Objective:To analyze the clinical application value of serum heme oxygenase (HO)-1expression level in non-alcoholic fatty liver disease (NAFLD) and, based on that, establish a diagnostic model combined with glucose regulatory protein 78 (GRP78) so as to clarify its diagnostic effectiveness and application value.Methods:A total of 210 NAFLD patients diagnosed by abdominal B-ultrasound and liver elastography were included, and at the same time, 170 healthy controls were enrolled. The general clinical data, peripheral blood cell counts, and biochemical indicators of the research subjects were collected. The expression levels of HO-1 and GRP78 were detected using an enzyme-linked immunosorbent assay. Multivariate analysis was used to screen independent risk factors for NAFLD. Visual output was performed through nomogram diagrams, and the diagnostic model was constructed. Receiver operating characteristic curve (ROC), calibration curve, and decision curve analysis (DCA) were used to evaluate the diagnostic effectiveness of NAFLD. Measurement data were analyzed using a t-test or Mann-Whitney U rank sum test to detect data differences between groups. Enumeration data were analyzed using the Fisher's exact probability test or the Pearson χ2 test. Results:Compared with the healthy control group, the white blood cell count, aspartate aminotransferase (AST), alanine aminotransferase, gamma-glutamyl transferase (GTT), fasting blood glucose (Glu), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), serum HO-1, and GRP78 levels were significantly increased in the NAFLD group patients ( P ?

Non-alcoholic fatty liver disease (NAFLD) has gradually become the most prevalent chronic liver disease in the world, but its pathogenesis has not been fully elucidated. Ferroptosis is a novel type of programmed cell death caused by iron-dependent lipid peroxidation. Heme oxygenase-1 is a recognized antioxidant enzyme and an important regulatory factor in ferroptosis that modulates ferroptosis through various pathways and, in turn, regulates NAFLD. This paper reviews the regulatory mechanism of heme oxygenase-1 on NAFLD in ferroptosis pathway, with a view to clarifying the occurrence and development mechanisms of NAFLD and providing new vision and targets for its prevention and treatment.

Non-alcoholic fatty liver disease (NAFLD) is a common concomitant disease in adults with type 2 diabetes mellitus (T2DM) and prediabetes. Therefore, T2DM/NAFLD patient populations are at high risk for cardiovascular disease. The occurrence and progression of non-alcoholic fatty liver disease-related liver fibrosis and cardiovascular disease have a severe impact on the patient’s prognosis and mortality rate. The American Diabetes Association's 2024 "Guidelines for the Standardized Management of Diabetes" put forward recommendations relevant to the screening, evaluation, treatment, and management of NAFLD in T2DM and prediabetic populations, as well as liver fibrosis. The important measures for decelerating liver inflammation and fibrosis progression and the risk of cardiovascular disease are based on improvements in lifestyle methods, weight loss, and blood sugar control.

Objective:To explore the diagnostic value of serum C-C chemokine ligand 5 (CCL5) in assessing the degree of liver fibrosis in patients with metabolic-associated fatty liver disease (MAFLD).Methods:71 MAFLD patients who visited the Department of Integrated Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, and underwent liver biopsy histopathology examinations between October 2021 and June 2023 were selected for diagnostic testing. Simultaneously, 71 healthy subjects who underwent physical examinations at the physical examination center of the hospital were selected as the control group. Serum CCL5 levels were detected using an enzyme-linked immunosorbent assay (ELISA). Routine blood tests, liver and kidney function tests, and other tests were conducted to analyze the expression level of CCL5 and its correlation with the above indicators. The aspartate aminotransferase/platelet ratio index (APRI) and fibrosis 4 index (FIB-4) were calculated. SPSS 26.0 software was used for statistical analysis. The area under the receiver operating characteristic curve (ROC) was used to evaluate the diagnostic efficacy of CCL5 for the degree of liver fibrosis in MAFLD. The combined diagnostic efficacy of APRI and FIB-4 was further analyzed for the degree of liver fibrosis in MAFLD.Results:The expression level of serum CCL5 gradually increased with the increase in liver fibrosis stage in patients with MAFLD, and the difference was statistically significant ( P<0.05). The AUC value of serum CCL5 for diagnosing significant liver fibrosis in MAFLD patients was 0.775, with a sensitivity of 65.7%, a specificity of 80.6%, and an optimal cutoff value of 49.845 ng/ml. The CCL5 and FIB-4 combination had the highest diagnostic value for significant liver fibrosis in patients with MAFLD, with an AUC of 0.802, a sensitivity of 91.4%, and a specificity of 61.1%. Conclusion:CCL5 has a high diagnostic value for significant liver fibrosis in MAFLD patients. Therefore, it is expected to become a non-invasive diagnostic marker for assessing the degree of liver fibrosis in MAFLD patients.

Objective:This study aimed to evaluate the diagnostic value of serum Golgi protein 73(GP73) alone and GP73 combined with liver stiffness measurement (LSM), aspartate aminotransferase/platelet ratio index (APRI), and 4-factor-based fibrosis index (FIB4) in diagnosing liver fibrosis in patients with chronic liver disease of different etiologies.Methods:A diagnostic test. A total of 68 patients who underwent liver biopsy in the Department of Traditional and Western Medical Hepatology of the Third Hospital of Hebei Medical University from October 2019 to December 2020 were selected to detect serum GP73 levels. iLivTouch was used to assess liver stiffness measurement (LSM). In addition, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), total bilirubin (TBil), direct bilirubin (DBil), triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL) levels, and peripheral platelet (PLT) counts were assayed. The correlation between GP73 and the above indexes was assessed, and APRI and FIB-4 were calculated. SPSS 21.0 statistical software was used for statistical analysis. The area under the receiver operating characteristic curve was calculated to evaluate diagnostic efficacy of GP73 in identifying hepatic fibrosis stages. Furthermore, the difference between GP73 and liver stiffness, as well as APRI and FIB4 in diagnosing significant fibrosis was assessed.Results:Based on liver biopsy, 13, 18, 17, and 20 cases were diagnosed as stages S0-1, S2, S3, and S4, respectively. The AUC of GP73 diagnosing hepatic fibrosis stage S≥3 and S=4 were 0.806 and 0.844 at cut-off points of 2.06 and 3.27 μg/L, and the sensitivity and specificity were 93.5%, 61.5%, 90.0%, 70.3%, respectively. In addition, GP73 levels were positively correlated with the degree of liver fibrosis ( r=0.547, P<0.001). Conclusions:The efficacy of serum GP73 level in diagnosing the degree of liver fibrosis in patients with chronic liver disease from different causes was significantly higher than that of APRI, FIB4, and LSM. The combination of GP73 and FIB4 can further improve the accuracy of diagnosis of liver fibrosis staging S≥3 and S=4, which is a reliable serological marker for the diagnosis of fibrosis in patients with chronic liver disease.

Objective:To analyze the clinical and pathological characteristics of chronic hepatitis B (CHB) patients with normal alanine aminotransferase (ALT) and not receiving antiviral therapy.Methods:This study retrospectively included CHB patients diagnosed by liver biopsy at the Third Hospital of Hebei Medical University from January 2008 to December 2022. According to the HBV DNA and HBeAg status of "immune tolerance period and immune control period", these patients were divided into three groups: chronic HBV carrier group, inactive HBsAg carrier group and indeterminate group including the patients that did not meet the inclusion criteria of the above two groups. Kruskal-Wallis H test was used for comparison of continuous data between multiple groups. Mann-Whitney U test was used for comparison of continuous data and ordered categorical data between two groups. Chi-square test or Fisher′s exact test was used for comparison of categorical data between two groups. Results:A total of 284 CHB patients with normal ALT were enrolled. There were 64, 88 and 132 cases in the chronic HBV carrier group, inactive HBsAg carrier group and indeterminate group, respectively. Histopathological analysis revealed that there were 182 (64.08%) cases with pathological inflammation grade (G) and/or fibrosis stage (S)≥2, 155 (54.58%) with S≥2 and 120 (42.25%) with G≥2. The proportion of patients with G and/or S≥2 in the indeterminate group [70.45% (93/132)] was higher than that in the chronic HBV carrier group [48.44% (31/64)] and inactive HBsAg carrier group [65.91% (58/88)] (both P<0.05). Patient′s age and the ratio of patients with S≥2 in the chronic HBV carrier group [33 years old, 39.06% (25/64)] were smaller than those in the inactive HBsAg carrier group [39 years old, 56.82% (50/88)] and the indeterminate group [39 years old, 60.61% (80/132)] (all P<0.05). Patients in the inactive HBsAg carrier group (19 U/L) had lower ALT levels than those in the chronic HBV carrier group (26 U/L) and the indeterminate group (23 U/L) (both P<0.05). The proportion of patients with cytoplasmic/cytoplasmic nuclear-type HBcAg was higher in patients with G and/or S≥2 than in patients with G and S<2 [73.08% (57/78) vs 32.08% (17/53), P<0.05], and the proportion of patients with cytoplasmic/cytoplasmic nuclear-type HBcAg increased gradually with age. The proportion of patients with cytoplasmic/cytoplasmic nuclear-type HBcAg was higher in patients with G and/or S≥2 than in patients with G and S<2 in the chronic HBV carrier status and indeterminate groups [93.33% (28/30) vs 43.33%(13/30), P<0.05; 59.46% (22/37) vs 12.50% (2/16); both P<0.05]. There was a statistically significant difference in the incidence of significant liver injury between patients≤ 30 years old and >30 years old [52.7% (39/74) vs 68.1% (143/210), P<0.05]. Conclusions:Significant liver injury occurred in 64.08% (182/284) of CHB patients with normal ALT not receiving antiviral therapy, which required the attention of clinicians. Among CHB patients with normal ALT, the expression site of HBcAg in hepatocytes was related to the occurrence of significant liver injury and could be expected to serve as an important indicator for predicting the patient′s status and the necessity of antiviral treatment. CHB patients with positive HBV DNA who were older than 30 years required antiviral treatment, and CHB patients≤30 years with normal ALT and significant hepatic tissue damage also required antiviral treatment.

Chronic hepatitis B virus (HBV) infection is a major problem affecting global public health. Appropriate antiviral therapy use can prevent or delay the occurrence of liver cirrhosis and liver cancer. Precise immunological classification can be helpful to formulate personalized therapy and management plans for HBV-infected patients. Antiviral therapy should be started early in those who meet antiviral indications, and nucleos(t)ide analogue therapeutic regimens alone or in combination with pegylated interferon alpha should be optimized according to antiviral therapy response, in order to maximize the realization of virological and serological response, improve clinical cure rate, and enhance long-term prognosis.

Objective:To clarify the clinical efficacy of first-line oral antiviral drugs tenofovir alafenamide (TAF), tenofovir disoproxil fumarate (TDF), and entecavir (ETV) in the treatment of chronic hepatitis B (CHB) and their safety profiles with lipid, bone, and kidney metabolism.Methods:458 CHB cases diagnosed and treated at the Department of Hepatology of Integrated Traditional Chinese and Western Medicine of the Third Hospital of Hebei Medical University from February 2010 to November 2022 were selected. TAF (175 cases), TDF (124 cases), and ETV (159 cases) were used as therapies. At 24 and 48 weeks, the virology, biochemical response, changes in liver stiffness measurement (LSM), and bone, kidney, and blood lipid metabolism safety profiles were compared and analyzed.Results:After 24 and 48 weeks of TAF, TDF, and ETV therapy, HBV DNA load decreased by 3.28, 2.69, and 3.14 log10 IU/ml and 3.28, 2.83, and 3.65 log10 IU/ml, respectively, compared with the baseline, and the differences between the three groups were statistically significant, P < 0.001. The complete virological response rates were 73.95%, 66.09%, 67.19%, and 82.22%, 72.48%, and 70.49%, respectively. The incidence rates of low-level viremia were 16.67%, 21.70%, and 23.08%, while poor response rates were 1.11%, 3.67%, and 4.10%. ALT normalization rates were 64.00%, 63.89%, 67.96%, and 85.33%, 80.56%, 78.64%, respectively, and there was no statistically significant difference among the groups. LSM was significantly improved in patients treated with TAF for 48 weeks, P = 0.022. Serum phosphorus level gradually decreased with the prolongation of TDF treatment. The TAF treatment group had a good safety profile for kidney, bone, and phosphorus metabolism, with no dyslipidemia or related occurrences of risk. Conclusion:There are some differences in the therapeutic effects of first-line anti-HBV drugs. TAF has the lowest incidence of low-level viremia after 48 weeks of treatment and has a good safety profile in kidney, bone, and blood lipid metabolism.

Treatment with molecular targeted drugs and immune checkpoint inhibitors (ICIs) has become the first-line treatment options for unresectable HCC (hepatocellular carcinoma) and is also one of the anti-recurrence therapies of choice for patients at high risk of recurrence following radical treatment. First-line molecular targeted drugs combined with ICIs or dual-immune therapy significantly increase the median overall survival and objective response rate compared to single-targeted drugs. Targeted therapy and immunotherapy are suitable for HCC patients with Child-Pugh classes A~B. Liver damage caused by targeted drugs includes abnormal transaminases and bilirubin and, in severe cases, hypoproteinemia, ascites, and other occurrences. ICIs-associated immune-mediated hepatitis (IMH) mostly occurs within one to three sessions of treatment (4~12 weeks) and can be treated with glucocorticoids. However, immunosuppressants such as mycophenolate mofetil may be used as necessary.Targeted drugs and ICIs with different mechanisms of action can be selected based on the systemic condition and tumor treatment needs following the restoration of normal liver function.

Primary hepatocellular carcinoma has a high degree of malignancy, insidious onset, and rapid progression that seriously threatens human life and health. With the continuous deepening of the study of the molecular characteristics of tumors, molecular targeted drugs have become an important treatment method for patients with advanced liver cancer. Liver injury is one of the common adverse reactions of targeted drugs, which needs to be paid attention to. This paper mainly briefly expounds on the occurrence condition, mechanism, risk factors, diagnosis, and treatment of liver injury caused by hepatocellular carcinoma targeted therapy in order to provide a reference for the safe clinical application of targeted drugs.