Allegretti, Andrew S.Subramanian, Ram M.Francoz, ClaireOlson, Jody C....
7页
查看更多>>摘要：Hepatorenal syndrome-acute kidney injury (HRS-AKI) is a serious complication of severe liver disease with a clinically poor prognosis. Supportive care using vasoconstrictors and intravenous albumin are the current mainstays of therapy. Terlipressin is an efficacious vasoconstrictor that has been used for 2 decades as the first-line treatment for HRS-AKI in Europe and has demonstrated greater efficacy in improving renal function compared to placebo and other vasoconstrictors. One of the challenges associated with terlipressin use is monitoring and mitigating serious adverse events, specifically adverse respiratory events, which were noted in a subset of patients in the recently published CONFIRM trial, the largest randomized trial examining terlipressin use for HRS-AKI. In this article, we review terlipressin's pharmacology, hypothesize how its mechanism contributes to the risk of respiratory compromise and propose strategies that will decrease the frequency of these events by rationally selecting patients at lower risk for these events.
查看更多>>摘要：Hepatocellular carcinoma (HCC) is the fourth most lethal malignancy with an increasing incidence worldwide. Management of HCC has followed several clinical staging systems that rely on tumour morphologic characteristics and clinical variables. However, these algorithms are unlikely to profile the full landscape of tumour aggressiveness and allow accurate prognosis stratification. Noninvasive imaging biomarkers on computed tomography (CT) or magnetic resonance imaging (MRI) exhibit a promising prospect to refine the prognostication of HCC. The Liver Imaging Reporting and Data System (LI-RADS) is a comprehensive system for standardizing the terminology, techniques, interpretation, reporting and data collection of liver imaging. At present, it has been widely accepted as an effective diagnostic system for HCC in at-risk patients. Emerging data have provided new insights into the potential of CT/MRI LI-RADS in HCC prognostication, which may help refine the prognostic paradigm of HCC that promises to direct individualized management and improve patient outcomes. Therefore, this review aims to summarize several prognostic imaging features at CT/MRI for patients with HCC; the available evidence regarding the use of LI-RDAS for evaluation of tumour biology and clinical outcomes, pitfalls of current literature, and future directions for LI-RADS in the management of HCC.
Veracruz, NicoletteGish, Robert G.Cheung, RamseyChitnis, Amit S....
9页
查看更多>>摘要：Background and Aims Advances in hepatitis B virus (HBV) and hepatitis C virus (HCV) therapies have improved morbidity and mortality, but global disparities in viral hepatitis outcomes remain. We evaluate global trends in the impact of HBV and HCV on disability-adjusted life years (DALYs). Methods Using data from the 2010-2019 Global Burden of Diseases Study (GBD), overall all-cause DALYs for patients with acute HBV or HCV, HBV- or HCV-related cirrhosis, and HBV- or HCV-related hepatocellular carcinoma (HCC) was calculated as the sum of years of life lost because of premature death and years lived with disability. DALYs were presented as age-standardized rates per 100 000 population stratified by age and sex. Results From 2010 to 2019, the overall global impact of HBV on DALYs per 100 000 decreased from 27.6 to 20.9 for acute HBV and 168.6 to 129.8 for HBV-related cirrhosis but remained stable for HBV-related HCC. The impact of HCV on DALYs per 100 000 decreased from 5.23 to 3.3 for acute HCV, 159.2 to 146.2 for HCV-related cirrhosis, and 37.5 to 34.9 for HCV-related HCC. We observed significant differences in the impact of HBV and HCV on DALYs when stratified by world regions. Conclusion Decreases in HBV and HCV DALYs from 2010 to 2019 were observed. Disparities in DALY improvements across world regions suggest unequal access to viral hepatitis care and treatment. Achieving goals of viral hepatitis elimination will require enhanced prevention efforts and funding for high-burden regions and regions that have not had substantial reductions in DALYs because of HBV and HCV.
查看更多>>摘要：Background and Aims: The immunologic features involved in the immune-tolerant phase of chronic hepatitis B (CHB) virus (HBV) infection are unclear. The hepatitis B virus X (HBx) protein disrupts IFN-beta induction by downregulating MAVS and may destroy subsequent HBV-specific adaptive immunity. We aimed to analyse the impacts of genetic variability of HBx in CHB patients on the immune-tolerant phase during long-term follow-up. Methods: Children with CHB in the immune-tolerant phase were recruited and followed longitudinally. HBx gene sequencing of infecting HBV strains was performed, and the effects of HBx mutations on the immune-tolerant phase were assessed. Restoration of the host immune response to end the immune-tolerant phase was investigated by immunoblotting, immunostaining, ELISA and reporter assays of MAVS/IFN-beta signalling in liver cell lines, patient liver tissues and the HBV plasmid replication system. Results: A total of 173 children (median age, 6.92years) were recruited. Patients carrying HBx R87G, I127V and R87G +I127V double mutations exhibited higher cumulative incidences of immune-tolerant phase breakthrough (p = .011, p = .006 and p = .017 respectively). Cells transfected with HBx R87G and I127V mutants and pHBV1.3-B6.3 replicons containing the HBx R87G and I127V mutations exhibited statistically increased levels of IFN-beta, especially under poly(I:C) stimulation or Flag-MAVS cotransfection. HA-HBx wild-type interacted with Flag-MAVS and enhanced its ubiquitination, but this ability was diminished in the R87G and 1127V mutants. Conclusions: HBx suppresses IFN-beta induction. R87G and 1127V mutation restored IFN-beta production by preventing MAVS degradation, contributing to curtailing the HBV immune-tolerant phase in CHB patients.
查看更多>>摘要：Background and Aims In vitro fertilization-embryo transfer (IVF-ET) may increase the risk of mother-to-child transmission (MTCT) of hepatitis B virus (HBV). The purpose of this study was to investigate the impact and safety of IVF-ET on MTCT in women with chronic HBV infection (CHB). Methods The data of 298 women who got pregnant by IVF-ET and their 375 children were collected retrospectively. Mothers were divided into the CHB group (n = 224) and the control group (HBsAg negative, n = 74). After birth, newborns were routinely vaccinated with the hepatitis B vaccine, and infants in the CHB group were injected with hepatitis B immunoglobulin within 2 h after birth. Demographic information, clinical data and laboratory test results were collected. The primary outcome measures were the MTCT rate of HBV, and the secondary outcome measures were the safety of the mother and infant. Results There was no case of HBV MTCT in all 282 newborns born in the CHB group and 93 neonates born in the control group. Of the two groups, the birth weight (3056.74 +/- 601.65 vs. 2926.24 +/- 704.86, P = .083), length (49.22 +/- 1.97 vs. 48.74 +/- 3.09, P = .167), 5-min Apgar score (9.97 +/- 0.21 vs. 9.90 +/- 0.51, P = .212), days of pregnancy (265.70 +/- 12.73 vs. 262.02 +/- 17.50, P = .064) and neonatal malformation rate (0.71% vs. 0, P = 1.000) were similar. Two cases of neonatal malformation occurred in the CHB group. The incidences of pregnancy and childbirth complications were similar between the two groups. Conclusion IVF-ET does not increase the risk of MTCT in women with chronic HBV infection, and it is safe for mothers and infants.
查看更多>>摘要：Purpose The purpose was to explore the value of liver fibrosis scores (fibrosis-4, BAAT score and BARD score) for incidence risk of stroke in a cohort study. Methods A total of 9088 participants without stroke history enrolled the follow-up. Three liver fibrosis scores (LFSs) including FIB-4, BARD score and BAAT score were adopted. The end point was stroke. Cox regression analysis was used to calculate hazard ratios and 95% confidence interval. Kaplan-Meier curve was used to show the probability of stoke in different levels of LFSs. Subgroup analysis showed the association between LFSs and stroke under different stratification. Restricted cubic spline could further explore whether there is a linear relationship between LFSs and stroke. Finally, we used C-statistics, Net Reclassification Index (NRI) and Integrated Discrimination Improvement (IDI) to assess the discriminatory power of each LFS for stroke. Results During a median follow-up time of 4.66 years, 272 participants had a stroke. Through the baseline characteristics, we observed that the stroke incidence population tends to be male and older. It was shown by Kaplan-Meier that three LFSs were associated with stroke and high levels of LFSs significantly increase the probability of stroke. In the univariate Cox regression analysis, the HR of stroke risk was 6.04 (4.14-8.18) in FIB-4, 2.10 (1.45-3.04) in BAAT score and 1.81 (1.38-2.38) in BARD score by comparing the high level with the low level at each LFSs. The adjusted HRs for three LFSs were 2.05 (1.33-3.15) in FIB-4, 1.61 (1.10-2.35) in BAAT score and 1.54 (1.17-2.04) in BARD score by comparing the high group with low group. We found that multivariable-adjusted HRs of three LFSs still increased for stroke when stratified by various factors in subgroup analysis. Moreover, after adding LFSs to original risk prediction model which consist of age, sex, drinking, smoking, hypertension, diabetes, low-density lipoprotein cholesterol, total cholesterol and triglycerides, we found that new models have higher C-statistics of stroke. Furthermore, we calculated Net Reclassification Index (NRI) and Integrated Discrimination Improvement (IDI) to show the ability of LFSs to predict stroke. Conclusions Our study showed that three LFSs were associated with stroke amongst middle-aged populations in rural areas of Northeast China. Furthermore, it suggests that LFSs can be used as a risk stratification tool to predict stroke.
查看更多>>摘要：Background and Aims ElastPQ is a point shear wave elastography technique used to non-invasively assess liver fibrosis. We compared liver stiffness measurements (LSM) by ElastPQ and fibroscan transient elastography (F-TE) in a cohort of patients with non-alcoholic fatty liver disease (NAFLD). We further evaluated the performance of ElastPQ in a subgroup of patients with available liver histology. Materials and Methods We included patients with NAFLD who presented in a dedicated multidisciplinary clinic. Anthropometric parameters, blood tests and elastography measurements were obtained using F-TE and ElastPQ as part of routine clinical care. Results We enrolled 671 patients with NAFLD, mean age 55.8 +/- 13 years, body mass index (BMI) 31.5 +/- 5.7 kg/m(2), 56.6% males, 41% diabetes, 53.7% hypertension, 68% dyslipidaemia. ElastPQ showed an excellent correlation with F-TE (Spearman's r = 0.80, p < .001), which was better for mild/moderate stages of fibrosis. Independent predictors of a >2 kPa discrepancy between the two techniques were a larger waist circumference and F-TE >= 10 kPa. In the subgroup of 159 patients with available histology, ElastPQ showed similar diagnostic accuracy with F-TE in staging liver fibrosis (ElastPQ area under the curves 0.84, 0.83, 0.86 and 0.95, for F >= 1, F >= 2, F >= 3 and F = 4 respectively). Optimal cut-off values of ElastPQ for individual fibrosis stages were lower than those of F-TE. Conclusions ElastPQ shows an excellent correlation with F-TE in patients with NAFLD, which was better for lower LSM. The optimal cut-off values of ElastPQ are lower than those of F-TE for individual stages of fibrosis. ElastPQ has similar diagnostic accuracy to F-TE for all stages of fibrosis.
查看更多>>摘要：Background and Aims Prior studies suggested that patients with autoimmune liver diseases (AiLDs) had an increased risk of cancer, whereas the causal effect remained unclear. Methods Meta-analyses concerning the relationship between AiLD and cancer risk were performed to calculate the pooled relative risk (RR) and corresponding 95% confidence intervals (CIs). Then, the associations with a p value of A total of 37 cohort studies covering more than 34 558 patients were included, and we observed an increased risk of overall cancers (pooled RR = 3.64, 95% CI: 2.64-5.03, p < .001) and cancer-related death (pooled RR = 2.48, 95% CI: 1.73-3.53, p < .001) for patients with AiLD. Besides, overall and several site-specific cancers risk were found in patients with primary biliary cholangitis (PBC), autoimmune hepatitis (AIH), and primary sclerosing cholangitis (PSC) (p < .05). However, associations between genetically predisposed AIH, PBC, and PSC and the risk of specific cancers did not reach a significant level, except for PBC and gastric cancer (OR = 0.96, 95% CI: 0.93-0.99; p = .02). Conclusions In addition to hepatobiliary cancer, results from the meta-analyses suggest that patients with AiLD might have an increased risk of several extrahepatobiliary cancers. However, the causal role of AiLD in cancer development needs to be further investigated.
查看更多>>摘要：Background and aims Patients with cirrhotic refractory ascites ineligible for transjugular intrahepatic shunt (TIPSS) have limited treatment options apart from repeated large volume paracentesis. The alfapump (R) is an implantable device mobilizing ascites from the peritoneal cavity to the bladder, from where it can be excreted. The aim of this observational cohort study was to prospectively investigate safety and efficacy of the device in a real-world cohort with cirrhotic refractory ascites and contraindications for TIPSS. Methods A total of 106 patients received an implant at 12 European centres and were followed up for up to 24 months. Complications, device deficiencies, frequency of paracentesis, clinical status and survival were recorded prospectively. Results Approximately half of the patients died on-study, about a quarter was withdrawn because of serious adverse events leading to explant, a sixth were withdrawn because of liver transplant or recovery, and nine completed follow-up. The most frequent causes of on-study death and complication-related explant were progression of liver disease and infection. The device reduced the requirement for large-volume paracentesis significantly, with more than half of patients not having required any post-implant. Survival benefits were not observed. Device-related reinterventions were predominantly caused by device deficiencies. A post-hoc comparison of the first 50 versus the last 50 patients enrolled revealed a decreased reintervention rate in the latter, mainly related to peritoneal catheter modifications. Conclusions The device reduced paracentesis frequency in a real-world setting. Technical complications were successfully decreased by optimization of management and device modification (NCT01532427).
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Wiley