Portal vein thrombosis (PVT) in compensated cirrhosis: A prospective cohort study on 898 patients
Filipe G. Nery1, 2, Cendrine Chaffaut3, 4, Bertrand Condat5, Emmanuelle de Raucourt6, Larbi Boudaoud6, Pierre-Emmanuel Rautou1, 10, Aurelie Plessier1, 10, Dominique Roulot7, 8, Jean Claude Trinchet9, 7, Dominique Valla1, 10, Sylvie Chevret3, 4
1Service d΄Hépatologie, Hôpital Beoujon, Paris, France; 2Instituto de Ciências Biomédicas Abel Salazar - Universidade do Porto, Porto, Portugal; 3DBIM, Hôpital Saint-Louis, Paris, France; 4UMR 717, Inserm, Universite Paris Diderot, Paris' France; 5Service d΄Hépato-gastroentérologie, Hôpital Saint-Camille, Bry-sur-Marne, France; 6Service d΄Hématologie Biologique, Hôpital Beaujon, Paris, France; 7UFR SMBH, Université Paris 13 Paris-Nord, Bobigny, France; 8Unité d΄Hépatologie, Hôpital Avicenne, Bobigny, France; 9Service d΄Hpato-gastroentérologie, Hôpital Jean Verdier, Bondy, France; 10Université Paris 7, Clichy, France
The causes and consequences of PVT in cirrhosis, mostly studied in advanced cases, remain unclear. This study aimed to assess prospectively, in patients with Child-Pugh A cirrhosis, (a) the reported risk factors for PVT development; and (b) the impact of PVT on the course of cirrhosis. This is a preplanned satellite study of a reported randomized trial of 3 vs 6 months as a screening interval for hepatocellular carcinoma (HCC) with Doppler ultrasonography, using a protocoled questionnaire for PVT (Trinchet, JC et al. Hepatology 2011). PVT cases developing within 6 months of a diagnosis of HCC were excluded. Aggravation was defined as a composite outcome including ascites, or prothrombin time < 45%, or bilirubin > 45μmol, or albumin < 28g/l, or creatinine > 115μmol/l, or hepatic encephalopathy. Multivariate Cox models were used to assess the cause-specific hazards of (a) PVT, including baseline, and time dependent (portal vein blood flow velocity, and aggravation prior to PVT) variables; and (b) aggravation, including baseline, and time dependent (PVT) variables. A total of 898 Child-Pugh A patients with cirrhosis of mixed etiology and a patent portal vein were followed-up a mean of 47 months. PVT developed in 101 patients, causing partial, complete, and variable obstruction in 82, 10 and 9 patients, respectively. The 5yr cumulative incidence of PVT was 11.9% (95%CI 9.6-14.2). An aggravation occurred in 221 patients (without, before, together with, and after PVT in 178, 14, 4, and 25, respectively), while 58 had PVT without aggravation. (a) Multivariate analysis showed an association of PVT development with baseline size of esophageal varices (p=0.004) and bilirubin (p=0.0007), but not with factor V or factor II gene mutations, or causes for liver disease, or aggravation prior to PVT. Results were similar for partial and complete obstruction. (b) By multivariate analysis, aggravation was associated with baseline age (p=0.004), size of esophageal varices (p=0.0004), creatinine (p<0.0001) and prothrombin time (p<0.0001), and with occurrence of PVT at any time prior to aggravation (1.65, 95%CI 1.03-2.65, p=0.038), but not with PVT occurring less than 6 months prior to aggravation. Conclusion: Development of PVT in compensated cirrhosis is related to subtle features of more severe disease at baseline but not a direct result of cirrhosis progression. Although PVT carries independent prognostic value for a poorer outcome, it is not a direct cause for aggravation. These data point to PVT and aggravation as discrete consequences of a common determinant for progression of cirrhosis, e. g. hepatic or intestinal microcirculatory dysfunction.
Dominique Valla - Board Membership: Sequana Medical; Independent Contractor: IRIS; Speaking and Teaching: Mayoly Spindler, MSD, Janssen Pharmaceuticals
The following people have nothing to disclose: Filipe G. Nery, Cendrine Chaffaut, Bertrand Condat, Emmanuelle de Raucourt, Larbi Boudaoud, Pierre-Emmanuel Rautou, Aurelie Plessier, Dominique Roulot, Jean Claude Trinchet, Sylvie Chevret