Mother‐to‐child transmission (MTCT) is a major obstacle in the elimination of hepatitis B virus (HBV) infection. Telbivudine (LdT) and tenofovir disoproxil fumarate (TDF) are the two most common antiviral medicines for preventing MTCT. However, the efficacy and safety of LdT and TDF in preventing HBV vertical transmission during the second to third trimester have not been compared rigorously. Therefore, we carried out a prospective multicentre cohort study of chronic hepatitis B in mothers with HBV DNA > 106 IU/mL, receiving LdT or TDF during the second to third trimester. Among the 893 mothers enrolled, 857 (LdT/TDF/untreated group (NTx) = 396/325/136) completed consecutive follow‐up with 854 infants (LdT/TDF/NTx = 395/323/136). LdT and TDF treatment resulted in a similar decrease of HBV DNA in mothers at delivery. Multivariate analysis indicated that only HBsAg titre at the baseline correlated with viral DNA decrease (P = 0.015). With intention‐to‐treat analysis, MTCT rates in the LdT, TDF and NTx group were 4.41%, 2.42% and 22.08%, respectively. An increasing vertical transmission rate was found to be closely associated with higher HBsAg titre, 5.32% and 17.65% infection rate was estimated in infants born to mothers with HBsAg > 4 and >5 log10 IU/mL, respectively. No serious side effects were reported in either mothers or infants. LdT and TDF treatments were well tolerated and showed comparable efficacy in reducing MTCT. Higher risk of MTCT was shown in pregnant women with HBsAg > 4 log10IU/mL.
The European Society for Clinical Nutrition and Metabolism (ESPEN) guidelines recommend Royal Free Hospital-Nutritional Prioritizing Tool (RFH-NPT) to identify malnutrition risk in patients with liver disease. However, little is known about the application of RFH-NPT to screen for the risk of malnutrition in China, where patients primarily suffer from hepatitis virus-related cirrhosis. A total of 155 cirrhosis patients without liver cancer or uncontrolled comorbid illness were enrolled in this prospective study. We administered the Nutritional Risk Screening 2002 (NRS-2002), RFH-NPT, Malnutrition Universal Screening Tool(MUST), and Liver Disease Undernutrition Screening Tool (LDUST) to the patients within 24 h after admission and performed follow-up observations for 1.5 years. The RFH-NPT and NRS-2002 had higher sensitivities (64.8% and 52.4%) and specificities (60% and 70%) than the other tools with regard to screening for the malnutrition risk in cirrhotic patients. The prevalence of nutritional risk was higher under the use of RFH-NPT against the NRS-2002(63% vs. 51%). RFH-NPT tended more easily to detect the malnutrition risk in patients with advanced Child-Pugh classes (B and C) and lower MELD scores (<15) compared with NRS-2002. The RFH-NPT score was an independent predictive factor for mortality. Patients identified as being at high malnutrition risk with the RFH-NPT had a higher mortality rate than those at a low risk; the same result was not obtained with the NRS-2002. Therefore, we suggest that using RFH-NPT improves the ability of clinicians to predict malnutrition risk in patients with cirrhosis primarily caused by hepatitis virus infection at an earlier stage.
Liver sinusoids serve as the first line of defense against extrahepatic stimuli from the intestinal tract. Hepatic stellate cells (HSCs) are pericytes residing in the perisinusoidal space that integrate cytokine-mediated inflammatory responses in the sinusoids and relay these signals to the liver parenchyma. Oxidative stress has been shown to promote inflammation during acute liver failure (ALF). Whether and how oxidative stress is involved in HSC inflammation during ALF remains unclear. Level of systemic oxidative stress is reflected by superoxide dismutase (SOD). Thus, ALF patients were recruited to investigate the correlation between plasma SOD levels and clinical features. Liver tissues were collected from chronic hepatitis patients by biopsy and from ALF patients who had undergone liver transplantation. SOD2 expression and HSCs activation were investigated by immunohistochemistry. Inflammation, mitophagy, and apoptosis were investigated by immunoblot analysis and flow cytometry in HSCs treated with lipopolysaccharide (LPS) and reactive oxygen species (ROS) donors. The plasma SOD level was significantly increased in patients with ALF compared with those with cirrhosis (444.4 ± 23.58 vs. 170.07 ± 3.52 U/ml, P < 0.01) and was positively correlated with the Model for End-Stage Liver Disease-Na score ( R = 0.4720, P < 0.01). In vivo observations revealed that SOD2 immunostaining was increased in ALF patients and mice models, and in vitro experiments demonstrated that LPS/ROS promoted inflammation via inhibiting mitophagy. Moreover, the regulation of inflammation was apoptosis independent in HSCs. LPS-induced increases in oxidative stress promote inflammation through inhibiting mitophagy in HSCs during the process of ALF, providing a novel strategy for the treatment of patients with ALF. NEW & NOTEWORTHY Here we demonstrate that the serum superoxide dismutase (SOD) level is significantly increased in patients with acute liver failure (ALF), and, correlated with the Model for End-Stage Liver Disease-Na score, SOD level dropped in the remission stage of ALF. We identify that, in liver tissue from ALF patients and mice models, manganese-dependent SOD was overexpressed, and show lipopolysaccharide/HO inhibits mitophagy via reactive oxygen species in hepatic stellate cells (HSCs). We show that inhibited mitophagy promotes inflammation in HSCs, whereas mitophagy inducer rescues HSCs from lipopolysaccharide-induced inflammation.
The seroprevalence of hepatitis B virus (HBV) and its impact on pregnancy outcomes of women from Shaanxi Province (China) was assessed. Risk factors for mother-to-child transmission (MTCT) were evaluated based on HBV-related seroprevalence data.Viral markers and biochemical parameters were assessed in HBsAg-positive mothers and their infants out of 13,451 cases recruited. A pretested and structured questionnaire was used to test the general HBV knowledge. Descriptive statistics and logistic regression analysis were done to reveal possible risk factors for MTCT.The overall prevalence of HBsAg in pregnant women was 7.07% (951/13,451), and a rate as high as 9.40% was observed. Among the HBsAg-positive pregnant women, 30.49% (290/951) were HBeAg-positive, 22.08% (210/951) had HBV DNA levels >106 IU/mL and only 16.19% with a high risk of MTCT (34/210) had received antiviral treatment. The overall MTCT rate was 5.21%. Noteworthy, the risk ratio and 95% confidence interval (95% CI) of MTCT in HBeAg-negative mothers with HBV DNA levels >2 × 103 IU/mL and HBsAg >104 IU/mL was 26.062 (2.633–258.024), which was significantly higher than that of HBeAg-positive mothers with HBV DNA level >106 IU/mL. Moreover, the awareness and knowledge about HBV transmission, risk factors, and intervention for MTCT were generally lacking among HBsAg-positive mothers.As a higher HBsAg seroprevalence and a higher MTCT rate among HBeAg-negative mothers with lower HBV DNA level was observed, our study emphasizes different interventional criteria for HBeAg-positive and HBeAg-negative mothers. Extensive health education, routine screening, and immunization against HBV during pregnancy are highly warranted to minimize the possibility of perinatal transmission.
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