Effect of Additional Clostridium butyricum on the Intestinal Flora of Chronic Hepatitis B Patients Treated with Entecavir.

INTRODUCTION: To explore the influence of intestinal flora on the occurrence, development and antiviral therapy of chronic hepatitis B (CHB), 16S rDNA amplification sequencing was performed to investigate the intestinal flora in CHB patients treated with entecavir (ETV) and Clostridium butyricum (CB). METHODS: CHB patients were divided into the ETV group (treatment with ETV alone) and ETV + CB group (treatment with ETV and CB). After 8-week treatment, feces samples were collected and processed for 16S rDNA amplicon sequencing; blood samples were collected for the biochemical, immunologic and virologic evaluations, which were compared between groups. RESULTS: ETV treatment for 8 weeks significantly decreased the serum levels of alanine aminotransferase (ALT), interleukin-6 (IL-6), IL-8, tumor necrosis factor-α (TNF-α) and HBV DNA compared to those before treatment, but there were no marked differences between the ETV group and ETV + CB group. The intestinal flora changed significantly in the CHB patients after ETV + CB treatment: there were marked differences in 13 unique species before treatment and 4 unique species after ETV + CB treatment; at the phylum level, the top five bacteria with significant difference between patients before treatment and ETV + CB patients were Firmicutes, Actinobacteria, Cyanobacteria, Euryarchaeota and Synergistetes. There were significant differences in 25 unique species in the ETV group and 4 unique species in the ETV + CB group; at the phylum level, the top five bacteria with significant difference between ETV patients and ETV + CB patients were Actinobacteria, Fusobacteria, Proteobacteria, Saccharibacteria and Synergistetes. CONCLUSION: ETV treatment improves the serum biochemical, immunologic and virologic variables, but additional CB fails to further improve these variables. Of note, additional CB affects the intestinal flora in the CHB patients treated with ETV.

Nomogram for predicting the risk of gastroesophageal varices after primary endoscopic prophylaxis for variceal hemorrhage in patients with cirrhosis.

BACKGROUND AND AIMS: The aim of this study was to identify predictors of non-high-risk gastroesophageal varices and evaluate the probability of the residual high-risk varices in cirrhosis patients after the primary endoscopic treatment. PATIENTS AND METHODS: Medical records of the patients with cirrhosis admitted for primary endoscopic prophylaxis gastroesophageal varices hemorrhage were retrospectively analyzed. The patients were divided into high-risk varices and non-high-risk varices groups according to the endoscopy. A nomogram was developed based on the results of multivariate Cox analyses. Accuracy of this model was validated by the concordance index (Harrell's c-index) and calibration curve. RESULTS: Altogether 117 patients were enrolled between March 2014 and April 2018. The multivariate Cox analyses identified spleen length <140 mm [odds ratio (OR) = 2.715; P = 0.037), small or medium size of esophageal varices (OR = 4.412; P = 0.017), unaccompanied with gastric varices (OR = 7.025; P = 0.003) and frequency of endoscopic variceal ligation ≥one time per 4 months (OR = 3.834; P = 0.034) as independent factors of non-high-risk varices. All significant predictors were incorporated into a nomogram to predict the residual high-risk varices, which showed a notable accuracy with the concordance index (0.833). CONCLUSION: The nomogram-based prediction of residual high-risk varices can be used for risk stratification in cirrhosis patients with gastroesophageal varices.

Hepatopulmonary syndrome: the role of intra-abdominal hypertension and a novel mouse model.

OBJECTIVE: Hepatopulmonary syndrome (HPS) is considered as a triad of chronic liver disease, pulmonary vascular ectasia and severe hypoxemia. The study aims to investigate the pathological mechanism of intra-abdominal pressure (IAP) in HPS and establish a novel mouse model. METHODS: Fifty male ICR mice were randomly divided into experimental and control group, receiving subcutaneous injection of carbon tetrachloride and water, respectively. Mice in experimental group were then divided into 4 sub-groups with the intraperitoneal injection of different volume of albumin to form different IAP (0, 5, 10 and 20 cmH2O). All the mice were then sacrificed 24 hours later and blood gas analysis was conducted. In addition, liver and lung histopathology was also examined. RESULTS: Blood gas analysis in different IAP suggested the respiratory alkalosis. Arterial partial pressure of oxygen significantly decreased in the IAP=10 cmH2O (68.13 ± 3.56, P<0.01) and 20 cmH2O (66.00 ± 3.78, P<0.01). Alveolar-arterial oxygen pressure difference increased markedly in the IAP=10 cmH2O (54.60 ± 6.80, P<0.001) and 20 cmH2O (57.04 ± 5.60, P<0.001). According to lung histopathology, macrophages were found to accumulate in the alveolar spaces and the widened alveolar walls were detected. In addition, there was visible blood stasis in the alveolar walls and numerous red blood cells extravasated into air space in the IAP=10 and 20 cmH2O. CONCLUSIONS: Our study suggested that intra-abdominal hypertension was a significant pathological mechanism of HPS. Meanwhile, we have established a novel mouse model that will now be optimized with further investigation of the mechanism and therapeutic targets of HPS.