Hepatitis delta genotype 5 is associated with favourable disease outcome and better response to treatment compared to genotype 1.

与基因型 1 相比,丁型肝炎基因型 5 与有利的疾病结局和更好的治疗反应相关。

  • 影响因子:9.32
  • DOI:10.1016/j.jhep.2019.12.028
  • 作者列表:"Spaan M","Carey I","Bruce M","Shang D","Horner M","Dusheiko G","Agarwal K
  • 发表时间:2020-01-22

BACKGROUND AND AIMS:Co-infection with HDV causes rapid progression to liver cirrhosis and hepatic decompensation. Factors that are associated with disease progression are poorly understood. In this study we aim to identify risk factors associated with disease progression and better characterise clinical differences and treatment response between HDV genotype 1 and 5. METHODS:In this retrospective study, all patients under our care between 2005 and 2016 with HBV/ HDV co-infection (HBsAg+, anti-HDV antibodies positive) were analysed. Patients were excluded if follow-up was less than 6 months, if they had HCV and/or HIV co-infection or an acute HDV infection. Demographic data, stage of liver disease, development of liver complications and treatment response were recorded. RESULTS:One-hundred seven patients (mean age 36.0yr, 57% male) were followed for a median period of 4.4yr (range 0.6-28.1yr). 64% was of African and 17% of European origin with 28% of patients being cirrhotic at first visit. 43% patients had actively replicating HDV virus (anti-HDV-IgG+, anti-HDV-IgM+ or HDV RNA+) and 57% of patients were HDV exposed (anti-HDV-IgG+, HDV RNA-). Actively replicating HDV patients more often developed liver complications compared to patients with exposed HDV (p=0.002), but no differences in baseline characteristics were observed. HDV patients with genotype 5 less often developed cirrhosis or hepatic decompensation compared to patients with genotype 1. Twenty-four patients were treated with peg-IFN and post-treatment response was significantly better in patients infected with genotype 5 (10% GT1 vs 64% GT5, p=0.013). CONCLUSION:Patients infected with hepatitis delta genotype 5 appear to have a better prognosis with fewer episodes of hepatic decompensation and better response to peg-IFN treatment compared to HDV patients with genotype 1.


背景和目的: HDV 合并感染可导致肝硬化和肝功能失代偿的快速进展。与疾病进展相关的因素知之甚少。在本研究中,我们旨在确定与疾病进展相关的危险因素,更好地描述 HDV 基因型 1 和 5 之间的临床差异和治疗反应。 方法: 在这项回顾性研究中,所有患者在我们的护理下,2005年和 2016 与 HBV/HDV 合并感染 (HBsAg +,抗 HDV 抗体阳性) 进行了分析。如果随访时间少于 6 个月,如果患者有 HCV 和/或 HIV 合并感染或急性 HDV 感染,则排除患者。记录人口统计学资料、肝病分期、肝脏并发症的发展和治疗反应。 结果: 57% 例患者 (平均年龄 36.0 岁,0.6 为男性) 的中位随访时间为 4.4 年 (范围-28.1 年)。64% 为非洲血统,17% 为欧洲血统,28% 的患者初诊时肝硬化。43% 例患者存在主动复制 HDV 病毒 (抗 HDV-IgG + 、抗 HDV-IgM + 或 HDV RNA +) 57% 的患者为 HDV 暴露 (抗 HDV-IgG +,HDV RNA-)。与暴露于 HDV 的患者相比,积极复制 HDV 患者更经常发生肝脏并发症 (p = 0.002),但未观察到基线特征的差异。与基因型 1 的患者相比,基因型 5 的 HDV 患者较少发生肝硬化或肝功能失代偿。 24 例患者接受 peg-IFN 治疗,基因型 5 感染患者治疗后反应明显较好 (10% GT1 vs 64% GT5,p = 0.013)。 结论: 与基因型 1 的 HDV 患者相比,基因型 5 感染的患者似乎具有更好的预后,肝功能失代偿发作更少,对 peg-IFN 治疗的反应更好。



作者列表:["Moon AM","Jiang Y","Rogal SS","Tapper EB","Lieber SR","Barritt AS 4th"]

METHODS:BACKGROUND:Opioids are often prescribed for pain in cirrhosis and may increase the risk of hepatic encephalopathy (HE). AIMS:To assess the association between opioids and HE in patients with well-compensated cirrhosis. METHODS:We used the IQVIA PharMetrics (Durham, NC) database to identify patients aged 18-64 years with cirrhosis. We excluded patients with any decompensation event from 1 year before cirrhosis diagnosis to 6 months after cirrhosis diagnosis. Over the 6 months after cirrhosis diagnosis, we determined the duration of continuous opioid use and classified use into short term (1-89 days) and chronic (90-180 days). We assessed whether patients developed HE over the subsequent year (ie 6-18 months after cirrhosis diagnosis). We used a landmark analysis and performed multivariable Cox proportional hazards regression to assess associations between opioid use and HE, adjusting for relevant confounders. RESULTS:The cohort included 6451 patients with compensated cirrhosis, of whom 23.3% and 4.7% had short-term and chronic opioid prescriptions respectively. Over the subsequent year, HE occurred in 6.3% patients with chronic opioid prescriptions, 5.0% with short-term opioid prescriptions and 3.3% with no opioid prescriptions. In the multivariable model, an increased risk of HE was observed with short-term (adjusted hazard ratio, HR 1.44, 95% CI 1.07-1.94) and chronic opioid prescriptions (adjusted HR 1.83, 95% CI 1.07-3.12) compared to no opioid prescriptions. CONCLUSION:In this national cohort of privately insured patients with cirrhosis, opioid prescriptions were associated with the risk of incident HE. Opioid use should be minimised in those with cirrhosis and, when required, limited to short duration.

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翻译标题与摘要 下载文献
作者列表:["Chen VL","Chen Y","Du X","Handelman SK","Speliotes EK"]

METHODS:BACKGROUND AND AIMS:Cirrhosis is characterized by extensive fibrosis of the liver and is a major cause of liver-related mortality. Cirrhosis is partially heritable but genetic contributions to cirrhosis have not been systemically explored. Here, we carry out association analyses with cirrhosis in two large biobanks and determine the effects of cirrhosis associated variants on multiple human disease/traits. METHODS:We carried out a genome-wide association analysis of cirrhosis as a diagnosis in UK BioBank (UKBB; 1088 cases vs. 407 873 controls) and then tested top-associating loci for replication with cirrhosis in a hospital-based cohort from the Michigan Genomics Initiative (MGI; 875 cases of cirrhosis vs. 30 346 controls). For replicating variants or variants previously associated with cirrhosis that also affected cirrhosis in UKBB or MGI, we determined single nucleotide polymorphism effects on all other diagnoses in UKBB (PheWAS), common metabolic traits/diseases and serum/plasma metabolites. RESULTS:Unbiased genome-wide association study identified variants in/near PNPLA3 and HFE, and candidate variant analysis identified variants in/near TM6SF2, MBOAT7, SERPINA1, HSD17B13, STAT4 and IFNL4 that reproducibly affected cirrhosis. Most affected liver enzyme concentrations and/or aspartate transaminase-to-platelet ratio index. PheWAS, metabolic trait and serum/plasma metabolite association analyses revealed effects of these variants on lipid, inflammatory and other processes including new effects on many human diseases and traits. CONCLUSIONS:We identified eight loci that reproducibly associate with population-based cirrhosis and define their diverse effects on human diseases and traits.

翻译标题与摘要 下载文献
作者列表:["Li H","Wieser A","Zhang J","Liss I","Markwardt D","Hornung R","Neumann-Cip AC","Mayerle J","Gerbes A","Steib CJ"]

METHODS:BACKGROUND:Spontaneous bacterial peritonitis (SBP) is a serious complication in patients with liver cirrhosis. In recent years, it has been postulated that the rate of multidrug-resistant organisms (MDROs) is increasing, especially in nosocomial SBP patients. Aim of the present work was to investigate this hypothesis and its possible clinical consequences. MATERIALS AND METHODS:One hundred and three culture-positive patients between 2007 and 2014 were compared with 81 patients between 2015 and 2017, to study the change of microbiological profiles and their clinical consequences. The cirrhosis patients with bacterascites requiring treatment were included as well. RESULTS:The most prevalent Gram-negative bacteria isolated from ascites were Enterobacterales (31.6%) and in Gram-positive pathogens Staphylococci (22.8%). There was a significant increase in MDROs (22.3% ICU 40.7%, P = .048), accompanied by an increased incidence of sepsis (from 21.4% to 37.0%, P = .021), hepatorenal syndrome (from 40.8% to 58.0%, P = .007) and the need of catecholamine therapy (from 21.4% to 38.8%, P = .036). Nosocomial origin correlated with higher MDRO proportion, more complications and lower antimicrobial susceptibility rates in 12 commonly used antibiotics. MDROs were confirmed as an isolated predictor for inpatient mortality and complications in multivariable logistic regression. CONCLUSIONS:The feeling in clinical practice that MDROs have increased in the last 11 years could be confirmed in our study in Munich, Germany. Nosocomial SBP correlated with significantly higher MDRO rates (nearly 50%) and complication rates. In our opinion, an antibiotic combination with comprehensive effect should be taken into account in nosocomial SBP patients in this region.