No abstract

Portal vein thrombosis (PVT) is the most common thrombotic event in liver transplant (LT) recipients, but its impact on mortality after LT has been analyzed in heterogeneous cohorts with mixed results. To conduct a meta-analysis on the impact of PVT on post-LT survival. A systematic search was conducted on studies (published from January 1986 to January 2018) that reported 30-day and 1-year mortality after LT of PVT patients. Four hundred twenty-seven articles were reviewed and 44 were included. Among 98 558 LT, 7257 (7.3%) involved patients with PVT. The mean quality was high (7.1 on the Newcastle-Ottawa scale). The 30-day pooled mortality rate was higher for patients with PVT (64/490; 13%) than for others (259/3357; 7%) (OR 2.29; 95% CI 1.43-3.68; P < 0.0001). One-year mortality was likewise higher in recipients with (853/6302; 13.5%) than in those without PVT (7476/75 355; 9.9%) (OR 1.38; 95% CI 1.14-1.66; P < 0.0001). Heterogeneity wasn't significant (I 46% and 65%). Patients whose PVT was complete had a higher 30-day pooled mortality rate (OR 5.65; 95% CI 2-15.96; P < 0.0001), and a 1-year mortality rate (OR 2.48; 95% CI 0.99-6.17; P = 0.38) than patients with partial PVT. PVT is common in LT candidates and it is associated with higher short- and medium-term mortality after LT.

BaCKgRoUND aND aIMS: Recent evidence suggests that acute kidney injury (AKI) is the main predictor of postparacentesis bleeding in patients with cirrhosis. To assess the factors responsible for bleeding tendency in AKI, we performed a prospective study comparing all three aspects of hemostasis (platelets, coagulation, and fibrinolysis) in patients with decompensated cirrhosis with and without AKI. appRoaCH aND ReSUltS: Primary hemostasis assessment included platelet aggregation and secretion (platelet function markers) and von Willebrand factor. Secondary hemostasis assessment included pro-coagulant (factor VIII and factor XIII) and anti-coagulant (protein C, protein S, and antithrombin) factors and thrombin generation. Tertiary hemostasis assessment included fibrinolytic factors and plasmin-antiplasmin complex. Eighty patients with decompensated cirrhosis were recruited (40 each with and without AKI). Severity of cirrhosis and platelet count were comparable between groups. Median serum creatinine was 1.8 mg/dL and 0.8 mg/dL in patients with and without AKI, respectively. At baseline, patients with cirrhosis and AKI had lower platelet aggregation and secretion, indicative of impaired platelet function (increased bleeding tendency), without differences in von Willebrand factor. Regarding coagulation factors, factor VIII was higher, whereas protein C, protein S, and antithrombin were all lower, which, together with increased thrombin generation, indicate hypercoagulability. In contrast, factor XIII was lower in AKI (increased bleeding tendency). Finally, while both hypofibrinolytic and hyperfibrinolytic changes were present in AKI, a higher plasmin-antiplasmin complex indicated a hyperfibrinolytic state. After AKI resolution (n = 23 of 40), platelet function and coagulation improved to levels observed in patients with cirrhosis patients without AKI; however, fibrinolysis remained hyperactivated. CoNClUSIoNS: In patients with decompensated cirrhosis, AKI is associated with both hypocoagulable and hypercoagulable features that can potentially increase the risk of both bleeding and thrombosis. (Hepatology 2020;72:1327-1340). P atients with decompensated cirrhosis have multiple and complex alterations of hemostasis that predispose them to both bleeding and thrombotic complications. (1) Although patients with cirrhosis are traditionally considered to be at high risk of bleeding from procedures, data regarding the correlation between hemostatic

Liver transplantation is an effective and widely used therapy for several patients with acute and chronic liver diseases. The discrepancy between the number of patients on the waiting list and available donors remains the key issue and is responsible for the high rate of waiting list mortality. The recent news is that the majority of patients with hepatitis C virus related liver disease will be cured by new antivirals therefore we should expect soon a reduction in the need of liver transplantation for these recipi-

ObjectiveThe benefit of direct-acting antivirals (DAAs) against HCV following successful treatment of hepatocellular carcinoma (HCC) remains controversial. This meta-analysis of individual patient data assessed HCC recurrence risk following DAA administration.DesignWe pooled the data of 977 consecutive patients from 21 studies of HCV-related cirrhosis and HCC, who achieved complete radiological response after surgical/locoregional treatments and received DAAs (DAA group). Recurrence or death risk was expressed as HCC recurrence or death per 100 person-years (100PY). Propensity score-matched patients from the ITA.LI.CA. cohort (n=328) served as DAA-unexposed controls (no-DAA group). Risk factors for HCC recurrence were identified using random-effects Poisson.ResultsRecurrence rate and death risk per 100PY in DAA-treated patients were 20 (95% CI 13.9 to 29.8, I2=74.6%) and 5.7 (2.5 to 15.3, I2=54.3), respectively. Predictive factors for recurrence were alpha-fetoprotein logarithm (relative risk (RR)=1.11, 95% CI 1.03 to 1.19; p=0.01, per 1 log of ng/mL), HCC recurrence history pre-DAA initiation (RR=1.11, 95% CI 1.07 to 1.16; p<0.001), performance status (2 vs 0, RR=4.35, 95% CI 1.54 to 11.11; 2 vs 1, RR=3.7, 95% CI 1.3 to 11.11; p=0.01) and tumour burden pre-HCC treatment (multifocal vs solitary nodule, RR=1.75, 95% CI 1.25 to 2.43; p<0.001). No significant difference was observed in RR between the DAA-exposed and DAA-unexposed groups in propensity score-matched patients (RR=0.64, 95% CI 0.37 to 1.1; p=0.1).ConclusionEffects of DAA exposure on HCC recurrence risk remain inconclusive. Active clinical and radiological follow-up of patients with HCC after HCV eradication with DAA is justified.

DAAs therapy in HCV-related cirrhotic patients is associated with significant changes in thrombin generation suggesting a reversal of hypercoagulability particularly in Child's A patients.

Concerns about an increased hepatocellular carcinoma (HCC) recurrence rate following direct-acting antiviral (DAA) therapy in patients with cirrhosis with a prior complete oncological response have been raised. Data regarding the impact of HCV treatment with DAAs on wait-list dropout rates in patients with active HCC and HCV-related cirrhosis awaiting liver transplantation (LT) are lacking. HCV-HCC patients listed for LT between January 2015 and May 2016 at Padua Liver Transplant Center were considered eligible for the study. After enrollment, patients were divided into 2 groups, depending on whether they underwent DAA treatment while awaiting LT or not. For each patient clinical, serological, and virological data were collected. HCC characteristics were radiologically evaluated at baseline and during follow-up (FU). For transplanted patients, pathological assessment of the explants was performed and recurrence rates were calculated. A total of 23 patients treated with DAAs and 23 controls were enrolled. HCC characteristics at time of LT listing were comparable between the 2 groups. Median FU was 10 and 7 months, respectively, during which 2/23 (8.7%) and 1/23 (4.3%) dropout events due to HCC progression were registered (P = 0.90). No significant differences in terms of radiological progression were highlighted (P = 0.16). A total of 9 out of 23 (39%) patients and 14 out of 23 (61%) controls underwent LT, and histopathological analysis showed no differences in terms of median number and total tumor volume of HCC nodules, tumor differentiation, or microvascular invasion. During post-LT FU, 1/8 (12.5%) DAA-treated patient and 1/12 (8.3%) control patient experienced HCC recurrence (P = 0.60). In conclusion, viral eradication does not seem to be associated with an increased risk of dropout due to neoplastic progression in HCV-HCC patients awaiting LT. Liver Transplantation 23 1103-1112 2017 AASLD.

It is common knowledge that cancer patients are more prone to develop venous thromboembolic complications (VTE). It is therefore not surprising that patients with hepatocellular carcinoma (HCC) present with a significant risk of VTE, with the portal vein being the most frequent site (PVT). However, patients with HCC are peculiar as both cancer and liver cirrhosis are conditions that can perturb the hemostatic balance towards a prothrombotic state. Because HCC-related hypercoagulability is not clarified at all, the aim of the present review is to summarize the currently available knowledge on epidemiology and pathogenesis of non-malignant thrombotic complications in patients with liver cirrhosis and HCC. They are at increased risk to develop both PVT and non-splanchnic VTE, indicating that both local and systemic factors can foster the development of site-specific thrombosis. Recent studies have suggested multiple and often interrelated mechanisms through which HCC can tip the hemostatic balance of liver cirrhosis towards hypercoagulability. Described mechanisms include increased fibrinogen concentration/polymerization, thrombocytosis, and release of tissue factor-expressing extracellular vesicles. Currently, there are no specific guidelines on the use of thromboprophylaxis in this unique population. There is the urgent need of prospective studies assessing which patients have the highest prothrombotic profile and would therefore benefit from early thromboprophylaxis.