An optimized hepatocellular carcinoma prediction model for chronic hepatitis B with well-controlled viremia.
- 作者列表："Lee HW","Park SY","Lee M","Lee EJ","Lee J","Kim SU","Park JY","Kim DY","Ahn SH","Kim BK
BACKGROUND AND AIMS:Hepatocellular carcinoma (HCC) risk in chronic hepatitis B (CHB) substantially decreased in the era of potent antiviral therapy. We developed an optimized HCC risk prediction model for CHB with well-controlled viremia by nucelos(t)ide analogs (NUCs). METHOD:We analyzed those who achieved virological response (VR; serum HBV-DNA<2,000 IU/ml on two consecutive assessments) by NUCs. Liver stiffness by transient elastography, ultrasonography, and laboratory tests were performed at the time of confirmed VR. Patients with decompensated cirrhosis or HCC at baseline were excluded. Multivariate Cox-regression analysis was used to determine key variables to construct a novel risk-scoring model. RESULTS:Among 1511 patients, 9.5% developed HCC. Cirrhosis on ultrasonography (adjusted HR [aHR] 2.47), Age (aHR 1.04), Male (aHR 1.9), Platelet count<135,000/uL (aHR 1.57), Albumin<4.5 g/dL (aHR 1.77), and liver Stiffness≥11 kPa (aHR 6.09) were independently associated with HCC. Using these, CAMPAS model was developed with c-index of 0.874. The predicted and observed HCC probabilities were calibrated with a reliable agreement. Such results were reproduced from internal validation and external validation among the independent cohort (n=252). The intermediate-risk (CAMPAS model score 75~161) and high-risk (score>161) groups were more likely to develop HCC compared to the low-risk group (score≤75) with statistical significances (HRs; 4.43 and 47.693, respectively; both p<0.001). CONCLUSION:CAMPAS model derived through comprehensive clinical evaluation of liver disease allowed the more delicate HCC prediction for CHB patients with well-controlled viremia by NUCs.
背景和目的：肝细胞癌在有效抗病毒治疗的时代，慢性乙型肝炎（CHB）的风险显著降低。我们利用nucelos（t）ide类似物（NUCs）建立了一个控制良好的病毒血症CHB的优化HCC风险预测模型。 方法：我们分析通过NUCs获得病毒学应答（VR；连续两次评估的血清HBV-DNA<2000iu/ml）的患者。在确认虚拟现实时，通过瞬时弹性成像、超声和实验室测试进行肝脏僵硬。排除基线时有失代偿期肝硬化或肝癌的患者。采用多元Cox回归分析确定关键变量，建立新的风险评分模型。 结果：1511人9.5%的患者发生肝癌。肝硬化超声检查（校正HR[aHR]2.47）、年龄（aHR 1.04）、男性（aHR 1.9）、血小板计数<135000/uL（aHR 1.57）、白蛋白<4.5g/dL（aHR 1.77）和肝硬度≥11kpa（aHR 6.09）独立与HCC相关。在此基础上，建立了c指数为0.874的CAMPAS模型。对预测和观察到的肝癌发生率进行了校正，结果符合得很好。这些结果来自独立队列的内部验证和外部验证（n=252）。中危组（CAMPAS模型评分75~161）和高危组（评分>161）较低危组（评分≤75）更易发生肝癌，有统计学意义（HRs分别为4.43和47.693，均p<0.001）。 C类结论：CAMPAS模型通过对肝脏疾病的综合临床评估，可以更精确地预测由NUCs控制的病毒血症CHB患者的HCC。
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.