Background
Weight gain after liver transplantation (LT) is a predictor of major morbidity and mortality post-LT; however, there are no data regarding weight loss following LT. The current study ...evaluates the effectiveness of standard lifestyle intervention in LT recipients.
Methods
All adult LT recipients with body mass index (BMI) ≥ 25 kg/m
2
who followed up in post-LT clinic from January 2013 to January 2016 were given standard lifestyle advice based on societal recommendations which was reinforced at 24 weeks. Patients were followed for a total of 48 weeks to assess the impact of such advice on weight. Primary outcome was achieving weight loss ≥ 5% of the body weight after 48 weeks of follow-up.
Results
A total of 151 patients with 86 (56.0%) overweight and 65 (44.0%) obese patients were enrolled in the study. The mean BMI at baseline increased from 30.2 ± 3.7 to 30.9 ± 4.3 kg/m
2
at 48-week follow-up (
p
= 0.001). Over the course of study, 58 (38.4%) patients lost any weight and weight loss greater than 5% and 10% occurred in only 18 (11.9%) and 8 (5.3%) of the entire cohort, respectively. Higher level of education was associated with increased likelihood of weight loss (OR 9.8, 95% CI 2.6, 36.9,
p
= 0.001), while nonalcoholic steatohepatitis as etiology of liver disease (HR 3.7, 95% CI 1.4, 9.7,
p
= 0.007) was associated with weight gain.
Conclusion
The practice of office-based lifestyle intervention is ineffective in achieving clinically significant weight loss in LT recipients, and additional strategies are required to mitigate post-LT weight gain.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Nonalcoholic steatohepatitis (NASH) is the leading indication for liver transplant (LT) in women and the elderly. Granular details into factors impacting survival in this population are needed to ...optimize management and improve outcomes.
Patients receiving LT for NASH cirrhosis from 1997 to 2017 across 7 transplant centers (NailNASH consortium) were analyzed. The primary outcome was all-cause mortality, and causes of death were enumerated. All outcomes were cross referenced with United Network for Organ Sharing and adjudicated at each individual center. Cox regression models were constructed to elucidate clinical factors impacting mortality.
Nine hundred thirty-eight patients with a median follow-up of 3.8 years (interquartile range, 1.60-7.05 years) were included. The 1-, 3-, 5-, 10-, and 15-year survival of the cohort was 93%, 88%, 83%, 69%, and 46%, respectively. Of 195 deaths in the cohort, the most common causes were infection (19%), cardiovascular disease (18%), cancer (17%), and liver-related (11%). Inferior survival was noted in patients >65 years. On multivariable analysis, age >65 (hazard ratio HR, 1.70; 95% confidence interval CI, 1.04-2.77; P = .04), end-stage renal disease (HR, 1.55; 95% CI, 1.04-2.31; P = .03), black race (HR, 5.25; 95% CI, 2.12-12.96; P = .0003), and non-calcineurin inhibitors-based regimens (HR, 2.05; 95% CI, 1.19-3.51; P = .009) were associated with increased mortality. Statin use after LT favorably impacted survival (HR, 0.38; 95% CI, 0.19-0.75; P = .005).
Despite excellent long-term survival, patients transplanted for NASH at >65 years or with type 2 diabetes mellitus at transplant had higher mortality. Statin use after transplant attenuated risk and was associated with improved survival across all subgroups, suggesting that careful patient selection and implementation of protocol-based management of metabolic comorbidities may further improve clinical outcomes.
The incidence and prevalence of metabolic syndrome (MetS) and type 2 diabetes mellitus (T2DM) are rising globally. MetS and T2DM are associated with significant morbidity and mortality, which is ...partly related to liver and cardiovascular disease. Insulin resistance is central to MetS and T2DM pathophysiology, and drives ectopic fat deposition in the liver, also known as metabolic dysfunction-associated steatotic liver disease (MASLD). MetS and T2DM are not only risk factors for developing MASLD but are also independently associated with disease progression to steatohepatitis, cirrhosis, and hepatocellular carcinoma. In addition to the risk of liver disease, MetS and T2DM are independent risk factors for cardiovascular disease (CVD), including coronary artery disease (CAD) and heart failure (HF). Importantly, there is a bidirectional relationship between liver and CVD due to shared disease pathophysiology in patients with MetS and T2DM. In this review, we have described studies exploring the relationship of MetS and T2DM with MASLD and CVD, independently. Following this we discuss studies evaluating the interplay between liver and cardiovascular risk as well as pragmatic risk mitigation strategies in this patient population.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Despite the high prevalence of covert hepatic encephalopathy (CHE) in cirrhotics without previous overt HE (OHE), its independent impact on predicting clinically relevant outcomes is unclear. The aim ...of this study was to define the impact of CHE on time to OHE, hospitalization, and death/transplant in prospectively followed up patients without previous OHE.
Outpatient cirrhotics without OHE were enrolled and were administered a standard paper-pencil cognitive battery for CHE diagnosis. They were systematically followed up and time to first OHE development, hospitalization (liver-related/unrelated), and transplant/death were compared between CHE and no-CHE patients at baseline using Cox regression.
A total of 170 cirrhotic patients (55 years, 58% men, 14 years of education, Model for End-Stage Liver Disease (MELD 9), 53% hepatitis C virus (HCV), 20% nonalcoholic etiology) were included, of whom 56% had CHE. The entire population was followed up for 13.0 ± 14.6 months, during which time 30% developed their first OHE episode, 42% were hospitalized, and 19% had a composite death/transplant outcome. Age, gender, etiology, the MELD score, and CHE status were included in Cox regression models for time to first OHE episode, hospitalization, death, and composite death/transplant outcomes. On Cox regression, despite controlling for MELD, those with CHE had a higher risk of developing OHE (hazard ratio: 2.1, 95% confidence interval 1.01-4.5), hospitalization (hazard ratio: 2.5, 95% confidence interval 1.4-4.5), and death/transplant (hazard ratio: 3.4, 95% confidence interval 1.2-9.7) in the follow-up period.
Covert HE is associated with worsened survival and increased risk of hospitalization and OHE development, despite controlling for the MELD score. Strategies to detect and treat CHE may improve these risks.
INTRODUCTION
Liver transplant (LT) recipients have an increased risk of developing cardiovascular disease (CVD) after transplant. Sex differences may be a significant determinant in the ...pathophysiology of CVD. However, sex‐differences in vascular dysfunction, an established precursor to CVD, have not been explored in LT recipients. The purpose of this study was to investigate the sex differences in vascular function and cardiometabolic risk‐factors to CVD among LT patients.
METHODS
Conduit artery endothelial function was measured via flow‐mediated dilation of the brachial artery (FMDBA) with duplex ultrasound in 23 age‐matched LT patients (11 Male, 12 Female; Mean ± SEM: Age 55 ± 2 years). Aortic pressure waves were synthesized from radial artery waveforms acquired by applanation tonometry and the use of a generalized transfer function. Novel plasma based cardiometabolic risk factors were assessed with nuclear magnetic resonance spectroscopy. Lipoprotein insulin resistance index (LPIR) was calculated as a weighted combination of concentrations and particle sizes of very low‐density, low‐density, and high‐density lipoproteins. Diabetes risk index (DRI) factors LPIR and branched‐chain amino acid levels to predict the risk of type 2 diabetes. Metabolic inflammation index (INFX) combines concentrations of the inflammation biomarker GlycA and high‐density lipoprotein particle subspecies.
RESULTS
Males had lower FMDBA than females (3.98 ± 0.63 vs 6.27 ± 0.43%, p < 0.01). There were no sex differences in aortic systolic pressure (Male vs Female; 129 ± 3 vs 118 ± 5 mmHg, p = 0.09), body mass index (38 ± 2 vs 36 ± 2 kg/m2, p = 0.61), LPIR (57 ± 7 vs 55 ± 7, p = 0.89), DRI (53 ± 7 vs 44 ± 6, p = 0.38), or INFX (47 ± 2 vs 54 ± 3, p = 0.13).
CONCLUSIONS
Males had poorer vascular endothelial function compared to females following LT, suggesting that males may be more susceptible to the development of CVD after LT. However, this increased risk cannot be explained by differences in traditional cardiometabolic risk factors. Future research should identify non‐traditional CVD risk factors that contribute to sex differences in vascular function towards implementing precision medicine for the prevention and management of CVD in LT patients.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
INTRODUCTION
Liver transplant (LT) recipients experience significant weight gain and an increased risk of cardiovascular disease (CVD) after transplant. The pathophysiology of this cardiometabolic ...burden is not fully understood. In the general population, weight gain and increased adiposity are associated with elevated circulating levels of fibroblast growth factor‐23 (FGF‐23). Increased FGF‐23 has been linked with CVD in other disease populations. This study tested the working hypothesis that weight gain after LT is associated withincreased levels of FGF‐23, that subsequently contribute to vascular dysfunction, an established precursor of CVD.
METHODS
We enrolled 21 LT patients (M/F: 9/12; Mean ± SEM, Age: 55 ± 2 yrs) and 8 age matched healthy controls (HC; M/F: 2/6; 47 ± 6 yrs). Vascular endothelial function was assessed with flow‐mediated dilation (FMD) of the brachial artery using duplex ultrasound. Aortic pressure waves were synthesized from radial artery waveforms acquired by applanation tonometry and the use of a generalized transfer function. Serum levels of FGF‐23 were assessed by enzyme linked immunosorbent assay (ELISA).
RESULTS
Higher body mass index (BMI) values were reported in LT patients (37 ± 1 kg/m2) compared to HC (26 ± 1 kg/m2, p = <0.001). Weight gain (BMI) was positively associated with serum FGF‐23 values (r = 0.5, p = 0.01). Central systolic pressures (125 ± 3 vs. 110 ± 6 mmHg, p = 0.01) and central pulse pressures (51 ± 4 vs. 39 ± 4 mmHg, p = 0.05) were higher in LT patients compared with controls. There was no difference in endothelial function (FMD) in LT patients (4.59 ± 0.55%) compared to their HC counterparts (6.08 ± 0.48%, p = 0.12). FGF‐23 values were not associated with measures of vascular function.
CONCLUSION
Weight gain is evident in LT patients and is correlated with higher serum FGF‐23 values. However, our findings do not suggest a relationship between serum levels of FGF‐23 and vascular function in LT recipients.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Coronary artery disease (CAD) assessment is a vital part of liver transplantation (LT) evaluation, as it allows for identification and medical optimization prior to transplantation. Although aspirin ...and statins are standard of care for CAD, they are not universally used in cirrhosis due to concerns about adverse events. Per protocol, coronary angiography was performed as part of the LT evaluation in all patients over the age of 50 years or with CAD risk factors, even if they were younger than 50. Optimal CAD medical management was defined as the use of both statin and aspirin, unless a contraindication was documented. Impact of these medications on hepatic decompensation, renal function, gastrointestinal bleeding, and need for transfusion was evaluated. CAD was detected in 84/228 (36.8%) patients. Lipid profile was similar in patients with and without CAD. In patients with CAD, statins were started in 19 (23%), while aspirin was used in 30 (36%) patients. In patients with obstructive or multivessel CAD, statin therapy was used only in 41% and 65%, respectively. Statins were more likely to be prescribed in patients with diabetes (32% versus 15%, P = 0.05) and history of dyslipidemia (38% versus 15%, P = 0.02). Use of statin therapy was not linked to hepatic decompensation, hospitalization, or rise in Model for End‐Stage Liver Disease (MELD). Similarly, use of aspirin therapy was not associated with increased risk acute variceal hemorrhage, gastrointestinal bleeding, or worsening anemia. In conclusion, in decompensated cirrhosis, lipid profile alone is unable to risk stratify patients with CAD. Statin and aspirin appear to be safe. However, they are significantly underutilized for the management of CAD in this patient population. Liver Transplantation 24 872–880 2018 AASLD.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Background & Aims
In non‐alcoholic fatty liver disease, presence of fibrosis is predictive of long‐term liver–related complications. Currently, there are no reliable and non‐invasive means of ...quantifying fibrosis in those with non‐alcoholic fatty liver disease. Therefore, we aimed to evaluate the performance of a panel of non‐invasive models in predicting fibrosis in non‐alcoholic fatty liver disease.
Methods
The accuracy of FibroMeter non‐alcoholic fatty liver disease, fibrosis 4 and four other non‐invasive models in predicting fibrosis in those with biopsy proven non‐alcoholic fatty liver disease was compared. These models were constructed post hoc in patients who had necessary clinical information collected within 2 months of a liver biopsy. The areas under receiver operating characteristics curves were compared for each model using Delong analysis. Optimum cut‐off for each model and fibrosis stage were calculated using the Youden index.
Results
The area under receiver operating characteristics curves for F ≥ 1 fibrosis for fibrosis 4 and FibroMeter non‐alcoholic fatty liver disease was 0.821 and 0.801 respectively. For F ≥ 3, the area under receiver operating characteristics curves was 0.866 for fibrosis 4 and 0.862 for FibroMeter non‐alcoholic fatty liver disease. Delong analysis showed the area under receiver operating characteristics curves was statistically different for fibrosis 4 and FibroMeter non‐alcoholic fatty liver disease compared with BARD, BAAT and aspartate aminotransferase:alanine aminotransferase ratio for F ≥ 1 and F ≥ 3. Area under receiver operating characteristics curves were significantly different for fibrosis 4 and FibroMeter non‐alcoholic fatty liver disease for F ≥ 3 compared with non‐alcoholic fatty liver disease fibrosis score. At a fixed sensitivity of 90%, FibroMeter non‐alcoholic fatty liver disease had the highest specificity for F ≥ 1 (52.4%) and F ≥ 3 (63.8%). In contrast, at a fixed specificity of 90%, fibrosis 4 outperformed other models with a sensitivity of 60.2% for F ≥ 1 and 70.6% for F ≥ 3 fibrosis.
Conclusion
These non‐invasive models of fibrosis can predict varying degrees of fibrosis from routinely collected clinical information in non‐alcoholic fatty liver disease.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Fatty liver is the commonest liver condition globally and traditionally associated with NAFLD. A consensus meeting was held in Chicago to explore various terminologies. Herein, we explore the ...proposed changes in nomenclature in a population data set from the US.
Statistical analysis was conducted using survey-weighted analysis. Assessment of fatty liver was conducted with vibration-controlled transient elastography. A controlled attenuation parameter of 288 dB/m was used to identify hepatic steatosis. Patients were classified into nonalcoholic steatotic liver disease, alcohol-associated steatotic liver disease, and viral hepatitis steatotic liver disease. Liver stiffness measures at ≥8.8, ≥11.7, and ≥14 kPa were used to identify clinically significant fibrosis, advanced fibrosis, and cirrhosis, respectively. A total of 5102 individuals were included in the analysis. Using a survey-weighted analysis, a total of 25.43%, 6.95%, and 0.73% of the population were classified as nonalcoholic steatotic liver disease, alcohol-associated steatotic liver disease, and viral hepatitis steatotic liver disease, respectively. A sensitivity analysis at controlled attenuation parameter of 248 dB/m and fatty liver index found similar distribution. In a comparison between nonalcoholic steatotic liver disease, alcohol-associated steatotic liver disease, and viral hepatitis steatotic liver disease, there was no significant difference between the odds of advanced fibrosis and cirrhosis between groups. However, viral hepatitis steatotic liver disease individuals were found to have a significantly higher odds of clinically significant fibrosis (OR: 3.76, 95% CI, 1.27-11.14, p =0.02) compared with nonalcoholic steatotic liver disease.
The current analysis assessed the proposed changes based on discussions from the consensus meeting. Although the definitions are an interim analysis of discussions, steatotic liver disease respects the underlying liver etiology and reduces stigma while increasing awareness of FL among viral and alcohol-associated steatosis/steatohepatitis.
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BFBNIB, FZAB, GIS, IJS, KILJ, OILJ, SBCE, SBMB, UL, UPUK
Background & Aims Covert hepatic encephalopathy (CHE) impairs quality of life (QOL) and can be difficult to diagnose. Patient-administered methods that do not require specialized tests or equipment ...might increase rates of detection. We performed a longitudinal study to determine whether demographic data and responses to a validated QOL questionnaire, the Sickness Impact Profile (SIP), can identify patients with CHE. Methods Patients with cirrhosis without prior overt HE were recruited from outpatient liver clinics at the Virginia Commonwealth University Medical Center, from August 2008 through February 2012. We performed cognitive tests on 170 patients (mean age, 55 y; mean model for end-stage liver disease score, 9; 50% with hepatitis C–associated and 11% with alcohol-associated cirrhosis). Patients also were given the SIP questionnaire (136 questions on 12 QOL topics, requiring a yes or no answer) at enrollment, at 6 months, and at 12 months. The proportion of patients that responded “yes” to each question was compared between those with and without CHE. Patient variables (noncognitive), demographics (age, education, sex, alcoholic etiology), and SIP questions that produced different responses between groups were analyzed by logistic regression and receiver operating characteristic analyses. Results Based on cognitive test results, 93 patients (55%) had CHE when the study began. They had a higher proportion of “yes” responses to 54 questions on the SIP questionnaire, across all categories. We developed a formula to identify patients with CHE based on age, sex, and responses to 4 SIP questions (a SIP CHE score). Baseline SIP CHE scores greater than 0 identified patients with CHE with 80% sensitivity and 79% specificity. Of the 98 patients who returned for the 6-month evaluation, 50% had CHE (the SIP CHE identified these patients with 88% sensitivity). Of the 50 patients who returned for the 12-month evaluation, 32% had CHE (the SIP CHE score identified these patients with 81% sensitivity). Conclusions We developed a system to identify patients with CHE based on age, sex, and responses to 4 SIP questions; this formula identified patients with CHE with more than 80% sensitivity over a 12-month period after the initial enrollment. Patient-administered CHE screening strategies that do not include specialized tests could increase the detection of CHE and improve therapy.
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