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.     

Risk factors for early death due to recurrence after liver resection for hepatocellular carcinoma: results of a multicenter study

BACKGROUND AND OBJECTIVES: Recurrence after partial liver resection for hepatocellular carcinoma (HCC) is a major cause of death from this disease. To identify risk factors for early death from recurrence after liver resection for HCC. METHODS: All 547 patients in this study had greater than 1 year of follow-up after complete resection of HCC (1980-1999) at one of the four hepatobiliary centers in Japan, France, and the United States. Patients who died of recurrence < or =1 year post-resection and all of those alive at least 1 year were compared. Survival and clinicopathological factors associated with death from recurrence within 1 year of resection were analyzed. RESULTS: Overall postoperative mortality rate was 5%. In the first postoperative year, 123 (22%) patients died. Of these, 53 (43%) died of recurrence, 30 (24%) of postoperative complications, and 40 (33%) of liver failure/hemorrhage. On multivariate analysis, tumor size greater than 5 cm (P < 0.02; odds ratio, 3.0), multiple tumors (P < 0.01; odds ratio, 3.3), and greater than 5 mitoses per 10 high-power fields (P < 0.03; odds ratio, 3) were associated with increased risk of early death due to recurrence. CONCLUSIONS: These findings enable identification of patients with HCC who are at high risk for early death due to recurrence following potentially curative resection who might be candidates for adjuvant therapy trials.     

Abnormality of the hepatic vein waveforms in cirrhotic patients with portal hypertension and its prognostic implications

Background and Aim:  We investigated the prognostic significance of changes in the Doppler hepatic vein (HV) waveforms in cirrhotic patients with portal hypertension and the mechanisms of these changes.
Methods:  A total of 103 consecutive patients were included in this study and their HV waveforms were classified into four types: type I, triphasic waveform; type II, biphasic waveform; type III, biphasic waveform with reduced phasic oscillations; and type IV, a flat waveform.
Results:  Type I was observed in 34, type II in 40, type III in 23, and type IV in six patients. The 5-year survival rates were 90%, 89%, 41%, and 0% in type I, II, III, and IV, respectively. Five variables including the Child–Pugh score, albumin, bilirubin, ascites, and HV waveform significantly correlated with the survival in a univariate analysis. A multivariate analysis only identified the HV waveform (type III and IV) to be an independent prognostic value. Even in Child–Pugh class B patients, the 5-year survival rate for type III or IV was as poor as 26% in comparison to 92% for type I or II. In contrast, in Child–Pugh class C patients, the 5-year survival rate for type I or II was as good as 63% in comparison to 25% for type III or IV. Furthermore, the changes in HV waveforms correlated with the extent of hepatic fibrosis, the increase in portal perfusion per liver volume, or the decrease in portal vascular resistance.
Conclusions:  Analyzing the HV waveforms was thus found to be a simple method for accurately assessing the prognosis in cirrhotic patients with portal hypertension.     

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。     

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.