Prevalence and risk factors of covert hepatic encephalopathy in cirrhotic patients: A multicenter study in China.

OBJECTIVE: We aimed to investigate the prevalence of covert hepatic encephalopathy (CHE) in cirrhotic patients in China and its risk factors. METHODS: A multicenter prospective observational study was conducted from January 2021 to March 2022 at 16 medical centers across China to investigate the risk factors of CHE and establish a prediction model for CHE episodes. RESULTS: A total of 528 patients were enrolled in the study. Based on both the psychometric hepatic encephalopathy score and Stroop test results, the prevalence of CHE was 50.4% (266/528), and the consistency between these two tests was 68.9%. Multivariate analysis showed that age (odds ratio [OR] 1.043, 95% confidence interval [CI] 1.022-1.063, P < 0.001), duration of education (OR 0.891, 95% CI 0.832-0.954, P = 0.001), comorbidities of cardiovascular diseases, hypertension, cerebral apoplexy or diabetes mellitus (OR 2.072, 95% CI 1.370-3.133, P < 0.001), Child-Pugh score (OR 1.142, 95% CI 1.029-1.465, P = 0.025), and blood urea nitrogen concentration (OR 1.126, 95% CI 1.038-1.221, P = 0.004) were associated with CHE episodes. According to the Chronic Liver Disease Questionnaire, CHE patients had lower scores for abdominal symptoms and systemic symptoms (P < 0.001), indicating a poor health-related quality of life. Based on a stepwise Cox regression hazard model, we established a nomogram for determining the probabilities of CHE episodes, and the area under the receiver operating characteristic curve was 0.733 (95% CI 0.679-0.788) and 0.713 (95% CI 0.628-0.797) in the training and validation cohorts. CONCLUSIONS: CHE is a common complication of cirrhosis in China. Large-scale studies with long-term follow-up are needed to determine the natural history of Chinese CHE patients.

Real-world study on HBsAg loss of combination therapy in HBeAg-negative chronic hepatitis B patients.

Combination therapy with pegylated interferon (PEG-IFN) and nucleos(t)ide analogues (NAs) can enhance hepatitis B surface antigen (HBsAg) clearance. However, the specific treatment strategy and the patients who would benefit the most are unclear. Therefore, we assessed the HBsAg loss rate of add-on PEG-IFN and explored the factors associated with HBsAg loss in chronic hepatitis B (CHB) patients. This was a real-world cohort study of adults with CHB. Hepatitis B e antigen (HBeAg)-negative NAs-treated patients with baseline HBsAg ≤1500 IU/ml and HBV DNA < the lower limit of detection, or 100 IU/ml, received 48 weeks of add-on PEG-IFN. The primary outcome of the study was the rate of HBsAg loss at 48 weeks of combination treatment. Using multivariable logistic regression analysis, we determined factors associated with HBsAg loss. HBsAg loss in 2579 patients (mean age: 41.2 years; 80.9% male) was 36.7% (947 patients) at 48 weeks. HBsAg loss was highest in patients from south-central and southwestern China (40.0%). Factors independently associated with HBsAg loss included: increasing age (odds ratio = 0.961); being male (0.543); baseline HBsAg level (0.216); HBsAg decrease at 12 weeks (between 0.5 and 1.0 log10 IU/ml [2.405] and >1.0 log10 IU/ml [7.370]); alanine aminotransferase (ALT) increase at 12 weeks (1.365); haemoglobin (HGB) decrease at 12 weeks (1.558). There was no difference in the primary outcomes associated with the combination regimen. In conclusion, HBsAg loss by combination therapy was higher in patients from southern China than those from the north. An increased chance of HBsAg loss was associated with baseline characteristics and dynamic changes in clinical indicators.

ICAM-1 controls development and function of ILC2.

Group 2 innate lymphoid cells (ILC2s) are emerging as key players in the pathogenesis of allergic airway inflammation. The mechanisms regulating ILC2, however, are not fully understood. Here, we found that ICAM-1 is required for the development and function of ILC2. ICAM-1-deficient (ICAM-1-/- ) mice displayed significantly lower levels of ILC2s in the bone marrow and peripheral tissues than wild-type controls. CLP transfer and in vitro culture assays revealed that the regulation of ILC2 by ICAM-1 is cell intrinsic. Furthermore, ILC2s from ICAM-1-/- mice were functionally impaired, as indicated by the diminished production of type-2 cytokines in response to IL-33 challenge. The reduction in lung ILC2s caused a clear remission of airway inflammation in ICAM-1-/- mice after administration of papain or Alternaria alternata. We further demonstrate that ILC2 defects caused by ICAM-1 deficiency are due to ERK signaling-dependent down-regulation of GATA3 protein. Collectively, these observations identify ICAM-1 as a novel regulator of ILC2.

[Hepatitis B virus (HBV) mutation in enhancer I (HBV Enh I)/X-promoter and the relationship between chronic HBV-related disease spectrum].

OBJECTIVE: To investigate the hepatitis B virus (HBV) mutation in the Enhancer I (HBV Enh I)/X-promoter and to analysis the relationship between chronic HBV-related disease spectrum. METHODS: 275 patients were enrolled in this study, including 100 cases of chronic hepatitis B (CHB), 74 cases of liver cirrhosis (LC), 101 cases of hepatocellular carcinoma (HCC), grouping by different HBV genotypes, using semi-nested PCR amplification of HBV Enh I/X-promoter and sequencing DNA, the mutations were determined by alignment to HBV reference sequence, the data was compared by chi2 test and analyzed by multivariate logistic regression. RESULTS: (1) Genotyping results: 61.48% (158/257) were infected with HBV genotype B, including 70 cases of CHB, 36 cases of LC and 52 cases of HCC; 38.52% (117/257) were infected with HBV genotype C, including 30 cases of CHB, 38 cases of LC and 49 cases of HCC. (2) In the patients were infected with HBV genotype B, A1123Y mutation in LC was significantly higher than in CHB (30.56% vs. 8.58%, chi2 = 8.533, P = 0.005, A = 4.693, 95% CI [1.567-14.056]), HCC was significantly higher than in CHB (28.85% vs. 8.58%, chi2 = 8.607, P = 0.003, A = 4.324,95% CI [1.544-2.109]); A1317G mutation in HCC was significantly higher than in CHB (30.77% vs. 7.14%, chi2 = 11.687, P = 0.001, A = 5.778, 95% CI [1.955-17.076]). In the patients were infected with HBV genotype C, T1323C mutation in HCC was significantly higher than in CHB (30.61% vs. 6.67%, chi2 = 6.318, P = 0.12, A = 6.176, 95% CI [1.301-29.331]). (3) Multivariate regression analyses showed that A1317G (OR = 5.706, 95% CI [1.770-18.837], P = 0.004) and T1323C (A = 5.810, 95% CI [1.114-30.306], P = 0.037) mutation were risk factors for HCC. CONCLUSION: HBV Enh I/X-promoter mutations were associated with the development of LC and HCC, the mutations can help to predict the occurrence of LC and HCC.

[Study on the copy numbers and mRNA expression levels of the programmed death-1 gene in chronic hepatitis B patients].

OBJECTIVE: To study the copy numbers and mRNA expression levels of the Programmed Death-1 gene in chronic hepatitis B patients and to analyze the differences of the copy numbers and mRNA expression levels of the gene in patients with different clinical outcomes. METHODS: Real time PCR was adopted to detect the PD-1 gene copy numbers and their mRNA expressions in peripheral blood mononuclear cells (PBMCs) from 27 samples from healthy donors in Control group, 31 samples from chronic asymptomatic HBV carriers (ASC, n=31), 19 samples from chronic severe hepatitis B patients (CSH, n=19) and 29 samples from Primary hepatitis B Virus-related hepatocarcinoma (PHC, n=29). The differences and relationship of copy numbers and their mRNA expression levels among those groups were compared and analyzed by adopting Chi-square test and Rank sum test. RESULTS: PD-1 gene copy number deviated from 0 copy to 3 copies among all the 106 samples. In control group, ASC group, CSH group and PHC group, the percentages of cases of haploid (single) were 37.0%, 35.5%, 26.3% and 6.9%, respectively, the percentages of cases of diploid (double) were 55.5%, 58.0%, 63.2% and 82.8%, respectively, and the percentages of cases of triploid (triple) were 3.7%, 6.5%, 10.5% and 10.3%, respectively. The percentage of cases of polyploid (diploid and triploid) in control group, ASC group, CSH group and PHC group were 59.3%, 64.5%, 73.7% and 93.1%, respectively. The different distribution of PD-1 gene copy number of polyploid was significant in total samples (x2=9.583, P<0.05). Compared with Control Group and ASC group, the percentage of cases of polyploid in PHC group was lower with the x2 equals to 8.985 and 7.215 respectively and both with P less than 0.05. The difference between the two groups was statistically significant. The mean PD-1 gene copy numbers for these four groups were 1.59+/-0.63, 1.70+/-0.52, 1.84+/-0.60 and 2.00+/-0.37 while the median were 0.002 54, 0.002 72, 0.002 55 and 0.001 33 respectively. Except the control group, there was a uptrend in the other three groups while PD-1 gene mRNA expression presented a downtrend. The mean of PD-1 gene copy numbers of 2 and their mRNA expression levels were 19.59, 32.57 and 33.22 for PHC, CSH and ASC groups among which PHC group had the lowest value, there was significant differences found in the comparison with F=5.395 and P<0.05. CONCLUSION: PD-1 gene copy numbers and their mRNA expression levels were different in chronic HBV infected patients with different transformation. It is valuable to follow up the patients with more than 1 copy number of PD-1 gene in long term.

[Population expansion of Spartina alterniflora and Phragmites australis at Jiuduansha, Shanghai based on cellular automata model].

Based on the field survey and the interpretation and analysis of satellite images about the population expansion patterns of Spartina alterniflora and Phragmites australis at Jiuduansha shoals in 1997-2004, and combined with 3S techniques, a cellular automata (CA) model was built to simulate the population dynamics of plants adaptable to salt marsh. The results showed that the model could well simulate the population expansion pattern and trend of S. alterniflora and P. australis at Jiuduansha, and strongly supported the hypothesis of space pre-emption and range expansion with simple advancing wave fronts of these two species. The native species P. australis shared the same niche with the exotic species S. alterniflora, but the range expansion rate of S. alterniflora was 2-4 times faster than that of P. australis. With the accretion of the Jiuduansha shoals, a rapid range expansion of S. alterniflora was predicted to last for a long period in the future. The CA model built in this study could gain valuable insights into the relationships between population expansion pattern and its ecological processes of exotic plant species, and was of significance for wetland biodiversity conservation and resources management.

[Study of laboratory characteristic of 4 patients with sporadic severe acute respiratory syndrome in 2004].

OBJECTIVE: To analyze the laboratory characteristics of patients with sporadic severe acute respiratory syndrome (SARS) in China. METHODS: The laboratory findings of the 4 cases with SARS occurring in Guangzhou, People's Republic of China, in 2004 were analyzed and compared with that during epidemic. RESULTS: Leukopenia and lymphocytopenia were seen in all the patients. Two patients had slightly decreased peripheral blood T lymphocyte count. Alanine aminotransferase (ALT) and aspartate transaminase (AST) levels increased slightly in 3 patients. No hypoxemia was seen in all the patients. Both SARS-IgM and IgG sero-conversion occurred earlier in all the patients with the titer increased more than 4-fold shortly. Neutralization test was positive in all the patients. SARS coronary virus (SARS-CoV) RNA was detected by polymerase chain reaction (PCR) in pharyngeal swabs only in 1 patient. CONCLUSION: The 4 sporadic SARS patients in 2004 have milder manifestations, shorter course of disease with no complications during an epidemic, compared with patients seen previously. The change in laboratory findings is less than that, which might be attributable to milder virulence of the SARS-CoV. The antibody appears earlier in these patients. The SARS-CoV is eliminated rapidly.

[Study on the damage of liver in patients with SARS].

OBJECTIVE: To study the changes in liver function and histopathology, and investigate the underlying mechanism and clinical significance of damage of liver in patients with severe acute respiratory syndrome (SARS). METHODS: According the clinical diagnostic standard of atypical pneumonia of Ministry of Health P. R. China, liver function was assessed in 110 SARS patients admitted from February 2003 to June 2003. Of them 8 SARS patients died, and the livers were pathologically examined, and their liver function parameters were compared with that of the 35 healthy controls. RESULTS: Alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), total bilirubin (TBil) of patients with SARS were higher than those of controls, they were (91.61+/-50.53) U/L vs. (32.91+/-10.56) U/L, (78.68+/-33.32) U/L vs. (29.43+/-8.89) U/L, (429.95+/-188.94) U/L vs. (200.83+/-44.86) U/L, (11.67+/-4.26) micromol/L vs. (8.44+/-3.86) micromol/L, all P<0.001. Albumin (ALB) and pro-albumin (PAB) of patients with SARS were lower than those of controls, they were (34.40+/-5.13) g/L vs. (42.09+/-6.79) g/L, (0.20+/-0.06) g/L vs. (0.34+/-0.05) g/L, both P<0.001. Direct reaction bilirubin (DBil), total bile acid (TBA), gamma-glutamyltransferase (GGT) and alkaline phosphatase (ALP) showed no marked difference between SARS patients and controls, all P>0.05. Non-specific inflammation in the liver was observed in pathological examination in 4 cases. ALT, AST, GGT and LDH were always 4 to 9 times of normal. The ratio of abnormality of ALT, AST and PAB were more than 80.0 percent, the ratio of abnormality of ALB was 42.7 percent, and less than 30.0 percent for other indexes. The average of LDH, ALT, and AST of dead patients were higher than those of the survivors. Histopathology of liver was non-specific hepatitis. CONCLUSION: The patients with SARS are prone to have mild non-specific hepatitis. It seldom causes the typical symptoms of hepatitis and it is easy to be ignored in clinic.

[Study on the myocardiac injury in patients with severe acute respiratory syndrome].

OBJECTIVE: To explore the myocardiac injury in patients with severe acute respiratory syndrome (SARS) and its clinical significance. METHODS: 37 SARS patients fulfilled the Guangdong provincial diagnostic criteria for infectious atypical pneumonia and 35 health controls were investigated. The serum levels of creatine kinase (CK), lactate dehydrogenase (LDH), aspartate transaminase (AST), troponin I (TnI), creatine kinase-MB (CK-MB) and myoglobin (MYO) were measured. RESULTS: CK, LDH and AST levels in patients were higher than those of control group (P < 0.01); furthermore, among patients the levels were higher in fatal cases than in survivors. The positive rates of TnI, CK-MB and MYO in patients were higher than those in controls (P < 0.05). CONCLUSION: The patients with SARS are subject to complicating myocardiac injury. Therefore, careful monitoring of the myocardiac enzyme profiles is of great importance in reducing the complications and mortality in patients with SARS.