Differential Survival Impact of Diabetes Mellitus on Hepatocellular Carcinoma: Role of Staging Determinants
- 作者列表："Ho, Shu-Yein","Yuan, Mei-Hsia","Chen, Chu-Chieh","Liu, Po-Hong","Hsu, Chia-Yang","Huang, Yi-Hsiang","Lei, Hao-Jan","Lee, Rheun-Chuan","Huo, Teh-Ia
Background Diabetes mellitus (DM) is common in patients with hepatocellular carcinoma (HCC) and may impact survival. Very few studies focused on the influence of DM in different clinical scenarios. We evaluated the prognostic impact of DM on HCC patients stratified by liver dysfunction, Milan criteria, and performance status defined in the Barcelona Clínic Liver Cancer staging parameters. Methods A prospective dataset of 3573 HCC patients between 2002 and 2016 was retrospectively analyzed. The multivariate Cox proportional hazards model was used to identify independent prognostic predictors. The Kaplan–Meier method with a log-rank test was applied to compare the survival distributions between different patient groups. Results Among all, DM was not an independent prognostic predictor in the Cox multivariate analysis ( p = 0.1044). In the subgroup analysis, DM was not a significant prognostic predictor in Child–Turcotte–Pugh class A or class B/C patients. However, DM was associated with a decreased survival in patients within the Milan criteria (hazard ratio [HR] 1.36, 95% confidence interval [CI] 1.155–1.601, p = 0.0002) and in those with the performance status 0 (HR 1.213, 95% CI 1.055–1.394, p = 0.0067) in the multivariate Cox analysis, but not in those beyond the Milan criteria and poor performance status. Conclusions DM is highly prevalent in HCC patients and has a distinct survival impact. DM is an independent survival predictor among patients within the Milan criteria and good performance status. These high-risk patients should be closely monitored, and aggressive anticancer treatment should be considered.
背景糖尿病 (DM) 在肝细胞癌 (HCC) 患者中很常见，可能会影响生存率。很少有研究关注 DM 在不同临床情况下的影响。我们根据巴塞罗那 clic 肝癌分期参数中定义的肝功能障碍、米兰标准和性能状态分层，评价了 DM 对 HCC 患者的预后影响。方法回顾性分析 3573 和 2002年 2016 例 HCC 患者的前瞻性数据集。使用多变量 Cox 比例风险模型确定独立的预后预测因子。采用 Kaplan-Meier 法及 log-rank 检验比较不同患者组之间的生存分布。结果 Cox 多因素分析中，DM 不是独立的预后因素 (p = 0.1044)。在亚组分析中，DM 不是 Child-Turcotte-Pugh a级或 B/C 级患者的显著预后预测因子。然而，在米兰标准范围内，DM 与患者生存率下降相关 (风险比 [HR] 1.36，95% 置信区间 [CI] 1.155-1.601，p = 0.0002) 在多变量 Cox 分析中，表现状态为 0 的患者 (HR 1.213，95% CI 1.055-1.394，p = 0.0067),但不是在那些超出米兰标准和糟糕的表现状态下。结论 DM 在 HCC 患者中非常普遍，并具有明显的生存影响。在米兰标准和良好表现状态的患者中，DM 是独立的生存预测因子。应密切监测这些高危患者，并考虑积极的抗癌治疗。
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.