A novel model based on serum N-glycan markers for evaluating stage of liver necroinflammation in treatment-naïve chronic hepatitis B patients.

This study aimed to establish a novel noninvasive model based on the serum N-glycan spectrum for providing an objective value for determining the stage of liver necroinflammation related to chronic hepatitis B (CHB) patients. N-glycan profiles of the sera of 295 treatment-naïve CHB patients were analyzed. N-glycan profiles were tested for different liver necroinflammation stages using DNA sequence-assisted fluorophore-assisted carbohydrate electrophoresis. A serum N-glycan model named N-glycan-LI (NGLI) using support vector machine was selected to evaluate the classification of liver necroinflammation (G < 2 and G ≥ 2). The area under the receiver operating characteristic curves (AUROCs) was 0.898 (training set, n = 236) and 0.911 (validation set, n = 59) regardless of the stage of liver fibrosis (AUROC = 0.886 and 0.926, respectively, in S < 2 and S ≥ 2 group). The NGLI correspondingly had the highest specificity (SP) of 90.79% and negative predictive value of 92.00% in an inactive stage (including immune-tolerant [IT] and inactive-carrier [IC] stage), had the highest positive predictive value of 95.18% in stage immune-active, and had the highest SP of 93.94% in grey zone IT + IC. N-glycan profiles appear to correlate well with hepatic necroinflammation in CHB when compared with liver biopsy. The newly developed model appears to reliably predict liver damage in naïve-treatment patients with CHB.

Noninvasive tests maintain high accuracy for advanced fibrosis in chronic hepatitis B patients with different nomenclatures of steatotic liver disease.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a new nomenclature proposed in 2023. We aimed to compare the diagnostic efficacy of noninvasive tests (NITs) for advanced fibrosis under different nomenclatures in patients with chronic hepatitis B (CHB). A total of 844 patients diagnosed with CHB and concurrent steatotic liver disease (SLD) by liver biopsy were retrospectively enrolled and divided into four groups. The performances of fibrosis-4 (FIB-4), gamma-glutamyl transpeptidase to platelet ratio index (GPRI), aspartate aminotransferase to platelet ratio index (APRI), and liver stiffness measurement (LSM) were compared among the four groups. The four NITs showed similar diagnostic efficacy for nonalcoholic fatty liver disease (NAFLD), MASLD, and metabolic dysfunction-associated fatty liver disease (MAFLD) in patients with CHB with advanced fibrosis. LSM showed the most stable accuracy for NAFLD (AUC = 0.842), MASLD (AUC = 0.846), and MAFLD (AUC = 0.863) compared with other NITs (p < 0.05). Among the four NITs, APRI (AUC = 0.841) and GPRI (AUC = 0.844) performed best in patients with CHB & MetALD (p < 0.05). The cutoff value for GPRI in patients with CHB & MetALD was higher than that in the other three groups, while further comparisons of NITs at different fibrosis stages showed that the median GPRI of CHB & MetALD (1.113) at F3-4 was higher than that in the CHB & MASLD group (0.508) (p < 0.05). Current NITs perform adequately in patients with CHB and SLD; however, alterations in cutoff values for CHB & MetALD need to be noted.

Correlations of PSGL-1 VNTR polymorphism with the susceptibility to severe HFMD associated with EV-71 and the immune status after infection.

Enterovirus 71 (EV-71) has strong neurotropism, and it is the main pathogen causing severe hand, foot, and mouth disease (HFMD). In clinical observations, significant differences were observed in the severity and prognosis of HFMD among children who were also infected with EV-71. Genetic differences among individuals could be one of the important causes of differences in susceptibility to EV-71-induced HFMD. As P-selectin glycoprotein ligand-1 (PSGL-1) is an important receptor of EV-71, the correlation between single-nucleotide polymorphisms (SNPs) in PSGL-1 and the susceptibility to severe HFMD following EV-71 infection is worth studying. Given the role of PSGL-1 in immunity, the correlations between PSGL-1 SNPs and the immune status after EV-71 infection are also worth studying. Meanwhile, PSGL-1 variable number of tandem repeats (VNTR) represents a research hotspot in cardiovascular and cerebrovascular diseases, but PSGL-1 VNTR polymorphism has not been investigated in HFMD caused by EV-71 infection. In this study, specific gene fragments were amplified by polymerase chain reaction, and PSGL-1 VNTR sequences were genotyped using an automatic nucleic acid analyzer. The correlations of PSGL-1 VNTR polymorphism with the susceptibility to EV-71-associated severe HFMD and the post-infection immune status were analyzed. The PSGL-1 VNTR A allele was identified as a susceptible SNP for severe HFMD. The risk of severe HFMD was higher for AA + AB genotype carriers than for BB genotype carriers. The counts of peripheral blood lymphocyte subsets were lower in AA + AB genotype carries than in BB genotype carries. In conclusion, PSGL-1 VNTR polymorphism is associated with the susceptibility to EV-71-induced severe HFMD and the immune status after infection. PSGL-1 VNTR might play a certain role in the pathogenesis of severe cases.

Regression in hepatic fibrosis in elderly Chinese patients with hepatitis C receiving direct-acting antiviral treatment.

BACKGROUND: Patients infected with Hepatitis C virus (HCV) are recommended to receive treatment with direct-acting antiviral agents (DAAs), which have been certified to obtain a high sustained virological response (SVR). However, little is known about the benefits of successful anti-viral treatment to elderly patients with hepatic fibrosis. In this study, we aimed to assess degree of fibrosis in elderly patients with chronic hepatitis C (CHC) treated with DAAs, and to evaluate the correlations between identified factors associated with these changes. METHODS: This study retrospectively enrolled elderly patients with CHC who received DAAs in Tianjin Second People's Hospital from April 2018 to April 2021. The degree of liver fibrosis was assessed using serum biomarkers and transient elastography (TE) expressed as the liver stiffness (LSM), while the hepatic steatosis was evaluated by controlled attenuated parameter (CAP). Changes in factors related to hepatic fibrosis were examined following treatment with DAAs, and associated prognostic factors were further evaluated. RESULTS: We included 347 CHC patients in our analysis, where 127 of these were elderly patients. For the elderly group, the median LSM was 11.6 (7.9-19.9) kPa, and this value was significantly reduced to 9.7 (6.2-16.6) kPa following DAA treatment. Similarly, GPR, FIB-4 and APRI indices were significantly reduced from 0.445 (0.275-1.022), 3.072 (2.047-5.129) and 0.833 (0.430-1.540) to 0.231 (0.155-0.412), 2.100 (1.540-3.034) and 0.336 (0.235-0.528), respectively. While in younger patients, the median LSM reduced from 8.8 (6.1-16.8) kPa to 7.2 (5.3-12.4) kPa, and the trends of GPR, FIB-4 and APRI were also consistent. The CAP in younger patients increased with statistical significance, but we did not observe any significant change in CAP for the elderly group. Based on multivariate analysis, age, LSM, and CAP before baseline were identified as determinants for LSM improvement in the elderly. CONCLUSION: In this study, we found that elderly CHC patients treated with DAA had significantly lower LSM, GPR, FIB-4, and APRI values. DAA treatment did not significantly change CAP. Furthermore, we observed correlations between three noninvasive serological evaluation markers and LSM. Finally, age, LSM, and CAP were identified as independent predictors of fibrosis regression in elderly patients with CHC.

ACT001 Alleviates chronic kidney injury induced by a high-fat diet in mice through the GPR43/AMPK pathway.

BACKGROUND: Roughly 10 -15% of global populace suffer from Chronic Kidney Disease(CKD). A major secondary disease that can progress to end-stage renal disease (ESRD) is obesity-associated kidney disease (ORG). Although clinical management strategies are currently available, morbidity and mortality rates are increasing. Thus, new solutions are needed. Intestinal permeability, systemic inflammation, and aberrant intestinal metabolites have all been linked to ORG. PURPOSE: ACT001 has anti-inflammatory, redox-regulatory and antitumour activities. The current study was designed to examine how ACT001 affects ORG and analyze the fundamental processes. METHODS: A high-fat diet (HFD) was used to generate ORG in female C57BL/6 J mice. ORG mice were divided into three groups at random: HFD, HFD + ACT001, HFD + polyphosphocholine (PPC). To assess renal and colonic damage, periodic acid-Schiff (PAS) and hematoxylin-eosin (HE) staining were used. Following that, renal inflammation, oxidative stress, lipid deposition, colonic inflammation, and intestinal permeability were evaluated by protein blotting, polymerase chain reaction (PCR), immunohistochemistry, and immunofluorescence staining. Lastly, the SCFAs content was assessed by gas chromatographymass spectrometry. RESULTS: Mice in the HFD group displayed more severe albuminuria, glomerular hypertrophy, renal oxidative damage, inflammation, and lipid accumulation than mice with the normal diet (ND) group, as well as lower levels of intestinal SCFA valproic acid, colonic inflammation, and tight junction protein downregulation. ACT001 treatment restores the content of valproic acid in intestinal SCFAs, promotes the binding of SCFAs to renal GPR43, activates the AMPK signalling pathway. Therefore, it promotes the Nrf2-Keap1 signalling pathway and inhibits the NF-κB signalling pathway. SCFAs, additionally, augment colonic GPR43 concentrations, diminishing NLRP3 inflammasome expression and restoring ZO-1 and occludin protein levels. CONCLUSION: This study is the first to look at ACT001's potential as a treatment for obesity-related kidney disease. Regulating GPR43 and AMPK signalling pathways, By controlling the GPR43 and AMPK signalling pathways, ACT001 improves colitis and the intestinal mucosal barrier, decreases renal lipid deposition, and suppresses inflammation and oxidative stress in the kidneys. According to this study, ACT001 could be a viable ORG therapy option.

The pathologic relevance of metabolic criteria in patients with biopsy-proven nonalcoholic fatty liver disease and metabolic dysfunction associated fatty liver disease: A multicenter cross-sectional study in China.

BACKGROUND: This study aimed to assess the association between metabolic syndrome (MetS) and severity of nonalcoholic fatty liver disease (NAFLD), and to discuss the pathological relevance of the diagnostic criteria in metabolic (dysfunction) associated fatty liver disease (MAFLD). METHODS: This was a multicenter, cross-sectional study. Patients with NAFLD confirmed by liver biopsy were enrolled between July 2016 and December 2018 from 14 centers across the mainland of China. Anthropometric and metabolic parameters were collected to assess the pathological relevance. RESULTS: Of 246 enrolled patients with NAFLD, 150 (61.0%) had the comorbidity of MetS. With the increase of metabolic components, the proportions of nonalcoholic steatohepatitis (NASH) and significant fibrosis were notably increased. The comorbid three metabolic components significantly increased the proportion of NASH, and further increase of metabolic components did not increase the proportion of NASH. However, the increase of metabolic components was parallel to the increase of the proportion of liver fibrosis. Among the 246 patients, 239 (97.2%) met the diagnostic criteria of MAFLD. Although non-MAFLD patients had less NASH, they present with similar proportion of significant fibrosis and cirrhosis. In the diagnostic criteria of MAFLD, BMI ≥ 23 kg/m2 was related to NASH (Mantel-Haenszel Common Estimate OR: 2.975; 95% CI: 1.037-8.538; P = 0.043), and T2DM was related to significant fibrosis (Mantel-Haenszel Common Estimate OR: 2.531; 95% CI: 1.388-4.613; P = 0.002). The homeostasis model assessment of insulin resistance (HOMA-IR) ≥ 2.5 was the most significant factor for NASH (OR: 4.100; 95% CI: 1.772-9.487; P = 0.001) and significant factor for liver fibrosis (OR: 2.947; 95% CI: 1.398-6.210; P = 0.004) after the adjustments of the BMI and diabetes. CONCLUSIONS: Metabolic dysregulations are important risk factors in NAFLD progression. The insulin resistance status may play a predominant role in the progression in MAFLD patients.

Individual patient data meta-analysis of controlled attenuation parameter (CAP) technology for assessing steatosis.

BACKGROUND & AIMS: The prevalence of fatty liver underscores the need for non-invasive characterization of steatosis, such as the ultrasound based controlled attenuation parameter (CAP). Despite good diagnostic accuracy, clinical use of CAP is limited due to uncertainty regarding optimal cut-offs and the influence of covariates. We therefore conducted an individual patient data meta-analysis. METHODS: A review of the literature identified studies containing histology verified CAP data (M probe, vibration controlled transient elastography with FibroScan®) for grading of steatosis (S0-S3). Receiver operating characteristic analysis after correcting for center effects was used as well as mixed models to test the impact of covariates on CAP. The primary outcome was establishing CAP cut-offs for distinguishing steatosis grades. RESULTS: Data from 19/21 eligible papers were provided, comprising 3830/3968 (97%) of patients. Considering data overlap and exclusion criteria, 2735 patients were included in the final analysis (37% hepatitis B, 36% hepatitis C, 20% NAFLD/NASH, 7% other). Steatosis distribution was 51%/27%/16%/6% for S0/S1/S2/S3. CAP values in dB/m (95% CI) were influenced by several covariates with an estimated shift of 10 (4.5-17) for NAFLD/NASH patients, 10 (3.5-16) for diabetics and 4.4 (3.8-5.0) per BMI unit. Areas under the curves were 0.823 (0.809-0.837) and 0.865 (0.850-0.880) respectively. Optimal cut-offs were 248 (237-261) and 268 (257-284) for those above S0 and S1 respectively. CONCLUSIONS: CAP provides a standardized non-invasive measure of hepatic steatosis. Prevalence, etiology, diabetes, and BMI deserve consideration when interpreting CAP. Longitudinal data are needed to demonstrate how CAP relates to clinical outcomes. LAY SUMMARY: There is an increase in fatty liver for patients with chronic liver disease, linked to the epidemic of the obesity. Invasive liver biopsies are considered the best means of diagnosing fatty liver. The ultrasound based controlled attenuation parameter (CAP) can be used instead, but factors such as the underlying disease, BMI and diabetes must be taken into account. Registration: Prospero CRD42015027238.

APOC3 rs2070666 Is Associated with the Hepatic Steatosis Independently of PNPLA3 rs738409 in Chinese Han Patients with Nonalcoholic Fatty Liver Diseases.

BACKGROUND AND AIM: The association between nonalcoholic fatty liver disease (NAFLD) and apolipoprotein C3 gene (APOC3) promoter region single-nucleotide polymorphisms (SNPs) rs2854117 and rs2854116 is controversial. The aim of this study was to investigate the relationship between other polymorphisms of APOC3 and NAFLD in Chinese. METHODS: Fifty-nine liver biopsy-proven NAFLD patients and 72 healthy control subjects were recruited to a cohort representing Chinese Han population. The polymorphisms in the exons and flanking regions of APOC3 and patatin-like phospholipase domain-containing protein 3 (PNPLA3) rs738409 polymorphisms were genotyped. RESULTS: Among the five SNPs (rs4225, rs4520, rs5128, rs2070666, and rs2070667) in APOC3, only rs2070666 (c.179 + 62 T/A) was significantly different in genotype and allele frequency (both p < 0.01) between groups of NAFLD and control. After adjusting for sex, age, serum triglycerides, total cholesterol, body mass index, and the PNPLA3 rs738409 polymorphism, the APOC3 rs2070666 A allele was an independent risk factor for NAFLD with an odds ratio (OR) of 3.683 and 95 % confidence interval (CI) of 1.037-13.084. The APOC3 rs2070666 A allele was linked to the fourth quartile of the controlled attenuation parameter values (OR 2.769, 95 % CI 1.002-7.651) in 131 subjects, and also linked to the significant histological steatosis (OR 4.986, 95 % CI 1.020-24.371), but neither to liver stiffness measurement values nor to hepatic histological activity and fibrosis in NAFLD patients. CONCLUSIONS: The APOC3 rs2070666 A allele is a risk factor for NAFLD independent of obesity, dyslipidemia, and PNPLA3 rs738409, and it might contribute to increased liver fat content in Chinese Han population.

[Value of controlled attenuation parameter in diagnosis of fatty liver using FibroScan].

OBJECTIVE: To investigate the value of controlled attenuation parameter (CAP) in the diagnosis of fatty liver using FibroScan in patients with chronic liver disease (CLD). METHODS: A prospective cohort study was performed for the patients with chronic hepatitis B (CHB), chronic hepatitis C (CHC), and non-alcoholic fatty liver disease (NAFLD) who underwent liver pathological examination followed by CAP measurement within 1 week in The Second People's Hospital of Tianjin from February 2013 to May 2014. According to related guidelines, hepatocyte steatosis was classified as S0: <5%, S1: 5%-33%, S2: 34%-66%, or S3: ≥67%. The receiver operating characteristic (ROC) curves were plotted with positive results as the diagnostic criteria, and the optimal cut-off values were determined at the maximum Youden index. Single linear regression and multiple stepwise regression were applied to analyze the influencing factors for CAP. RESULTS: A total of 427 patients were enrolled, consisting of 19 patients (4.4%) with NAFLD, 383 (89.7%) with CHB, and 25 (5.9%) with CHC. The optimal cut-off values for CAP in the diagnosis of steatosis ≥5%, ≥34%, and ≥67% were 230 dB/m, 252 dB/m, and 283 dB/m, respectively, and the areas under the ROC curve were 0.803, 0.942, and 0.938, respectively (Z = 14.194, 28.385, and 16.486, respectively, all P < 0.01). CAP differentiated S0 from S1, S1 from S2, S0 from S2, S0 from S3, and S1 from S3 (Z = 10.109, 10.224, 47.81, 29.917, and 10.999, all P < 0.01), but was not able to differentiate S2 from S3 (Z = 0.656, P = 0.5116). The single linear regression and multiple stepwise regression analyses showed that only body mass index (BMI; B = 4.001, P < 0.01) and hepatic steatosis (B = 33.015, P = 0.000) were correlated with CAP. The coincidence rates between CAP and liver pathological diagnosis were 77.4%, 81.0%, and 96.2% for S0, S3, and ≥S2, respectively. CONCLUSION: CAP has a good value in the diagnosis of fatty liver in CLD patients, and can well differentiate between all stages of fatty liver except S2 and S3. CAP is influenced by BMI, but is not found to be associated with liver fibrosis, inflammation, liver stiffness measurement, and etiology.

Impact of skin capsular distance on the performance of controlled attenuation parameter in patients with chronic liver disease.

BACKGROUND & AIMS: Controlled attenuation parameter (CAP) is a non-invasive method for evaluating hepatic steatosis. However, larger skin capsular distance (SCD) can affect the accuracy. The aim of this study was to investigate the impact of SCD on the diagnostic performance of CAP and liver stiffness measurement (LSM). METHODS: Of 101 patients with non-alcoholic fatty liver disease (NAFLD) and 280 patients with chronic hepatitis B (CHB) who underwent liver biopsy were prospectively recruited. CAP, LSM and SCD were performed using FibroScan with M probe. The areas under receiver operating characteristics curves (AUROCs) were calculated to determine the diagnostic efficacy. The optimal thresholds were defined by the maximum Youden index. RESULTS: SCD (B 30.34, P < 0.001) and hepatic steatosis (B 23.04, P < 0.001) were independently associated with CAP by multivariate analysis. The AUROCs were slightly higher for SCD <25 mm compared to those for SCD ≥25 mm for steatosis ≥5% (0.88 vs. 0.81), >33% (0.90 vs. 0.85) and >66% (0.84 vs. 0.72). For SCD <25 mm, the optimal CAP cut-offs for differentiating steatosis ≥5%, >33% and >66% were 255.0 dB/m, 283.5 dB/m and 293.5 dB/m. However, cut-offs were elevated by approximately 60-70 dB/m for SCD ≥25 mm. When stratified by fibrosis grade, LSM was significantly affected by SCD ≥25 mm for advanced fibrosis (≥F3) in NAFLD, but not in CHB. CONCLUSION: CAP is a promising tool for detecting and quantifying hepatic steatosis. SCD ≥25 mm may cause overestimation of steatosis. Similarly, SCD ≥25 mm affects the detection of advanced fibrosis by LSM in NAFLD patients.

Controlled attenuation parameter for noninvasive assessment of hepatic steatosis using Fibroscan®: validation in chronic hepatitis B.

BACKGROUND AND AIM: The controlled attenuation parameter (CAP) using transient elastography (TE) was validated in chronic hepatitis C to evaluate hepatic steatosis; however, limited data are available on chronic hepatitis B (CHB). Therefore, we assessed the accuracy and the efficacy of CAP for the detection of steatosis in CHB. METHODS: Consecutive CHB patients underwent liver biopsy and liver stiffness measurements (LSM) with simultaneous CAP determination using the M probe of the TE. The area under the receiver operating characteristics curve (AUROC) was used to evaluate the performance of CAP in diagnosing steatosis compared with biopsy. RESULTS: A total of 340 patients were included: 60 % were male, the median age was 37 years; the body mass index (BMI) was ≥ 28 kg/m(2) for 14 % of the subjects; and the distribution of the steatosis grade was S0 58.2 %, S1 34.2 %, S2 5.0 % and S3 2.6 %. The median (range) of CAP was 218 (100-400) dB/m, and CAP correlated with the BMI (ρ = 3.622) and steatosis grade (ρ = 29.203) according to a multivariate analysis (both P < 0.001). CAP could detect the different grades of steatosis: ≥ S1 with AUROC of 0.81 at a cutoff of 224 dB/m, ≥ S2 with AUROC of 0.90 at a cutoff of 236 dB/m and ≥ S3 with AUROC of 0.97 at a cutoff of 285 dB/m. Furthermore, the LSM and fibrosis and activity grades on biopsy did not influence the CAP performance. CONCLUSIONS: CAP presented excellent diagnostic performance for severe steatosis with high sensitivity and specificity in Chinese patients with CHB.

[Impact of liver steatosis on the curative effect of pegylated interferon-alpha-2a in patients with chronic hepatitis B].

OBJECTIVE: To investigate the impact of hepatic steatosis on virologic response to treatment with pegylated interferon-alpha-2a (PEG-IFNα-2a) in chronic hepatitis B (CHB) patients. METHODS: We retrospectively analyzed 50 biopsy-proven cases of CHB in patients who had been administered a 48-week course of PEG-IFNα-2a in our hospital between 2005 and 2009. The patients were stratified according to presence of steatosis confirmed by pathological findings, with 28 in the non-steatosis group and 22 in the steatosis grouP(21 with mild steatosis,and 1 with moderate steatosis). RESULTS: from blood routine test,hepatic and renal function tests, fasting blood glucose test, thyroid function test and blood lipid test were collected for analysis, as were results from hepatitis B viral load test and detection of hepatitis B virus (HBV) markers and autoantibodies. The efficacy of antiviral treatment and side effects were compared between the stratified groups by statistically comparing the results from before and after the 48 weeks of treatment. RESULTS: At the end of treatment, the non-steatosis group had 42.9% of patients with undetectable HBV-DNA ( less than 500 copies/ml), a hepatitis B e antigen (HBeAg) seroconversion rate of 31.6% and a complete response rate of 39.3%. The steatosis group had a lower rate of patients with undetectable HBV-DNA (40.9%) and higher rates of HBeAg seroconversion (33.3%) and complete response (40.9%), but none of the differences reached the threshold for statistical significance (x2=0.012, 0.019, 0.014 and P=0.560,0.600,0.568 respectively). Both groups showed significant increases in triglyceride levels after treatment (steatosis group:t =-2.164, P=0.040; non-steatosis group:t =-2.863, P=0.009), and there was a significant difference between the two groups (t=2.41, P=0.020). CONCLUSION: Our study did not show that mild hepatic steatosis affected the efficiency of a 48-week course of PEG-IFNα-2a treatment for patients with CHB.

[A multi-center clinical study of a novel controlled attenuation parameter for assessment of fatty liver].

OBJECTIVE: To evaluate the controlled attenuation parameter (CAP) assessment of fatty liver and choose a cut-off value of hepatic steatosis more than 5%. METHODS: Consecutive patients, 18 years or older, who had undergone percutaneous liver biopsy and CAP measurement were recruited from five liver healthcare centers in China. All enrollees were categorized as hepatic steatosis grade S0 (<5%) or S1 (5%). An M-probe equipped FibroScan 502 was used to capture CAP values. Receiver operating characteristic (ROC) curves were plotted, and the areas under (AU) the curves were calculated to determine the diagnostic efficacy. The CAP cut-off values at the optimal thresholds were defined by maximum Youden indices; sensitivity and specificity were also calculated. RESULTS: A total of 332 patients were enrolled in the study, including 67 patients with non-alcoholic fatty liver disease (NAFLD) and 265 with chronic hepatitis B (CHB) viru: infection. The median age (inter quartile range, IQR) of the study cohort was 39.0 (32.0-50.5) years-old. There were 46 males (68.7%) in the NAFLD group, with a median age of 37.0 (28.0-45.0) years-old, and 182 males (68.7%) in the CHB group; the differences between the two groups in median age and male: female ratio did not reach statistical significance. Multivariate linear regression analysis identified steatosis grade and body mass index (BMI) as independently associated with CAP. The median (IQR) CAP values among patients with S0 and S1 grade steatosis were 215.0 (190.0-241.0) dB/m and 294.0 (255.0-325.5) dB/m (P<0.001), respectively. For all patients, when BMI was <25 kg/m2, the ability of the AUROC of the CAP to discriminate hepatic steatosis more than or equal to 5% was 0.853, and the optimal cut-off value was 244.5 dB/m; however, when BMI≥25 kg/m2, the AUROC was 0.835 and the optimal cut-off value 269.5 dB/m. CONCLUSION: CAP can identify hepatic steatosis more than or equal to 5% and is applicable for the diagnosis of fatty liver if it is adjusted for BMI.

Exploring the role of mitochondrial proteins SIRT5 and MRPL33 through Mendelian randomization in primary biliary cholangitis.

BACKGROUND: Primary biliary cholangitis (PBC) is an autoimmune liver disease characterized by elevated serum antimitochondrial antibody levels in 90-95 % of cases. However, the exact causal relationship between mitochondrial proteins and PBC remains unclear. This study aims to investigate and clarify this relationship. METHODS: Genome-wide association data for mitochondrial proteins and PBC were obtained from public databases. The assessment of causal relationships between exposures and outcomes employed the Inverse Variance Weighted (IVW) method, MR Egger regression, and Weighted Median. Sensitivity analyses were systematically carried out to appraise the robustness of the Mendelian Randomization (MR) findings. RESULTS: The analysis revealed two mitochondrial proteins exhibiting a causal relationship with PBC. Elevated SIRT5 levels demonstrated a positive correlation with an augmented susceptibility to PBC in the IVW approach (odds ratio, OR: 1.2907, 95 % CI: 1.062-1.568, p = 0.0102). Conversely, increased MRPL33 levels were associated with a decreased risk of PBC (OR: 0.8957, 95 % CI: 0.807-0.993, p = 0.0376). Sensitivity analysis corroborated these findings consistently. CONCLUSION: This investigation advances the notion of a potential causal association between elevated SIRT5 levels and an increased risk of PBC, alongside a decreased risk of PBC linked to elevated MRPL33 levels. The identified mitochondrial proteins may serve as viable biomarkers, offering pertinent insights for the understanding and addressing of PBC.

Establishment and validation of an adherence prediction system for lifestyle interventions in non-alcoholic fatty liver disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide, affecting about 1/4th of the global population and causing a huge global economic burden. To date, no drugs have been approved for the treatment of NAFLD, making the correction of unhealthy lifestyles the principle method of treatment. Identifying patients with poor adherence to lifestyle correction and attempting to improve their adherence are therefore very important. AIM: To develop and validate a scale that can rapidly assess the adherence of patients with NAFLD to lifestyle interventions. METHODS: The Exercise and Diet Adherence Scale (EDAS) was designed based on compilation using the Delphi method, and its reliability was subsequently evaluated. Demographic and laboratory indicators were measured, and patients completed the EDAS questionnaire at baseline and after 6 months. The efficacy of the EDAS was evaluated in the initial cohort. Subsequently, the efficacy of the EDAS was internally verified in a validation cohort. RESULTS: The EDAS consisted of 33 items in six dimensions, with a total of 165 points. Total EDAS score correlated significantly with daily number of exercise and daily reduction in calorie intake (P < 0.05 each), but not with overall weight loss. A total score of 116 was excellent in predicting adherence to daily reduction in calorie intake (> 500 kacl/d), (sensitivity/specificity was 100.0%/75.8%), while patients score below 97 could nearly rule out the possibility of daily exercise (sensitivity/specificity was 89.5%/44.4%). Total EDAS scores ≥ 116, 97-115, and < 97 points were indicative of good, average, and poor adherence, respectively, to diet and exercise recommendations. CONCLUSION: The EDAS can reliably assess the adherence of patients with NAFLD to lifestyle interventions and have clinical application in this population.

Direct-acting antivirals failed to reduce the incidence of hepatocellular carcinoma occurrence in hepatitis C virus associated cirrhosis: A real-world study.

BACKGROUND: Direct-acting antivirals (DAAs) revolutionized the treatment of chronic hepatitis C virus (HCV)-associated disease achieving high rates of sustained virological response (SVR). However, whether DAAs can reduce the occurrence of hepatocellular carcinoma (HCC) in patients with HCV-associated cirrhosis who are at high risk have not been concluded. AIM: To investigate the effect of DAAs on the occurrence of HCC in patients with HCV-associated cirrhosis after achieving SVR. METHODS: Of 427 inpatients with HCV-associated cirrhosis were enrolled in Tianjin Second People's Hospital from January 2014 to April 2020. 118 patients weren't received antiviral treatment with any reasons named non-antiviral treatment group, and 236 patients obtained from the 309 DAAs treatment patients according to the propensity score matching named DAAs treatment group. Demographic information and laboratory data were collected from baseline and the following up. Kaplan-Meier curve and Log-Rank test were used to compare the incidence and cumulative incidence of HCC between the two groups. Cox proportional risk regression was used to re-evaluate the risk factors for HCC. RESULTS: HCC incidence was 4.68/100PY (95%CI, 3.09-6.81) in the DAAs treatment group, while it was 3.00/100PY (95%CI, 1.50-5.37) in the non-antiviral treatment group, and the relative risk was 1.82 (95%CI, 0.93-3.53, P > 0.05). The incidence of HCC at 12, 24, 36 and 48 months was 3.39%, 6.36%, 8.47% and 10.17% in the DAAs treatment group, and it was 0%, 0%, 3.39% and 9.32% in the non-antiviral treatment group, respectively. Age > 58 [hazard ratio (HR) = 1.089; 95%CI, 1.033-1.147; P = 0.002] and liver stiffness measurement > 27.85 kPa (HR = 1.043; 95%CI, 1.022-1.065; P = 0.000) were risk factors for HCC in all patients (n = 427), and DAAs treatment didn't show protective efficacy. CONCLUSION: DAAs treatment seems failed to reduce the incidence of HCC occurrence in HCV-associated cirrhosis in 48 months, and even increased the incidence of HCC in 36 months.

Impact of metabolic dysfunction-associated steatotic liver disease on the efficacy of immunotherapy in patients with chronic hepatitis B-related hepatocellular carcinoma.

OBJECTIVE: To investigate the impact of metabolic dysfunction-associated steatotic liver disease (MASLD) on the efficacy of immune checkpoint inhibitor (ICI)-based therapy in patients with chronic hepatitis B (CHB)-related hepatocellular carcinoma (HCC). METHODS: A total of 155 patients with CHB-related HCC who received ICI-based therapy (in the Department of Hepatology, Tianjin Second People's Hospital and Department of Hepatobiliary Oncology, Tianjin Medical University Cancer Institute & Hospital) between April 2021 and December 2023 were evaluated. Patients were divided into two groups: MASLD concurrent with CHB [MASLD-CHB] (n = 38), and CHB (n = 117). RESULTS: The median progression-free survival (PFS, 6.9 months vs. 9.3 months; P = 0.001), progressive disease (57.89% vs. 37.61%; P = 0.028), and disease control rate (42.11% vs. 62.39%; P = 0. 028) in the MASLD-CHB group were significantly worse than the CHB group. The median overall survival was not attained. The percentage of CD4+PD1+ (17. 56% vs. 8.89%; P < 0.001) and CD8+PD1+ T cells (10.50% vs. 7.42%; P = 0.005) in patient samples from the MASLD-CHB group were significantly higher than the CHB group. Concurrent MASLD [hazard ratio (HR) = 1.921; 95% CI, 1.138-3.245; P = 0.015] and alpha-fetoprotein levels after 3 months of treatment (HR = 2.412; 95% CI, 1.360-4.279; P = 0.003) were independent risk factors for PFS in all patients. CONCLUSIONS: ICI-based therapy in patients with CHB-related HCC and concurrent MASLD resulted in poorer efficacy and shorter PFS compared to patients with CHB-related HCC alone.