A phase 3, open-label study of daclatasvir plus asunaprevir in Asian patients with chronic hepatitis C virus genotype 1b infection who are ineligible for or intolerant to interferon alfa therapies with or without ribavirin
PubMed | Shanghai JiaoTong University, Catholic University of Korea, Tangdu Hospital, Tianjin Second Peoples Hospital and 10 more.
Type: Journal Article | Journal: Journal of gastroenterology and hepatology | Year: 2016
Daclatasvir plus asunaprevir has demonstrated efficacy and safety in patients with chronic hepatitis C virus genotype 1b infection. This study focused on evaluating daclatasvir plus asunaprevir in interferon (ribavirin)-ineligible or -intolerant Asian patients with genotype 1b infection from mainland China, Korea, and Taiwan.Interferon (ribavirin)-ineligible and -intolerant patients with genotype 1b infection received daclatasvir 60mg tablets once daily plus asunaprevir 100mg soft capsules twice daily for 24weeks. The primary endpoint was sustained virologic response at post-treatment week 24 (SVR24).Of the 159 patients treated, 89.3% were Chinese, 65.4% were female, and 73.6% were interferon-intolerant. Cirrhosis was present in 32.7% of patients, and 40.3% had IL28B non-CC genotypes. SVR24 was achieved by 145/159 (91.2%) patients (100% concordance with SVR12) and was similarly high in cirrhotic patients (47/52, 90.4%). SVR24 was higher in patients without baseline NS5A (L31M or Y93H) resistance-associated variants (RAVs) (137/139, 98.6%), including those with cirrhosis (43/44, 97.7%). Prevalence of baseline NS5A RAVs was low (19/159, 11.9%), particularly in mainland China (10/127, 7.9%). One death (0.6%), five serious adverse events (3.1%), and three grade 4 laboratory abnormalities (1.9%) occurred on treatment; none were considered related to study drugs. Two patients (1.3%) discontinued because of adverse events. Treatment was generally well tolerated regardless of cirrhosis status.Daclatasvir plus asunaprevir achieved a SVR24 rate of 91.2%, rising to 98.6% in patients without baseline NS5A RAVs, and was generally well tolerated in interferon (ribavirin)-ineligible or -intolerant patients with genotype 1b infection from mainland China, Korea, and Taiwan.
PubMed | Chinese University of Hong Kong, University of Bordeaux 1, Shanghai JiaoTong University, Tianjin Second Peoples Hospital and 11 more.
Type: | Journal: Journal of hepatology | Year: 2016
The prevalence of fatty liver underscores the need for non-invasive characterization of steatosis, such as the ultrasound-based controlled attenuation parameter (CAP). Despite good diagnostic accuracy, clinical use of CAP is limited due to uncertainty regarding optimal cut-offs and the influence of covariates. We therefore conducted an individual patient data meta-analysis.A review of the literature identified studies containing histology controlled CAP data (M probe, vibration controlled transient elastography with Fibroscan) for grading of steatosis (S0-S3). Receiver operating characteristic analysis after correcting for center effects was used as well as mixed models to test the impact of covariates on CAP. The primary outcome was establishing CAP cut-offs for distinguishing steatosis grades.Data from 19/21 eligible papers were provided, comprising 3830/3968 (97%) of patients. Considering data overlap and exclusion criteria, 2735 patients were included in the final analysis (37% hepatitis B, 36% hepatitis C, 20% NAFLD/NASH, 7% other). Steatosis distribution was 51%/27%/16%/6% for S0/S1/S2/S3. CAP values in dB/m (95% CI) were influenced by several covariates with an estimated shift of 10 (4.5-17) for NAFLD/NASH patients, 10 (3.5-16) for diabetics and 4.4 (3.8-5.0) per BMI unit. Areas under the curves were 0.823 (0.809-0.837) and 0.865 (0.850-0.880) respectively. Optimal cut-offs were 248 (237-261) and 268 (257-284) for those above S0 and S1 respectively.CAP provides a standardized non-invasive measure of hepatic steatosis. Prevalence, etiology, diabetes, and BMI deserve consideration when interpreting CAP. Longitudinal data are needed to demonstrate how CAP relates to clinical outcomes.There is an increase in fatty liver for patients with chronic liver disease, linked to the epidemic of the obesity. Invasive liver biopsies are considered the best means of diagnosing fatty liver. The ultrasound based controlled attenuation parameter (CAP) can be used instead, but factors such as the underlying disease, BMI and diabetes must be taken into account.
Xie L.,Tsinghua University |
Xie L.,Northeastern University China |
Wang T.,Tsinghua University |
Huang T.,Tsinghua University |
And 4 more authors.
Scientific Reports | Year: 2014
A novel label-free method based on breathing-induced vapor condensation was developed for detection of genetic point mutation. The dew-inspired detection was realized by integration of target-induced DNA ligation with rolling circle amplification (RCA). The vapor condensation induced by breathing transduced the RCA-amplified variances in DNA contents into visible contrast. The image could be recorded by a cell phone for further or even remote analysis. This green assay offers a naked-eye-reading method potentially applied for point-of-care liver cancer diagnosis in resource-limited regions.
PubMed | Phd Tianjin Institute Of Hepatology and Tianjin Second Peoples Hospital
Type: Journal Article | Journal: Pakistan journal of medical sciences | Year: 2017
To determine the role of serum procalcitonin (PCT) and C-reactive protein (CRP) in predicting spontaneous bacterial peritonitis (SBP) in patients with advanced liver cirrhosis.A total of 88 patients with advanced liver cirrhosis were enrolled for this study, which included 40 cases with SBP and 48 cases with CNNA. Bacterial cultures, ascitic fluid (AF) leukocyte, C-reactive protein (CRP) and serum PCT measurements were carried out prior to the use of antibiotics. Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic performance of procalcitonin levels.Serum PCT levels in advanced liver cirrhotic patients with SBP were significantly higher than those with CNNA. We used PCT 0.78 ng/mL as optimal cutoff value to diagnose SBP, for which the sensitivity and specificity was 77.5% and 60.4%. The area under the curve (AUC) was 0.706 (95% confidence interval: 0.576-0.798). The PCT level was significantly correlated with the AF WBC count (rs=0.404, P<0.01). However, there was no significant difference between SBP and CNNA patients in serum CRP levels.According to our findings, serum PCT levels seem to provide an early diagnostic accuracy in advanced liver cirrhotic patients with SBP.
PubMed | Tianjin University of Traditional Chinese Medicine, Nankai University, Tianjin Second Peoples Hospital and Tianjin Peoples Hospital
Type: | Journal: Molecular and cellular biochemistry | Year: 2017
At present, the main therapy for chronic renal failure (CRF) is dialysis and renal transplantation, but neither obtains satisfactory results. Human umbilical cord mesenchymal stem cells (huMSCs) are isolated from the fetal umbilical cord which has a high self-renewal and multi-directional differentiation potential. Icariin (ICA), a kidney-tonifying Chinese Medicine can enhance the multipotency of huMSCs. Therefore, this work seeks to employ the use of ICA-treated huMSCs for the treatment of chronic renal failure. Blood urea nitrogen and creatinine (Cr) analyses showed amelioration of functional parameters in ICA-treated huMSCs for the treatment of CRF rats at 3, 7, and 14 days after transplantation. ICA-treated huMSCs can obviously increase the number of cells in injured renal tissues at 3, 7, and 14 days after transplantation by optical molecular imaging system. Hematoxylin-eosin staining demonstrated that ICA-treated huMSCs reduced the levels of fibrosis in CRF rats at 14days after transplantation. Superoxide dismutase and Malondialdehyde analyses showed that ICA-treated huMSCs reduced the oxidative damage in CRF rats. Moreover, transplantation with ICA-treated huMSCs decreased inflammatory responses, promoted the expression of growth factors, and protected injured renal tissues. Taken together, our findings suggest that ICA-treated huMSCs could improve the kidney function in CRF rats.
Wang C.-Y.,Tianjin Second Peoples Hospital |
Lu W.,Tianjin Second Peoples Hospital |
Hu D.-S.,Tianjin Second Peoples Hospital |
Wang G.-D.,Rizhao Peoples Hospital |
Cheng X.-J.,Tianjin Medical University
World Journal of Gastroenterology | Year: 2014
AIM: To study the diagnostic value of controlled attenuation parameter (CAP), evaluated by transient elastography, for liver steatosis in patients with chronic hepatitis B (CHB).METHODS: Eighty-eight patients with CHB were enrolled in this study. All of the patients were subjected to transient elastography to determine CAP. These patients also underwent liver biopsy in the same period. Using liver biopsy as a reference, we determined receiver operating characteristic (ROC) curves for different endpoints. Areas under the ROC curves (AUCs) were used to evaluate the diagnostic importance of CAP for liver steatosis in patients with CHB.RESULTS: A positive correlation was observed between the AUCs of CAP and liver pathological stage (r = 0.582, P < 0.05). CAP was not correlated with inflammation degree and fibrosis degree (r = -0.025, P < 0.05; r = 0. 068, P < 0.05). The mean CAP value at S0 was 209.59 ± 41.25 dB/m, 223.84 ± 35.28 dB/m at S1, 274.17 ± 43.69 dB/m at S2, and 312.50 ± 25.44 dB/m at S3. CAP values among S0, S1, S2, and S3 were significantly different (F = 17.79, P < 0.01). The AUC values for CAP were 0.711 (0.592-0.870), 0.868 (0.748-0.989), and 0.974 (0.922-1.026) for S1, S2, and S3, respectively. The optimal cut-off values were 219.5, 230.0, and 283.5 dB/m.CONCLUSION: CAP is a novel tool that can be used to assess the degree of steatosis. © 2014 Baishideng Publishing Group Inc. All rights reserved.
Yang X.,Fudan University |
Yang X.,Kunming Medical University |
Gao J.Y.,Yeshiva University |
Wang J.,Tianjin Second Peoples Hospital |
Cheng J.,Fudan University
Discovery Medicine | Year: 2015
Chronic hepatitis B (CHB) virus infection can cause persistent hepatic inflammation and cirrhosis, which may lead to hepatocellular carcinoma (HCC). CHB is considered the dominant cause of HCC in Asia because of the endemic status of hepatitis B virus (HBV) infection. A persistently high viral load, long duration of infection, and cirrhosis are the major risk factors for developing HCC in CHB patients. Antiviral therapies using interferon (IFN) and nucleos(t)ide analogues (NAs) could suppress viral replication, reduce liver injury, and preserve liver function, thereby lowering the risk of developing HCC. Recurrence of HCC after therapy is closely related to high levels of HBV DNA at the initial stage. Western studies have found that persistent antiviral treatments on CHB patients could not only reduce their risk of developing HCC, but also prevent or delay HCC recurrence after liver transplantation, hepatic resection, or radiation therapies. This review will focus on Asian clinical studies, where there is a higher prevalence of CHB and HCC. The outcomes of antiviral therapies on HCC in these Asian studies were compared to those in the Western studies. © 2015, Discovery Medicine.
Luo M.,Ningxia Peoples Hospital |
Guo J.-Y.,Ningxia Peoples Hospital |
Cao W.-K.,Tianjin Second Peoples Hospital
World Journal of Gastroenterology | Year: 2015
Hepatic encephalopathy (HE) is a severe neuropsychiatric syndrome that most commonly occurs in decompensated liver cirrhosis and incorporates a spectrum of manifestations that ranges from mild cognitive impairment to coma. Although the etiology of HE is not completely understood, it is believed that multiple underlying mechanisms are involved in the pathogenesis of HE, and one of the main factors is thought to be ammonia; however, the ammonia hypothesis in the pathogenesis of HE is incomplete. Recently, it has been increasingly demonstrated that inflammation, including systemic inflammation, neuroinflammation and endotoxemia, acts in concert with ammonia in the pathogenesis of HE in cirrhotic patients. Meanwhile, a good number of studies have found that current therapies for HE, such as lactulose, rifaximin, probiotics and the molecular adsorbent recirculating system, could inhibit different types of inflammation, thereby improving the neuropsychiatric manifestations and preventing the progression of HE in cirrhotic patients. The antiinflammatory effects of these current therapies provide a novel therapeutic approach for cirrhotic patients with HE. The purpose of this review is to describe the inflammatory mechanisms behind the etiology of HE in cirrhosis and discuss the current therapies that target the inflammatory pathogenesis of HE. © 2015 Baishideng Publishing Group Inc. All rights reserved.
Li S.,Tianjin Second Peoples Hospital
World Chinese Journal of Digestology | Year: 2013
Hepatic fibrosis is characterized by progressive inflammation and deposition of extracellular matrix components. Several recent studies have demonstrated that the rennin-angiotensin system (RAS) plays a key role in hepatic fibrosis. In this review, we provide a comprehensive update of the role of the RAS in the pathogenesis of hepatic fibrosis. We will discuss the profibrotic mechanisms activated by the RAS. Studies that have utilized angiotensin receptor blockers and angiotensin-converting enzyme inhibitors to modulate the RAS to ameliorate hepatic fibrosis will also be discussed. © 2013 Baishideng. All rights reserved.
Joomye S.,Tianjin Medical University |
Yan D.,Tianjin Medical University |
Wang H.,Tianjin Medical University |
Zhou G.,Tianjin Second Peoples Hospital |
Wang G.,Tianjin Medical University
BMC Anesthesiology | Year: 2014
Background: We devised this study to quantify the effect of age on the consumption of cisatracurium under general anaesthesia, using a computer controlled closed loop infusion system. We further investigated this effect on, sufentanil and propofol consumption.Methods: 74 patients of physical status I and II, requiring general anaesthesia for elective abdominal surgery, were assigned to three groups. Patients in group 1 were aged from 20 to 45, group 2 were from 46 to 64, and group 3 above 65 years old. General Anesthesia was maintained with propofol and muscle paralysis was maintained using a closed-loop computer controlled infusion of cisatracurium. For analgesia, intermittent bolus of sufentanil 10 μg was given.Results: Cisatracurium consumption in group 1, 2 and 3 were 1.8 ± 0.3, 1.6 ± 0.4 and 1.3 ± 0.4 μg/kg/min respectively. There was significant difference of cisatracurium consumption between group 1 and 3 (P = 0.002), and the consumption of cisatracurium in group 3 was less as compared with group 2 (P = 0.04). The average recovery index of patients in group 1, 2 and 3 were 8.8 ± 2.6, 11.5 ± 2.9 and 12.7 ± 2.5 minutes respectively. There were difference between group 1 and 2 (P = 0.02). As compared with group 1, the recovery index was still longer in group 3 (P = 0.001). Patients in group 1, 2 and 3 consumed an average sufentanil 0.4 ± 0.1, 0.4 ± 0.1 and 0.3 ± 0.1 μg/kg/hr, respectively. There were statistical significant between group 1 and 3 (P < 0.0001), and the same trend was found between group 2 and 3 (P = 0.03). The Consumption of propofol in group 1, 2 and 3 were 5.1 ± 0.4, 4.3 ± 0.6 and 3.1 ± 0.5 mg/kg/hr. The difference in the propofol consumption was found statistically significant when comparing between any two groups.Conclusion: We concluded that the sensitivity of anesthetic agents increased with age. Less medication was required to achieve a desirable effect in older patients specially those above 65 years of age, and the drug effect was prolonged.Trial registration: ClinicalTrials.gov Identifier: NCT01785446. © 2014 Joomye et al.; licensee BioMed Central Ltd.