Validation of conventional non-invasive fibrosis scoring systems in patients with metabolic associated fatty liver disease.

BACKGROUND: Non-invasive fibrosis scores are not yet validated in the newly defined metabolic associated fatty liver disease (MAFLD). AIM: To evaluate the diagnostic performance of four non-invasive scores including aspartate aminotransferase to platelet ratio index (APRI), fibrosis-4 index (FIB-4), body mass index, aspartate aminotransferase/alanine aminotransferase ratio, diabetes score (BARD), and nonalcoholic fatty liver disease fibrosis score (NFS) in patients with MAFLD. METHODS: Consecutive patients with histologically confirmed MAFLD were included. The discrimination ability of different non-invasive scores was compared. RESULTS: A total of 417 patients were included; 156 (37.4%) of them had advanced fibrosis (Metavir ≥ F3). The area under receiver operating characteristic curve of FIB-4, NFS, APRI, and BARD for predicting advanced fibrosis was 0.736, 0.724, 0.671, and 0.609, respectively. The area under receiver operating characteristic curve of FIB-4 and NFS was similar (P = 0.523), while the difference between FIB-4 and APRI (P = 0.001) and FIB-4 and BARD (P < 0.001) was statistically significant. The best thresholds of FIB-4, NFS, APRI, and BARD for diagnosis of advanced fibrosis in MAFLD were 1.05, -2.1, 0.42, and 2. A subgroup analysis showed that FIB-4, APRI, and NFS performed worse in the pure MAFLD group than in the hepatitis B virus-MAFLD group. CONCLUSION: APRI and BARD scores do not perform well in MAFLD. The FIB-4 and NFS could be more useful, but a new threshold is needed. Novel non-invasive scoring systems for fibrosis are required for MAFLD.

[Retracted] Anticancer and apoptotic activities of oleanolic acid are mediated through cell cycle arrest and disruption of mitochondrial membrane potential in HepG2 human hepatocellular carcinoma cells.

Following the publication of the above paper, a concerned reader drew to the Editor's attention that several figures (principally, Figs. 3, 6 and 8) contained data that bore striking similarities to data published in other papers, some of which had been published around the same time and written by different authors based at different research institutions. After having conducted an independent investigation in the Editorial Office, the Editor of Molecular Medicine Reports has determined that this article should be retracted from the Journal on account of a lack of confidence concerning the originality and the authenticity of the data. The authors were asked for an explanation to account for these concerns, but the Editorial Office never received any reply. The Editor regrets any inconvenience that has been caused to the readership of the Journal. [the original article was published in Molecular Medicine Reports 12: 5012­5018, 2015; DOI: 10.3892/mmr.2015.4033].

Clinic-pathological features of metabolic associated fatty liver disease with hepatitis B virus infection.

BACKGROUND: Metabolic associated fatty liver disease (MAFLD) is a novel concept proposed in 2020. AIM: To compare the characteristics of MAFLD and MAFLD with hepatitis B virus (HBV) infection. METHODS: Patients with histopathologically proven MAFLD from a single medical center were included. Patients were divided into MAFLD group (without HBV infection) and HBV-MAFLD group (with HBV infection). Propensity score matching was utilized to balance the baseline characteristics between two groups. RESULTS: A total of 417 cases with MAFLD were included, 359 (86.1%) of whom were infected with HBV. There were significantly more males in the HBV-MAFLD group than in the MAFLD group (P < 0.05). After propensity score matching, 58 pairs were successfully matched with no significant differences found in gender, age, body mass index, lipid levels, liver enzymes, and the other metabolic associated comorbidities between the two groups (P > 0.05). The rank sum test results showed that the degree of liver steatosis in the MAFLD group was more severe than that in the HBV-MAFLD group, while the degree of inflammation and fibrosis in the liver was less severe (P < 0.05). In multivariate analysis, HBV infection was associated with significantly lower grade of hepatic steatosis [odds ratio (OR) = 0.088, 95% confidence interval (CI): 0.027-0.291] but higher inflammation level (OR = 4.059, 95%CI: 1.403-11.742) and fibrosis level (OR = 3.016, 95%CI: 1.087-8.370) after adjusting for age, gender, and other metabolic parameters. CONCLUSION: HBV infection is associated with similar metabolic risks, lower steatosis grade, higher inflammation, and fibrosis grade in MAFLD patients.

Development of a novel score for the diagnosis of bacterial infection in patients with acute-on-chronic liver failure.

BACKGROUND: The diagnosis of bacterial infection is difficult in patients with acute-on-chronic liver failure (ACLF). AIM: To evaluate the diagnostic accuracy of widely used parameters for bacterial infection in ACLF and to develop a simple scoring system to improve diagnostic efficiency. METHODS: This was a retrospective study. Procalcitonin (PCT), white blood cells (WBC), proportion of neutrophils (N%), and C-reactive protein (CRP) were examined. Logistic regression was used to select variables for the scoring models and receiver operating characteristic curve (ROC) analysis was used to evaluate the diagnostic value of different indices. RESULTS: This study included 386 patients with ACLF, 169 (43.78%) of whom had bacterial infection on admission. The area under the ROC (AUROC) of PCT, CRP, WBC and N% for the diagnosis of bacterial infection ranged from 0.637 to 0.692, with no significant difference between them. Logistic regression showed that only N%, PCT, and CRP could independently predict infection. A novel scoring system (infection score) comprised of N%, PCT and CRP was developed. The AUROC of the infection score was 0.740, which was significantly higher than that for the other four indices (infection score vs N%, PCT, CRP, and WBC, P = 0.0056, 0.0001, 0.0483 and 0.0008, respectively). The best cutoff point for the infection score was 4 points, with a sensitivity of 78.05%, a specificity of 55.29%, a positive predictive value of 57.91% and a negative predictive value of 76.16%. CONCLUSION: The infection score is a simple and useful tool for discriminating bacterial infection in ACLF.

Anticancer and apoptotic activities of oleanolic acid are mediated through cell cycle arrest and disruption of mitochondrial membrane potential in HepG2 human hepatocellular carcinoma cells.

Hepatocellular carcinoma (HCC) is an aggressive form of cancer, with high rates of morbidity and mortality, a poor prognosis and limited therapeutic options. The objective of the present study was to demonstrate the anticancer activity of oleanolic acid in HepG2 human HCC cells. Cell viability was evaluated using an MTT assay, following administration of various doses of oleanolic acid. The effect of oleanolic acid on cell cycle phase distribution and mitochondrial membrane potential was evaluated using flow cytometry with propidium iodide and rhodamine­123 DNA­binding cationic fluorescent dyes. Fluorescence microscopy was employed to detect morphological changes in HepG2 cells following oleanolic acid treatment. The results revealed that oleanolic acid induced a dose­dependent, as well as time­dependent inhibition in the growth of HepG2 cancer cells. Following acridine orange and ethidium bromide staining, treatment with various doses (0, 5, 25 and 50 µM) of oleanolic acid induced typical morphological changes associated with apoptosis, including cell shrinkage, membrane blebbing, nuclear condensation and apoptotic body formation. Cell cycle analysis revealed that oleanolic acid induced cell cycle arrest in HepG2 cells at the sub­G1 (apoptotic) phase of the cell cycle, in a dose­dependent manner. Staining with Annexin V­fluorescein isothiocyanate and propidium iodide revealed that apoptosis occurred early in these cells. Oleanolic acid treatment also resulted in fragmentation of nuclear DNA in a dose­dependent manner, producing the typical features of DNA laddering on an agarose gel. The results also demonstrated that oleanolic acid treatment resulted in a potent loss of mitochondrial membrane potential, which also occurred in a dose­dependent manner. Therefore, oleanolic acid may be used as a therapeutic agent in the treatment of human HCC.

Hepatitis B surface antigen in late hepatitis B infection.

Hepatitis B surface antigen (HBsAg) levels are used to evaluate and monitor clinical phases of chronic hepatitis B infection but their clinical significance is unclear in the late complications, cirrhosis of the liver and hepatocellular carcinoma. This study aimed to evaluate HBsAg levels across the whole natural history of hepatitis B virus infection, including late complications. This retrospective, cross-sectional study enrolled 838 treatment-naive patients diagnosed with chronic hepatitis B infection at First Affiliated Hospital of Fujian Medical University between 2009 and 2012. Patients were classified into six groups: immunotolerance, immunoclearance, low replicative, negative hepatitis e (HBeAg) phases, liver cirrhosis, and hepatocellular carcinoma. Main outcome measures were serum HBsAg, HBeAg, HBV DNA, total bilirubin, albumin, alanine and aspartate aminotransferase, and quantitative correlation of HBsAg with HBV DNA. HBsAg levels declined significantly between clinical phases of infection (all P < 0.001) and were significantly lower in decompensated than in compensated cirrhosis (2.90 vs. 3.30, P < 0.001) but not significantly different between early versus advanced hepatocellular carcinoma. Significant positive correlations were observed between serum HBsAg and HBV DNA at immunoclearance and HBeAg negative phases, compensated and decompensated liver cirrhosis and advanced but not early hepatocellular carcinoma (all P < 0.001). HBsAg and HBV DNA were significantly higher in HBeAg positive patients with advanced hepatocellular carcinoma (P < 0.001). HBsAg levels differ significantly between chronic hepatitis B infection phases, decreasing progressively from chronic infection to cirrhosis and hepatocellular carcinoma. Significant correlations are found between serum HBsAg and HBV DNA.

A new model for predicting liver cirrhosis in chronic hepatitis B virus carriers with low serum alanine transaminase activity.

OBJECTIVES: To develop a cirrhosis-predicted model in chronic hepatitis B virus carriers with alanine transarninase (ALT) less than two times the upper limit of normal (ULN). METHODS: Treatment-naive patients (n=278), who had undergone liver biopsies, were randomly divided into two groups - a training group and a validation group. Thirteen bio-clinical parameters were analyzed. A liver cirrhosis-predicting model (PPT model) was constructed using multivariate analysis. The diagnostic value of the model was analyzed by the receiving operating characteristics (ROC) method and compared with other available models. RESULTS: A PPT model to predict liver cirrhosis was derived from three independent predictors of liver fibrosis [platelet count (PLT), prothrombin time (PT) and total bile acid (TBA)]. PPT model predicted cirrhosis with an area under the ROC (AUROC) curve of 0.83, a positive predictive value of 86.7% and a negative predictive value of 95.2%. Compared with APRI, FIB-4, age-AST model, AP index and APGA model, PPT model had the highest correlation coefficient (r=0.49) and greater predictive performance (AUROC of 0.83). CONCLUSIONS: The PPT model was accurate in predicting cirrhosis and may reduce the need for liver biopsy in chronic hepatitis B virus carriers with ALT less than two times ULN.

[Prolonged duration of the routine pegylated-interferon alfa-2a therapy produces superior virological response in HBeAg-positive chronic hepatitis B patients: a single-center cohort study].

OBJECTIVE: Hepatitis B e antigen (HBeAg) seroconversion and/or hepatitis B surface antigen (HBsAg) clearance are considered as good prognostic indicators of treatment outcome in HBeAg-positive chronic hepatitis B (CHB) patients. While a sustained virological response (SVR) can be achieved by a finite 48-week course of pegylated-interferon alfa-2a (Peg-IFNalpha-2a), it has been suggested that longer-term treatment can improve the rate of SVR. Therefore, the aim of this study was to compare the effects of prolonged and routine Peg-IFNa-2a therapy in patients with HBeAg-positive CHB. METHODS: Eighty-six consecutive patients diagnosed with HBeAg-positive CHB at our hospital between September 2006 and October 2009 were enrolled in the study. The patients were randomly assigned to receive Peg-IFNa-2a (180 mug once weekly) for either 48 weeks (routine therapy group, n = 53) or 72 weeks (prolonged therapy group, n = 33). Serum samples were collected from each patient every three months until the end of the 24-week follow-up, and standard viral and biochemical tests were carried out. Relapse was defined as HBV DNA concentrations more than 105 copies/mL or an HBeAg-positive test at the end of the 24-week follow-up. Chi-squared test and the t-test were used to determine the significance of intergroup differences. Logistic regression analysis was employed to determine the correlation of outcome parameters to treatment duration, expressed as odds ratio (OR) with 95% confidence interval (CI). RESULTS: The two treatment groups were similar at baseline (pre-treatment) in demographic data, sex ratio, age, alanine aminotransferase (ALT) level, HBV DNA load, and semi-quantitative level of HBeAg (s/co) (all, P more than 0.05). At the end of the 24-week follow-up, there were significant differences between the 48-week treatment group and the 72-week treatment group in patients with HBV DNA negativity (62.3% vs. 97.0%, x2 = 13.273, P = 0.000), HBeAg seroconversion (39.6% vs. 57.6%, x2 = 6.765, P = 0.009), HBsAg clearance (15.1% vs. 36.4%, x2 = 5.155, P = 0.023), and relapse (58.5% vs. 33.3%, x2 = 6.713, P = 0.010). Logistic regression analysis indicated that therapy duration was correlated to HBeAg clearance (OR = 3.702, 95% CI: 1.225 to 11.188) and male sex (OR = 3.005, 95% CI: 1.038 to 8.696) but not to HBeAg level at baseline (OR = 0.999, 95% CI: 0.998 to 1.000) or age (OR = 0.902, 95% CI: 0.839 to 0.970). CONCLUSION: In this single-center cohort study, superior therapeutic benefit was achieved by extending the Peg-IFNa-2a therapy out to 72 weeks for patients with HBeAg-positive CHB. The prolonged duration therapy produced a higher HBsAg loss ratio, HBeAg seroconversion ratio, HBV DNA negativity ratio, and a lower relapse ratio. Furthermore, HBeAg clearance was positively correlated with duration and male sex.