ABSTRACT Background and Aims The impact of bulevirtide in patients awaiting liver transplantation (LT) for decompensated liver disease and/or hepatocellular carcinoma (HCC) is unclear. We assessed clinical, virological, and biochemical responses to bulevirtide in patients with chronic hepatitis delta virus (HDV) awaiting LT and compared outcomes with a cohort of similar untreated patients. Methods Consecutive HDV‐infected patients waiting for LT since bulevirtide approval were included. Patients receiving 2 mg of bulevirtide daily had clinical, biological, and virological data collected at baseline, Week 24, Week 48, at LT, and post‐LT. Patients not receiving bulevirtide had data collected at baseline, LT, and post‐LT for comparison. Results Forty‐one patients from nine LT centers were included. In the bulevirtide group (20 patients; mean age 52.8 ± 9.98 years; 75% male), 65%, 10% and 25% were Child‐Pugh A, B and C, respectively. Fifteen completed 48 weeks of therapy. At 48 weeks, median HDV RNA decreased by 2.56 log IU/mL ( p = 0.004). Virological and biochemical responses were obtained in 73.3% and 66.6% of patients. Twelve patients (60%) underwent LT. No serious adverse events occurred. Bulevirtide improved liver function, enabling one (7.1%) HCC patient to undergo chemoembolization while on the WL and leading to delisting of three (15%) other patients. In untreated patients (mean age 42.9 ± 7.9 years; 76.2% Child‐Pugh C), none were delisted. Three‐month transplant‐free survival was 76.9% in the bulevirtide group versus 36.7% ( p = 0.007) in the control group. Conclusions Bulevirtide demonstrates safety and efficacy in HDV‐infected patients listed on the LT waiting list and may potentially improve pre‐transplant outcomes.
Liver tumors are common and may be unamenable to surgery or ablative treatments. Consequently, other treatments have been devised. To assess the safety and efficacy of transarterial radioembolization (TARE) with Yttrium-90 for hepatocellular carcinoma (HCC), liver-dominant hepatic colorectal cancer metastases (mCRC), and cholangiocarcinoma (CCA), performed according to current recommendations, we conducted a single-center retrospective study in 70 patients treated with TARE (HCC, n = 44; mCRC, n = 20; CCA, n = 6). Safety and toxicity were assessed using the National Cancer Institute Common Terminology Criteria. Treatment response was evaluated every 3 months on imaging studies using Response Evaluation Criteria in Solid Tumors (RECIST) or mRECIST criteria. Overall survival and progression-free survival were estimated using the Kaplan-Meier method. The median delivered dose was 1.6 GBq, with SIR-Spheres® or TheraSphere® microspheres. TARE-related grade 3 adverse events affected 17.1% of patients. Median follow-up was 32.1 months. Median progression-free survival was 5.6 months and median overall time from TARE to death was 16.1 months and was significantly shorter in men. Progression-free survival was significantly longer in women (HR, 0.49; 95%CI, 0.26–0.90; p = 0.031). Risk of death or progression increased with the number of systemic chemotherapy lines. TARE can be safe and effective in patients with intermediate- or advanced-stage HCC, CCA, or mCRC refractory or intolerant to appropriate treatments.
Abstract Background & Aims C282Y homozygotes with serum ferritin ( SF ) levels >1000 μg/L and/or increased serum transaminase levels are at risk of severe F3/F4 fibrosis. Current practical guidelines recommend liver biopsy in such individuals. This prospective observational cohort study aimed to evaluate non‐invasive alternative means such as hyaluronic acid ( HA ) and transient elastography ( TE ) for the assessment of severe fibrosis in patients with SF >1000 μg/L or elevated transaminases. Methods Between September 2005 and April 2013, 77 patients diagnosed C282Y homozygotes underwent a liver biopsy because of SF >1000 μg/L and/or increased transaminases according to current guidelines, with concomitant TE . All of them had clinical and biological evaluation, including HA measurement in 52 cases. Results A total of 19.5% of patients had F3–F4 severe fibrosis. HA was higher in patients with severe fibrosis, but did not accurately predict severe fibrosis. TE was significantly higher in patients with severe fibrosis (17.2 vs. 4.9 kP a; P < 0.05) and was able to accurately predict fibrosis stage in 47/61 (77%) patients with valid measurement using a lower threshold of 6.4 kP a and an upper threshold of 13.9 kP a. Efficient assessment of severe fibrosis was not possible in patients with intermediate TE values. Conclusion An algorithm that successively employed SF and TE can accurately classify severe fibrosis in 61% of patients, restricting the need for liver biopsy to the 39% of patients with intermediate or unvalid TE values. This algorithm should be validated in independent cohorts before extended use.
The beneficial effect of one graft on another has been reported in combined transplantation but the associated mechanisms and biological influence of each graft have not yet been established.In multiple analyses, we explored the PBMC phenotype and signature of 45 immune-related messenger RNAs and 754 microRNAs from a total of 235 patients, including combined liver-kidney transplant recipients (CLK), patients with a liver (L-STA) or kidney (K-STA) graft only under classical immunosuppression and patients with tolerated liver (L-TOL) or kidney grafts (K-TOL).CLK show an intermediary phenotype with a higher percentage of peripheral CD19(+) CD24(+) CD38(Low) memory B cells and Helios(+) Treg cells, two features associated with tolerance profiles, compared to L-STA and K-STA (P < 0.05, P < 0.01). Very few miRNA were significantly differentially expressed in CLK vs. K-STA and even fewer when compared to L-STA (35 and 8, P < 0.05). Finally, CLK are predicted to share common miRNA targets with K-TOL and even more with L-TOL (344 and 411, P = 0.005). Altogether CLK display an intermediary phenotype and gene profile, which is closer to that of liver transplant patients, with possible similarities with the profiles of tolerant patients.These data suggest that CLK patients show the immunological influence of both allografts with liver having a greater influence.
