Development and validation of a noninvasive prediction model of autoimmune hepatitis in patients with liver diseases.

BACKGROUND AND AIMS: There is no golden standard for the diagnosis of autoimmune hepatitis which still dependent on liver biopsy currently. So, we developed a noninvasive prediction model to help optimize the diagnosis of autoimmune hepatitis. METHODS: From January 2017 to December 2019, 1739 patients who had undergone liver biopsy were seen in the second hospital of Nanjing, of which 128 were here for consultation. Clinical, laboratory, and histologic data were obtained retrospectively. Multivariable logistic regression analysis was employed to create a nomogram model that predicting the risk of autoimmune hepatitis. Internal and external validation was both performed to evaluate the model. RESULTS: A total of 1288 patients with liver biopsy were enrolled (1184 from the second hospital of Nanjing, the remaining 104 from other centers). After the univariate and multivariate logistic regression analysis, nine variables including ALT, IgG, ALP/AST, ALB, ANA, AMA, HBsAg, age, and gender were selected to establish the noninvasive prediction model. The nomogram model exhibits good prediction in diagnosing autoimmune hepatitis with AUROC of 0.967 (95% CI: 0.776-0.891) in internal validation and 0.835 (95% CI: 0.752-0.919) in external validation. CONCLUSIONS: ALT, IgG, ALP/AST, ALB, ANA, AMA, HBsAg, age, and gender are predictive factors for the diagnosis of autoimmune hepatitis in patients with unexplained liver diseases. The predictive nomogram model built by the nine predictors achieved good prediction for diagnosing autoimmune hepatitis.

Transjugular liver biopsy: enlarge the indications for liver biopsy with reliable diagnostic quality.

BACKGROUND: Complications and diagnostic efficiency for liver biopsy are main concerns for clinicians. This study aimed to assess the safety and efficacy of transjugular liver biopsy (TJLB) compared with percutaneous liver biopsy (PLB) when patients had equal level of liver function and number of passes, using propensity score matching (PSM). METHODS: The clinical and pathological data of patients who received TJLB or PLB between January 2012 and October 2022 were collected. Matching factors included age, gender, cirrhosis, portal hypertension, liver function, creatinine, number of passes, hemodialysis, history of anti-coagulation and anti-platelet, and comorbidities. Coagulation indexes were not considered as matching factors due to different indications of the two techniques. RESULTS: 2711 PLBs and 30 TJLBs were evaluated. By PSM, 75 patients (50 PLBs, 25 TJLBs) were matched. The complication rates for TJLB and PLB were 4.0% (1/25) and 10.0% (5/50) (P > 0.05). Two PLBs had hepatic hemorrhage, one of which required only close monitoring (Grade 1) and the other needed hemostasis and rehydration therapy (Grade 2). The other 3 cases presented with mild abdominal pain (Grade 1). And only one TJLB presented with mild pain. The median number of complete portal tracts were 6.0 and 10.0 for TJLBs and PLBs (P < 0.05). Moreover, the median length of sample for TJLBs and PLBs were 10.0 and 16.5 mm (P < 0.05). The diagnostic efficiency of hepatopathy of unknown etiology of TJLB versus PLB groups before and after matching were 96.4% vs. 94.1% and 95.7% vs. 93.2%, respectively (P > 0.05). CONCLUSION: TJLB is an effective invasive diagnostic procedure that expands indications for liver biopsy with reliable diagnostic quality.

Aberrant cytokeratin 7 expression by hepatocytes can predict the ductopenia grade in primary biliary cholangitis.

BACKGROUND: Aberrant cytokeratin 7 expression by hepatocytes (CK7+Hs) is the hallmark characteristic of cholestasis diseases, especially in ductopenia diseases such as primary biliary cholangitis (PBC). This study attempted to evaluate the differences and relationships between the clinical and histological features of aberrant cytokeratin 7 (CK7) expression by hepatocytes in PBC patients. METHODS: The clinicopathological data of patients diagnosed with PBC at the Second Hospital of Nanjing between January 2016 and September 2018 were analysed with SPSS 20.0. RESULTS: Eighty-nine PBC patients who underwent liver biopsy were enrolled in this study, and 15, 29 and 45 patients had aberrant CK7 expression by hepatocytes (CK7+Hs (2 +), CK7+Hs (1 +), and CK7-Hs, respectively). There were significant differences in TB, DB, ALP, TA, IgM, interface activity, and ductopenia grade between patients with CK7-Hs and CK7+Hs (2 +) (P < 0.05). The ductopenia grade was also significantly different between patients with CK7+Hs (2 +) and CK7+Hs (1 +) according to sex (P < 0.05). Upon merging the data of CK7+Hs (2 +) and CK7+Hs (1 +) into CK7+Hs, we found significant differences in AMA, AMA-M2, anti-gp210, TB, DB, ALP, TA, IgM, fibrosis, and ductopenia grade between CK7+Hs and CK7-Hs (P < 0.05). The odds ratios (ORs) (and 95% confidence intervals (CIs)) of CK7+Hs according to anti-gp210, ductopenia grade, and interface activity were 6.413 (95% CI 1.363-30.162), 4.145 (95% CI 1.898-9.052) and 3.247 (95% CI 1.556-6.775), respectively (P < 0.05). Spearman's rank correlation according to interface activity and ductopenia grade in patients with CK7+Hs (2 + , 1 + , 0) was r = 0.359 (P = 0.001) and r = 0.396 (P < 0.001), respectively. CONCLUSION: CK7+Hs serves as a cholestasis index of PBC and are associated with the ductopenia grade and interface activity. Aberrant cytokeratin 7 expression by hepatocytes can predict the ductopenia grade in primary biliary cholangitis.

Study on the mechanism of action of Scutellaria barbata on hepatocellular carcinoma based on network pharmacology and bioinformatics.

Background: Hepatocellular carcinoma is one of the most common cancers with the characteristics of invasion and high mortality. Current forms of prevention remain severe. Scutellaria barbata is widely used in traditional Chinese medicine treatment of various tumors. This study explored the mechanism of Scutellaria barbata in the treatment of hepatocellular carcinoma by network pharmacology and bioinformatics. Methods: The active ingredients of Scutellaria barbata and potential targets for the treatment of hepatocellular carcinoma were collected by network pharmacology. The protein interaction network was constructed to screen the core targets, and the association between the core targets and diseases was further verified by bioinformatics methods. Finally, the active ingredients corresponding to the targets closely related to the disease were screened for AMDE characteristics analysis. Molecular docking of drug-like ingredients with corresponding targets was performed. We used CCK-8 kit to determine the effect of active ingredients on cell proliferation. Results: 29 candidate active ingredients and 461 related targets of Scutellaria barbata were screened. A total of 8238 potential therapeutic targets for hepatocellular carcinoma were indentified. Finally, 373 potential targets for the treatment of HCC were obtained. The active ingredients: wogonin, Rhamnazin, eriodictyol, quercetin, baicalein, and luteolin, etc. The core targets were CDK1, CDK4, SRC, and E2F1. A total of 3056 GO enrichment entries were obtained, and 180 enrichment results were obtained by KEGG pathway analysis. Genes were mainly enriched in PI3K-Akt signaling pathway, IL-17 signaling pathway, TNF signaling pathway, apoptosis pathway, and hepatocellular carcinoma pathway. Molecular docking results showed that the screened compounds had strong binding ability with the corresponding target proteins. CCK8 assays showed that Rhamnazin and Luteolin suppressed the proliferation of HCC cells significantly compared with controls. Conclusion: This study revealed that the mechanism of Scutellaria barbata in the treatment of hepatocellular carcinoma may be that the active ingredients inhibit the expression of core genes and block the PI3K-AKT signaling pathway to inhibit the proliferation, and migration and induce apoptosis of cancer cells.