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Extra-hepatic comorbidity burden significantly increases 90-day mortality in patients with cirrhosis and high model for endstage liver disease.

ABSTRACT: BACKGROUND:We examined how extra-hepatic comorbidity burden impacts mortality in patients with cirrhosis referred for liver transplantation (LT). METHODS:Adults with cirrhosis evaluated for their first LT in 2012 were followed through their clinical course with last follow up in 2019. Extra-hepatic comorbidity burden was measured using the Charlson Comorbidity Index (CCI). The endpoints were 90-day transplant free survival (Cox-Proportional Hazard regression), and overall mortality (competing risk analysis). RESULTS:The study included 340 patients, mean age 56?±?11, 63% male and MELD-Na 17.2?±?6.6. The CCI was 0 (no comorbidities) in 44%, 1-2 in 44% and?>?2 (highest decile) in 12%, with no differences based on gender but higher CCI in patients with fatty and cryptogenic liver disease. Thirty-three (10%) of 332 patients not receiving LT within 90?days died. Beyond MELD-Na, the CCI was independently associated with 90-day mortality (hazard ratio (HR), 1.32 (95% confidence interval (CI) 1.02-1.72). Ninety-day mortality was specifically increased with higher CCI category and MELD ?18 (12% (CCI?=?0), 22% (CCI?=?1-2) and 33% (CCI?>?2), (p =?0.002)) but not MELD-Na ?17. At last follow-up, 69 patients were alive, 100 underwent LT and 171 died without LT. CCI was associated with increased overall mortality in the competing risk analysis (Sub-HR 1.24, 95%CI 1.1-1.4). CONCLUSIONS:Extra-hepatic comorbidity burden significantly impacts short-term mortality in patients with cirrhosis and high MELD-Na. This has implications in determining urgency of LT and mortality models in cirrhosis and LT waitlisting, especially with an ageing population with increasing prevalence of fatty liver disease.

SUBMITTER: Coppel S

PROVIDER: S-EPMC7493147 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Extra-hepatic comorbidity burden significantly increases 90-day mortality in patients with cirrhosis and high model for endstage liver disease.

Coppel Scott S Mathur Karan K Ekser Burcin B Patidar Kavish R KR Orman Eric E Desai Archita P AP Vilar-Gomez Eduardo E Kubal Chandrashekhar C Chalasani Naga N Nephew Lauren L Ghabril Marwan M

BMC gastroenterology 20200916 1

<h4>Background</h4>We examined how extra-hepatic comorbidity burden impacts mortality in patients with cirrhosis referred for liver transplantation (LT).<h4>Methods</h4>Adults with cirrhosis evaluated for their first LT in 2012 were followed through their clinical course with last follow up in 2019. Extra-hepatic comorbidity burden was measured using the Charlson Comorbidity Index (CCI). The endpoints were 90-day transplant free survival (Cox-Proportional Hazard regression), and overall mortalit ...[more]

PMID: 32938387

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Project description:Background: Liver cirrhosis is a relevant comorbidity with increasing prevalence. Postoperative decompensation and development of complications in patients with cirrhosis remains a frequent clinical problem. Surgery has been discussed as a precipitating event for decompensation and complications of cirrhosis, but the underlying pathomechanisms are still obscure. The aim of this study was to analyze the role of abdominal extrahepatic surgery in cirrhosis on portal pressure and fibrosis in a preclinical model. Methods: Compensated liver cirrhosis was induced using tetrachlormethane (CCL4) inhalation and bile duct ligation (BDL) models in rats, non-cirrhotic portal hypertension by partial portal vein ligation (PPVL). Intestinal manipulation (IM) as a model of extrahepatic abdominal surgery was performed. 2 and 7 days after IM, portal pressure was measured in-vivo. Hydroxyproline measurements, Sirius Red staining and qPCR measurements of the liver were performed for evaluation of fibrosis development and hepatic inflammation. Laboratory parameters of liver function in serum were analyzed. Results: Portal pressure was significantly elevated 2 and 7 days after IM in both models of cirrhosis. In the non-cirrhotic model the trend was the same, while not statistically significant. In both cirrhotic models, IM shows strong effects of decompensation, with significant weight loss, elevation of liver enzymes and hypoalbuminemia. 7 days after IM in the BDL group, Sirius red staining and hydroxyproline levels showed significant progression of fibrosis and significantly elevated mRNA levels of hepatic inflammation compared to the respective control group. A progression of fibrosis was not observed in the CCL4 model. Conclusion: In animal models of cirrhosis with continuous liver injury (BDL), IM increases portal pressure, and development of fibrosis. Perioperative portal pressure and hence inflammation processes may be therapeutic targets to prevent post-operative decompensation in cirrhosis.

Project description:BACKGROUND:Mortality rates associated with acute kidney injury (AKI) vary among critically ill patients. Outcomes are often not corrected for severity or duration of AKI. Our objective was to analyse whether a new variable, AKI burden, would outperform 1) presence of AKI, 2) highest AKI stage, or 3) AKI duration in predicting 90-day mortality. METHODS:Kidney Diseases: Improving Global Outcomes (KDIGO) criteria using creatinine, urine output and renal replacement therapy were used to diagnose AKI. AKI burden was defined as AKI stage multiplied with the number of days that each stage was present (maximum five), divided by the maximum possible score yielding a proportion. The AKI burden as a predictor of 90-day mortality was assessed in two independent cohorts (Finnish Acute Kidney Injury, FINNAKI and Simple Intensive Care Studies I, SICS-I) by comparing four multivariate logistic regression models that respectively incorporated either the presence of AKI, the highest AKI stage, the duration of AKI, or the AKI burden. RESULTS:In the FINNAKI cohort 1096 of 2809 patients (39%) had AKI and 90-day mortality of the cohort was 23%. Median AKI burden was 0.17 (IQR 0.07-0.50), 1.0 being the maximum. The model including AKI burden (area under the receiver operator curve (AUROC) 0.78, 0.76-0.80) outperformed the models using AKI presence (AUROC 0.77, 0.75-0.79, p?=?0.026) or AKI severity (AUROC 0.77, 0.75-0.79, p?=?0.012), but not AKI duration (AUROC 0.77, 0.75-0.79, p?=?0.06). In the SICS-I, 603 of 1075 patients (56%) had AKI and 90-day mortality was 28%. Median AKI burden was 0.19 (IQR 0.08-0.46). The model using AKI burden performed better (AUROC 0.77, 0.74-0.80) than the models using AKI presence (AUROC 0.75, 0.71-0.78, p?=?0.001), AKI severity (AUROC 0.76, 0.72-0.79. p?=?0.008) or AKI duration (AUROC 0.76, 0.73-0.79, p?=?0.009). CONCLUSION:AKI burden, which appreciates both severity and duration of AKI, was superior to using only presence or the highest stage of AKI in predicting 90-day mortality. Using AKI burden or other more granular methods may be helpful in future epidemiological studies of AKI.

Project description:Background and Purpose- We assessed ethnic differences in medication adherence 3 months poststroke in a population-based study as an initial step in investigating the increased stroke recurrence risk in Mexican Americans compared with non-Hispanic whites. Methods- Ischemic stroke cases from 2008 to 2015 from the Brain Attack Surveillance in Corpus Christi project in Texas were followed prospectively for 3 months poststroke to assess medication adherence. Medications in 5 drug classes were analyzed: statins, antiplatelets, anticoagulants, antihypertensives, and antidepressants. For each drug class, patients were considered adherent if they reported never missing a dose in a typical week. The χ2 tests or Kruskal-Wallis nonparametric tests were used for ethnic comparisons of demographics, risk factors, and medication adherence. A multivariable logistic regression model was constructed for the association of ethnicity and medication nonadherence. Results- Mexican Americans (n=692) were younger (median 65 years versus 68 years, P<0.001), had more diabetes mellitus ( P<0.001) and hypertension ( P<0.001) and less atrial fibrillation ( P=0.003), smoking ( P=0.003), and education ( P<0.001) than non-Hispanic whites (n=422). Sex, insurance status, high cholesterol, previous stroke/transient ischemic attack history, excessive alcohol use, tPA (tissue-type plasminogen activator) treatment, National Institutes of Health Stroke Scale score, and comorbidity index did not significantly differ by ethnicity. There was no significant difference in medication adherence for any of the 5 drug classes between Mexican Americans and non-Hispanic whites. Conclusions- This study did not find ethnic differences in medication adherence, thus challenging this patient-level factor as an explanation for stroke recurrence disparities. Other reasons for the excessive stroke recurrence burden in Mexican Americans, including provider and health system factors, should be explored.

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Extra-hepatic comorbidity burden significantly increases 90-day mortality in patients with cirrhosis and high model for endstage liver disease.

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Extra-hepatic comorbidity burden significantly increases 90-day mortality in patients with cirrhosis and high model for endstage liver disease.

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