Objective To investigate the value of international standardized ratio-to-platelet ratio (INPR) versus aspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis-4 (FIB-4) in the diagnosis of liver fibrosis in patients with primary cholangitis (PBC). Methods A retrospective analysis was performed for the patients who underwent liver biopsy and were diagnosed with PBC in The First Affiliated Hospital of Zhengzhou University from October 2013 to March 2021. Scheuer score was used to systematically evaluate the degree of liver fibrosis (S0-S4 stage). According to the results of liver biopsy, the degree of liver fibrosis was classified as significant liver fibrosis (≥S2), progressive liver fibrosis (≥S3), and liver cirrhosis (S4). Related data including general information, liver function, routine blood test results, and blood coagulation were collected, and related formulas were used to calculate the values of the noninvasive serological models INPR, APRI, and FIB-4. The Kruskal-Wallis H test was used for comparison of continuous data between multiple groups, and the chi-square test was used for comparison of categorical data between multiple groups. A Spearman correlation analysis was used to evaluate the correlation between noninvasive models and liver fibrosis stage. The receiver operating characteristic (ROC) curve was used to evaluate the efficacy of the noninvasive serological models in the diagnosis of liver fibrosis degree, and the DeLong method was used for comparison of the area under the ROC curve (AUC). Results A total of 143 patients with PBC were enrolled in the study, among whom 4 had stage S0 liver fibrosis, 50 had stage S1 liver fibrosis, 46 had stage S2 liver fibrosis, 26 had stage S3 liver fibrosis, and 17 had stage S4 liver fibrosis. There was a significant difference in INPR value between the PBC patients with different liver fibrosis degrees ( χ 2 =27.347, P < 0.001). INPR value gradually increased with the aggravation of liver fibrosis degree, and INPR was positively correlated with liver fibrosis degree ( r =0.419, P < 0.01). The ROC curve analysis showed that INPR, APRI, and FIB-4 had an AUC of 0.691, 0.706, and 0.742, respectively, in the diagnosis of significant liver fibrosis (≥S2) in PBC patients, at the corresponding cut-off values of 0.63, 0.59, and 2.68, respectively. INPR, APRI, and FIB-4 had an AUC of 0.731, 0.675, and 0.756, respectively, in the diagnosis of progressive hepatic fibrosis (≥S3) in PBC patients, at the corresponding cut-off values of 0.64, 1.23, and 4.63, respectively. INPR, APRI, and FIB-4 had an AUC of 0.820, 0.786, and 0.818, respectively, in the diagnosis of liver cirrhosis (S4) in PBC patients, at the corresponding cut-off values of 0.95, 1.26, and 4.63, respectively. In the evaluation of significant liver fibrosis, progressive liver fibrosis, and liver cirrhosis, there was no significant difference in AUC between INPR and APRI/FIB-4 (all P > 0.05). Conclusion INPR is a simple and accurate noninvasive model for the evaluation of liver fibrosis and has a certain value in the diagnosis of liver fibrosis in PBC.

Objective To investigate the value of age and D-dimer (D-D) combined with Model for End-Stage Liver Disease (MELD) score in predicting the prognosis of patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). Methods A total of 111 patients with HBV-ACLF who were hospitalized in The First Affiliated Hospital of Zhengzhou University from December 2019 to October 2021 were enrolled, and according to their prognosis on day 90 after confirmed diagnosis, they were divided into survival group with 49 patients and death group with 62 patients. Related clinical data were collected, including age, sex, underlying liver diseases, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil), Albumin (Alb), D-D, prothrombin time (PT), plasma fibrinogen (FIB), prothrombin activity (PTA), international normalized ratio (INR), serum creatinine (SCr), and serum sodium (Na), and MELD score was calculated. Immunoturbidimetric assay was used to measure the plasma level of D-D. The t -test or the Mann-Whitney U test was used for comparison of continuous data between the two groups, and the chi-square test was used for comparison of categorical data between the two groups; a binary Logistic regression analysis was used to investigate the independent risk factors for the prognosis of patients, and the receiver operating characteristic (ROC) curve was used to predict the accuracy of variables. Results There were significant differences between the two groups in age, TBil, D-D, PT, PTA, INR, SCr, Na, and MELD score (all P < 0.05). The binary Logistic regression analysis showed that age (odds ratio [ OR ]=1.088, 95% confidence interval [ CI ]: 1.001-1.183, P =0.047), D-D ( OR =1.521, 95% CI : 1.078-2.145, P =0.017), and MELD score ( OR =1.892, 95% CI : 1.408-2.543, P < 0.001) were independent risk factors for the prognosis of HBV-ACLF patients. Age, MELD score and D-D had an area under the ROC curve (AUC) of 0.664, 0.869, and 0.887, respectively, in predicting the prognosis of HBV-ACLF, while D-D combined with age, age combined with MELD score, D-D combined with MELD score, and the combination of these three indicators had an AUC of 0.895, 0.906, 0.965, and 0.970, respectively. A combination of the three indices had a significantly increased AUC compared with other indices except D-D combined with MELD score. and the combination of these three indicators had relatively high sensitivity (0.935) and specificity (0.918). Conclusion Age, D-D, and MRLD score are independent risk factors for the prognosis of HBV-ACLF, among which D-D and MELD score have a good value in predicting prognosis, and the combination of these three indicators has a significantly better predictive value.

Nowadays potential preclinical drugs for the treatment of nonalcoholic steatohepatitis (NASH) have failed to achieve expected therapeutic efficacy because the pathogenic mechanisms are underestimated. Inactive rhomboid protein 2 (IRHOM2), a promising target for treatment of inflammation-related diseases, contributes to deregulated hepatocyte metabolism-associated nonalcoholic steatohepatitis (NASH) progression. However, the molecular mechanism underlying Irhom2 regulation is still not completely understood. In this work, we identify the ubiquitin-specific protease 13 (USP13) as a critical and novel endogenous blocker of IRHOM2, and we also indicate that USP13 is an IRHOM2-interacting protein that catalyzes deubiquitination of Irhom2 in hepatocytes. Hepatocyte-specific loss of the Usp13 disrupts liver metabolic homeostasis, followed by glycometabolic disorder, lipid deposition, increased inflammation, and markedly promotes NASH development. Conversely, transgenic mice with Usp13 overexpression, lentivirus (LV)- or adeno-associated virus (AAV)-driven Usp13 gene therapeutics mitigates NASH in 3 models of rodent. Mechanistically, in response to metabolic stresses, USP13 directly interacts with IRHOM2 and removes its K63-linked ubiquitination induced by ubiquitin-conjugating enzyme E2N (UBC13), a ubiquitin E2 conjugating enzyme, and thus prevents its activation of downstream cascade pathway. USP13 is a potential treatment target for NASH therapy by targeting the Irhom2 signaling pathway.