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Introduction: Patients with thrombocytopenia and chronic liver disease are at increased risk of bleeding during invasive procedures due to low platelet counts. Lusutrombopag, an orally active thrombopoietin receptor agonist, increases platelet count and reduces the need for platelet transfusion in chronic liver disease patients with thrombocytopenia undergoing a planned invasive procedure. The safety of lusutrombopag in patients with Child-Pugh class C chronic liver disease is not known. The present analysis was performed to determine the pharmacokinetics, efficacy, and safety of lusutrombopag in patients with Child-Pugh class C chronic liver disease.Methods: Data for patients with Child-Pugh class C chronic liver disease were collected from three data sets: a phase 1/2 Child-Pugh class C study (n = 5) (JapicCTI-163289 [Japan Pharmaceutical Information Center]), a phase 3 pivotal study (L-PLUS 2, n = 3) (NCT02389621 [Clinicaltrials.gov]), and ongoing post-marketing surveillance (n = 27) (JapicCTI-163432 [Japan Pharmaceutical Information Center]). Patients received lusutrombopag at 3 mg for up to 7 days. Safety and efficacy assessments were collected from two clinical studies and the post-marketing surveillance; pharmacokinetic data were collected from the phase 1/2 study.Results: Mean Cmax and AUC0-τ were lower in Child-Pugh class C patients than Child-Pugh class A and B; individual patients' Cmax and AUC0-τ values overlapped among Child-Pugh classes. In lusutrombopag patients who did not receive platelet transfusion (n = 4 in phase 1/2, n = 1 in phase 3, n = 24 in post-marketing surveillance), the median (range) maximum platelet count was 88.5 × 109/L (54-105 × 109/L), 80 × 109/L, and 91 × 109/L (41-186 × 109/L; n = 23), respectively. There were no treatment-related adverse events or treatment-related serious adverse events. One patient from the phase 1/2 study had a non-serious portal vein thrombosis, which was not considered treatment-related.Conclusions: The analysis presented in this study suggests that lusutrombopag increases platelet counts in Child-Pugh class C patients and is safe and well tolerated in this patient population.Trial Registration: L-PLUS 2: NCT02389621 (Clinicaltrials.gov). Phase 1/2: JapicCTI-163289 (Japan Pharmaceutical Information Center [JAPIC]). Post-marketing surveillance: JapicCTI-163432 (JAPIC). [ABSTRACT FROM AUTHOR]

Purpose: Balloon-occluded retrograde transvenous obliteration (B-RTO) has shown great potential in controlling acute gastric variceal hemorrhage, although rebleeding related to the procedure may occur in a small percentage of patients. The purpose of this study was to identify risk factors of perioperative rebleeding and prognostic factors of postoperative survival in B-RTO performed for acute episodes of gastric variceal hemorrhage. Methods: We retrospectively analyzed 39 consecutive patients who underwent B-RTO for gastric variceal rupture at our hospital between June 2003 and May 2011. Uni- and multi-variate analyses were performed to assess risk factors for perioperative rebleeding and prognostic factors for postoperative survival. Results: Surgical success and complete eradication of varices were achieved in 36 cases (92.3 %) and 35 cases (89.7 %), respectively. Six patients experienced rebleeding either intraoperatively ( n = 3) or within 1 h after B-RTO ( n = 3). Child-Pugh class C was identified as a risk factor for rebleeding on univariate ( P = 0.018) and multivariate analyses (odds ratio, 6.003; P = 0.014). With a median follow-up of 23 months (range 0-106.6 months), overall survival rates at 1, 3, and 5 years were 91.7, 74.7, and 67.2 %, respectively. Multivariate analyses revealed Child-Pugh class C as a prognostic factor for survival (relative risk, 4.014; P = 0.023). Conclusion: Although B-RTO is generally effective in the treatment of acute gastric variceal rupture, patients classified as Child-Pugh class C have a higher risk of perioperative rebleeding and shorter survival. [ABSTRACT FROM AUTHOR]

Therapeutic drug monitoring for voriconazole, an antifungal agent, is essential for maximizing efficacy and preventing toxicity. The aim of this study was to elucidate the optimal maintenance dose of voriconazole in patients with severe liver cirrhosis (Child-Pugh class C) by reviewing the plasma trough concentrations obtained by therapeutic drug monitoring and daily doses of voriconazole. We retrospectively evaluated 6 patients with Child-Pugh class C cirrhosis who received oral voriconazole treatment and were liver transplant recipients or were awaiting liver transplantation. We compared their voriconazole trough concentrations and daily maintenance doses to those of patients who did not have liver cirrhosis (n=56). We found that plasma voriconazole trough concentrations in all patients with Child-Pugh class C were almost within therapeutic range, and the median plasma trough concentration at steady state was not significantly different from that of patients who did not have liver cirrhosis. In addition, the median daily maintenance dose of voriconazole was significantly lower (2.13 mg/kg/d) than that of the control patients (6.27 mg/kg/d), suggesting that trough voriconazole concentrations are elevated in Child-Pugh class C patients. Thus, we conclude that oral voriconazole maintenance doses in patients with Child-Pugh class C should be reduced to approximately one-third that of patients with normal liver function, with the follow-up dose adjusted by therapeutic drug monitoring.