DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for cirrhosis of liver — screening already-approved drugs against its 42-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleCirrhosis of liver maps to a 42-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 cirrhosis of liver 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
nuclear receptor subfamily 3 group C member 2 (NR3C2) — NR3C2 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 2,2-difluoro-3-hydroxypropyldrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 4PF3 · 1.1 Å · ligand 6-[1-(2,2-difluoro-3-hydroxypropyl)-5-(4-fluorophenyl)-3-methyl-1H-pyrazol-4-yl]-2H-1,4-benzoxazin-3(4H)-one (HFN). Experimental structure, not a prediction.
What the evidence adds up to
An estimated 1 million people in Germany have hepatic cirrhosis, the final stage of chronic inflammation of the liver. The main complications are variceal bleeding, ascites, hepatocellular carcinoma, encephalopathy, and infection leading to organ failure. Endoscopic ligation and beta-blockers are used to prevent variceal bleeding; terlipressin is used for acute haemorrhage and type 1 hepatorenal syndrome. Ascites is treated with spironolactone, sometimes combined with a loop diuretic. A transjugular intrahepatic portosystemic shunt (TIPS) is used for severe or repeat variceal haemorrhage or refractory ascites. Antibiotics are used for acute haemorrhage, spontaneous bacterial peritonitis, and encephalopathy. Treatment of hepatocellular carcinoma depends on its spread and the degree of decompensation. Liver transplantation should be considered in every case. Cirrhosis is responsible for almost 2% of deaths in Europe.
The goal of treatment in decompensated cirrhosis is to improve liver function, stabilise the disease, or reverse decompensation, and to reduce mortality. However, there are few studies on the reversal of cirrhotic decompensation or re-compensation. The effect of prophylactic treatment on re-compensation, the evaluation indicators and duration of re-compensation, and whether hepatic lobule structure and microvessels can be reconstructed are unclear and require further research. There has been some success but not complete eradication of the disease. Risk factors including chronic hepatitis B and C, autoimmune hepatitis, Wilson disease, and especially alcohol remain a daunting task to treat. Patients who are compliant to treatment are relatively easy to address; without treatment the complications are devastating and lead to death.
No drug repurposing data are presented in these abstracts. No experimental treatments, novel compounds, or repurposed agents are tested or discussed. The management described is entirely based on established therapies for complications and on liver transplantation for end-stage disease. The abstracts do not report any survival or response rates for any drug.
What is still missing are controlled trials specifically designed to test whether any existing drug can achieve re-compensation of cirrhosis, agreed definitions and endpoints for re-compensation, and studies that stratify patients by aetiology and stage of decompensation. The molecular mechanisms that might be targeted to reverse fibrosis or reconstruct hepatic architecture remain incompletely understood. Funding for such trials and for basic research into the structural reversal of cirrhosis is lacking.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Pharmacology & Toxicology · 1994 · 20 citations
Pharmacokinetics of a Single Oral Dose of Clobazam in Patients with Liver Disease
AbstractThe pharmacokinetic effect of a single oral in dose of 20 mg clobazam was studied in 15 patients with liver disease and in 6 healthy volunteers. Plasma concentrations of clobazam and its main metabolite, norclobazam, were measured by gas liquid chromatography. Clobazam was rapidly absorbed. Peak plasma concentrations were 350 +/- 63 ng/ml at 1.7 +/- 0.8 hr in healthy volunteers, 239 +/- 70 ng/ml at 3 +/- 1.9 hr in patients with viral hepatitis and 240 +/- 113 ng/ml at 2.5 +/- 1.5 hr in patients with cirrhosis. Total distribution volume was 173 +/- 88 l and 168 +/- 71 l in patients with viral hepatitis and cirrhosis respectively, and 81 +/- 20 l in volunteers. Corresponding half-life values were 47 +/- 18 hr and 51 +/- 21 hr in patients and 22 +/- 6.3 hr in volunteers. The difference between patients was not significant, whereas the difference between patients and volunteers was significant.
Current Hepatology Reports · 2018 · 17 citations · open access
The Role of Anticoagulation in Treating Portal Hypertension
AbstractPURPOSE OF REVIEW: To revise experimental and clinical data supporting a less traditional role of anticoagulation for treating portal hypertension in patients with cirrhosis. RECENT FINDINGS: Portal hypertension is the main driver of complications such as ascites, variceal hemorrhage, and hepatic encephalopathy, with inflammation as a key component. The traditional view of cirrhosis as a pro-hemorrhagic condition has recently changed, prothrombotic complications being recognized as frequently as the hemorrhagic ones. Several data indicate a close relationship between inflammation, prothrombotic status, worsening of hepatic fibrosis, and portal hypertension both in animal models and in patients with chronic liver disease. These findings indicate that anticoagulation may represent a potent tool to act on fibrogenesis and therefore consequently to treat portal hypertension. All anticoagulants have good to optimal safety profiles and can be used in patients with advanced chronic liver disease with confidence. SUMMARY: Anticoagulation has a role as a pleiotropic treatment of portal hypertension in cirrhosis.
Deutsches Ärzteblatt international · 2013 · 12 citations
The Conservative and Interventional Treatment of the Complications of Liver Cirrhosis
AbstractBACKGROUND: It is estimated that 1 million persons in Germany suffer from hepatic cirrhosis, which is the final stage of chronic inflammation of the liver. Cirrhosis has multiple causes, all of which lead to structural changes of the liver and to portal hypertension. The main complications of cirrhosis arise in turn: These include bleeding from collateral veins, ascites, hepatocellular carcinoma, encephalopathy, and infection leading to organ failure. METHODS: We present the treatment of the main complications of liver cirrhosis with reference to the relevant literature (phase II and III trials, meta-analyses, and reviews). RESULTS: Endoscopic treatment (ligation) is used for the primary and secondary prophylaxis of variceal bleeding. Drugs to lower portal pressure (e.g., beta-blockers) are an established means of preventing initial or recurrent variceal bleeding over the long term. Vasoconstrictors such as terlipressin are mainly used to treat acute hemorrhage and type 1 hepatorenal syndrome. The main treatment of ascites is with spironolactone, in combination with a loop diuretic where indicated. A shunt (TIPS) is used to treat severe or repeat variceal hemorrhage or refractory ascites. Antibiotics play a well-established role in the treatment of acute hemorrhage, in the treatment and prevention of spontaneous bacterial peritonitis, and in the treatment of encephalopathy. The treatment of hepatocellular carcinoma depends on its extent of spread and on the degree of decompensation of cirrhosis. CONCLUSION: For most of the main complications of liver cirrhosis, there are treatments that have been well-tested in randomized trials. Liver transplantation should also be considered in every case.
[Reversal of cirrhotic decompensation: re-compensation].
AbstractLiver cirrhosis is the end stage of chronic liver disease and as the disease progresses to decompensated stage cirrhosis, the mortality rate of patients' increases significantly. The goal of controlling the etiology or treatment in decompensated stage cirrhosis is to improve the liver function of patients, stabilize the disease condition or reverse decompensation, reduce the recurrence of decompensated events and reduce the mortality rate. However, presently, there are few studies on the reversal of cirrhotic decompensation/ re-compensation. Moreover, the effect of prophylactic treatment on re-compensation, evaluation indicators and duration of re-compensation, structure of hepatic lobules and whether microvessels can be reconstructed are unclear, so require further research.
Cirrhosis: Reviewing the Literature and Future Perspectives
AbstractCirrhosis is the final stage of chronic liver disease and has many causes, including viral hepatitis, excessive alcohol intake, and non-alcoholic steatohepatitis. When decompensated cirrhosis develops, complications occur that affect quality of life and patient survival. Cirrhosis has a large burden of disease and is responsible for almost 2% of deaths in Europe. Cirrhotic patients are in need of early diagnosis and a careful follow-up for the prevention and detection of complications. The ultimate treatment for end-stage cirrhosis is liver transplantation. This review will cover clinical aspects of cirrhosis and uncover future trends in the care of these patients.
AbstractLiver cirrhosis and its complications affect millions of patients of all ages around the globe and present treating physicians with perplexing problems, given the variety of etiologies and the critical nature of hepatic physiology. This book is a collection of chapters offering the distilled knowledge of various worldwide experts in hepatic surgery and hepatic physiology. The various debates that are presented regarding the diagnosis and treatment of liver cirrhosis and its significant complications, in addition to the most up-to-date information regarding molecular aspects, provide the reader with the full spectrum of knowledge in this challenging and continuously evolving field.
Journal of Basic and Clinical Pharmacy · 2016 · 3 citations
Unusual Case of an Alcoholic with Liver Injury from Sulfasalazine Use
AbstractA 57-year-old male with a history of alcoholism presented to the emergency room with abdominal pain, jaundice, transaminitis, and hyperbilirubinemia. Due to the history of alcoholism, it was initially presumed that the patient had alcoholic hepatitis but further investigation revealed that he was recently started on sulfasalazine for the treatment of rheumatoid arthritis. Upon cessation of the drug, the patient's liver function tests significantly improved over a few days and eventually normalized within weeks. This case was interesting as the patient's history of alcoholism disguised the actual diagnosis. Furthermore, the late presentation of sulfasalazine-induced liver injury is uncommon as it commonly presents 2-4 weeks after initiation of therapy.
Journal of Liver Research Disorders & Therapy · 2016 · 1 citations
Exciting Results with Injection Darbepoietin Alfa and Pegfilgrastim in Patients with Decompensated Liver Cirrhosis
Abstract1.1.Introduction: Dysregulated erythropoietin (EPO) plasma levels may play a role in the patho physiology of liver cirrhosis. No report of Darbepoetin alpha and Pegylated Filgrastim use in Liver cirrhosis.
1.2.Aims and methods:To study the benefits of Darbepoetin and Pegfilgrastim in patients with de-compensated liver cirrhosis. Prospectively clinical data recorded since October 2014. Patients with active bleed, hepato renal syndrome, hepatoma, portal vessel thrombosis were excluded. Patients started on Injection Darbepoetin alpha 200 microgram and Injection Pegfilgrastim 6 mg subcutaneously every 15 days, total three visits of patients, then three month follow up planned. Improvement in clinical, laboratory parameters analyzed. Median calculated, Wilcoxon Signed-Rank Test applied to compare both groups.
1.3.Results and discussion:N=22 all male, 3 lost to follow up, aetiology of cirrhosis were Non-alcoholic Fatty Liver Disease 5, Hepatitis B Virus 3, Hepatitis C Virus 2 and Alcohol 12. Median age 59 years (range: 40 to 70). Improvement in Haemoglobin from 10.1 gram% (range 5.9-13.4 gm%) to 10.6 gm % (range: 7.5-13.7 gm%) p value 0.00374, Total leukocyte count from 5100/cu mm to 7100/cu mm p value 0.00214, Platelet count 90,000/cu mm to 146,000/cu mm, p value 0.00096, INR 1.7 (range 1.5-4.8) to 1.4 p value 0.00064, Albumin 2.4 gram/dl (range 1.6-2.9) to 2.5 gm/dl (range 1.8-3.5) P value 0.043, Child score from 10 to 8 P value 0.007, ascites score 2 to 1, P value 0.00222. No significant improvement in Serum creatinine, sodium, potassium, calcium, bilirubin, total protein and hepatic encephalopathy. High cost of medicine was the limiting factor.
1.4.Conclusion:Our study suggests that Darbepoetin Alpha and Pegfilgrastim is significantly effective in improving hematology, International normalized ratio, Albumin, ascites and Child score of liver cirrhosis patients.
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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