1.
Sclerotherapy versus sham or no intervention for primary prophylaxis of oesophageal variceal bleeding in children with chronic liver disease or portal vein thrombosis.
Gattini, D, Cifuentes, LI, Torres-Robles, R, Gana, JC
The Cochrane database of systematic reviews. 2020;(3):CD011573
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Abstract
BACKGROUND Portal hypertension commonly accompanies advanced liver disease and often gives rise to life-threatening complications, including bleeding (haemorrhage) from oesophageal and gastrointestinal varices. Variceal bleeding commonly occurs in children with chronic liver disease or portal vein obstruction. Therefore, prevention is important. Primary prophylaxis of variceal bleeding in adults is the established standard of care because of the results of numerous randomised clinical trials demonstrating the efficacy of non-selective beta-blockers or endoscopic variceal ligation in decreasing the incidence of variceal bleeding. In children, band ligation, beta-blockers, and sclerotherapy have been proposed as alternatives for primary prophylaxis of oesophageal variceal bleeding. However, it is unknown whether those treatments are of benefit or harm when used for primary prophylaxis in children. OBJECTIVES To assess the benefits and harms of sclerotherapy compared with sham or no intervention for primary prophylaxis of oesophageal variceal bleeding in children with chronic liver disease or portal vein thrombosis. SEARCH METHODS We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, PubMed, Embase Elsevier, and two other registers in February 2019. We scrutinised the reference lists of the retrieved publications, and performed a manual search of the main paediatric gastroenterology and hepatology conference (NASPGHAN and ESPGHAN) abstracts from January 2008 to December 2018. We searched four registries for ongoing clinical trials. There were no language or document type restrictions. SELECTION CRITERIA We included randomised clinical trials irrespective of blinding, language, or publication status assessing sclerotherapy versus sham or no intervention for primary prophylaxis of oesophageal variceal bleeding in children with chronic liver disease or portal vein thrombosis. DATA COLLECTION AND ANALYSIS We used standard Cochrane methodology to perform this systematic review. We used the intention-to-treat principle to analyse outcome data, and GRADE to assess the certainty of evidence per outcome. MAIN RESULTS We found only one randomised clinical trial that fulfilled our inclusion criteria. The trial was at high risk of bias. The trial included 108 Brazilian children with median age of 4.3 years (range 11 months to 13 years). Fifty-six children were randomised to prophylactic sclerotherapy (ethanolamine oleate 2%) and 52 children to no intervention (control). Children were followed up for a median of 4.5 years. Eight children (six from the sclerotherapy group versus two from the control group) dropped out before the end of the trial. The follow-up was from 18 months to eight years. Mortality was 16% (9/56 children) in the sclerotherapy group versus 15% (8/52 children) in the control group (risk ration (RR) 1.04, 95% confidence interval (CI) 0.44 to 2.50; very low-certainty evidence). Upper gastrointestinal bleeding occurred in 21% (12/56) of the children in the sclerotherapy group versus 46% (24/52) in the control group (RR 0.46, 95% CI 0.26 to 0.83; very low-certainty evidence). There were more children with congestive hypertensive gastropathy in the sclerotherapy group than in the control group (14% (8/56) versus 6% (3/52); RR 2.48, 95% CI 0.69 to 8.84; very low-certainty evidence). The incidence of gastric varices was similar between the sclerotherapy group and the control group (11% (6/56) versus 10% (5/52); RR 1.11, 95% CI 0.36 to 3.43; very low-certainty evidence). The incidence of bleeding from gastric varices was higher in the sclerotherapy group than in the control group (4% (3/56) versus 0% (0/52); RR 6.51, 95% CI 0.34 to 123.06; very low-certainty evidence). The study did not assess health-related quality of life. Oesophageal variceal bleeding occurred in 5% (3/56) of the children in the sclerotherapy group versus 40% (21/52) of the children in the control group (RR 0.13, 95% CI 0.04 to 0.42; very low-certainty evidence). The most prevalent complications (defined as non-serious) were pain and fever after the procedure, which promptly resolved with analgesics. However, numerical data on the frequency of these adverse events and their occurrences in the two groups were lacking. No funding information was provided. We found no ongoing trials. AUTHORS' CONCLUSIONS The evidence, obtained from one randomised clinical trial at high risk of bias, is very uncertain on whether sclerotherapy has an influence on mortality and if it may decrease first upper gastrointestinal or oesophageal variceal bleeding in children. The evidence is very uncertain on whether sclerotherapy has an influence on congestive hypertensive gastropathy, incidence on gastric varices, and incidence of bleeding from gastric varices. Health-related quality of life was not measured. There were no serious events caused by sclerotherapy, and analysis of non-serious adverse events could not be performed due to lack of numerical data. The GRADE assessment of each outcome showed a very low-certainty evidence. The results of the trial need to be interpreted with caution. Larger randomised clinical trials, following the SPIRIT and CONSORT statements, assessing the benefits and harms of sclerotherapy compared with sham or no intervention for primary prophylaxis of oesophageal variceal bleeding in children with chronic liver disease or portal vein thrombosis are needed. The trials should include important clinical outcomes such as death, failure to control bleeding, and adverse events.
2.
Comparing the efficacy and safety of direct oral anticoagulants with vitamin K antagonist in cerebral venous thrombosis.
Lee, GKH, Chen, VH, Tan, CH, Leow, AST, Kong, WY, Sia, CH, Chew, NWS, Tu, TM, Chan, BPL, Yeo, LLL, et al
Journal of thrombosis and thrombolysis. 2020;(3):724-731
Abstract
Cerebral venous thrombosis (CVT) causes significant disability and mortality. Current guidelines for CVT management support the initial use of unfractionated heparin or low molecular weight heparin followed by longer-term oral vitamin K antagonist (VKA). There has been increasing, albeit limited, evidence for the use of direct oral anticoagulants (DOAC) as an alternative to VKA. We performed a systematic review and meta-analysis of studies that compared the safety and efficacy of DOACs to VKA in treating CVT. A comprehensive literature search was carried out in Medline, Embase and Cochrane Stroke Group Trials Register using a suitable keyword/MeSH term search strategy. All studies published in English comparing outcomes of patients with CVT treated with DOAC or VKA were included. In total, 6 studies (5 observational studies and 1 randomized clinical trial) comprising 412 patients (age range 16-83 years) were analyzed. DOAC was used in 151 patients, while 261 received VKA. The follow-up period was 3-11 months. The efficacy of DOACs was comparable with VKA in terms of partial or full thrombus recanalization (RR 1.02, 95% CI 0.89-1.16) and excellent functional recovery with modified Rankin scale < 2 (RR 1.02, 95% CI 0.93-1.13). Patients treated with DOAC developed lower major bleeding events when compared to VKA, although this did not reach statistical significance (RR 0.44, 95% CI 0.12-1.59). We provide preliminary evidence to support DOAC as effective and safe alternatives to VKA in CVT treatment. We await the results of upcoming randomized trials to further support our results and validate the use of DOAC.
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Systematic review of hepatic arterial infusion chemotherapy versus sorafenib in patients with hepatocellular carcinoma with portal vein tumor thrombosis.
Liu, M, Shi, J, Mou, T, Wang, Y, Wu, Z, Shen, A
Journal of gastroenterology and hepatology. 2020;(8):1277-1287
Abstract
BACKGROUND AND AIM The prognosis of hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) is very poor. This study aimed to evaluate hepatic arterial infusion chemotherapy (HAIC) versus sorafenib (SORF) in the treatment of HCC with PVTT. METHODS Studies were identified online in Embase and MEDLINE before October 31, 2019. The end-points were overall survival (OS), progression-free survival (PFS), disease control rate (DCR), and safety. RESULTS Six studies with 417 cases were included in this systematic review. Meta-analyses demonstrated that HAIC is superior to SORF with respect to OS (hazard ratio [HR]: 0.50, 95% confidence interval: 0.38-0.66, P < 0.001) and PFS (HR: 0.47, 95% confidence interval: 0.31-0.73, P = 0.001) irrespective of research territoriality and study quality. Our systematic review also demonstrated that HAIC is superior to SORF with respect to DCR. Subgroup analysis demonstrated that the advantage is more obvious in the treatment of types III-IV PVTT with respect to OS (HR: 0.29, P < 0.001) and PFS(HR: 0.39, P < 0.001). HAIC caused more grades 3-4 neutropenia (HR: 10.71), anemia (HR: 7.55), leukopenia (HR: 10.38), and thrombocytopenia (HR: 13.09) than SORF. However, HAIC caused fewer cases of grades 3-4 aspartate aminotransferase rising (HR: 0.21), diarrhea (HR: 0.14), and hand-foot syndrome (HR: 0.14) than SORF. CONCLUSIONS This systematic review demonstrated that HAIC is superior to SORF in HCC with PVTT with respect to OS, PFS, and DCR, especially in HCC with types III-IV PVTT. HAIC caused more myelosuppression, whereas SORF is associated with diarrhea and hand-foot syndrome. Further randomized controlled trials are warranted.