Showing papers by "Hainv Gao published in 2022"

Rifaximin Modulates the Gut Microbiota to Prevent Hepatic Encephalopathy in Liver Cirrhosis Without Impacting the Resistome

Abstract: The gut microbiota has an important role in the pathogenesis of hepatic encephalopathy(HE). Rifaximin, an intestinal non-absorbable antibacterial agent, is effective in the treatment of HE. However, whether long-term prophylactic use induces antibacterial resistance and its mechanism for treating HE remains unclear. This prospective study assessed the impact of 12 weeks rifaximin administration on the gut microbiota and resistome in cirrhotic patients. Fecal sampling was conducted 1 day before the first rifaximin administration and at Weeks 1, 2, 4, 6, 8, 10, 12 of the study. Thirty cirrhotic patients who were in remission from recurrent HE was enrolled to receive rifaximin (400mg TID for 12 weeks). Rifaximin improved hyperammonemia and cognitive function in the 21 patients who completed rifaximin treatment. The dynamic observations showed the gut microbiota diversity, composition and the number of resistance genes, plasmids, insertion sequences did not change significantly during the period(P>0.05). Metabolic pathways such as aromatic amino acids, tryptophan synthesis, urea cycle, and LPS synthesis reduced. No new antimicrobial resistance genes was emergenced. However, the number of aminoglycosides, rifamycin and phenolic resistance genes increased, whereas tetracycline, fosfomycin and cephamycin decreased (P<0.05). Changes in the abundance of E. coli, K. pneumoniae, and B. longum strains correlated with changes of resistance genes. Prophylactic use of rifaximin for 12 weeks improved hyperammonemia and neurophysiological function, maintained gut microbiota diversity, composition and did not change the overall resistome. Rifaximin altered expression of HE-related metabolic pathways. All of these effects could play a key role in preventing HE. Clinical Trial Registration: ChiCTR1900022234 (registered at the Chinese Clinical Trial Registry).

The abundance of bifidobacterium in relation to visceral obesity and serum uric acid

Abstract: Gut microbiome has been shown to play a role in the development of obesity in recent studies. Most of these studies on obesity were based on the BMI classification criteria, which doesn't distinguish Visceral adipose tissue (VAT) from subcutaneous adipose tissue (SAT). Some studies showed that VAT has a higher risk of inducing metabolic diseases than SAT. This study focused on the visceral obesity defined by increased visceral fat area. The present study was designed to investigate the association of visceral obesity with gut predominant microbiota and metabolic status. This study included 372 healthy individuals from medical examination center in Shulan Hangzhou Hospital. Quantitative polymerase chain reaction (q-PCR) technique was used to detect ten kinds of gut predominant bacteria in fresh feces. Visceral fat area (VFA) was measured by the bioimpedance analyzer (INBODY720, Korea). The abundance of Bifidobacterium significantly decreased in the visceral obesity group. Compared with the lean group, Visceral obesity group had significantly higher levels of LDL, TG, FBG, serum uric acid (SUA) and lower levels of HDL. SUA was an independent impact factor for Bifidobacterium. SUA was negatively correlated with Bifidobacterium and positively correlated with VFA. In the mediation analysis, SUA showed significant mediation effect. SUA may be a mediating factor between decreased Bifidobacterium and increased VAT.

Validation of the GALAD model and establishment of a new model for HCC detection in Chinese patients

Abstract: Background GALAD model is a statistical model used to estimate the possibility of hepatocellular carcinoma (HCC) in patients with chronic liver disease. Many studies with other ethnic populations have shown that it has high sensitivity and specificity. However, whether this model can be used for Chinese patients remains to be determined. Our study was conducted to verify the performance of GALAD model in a Chinese cohort and construct a new model that is more appropriately for Chinese populations. Methods There are total 512 patients enrolled in the study, which can be divided into training set and validation set. 80 patients with primary liver cancer, 139 patients with chronic liver disease and 87 healthy people were included in the training set. Through the ROC(receiver operating characteristic) curve analysis, the recognition performance of GALAD model for liver cancer was evaluated, and the GAADPB model was established by logistic regression, including gender, age, AFP, DCP, total protein, and total bilirubin. The validation set (75 HCC patients and 130 CLD patients) was used to evaluate the performance of the GAADPB model. Result The GALAD and GAADPB achieved excellent performance (area under the receiver operating characteristic curve [AUC], 0.925, 0.945), and were better than GAAP, Doylestown, BALAD-2, aMAP, AFP, AFP-L3%, DCP and combined detection of AFP, AFP-L3 and DCP (AUCs: 0.894, 0.870, 0.648, 0.545, 0.879, 0.782, 0.820 and 0.911) for detecting HCC from CLD in the training set. As for early stage of HCC (BCLC 0/A), GAADPB had the best sensitivity compared to GALAD, ADP and DCP (56.3%, 53.1%, 40.6%, 50.0%). GAADPB had better performance than GALAD in the test set, AUC (0.896 vs 0.888). Conclusions The new GAADPB model was powerful and stable, with better performance than the GALAD and other models, and it also was promising in the area of HCC prognosis prediction. Further study on the real-world HCC patients in China are needed.

Efficacy and safety of alfosbuvir plus daclatasvir in Chinese patients with hepatitis C virus genotypes 1, 2, 3, and 6 infection: An open‐label, phase 2 study

Abstract: Alfosbuvir is a novel potent HCV NS5B polymerase inhibitor in development for the treatment of chronic HCV infection. Our previous studies indicated that alfosbuvir monotherapy was well‐tolerated and druggable in healthy subjects and HCV‐infected patients. Here, we evaluate the efficacy and safety of alfosbuvir in combination with daclatasvir in Chinese patients with HCV genotype 1, 2, 3 or 6. In this open‐label study, patients with chronic HCV infection were randomly assigned with a 1:1:1 ratio to receive 12 weeks of daclatasvir 60 mg plus alfosbuvir at a dose of 400, 600 or 800 mg (Cohort A, B or C) daily. Randomization was stratified by HCV genotype and the presence or absence of cirrhosis at screening. The primary endpoint was a sustained virologic response 12 weeks after the end of treatment (SVR12). A total of 124 patients were enrolled in the study, all of whom were available for post‐treatment week 12 assessments. SVR12 was achieved in 92.7% (38/41), 95.2% (40/42) and 100% (41/41) of patients in Cohort A, B and C respectively. The most common adverse events were hepatic steatosis, upper respiratory tract infection, hypercholesterolaemia, hypertriglyceridaemia, blood bilirubin increased, and total bile acids increased. There were no discontinuations due to adverse events, and no treatment‐related serious adverse events were reported. Once‐daily oral administration of alfosbuvir plus daclatasvir were highly effective and safe in Chinese patients infected with HCV genotype 1, 2, 3 or 6, suggesting this regimen could be a promising drug candidate for HCV treatment irrespective of genotype.

Decreased vitamin D-binding protein level portends poor outcome in acute-on-chronic liver failure caused by hepatitis B virus

Abstract: Background/Aims Acute-on-chronic liver failure (ACLF) is a catastrophic illness. Few studies investigated the prognostic value of vitamin D-binding protein (VDBP) for hepatitis B virus (HBV)-related ACLF (HBV-ACLF) resulted in conflicting results. Methods Two prospective HBV-ACLF cohorts (n=287 and n=119) were enrolled to assess and validate the prognostic performance of VDBP. Results VDBP levels in the non-survivors were significantly lower than in the survivors (P<0.001). Multivariate Cox regression demonstrated that VDBP was an independent prognostic factor for HBV-ACLF. The VDBP level at admission gradually decreased as the number of failed organs increased (P<0.001), and it was closely related to coagulation failure. The areas under the receiver operating characteristic curve (AUCs) of the Child-Pugh-VDBP and chronic liver failure-sequential organ failure assessment (CLIF–SOFA)-VDBP scores were significantly higher than those of Child-Pugh (P<0.001) and CLIF-SOFA (P=0.0013). The AUCs of model for end-stage liver disease (MELD)-VDBP were significantly higher than those of MELD (P= 0.0384) only in the case of cirrhotic HBV-ACLF patients. Similar results were validated using an external multicenter HBV-ACLF cohort. By longitudinal observation, the VDBP levels gradually increased in survivors (P=0.026) and gradually decreased in non-survivors (P<0.001). Additionally, the VDBP levels were found to be significantly decreased in the deterioration group (P=0.012) and tended to be decreased in the fluctuation group (P=0.055). In contrast, they showed a significant increase in the improvement group (P=0.036). Conclusions The VDBP was a promising prognostic biomarker for HBV-ACLF. Sequential measurement of circulating VDBP shows value for the monitoring of ACLF progression.