Metabolic dysfunction-associated fatty liver disease increases the risk of complications after radical resection in patients with hepatocellular carcinoma.

BACKGROUND AND AIMS: The prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD) in hepatocellular carcinoma (HCC) patients is increasing, yet its association with postoperative complications of HCC remains unclear. The aim of this study was to investigate the impact of MAFLD on complications after radical resection in HCC patients. METHODS: Patients with HCC who underwent radical resection were included. Patients were stratified into MAFLD group and non-MAFLD group. Clinical features and post-hepatectomy complications were compared between the two groups, and logistic regression analysis was used to determine independent risk factors associated with post-hepatectomy complications. RESULTS: Among the 936 eligible patients with HCC who underwent radical resection, concurrent MAFLD was diagnosed in 201 (21.5%) patients. Compared to the non-MAFLD group, the MAFLD group exhibited a higher incidence of complications, including infectious and major complications after radical resection in HCC patients. The logistic regression analysis found that MAFLD was an independent risk factor for complications, including infectious and major complications in HCC patients following radical resection (OR 1.565, 95%CI 1.109-2.343, P = 0.012; OR 2.092, 95%CI 1.386-3.156, P < 0.001; OR 1.859, 95% CI 1.106-3.124, P = 0.019; respectively). Subgroup analysis of HBV-related HCC patients yielded similar findings, and MAFLD patients with type 2 diabetes mellitus (T2DM) exhibited a higher incidence of postoperative complications compared to those without T2DM (all P < 0.05). CONCLUSIONS: Concurrent MAFLD was associated with an increased incidence of complications after radical resection in patients with HCC, especially MAFLD with T2DM.

Diagnostic value of liver stiffness measurement combined with risk scores for esophagogastric variceal bleeding in patients with hepatitis B cirrhosis.

PURPOSE: To assess the predictive value of liver stiffness measurement (LSM) and three bleeding risk scoring systems for esophagogastric varices bleeding (EGVB) in patients with hepatitis B cirrhosis during hospitalization. METHODS: In this study, 210 patients who had hepatitis B cirrhosis were selected as the subjects. They were categorized into two groups based on whether EGVB occurred during hospitalization: a bleeding group (70 cases) and a non-bleeding group (140 cases). Logistic regression was used to analyze the factors related to the occurrence of EGVB, and the diagnostic performance was evaluated using a receiver operating characteristic (ROC) curve. RESULTS: Significant differences were observed between the two groups in systolic blood pressure, platelet count, albumin, urea nitrogen, LSM, pre-endoscopic Rockall score (PRS), Glasgow-Blatchford score (GBS), and AIMS65 score (P < 0.05). The correlation analysis showed that LSM had significant positive relationship with PRS, GBS and AIMS65 score. Logistic regression analysis revealed that LSM and GBS score were independent risk factors for EGVB occurrence during hospitalization. ROC curve analysis showed that the combined prediction model of LSM and GBS score had the best prediction performance for EGVB occurrence, with an ROC curve area of 0.811, which was significantly better than the three risk scoring systems (P < 0.05), but similar to the predicted value of LSM (P = 0.335). CONCLUSIONS: The combination of LSM and GBS score can significantly improve the predictive efficacy of EGVB occurrence in patients with hepatitis B cirrhosis during hospitalization, which has important clinical significance for patients' prognosis.

A novel small-animal locomotor activity recording device for biological clock research.

The rodent running-wheel recording apparatus is a reliable approach for studying circadian rhythm. This study demonstrated how to construct a simple and intelligent running-wheel recording system. The running wheel was attached to the cage's base, whereas the Hall sensor was attached to the cage's cover. Then, the RJ25 adaptor relayed the running signal to the main control board. Finally, the main control board was connected to the USB port of the computer with the USB connection. Data were collected using the online-accessible, self-created software Magturning. Through Magturning, generated data were saved and exported in real time. Afterward, the device was validated by collecting data on the locomotor activities of mice under different light conditions. In conclusion, this new device can record circadian activity of rodents. Our device is appropriate for interdisciplinary investigations related to biological clock research.

Tenofovir alafenamide significantly increased serum lipid levels compared with entecavir therapy in chronic hepatitis B virus patients.

BACKGROUND: Tenofovir alafenamide (TAF) has a serum lipid-raising effect in patients with HIV; however, its effect on serum lipids and nonalcoholic fatty liver disease (NAFLD) risk in patients with chronic hepatitis B (CHB) is unclear. AIM: To compare the effects of TAF and entecavir (ETV) on serum lipid levels in patients with CHB. METHODS: In this retrospective cohort study, the data including the clinical features, serum lipids, and metabolic factors of patients with CHB at baseline and approximately 1 year after TAF or ETV treatment were collected and analyzed. We used propensity score-matched models to assess the effects on high-density lipoprotein, low-density lipoprotein, triglycerides, and total cholesterol (TCHO). RESULTS: A total of 336 patients (75.60% male) were included; 63.69% received TAF and 36.31% received ETV. Compared with the ETV group, the TAF group had significantly higher TCHO levels after treatment (4.67 ± 0.90 vs 4.36 ± 1.05, P = 0.006). In a propensity score-matched model for body mass index, age, sex, smoking, drinking, presence of comorbidities such as NAFLD, cirrhosis, diabetes mellitus, and hypertension, TAF-treated patients had significantly increased TCHO levels compared to that at baseline (P = 0.019). There was no difference for the ETV group. Body mass index, sex, hypertension, baseline TCHO, and creatine kinase-MB isoenzyme levels were significantly associated with elevated TCHO levels in logistic regression analysis. However, 1-year TAF treatment did not increase the incidence of NAFLD. CONCLUSION: A greater increase in TCHO was observed in patients with CHB receiving TAF compared to those receiving ETV. However, TAF-induced dyslipidemia did not increase the incidence of NAFLD.

Liver Stiffness Measurement can Predict Liver Inflammation in Chronic Hepatitis B Patients with Normal Alanine Transaminase.

Background and Aims: To determine whether liver stiffness measurement (LSM) indicates liver inflammation in chronic hepatitis B (CHB) with different upper limits of normal (ULNs) for alanine aminotransferase (ALT). Methods: We grouped 439 CHB patients using different ULNs for ALT: cohort I, ≤40 U/L (439 subjects); cohort II, ≤35/25 U/L (males/females; 330 subjects); and cohort III, ≤30/19 U/L (males/females; 231 subjects). Furthermore, 84 and 96 CHB patients with normal ALT (≤40 U/L) formed the external and prospective validation groups, respectively. We evaluated the correlation between LSM and biopsy-confirmed liver inflammation, and determined diagnostic accuracy using area under the curve (AUC). A noninvasive LSM-based model was developed using multivariate logistic regression. Results: Fibrosis-adjusted LSM values significantly increased with increasing inflammation. The AUCs of LSM in cohorts I, II, and III were 0.799, 0.796, and 0.814, respectively, for significant inflammation (A≥2) and 0.779, 0.767, and 0.770, respectively, for severe inflammation (A=3). Cutoff LSM values in all cohorts for A≥2 and A=3 were 6.3 and 7.5 kPa, respectively. Internal, external, and prospective validations showed high diagnostic accuracy of LSM for A≥2 and A=3, and no significant differences in AUCs among the four groups. LSM and globulin independently predicted A≥2. The AUC of an LSM-globulin model for A≥2 exceeded those of globulin, ALT, and AST, but was similar to that of LSM. Conclusions: LSM predicted liver inflammation and guided the indication of antiviral therapy for CHB in patients with normal ALT.

The impact of metabolic dysfunction-associated fatty liver disease on the prognosis of patients with hepatocellular carcinoma after radical resection.

BACKGROUND: Metabolic dysfunction-associated fatty liver disease (MAFLD) is recently proposed an entity by a group of international experts. However, the impact of MAFLD on the prognosis of patients with hepatocellular carcinoma (HCC) is not clear. The aim of this study was to explore the influence of MAFLD for the prognosis of HCC after radical resection. METHODS: HCC patients who received radical resection were enrolled. The recurrence-free survival (RFS) and overall survival (OS) were compared between MAFLD and non-MAFLD. RESULTS: A total of 576 HCC patients were included, and among them 114 (19.8%) met the diagnostic criteria of MAFLD. The median RFS was 34.0 months in the MAFLD group and 19.0 months in the non-MAFLD group. The 1-, 3-, and 5-year RFS rates were 64.9%, 49.1% and 36.1% in the MAFLD group, which were higher than those of the non-MAFLD group (59.4%, 35.3% and 26.5%, respectively, P = 0.01). The mean OS was 57.0 months in the MAFLD group and 52.2 months in the non-MAFLD group. There was no statistical difference in OS rate between the MAFLD group and non-MAFLD group. Similar results were found in HBV-related HCC patients in the subgroup analysis. Univariate analysis revealed that MAFLD was a protective factor for RFS in HCC patients after radical resection (P < 0.05), and there was no association between MAFLD and OS rate (P > 0.05). Multivariate analysis demonstrated that MAFLD was not an independent protective factor for HCC patients with radical resection. CONCLUSIONS: MAFLD improves RFS rate in HCC patients with radical resection, but is not an independent protective factor and not associated with OS rate.

Gasdermin D Inhibitor Necrosulfonamide Alleviates Lipopolysaccharide/D-galactosamine-induced Acute Liver Failure in Mice.

Background and Aims: Acute liver failure (ALF) is associated with high mortality. Gasdermin D (GSDMD) is the executioner of pyroptosis and is involved in the pathophysiology of immune dysregulation This study investigated the role of the GSDMD inhibitor necrosulfonamide (NSA) in ALF. Methods: An ALF model was established by lipopolysaccharide/D-galactosamine challenge in C57BL/6J mice. Mice were divided into four groups: normal controls (control group), ALF group (ALF group), dimethyl sulfoxide group (DMSO group), and NSA intervention group (NSA group). Survival was monitored, liver damage was determined by hematoxylin and eosin staining, and serum alanine aminotransferase (ALT). Underlying mechanisms were explored by quantitative real-time PCR, western blotting, and enzyme-linked immunosorbent assays. Results: Pyroptosis was activated in ALF model mice. Mice treated with GSDMD inhibitor NSA developed less severe liver failure. NSA reduced the expression of GSDMD, NLRP3, cleaved caspase-1, cleaved caspase-11, and secretion of interleukin-1 beta in ALF mice model. Conclusions: Pyroptosis was activated in ALF. NSA alleviated ALF via the pyroptosis pathway.

Gut microbiota of hepatitis B virus-infected patients in the immune-tolerant and immune-active phases and their implications in metabolite changes.

BACKGROUND: The microbes and metabolomics of microbiota dysbiosis in the gut in the different phases of hepatitis B virus (HBV) infection are not fully understood. AIM: To investigate the specific gut microbiota and metabolites of the immune-tolerant (IT) and immune-active (IA) phases of chronic hepatitis B (CHB). METHODS: Clinical fecal samples from healthy individuals and patients in the IT and IA phases of HBV infection were collected. Next, non-target metabolomics, bioinformatics, and 16S rDNA sequencing analyses were performed. RESULTS: A total of 293 different metabolites in 14 phyla, 22 classes, 29 orders, 51 families, and 190 genera were identified. The four phyla of Firmicutes, Bacteroidetes, Actinobacteria, and Proteobacteria were the most abundant, accounting for 99.72%, 99.79%, and 99.55% in the healthy controls, IT-phase patients, and IA-phase patients, respectively. We further identified 16 genera with different richness in the IT phase and IA phase of HBV infection. Of the 134 named metabolites, 57 were upregulated and 77 were downregulated. A total of 101 different metabolic functions were predicted in this study, with 6 metabolic pathways having the highest enrichments, namely carbohydrate metabolism (14.85%), amino acid metabolism (12.87%), lipid metabolism (11.88%), metabolism of cofactors and vitamins (11.88%), xenobiotic biodegradation (9.9%), and metabolism of terpenoids and polyketides (7.92%). CONCLUSION: These findings provide observational evidence of compositional alterations of the gut microbiome and some related metabolites in patients with IT-phase or IA-phase HBV infection. Further studies should investigate whether microbiota modulation can facilitate the progression of CHB and the cause-effect relationship between the gut microbiota and CHB.

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.

A novel HBsAg-based model for predicting significant liver fibrosis among Chinese patients with immune-tolerant phase chronic hepatitis B: a multicenter retrospective study.

BACKGROUND: Hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) in the immune-tolerant (IT) phase is significantly associated with high risk for hepatocellular carcinoma, suggesting requirement for antiviral therapy, particularly for those with histological liver injury. This study aimed to establish a non-invasive panel to assess significant liver fibrosis in IT chronic hepatitis B. PATIENTS AND METHODS: One hundred and thirteen IT-phase CHB patients were retrospectively recruited and divided into two histopathological groups according to their histological profiles: necroinflammatory score <4 (N <4)/fibrosis score ⩽1 (F0-1), and necroinflammatory score ⩾4 (N ⩾4)/fibrosis score ⩾2 (F2-4). Multivariate analysis was conducted to assess the predictive value of the non-invasive model for significant liver fibrosis. RESULTS: IT-phase CHB patients with N <4/F0-1 had significantly higher HBsAg levels than those with N ⩾4/F2-4. The optimal HBsAg level of log 4.44 IU/mL for significant liver fibrosis (F ⩾2) gave an area under the curve (AUC) of 0.83, sensitivity of 81.1%, specificity of 81.6%, positive predictive value (PPV) of 68.2%, and negative predictive value (NPV) of 89.9%. An IT model with HBsAg and gamma glutamyl transpeptidase (GGT) in combination was established, and it had an AUC of 0.86, sensitivity of 86.5%, specificity of 81.6%, PPV of 69.6, NPV of 92.5, and accuracy of 83.2% to predict F ⩾2 in the IT-phase CHB patients. Notably, the IT model exhibited higher predictive value than the existing aspartate aminotransferase-to-platelet ratio index, Fibrosis-4 score, and GGT to platelet ratio. CONCLUSION: The established IT model combining HBsAg and GGT has good performance in predicting significant liver fibrosis in IT-phase CHB patients.

[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].

Effect of liver inflammation on accuracy of FibroScan device in assessing liver fibrosis stage in patients with chronic hepatitis B virus infection.

BACKGROUND: Transient elastography (FibroScan) is a new and non-invasive test, which has been widely recommended by the guidelines of chronic hepatitis B virus (HBV) management for assessing hepatic fibrosis staging. However, some confounders may affect the diagnostic accuracy of the FibroScan device in fibrosis staging. AIM: To evaluate the diagnostic value of the FibroScan device and the effect of hepatic inflammation on the accuracy of FibroScan in assessing the stage of liver fibrosis in patients with HBV infection. METHODS: The data of 416 patients with chronic HBV infection who accepted FibroScan, liver biopsy, clinical, and biological examination were collected from two hospitals retrospectively. Receiver operating characteristic (ROC) curves were used to analyze the diagnostic performance of FibroScan for assessing the stage of liver fibrosis. Any discordance in fibrosis staging by FibroScan and pathological scores was statistically analyzed. Logistic regression and ROC analyses were used to analyze the accuracy of FibroScan in assessing the stage of fibrosis in patients with different degrees of liver inflammation. A non-invasive model was constructed to predict the risk of misdiagnosis of fibrosis stage using FibroScan. RESULTS: In the overall cohort, the optimal diagnostic values of liver stiffness measurement (LSM) using FibroScan for significant fibrosis (≥ F2), severe fibrosis (≥ F3), and cirrhosis (F4) were 7.3 kPa [area under the curve (AUC) = 0.863], 9.7 kPa (AUC = 0.911), and 11.3 kPa (AUC = 0.918), respectively. The rate of misdiagnosis of fibrosis stage using FibroScan was 34.1% (142/416 patients). The group of patients who showed discordance between fibrosis staging using FibroScan and pathological scores had significantly higher alanine aminotransferase and aspartate aminotransferase levels, and a higher proportion of moderate to severe hepatic inflammation, compared with the group of patients who showed concordance in fibrosis staging between the two methods. Liver inflammation activity over 2 (OR = 3.53) was an independent risk factor for misdiagnosis of fibrosis stage using FibroScan. Patients with liver inflammation activity ≥ 2 showed higher LSM values using FibroScan and higher rates of misdiagnosis of fibrosis stage, whereas the diagnostic performance of FibroScan for different fibrosis stages was significantly lower than that in patients with inflammation activity < 2 (all P < 0.05). A non-invasive prediction model was established to assess the risk of misdiagnosis of fibrosis stage using FibroScan, and the AUC was 0.701. CONCLUSION: Liver inflammation was an independent risk factor affecting the diagnostic accuracy of FibroScan for fibrosis stage. A combination of other related non-invasive factors can predict the risk of misdiagnosis of fibrosis staging using FibroScan.

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.

Serum ceruloplasmin can predict liver fibrosis in hepatitis B virus-infected patients.

BACKGROUND: The presence of significant liver fibrosis in hepatitis B virus (HBV)-infected individuals with persistently normal serum alanine aminotransferase (PNALT) levels is a strong indicator for initiating antiviral therapy. Serum ceruloplasmin (CP) is negatively correlated with liver fibrosis in HBV-infected individuals. AIM: To examine the potential value of serum CP and develop a noninvasive index including CP to assess significant fibrosis among HBV-infected individuals with PNALT. METHODS: Two hundred and seventy-five HBV-infected individuals with PNALT were retrospectively evaluated. The association between CP and fibrotic stages was statistically analyzed. A predictive index including CP [Ceruloplasmin hepatitis B virus (CPHBV)] was constructed to predict significant fibrosis and compared to previously reported models. RESULTS: Serum CP had an inverse correlation with liver fibrosis (r = -0.600). Using CP, the areas under the curves (AUCs) to predict significant fibrosis, advanced fibrosis, and cirrhosis were 0.774, 0.812, and 0.853, respectively. The CPHBV model was developed using CP, platelets (PLT), and HBsAg levels to predict significant fibrosis. The AUCs of this model to predict significant fibrosis, advanced fibrosis, and cirrhosis were 0.842, 0.920, and 0.904, respectively. CPHBV was superior to previous models like the aspartate aminotransferase (AST)-to-PLT ratio index, Fibrosis-4 score, gamma-glutamyl transpeptidase-to-PLT ratio, Forn's score, and S-index in predicting significant fibrosis in HBV-infected individuals with PNALT. CONCLUSION: CPHBV could accurately predict liver fibrosis in HBV-infected individuals with PNALT. Therefore, CPHBV can be a valuable tool for antiviral treatment decisions.

Association between NAFLD and risk of prevalent chronic kidney disease: why there is a difference between east and west?

BACKGROUNDS: There is a discrepancy between west and east on the relationship between non-alcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD). This study aimed to find out the possible reason for this and to clarify the association between NAFLD and CKD by analyzing two population-based datasets from the US and China. METHODS: Two health examination datasets from China and the US were used. CKD was defined as an estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73m2 or and/or abnormal albuminuria and/or overt proteinuria. Binary logistic regression was used to examine the association between NAFLD and CKD. RESULTS: A total of 60,965 participants were analyzed, including 11,844 from the US and 51,229 from China. The prevalence of NAFLD was 27.12% in the Chinese population and 36.08% in the US population (p < 0.001). The proportions of CKD and late stage CKD (stages 3-5) were higher in the US population than the Chinese one. NAFLD was independently associated with an increased risk of CKD in Chinese population, whereas in the US population, the NAFLD was not an independent risk factor of CKD. In subgroup analyses which excluded late stages CKD (stages 3-5), the risks of mild renal function decline became consistent: NAFLD was associated with early stages of CKD but not the late stages of CKD in both populations. CONCLUSION: NAFLD increased the risk of early stages of CKD in both Chinese and the US population. The conflicting results reported by previous studies might result from the different proportion of late stages of CKD.

Novel predictive models using serum ceruloplasmin levels for hepatic steatosis in patients with chronic hepatitis B infection.

AIMS: To evaluate the significance of serum ceruloplasmin (CP) to diagnosis hepatic steatosis (HS) in Chronic hepatitis B (CHB) patients. METHODS: A total of 360 CHB patients with HS (n = 136) or without HS (n = 224) were included. Relationships between CP and HS degrees were analyzed by Spearman rank correlation. HS-predictive models including CP were constructed using multivariate logistic regression analysis and compared to other HS predicting indexes. RESULTS: Serum CP were significantly higher in CHB patients with HS than in patients without HS (P < 0.001) and were positively correlated with HS degree (r = 0.487, P < 0.001). The area under the receiver-operating characteristic curves (AUCs) of using CP to predict HS (S ≥ 1), moderate and severe steatosis (S ≥ 2) and severe steatosis (S = 3) were 0.758, 0.794 and 0.883, respectively. Multivariate analysis showed that CP, age, high density lipoprotein (HDL) and hemoglobin were independent predictors of HS, and CP, body mass index and HDL were independent predictors of moderate and severe HS. Two novel indexes for predicting HS of CHB patients were generated. The AUC of HSCHB-1 (for S ≥ 1) and HSCHB-2 (for S ≥ 2) were 0.881 and 0.916 in the training group, and 0.865 and 0.841 in the validation group, respectively. HSCHB-1 was superior to HS index (P < 0.001), fatty liver disease index (P = 0.0043) and steatosis index of patients with hepatitis B virus infection (P = 0.0029) in predicting HS in CHB patients. CONCLUSIONS: HS of CHB patients was positively associated with serum CP. HSCHB-1 and HSCHB-2 with inclusion of CP are two novel models for predicting HS in CHB patients.

Efficacy and safety of autologous stem cell transplantation for decompensated liver cirrhosis: A retrospective cohort study.

AIM: To evaluate the long-term efficacy and safety of autologous stem cell transplantation (SCT) for decompensated liver cirrhosis. METHODS: Consecutive patients with decompensated liver cirrhosis were included and assigned into the SCT group and non-transplantation (non-SCT) group according to whether they received SCT treatment. Patients were followed up for ten years. The long-term survival rate and incidence of hepatocellular carcinoma (HCC) were compared between groups. RESULTS: A total of 159 patients were enrolled, including 27 cases in the SCT group and 132 cases in the non-SCT group. The baseline characteristics were significantly different between the two groups. Propensity score matching (PSM) was used to match SCT and non-SCT patients. After PSM, 92 subjects were enrolled in the final analysis, including 23 cases in the SCT group and 69 cases in the non-SCT group. The overall mortality was 73.9% and 55.1%, and the median survival period was 48 and 64 mo, respectively. However, no significant difference was found in the long-term survival rate between the two groups (P > 0.05). In addition, the incidence of HCC was higher in the SCT group than in the non-SCT group (47.8% vs 21.7%, P < 0.05). After adjusting for other covariates, SCT (OR = 3.065, 95%CI: 1.378-6.814) and age (OR = 1.061, 95%CI: 1.021-1.102) were independently correlated with the development of HCC in this decompensated liver cirrhosis cohort. CONCLUSION: Autologous SCT may fail to improve the long-term efficacy and increase the incidence of HCC for decompensated liver cirrhosis. Close monitoring of HCC is strongly recommended in patients undergoing autologous SCT.

Polycystic kidney and hepatic disease 1 gene mutations in von Meyenburg complexes: Case report.

Von Meyenburg complexes (VMCs) are a rare type of ductal plate malformation. We herein report two Chinese families with VMCs, and the suspicious gene mutation of this disease. Proband A was a 62-year-old woman with abnormal echographic presentation of the liver. She received magnetic resonance imaging (MRI) examination and liver biopsy, and the results showed she had VMCs. Histologically proved hepatocellular carcinoma was found 1 year after the diagnosis of VMCs. Proband B was a 57-year-old woman with intrahepatic diffuse lesions displayed by abdominal ultrasonography. Her final diagnoses were VMCs, congenital hepatic fibrosis, and hepatitis B surface e antigen-negative chronic hepatitis B after a series of examinations. Then, all the family members of both proband A and proband B were screened for VMCs by MRI or ultrasonography. The results showed that four of the 11 family members from two families, including two males and two females, were diagnosed with VMCs. DNA samples were extracted from the peripheral blood of those 11 individuals of two VMCs pedigrees and subjected to polymerase chain reaction amplification of the polycystic kidney and hepatic disease 1 (PKHD1) gene. Two different mutation loci were identified. Heterozygous mutations located in exon 32 (c.4280delG, p.Gly1427ValfsX6) in family A and exon 28 (c.3118C>T, p.Arg1040Ter) in family B were detected. We speculate that PKHD1 gene mutations may be responsible for the development of VMCs.

Downregulation of lncRNA OGFRP1 inhibits hepatocellular carcinoma progression by AKT/mTOR and Wnt/ß-catenin signaling pathways.

INTRODUCTION: Increasing evidence demonstrates that long noncoding RNAs (lncRNAs) play important roles in the progression of hepatocellular carcinoma (HCC) by regulating gene expression. However, the identification of functional lncRNAs in HCC remains insufficient. Our study aimed to investigate the function of lncRNA OGFRP1, which has not been functionally researched before, in Hep3B and HepG2 cells. METHODS: lncRNA OGFRP1 in HCC cells was down-regulated by using RNAi technology. Quantitative real-time polymerase chain reaction was used to determine the mRNA expression of lncRNA OGFRP1. Cell proliferation was examined by CCK8 and clone formation assays. Cell cycle and apoptosis were analyzed by flow cytometry. Cell migration and invasion were assessed by using Scratch assay and transwell assay, respectively. Protein expression of signaling pathways was determined by using Western blot. RESULTS: Cell proliferation of Hep3B was significantly inhibited by down-regulation of lncRNA OGFRP1 (P<0.05). Moreover, siOGFRP1 transfection induced Hep3B cell cycle arrest and apoptosis by regulating the expression of related proteins. Cell migration and invasion of Hep3B were also significantly inhibited by down-regulation of lncRNA OGFRP1. Wnt/ß-catenin signaling pathway, involved in epithelial-mesenchymal transition (EMT), was inactivated by lncRNA OGFRP1 downregulation, including decreased expression of Wnt3a, ß-catenin, N-cadherin and vimentin and increased expression of E-cadherin. We also found that the inhibitory effect of lncRNA OGFRP1 knockdown on Hep3B was mediated by the AKT/mTOR signaling pathway and IGF-1, an AKT signaling activator, could rescue the cellular phenotype. However, knockdown of lncRNA OGFRP1 did not influence cell proliferation, migration and invasion in HepG2 cells. CONCLUSION: We found that downregulation of lncRNA OGFRP1 suppressed the proliferation and EMT of HCC Hep3B cells through AKT and Wnt/ß-catenin signaling pathways. However, lncRNA OGFRP1 exhibited a differentiated function in different HCC cell lines, which required further study in the future.