No abstract

A I M : To i n v e s t i g a t e t h e s u p p r e s s i v e e f f e c t o f saikosaponin-d (SSd) on hepatic fibrosis in rats inducedby CCl4 injections in combination with alcohol and high fat, low protein feeding and its relationship with the expression of nuclear factor-κB (NF-κB), tumor necrosis factor-alpha (TNF-α) and interleukins-6 (IL-6). METHODS:Hepatic fibrosis models were induced by subcutaneous injection of CCl4 at a dosage of 3 mL/kg in rats. At the same time, rats in treatment groups were injected intraperitoneally with SSd at different doses (1.0, 1.5 and 2.0 mg/kg) once daily for 6 wk in combination with CCl4, while the control group received olive oil instead of CCl4. At the end of the experiment, rats were anesthetized and killed (except for 8 rats which died during the experiment; 2 from the model group, 3 in high-dose group, 1 in medium-dose group and 2 in lowdose group). Hematoxylin and eosin (HE) staining and Van Gieson staining were used to examine the changes in liver pathology. The levels of alanine aminotransferase (ALT), triglyeride (TG), albumin (ALB), globulin (GLB), hyaluronic acid (HA) and laminin (LN) in serum and the content of hydroxyproline (HYP) in liver were measured by biochemical examinations and radioimmuneoassay, respectively. In addition, the expression of TNF-α and IL-6 in liver homogenate was evaluated by enzymelinked immunosorbent assay (ELISA) and the levels of NF-κBp65 and I-κBα in liver tissue were analyzed by Western blotting. 42.15 ± 8.25 ng/mL vs 19.83 ± 3.12 ng/mL, LN: 27.56 ± 4.21 ng/mL vs 13.78 ± 2.57 ng/mL, HYP: 27.32 ± 4.32 μg/mg vs 16.20 ± 3.12 μg/mg, TNF-α: 4.38 ± 0.76 ng/L vs 1.94 ± 0.27 ng/L, IL-6: 28.24 ± 6.37 pg/g vs 12.72 ± 5.26 pg/g, respectively, P < 0.01). SSd also decreased ALB in serum (28.49 ± 4.93 g/L vs 37.51 ± 3.17 g/L, P < 0.05). Moreover, the expression of NF-κB p65 in the liver of treated groups was lower than that in model groups while the expression of I-κBα was higher in treated group than in model group (P < 0.01). The expression of NF-κBp65 and TNF-α had a positive correlation with the level of HA in serum of rats after treatment with CCl4 (r = 0.862, P < 0.01; r = 0.928, P < 0.01, respectively). RESULTS: CONCLUSION:SSd attenuates CCl4-induced hepatic fibrosis in rats, which may be related to its effects of hepato-protective and anti-inflammation properties, the down-regulation of liver TNF-α, IL-6 and NF-κBp65 expression and the increased I-κBα activity in liver.

IMPORTANCE Atezolizumab plus bevacizumab as a first-line therapy for patients with unresectable or metastatic hepatocellular carcinoma has been shown to improve overall and progression-free survival compared with standard sorafenib treatment. However, because of the high cost of atezolizumab plus bevacizumab, assessment of its value by considering both efficacy and cost is needed.OBJECTIVE To evaluate the cost-effectiveness of atezolizumab plus bevacizumab vs sorafenib for patients with unresectable or metastatic hepatocellular carcinoma from a US payer perspective. DESIGN, SETTING, AND PARTICIPANTS This economic evaluation was performed from Junethrough September 2020, with a 6-year investment time period. Hypothetical patients were male and female adults 18 years or older who had a diagnosis of locally advanced metastatic or unresectable hepatocellular carcinoma confirmed by histologic or clinical features. MAIN OUTCOMES AND MEASURESHealth care costs (adjusted to 2020 US dollars), life-years, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER) of atezolizumab plus bevacizumab vs sorafenib were examined using a partitioned survival model. One-way deterministic and probabilistic sensitivity analyses were used to examine model uncertainty. The model was also used to estimate price reductions of atezolizumab plus bevacizumab that would achieve more favorable cost-effectiveness. RESULTSIn the base case analysis of a hypothetical sample of 424 patients, atezolizumab plus bevacizumab was associated with an increase of 0.623 life-years (1.840 vs 1.218 life-years) and 0.484 QALYs (1.412 vs 0.928 QALYs

No abstract

BACKGROUNDRegimens involving direct-acting antiviral agents (DAAs) are recommended for the treatment of infection with hepatitis C virus (HCV) genotypes 1, 2 and 3. But real-world data is still not enough, especially in Asia.AIMTo investigate the efficacy and safety of DAA-based regimens in a real-life setting in China.METHODSThis study included 366 patients infected with HCV genotypes 1, 2 and 3, with or without cirrhosis, who were observed between May 2015 and December 2018. They were treated with ledipasvir and sofosbuvir (SOF) (genotype 1) with or without ribavirin (RBV), SOF and RBV (genotype 2), or SOF and daclatasvir (genotype 3), with or without RBV, for 12 or more wk. The participants’ sustained virological responses (SVR) at post-treatment week 12 (SVR12) was the primary endpoint. The occurrence of adverse events and drug-drug interactions were recorded.RESULTSIn the 366 patients, genotype 1 (59.0%) was the most common genotype, followed by genotypes 2 (34.4%) and 3 (6.6%). Liver cirrhosis was diagnosed in 154 (42.1%) patients. Fifty (13.7%) patients were treatment-experienced. Intention-to-treat analysis revealed that SVR12 was 86.3% (316/366). For modified intention-to-treat analysis, SVR12 was achieved in 96.6% of overall patients (316/327), 96.3% in patients with genotype 1, 97.5% in those with genotype 2, and 95.0% in those with genotype 3. Most of the treatment failures were due to lack of follow-up (3 cases had non-responses, 1 had virological breakthrough, 11 relapsed and 36 did not participate in the follow-up). There was no significant difference in SVR between different genotypes and liver statuses (P < 0.05). Patients with lower alanine aminotransferase levels at baseline who achieved an end of treatment response were more likely to achieve SVR12 (P < 0.05). High SVR was observed regardless of age, gender, liver status, alpha-fetoprotein, HCV RNA levels or history of antiviral therapy (P > 0.05 for all). The cumulative hepatocellular carcinoma occurrence and recurrence rate after using the DAAs was 0.9%. Most of the adverse events were mild. We found two cases of special adverse events. One case involved facial and bilateral lower extremity edema, and the other case showed an interesting change in lipid levels while on medication. No severe adverse events were noted.CONCLUSIONThe DAA-based regimens tested in this study have excellent effectiveness and safety in all patients infected with HCV genotypes 1, 2 and 3, including those with cirrhosis.

Severe hand, foot, and mouth disease (HFMD) is likely to develop critical complications such as brainstem encephalitis, acute pulmonary edema, and circulatory failure, which cause child mortality during outbreaks. This study aims to investigate factors that predict the severity of HFMD. One hundred sixteen in-patient children with severe HFMD and 202 with mild HFMD were retrospectively enrolled. Potential factors were collected for each child including sex, age, residence, modes of delivery, birth weight, virus types causing HFMD, and virus exposure history. Univariate and multivariable logistic regression were used to determine which factors were associated with HFMD severity. In the univariate analysis, breastfeeding (OR 0.514, 95 % CI 0.309-0.856), rural residence (OR 1.971, 95 % CI 1.239-3.137), current Enterovirus 71 (EV71) infection (OR 2.539, 95 % CI 1.504-4.287), and previous Epstein-Barr virus (EBV) exposure (OR 3.136, 95 % CI 1.863-5.278) were each associated with the severity of HFMD. In the multivariate model, breastfeeding (OR 0.570, 95 % CI 0.332-0.980), rural residence (OR 1.973, 95 % CI 1.202-3.237), current EV71 infection (OR 2.290, 95 % CI 1.315-3.987), and previous EBV exposure (OR 2.550, 95 % CI 1.470-4.422) remained independently associated with the severity of HFMD. In conclusion, previous EBV exposure, EV71 infection, and rural residence are risk factors for severe HFMD; breastfeeding is a protective factor.

BackgroundSevere hand, foot, and mouth disease (HFMD) is sometimes associated with serious complications such as acute heart failure that can cause substantial child mortality. N-terminal pro-brain natriuretic peptide (NT-proBNP) is a sensitive and specific biomarker of congestive heart failure. The aim of this study was to use plasma NT-proBNP levels to establish the severity of childhood HFMD.MethodsA retrospective study was performed in 128 Chinese patients with severe HFMD and 88 patients with mild HFMD treated between January 2014 and October 2015. Univariate and multiple logistic regression analyses were used to analyze the risk factors for severe HFMD. NT-proBNP levels were analyzed in 128 severe HFMD patients, and the predictive value of NT-proBNP was assessed by receiver operating characteristic analyses.ResultsMultivariate analysis controlling for several potential confounders showed that enterovirus 71 infection [odds ratio (OR) 19.944, 95 % confidence interval (CI) 6.492–61.271], peripheral WBC count (OR 3.428, 95 % CI 1.186–9.914), fasting glucose (OR 19.428, 95 % CI 2.236–168.784), procalcitonin (OR 9.084, 95 % CI 3.462–23.837, and NT-proBNP (>125 pg/mL) (OR 16.649, 95 % CI 4.731–58.585) were each associated with the severity of HFMD. The 45 dead severe patients had higher pre-procedural levels of NT-proBNP than the 83 cured severe patients (12776 ± 13115 versus 1435 ± 4201 pg/mL, P < 0.001). An NT-proBNP cutoff value of 982 pg/mL predicted mortality with 87 % sensitivity and 86 % specificity.ConclusionPlasma NT-pro-BNP level appears to be a useful biological marker for predicting the severity and mortality of HFMD.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-016-1929-9) contains supplementary material, which is available to authorized users.

Hand, foot, and mouth disease (HFMD) caused by enterovirus 71 (EV71) presents with a wide variety of clinical manifestations. Host immune response is a factor that influences disease susceptibility and severity. We investigated the potential association of gene polymorphisms in the pattern recognition receptor (PRR) pathway with the risk and severity of EV71 infection. A total of 180 EV71 HFMD cases (108 severe case; 72 mild cases) were enrolled. A group of 201 sex- and age-matched children was included as a control. All subjects were genotyped for the most common single-nucleotide polymorphisms (SNPs) in the PRR and the PRR signaling pathway using the SNPscan multiple SNP typing method. Binary logistic regression analysis revealed statistically significant differences in polymorphism of RIG-1 between patients and controls (rs3739674 G vs C: OR = 1.502, 95%CI: 1.120-2.014; rs9695310 G vs C: OR = 1.782, 95%CI: 1.312-2.419). Polymorphisms of RIG-1 rs3739674 (G vs C: OR = 2.047, 95%CI: 1.307-3.205) and TLR3 rs5743305 (A vs T: OR = 0.346, 95%CI: 0.212-0.566) were found to be associated with disease severity. The results indicated that RIG-1 (rs3739674 and rs9695310) polymorphisms are associated with an increased risk of EV71-induced HFMD in Chinese children, whereas RIG-1 rs3739674 and TLR3 rs5743305 polymorphisms are associated with disease severity. These findings support an important role of innate immune mechanism in EV71 infection.