The introduction of new preclinical models for in vitro drug discovery and testing based on 3D tissue-specific extracellular matrix (ECM) is very much awaited. This study was aimed at developing and validating a co-culture model using decellularized human liver 3D ECM scaffolds as a platform for anti-fibrotic and anti-cancer drug testing. Decellularized 3D scaffolds obtained from healthy and cirrhotic human livers were bioengineered with LX2 and HEPG2 as single and co-cultures for up to 13 days and validated as a new drug-testing platform. Pro-fibrogenic markers and cancer phenotypic gene/protein expression and secretion were differently affected when single and co-cultures were exposed to TGF-β1 with specific ECM-dependent effects. The anti-fibrotic efficacy of Sorafenib significantly reduced TGF-β1-induced pro-fibrogenic effects, which coincided with a downregulation of STAT3 phosphorylation. The anti-cancer efficacy of Regorafenib was significantly reduced in 3D bioengineered cells when compared to 2D cultures and dose-dependently associated with cell apoptosis by cleaved PARP-1 activation and P-STAT3 inhibition. Regorafenib reversed TGF-β1-induced P-STAT3 and SHP-1 through induction of epithelial mesenchymal marker E-cadherin and downregulation of vimentin protein expression in both co-cultures engrafting healthy and cirrhotic 3D scaffolds. In their complex, the results of the study suggest that this newly proposed 3D co-culture platform is able to reproduce the natural physio-pathological microenvironment and could be employed for anti-fibrotic and anti-HCC drug screening.

The relationship between ammonia and liver-related complications (LRCs) in acute-on-chronic liver failure (ACLF) patients is not clearly established. This study aimed to evaluate the association between ammonia levels and LRCs in patients with ACLF. The study also evaluated the ability of ammonia in predicting mortality and progression of LRCs. The study prospectively recruited ACLF patients based on the APASL definition from the ACLF Research Consortium (AARC) from 2009 to 2019. LRCs were a composite endpoint of bacterial infection, overt hepatic encephalopathy (HE), and ascites. A total of 3871 cases were screened. Of these, 701 ACLF patients were enrolled. Patients with LRCs had significantly higher ammonia levels than those without. Ammonia was significantly higher in patients with overt HE and ascites, but not in those with bacterial infection. Multivariate analysis found that ammonia was associated with LRCs. Additionally, baseline arterial ammonia was an independent predictor of 30-day mortality, but it was not associated with the development of new LRCs within 30 days. In summary, baseline arterial ammonia levels are associated with 30-day mortality and LRCs, mainly overt HE and ascites in ACLF patients.

We report a case of a 52-year-old woman without previous underlying liver disease, presenting with progressive jaundice and diagnosed with autoimmune hepatitis after 2 doses of an inactivated coronavirus disease 2019 (CoronaVac) vaccine. All serology and histology were compatible with autoimmune hepatitis. Symptoms were improved and liver function tests were normalized after treatment with steroids and azathioprine.

The psychometric hepatic encephalopathy score (PHES) is the gold standard for diagnosing minimal hepatic encephalopathy (MHE). Screening for MHE is frequently overlooked in clinical practice due to time constraints. Furthermore, the simplified animal naming test (S-ANT1) is a new simple tool for evaluating MHE in cirrhotic patients. The purpose of this study was to standardize the PHES in a healthy Thai population, assess the prevalence of MHE, and validate the S-ANT1 in detecting MHE in patients with cirrhosis. The study included 194 healthy controls and 203 cirrhotic patients without overt HE. Psychometric tests and the S-ANT1 were administered to all participants. Multiple linear regression was used to analyze factors related to PHES results, and formulas were developed to predict the results for each PHES subtest. In healthy controls, age and education were predictors of all five subtests. The PHES of the control group was −0.26 ± 2.28 points, and the threshold for detecting MHE was set at ≤ −5 points. The cirrhotic group had PHES values of −2.6 ± 3.1 points. Moreover, MHE was found to be present in 26.6% of cirrhotic patients. S-ANT1 had a moderate positive correlation with PHES (r = 0.44, p < 0.001). S-ANT1 < 22 named animals detected MHE with a sensitivity of 71.2%, specificity of 65%, and area under the receiver operating curve of 0.68 (p < 0.001). In conclusion, Thai PHES normative data have been developed to detect MHE in cirrhotic patients who do not have overt HE. The optimal cutoff for detecting MHE in Thai cirrhotic patients was PHES ≤ −5 points and S-ANT1 < 22 named.

BACKGROUND Diagnosing bacterial infections (BI) in patients with cirrhosis can be challenging because of unclear symptoms, low diagnostic accuracy, and lengthy culture testing times. Various biomarkers have been studied, including serum procalcitonin (PCT) and presepsin. However, the diagnostic performance of these markers remains unclear, requiring further informative studies to ascertain their diagnostic value. AIM To evaluate the pooled diagnostic performance of PCT and presepsin in detecting BI among patients with cirrhosis. METHODS We performed a systematic search of the MEDLINE, EMBASE, and Scopus databases for studies that evaluated the diagnostic role of PCT and presepsin from inception to June 2024. Sensitivity and specificity values were pooled using a random effects model. BI was diagnosed based on clinical manifestations, physical examination, laboratory data, and radiological findings. RESULTS Of the 6639 articles retrieved, 28 met the inclusion criteria and included 4287 patients with 1789 cases of BI (41.7%). The bivariate pooled sensitivity and specificity estimates of PCT for BI diagnosis were 0.73 [95% confidence interval (CI): 0.64-0.81] and 0.83 (95%CI: 0.79-0.87), respectively. The diagnostic odds ratio (DOR) of PCT was 17.21 (95%CI: 9.57-30.95). Presepsin showed a pooled sensitivity of 0.75 (95%CI: 0.60-0.86), specificity of 0.80 (95%CI: 0.68-0.88), and DOR of 12.33 (95%CI: 5.10-29.83) for diagnosing BI. The pooled sensitivity and specificity of PCT for diagnosing spontaneous bacterial peritonitis (SBP) were 0.76 (95%CI: 0.67-0.84) and 0.87 (95%CI: 0.78-0.92), respectively. The positive likelihood ratio of PCT was 5.57 (95%CI: 3.34-9.29), which was sufficiently indicative of SBP. The DOR of PCT was 29.50 (95%CI: 12.30-70.80). CONCLUSION PCT and presepsin have high sensitivity and specificity for detecting BI in patients with cirrhosis. Furthermore, PCT has good diagnostic value as a rule-in test for SBP diagnosis.