DeCure's autonomous Psychiatry AI scientist is researching a drug-repurposing hypothesis for alcoholic liver cirrhosis — 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 moduleAlcoholic liver cirrhosis 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 alcoholic liver cirrhosis 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
serpin family A member 1 (SERPINA1) — SERPINA1 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 5rdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 1IZ2 · 2.2 Å · ligand (5R)-5-[(2R)-2-hydroxynonyl]-beta-D-xylulofuranose (Z6W). Experimental structure, not a prediction.
What the evidence adds up to
In a prospective study of 165 patients with decompensated alcoholic cirrhosis followed for a median of 61 months, 70% died during follow-up. Median overall survival was 61 months (95% CI 48–74), but after onset of hepatic encephalopathy median survival fell to 14 months (95% CI 5–23). Baseline MELD score, age, development of hepatic encephalopathy, and continued alcohol use were independently associated with mortality. Ascites was the most common first decompensation, occurring in 51% of patients. Hepatocellular carcinoma developed in 11% of patients. The authors note that the mortality rate in their cohort was lower than in older studies, which they attribute to improvements in clinical management.
A 1983 study comparing patients who stopped drinking with those who continued found that four-year survival was significantly higher in the abstinent group. Continued drinking worsened prognosis. In the 2011 cohort, 60% of patients achieved abstinence during follow-up, and persistence of alcohol use remained an independent predictor of death.
A 2025 analysis of liver biopsy samples from 13 patients with alcohol-related cirrhosis, 19 with hepatitis B cirrhosis, 15 with hepatitis C cirrhosis, and 6 normal controls found that expression of Beclin-1, caspase-3, and Bcl-2 was significantly higher in all cirrhosis groups than in controls (p<0.001). LC3 expression did not differ between groups. Beclin-1 and caspase-3 were positively correlated (r=0.582), while Bcl-2 and caspase-3 were negatively correlated (r=-0.608). The authors conclude that both autophagic and apoptotic pathways are active in cirrhosis, but these pathways were more prominently activated in viral cirrhosis than in alcoholic cirrhosis.
A 2009 review states that up to 40% of patients with severe alcoholic hepatitis die within six months. A 2002 symposium summary covers research on inflammatory mediators, endotoxin signalling, fatty acid ethyl esters, and cyclic gene expression in alcohol-fed rats, but provides no clinical outcome data. What remains missing is a randomised trial testing any specific drug in alcoholic cirrhosis with survival as the endpoint, adequate funding for such a trial, and a method to stratify patients by the dominant cell-death pathway (autophagy versus apoptosis) before assigning therapy.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
New England Journal of Medicine · 2009 · 860 citations
Alcoholic Hepatitis
AbstractThe association between alcohol intake and alcoholic liver disease has been well documented, although cirrhosis of the liver develops in only a small proportion of heavy drinkers. This review focuses on alcoholic hepatitis, a treatable form of alcoholic liver disease. Since up to 40% of patients with severe alcoholic hepatitis die within 6 months after the onset of the clinical syndrome, appropriate diagnosis and treatment are essential.
Journal of Clinical Gastroenterology · 2011 · 76 citations
Long-term Clinical Course of Decompensated Alcoholic Cirrhosis
AbstractBACKGROUND: Prognosis of decompensated alcoholic cirrhosis is based mainly on studies that included patients with different severities of liver disease and did not recognize either hepatitis C virus epidemic or changes in clinical management of cirrhosis. AIM: To define the long-term course after the first hepatic decompensation in alcoholic cirrhosis. METHODS: Prospective inclusion at the start point of decompensated cirrhosis of 165 consecutive patients with alcoholic cirrhosis without known hepatocellular carcinoma hospitalized from January 1998 to December 2001 was made. Follow-up was maintained until death or the end of the observation period (April 1, 2010). RESULTS: The patients were followed for 835.75 patient years. Median age was 56 years (95% confidence interval: 54-58). Baseline Child-Pugh score was 9 (95% CI: 8-9), and model for end-stage liver disease (MELD) was 13.8 (95% CI: 12.5-14.7). Ascites was the most frequent first decompensation (51%). During follow-up, 99 (60%) patients were abstinent, hepatocellular carcinoma developed in 18 (11%) patients, and 116 patients died (70%). Median overall survival was 61 months (95% CI: 48-74). Median survival probability after onset of hepatic encephalopathy (HE) was only 14 months (95% CI: 5-23). Age, baseline MELD, albumin, development of HE, and persistence of alcohol use were independently correlated with mortality. CONCLUSIONS: Patients with alcoholic cirrhosis show a high frequency of complications. The low mortality rate in our cohort of patients probably reflects the improvement in the management of patients with cirrhosis; it is mainly influenced by baseline MELD, age, HE development, and continued abstinence. Patients who develop HE should be considered for hepatic transplantation.
Alcoholism Clinical and Experimental Research · 2002 · 43 citations · open access
Pathogenesis of Alcoholic Liver Disease–Recent Advances
AbstractThe article summarizes the proceedings of a symposium on recent advances in research on the pathogenesis of alcoholic liver disease at the 2001 RSA meeting in Montreal, Canada. The chairs were Amin A. Nanji and Samuel W. French. The presentations were (1) Role of inflammatory mediators in alcoholic liver injury by Amin A. Nanji, (2) Role of endotoxin, lipopolysaccharide binding protein, CD14 and Toll receptors in alcoholic liver injury by Grace Su, (3) Fatty acid ethyl esters: toxicity, metabolism and markers of ethanol intake by Michael Laposata, and (4) Cyclic changes in gene expression when rats are fed alcohol at a constant rate by Samuel W. French.
Effect of continued drinking on prognosis of alcoholic liver cirrhosis.
AbstractThe prognoses of patients with alcoholic liver cirrhosis were compared between those who continued to drink and those who stopped. Clinical criteria were strictly set so as to control other variables affecting the prognoses. Four-year survival was significantly higher in the patients who stopped drinking than in those who continued to drink. Continued drinking worsens the prognosis of patients with alcoholic liver cirrhosis.
Saudi Medical Journal · 2025 · 0 citations · open access
Comparative analysis of autophagy and apoptosis pathways in viral and alcoholic cirrhosis
Abstract<h3>Objectives:</h3> To study the different cellular death mechanisms between viral cirrhosis and alcoholic cirrhosis. The research investigated autophagy and apoptosis mechanisms in hepatitis B virus (HBV), hepatitis C virus (HCV) and alcohol-induced cirrhosis. <h3>Methods:</h3> The research team analyzed biopsy samples from the liver which were obtained at Florence Nightingale Hospitals, Istanbul, Turkey. The experimental protocols were performed between February 2021 and February 2023. The study included 19 HBV, 15 HCV, 13 alcohol-related cirrhosis patients and 6 normal liver tissues. Beclin-1, Caspase-3, Bcl-2 and LC3 expressions were evaluated by immunohistochemistry. <h3>Results:</h3> Staining intensity as well as extent underwent evaluation through H-score methodology. The expression levels of Beclin-1 (control: 0.7±0.3, HBV: 6.0±1.4, HCV: 5.1±1.3, alcohol: 4.8±1.2), caspase-3 (control: 0.4±0.2, HBV: 6.0±1.4, HCV: 5.1±1.2, alcohol: 5.5±1.3) and Bcl-2 (control: 0.3±0.2, HBV: 5.5±1.2, HCV: 4.8±1.1, alcohol: 4.6±1.1) were significantly higher than those of the control group (<i>p</i><0.001). LC3 expression revealed no between-group differences. A positive association for Beclin-1 with Caspase-3 (r=0.582) alongside negative association for Bcl-2 with Caspase-3 (r=-0.608) was documented. <h3>Conclusion:</h3> Our findings suggest that both autophagic and apoptotic pathways are active in the pathogenesis of cirrhosis. Similar cell death mechanisms were found to be involved in viral and alcoholic cirrhosis, but these pathways were more prominently activated in viral cirrhosis.
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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