Incidence, predictive factors and clinical significance of development of portal vein thrombosis in cirrhosis: A prospective study.

BACKGROUND AND AIMS: The role of portal vein thrombosis (PVT) in the natural history of cirrhosis is controversial. There are few prospective studies validating risk factors for development of PVT. We analysed the incidence, factors associated with PVT development and its influence on cirrhosis decompensations and orthotopic liver transplant (OLT)-free survival. METHODS: In this prospective observational study between January 2014 and March 2019, 445 consecutive patients with chronic liver disease were screened and finally 241 with cirrhosis included. Factors associated with PVT development and its influence on cirrhosis decompensations and OLT-free survival by time dependent covariate coding were analysed. RESULTS: Majority of patients belonged to Child-Pugh class A 184 (76.3%) and the average MELD score was 10 ± 5. Previous cirrhosis decompensations occurred in 125 (52.1%), 63 (26.1%) were on NSBB and 59 (27.2%) had undergone banding for bleeding prophylaxis. Median follow-up was 29 (1-58) months. Cumulative incidence of PVT was 3.7% and 7.6% at 1 and 3 years. Previous decompensation of cirrhosis and low platelet counts but not NSBB independently predicted the development of PVT. During follow-up, 82/236 (34.7%) patients developed cirrhosis decompensations. OLT-free survival was 100% and 82.8% at 3 years, with and without PVT respectively. MELD score, but not PVT, independently predicted cirrhosis decompensations (HR 1.14; 95%CI:1.09-1.19) and OLT-free survival (HR 1.16;95%CI:1.11-1.21). CONCLUSION: Previous decompensations of cirrhosis and thrombocytopenia predict PVT development in cirrhosis suggesting a pathophysiologic role for severity of portal hypertension. PVT development did not independently predict cirrhosis decompensations or lower OLT-free survival.

Anticoagulation in Cirrhosis and Portal Vein Thrombosis Is Safe and Improves Prognosis in Advanced Cirrhosis.

BACKGROUND: The role of portal vein thrombosis (PVT) in the natural history of cirrhosis is controversial. AIMS: We analyzed the safety and effect of anticoagulant therapy (AT) on PVT recanalization and orthotopic liver transplant (OLT)-free survival. METHODS: Eighty consecutive patients from a prospective registry of cirrhosis and non-tumoral PVT at a tertiary center were analyzed. AT effect on PVT recanalization and OLT-free survival was determined by time-dependent Cox regression analysis. RESULTS: Average MELD score was 15 ± 7. Portal hypertension-related complications at PVT diagnosis were present in 65 (81.3%) patients. Isolated portal vein trunk/branch thrombosis was present in 53 (66.3%) patients. AT was started in 37 patients. AT was stopped in 17 (45.9%) patients, in 4 (10.8%) due to bleeding events. No variceal bleeding occurred while on AT. Anticoagulation was restarted in 6/17 (35.2%) patients due to rethrombosis. In 67 patients with adequate follow-up imaging, AT significantly increased the rate of PVT recanalization compared with those who did not receive anticoagulation [51.4% (18/35) vs 6/32 (18.8%), p = 0.005]. OLT-free survival after a median follow-up of 25 (1-146) months was 32 (40%). Although there was no significant effect of AT on overall OLT-free survival, OLT-free survival was higher among patients with MELD ≥ 15 receiving AT compared to those who did not (p = 0.011). Baseline MELD at PVT detection independently predicted PVT recanalization (HR 1.11, 95% CI 1.01-1.21, p = 0.027) and mortality/OLT (HR 1.12, 95% CI 1.05-1.19, p < 0.001). CONCLUSIONS: Although AT did not improve overall OLT-free survival, it was associated with higher survival in advanced cirrhosis. Anticoagulation increased PVT recanalization and should be maintained after PVT recanalization to avoid rethrombosis.

Elevated nitric oxide and 3',5' cyclic guanosine monophosphate levels in patients with alcoholic cirrhosis.

AIM: To evaluate whether serum levels of nitric oxide (NO*) and plasma levels of cyclic guanosine monophosphate (cGMP) and total glutathione (GSH) are altered in patients with alcoholic cirrhosis and to examine their correlation with the severity of liver disease. METHODS: Twenty-six patients with alcoholic liver cirrhosis were studied. Serum levels of NO* and plasma levels of cGMP and GSH were measured in 7 patients with compensated alcoholic cirrhosis (Child-Pugh A) and 19 patients with advanced cirrhosis (Child-Pugh B and C). The model for end-stage liver disease (MELD) score was evaluated. Sixteen healthy volunteers served as controls. Liver enzymes and creatinine levels were also tested. RESULTS: NO* and cGMP levels were higher in patients with Child-Pugh B and C cirrhosis than in Child-Pugh A cirrhosis or controls (NO*: 21.70 +/- 8.07 vs 11.70 +/- 2.74; 21.70 +/- 8.07 vs 7.26 +/- 2.47 micromol/L, respectively; P < 0.001) and (cGMP: 20.12 +/- 6.62 vs 10.14 +/- 2.78; 20.12 +/- 6.62 vs 4.95 +/- 1.21 pmol/L, respectively; P < 0.001). Total glutathione levels were lower in patients with Child-Pugh B and C cirrhosis than in patients with Child-Pugh A cirrhosis or controls (16.04 +/- 6.06 vs 23.01 +/- 4.38 or 16.04 +/- 6.06 vs 66.57 +/- 26.23 micromol/L, respectively; P < 0.001). There was a significant correlation between NO* and cGMP levels in all patients with alcoholic cirrhosis. A significant negative correlation between reduced glutathione/glutathione disulfide and the MELD score was found in all cirrhotic patients. CONCLUSION: Our results suggest a role for oxidative stress in alcoholic liver cirrhosis, which is more significant in decompensated patients with higher levels of NO* and cGMP and lower GSH levels than in compensated and control patients. Altered mediator levels in decompensated patients may influence the hemodynamic changes in and progression of liver disease.