DeCure's autonomous Cardio AI scientist is researching a drug-repurposing hypothesis for hepatic vein thrombosis — screening already-approved drugs against its 3-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleHepatic vein thrombosis maps to a 3-gene Open Targets module — the target space DeCure's AI scientist screens approved drugs against.
DeCure.ai methodSignature reversal (LINCS) plus network proximity (STRING) rank already-approved drugs likely to perturb this module — the same engine that produces DeCure.ai's repurposing hypotheses.
Repurposing thesisScreening approved medicines against this disease module, then publishing the evidence for the strongest candidate. Known pharmacology and human exposure data make the first question sharper — they do not establish safety or efficacy in a new indication.
Research record
01
ResearchComing soon
Candidate research + dossier — target rationale, drug-repurposing thesis and evidence pack.proof: Published dossier + on-chain hash
02
ValidationComing soon
In-vitro biological validation at a contract research org (CRO).proof: CRO contract + in-vitro report
03
Peer review & paperComing soon
Peer-reviewed paper published open-access (preprint + journal).proof: DOI + open-access link + on-chain hash
Current lead
No approved-drug candidate for hepatic vein thrombosis is corroborated in the literature DeepSearch retrieved. Some conditions are managed with non-pharmacological care — a device, surgery or physical therapy — rather than a medicine; that may be the case here, or the literature we found may simply be too sparse yet to support a drug-repurposing angle.
Molecular view
Janus kinase 2 (JAK2) — JAK2 is one of the genes genetically linked to this disease in Open Targets — shown as context, not as a drug target we're pursuing: no approved-drug candidate for this disease is yet corroborated in the literature we found.
Loading structure…
helix sheet apo structuredrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 4Z32 · 3.04 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
In a 13-year Jordanian single-centre series of 155 living donor liver transplant recipients, five patients developed early hepatic artery thrombosis. All five had Child-Pugh C cirrhosis with a mean MELD score of 32. After surgical revision, the first patient had recurrent thrombosis; all five received catheter-directed local thrombolysis and subsequently rethrombosed. Despite persistent thrombosis, four of the five patients maintained long-term graft function. Cumulative survival was 80% at one year, 80% at five years, and 60% at ten years. One patient showed spontaneous recanalisation of the hepatic artery. The authors concluded that when retransplantation is not possible and interventional approaches fail, conservative management with close monitoring of liver function and collateral circulation may be pursued.
Two earlier papers discuss prothrombotic mechanisms in cirrhosis. One reports that thrombin activation and microthrombosis of intrahepatic portal venules are common in cirrhosis, partly due to relative protein C deficiency and altered coagulation balance. It presents two cases of cryptogenic cirrhosis in which a factor V Leiden mutation or a 4G/5G PAI-1 polymorphism were the only identifiable risk factors, suggesting these mutations may accelerate fibrogenesis or even cause cirrhosis in some patients. The other paper notes that chronic liver disease predisposes to thrombotic events because of portal hypertension and venous stasis, and that the haemostatic balance is unstable due to reduced production of both procoagulant factors and anticoagulants such as protein C and antithrombin.
The Jordanian series is small and retrospective, with no control group. It does not address hepatic vein thrombosis (Budd-Chiari syndrome) directly, only hepatic artery thrombosis after transplant. The two mechanistic papers are case reports and narrative reviews, not controlled trials. What is still missing is prospective data on anticoagulation strategies in cirrhotic patients with venous thromboembolism, randomised trials comparing conservative management with interventional or surgical approaches for hepatic vessel thrombosis, and validated methods to stratify patients by thrombotic risk and bleeding risk simultaneously.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Clinical and Molecular Hepatology · 2016 · 39 citations · open access
Recurrent acute portal vein thrombosis in liver cirrhosis treated by rivaroxaban
AbstractCirrhosis can occur with the development of portal vein thrombosis (PVT). PVT may aggravate portal hypertension, and it can lead to hepatic decompensation. The international guideline recommends for anticoagulation treatment to be maintained for at least 3 months in all patients with acute PVT. Low-molecular-weight-heparin and changing to warfarin is the usual anticoagulation treatment. However, warfarin therapy is problematic due to a narrow therapeutic window and the requirement for frequent dose adjustment, which has prompted the development of novel oral anticoagulants for overcoming these problems. We report a 63-year-old female who experienced complete resolution of recurrent acute PVT in liver cirrhosis after treatment with rivaroxaban.
Experimental and Clinical Transplantation · 2021 · 3 citations
Early Hepatic Artery Thrombosis After Living Donor Liver Transplant: A 13-Year Single-Center Experience in Jordan
AbstractOBJECTIVES: Early hepatic artery thrombosis is a serious complication that may follow living donor liver transplant. Acute graft loss and patient morbidity and mortality are possible consequences. The therapeutic algorithm includes surgical or interventional revascularization, conservative approaches, or retransplantation. MATERIALS AND METHODS: Among 155 patients who underwent living donor liver transplant at our transplant center from 2004 to 2020, there were 5 who developed hepatic artery thrombosis. From our 13- year experience, we herein present their demographic and clinical characteristics, radiological imaging findings, perioperative courses, and the postoperative follow-up. RESULTS: All patients displayed advanced liver disease with a Child-Pugh score of C and a mean Model for End-Stage Liver Disease score of 32. Underlying causes for end-stage liver disease included hepatitis B and C infection and cryptogenic liver cirrhosis. The mean patient age was 49 years; 2 patients were female. Living donor liver transplant was performed with donor tissue from immediate kin, according to Jordanian allocation rules. The diagnosis of hepatic artery thrombosis was made by Doppler ultrasonography and confirmed via computed tomography. After surgical revision of the anastomosis, our first patient experienced thrombotic recurrence. All patients received interventional catheterization with local thrombolysis and subsequently developed rethrombosis. Despite prevalent thrombosis, 4 patients achieved long-term survival without further deterioration of liver function. Cumulative 1-year, 5-year, and 10-year survival rates were 80%, 80%, and 60%, respectively. Spontaneous recanalization of the hepatic artery was observed in 1 patient. CONCLUSIONS: Favorable long-term outcomes are achievable in patients with persistent hepatic artery thrombosis. When retransplant is not feasible and interventional approaches fail, conservative treatment with careful observation of liver function should be implemented. Attentive observation of collateral circulation toward the liver, distal of the thrombosis, may be beneficial to both graft and patient survival.
Revista Española de Enfermedades Digestivas · 2016 · 3 citations
Cryptogenetic liver cirrhosis and prothrombotic mutations - A mere association?
AbstractThrombin activation and microthrombosis of intrahepatic portal venules is a common feature in liver cirrhosis, due in part to relative protein C deficiency and altered coagulation-anticoagulation-fibrinolysis balance. Extension of this microthrombotic process to larger portal vessels explains the increased incidence of portal vein thrombosis in liver cirrhosis. Thrombin not only leads to thrombosis, but also activates liver stellate cells and promotes fibrogenesis. Also, ischemia associated with thrombosis up-regulates the expression and secretion of growth factors involved in fibrogenesis. The coincidence in a given patient of prothrombotic mutations, such as factor V Leiden or PAI-1 polymorphisms, can accelerate the fibrogenetic process. We hereby present two cases of liver cirrhosis in which etiologic evaluation was negative except for the finding of a factor V Leiden mutation in one case and the 4G/5G PAI polymorphism in the second case. These observations support the hypothesis that these mutations may be involved in the etiology of some cases of cirrhosis, or, at least, accelerate the evolution of the disease. It is therefore convenient to search for the presence of prothrombotic mutations in patients with cryptogenetic cirrhosis.
AME Medical Journal · 2017 · 0 citations · open access
Cirrhotic patients with venous thromboembolism: how to deal with an unstable balance?
AbstractChronic liver disease may predispose patients to thrombotic events for local risk factors, such as portal hypertension and consequent venous stasis, which can lead to portal vein thrombosis (1). Moreover, the delicate haemostatic balance between reduced production of procoagulant factors and decreased levels of anticoagulants (such as protein C and antithrombin) (2)
Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works (targeted per-candidate search), resolved on OpenAlex.
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