End-stage Liver Disease Mortality Research Articles

Prognostic value of neutrophil-to-lymphocyte ratio in end-stage liver disease: A meta-analysis.

The neutrophil-to-lymphocyte ratio (NLR) is commonly utilized as a prognostic indicator in end-stage liver disease (ESLD), encompassing conditions like liver failure and decompensated cirrhosis. Nevertheless, some studies have contested the prognostic value of NLR in ESLD. To investigate the ability of NLR to predict ESLD. Databases, such as Embase, PubMed, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Weipu, and Wanfang, were comprehensively searched to identify studies published before October 2022 assessing the prognostic ability of NLR to predict mortality in patients with ESLD. Effect sizes were calculated using comprehensive meta-analysis software and SATAT 15.1. A total of thirty studies involving patients with end-stage liver disease (ESLD) were included in the evaluation. Among the pooled results of eight studies, it was observed that the Neutrophil-to-Lymphocyte Ratio (NLR) was significantly higher in non-survivors compared to survivors (random-effects model: standardized mean difference = 1.02, 95% confidence interval = 0.67-1.37). Additionally, twenty-seven studies examined the associations between NLR and mortality in ESLD patients, reporting either hazard ratios (HR) or odds ratios (OR). The combined findings indicated a link between NLR and ESLD mortality (random-effects model; univariate HR = 1.07, 95%CI = 1.05-1.09; multivariate HR = 1.07, 95%CI = 1.07-1.09; univariate OR = 1.29, 95%CI = 1.18-1.39; multivariate OR = 1.29, 95%CI = 1.09-1.49). Furthermore, subgroup and meta-regression analyses revealed regional variations in the impact of NLR on ESLD mortality, with Asian studies demonstrating a more pronounced effect. Increased NLR in patients with ESLD is associated with a higher risk of mortality, particularly in Asian patients. NLR is a useful prognostic biomarker in patients with ESLD.

Serum ammonia variation predicts mortality in patients with hepatitis B virus-related acute-on-chronic liver failure.

Hyperammonemia is critical to the development of hepatic encephalopathy (HE) and is associated with mortality in end-stage liver disease. This study investigated the clinical value of ammonia variation in hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) patients. A total of 276 patients with HBV-ACLF were retrospectively recruited. Patients' ammonia levels were serially documented. Baseline ammonia, Peak ammonia (highest level), and Trough ammonia (lowest level) were particularly corrected to the upper limit of normal (AMM-ULN). The primary endpoint was 28-day mortality. The 28-day, 3-month, and 12-month mortality rates were 19.2, 25.7, and 28.2%, respectively. A total of 51 (18.4%) patients had overt HE (grade 2/3/4). Peak AMM-ULN was significantly higher in patients with overt HE and non-survivors compared with their counterparts (P < 0.001). Following adjustment for significant confounders, high Peak AMM-ULN was an independent predictor of overt HE (hazard ratio, 1.031, P < 0.001) and 28-day mortality (hazard ratio, 1.026, P < 0.001). The cut-off of Peak AMM-ULN was 1.8, determined by using the X-tile. Patients with Peak AMM-ULN appearing on days 1-3 after admission had a higher proportion of overt HE and mortality compared to other groups. Patients with decreased ammonia levels within 7 days had better clinical outcomes than those with increased ammonia. Serum Peak ammonia was independently associated with overt HE and mortality in HBV-ACLF patients. Serial serum ammonia may have prognostic value.

Trends of Mortality in End-Stage Liver Disease - China, 2008-2020.

Liver cancer and cirrhosis represent the most prevalent forms of end-stage liver diseases (ESLDs). Notably, in China, deaths attributed to ESLDs contribute significantly to the global mortality rate of these disorders. Enhanced comprehension of the mortality profile associated with ESLDs in China could provide crucial insights into intervention prioritization, which could in turn help reduce the overall global burden of these diseases. Data were obtained from China's Disease Surveillance Points system. The presentation includes both crude and age-standardized mortality rates, stratified by sex, residential location, and region. Using Joinpoint Regression, trends in annual mortality rates were estimated from the period of 2008 to 2020 and expressed as the average annual percentage change (AAPC). In 2020, the gross mortality rate of ESLD stood at 30.08 cases per 100,000 individuals. A higher age-standardized ESLD mortality rate was observed in males and rural populations in comparison to their female and urban counterparts, respectively. Noticeably, the highest mortality rates associated with liver cancer and cirrhosis were reported in South and Southwest China, respectively. A positive correlation was noticed between age-specific ESLD mortality rates and advancing age. Interestingly, an annual decrease in the ESLD mortality rate was observed from 2008 to 2020. In urban contexts, the AAPC of cirrhosis was noted to be higher than that of liver cancer. The mortality rate associated with ESLDs in China decreased between 2008 and 2020. Nevertheless, the death burden attributable to ESLD continues to be alarmingly high. Future initiatives should prioritize the reduction of ESLD mortality in particular populations: males, elderly individuals, and those residing in rural regions of South and Southwest China. The emphasis of future interventions should be placed on antiviral therapy for adults diagnosed with viral hepatitis, and on the prevention of hepatitis B virus (HBV) infection across all demographics.

Medicaid Expansion Association With End-Stage Liver Disease Mortality Depends on Leniency of Medicaid Hepatitis C Virus Coverage.

The Affordable Care Act expanded Medicaid around the same time that direct-acting antivirals became widely available for the treatment of hepatitis C virus (HCV). However, there is significant variation in Medicaid HCV treatment eligibility criteria between states. We explored the combined effects of Medicaid expansion and leniency of HCV coverage under Medicaid on liver outcomes. We assessed state-level end-stage liver disease (ESLD) mortality rates, listings for liver transplantation (LT), and listing-to-death ratios (LDRs) for adults aged 25 to 64years using data from United Network for Organ Sharing and Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research. States were divided into 4 nonoverlapping groups based on expansion status on January 1, 2014 (expansion versus nonexpansion) and leniency of Medicaid HCV coverage (lenient versus restrictive coverage). Joinpoint regression analysis evaluated the significant changes in slope over time (joinpoints) during the pre-expansion (2009-2013) and postexpansion (2014-2018) time periods. We found significant changes in the annual percent change for population-adjusted ESLD deaths between 2014 and 2015 in all cohorts except for the nonexpansion/restrictive cohort, in which deaths increased at the same annual percent change from 2009 to 2018 (annual percent change of +2.5%; 95% confidence interval [CI], 1.8-3.3]). In the expansion/lenient coverage cohort, deaths increased at an annual percent change of +2.6% (95% CI, 1.8-3.5) until 2014 and then tended to decrease at an annual percent change of -0.4% (95% CI, -1.5 to 0.8). LT listings tended to decrease over time for all cohorts. For LDRs, only the expansion/lenient and expansion/restrictive cohorts had statistically significant joinpoints. Improvements in ESLD mortality and LDRs were associated with both Medicaid expansion and leniency of HCV coverage under Medicaid. These findings suggest the importance of implementing more lenient and widespread public health insurance to improve liver disease outcomes, including mortality.

S3285 The Negative Predictive Value of Dobutamine Stress Echocardiography for Identifying Coronary Artery Disease in Liver Transplant Evaluation

INTRODUCTION: Coronary artery disease (CAD) is associated with increased morbidity and mortality in end-stage liver disease (ESLD) patients undergoing liver transplant(LT). Dobutamine stress echocardiography (DSE) has gained preference over other screening tests for detecting CAD in ESLD patients due to the chronic systemic vasodilatation, increased cardiac output, and poor exercise tolerance. This study aimed to evaluate the negative predictive value and the accuracy of DSE for the diagnosis of obstructive CAD, using coronary angiography as the reference in ESLD patients. METHODS: This is a retrospective single-center study at Methodist University Hospital, Memphis TN, which included patients with ESLD undergoing LT evaluation. We reviewed patients from three consecutive years and identified the patients who underwent DSE as part of pre-transplant evaluation along with coronary angiography within six months of DSE. A total of 94 patients were identified that had both a DSE along with coronary angiography for LT evaluation. Beta-blockers were held prior to DSE, and the target heart rate for DSE was 85% age-predicted maximum heart rate. Of the 94 patients, nine patients did not achieve a maximal heart rate despite maximal medication. An analysis was performed with the remaining 85 patients. Patients were referred for coronary angiography if DSE was abnormal or with a normal DSE in the presence of ≥1 risk factor(s) for CAD. Significant CAD was defined as ≥70% obstruction or fractional flow reserve < 0.80. RESULTS: A total of 22 patients had a DSE positive test and were referred to coronary angiography: 5/22(23%) patients had positive coronary angiography and 18/22(82%) had negative coronary angiography. The sensitivity in this group was 63% and specificity of 78%. Interestingly, 63 patients were referred for coronary angiography with a negative DSE due to CAD risk factors: 3/63(5%) patients had a positive coronary angiography, and 60/63(95%) patients had a negative coronary angiography. The negative predictive value of DSE at detecting obstructive CAD in ESLD patients is 95% (Table 1). The accuracy of DSE at detecting obstructive CAD in ESLD patients is 76%. CONCLUSION: Due to the hemodynamics of the ESLD patients, the sensitivity of DSE is limited. However, the negative predictive value is high (95%) to use DSE as a cost-effective, non-invasive screening test to rule out CAD.Table 1

Treatment in disproportionately minority hospitals is associated with an increased mortality in end-stage liver disease.

Racial and ethnic disparities are a barrier in delivery of healthcare across the USA. Care for minority patients tends to be clustered into a small number of providers at minority hospitals, which has been associated with worse clinical outcomes in several conditions. However, the outcomes of treatment in patients with end-stage liver disease (ESLD) at predominately minority hospitals are unknown. We investigated the burden of the problem. We utilized the nationwide in-patient sample (NIS) to conduct a retrospective nationwide cohort analysis. All patients >18 years of age admitted with ESLD were included in the analysis. A multivariate logistic regression model was used to study the mortality rate among patients with ESLD treated at minority hospitals compared to nonminority hospitals. A total of 53 281 467 hospitalizations from the 2008 to 2014 NIS were analyzed. There were 163 470 patients with ESLD that met inclusion criteria. In-hospital mortality rates for all races were 8.0 and 8.1% in black and Hispanic minority hospitals, respectively, compared to 7.3% in nonminority hospitals (P < 0.01). On multivariate analysis, treatment of ESLD in black and Hispanic minority hospitals was associated with 11% [odds ratio (OR), 1.11; 95% confidence interval (CI), 1.03-1.20; P < 0.01] and 22% (OR, 1.22; 95% CI, 1.09-1.37; P < 0.01) increased odds of death, respectively, compared to treatment in nonminority hospitals regardless of patient's race. Patients with ESLD treated at minority hospitals are faced with an increased mortality rate regardless of patient's race. This study highlights another quality gap that needs improvement to affect overall survival among patients with ESLD.

Muscle strength and physical performance, rather than muscle mass, correlate with mortality in end-stage liver disease.

Sarcopenia is characterized by the loss of skeletal muscle mass, strength and performance. The study aimed to provide cut off values of various Sarcopenia parameters [computerized tomography skeletal muscle index (SMI), handgrip strength (HGS), gait velocity and chair stand] to predict mortality in end-stage liver disease (ESLD). The inclusion criteria were age 18-75 years, model for end-stage liver disease > 15. All patients with advanced heart, lung, kidney diseases, active malignancy were excluded from the study. Sarcopenia indices were compared between survivors and non-survivors to find cut off value for prediction of mortality in ESLD patients. One hundred sixty-one subjects suffering from ESLD were enrolled. The cutoff value of the SMI to identify high risk of mortality in sarcopenia patients is ≤21.2 cm2/m2, area under the curve (AUC) 0.537 [95% confidence interval (CI) 0.456-0.616]. The cutoff value of the hand grip strength to identify high-risk mortality is ≤25.3 kilogram-force, AUC 0.682 (95% CI 0.604-0.753). The cutoff value of the gait velocity for the same is as ≤0.84 m/s, AUC 0.551 (95% CI 0.459-0.641). The cutoff value of the chair stand is ≥20.9 seconds, AUC 0.956 (95% CI 0.910-0.983). In the multivariate analysis, HGS, gait velocity and chair stand correlated with mortality. The current study is a comprehensive Asian study that gives the cut off values of Sarcopenia: muscle mass, strength and performance which identify high risk of mortality in ESLD patients. Muscle strength and performance correlated with mortality.

Exercise and physical activity for patients with end-stage liver disease: Improving functional status and sarcopenia while on the transplant waiting list.

Sarcopenia and physical deconditioning are frequent complications in patients with cirrhosis and end-stage liver disease (ESLD). They are the end result of impaired dietary intake, chronic inflammation, altered macronutrient and micronutrient metabolism, and low physical activity. Frailty is the end result of prolonged sarcopenia and physical deconditioning. It severely affects a patient's functional status and presents in approximately 1 in 5 patients on the liver transplantation waiting list. Sarcopenia, poor physical fitness/cardiopulmonary endurance (CPE), and frailty are all associated with increased mortality in ESLD. Clinical trials addressing the usefulness of exercise in patients with cirrhosis have shown that it improves the metabolic syndrome, sarcopenia, CPE, health-related quality of life, and hepatic venous pressure gradient. Although evidence on the benefits of exercise on clinical outcomes derived from large clinical trials is still missing, based on existing literature from multiple medical subspecialties, we believe that an exercise program coupled to a tailored nutritional intervention benefits both cardiopulmonary and musculoskeletal functions, ultimately translating into improved functional status, sense of well-being, and possibly less complications from portal hypertension. In conclusion, although supervised exercise training is the prevailing approach to manage ESLD patients, such intervention is not sustainable or feasible for most patients. Innovative home-based physical activity interventions may be able to effectively reach a larger number of patients. Liver Transplantation 24 122-139 2018 AASLD.

Obesity is independently associated with infection in hospitalised patients with end-stage liver disease.

Infection is the most common cause of mortality in end-stage liver disease (ESLD). The impact of obesity on infection risk in ESLD is not established. To characterise the impact of obesity on infection risk in ESLD. We evaluated the association between infection and obesity in patients with ESLD. Patients grouped as non-obese, obesity class I-II and obesity class III were studied using the Nationwide Inpatient Sample. Validated diagnostic code based algorithms were utilised to determine weight category and infections, including bacteraemia, skin/soft tissue infection, urinary tract infection (UTI), pneumonia/respiratory infection, Clostridium difficile infection (CDI) and spontaneous bacterial peritonitis (SBP). Risk factors for infection and mortality were assessed using multivariable logistic regression analysis. Of 115 465 patients identified, 100 957 (87.5%) were non-obese and 14 508 (12.5%) were obese, with 9489 (8.2%) as obesity class I-II and 5019 (4.3%) as obesity class III. 37 117 patients (32.1%) had an infection diagnosis. Infection was most prevalent among obesity class III (44.0%), followed by obesity class I-II (38.9%) and then non-obese (31.9%). In multivariable modelling, class III obesity (OR = 1.41; 95% CI 1.32-1.51; P < 0.001), and class I-II obesity (OR = 1.08; 95% CI 1.01-1.15; P = 0.026) were associated with infection. Compared to non-obese patients, obese individuals had greater prevalence of bacteraemia, UTI, and skin/soft tissue infection as compared to non-obese patients. Obesity is newly identified to be independently associated with infection in end-stage liver disease. The distribution of infection sites varies based on weight category.

End-Stage Liver Disease in a State Prison Population

Information on the epidemiology of end-stage liver disease (ESLD) in US correctional populations is limited. We examined the prevalence, mortality and clinical characteristics of ESLD in the nation's second largest state prison system. We collected and analyzed medical and demographic data from 370,511 offenders incarcerated in Texas' prison system during a 3.5-year period. ESLD was diagnosed in 484 inmates (131/100,000); 213 (57/100,000) died of ESLD. Offenders who were Hispanic, 30-49 years of age, > or =50 years of age, HIV monoinfected, hepatitis C virus (HCV) monoinfected, or HIV/HCV coinfected had elevated ESLD prevalence and mortality rates. ESLD mortality in Texas' prison population is approximately 3 times higher than that of the general population, reflecting elevated rates of HCV and HIV/HCV coinfection among prisoners. Ultimately, the only viable treatment option for many prisoners with ESLD will be liver transplantation. The enormous costs of organ transplantation and immunosuppressive therapy are staggering and have the potential to decimate the healthcare budgets of most prison systems. Consequently, it is imperative that correctional healthcare programs expand HCV treatment and prevention strategies.

High frequency of chronic end-stage liver disease and hepatocellular carcinoma in a Hispanic population.

Texas has the highest mortality from hepatocellular carcinoma in the USA. Because end-stage liver disease mortality is most marked in the Hispanic population in the Lower Rio Grande Valley, the aim of the present paper was to estimate the prevalence of end-stage liver disease and associated factors in Brownsville. A cross-sectional study was carried out, abstracting medical charts in a community-based clinic and a hospital. A matched case-control analysis was performed. Cases had an International Classification of Disease (9th revision; ICD9) code 155.0 or 571.0-9 (primary liver cancer or chronic liver disease) recorded; age- and sex-matched controls did not have these codes. A total of 176 cases and 352 controls was collected. The main outcome measure was the prevalence and risk factors for end-stage liver disease. Conservative prevalence of end-stage liver disease: 126/100,000 (386/100,000, male). Eleven out of 176 had hepatocellular carcinoma. Median age was 57 years; 72% male, 94% Hispanic. Among significant risk factors were history of hepatitis (odds ratio (OR): 19.3; 95% confidence interval (CI): 8.0-46.4), any history of alcohol use (OR: 6.6; 95%CI: 4-10.8) and history of illegal drug use (OR: 1.9; 95%CI: 1.2-2.9). Fifteen cases with no known risk factors were classified as cryptogenic cirrhosis. Only four cases out of 176 had been referred for liver transplant. The prevalence of end-stage liver disease in the Lower Rio Grande Valley is extremely high, with no single satisfactory explanation and with acute health disparities. Careful follow up of cryptogenic cirrhosis in this population may or may not lead to a new source of liver disease.

Impact of acute renal failure on mortality in end-stage liver disease with or without transplantation

Acute renal failure (ARF) is traditionally considered a poor prognostic factor in end-stage liver disease and is associated with a mortality approaching 90%. While the increased use of orthotopic liver transplantation (OLTX) has changed the outcome for patients with end-stage liver disease (ESLD), it is not clear whether this has affected the outcome of patients with ESLD and ARF. We prospectively followed the course of ARF in 177 patients with ESLD being evaluated for OLTX. Of these patients 111 received OLTX. In-hospital mortality was compared to that of 316 ESLD patients without ARF, of these 196 received OLTX. Variables include severity of illness as assessed by APACHE II, co-morbid conditions, oliguria, need for renal replacement therapy, and etiologies of ESLD and ARF. These variables were evaluated with respect to the outcome in-hospital mortality by multiple regression analysis for patients with ARF. Mortality was significantly higher in oliguric versus non-oliguric patients and in patients who required renal replacement therapy. Mortality correlated strongly with the number of co-morbid conditions, especially sepsis, encephalopathy, respiratory failure, and DIC. For OLTX recipients who developed ARF, no significant difference in survival occurred whether the ARF was pre-OLTX or post-OLTX. ARF was associated with an increased mortality consistent with the known adverse prognostic effect of ARF in ESLD. However, the effect of ARF on mortality was remarkably reduced in patients who received a functioning OLTX. Since expected mortality generated from APACHE II scores was higher in the ARF groups, it is not clear that there is an additional effect of ARF beyond the physiologic derangements captured by APACHE II. ARF per se should not necessarily be a contraindication to liver transplant.