Body mass index and its association with clinical outcomes in acute liver failure

Pathogenesis of Liver Injury in Acute Liver Failure

Serum Apoptosis Markers in Acute Liver Failure: A Pilot Study

Krishnan et al’s article is a comprehensive and vigorous retrospective cohort study regarding the association between obesity and clinical outcomes in acute liver failure (ALF). Among patients with ALF in the United States, mean body mass index (BMI) was significantly greater in those who underwent liver transplantation or who died than among survivors, although acetaminophen induced ALF was the most common etiology. A high BMI was associated with renal failure and high grades of hepatic encephalopathy. The prevalence of obesity and its related fatty liver diseases, such as metabolic dysfunction-associated fatty liver disease/ metabolic dysfunction-associated steatotic liver disease and metabolic dysfunction-associated steatohepatitis, has increased worldwide. Obesity is related to increased serum cytokines and immune abnormalities. These findings may explain why ALF in patients with high BMI is associated with worse clinical outcomes. Further studies are needed to determine the associations among BMI, ALF and acute-on-chronic liver failure.

Predicting outcome in acute liver failure: Are we there yet?

We conducted a systematic review of observational studies to examine the effects of body mass index (BMI) and obesity (BMI ≥ 30 kg/m2 ) on coronavirus disease 2019 (COVID-19). Medline, Embase, and the Cochrane Library were searched. Sixteen articles were finally included in the meta-analysis, and a random effects model was used. BMI was found to be higher in patients with severe disease than in those with mild or moderate disease (MD 1.6, 95% CI, 0.8-2.4; p = .0002) in China; however, the heterogeneity was high (I2 = 75%). Elevated BMI was associated with invasive mechanical ventilation (IMV) use (MD 4.1, 95% CI, 2.1-6.1; p < .0001) in Western countries, and this result was consistent across studies (I2 = 0%). Additionally, there were increased odds ratios of IMV use (OR 2.0, 95% CI, 1.4-2.9; p < .0001) and hospitalization (OR 1.4, 95% CI, 1.3-1.60; p < .00001) in patients with obesity. There was no substantial heterogeneity (I2 = 0%). In conclusion, obesity or high BMI increased the risk of hospitalization, severe disease and invasive mechanical ventilation in COVID-19. Physicians must be alert to these early indicators to identify critical patients.

The aim of this study was to respectively explore the relationships between physical activity and sedentary behaviors and cardiovascular disease (CVD) and all-cause mortality risk in overweight/obese middle-aged and older patients, and also assess the interaction between physical activity and sedentary behaviors. Data of middle-aged and older adults with body mass index (BMI) ≥25 kg/m2 were extracted from the National Health and Nutrition Examination Surveys (NHANES) database in 2007-2018 in this retrospective cohort study. Weighted univariate and multivariate logistic regression analyses were used to explore the associations between physical activity and sedentary behaviors and CVDs; weighted univariate and multivariate Cox regression analyses were used to explore the relationships between physical activity and sedentary behaviors with the risk of all-cause mortality. The interaction effect between physical activity and sedentary behaviors on CVD and all-cause mortality was also assessed. We further explored this interaction effect in subgroups of age and BMI. The evaluation indexes were odds ratios (ORs), hazard ratios (HRs), and 95% confidence intervals (CIs). Among 13,699 eligible patients, 1,947 had CVD, and 1,560 died from all-cause mortality. After adjusting for covariates, patients who had high sedentary time seemed to have both high odds of CVD [OR = 1.24, 95% CI: (1.06-1.44)] and a high risk of all-cause mortality [HR = 1.20, 95% CI: (1.06-1.37)]. Furthermore, being insufficiently active was linked to high odds of CVD [OR = 1.24, 95% CI: (1.05-1.46)] as well as a high risk of all-cause mortality [HR = 1.32, 95% CI: (1.15-1.51)]. High sedentary time and being insufficiently active had an interaction effect on both high odds of CVD [OR = 1.44, 95% CI: (1.20-1.73)] and high risk of all-cause mortality [HR = 1.48, 95% CI: (1.24-1.76)]. Individuals of different ages with/without obesity need to focus on the potential CVD/mortality risk of high sedentary time and low physical activity (all P < 0.05). Reducing sedentary time combined with increasing physical activity may benefit health by reducing both the risk of CVD and all-cause mortality in overweight or obese middle-aged and older adults.

Elevated body mass index (BMI) and waist circumference (WC) are associated with increased mortality risk, but it is unclear which anthropometric measurement most highly relates to mortality. We examined single and combined associations between BMI, WC, waist-hip ratio (WHR) and all-cause, cardiovascular disease (CVD) and cancer mortality. We used Cox proportional hazard regression models to estimate relative risks of all-cause, CVD and cancer mortality in 8061 adults (aged 18-74 years) in the Canadian Heart Health Follow-Up Study (1986-2004). Models controlled for age, sex, exam year, smoking, alcohol use and education. There were 887 deaths over a mean 13 (SD 3.1) years follow-up. Increased risk of death from all-causes, CVD and cancer were associated with elevated BMI, WC and WHR (P<0.05). Risk of death was consistently higher from elevated WC versus BMI or WHR. Ascending tertiles of each anthropometric measure predicted increased CVD mortality risk. In contrast, all-cause mortality risk was only predicted by ascending WC and WHR tertiles and cancer mortality risk by ascending WC tertiles. Higher risk of all-cause death was associated with WC in overweight and obese adults and with WHR in obese adults. Compared with non-obese adults with a low WC, adults with high WC had higher all-cause mortality risk regardless of BMI status. [corrected] BMI and WC predicted higher all-cause and cause-specific mortality, and WC predicted the highest risk for death overall and among overweight and obese adults. Elevated WC has clinical significance in predicting mortality risk beyond BMI.

Rural areas have higher cardiovascular disease (CVD) incidence and age-adjusted mortality rates in the general population. However, the impact of rurality on CVD development and outcomes in patients with prostate cancer (PC) remains unclear. This retrospective cohort study used the SEER-Medicare database to analyze males aged ≥65 years diagnosed with PC between 2009 and 2017. The primary exposures were patient rurality status (metropolitan, urban, or rural) and patient-provider rurality, which combined the provider's status (metropolitan vs nonmetropolitan) with the patient's rurality. The primary outcomes included post-PC CVD (comprising heart failure, atrial fibrillation, acute myocardial infarction, peripheral artery disease, and ischemic stroke), cardiovascular mortality (CVDm), prostate cancer-specific mortality (PCSm), and all-cause mortality. Multivariable Fine-Gray and extended Cox models were used to assess the impact of rurality impact on these outcomes. A total of 103,327 older men were included in the study, of whom 3,631 were from rural areas and 1,857 were rural patients with nonmetropolitan providers. Compared with metropolitan patients, those from rural areas had a 28% higher risk of PCSm (subdistribution hazard ratio [SHR], 1.28; 95% CI, 1.14-1.44) and a 15% higher risk of all-cause mortality (adjusted hazard ratio [aHR], 1.15; 95% CI, 1.07-1.23). Compared with urban patients, rural patients had a 7% higher risk of CVD (SHR, 1.07; 95% CI, 1.01-1.13). No significant differences were observed in CVDm. Among patients receiving androgen deprivation therapy (n=16,811), rurality was associated with a 27% higher risk of PCSm (SHR, 1.27; 95% CI, 1.07-1.51) and a 29% higher risk of all-cause mortality (aHR, 1.29; 95% CI, 1.12-1.49). Rural patients who received care from nonmetropolitan providers had higher risks of PCSm and all-cause mortality compared with those treated by metropolitan providers. Rurality is associated with higher risks of CVD, PCSm, and all-cause mortality compared with metropolitan and urban patients. Provider rurality further increases these risks, underscoring the critical role of health care access and quality in rural health disparities.

Adipose deposition and Barrett’s esophagus: Is all fat created equal?

In patients with acute liver failure (ALF) who suffer from massive hepatocyte loss, liver progenitor cells (LPCs) take over key hepatocyte functions, which ultimately determines survival. This study investigated how the expression of hepatocyte nuclear factor 4α (HNF4α), its regulators, and targets in LPCs determines clinical outcome of patients with ALF. Clinicopathological associations were scrutinized in 19 patients with ALF (9 recovered and 10 receiving liver transplantation). Regulatory mechanisms between follistatin, activin, HNF4α, and coagulation factor expression in LPC were investigated in vitro and in metronidazole-treated zebrafish. A prospective clinical study followed up 186 patients with cirrhosis for 80months to observe the relevance of follistatin levels in prevalence and mortality of acute-on-chronic liver failure. Recovered patients with ALF robustly express HNF4α in either LPCs or remaining hepatocytes. As in hepatocytes, HNF4α controls the expression of coagulation factors by binding to their promoters in LPC. HNF4α expression in LPCs requires the forkhead box protein H1-Sma and Mad homolog 2/3/4 transcription factor complex, which is promoted by the TGF-β superfamily member activin. Activin signaling in LPCs is negatively regulated by follistatin, a hepatocyte-derived hormone controlled by insulin and glucagon. In contrast to patients requiring liver transplantation, recovered patients demonstrate a normal activin/follistatin ratio, robust abundance of the activin effectors phosphorylated Sma and Mad homolog 2 and HNF4α in LPCs, leading to significantly improved coagulation function. A follow-up study indicated that serum follistatin levels could predict the incidence and mortality of acute-on-chronic liver failure. These results highlight a crucial role of the follistatin-controlled activin-HNF4α-coagulation axis in determining the clinical outcome of massive hepatocyte loss-induced ALF. The effects of insulin and glucagon on follistatin suggest a key role of the systemic metabolic state in ALF.

Objective:To investigate the impact of lean status as per body mass index (BMI) on mortality in cases of non-alcoholic fatty liver disease (NAFLD).Methods:A systematic search was conducted in PubMed, Embase, and Scopus to identify relevant studies published from the inception of each database up to July 31, 2024. Observational studies that reported data on the mortality outcomes of NAFLD patients with different BMI, and provided adjusted estimates were included. The Newcastle-Ottawa Scale (NOS) was used for quality assessment. Pooled effect sizes were reported as hazard ratio (HR) with 95% confidence intervals (CI).Results:Fourteen studies were included, of which majority were retrospective cohort studies (n=10). Objective assessment method for NAFLD i.e., imaging and/or biopsy was used in 10 studies. Compared to NAFLD patients with high BMI, lean patients had higher risk of all-cause mortality (HR 1.34, 95% CI: 1.23, 1.47), with no publication bias for any of the outcomes. Lean status correlated with elevated risk of liver disease-related mortality (HR 2.14, 95% CI: 1.18, 3.87) but had similar risk of cardiovascular (HR 0.92, 95% CI: 0.65, 1.30) and cancer-related mortality (HR 1.20, 95% CI: 0.90, 1.60).Conclusion:Lean status of NAFLD patients correlates with higher risk of all-cause and liver disease-related mortality compared to patients with high BMI. There is a need for tailored interventions and further research to understand specific mortality risks in this subgroup of patients.

Association between inflammation, body mass index, and long-term outcomes in patients after percutaneous coronary intervention: A large cohort study.

Background Frailty is a geriatric syndrome characterised by sarcopenia, malnutrition, and chronic inflammation that leads to adverse health outcomes including dependency, low quality of life, and higher risk for morbidity and mortality. It was the aim of this study to examine the relationship between frailty status and risk of all-cause and cause-specific mortality. Methods The study is based on data from the Survey on Health, Aging and Retirement in Europe (SHARE) including 11 European countries with an 11-year follow up. 24,634 participants with a mean age of 64.2 (9.8) 53.6% female, were analysed. Frailty status was calculated using the SHARE- Frailty Instrument, categorizing the participants as robust, pre-frail, and frail. Cox Proportional Hazard models were used to estimate the risk of all-cause and cause-specific (stroke, heart attack, other cardiovascular disease, cancer, respiratory illness, infectious, digestive and other) mortality in frail and pre-frail subjects compared to robust persons. Results 14.7% and 6.9% were found to be pre-frail or frail at the baseline. During the follow-up, we observed both pre-frailty and frailty being associated with a higher risk of all-cause and cause-specific mortality in the unadjusted model. After adjusting for sex, age, education level, body mass index, smoking, alcohol consumption and a number of comorbidities, frailty was associated with a higher risk of all-cause mortality [HR 1.56 (95% CI 1.37-1.78)], and mortality due to other cardiovascular diseases [HR 1.88 (95% CI 1.27-2.76)], cancer [HR 1.47 (95% CI 1.14-1.90)], and respiratory disease HR [1.82 (95% CI 1.10-3.01)]. Furthermore, pre-frailty was associated with a higher risk of all-cause mortality [HR 1.27 (95% CI 1.14-1.42)] and other cardiovascular disease mortality [HR 1.70 (95% CI 1.22-2.35)]. Conclusions Our study showed that baseline pre-frailty and frailty are associated with increased all-cause and cause-specific mortality over an 11-year follow up. Key messages Frailty but also pre-frailty leads to a higher mortality, even when adjusted for morbidity, lifestyle factors, and socio-demographic factors. More effort is needed to prevent, detect, and treat frailty and pre-frailty, both, on individual and on community level.

Aetiology and outcome of acute liver failure

Introduction: Acute liver failure is one of the common causes of death in pediatric gastroenterology and hepatology department. Outcome is different according to aetiology.&#x0D; Objective: To observe the aetiology, outcome and prognostic factors of pediatric acute liver failure.&#x0D; Methods: Consecutive 62 children aged 2 to 16 years of age who were diagnosed as acute liver failure from November 2015 to April 2018 were included in this study. All the clinical profiles, laboratory data and outcome were recorded in a preformed data sheet. Data were analysed by SPSS for Windows version 20.&#x0D; Results: Mean age was 8.5 years. Thirty-nine (62.9%) patients were between 5-10 years of age. Male were 53%. We made a diagnosis of 39 (63%) patients as Wilson disease alone, Another 3 Wilson disease acute liver failure patients had concomitent with either HAV, HEV or HSV in each one. HAV only was responsible for 17 patients and HEV for 1. One patient was Haemophagocyic lymphohistiocytosis and aetiology could not be identified in 1 patient. The overall death in study population was 48% (30). Twenty-four (57%) of 42 acute liver failure patients due to Wilson disease had died. Five (29%) of 17 patients due to HAV infection and 1 patient with HLH died. Ascites, high total bilirubin, high INR and etiology like Wilson disease were the worse pronostic factors for outcome of acute liver failure in children.&#x0D; Conclusion: Wilson disease was the most common aetiology of acute liver failure in children in this study. Early diagnosis is essential as outcome was worse. Majority of viral etiology improved with supportive care.&#x0D; Anwer Khan Modern Medical College Journal Vol. 10, No. 1: Jan 2019, P 56-61