终末期肝病临床营养指南

终末期肝病患者普遍存在营养不良。营养不良是影响终末期肝病患者生存率的独立危险因素。应作为和腹水、肝性脑病等同样重要的并发症进行诊治。但是迄今为止,我国尚无针对终末期肝病患者的临床营养指南。为了规范终末期肝病患者临床营养诊疗,中华医学会肝病学分会、中华医学会消化病学分会共同组织国内有关专家编写了《终末期肝病临床营养指南》。旨在帮助临床医生在终末期肝病患者临床营养不良和营养风险筛查、营养评定、营养支持治疗和随访管理作出合理决策。     

Child和MELD动态评分在肝硬化患者预后评估中的临床比较

目的分析Child、终末期肝病模型(model of end-stage liver disease,MELD)动态评分在失代偿期肝硬化患者预后风险评估中的临床意义。方法回顾性选取失代偿期肝硬化患者142例,根据转归情况分为死亡组和非死亡组,其中死亡组41例。根据患者住院资料进行Child和MELD评分,由两次住院Child和MELD评分结果,计算Child和MELD动态变化率(△Child、△MELD),并进行Kaplan-Meier生存分析、ROC曲线分析及COX多因素回归分析。结果死亡组Child、△Child、MELD、△MELD中位数均显著高于非死亡组(P0.05);Kaplan-Meier生存分析显示,Child C级、△Child≥1、MELD≥15分、△MELD≥1患者的生存率均明显降低(P0.01);ROC曲线分析显示,Child、△Child、MELD、△MELD对失代偿期肝硬化的死亡风险的预测差异均有统计学意义(P0.05),但Child与MELD、△Child与△MELD的AUC值比较,差异有统计学意义(P0.05);COX多因素回归分析显示,MELD、△MELD并不是死亡风险的独立预测因素,Child、△Child是肝硬化患者死亡风险的独立因素,其风险比分别为1.261和2.055。结论 MELD评分在肝硬化患者死亡风险的预后评估中并不优于Child评分,相反,在一定范围内,Child评分要优于MELD评分。     

急性脑梗死患者并发胃肠道感染临床特点及危险因素分析

背景急性脑梗死(acute cerebral infarction, ACI)为临床常见急危重症,患者多有高龄、基础疾病多等特点,住院期间常出现多部位感染.已有大量研究证实呼吸道及泌尿道为常见感染灶,但临床发现,有不少患者住院期间并发胃肠道感染,影响疾病预后,并延长住院时间,但尚无文献对这部分患者进行研究报道.本研究旨在明确这部分患者临床特点及危险因素.目的探讨ACI患者住院期间并发胃肠道感染的危险因素.方法收集2018-01/2019-01在湖州市第一人民医院收治的ACI患者931例,其中住院期间并发胃肠道感染患者41例,未并发胃肠道感染患者890例,详细收集患者信息,比较患者相一般情况及实验室检查,明确并发胃肠道感染的危险因素.结果 ACI患者合并胃肠道感染组与未合并感染组在合并慢性阻塞性肺病(chronic obstructive pulmonary disease,COPD)、美国国立卫生研究院卒中量表(national institute of health stroke scale,NIHSS)、白蛋白、早期肠内营养方面存在统计学差异.将以上变量纳入Logistic回归分析,结果显示合并COPD、NIHSS≥15为ACI患者合并胃肠道感染独立危险因素,而早期肠内营养有助于避免并发胃肠道感染.结论 ACI患者合并COPD、NIHSS≥15为ACI患者合并胃肠道感染独立危险因素,而住院期间早期进行肠内营养有助于降低胃肠道感染发生率.     

重视肝硬化患者门静脉压力的检测——从研究工具到临床应用

肝硬化是各种致病因素长期作用于肝脏引起肝细胞损伤、纤维化和结节再生的结果.肝硬化逐渐进展所产生的并发症如食管胃静脉曲张破裂出血、肝性脑病、肝肾综合征、肝细胞癌等才是造成患者死亡的主要原因. 了解肝硬化的自然病史以及寻找预测其预后的指标对于检测肝硬化进展、预防其并发症的发生有重要意义. 用Child - Pugh分数评估肝硬化严重度,从而预测Child -Pugh A、B、C级患者的预后;用终末期肝硬化MELD或MELD- Na等评分系统预测终末期肝硬化预后并对肝移植器官分配需求做出判断已得到大家的公认.肝活检及企图替代肝活检的多种无创检测手段对肝纤维化的诊断有一定作用,但它们均不能对慢性肝病进展到肝硬化及其并发症进行预测.     

终末期肝病患者营养不良及营养治疗研究进展

终末期肝病患者几乎均存在不同程度的营养和代谢障碍。尽管营养不良不包括在Child分级及Meld评分中，但一些进展性的临床研究均表明，营养不良的严重程度与肝病患者的预后关系密切。因此，营养不良应与终末期肝病的并发症如肝性脑病、腹水、消化道出血等同样引起临床医生的注意。终末期肝病患者由于机体高代谢、摄入量少、     

老年肝硬化患者营养状况及其相关因素

目的 评价并分析老年肝硬化病人营养状况与各临床相关因素的相关性.方法 通过主观全面评估及营养风险筛查方法对肝硬化病人实施评估及筛查,对老年组和非老年组营养不良及营养风险发生率进行对比,分析老年肝硬化患者营养状况同住院时间、Child等级、并发症及与临床相关因素的相关性.结果 老年组营养不良及营养风险发生率均明显高于非老年组(P＜0.05);老年组营养不良者及营养风险者平均住院时间均明显长于无营养不良及无营养风险病人(P＜0.05);老年组Child A及C级人数少于非老年组(P＜0.05);老年组患者与非老年患者体质量、体质量指数、上臂围、三头肌皮脂厚度、尿素氮、肌酐、谷丙转氨酶、谷草转氨酶均无明显差异(P＞0.05).结论 老年肝硬化病人发生营养不良及存在营养风险的发生率显著上升,住院时间显著延长;在对原发病进行治疗的同时,应提供合理的营养支持.     

终末期肝病模型评估良性肝病患者肝移植预后

肝移植是治疗终末期肝病的有效手段,但供体短缺严重制约了其临床开展,因此建立公平、合理、有效的患者评估标准指导器官分配已成为移植领域的研究热点之一.本研究回顾性分析了终末期肝病模型(MELD)对良性终末期肝病患者接受肝移植术后生存的预测,并采用Cox比例风险模型筛选出影响移植受体存活的危险因素,初步构建了基于我中心良性终末期肝病肝移植受体的术前评估预测模型.     

13C-美沙西丁呼气试验对亚临床肝性脑病的临床价值分析

目的探讨13C-美沙西丁呼气试验对亚临床肝性脑病(SHE)发病率和预后判断等方面的临床应用价值.方法随机选择72例肝硬化患者和31例正常人作为研究对象,对所有受试者进行数字连接试验和智商(IQ)检测,以明确有无SHE,并同步进行13C-美沙西丁呼气试验、血氨等检测.比较13C-美沙西丁呼气试验的肝功能分级与临床Child Pugh分级的关系;采用多因素相关分析,比较13C-美沙西丁呼气试验的分级指标、血氨指标对并发SHE的关系;随访所有肝硬化患者的13C-美沙西丁呼气试验分级结果与SHE的关系.结果肝硬化患者13C-美沙西丁呼气试验的肝功能分级与临床Child Pugh分级的差别无统计学意义(P＞0.05).13C-美沙西丁呼气试验分级为病理性肝损害、Child Pugh A级的两组肝硬化患者中无SHE,SHE患者均出现在13C-美沙西丁呼气试验分级为Child B级或Child C级且血氨值为(90.56±13.66)μmol/L或更高的患者中.在肝硬化患者13C-美沙西丁呼气试验的肝功能分级中,Child C级中SHE的发病率高于Child B级(P＜0.05).随访发现,13C-美沙西丁呼气试验为Child B级和Child C级患者存在并发SHE的危险.结论13C-美沙西丁呼气试验可作为SHE发病的重要评判因素之一并有助于对肝硬化并发SHE的预后判断.     

血清D-二聚体与肝硬化Child-Pugh分级及并发症的关系

目的探讨血清D-二聚体(D-D)与肝硬化Child-Pugh分级及并发症之间的关系。方法 92例肝硬化患者按照Child-Pugh分级分为Child A、Child B、Child C三级,30名同期健康体检者为对照组。检测并比较各组的血清D-D、PT、APTT和FIB水平,并观察其与Child-Pugh分级及临床预后的关系。结果肝硬化Child A级的血清D-D及凝血指标与对照组相比差异无统计学意义(P0.05),Child B级和C级的血清D-D、PT及APTT水平显著高于对照组及Child A级(P0.05),且Child C级显著高于B级(P0.05);Child B级和C级的FIB显著低于Child A级和对照组,且Child C级显著低于Child B级(P0.05)。血清D-D与PT、APTT呈显著正相关性,与FIB呈显著负相关性(P0.05);有肝硬化并发症(门静脉血栓形成、上消化道出血、肝性脑病、腹腔积液)患者的血清D-D水平显著高于无并发症患者(P0.05)。结论血清D-D水平与肝硬化Child-Pugh分级及临床预后密切相关,检测血清D-D水平对于判断肝硬化严重程度、并发症具有重要参考价值。     

乙肝肝硬化并发自发性细菌性腹膜炎危险因素分析

目的探讨乙肝肝硬化并发自发性细菌性腹膜炎（SBP）的有关危险因素。方法收集2006年1月～2009年6月我科收治的372例乙肝肝硬化患者的临床资料,将其分为并发SBP组（91例）和未并发SBP组（281例）,并对其临床资料进行回顾性分析。结果SBP组年龄、Child—Pugh分级、脾脏厚度、门脉径主干宽度、总胆红素等均高于无SBP组,白蛋白低于无SBP组,差异均有显著性（P〈0．05）;而两组的性别、丙氨酸氨基转移酶、甲胎蛋白、HBV—DNA定量等指标比较差异无显著性（P〉0．05）。结论老年人、Child—Pugh分级C级、严重低白蛋白血症、脾脏肿大、门脉径主干增宽、高胆红素血症均为乙肝肝硬化并发SBP的危险因素。     

Child-Pugh class, nutritional indicators and early liver transplant outcomes.

BACKGROUND/AIMS: Patients with chronic liver disease undergoing liver transplantation have reduced body fat and muscle mass. The extent to which nutritional indicators and Child-Pugh class are predictive of postoperative outcome in adults is unclear. The aims of this study were to determine in adult patients undergoing transplant 1) the influence of preoperative Child-Pugh class and nutritional indicators on early transplant outcomes and one-year survival, 2) the relationship between nutritional indicators and Child-Pugh class and disease type. This study included 80 patients (1990-1994). METHODOLOGY: The nutritional indicators utilized were grip strength, triceps skinfold thickness and uncorrected mid-arm muscle area. Measured outcomes were ventilator time, intensive care stay, postoperative hospital stay and one-year survival. RESULTS: Early morbidity was determined in survivors. Child-Pugh class C patients required longer ventilation and spent more time in the intensive care unit than Child-Pugh classes A and B. No significant relationships were found for length of hospital stay. Relationships between the nutritional indicators (when controlled for Child-Pugh class) and early morbidity could not be determined due to insufficient data. No relationship was established between one-year survival and Child-Pugh class or the nutritional indicators. Grip strength and mid-arm muscle area were lower in the patients in Child-Pugh classes B and C. Parenchymal liver disease was associated with lower grip strength and mid-arm muscle area when compared to cholestatic disease. CONCLUSIONS: Child-Pugh class C is associated with greater early postoperative morbidity. Advanced Child-Pugh class is also associated with diminished muscle status and parenchymal disease.     

Hyperfibrinolysis increases the risk of gastrointestinal hemorrhage in patients with advanced cirrhosis.

Sixty-one patients with different degrees of liver failure, 23 with Child-Pugh class B and 38 with Child-Pugh class C, were studied and observed for 3 yr. Coagulation index analysis showed significantly lower values of prothrombin activity, more prolonged activated partial thromboplastin time, higher bilirubin and fibrinogen degradation products values in class C patients. Among all patients, 28 had fibrinogen degradation products values greater than 10 micrograms/ml, and in these patients a hyperfibrinolytic state was confirmed by higher values of circulating plasminogen activator antigen (17.3 +/- 8.7 ng/ml vs. 5.41 +/- 1.9 ng/ml; p less than 0.0001) and activity (6.6 +/- 2.1 IU/ml vs. 1.92 +/- 1.12 IU/ml; p less than 0.0001) and significantly lower plasminogen activator inhibitor antigen (6.4 +/- 3.5 ng/ml vs. 15.8 +/- 5.6 ng/ml; p less than 0.0001) and activity (3.6 +/- 2.2 IU/ml vs. 8.5 +/- 3.9 IU/ml; p less than 0.0001). Patients with positive fibrinogen degradation products had higher serum bilirubin (6 +/- 4 mg/dl vs. 2 +/- 2 mg/dl; p less than 0.0001) and lower fibrinogen (156 +/- 52 mg/dl vs. 194 +/- 62 mg/dl; p less than 0.02) than patients without hyperfibrinolysis. During the follow-up period, 41 patients died, 22 from fatal gastrointestinal hemorrhage and 19 from liver failure. Thirty patients experienced fatal (22 patients) and nonfatal (8 patients) gastrointestinal hemorrhage. Patients with positive fibrinogen degradation products or class C had a higher risk of gastrointestinal bleeding than patients with negative fibrinogen degradation products (odds ratio = 8) or class B (odds ratio = 3.5), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

肝硬化病人血清A/G比值的变化及其意义

目的：探讨肝硬化病人血清A／G比值的变化及其意义。方法：检测106例对照组与839例肝硬化病人的血清A/G比值，并分析血清A／G比值变化与肝硬化病人的预后、肝功能损害程度及是否并发上消化道出血等的关系。结果：肝硬化病人血清A／G比值显著低于对照组；肝硬化死亡组血清A／G比值显著低于存活组；肝硬化肝功能B级组血清A／G比值显著低于肝功能A级组，肝功能G级组血清A/G比值显著低于肝功能A级组与B级组；肝硬化末并发上消化道出血组血清A／G比值显著低于并发上消化道出血组。结论：肝硬化病人血清A／G比值明显降低，并与肝硬化病人的预后、肝功能损害程度及是否并发上消化道出血等因素有密切关系。     

乙肝肝硬化并发肝肾综合征危险因素Logistic回归分析

目的探讨乙肝肝硬化并发肝肾综合征(HRS)的危险因素。方法 2004年1月～2011年1月本院收治的乙肝肝硬化患者642例(其中发生肝肾综合征46例),收集患者的性别、年龄,发现乙肝病史时程,Child-Pugh评分,丙氨酸氨基转移酶、天门冬氨酸氨基转移酶、碱性磷酸酶、γ-谷氨酰转移酶、胆碱酯酶、血钠、白蛋白、前白蛋白、总胆红素、凝血酶原时间和活化部分凝血活酶时间、腹水程度,是否存在感染、消化道出血、强烈利尿、大量放腹水及应用氨基糖苷类药物等相关资料,进行单因素和多因素非条件Logistic回归模型分析。结果单因素和多因素非条件Logistic回归分析显示,Child-Pugh评分、腹水程度、感染是并发HRS的危险因素(P<0.05),OR值分别为6.21、3.57和4.56。结论Child-Pugh评分C级、大量腹水、伴发感染为乙肝肝硬化并发HRS的独立危险因素,对于该类患者应采取适当的干预措施。     

乙型肝炎肝硬化患者院内获得性感染相关危险因素分析*

目的 分析影响乙型肝炎肝硬化患者发生院内获得性感染相关的危险因素,以为临床诊治提供可借鉴的经验。方法 2015年1月~2017年1月在我院诊治的乙型肝炎肝硬化患者280例,查阅出院病历,结合临床症状、体征、血白细胞或/和中性粒细胞比率增高、血降钙素原水平升高、细菌培养阳性和影像学检查结果并参照卫生部2001年颁布的《医院感染诊断标准》诊断感染,对影响患者院内感染的因素先行单因素分析,再对有显著意义的因素采用多元Logistic回归分析。结果 在280例乙型肝炎肝硬化患者中,发生院内感染57例（20.4%）,其中自发性细菌性腹膜炎18例（31.6%）,呼吸道感染12例（21.1%）,胃肠道感染10例（17.5%）,泌尿系感染7例（12.3%）和败血症10例（17.5%）;经单因素分析显示,年龄（x²=7.416,P=0.006）、住院时间（t=28.247,P<0.001）、血清白蛋白（t=2.661,P=0.008）、CD4⁺T淋巴细胞ATP值（t=8.122,P<0.001）、Child-Pugh分级（x²=10.577,P=0.005）、侵入性操作（x²=29.214,P<0.001）、腹水（x²=25.776,P<0.001）、消化道出血（x²=111.434,P<0.001）为影响乙型肝炎肝硬化患者发生院内获得性感染的相关危险因素,而感染与患者性别和是否发生肝性脑病无显著性相关（P>0.05）;经多因素Logistic回归分析,结果显示,年龄、侵入性操作、腹水、消化道出血、住院时间和血清白蛋白水平是发生院内获得性感染的独立危险因素。结论 乙型肝炎肝硬化患者易发生院内感染,尤其是年龄较大、肝储备功能差、出现并发症和住院时间较长者。临床医生应该对这类患者给予特殊的关怀,严格无菌操作,预防并发症发生,促进肝功能恢复。     

Risk factors and survival of early bleeding after esophageal variceal ligation

BACKGROUND/AIMS: In cirrhotic patients, esophageal variceal bleeding (EVB) is still unpredictable and continues despite initial adequate treatment that is associated with great mortality. Bacterial infections are frequently diagnosed in cirrhotic patients with gastrointestinal bleeding (GIB). The aims of this study were to analyze the clinical risk factors and survival of early bleeding after endoscopic variceal ligation (EVL). METHODOLOGY: A total of 96 cirrhotic patients with esophageal varices who received elective or emergent EVL procedure were analyzed. The variables for risk factors analysis included bacterial infection, hepatocellular carcinoma (HCC) with or without portal vein thrombosis, etiology of cirrhosis, Child-Pugh status, and basic laboratory data. There were 19 patients with bleeding episode or rebleeding within 14 days after EVL. The remaining 77 patients were without bleeding event after EVL. RESULTS: Patients with Child C cirrhosis (odds ratio, 7.27; 95% CI, 2.20-24.07, P = 0.001) and bacterial infection (odds ratio, 130.29; 95% CI, 14.70-1154, P < 0.001) were independently associated with the early bleeding after EVL. However, there was no significant difference in long-term survival between patients with and without early bleeding after EVL. CONCLUSIONS: Bacterial infection and end-stage liver cirrhosis (Child C) are the independent risk factors for early bleeding after EVL. We should closely monitor the symptoms/signs of infection and empirical antibiotics should be administered once infection is suspected or documented, especially in cirrhotic patients with poor liver reserve.     

Decreased serum total T3 level in hepatitis B and C related cirrhosis by severity of liver damage

Objective. Thyroid hormones profile in patients with hepatic cirrhosis due to chronic HBV and HCV infections was evaluated in order to find any relationship between thyroid hormones and severity of liver damage. Material and methods. Patients with the diagnosis of hepatic cirrhosis due to hepatitis B or C were screened for thyroid function status. Child-Pugh and model for end-stage liver disease (MELD) scores were calculated. Considering each thyroid function test, patients were divided into two groups with lower than normal and normal range of thyroid hormones, separately for each (for TSH, normal and upper than nor- mal). The correlation between thyroid function tests and severity of liver disease was taken into account. Results. Number of patients with a T3 level lower than normal range (70-110 ng/dL) significantly increased along with Child-Pugh scores A, B and C. A negative correlation was found between Child-Pugh scores and total serum T3 level (r = -0.453, P < 0.001). Also a reverse correlation was observed between MELD score and T3 levels (r = -0.305, P = 0.14). Conclusion. In conclusion serum T3 concentration is a good index of hepatic function, decreasing by the severity of liver damage.     

失代偿期乙型肝炎肝硬化患者发生医院感染临床特点及危险因素分析*

目的 分析失代偿期乙型肝炎肝硬化患者住院期间发生医院感染的临床特点及其危险因素。方法 2016年2月～2018年12月我院收治的失代偿期乙型肝炎肝硬化患者100例,查阅出院病历资料,分析患者发生医院感染的临床特点,应用Logistic 回归分析影响感染发生的因素。结果 100例失代偿期乙型肝炎肝硬化患者在住院期间发生医院感染者25例(25.0%),其中呼吸道感染10例(40.0%),腹膜感染7例(28.0%),肠道感染4例(16.0%);大肠埃希菌感染5例(29.4%),金黄色葡萄球菌感染4例(23.5%),肺炎克雷伯菌感染2例(11.8%),铜绿假单孢菌感染2例(11.8%),肺炎链球菌感染2例(11.8%);单因素分析显示不同性别、是否发生肝性脑病、是否预防性应用抗菌药物患者感染发生率无显著性差异(P>0.05),而不同年龄、住院时间长短、不同肝功能分级、是否行侵入性操作、血清白蛋白和血清胆红素高低、有无腹水和是否应用抗病毒药物患者医院感染发生率差异显著,经多因素回归分析显示年龄≥60岁(OR=4.176,P=0.023)、住院时间≥1月(OR=44.116,P=0.021)、肝功能分级差(OR=5.160,P=0.009)、进行了侵入性操作(OR=5.265,P=0.003)和有腹水(OR=2.921,P=0.033)为影响患者发生院内感染的独立危险因素。结论 失代偿期乙型肝炎肝硬化患者在住院期间易发生医院感染,对于感染高危人群应予以高度关注,重视手卫生和适度隔离,以减少院内感染的发生。     

Serum C3 complement concentrations correlate with liver function in patients with liver cirrhosis

BACKGROUND/AIMS: The aim of this study was to investigate whether C3 and C4 serum complement concentrations have prognostic relevance for patients with liver cirrhosis. METHODOLOGY: Serum complement concentrations of C3 and C4 were measured in 69 patients with liver cirrhosis and correlated with the Child-Pugh score. RESULTS: C3 concentrations were 1.06+/-0.21 g/L in patients with Child-Pugh A liver cirrhosis and significantly lower in Child-Pugh B (0.78+/-0.24 g/L) and even lower Child-Pugh C (0.49+/-0.14 g/L) (p=0.006 B vs. A, p<0.001 C vs. B). Patients with consecutive hepatorenal syndrome (HRS) had the lowest C3 concentrations (0.44+/-0.05 g/L (Child-Pugh C +HRS) vs. 0.54+/-0.06g/dL (Child-Pugh C -HRS); p<0.05). C4 concentrations were 0.21+/-0.08 in Child-Pugh A and significantly lower in Child-Pugh B (0.11+/-0.04) and Child-Pugh C (0.09+/-0.04) patients (p<0.001). There was a negative correlation between C3 (r = -0.81, p<0.001) and C4 (r = -0.51, p<0.05) concentrations and the Child-Pugh score. CONCLUSIONS: Serum complement concentrations of C3 and C4 correlate negatively with the Child-Pugh score in patients with liver cirrhosis. C3 concentrations are lower in those Child-Pugh C cirrhosis patients with consecutive development of HRS.     

Risk factors and clinical presentation of portal vein thrombosis in patients with liver cirrhosis

BACKGROUND/AIMS: Portal vein thrombosis in patients with liver cirrhosis is usually associated to hepatocellular carcinoma. Clinical presentation of non-neoplastic portal vein thrombosis (PVT) in cirrhotic patients has not been specifically studied and risk factors of PVT in this group of patients are still poorly understood. METHODS: We studied all patients with PVT and liver cirrhosis admitted to our Unit from January 1998 to December 2002. They were paired (by gender, age and Child-Pugh score) to a group of cirrhotic patients without PVT and screened for acquired and inherited thrombophilic risk factors. These factors together with the site of thrombosis and the severity of the liver disease were correlated to the clinical presentation of PVT. RESULTS: Out of a total of 701 cirrhotic patients admitted to our hospital and routinely screened with Doppler ultrasound, 79 (11.2%) were found to have PVT. Of these, 34 (43%) were asymptomatic and 45 (57%) were symptomatic (31 presented with portal hypertensive bleed and 14 with abdominal pain, 10 of whom had intestinal infarction). Mesenteric vein involvement was never asymptomatic and lead to intestinal ischemia or infarction. Most patients were in class Child-Pugh B and C. Among thrombophilic risk factors studied only the mutation 20210 of the prothrombin gene resulted independently associated to PVT. CONCLUSIONS: Portal vein thrombosis may be completely asymptomatic in patients with liver cirrhosis; however in more than half of cases presents with life-threatening complications such as gastrointestinal haemorrhage and intestinal infarction. Cirrhotic patients with PVT usually have an advanced liver disease and the presence of the mutation 20210 of the prothrombin gene increases more than fivefold the risk of PVT.