Increased thrombin generation in splanchnic vein thrombosis is related to the presence of liver cirrhosis and not to the thrombotic event

Introduction

In recent years there have been increasing evidence associating liver disease with hypercoagulability, rather than bleeding. The aim of the study was to evaluate the haemostatic potential in patients with liver disease.

Patients and methods

We measured thrombin generation in the presence and absence of thrombomodulin in patients with portal vein thrombosis (PVT, n = 47), Budd-Chiari syndrome (BCS, n = 15) and cirrhosis (n = 24) and compared the results to those obtained from healthy controls (n = 21). Fifteen patients with PVT and 10 patients with BCS were treated with warfarin and were compared to an equal number of patients with atrial fibrillation matched for prothrombin time-international normalized ratio. We assessed resistance to thrombomodulin by using ratios [marker measured in the presence/absence of thrombomodulin].

Results

There were no differences in thrombin generation between patients on warfarin treatment and their controls. Cirrhotic patients generated more thrombin in the presence of thrombomodulin and exhibited thrombomodulin resistance compared to controls [p = 0.006 for endogenous thrombin potential (ETP) and p < 0.001 for peak thrombin and both ratios ETP and peak] and patients with non-cirrhotic PVT (p = 0.001, p = 0.006, p < 0.001, p < 0.001 for ETP, peak, ratio ETP, ratio peak, respectively). The patients with cirrhotic PVT exhibited higher ETP (p = 0.044) and peak (p = 0.02) in the presence of thrombomodulin than controls, as well as thrombomodulin resistance (ETP and peak ratios: p = 0.001).

Conclusions

Hypercoagulability and thrombomodulin resistance in patients with cirrhosis were independent of the presence of splanchnic vein thrombosis. The hypercoagulability in patients with cirrhotic PVT could have implications for considering longer or more intensive treatment with anticoagulants in this group.     

Comparative dosing and efficacy of sorafenib in hepatocellular cancer patients with varying liver dysfunction

Background

Sorafenib is the only FDA-approved systemic therapy for advanced hepatocellular carcinoma (HCC). In clinical practice, dose reductions are often required, although there are limited efficacy data related to dose modifications. Given the prevalence of HCC in South Texas, we assessed the efficacy and safety of sorafenib therapy in relation to dose and Child Pugh (CP) score.

Methods

A retrospective analysis was done of advanced HCC patients, starting sorafenib at 400 mg twice daily, or at physician discretion at 400 mg daily, with the goal of titrating to twice daily. Overall survival (OS) and progression-free survival (PFS) were assessed.

Results

Among 107 patients, median OS (mOS) was 10.2 months; median PFS (mPFS) was 5.2 months. mOS for sorafenib 400 mg/day was 6.6 vs. 800 mg/day was 12.8 months [hazard ratio (HR), 0.59; P=0.04]; mPFS was 3.5 vs. 5.9 months, respectively (HR, 0.66; P=0.07). For Child Pugh A class (CP-A) patients, mOS was 15.8 months for 400 mg/day vs. 12.8 months for 800 mg/day (HR, 1.48; P=0.35); mPFS was 9.0 vs. 5.9 months, respectively (HR, 1.23; P=0.56). For Child Pugh B class (CP-B) patients, mOS was 5.0 months for 400 mg/day vs. 11.2 months for 800 mg/day (HR, 0.33; P=0.002); mPFS was 2.1 vs. 5.6 months, respectively (HR, 0.41; P=0.006). No differences in adverse events (AEs) were observed in CP-A vs. CP-B.

Conclusions

Patients with CP-A or CP-B advanced HCC should be offered sorafenib at 400 mg twice daily with optimal management of AEs in order to improve survival.     

肝硬化患者血清胆碱酯酶与透明质酸和Child-Pugh分级的关系

目的探讨肝硬化患者血清胆碱酯酶((CHE)活性与透明质酸(HA)和child-Pugh分级的相关性。方法采用速率法和放射免疫法(RIA)测定了81例肝硬化患者、对照组30例血清CHE活性和肝纤维化标志物HA水平。结果肝硬化Child-A、Child-B、Child-C级患者,CHE活性依次降低,肝纤维化标志物HA水平依次升高,且相差显著。CHE活性与HA水平呈显著负相关。CHE活性降低和HA水平升高与Child-Pugh分级具有一致性。结论血清CHE活性水平可反映肝硬化的严重程度,血清CHE活性是评估肝硬化患者肝组织纤维化敏感而准确的指标,对评估手术治疗风险、病情变化及预后有一定的临床参考价值。     

Hepatic phenylalanine metabolism measured by the [13C]phenylalanine breath test

BACKGROUND: The amino acid clearance test including phenylalanine is known to reflect liver functional reserve, which correlates with surgical outcome; however, the procedure is not clinically useful because of its laborious and time-consuming nature. This study evaluates whether phenylalanine oxidation capacity measured by a breath test could reflect liver functional reserve. DESIGN: We determined phenylalanine oxidation capacity in 42 subjects using the L-[1-13C]phenylalanine breath test (PBT). The 13CO2 breath enrichment was measured at 10-min intervals for 120 min after oral administration of 100 mg of L-[1-13C]phenylalanine. Subjects were divided into the following three groups according to their plasma retention rate of indocyanine green at 15 min (ICG R15): Group I (ICG R15 < 10%), Group II (ICG R15 10--20%), and Group III (ICG R15 > 20%). First, we determined the parameters of the phenylalanine oxidation capacity that differentiated these groups and then, using these parameters, we compared the PBT with the ICG clearance test, Child-Pugh classification score and standard liver blood tests. RESULTS: The %13C dose h(-1) at 30 min and cumulative excretion at 80 min were significantly different among the three groups (P < 0.05). These two parameters significantly correlated with the ICG R15, Child-Pugh classification score (P < 0.0001) and results of standard liver blood tests (P < 0.05). CONCLUSIONS: Phenylalanine oxidation capacity measured by the PBT was reduced according to the severity of liver injury assessed by the ICG clearance test, Child-Pugh classification, and standard liver blood tests. These results indicate that the PBT can be used as a noninvasive method to determine liver functional reserve.     

Evaluation of hernia repair operation in Child-Turcotte-Pugh class C cirrhosis and refractory ascites

BACKGROUND AND AIM: Abdominal wall hernia is a common feature of decompensated liver cirrhosis and frequently causes life-threatening complications or severe pain. However, there have been no data reported on postoperative mortality, hepatic functional deterioration and recurrence rate according to Child-Turcotte-Pugh (CTP) class and to the presence of refractory ascites. METHODS: The study population comprised 53 liver cirrhosis patients who underwent hernia repair operation. Comparisons were made of 30-day mortality among the different CTP classes, and between those with or without refractory ascites. Liver function was also analyzed just before the operation, in the immediate postoperative period, and in the remote postoperative period. RESULTS: Seventeen patients were in CTP class A, 27 patients in class B, and 9 patients in class C. The median follow-up duration was 24 months. There was single 30-day postoperative mortality in class C, and no CTP class deterioration after 30 days of operation. There was no mortality or recurrences in 17 patients with medically refractory ascites. The difference in 30-day mortality according to CTP class and the presence of refractory ascites did not show statistical significance (P = 0.17 and 0.97, respectively). CONCLUSION: Hernia operation could be done safely in CTP class A and B with low rate of recurrences, and there was no definitive increase in the operative risk in class C. In addition, refractory ascites did not increase operative risk and recurrence rate. Therefore, surgical repair might be recommended even in patients with refractory ascites and poor hepatic function to prevent life-threatening complications or severe pain.     

The ADOPT‐LC score: a novel predictive index of in‐hospital mortality of cirrhotic patients following surgical procedures,based on a national survey

Aim

We aimed to develop a model for predicting in‐hospital mortality of cirrhotic patients following major surgical procedures using a large sample of patients derived from a Japanese nationwide administrative database.

Methods

We enrolled 2197 cirrhotic patients who underwent elective (n = 1973) or emergency (n = 224) surgery. We analyzed the risk factors for postoperative mortality and established a scoring system for predicting postoperative mortality in cirrhotic patients using a split‐sample method.

Results

In‐hospital mortality rates following elective or emergency surgery were 4.7% and 20.5%, respectively. In multivariate analysis, patient age, Child–Pugh (CP) class, Charlson Comorbidity Index (CCI), and duration of anesthesia in elective surgery were significantly associated with in‐hospital mortality. In emergency surgery, CP class and duration of anesthesia were significant factors. Based on multivariate analysis in the training set (n = 987), the Adequate Operative Treatment for Liver Cirrhosis (ADOPT‐LC) score that used patient age, CP class, CCI, and duration of anesthesia to predict in‐hospital mortality following elective surgery was developed. This scoring system was validated in the testing set (n = 986) and produced an area under the curve of 0.881. We also developed iOS/Android apps to calculate ADOPT‐LC scores to allow easy access to the current evidence in daily clinical practice.

Conclusion

Patient age, CP class, CCI, and duration of anesthesia were identified as important risk factors for predicting postoperative mortality in cirrhotic patients. The ADOPT‐LC score effectively predicts in‐hospital mortality following elective surgery and may assist decisions regarding surgical procedures in cirrhotic patients based on a quantitative risk assessment.