Similar risk of hepatocellular carcinoma during long-term entecavir or tenofovir therapy in Caucasian patients with chronic hepatitis B.
- 作者列表："Papatheodoridis GV","Dalekos GN","Idilman R","Sypsa V","Van Boemmel F","Buti M","Calleja JL","Goulis J","Manolakopoulos S","Loglio A","Papatheodoridi M","Gatselis N","Veelken R","Lopez-Gomez M","Hansen BE","Savvidou S","Kourikou A","Vlachogiannakos J","Galanis K","Yurdaydin C","Esteban R","Janssen H","Berg T","Lampertico P
BACKGROUND & AIMS:The incidence of hepatocellular carcinoma (HCC) was recently reported to be lower in Asian chronic hepatitis B (CHB) patients treated with tenofovir disoproxil fumarate (TDF) than entecavir (ETV), but this finding remains controversial. We assessed whether there was a difference between ETV and TDF treated patients of the well monitored, multicenter European PAGE-B cohort in the HCC incidence and other patient outcomes. METHODS:We included 1935 Caucasians with CHB, with or without compensated cirrhosis, treated with ETV (n=772) or TDF (n=1163) monotherapy. Mean follow-up has been 7.1±3.0 years from ETV/TDF onset. RESULTS:The 5-year cumulative HCC incidence was 5.4% in ETV and 6.0% in TDF treated patients (log-rank, P=0.321) without significant difference in any patient subgroup [with or without cirrhosis, naive or experienced to oral antiviral(s) (total, with or without cirrhosis)]. In multivariable Cox regression analyses, the hazard of HCC was similar between ETV and TDF treated patients after adjustment for several HCC risk factors. ETV and TDF treated patients had similar rates of on-therapy biochemical and virological remission, HBsAg loss, liver transplantation and/or death. Elastographic reversion of cirrhosis at year 5 (liver stiffness <12 kPa) was observed in 245/347 (70.6%) patients with pretreatment cirrhosis being more frequent in TDF than ETV treated patients (73.8% vs 61.5%, P=0.038). CONCLUSION:In Caucasian CHB patients, with or without cirrhosis, ETV and TDF long-term monotherapy is associated with similar HCC risk and rates of biochemical and virological remission, HBsAg loss and liver transplantation or death, but TDF seems to result in more frequent elastographic reversion of cirrhosis at year 5.
背景与目的: 肝细胞癌 (HCC) 的发病率最近被报道在亚洲慢性乙型肝炎 (CHB) 患者用富马酸替诺福韦酯 (TDF) 治疗较低比恩替卡韦 (ETV)，但这一发现仍有争议。我们评估了受良好监测的多中心欧洲 PAGE-B 队列的 ETV 和 TDF 治疗患者在 HCC 发生率和其他患者结局方面是否存在差异。 方法: 我们纳入了 1935 例 CHB 白种人，伴或不伴代偿性肝硬化，接受 ETV (n = 772) 或 TDF (n = 1163) 单药治疗。ETV/TDF 发病后平均随访 7.1 ± 3.0 年。 结果: ETV 的 5 年累积 HCC 发生率为 5.4%，TDF 治疗患者为 6.0% (log-rank，P = 0.321) 任何患者亚组 [伴或不伴肝硬化，幼稚或经历口服抗病毒药物 (总，伴或不伴肝硬化)] 无显著差异。在多变量 Cox 回归分析中，调整了几个 HCC 危险因素后，ETV 和 TDF 治疗患者的 HCC 风险相似。ETV 和 TDF 治疗的患者在治疗生化和病毒学缓解率相似，HBsAg 消失，肝移植和/或死亡。在 245/347 (70.6%) 治疗前肝硬化患者中观察到 5 年肝硬化的弹性成像逆转 (肝硬度 <12 kPa)，TDF 比 ETV 治疗患者更频繁 (73.8% vs 61.5%, P = 0.038)。 结论: 在高加索 CHB 患者中，有或没有肝硬化，ETV 和 TDF 长期单药治疗与相似的 HCC 风险和生化和病毒学缓解率相关,HBsAg 消失和肝移植或死亡，但 TDF 似乎导致肝硬化 5 年更频繁的弹性成像逆转。
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.
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.
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.