 68 (±71) months. The mean (± SD) age of the cohort was 63 (±8.6) years old. Most recipients were male (70%). Baseline alanine transaminase, total bilirubin, and HCV ribonucleic acid (RNA) values (± SD) were 76.8 (±126) mg/dL, 0.8 (±1.3) U/L, and 8,010,421.9 (±12,420,985) IU/mL, respectively. Five of 43 recipients who were treated with ribavirin required drug cessation due to side effects, with 4 of those being anemia complications. No recipient discontinued the ledipasvir/sofosbuvir. Eighty-one percent of recipients had undetectable viral levels at 4 weeks after starting therapy, and all recipients had complete viral suppression at the end of therapy. The sustained viral response at 12 weeks after completion of therapy was 94%. Conclusion : Ledipasvir and sofosbuvir with and without ribavirin therapy is an effective and well-tolerated interferon-free treatment for recurrent HCV infection after LT. Anemia is not uncommon in LT recipients receiving ribavirin.

Curing Hepatitis C in Liver Transplant Recipients Is Associated with Changes in Immunosuppressant Use.

BACKGROUND AND AIMS: All-oral interferon-free antivirals are highly effective in treating recurrent hepatitis C (HCV) infection in liver transplant (LT) recipients. The aim of the study was to assess immunosuppression needs after achieving a sustained viral response (SVR). METHODS: We compared immunosuppression needs before and after achieving a SVR in adult LT recipients treated for recurrent HCV infection with all-oral direct acting agents. RESULTS: We identified 52 liver LT treated recipients who achieved a SVR. The median (25th and 75th percentile interquartile range [IQR]) age was 62 years (57.75, 65). Most recipients received tacrolimus (TAC) for their immunosuppressant regimen. After achieving SVR, there was no statistically significant difference in daily dose of TAC unadjusted per weight (p > 0.05). However, there was a statistically significant decrease in daily dose of TAC adjusted per weight, serum levels of TAC, and the product of glomerular filtration rate and TAC. No statistically significant differences in cyclosporine unadjusted/adjusted per weight daily dose or serum levels were noted. CONCLUSIONS: Immunosuppression needs were increased for those patients treated with TAC but not cyclosporine. LT recipients prescribed TAC require close monitoring after treatment completion to avoid potential risk of acute rejection.

Hepatitis C Infection in the Elderly.

Hepatitis C virus (HCV) infection in the elderly population is a global medical burden and healthcare utilization concern. The majority of patients with hepatitis C in the USA are "baby boomers," who were born between 1945 and 1965. Consistently worldwide, HCV infection in elderly population is overrepresented and poses public health concerns. These individuals have been infected now for over two decades and are presenting with advanced liver disease. Traditionally, the use of pegylated interferon-based therapy has been limited in the elderly because of its adverse effects. The sustained virologic responses have also tended to be lower in the elderly than in younger adults. The emergence of non-interferon-based therapy with direct acting antiviral agents has expanded the pool of patients eligible for treatment. These agents have been found to be effective, tolerable, and safe in the elderly population.

Antiviral Therapy in Elderly Patients With Hepatitis C Virus Infection.

The emergence of direct-acting antiviral (DAA) agents has revolutionized the treatment schema for hepatitis C virus (HCV) infection. From cure rates to tolerability, DAA agents have shown outstanding profiles compared with the prior therapy of pegylated interferon with ribavirin. However, the efficacy and safety profiles of DAA therapy in older patients, particularly the elderly, have been unclear, and patients in the 1945 to 1965 birth cohort constitute the largest proportion of the HCV population in the United States. Treating elderly patients with pegylated interferon and ribavirin has been challenging due to the frequent presence of multiple comorbidities in the elderly and high discontinuation rates caused by adverse events. Now, as more DAA agents have become widely studied and approved, subgroup analyses for the elderly population are being elucidated. Analysis of the current literature shows that these agents have been effective, well tolerated, and safe in the elderly population. This article highlights the efficacy and safety differences in interferon-based therapy and interferon-free regimens for elderly patients with HCV infection.

Border formation in a Bmp gradient reduced to single dissociated cells.

Conversions of signaling gradients into sharp "all-or-none" borders are fundamental to tissue and organismal development. However, whether such conversions can be meaningfully reduced to dissociated cells in culture has been uncertain. Here we describe ultrasensitivity, the phenomenon equivalent to an all-or-none response, in dissociated neural precursor cells (NPCs) exposed to bone morphogenetic protein 4 (Bmp4). NPC ultrasensitivity is evident at the population and single-cell levels based on Msx1 induction, a well known Bmp target response, and occurs in the context of gene expression changes consistent with Bmp4 activity as a morphogen. Dissociated NPCs also display immediate early kinetics and irreversibility for Msx1 induction after brief Bmp4 exposure, which are attractive features for initial border formation. Relevance to border formation in vivo is provided by Bmp4 gain-of-function studies in explants and evidence for single-cell ultrasensitivity in normal and mutant Bmp gradient contexts in the developing forebrain. Together, these studies demonstrate relatively simple, robust, and reducible cell-intrinsic properties that contribute to developmental border formation within a signaling gradient.