Trends in respiratory diseases before and after the COVID-19 pandemic in China from 2010 to 2021.

BACKGROUND: The ongoing benefits of coronavirus disease 2019 (COVID-19) nonpharmaceutical interventions (NPIs) for respiratory infectious diseases in China are still unclear. We aimed to explore the changes in seven respiratory infectious diseases before, during, and after COVID-19 in China from 2010 to 2021. METHODS: The monthly case numbers of seven respiratory infectious diseases were extracted to construct autoregressive integrated moving average (ARIMA) models. Eight indicators of NPIs were chosen from the COVID-19 Government Response Tracker system. The monthly case numbers of the respiratory diseases and the eight indicators were used to establish the Multivariable generalized linear model (GLM) to calculate the incidence rate ratios (IRRs). RESULTS: Compared with the year 2019, the percentage changes in 2020 and 2021 were all below 100% ranging from 3.81 to 84.71%. Pertussis and Scarlet fever started to increase in 2021 compared with 2020, with a percentage change of 183.46 and 171.49%. The ARIMA model showed a good fit, and the predicted data fitted well with the actual data from 2010 to 2019, but the predicted data was bigger than the actual number in 2020 and 2021. All eight indicators could negatively affect the incidence of respiratory diseases. The seven respiratory diseases were significantly reduced during the COVID-19 pandemic in 2020 and 2021 compared with 2019, with significant estimated IRRs ranging from 0.06 to 0.85. In the GLM using data for the year 2020 and 2021, the IRRs were not significant after adjusting for the eight indicators in multivariate analysis. CONCLUSION: Our study demonstrated the incidence of the seven respiratory diseases decreased rapidly during the COVID-19 pandemic in 2020 and 2021. At the end of 2021, we did see a rising trend for the seven respiratory diseases compared to the year 2020 when the NPIs relaxed in China, but the rising trend was not significant after adjusting for the NPIs indicators. Our study showed that NPIs have an effect on respiratory diseases, but Relaxation of NPIs might lead to the resurgence of respiratory diseases.

Distinct common signatures of gut microbiota associated with damp-heat syndrome in patients with different chronic liver diseases.

Background: Chronic hepatitis B (CHB) and non-alcoholic fatty liver disease (NAFLD) are prevalent in China. According to traditional Chinese medicine (TCM) theory, damp-heat (DH) syndrome is common in chronic liver disease. However, the biological characteristics related to quantitative diagnosis remain to be determined. This study aimed to identify the consistent alterations in the gut microbiota associated with DH syndrome in patients with CHB or NAFLD. Methods: A total of 405 individuals were recruited, of which 146 were participants who met the consistent TCM diagnosis by three senior TCM physicians and were typical syndromes. All participants were required to provide fresh stool and serum samples. The gut microbiota was assessed by fecal 16S rRNA gene sequencing, and the serum metabolite profiles of participants were quantified by an ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) system. DH syndrome-related bacteria taxa were identified based on the 146 individuals with typical syndromes and validated in all 405 volunteers. Results: The results showed that CHB and NAFLD patients with typical TCM DH syndrome had consistently elevated serum total bile acid (TBA) levels. Significant alterations in microbial community were observed according to TCM syndromes identification. A total of 870 microbial operational taxonomic units and 21 serum metabolites showed the same variation trends in both the CHB and NAFLD DH syndrome groups. The functional analysis predicts consistent dysregulation of bile acid metabolism. Five genera (Agathobacter, Dorea, Lachnospiraceae_NC2004_group, Subdoligranulum, and unclassified_c__Clostridia) significantly decreased in abundance in patients with DH syndrome. We utilize these five genera combined with TBA to construct a random forest classifier model to predict TCM diagnosis. The diagnostic receiver-operator characteristic (ROC) areas for DH syndrome were 0.818 and 0.791 in internal tenfold cross-validation and the test set based on all 405 individuals, respectively. Conclusion: There are common signatures of gut microbiota associated with DH syndrome in patients with different chronic liver diseases. Serum TBA combined with DH-related genera provides a good diagnostic potential for DH syndrome in chronic liver disease.

Risk prediction models for hepatocellular carcinoma in chronic hepatitis B patients on antiviral therapy: A meta-analysis.

BACKGROUND AND AIMS: The risk prediction of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB) is a challenge especially in the era of antiviral therapy. The aim of this meta-analysis was to comprehensively evaluate the performance of existing HCC prediction scores in HCC prediction on antivirals. METHODS: We searched PubMed, Web of Science and Cochrane Library for relevant prospective studies from the inception to August 24, 2021. The areas under the receiver operating characteristics (AUROCs) and their relevant 95% confidence intervals (CIs) of the risk prediction models were calculated. RESULTS: Nine eligible articles with 21561 patients (HCC developed in 947patients, 4.39%; mean follow-up duration: 5 years) and 14 predictive risk scores were included. The pooled AUROC of all included scores for 3-year and 5-year prediction of HCC was 0.72 (95%CI 0.68-0.76) and 0.80 (95%CI 0.76-0.83), with the corresponding sensitivity of 0.84 (95% CI 0.71-0.92) and 0.91(95% CI 0.86-0.95) and specificity of 0.46 (95% CI 0.30-0.63) and 0.48 (95% CI 0.37-0.59), respectively. All the 14 prediction models, as a whole, performed well in different populations, whether they include factor cirrhotic status or not; while those integrated viral load were less accurate (sensitivity 0.78, specificity of 0.57). CONCLUSIONS: In patients with CHB on antivirals, the scores included in our meta-analysis have been proven to be useful for mid-long term HCC prediction. Viral load seems not useful, whereas cirrhosis and its objective surrogates remain the predominant components. These models are expected to translate clinical benefits if used in complementarity with regular HCC surveillance.

Comparison of the clinical features and therapeutics of COVID-19 in cardio-cerebrovascular disease (CCVD) and non-CCVD patients.

Cardio-cerebrovascular disease (CCVD) is a major comorbidity of Coronavirus disease 2019 (COVID-19). However, the clinical characteristics and outcomes remain unclear. In this study, 102 cases of COVID-19 from January 22, 2020 to March 26, 2020 in Xixi Hospital of Hangzhou were included. Twenty cases had pre-existing CCVD. Results showed that compared with non-CCVD patients, those with CCVD are more likely to develop severe disease (15% versus 1%), and the proportion of pneumonia severity index grade IV was significantly higher (25% versus 3.6%). Computed tomography images demonstrated that the proportion of multiple lobe lesion involvement was significantly higher in the CCVD group than in the non-CCVD group (90% versus 63.4%). Compared with non-CCVD group, the levels of C-reactive protein, fibrinogen, D-dimer, and serum amyloid-A were higher, whereas the total protein and arterial partial PaO2 were lower in the CCVD group. Although no statistical difference was observed in the outcomes between groups, CCVD patients received more intensive comprehensive treatment to improve COVID-19 symptoms compared with non-CCVD patients. Integrated Chinese and Western medicine treatments have certain advantages in controlling the severe conversion rate and mortality of COVID-19. In addition, given that COVID-19 patients are usually related to coagulation disorders and thrombosis risk, the application of Chinese medicine in promoting blood circulation and removing stasis should be strengthened.

Longitudinal Progression of Estimated GFR in HIV-1-Infected Patients with Normal Renal Function on Tenofovir-Based Therapy in China.

PURPOSE: Estimated glomerular filtration rate (eGFR) decline in HIV-1-infected patients exposure to tenofovir disoproxil fumarate (TDF) has been widely assessed using linear models, but nonlinear assumption is not well validated. We constructed a retrospective cohort study to assess whether eGFR decline follows nonlinearity during antiviral therapy. PATIENTS AND METHODS: We examined 823 (299 of TDF users and 524 of non-TDF users) treatment-naïve HIV-1-infected participants (age ≥ 17 years, initial eGFR ≥ 90 mL/min/1.73m2). Estimated GFR trajectories were compared by one-linear and piecewise-linear mixed effects models, before and after propensity score matching, respectively. Whether the incidence of renal dysfunction (reduced renal function [RRF], eGFR < 90 mL/min/1.73 m2 and rapid kidney function decline [RKFD], eGFR > -3 mL/min/1.73 m2/year) follows nonlinearity was assessed by logistic regression. RESULTS: The median follow-up time of this study was 10 (interquartile range, 2-20) months, during which 178 (21.6%) experienced RRF, and 451 (54.8%) experienced RKFD. The slopes (mL/min/1.73 m2/year) of eGFR were -5.31 (95% CI: -6.57, -4.06) before 1.40 years, 4.83 (95% CI: 1.38, 8.28) from years 1.40 to 2.30 and -3.71 (95% CI: -5.97, -1.45) after 2.30 years among TDF users. Within years 1.40-2.30, each year of TDF exposure was associated with a 78% decreased risk of RKFD (95% CI: -91%, -49%). In comparison, eGFR increased slightly at the initiation of antiviral therapy, declined after 2.15 years (-4.96; 95% CI: -5.76, -4.17) among non-TDF users. Such a progression nonlinear trajectory was missed on the assumption of one-linearity, whether in TDF or non-TDF users. CONCLUSION: Over the piecewise mixed-effects analyses with the advantage of revealing the true nature of the exposure outcome relationships, an interesting reverse S-shaped relationship was observed. A routine screen based on nonlinearity could be more helpful for patient management.

Prevalence and short-term outcome of acute kidney injury in patients with acute-on-chronic liver failure: A meta-analysis.

Acute kidney injury (AKI) in patients with acute-on-chronic liver failure (ACLF) is a distinct syndrome to that in patients with cirrhosis, yet is less characterized. The aim of this meta-analysis was to investigate the impact of AKI on outcome of ACLF. We searched PubMed, Web of Science and Cochrane Library for original articles that evaluated the impact of AKI on outcome of ACLF from 2011 to 2019. Odds ratio (OR) with 95% confidence interval (CI) for 1-month and 3-month mortality was calculated. The response rate of vasoconstrictor for hepatorenal syndrome (HRS)-AKI was assessed. Eight relevant articles with 3610 patients were included. The prevalence of AKI in ACLF patients was 41% (95% CI 32%-50%). The presence of AKI was significantly associated with 1-month mortality of ACLF (OR 3.98, 95% CI 3.09-5.12; P < .001) and 3-month mortality (OR 4.98, 95% CI 3.59-6.92; P < .001). Additionally, patients with AKI stage ≥2 showed a higher 3-month mortality than stage 1 (OR 3.89, 95% CI 2.60-5.82; P < .001), and those of stage 3 had a higher mortality than stage ≤2 (OR 3.77, 95% CI 2.10-6.77; P < .001). The pooled response rate of vasoconstrictors was 32% (95% CI 26%-37%). This meta-analysis indicated that about 40% of ACLF patients complicated with AKI and the presence of AKI substantially increased the short-term mortality, together with a poor response rate of vasoconstrictors for HRS-AKI.

Low vitamin D levels are associated with high viral loads in patients with chronic hepatitis B: a systematic review and meta-analysis.

BACKGROUND: Previous studies have investigated the vitamin D status in patients with chronic hepatitis B virus (HBV) infection and its relationship with HBV replication, the results however were inconsistent. The present meta-analysis was carried out to compare the vitamin D levels between patients with chronic hepatitis B (CHB) and healthy controls, and to determine whether vitamin D levels were correlated with HBV viral loads significantly. METHODS: A systematic search was conducted via PubMed, Web of Science, EMBASE and the Cochrane Library to identify eligible studies until September 28, 2017. We calculated pooled mean difference (MD) and 95% confidence intervals (CI) to quantitatively estimate the difference of vitamin D levels between CHB patients and controls. In addition, correlation between serum vitamin D levels and HBV viral loads was defined by summary correlation coefficient (r value) and the corresponding 95% CI. RESULTS: A total of 7 studies involving 814 CHB patients and 696 healthy controls were included. A significantly decreased vitamin D levels was found in CHB patients compared with healthy controls: pooled MD (95% CI) was - 2.03 ng/mL (- 2.60, - 1.46). Latitude-stratified subgroup analysis indicated this difference was more obvious in low latitude areas, with a bigger pooled MD (95% CI) of - 2.72 ng/mL (- 4.57, - 0.87). In addition, we observed an inverse correlation between serum vitamin D levels and HBV viral loads: pooled r (95% CI) was - 0.41(- 0.54, - 0.27). CONCLUSIONS: Our results showed that vitamin D levels were lower in CHB patients than that of healthy controls and inversely correlated with HBV viral loads, although future comprehensive studies are needed to clarify the underlying mechanisms.

Relationship of serum uric acid level with non-alcoholic fatty liver disease and its inflammation progression in non-obese adults.

AIM: This study aimed to evaluate the relationship between serum uric acid (SUA) level and non-alcoholic fatty liver disease (NAFLD) in non-obese adults. METHODS: A cross-sectional study was carried out among 4098 adults, including 1936 non-obese and 2162 obese individuals. An additional 93 non-obese adults with biopsy-proven NAFLD were also included. RESULTS: The overall prevalence of NAFLD was 39.51% in the study group, and 14.88% in non-obese adults. The NAFLD patients had significantly higher SUA levels than controls in both men and women. The non-obese group had a higher NAFLD risk with increased SUA levels than the obese group, with odd ratios (95% confidence interval) of 2.559 (1.870-3.503) and 1.692 (1.371-2.087), respectively. In 93 non-obese adults with biopsy-proven NAFLD, SUA levels were significantly higher in those with non-alcoholic steatohepatitis. The prevalence of non-alcoholic steatohepatitis and lobule inflammation tended to increase to 57.58% and 66.67% as the SUA level increased to the fourth quartile. Subjects with hyperuricemia had significantly higher NAFLD activity scores and more serious lobule inflammation than the normal group. CONCLUSION: Non-obese adults have higher NAFLD risk with increased SUA levels than obese individuals, and the inflammation progression of NAFLD is associated with increased SUA level in non-obese subjects.

[Correlation between Constitution of Yin Deficiency Syndrome and Polymorphism of HLA-DQA1/Treatment Response of Peg-IFNalpha Therapy in HBeAg Positive Chronic Hepatitis B Patients].

OBJECTIVE: To observe the correlation between constitution of yin deficiency syndrome (YDS) and polymorphism of HLA-DQA1/treatment response of Peg-lFNalpha therapy in HBeAg positive chronic hepatitis B (CHB) patients, and to explore constitution of Chinese medicine (CM) in response of interferon therapy. METHODS: Totally 120 HBeAg positive CHB patients who were treated with Peg-IFNalpha were enrolled, and assigned to YDS group (59 cases) and non-YDS group (61 cases) according to classification of CM constitutions. All patients were subcutaneously injected with Peg-IFNalpha-2b (1.0 microg/kg body weight) or Peg-IFNalpha-2a (180 microg), once per week. Effective efficacy was primarily judged when complete response (CR) or partial response (PR) was obtained at month 6. Those with CR or PR completed 1 year therapeutic course. HLA-DQA1 gene types were detected by polymerase chain reaction sequence specific primers (PCR-SSP). The distribution difference of CM constitutions in patients with CR or PR and their inter-group HLA-DQA1 allele frequency were compared. RESULTS: Different treatment responses of Peg-IFNalpha were observed in CHB patients of two different CM constitutions. The ratio of CR + PR was 61.0% (36/59) in YDS group, obviously lower than that in NYDS group [78.7% (48/61), P < 0. 05]. Patients with CR had a lower allele frequency of HLA-DQA1 * 0501 than those with no-response [14.8% (8/54) vs. 30.6% (22/72)] with statistical difference (P < 0.05). Patients with CR had a higher allele frequency of HLA-DQA1 * 0601 than those with no-response [18.5% (10/54) vs. 5.6% (4/72)] with statistical difference (P < 0.05). The allele frequency of HLA-DQA1 * 0301 was lower in YDS group than in non-YDS group [2. 5% (3/118) vs. 9.8% (12/122)] with statistical difference (P < 0.05). The allele frequency of HLA-DQA1 * 0501 was higher in YDS group than in non-YDS group [33.9% (40/118) vs. 18.9% (23/122)] with statistical difference (P < 0.05). Yet statistical significance was lost after adjustment (Pc > 0.05 for both). CONCLUSIONS: Both constitutions of CM and HLA-DQA1 gene polymorphism af- fect HBeAg positive CHB patients' response to Peg-INFalpha. Constitutions of YDS and HLA-DQA1 * 0501 was not favorable to response, their association needed to be further studied.

Increased ratio of neutrophil elastase to α1-antitrypsin is closely associated with liver inflammation in patients with nonalcoholic steatohepatitis.

An imbalance between neutrophil elastase (NE) and its inhibitor α1-antitrypsin (A1 AT) is known to contribute to the development of obesity-related inflammation. This study aimed to investigate the role of the NE-A1 AT system in the histological progression of non-alcoholic fatty liver disease (NAFLD), and to evaluate the ability of it to predict nonalcoholic steatohepatitis (NASH). A total of 252 adults (NAFLD group, n = 202; healthy group, n = 50) were recruited. Clinical biochemical characteristics, NE and A1 AT concentrations were measured in all subjects. Among the NAFLD group, 86 patients had previously undergone liver biopsy and information on histological characteristics was consequently available. The area under the receiver operating characteristic curve (AUC) was used to determine the predictive accuracy of the NE-A1 AT system for NASH. NAFLD patients had an elevated serum NE concentration and a reduced A1 AT level with consequent NE/A1 AT imbalance. NE increased in the early stage of steatosis, preceding the decline in A1 AT, dating from the onset of NASH (NAS 3-4), and subsequently NE/A1 AT increased in the presence of NASH. Nonetheless, this increase began to resolve as the disease state progressed to advanced fibrosis. A1 AT had a sensitivity (SEN) of 83.8% and a specificity (SP) of 83.3% with the optimal cut-off of -1459.43, NE/A1 AT had a SEN of 88.8% and a SP of 83.3% with cut-off of 0.363 to predict NASH. An increased NE: A1 AT ratio is closely associated with liver Inflammation in patients with NASH and could serve as a novel marker to predict NASH in humans.

ZJU index: a novel model for predicting nonalcoholic fatty liver disease in a Chinese population.

Non-alcoholic fatty liver disease (NAFLD) is an important health issue worldwide. We aimed to develop a simple model to determine the presence of NAFLD in a Chinese population. A cross-sectional study with 9602 subjects was conducted. Potential predictors were entered into a stepwise logistic regression analysis to obtain the model. We used 148 patients with liver biopsy to validate this model. The model, named the ZJU index, was developed based on body mass index (BMI), fasting plasma glucose (FPG), triglycerides (TG), and the serum alanine aminotransferase (ALT) to serum aspartate transaminase (AST) ratio. The area under the receiver operating characteristic curve (AUROC) of the ZJU index to detect NAFLD was 0.822. At a value of <32.0, the ZJU index could rule out NAFLD with a sensitivity of 92.2%, and at a value of >38.0, the ZJU index could detect NAFLD with a specificity of 93.4%. In patients with liver biopsy, the ZJU index could detect steatosis with good accuracy, with an AUROC of 0.896. This study revealed that the ZJU index is a helpful model to detect NAFLD for community physicians in China. It was validated not only by a validation cohort but also by pathological data.

Low Serum Hepatitis B Surface Antigen Level Predicts Compensated Cirrhosis Caused by Chronic Hepatitis B in HBeAg Positive Patients in East China.

BACKGROUNDS: Serum hepatitis B surface antigen (HBsAg) levels are associated with fibrosis in patients with chronic hepatitis B (CHB) infection. OBJECTIVES: The aim of our study was to evaluate serum HBsAg level as a biomarker for compensated cirrhosis in hepatitis B e antigen (HBeAg) positive CHB patients. PATIENTS AND METHODS: Two-hundred and one HBeAg-positive Chinese CHB patients with or without cirrhosis were enrolled in this retrospective study. Cirrhosis was diagnosed based on liver biopsy. Furthermore, patients with decompensated cirrhosis were excluded. A statistical analysis was performed regarding the association between serum HBsAg level and compensated cirrhosis. RESULTS: Patients with compensated cirrhosis had a significantly lower mean serum HBsAg level compared to those without cirrhosis (3.27 Log10 IU/mL VS 4.17 Log10 IU/mL, P < 0.001). Furthermore, examining the correlation with compensated cirrhosis revealed that lower level of serum HBsAg was a significant factor in multivariate analysis. The area under the receiver operating characteristics curve of serum HBsAg was 0.856 for compensated cirrhosis. A positive predictive value of 66.2% and negative predictive value of 90.7% were obtained with a cut-off value of < 3.60 Log10 IU/mL (4000 IU/mL) of serum HBsAg. Moreover, the rate of compensated cirrhosis increased to 75.0% after combining with APRI > 2. CONCLUSIONS: In HBeAg positive CHB patients, low serum HBsAg level is a useful predictor of compensated cirrhosis.

Neutrophils Play a Crucial Role in the Early Stage of Nonalcoholic Steatohepatitis via Neutrophil Elastase in Mice.

Neutrophils infiltration in liver is one of the typical histological characteristics of nonalcoholic steatohepatitis (NASH) in both animal models and human subjects. This study was aimed to investigate the role of neutrophils in the process of NASH and its underling mechanisms. C57BL/6J mice were fed with either standard chow (SC) or methionine/choline-deficient (MCD) diet for 1, 2, 4, 8 weeks, respectively. C57BL/6J APOE(-/-) mice were fed with SC or high-fat high-cholesterol (HFHC) diet. Anti-Ly6G antibody was employed to deplete neutrophils and sivelestat was used to inhibit neutrophil elastase (NE). MCD-diet-receiving mice with neutrophil depletion had much lower serum ALT activity, liver inflammation, and mRNA levels of proinflammatory genes in the early stage of NASH (1 and 2 weeks) when compared to non-neutrophil-depleted mice. NE inhibitor sivelestat could recapitulate the effects of neutrophil depletion in APOE(-/-) mice fed with HFHC diet. As the disease progressed (4 and 8 weeks), neutrophil depletion did not lower serum ALT levels and liver lesions due to activation of Kupffer cells. Finally, we found neutrophils also affected anti-inflammation cytokine interleukin-1 receptor antagonist mRNA expression. Neutrophils play a crucial role in the early stage of NASH via NE.

[Development and evaluation of a high-fat/high-fructose diet-induced nonalcoholic steatohepatitis mouse model].

OBJECTIVE: To develop and evaluate a mouse model of nonalcoholic steatohepatitis (NASH) induced by a high-fat and high-fructose (HFHFr) diet. METHODS: Six-week-old C3H mice were randomly divided into groups for HFHFr diet experimental modeling, high fat-only (HF) diet controls, high fructose-only (HFr) diet controls, and standard chow (SC) diet controls. The standard HFHFr diet was modified so that it consisted of 76.5% standard chow, 12% lard, 1% cholesterol, 5% egg yolk powder, 5% whole milk powder, and 0.5% sodium cholate, along with 20% fructose drinking water. At the end of experimental weeks 4, 8, and 16, measurements were taken for the NASH-related parameters of body mass, serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), lipid profile, and wet liver weight (upon sacrifice). In addition, histological changes in the liver were evaluated by hematoxylin-eosin (HE) and oil red O staining. The significance of differences between groups was assessed by statistical analysis, using the METHODS: of t-test, Wilcoxon rank sum test, x2 test, F test or Fisher's test as appropriate. RESULTS: As compared to the mice in the SC group at the corresponding time points, the mice in the HFHFr and HF groups showed significantly higher body mass and wet liver weight, as well as more extensive and robust lipid disposition in hepatic tissues as evidenced by oil red O staining. However, HE staining indicated that the HFHFr and HF groups had different degrees of macrosteatosis accompanied with intralobular inflammatory foci, with the former showing more remarkable NASH-related histological changes. Analysis at the end of week 16 showed that about 80% of the mice in the HFHFr group had developed NASH [nonalcoholic fatty liver disease (NAFLD) activity score (NAS): less than 5]. The levels of low-and high-density lipoprotein (LDL and HDL) cholesterol, as well as the levels of ALT and AST, were increased from the end of week 4 to the end of week 8 for the HFHFr and HF groups. At the end of week 16, the two groups differed in the extent of increase in total cholesterol and LDL and HDL cholesterol, with only the HFHFr group showing statistically significant changes. Specifically, at the end of week 16, the HFHFr group showed ALT levels of 108.5 +/- 93.34 U/L (F=5.099, P =0.005 vs. HF group: 44.30 +/- 35.71 U/L, HFr group: 46.70 +/- 17.95 U/L, SC group: 24.70 +/- 6.57 U/L), AST levels of 316.30 +/- 208.98 U/L (F=6.654, P=0.001 vs. HF: 132.12 +/- 75.43 U/L, HFr: 143.30 +/- 38.53 U/L, SC: 122.60 +/- 12.76 U/L), total cholesterol levels of 5.18 +/- 0.58 mmol/L (F=72: 470, P =0.000 vs. HF: 3.94 +/- 0.75 mmol/L, HFr: 2.30 +/- 0.50 mmol/L, SC: 2.02 +/- 0.24 mmol/L), HDL cholesterol levels of 3.05 +/- 0.49 mmol/L (F=25.413, P =0.000 vs. HF: 2.65 +/- 0.54 mmol/L HFr: 1.77 +/- 0.47 mmol/L, SC: 1.58 +/- 0.16 mmol/L), LDL cholesterol levels of 1.11 +/- 0.23 mmol/L (F =83.297, P =0.000 vs. HF: 0.72 +/- 0.17 mmol/L, HFr: 0.27 +/- 0.04 mmol/L, SC: 0.20 +/- 0.05 mmol/ L). CONCLUSION: The present study suggests that a mouse model of NASH can be successfully induced by a 16-week modified HFHFr diet.

Non-alcoholic fatty liver disease (NAFLD) fibrosis score predicts 6.6-year overall mortality of Chinese patients with NAFLD.

The non-alcoholic fatty liver disease (NAFLD) fibrosis score (NFS) has emerged as a useful predictor of long-term outcome in NAFLD patients. We evaluated the predictive performance of the NFS for overall mortality in a Chinese population with NAFLD. All NAFLD patients diagnosed ultrasonographically at Xixi Hospital of Hangzhou between 1996 and 2011 were retrospectively recruited to the study. Outcome was determined by interview and causes of death were confirmed by medical records. The area under the receiver operating characteristic curve (AUCROC ) was used to determine the predictive accuracy of the NFS, BARD (body mass index, aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio, diabetes) score, FIB-4 index and the AST/platelet ratio index (APRI) for mortality. Data from a total of 180 eligible patients (median age 39 years; 96 men) were analysed, with 12 deaths over a median follow-up period of 6.6 years (range 0.5-14.8 years). Using Cox model analysis, the NFS as a continuous variable was identified as the only predictor for all-cause mortality (hazard ratio 2.743, 95% confidence interval (CI) 1.670-4.504). The NFS yielded the highest AUCROC of 0.828 (95% CI 0.728-0.928, P < 0.05), followed by the FIB-4 index, APRI and BARD score (AUCROC 0.806 (P < 0.05), 0.732 (P < 0.05) and 0.632, respectively). The data indicated that the NFS is a useful predictor of 6.6-year all-cause mortality for Chinese patients with NAFLD.

Toll-like receptor-4 signalling in the progression of non-alcoholic fatty liver disease induced by high-fat and high-fructose diet in mice.

The aim of the present study was to investigate Toll-like receptor-4 (TLR4) signalling at different stages of non-alcoholic fatty liver disease (NAFLD) induced by a high-fat, high-fructose (HFHFr) diet in mice. Both TLR4 wild-type (WT) and mutant (TLR4(mut) ) mice were fed either standard chow (SC) or the HFHFr diet for different periods of time from 4 to 16 weeks. Pathological characteristics and function of the liver were assessed. Simple steatosis, steatohepatitis and hepatic fibrosis occurred sequentially in Week 4, 8 and 16 in WT mice fed with the HFHFr. Expression of TLR4, myeloid differentiation factor 88 (MyD88), interferon regulatory factor (IRF) 3 and IRF7 started to increase at Week 4, peaked at Week 8 and then declined to basal levels at Week 16. This pattern was consistent with changes in inflammation in the liver revealed by haematoxylin and eosin staining. However, lipid accumulation, inflammation and fibrosis in livers of TLR4(mut) mice fed the HFHFr diet were significantly alleviated. In addition, the expression of activin A in WT mice fed the HFHFr diet increased at Week 16. The data suggest that TLR4 signalling mediates non-alcoholic steatohepatitis before fibrosis and that activin A is subsequently involved in NAFLD.

Prognostic performance of a series of model for end-stage liver disease and respective Δ scores in patients with hepatitis B acute-on-chronic liver failure.

The present study aimed to compare the short-term prognostic performance of a series of model for end-stage liver disease (MELD) and respective delta (∆) scores scoring systems in a population with acute-on-chronic hepatitis B liver failure (ACHBLF), and to investigate the potential effects from antivirals. A total of 77 patients with ACHBLF of mean age 46 years, 82% male, with 58.4% receiving antivirals, were recruited for this study. The ∆ scores for MELDs were defined as the changes one week after admission. Thirty­eight (49%) patients (22 treated with antivirals) died within three months. The mean MELD and ∆MELD scores of the survival group were 19.5 ± 4.4 and 0.2 ± 3.7 respectively, and those of the mortality group were 23.5 ± 5.5 and 7.9 ± 6, respectively. The area under the receiver operating characteristic curve (AUC) for MELD, integrated MELD (iMELD), MELD with the addition of serum sodium (MELD-Na), updated MELD (upMELD), MELD excluding the international normalized ratio (INR; MELD-XI), United Kingdom MELD (UKMELD) and their ∆ scores were 0.72, 0.81, 0.77, 0.69, 0.65, 0.77 and 0.86, 0.83, 0.83, 0.82, 0.79 and 0.79, respectively. iMELD and MELD-Na significantly improved the accuracy of MELD (P<0.05). A cut-off value of 41.5 for the iMELD score can prognose 71% of mortalities with a specificity of 85%. In each pair of models, the ∆ score was superior to its counterpart, particularly when applied to patients with MELD ≤ 30. Decreased accuracy was observed for all models in the subset of patients treated with antivirals, although their baseline characteristics were comparable to those of untreated patients, while iMELD, MELD-Na and respective ∆ models remained superior with regard to the predictability. The iMELD and MELD-Na models predicted three-month mortality more accurately, while the ∆ models were superior to their counterparts when MELD ≤ 30; however, their performance was altered by antivirals, and thus requires optimization.

[The relationship between serum HBsAg levels and liver inflammation and fibrosis in patients with chronic hepatitis B].

OBJECTIVE: To investigate the relation of hepatitis B surface antigen (HBsAg) level with chronic hepatitis B (CHB) and liver inflammation and fibrosis. METHODS: A total of 301 patients who diagnosed CHB and underwent liver biopsy were enrolled into the study. Meantimes, the biochemical markers, ferritin (FERR), serum HBsAg and HBV DNA quantitation were detected. The relation between HBsAg level and liver pathology were determined by spearman rank correlation analysis. The receiver operating characteristic curve was used to evaluate the accuracy of HBsAg level for liver inflammation and fibrosis. RESULTS: The body mass index (BMI), age, gender, genotype and family history had no effective on liver inflammation and fibrosis (P < 0.05). With the progressing of inflammation and fibrosis, the serum AST and ALT raise obviously (chi2 = 71.193, 96.344, 47.847, 63.981; P = 0.000, 0.000, 0.000, 0.000). When fibrosis reached to S4, the level of HBV DNA decreased obviously (chi2 = 33. 322; P = 0.000). With the aggravation of inflammation and fibrosis, the serum HBsAg gradually descended (chi2 = 68.173,15.719; P = 0.000, 0.000). The areas under operating characteristics curves of HBsAg predicted < or = G3 and < or = S3 were 0.732 and 0.793, and the specificity were 0.778, 0.891, and sensitivity were 0.685, and 0.633, respectively. CONCLUSION: The level of HBsAg of Chinese CHB patients descended gradually with the aggravation of liver inflammation and fibrosis. The serum HBsAg had a higher specificity to predict < or = G3 and < or = S3 of CHB patients. But there had superiority of predicting fibrosis than inflammation.

[Clinical research of the relation of hepatitis B surface antigen (HBsAg) quantification and hepatic tissue pathological staging].

OBJECTIVE: To explore the correlation of serum hepatitis B surface antigen (HBsAg) level and hepatic tissue pathological staging in the chronic hepatitis B infected persons. METHODS: Collect the clinical data of 272 cases who are HBsAg-positive more than 6 months and accepted hepatic biopsy in our hospital. Detect serum HBsAg quantification, ALT, HBV DNA, complete blood count, hepatic tissue pathological staging, grouping the cases according to the stage of inflammation and the fibrosis degree respectively. Observe serum HBsAg quantification, HBV DNA and the stage of inflammation and the fibrosis degree. Analyse the correlation between HBsAg quantification and HBV DNA. RESULTS: The correlation of serum HBsAg level and HBV DNA is notable. Serum HBsAg level is a variable affecting hepatic tissue pathological stage significantly. CONCLUSIONS: Serum HBsAg level is a marker having higher specificity and sensitivity to diagnose the hepatic fibrosis.