Simonetto, Douglas A.

Physiologic aging leads to attrition of telomeres and replicative senescence. An acceleration of this process has been hypothesized in the progression of chronic liver disease. We sought to examine the association of telomere length (TL) with liver disease and its impact on mortality risk. A cohort of 7,072 adults with leukocyte TL measurements from the National Health and Nutrition Examination Survey 1999‐2002 with mortality follow‐up through 2015 was analyzed. Liver disease was defined by aminotransferase levels and classified into etiology‐based and advanced fibrosis categories. Multivariable‐adjusted linear regression models estimated effect sizes, with 95% confidence intervals (CIs), of the presence of liver disease on TL. Cox regression models evaluated associations between TL and all‐cause mortality risk using adjusted hazard ratios (HRs). The cohort was representative of the US population with mean age 46.1 years and mean TL 5.79 kilobase pairs. No overall association between TL and liver disease was found; however, there was a significant negative association of TL and advanced liver fibrosis in individuals aged 65 and above. The liver disease cohort (HR 1.22, 95% CI 0.99‐1.51) and those with metabolic syndrome (HR 1.26, 95% CI 0.96‐1.67) had increased mortality risk with shorter TL. The relationship between TL and all‐cause mortality was stronger in women (HR 1.51, 95% CI 1.02‐2.23) and in non‐Hispanic Whites (HR 1.37, 95% CI 1.02‐1.84). Conclusion: Shortened leukocyte TL is independently associated with advanced liver disease at older ages, and with a higher risk of all‐cause mortality in those with liver disease. These associations reaffirm the need to better understand the role of telomeres in the progression of liver disease.

Alcohol‐associated hepatitis (AAH) is a severe form of liver injury with mortality as high as 30%‐40% at 90 days. As a result of altered immune function in AAH, bacterial infections are common and are associated with poor outcomes. However, determining the risk and subsequent development of infection in patients with AAH remain challenging. We performed a retrospective study of consecutive patients admitted with a diagnosis of AAH at two independent tertiary centers from 1998 to 2018 (test cohort, n = 286) who developed infections following hospitalization. The diagnosis of AAH was confirmed by manual chart review according to the recent National Institute on Alcohol Abuse and Alcoholism definition. Infections were categorized by location and time of diagnosis as hospital‐acquired infection (48 hours after admission until discharge) and posthospital infections (up to 6 months following discharge). The cohort was 66% men, and the median age was 48 (21‐83) years. Corticosteroids were used in 32% of all patients with AAH. The overall infection rate was 24%. Of those with infections, 46% were hospital acquired and 54% were acquired after hospitalization. Variables found to be significant risk factors for bacterial infection included the presence of ascites on admission (hazard ratio [HR], 2.06), corticosteroid administration (HR, 1.70), Model for End‐Stage Liver Disease (MELD) >23 (HR, 2.61), and white blood cell (WBC) count on admission per point (HR, 1.02). Conclusion: In this multicenter cohort study of patients hospitalized with AAH, MELD score, ascites, WBC count, and use of corticosteroids were identified as significant predictors of the development of bacterial infection. We created a novel predictive equation that may be used to aid in the identification of patients with AAH at high risk of infection.

Background: Obesity paradox is a phenomenon in which obesity increases the risk of obesity-related chronic diseases but paradoxically is associated with improved survival among obese patients with these diagnoses. Objectives: The aim of this study was to explore the obesity paradox among critically ill patients with cirrhosis admitted to the Intensive Care Unit. Methods: A retrospective cohort of 1,143 consecutive patients with cirrhosis admitted to the ICU between January of 2006 and December of 2015 was analyzed. Primary outcome of interest was in-hospital mortality with secondary end points including ICU and short-term mortality at 30 days post ICU admission. Results: Logistic regression with generalized additive models was used, controlling for clinically relevant and statistically significant factors to determine the adjusted relationship between body mass index (BMI) and ICU, post-ICU in-hospital, and 30 day mortality following ICU discharge. ICU and hospital length of stay was similar across all BMI classes. Adjusted ICU mortality was also similar when stratified by BMI. However, a significant reduction in post-ICU hospital mortality was observed in class I and II obese patients with cirrhosis (BMI 30-39.9 kg/m 2 ) compared to normal BMI (OR = 0.41; 95% CI, 0.20 to 0.83; P = 0.014). Similarly, overweight (BMI 25-29.9 kg/m 2 ) and class I and II obese patients with cirrhosis had significantly lower 30-day mortality following ICU discharge (OR = 0.52, 95% CI 0.31 to 0.87; P = 0.014; OR = 0.50, 95% CI 0.29 to 0.86; P = 0.012, respectively) compared to those with normal BMI. Conclusion: The signal of obesity paradox is suggested among critically ill patients with cirrhosis.

ABSTRACT Purpose: Evidence regarding the utility of systemic steroids in treating patients with cirrhosis and septic shock remains equivocal. This study aimed to evaluate and elucidate the association of steroid use with outcomes and adverse effects in a cohort of patients with cirrhosis and septic shock. Patients and methods: Retrospective cohort study of patients with cirrhosis and septic shock admitted to a tertiary hospital intensive care unit (ICU) from January 2007 to May 2017, using a validated ICU Datamart. Patients who received vasopressors within 6 h of ICU admission were included in the multivariate analysis. The effect of steroids on outcomes was evaluated using multivariable regression, adjusting for confounding variables. Results: Out of 179 admissions of patients with cirrhosis and septic shock, 56 received steroids during the ICU admission. Patients who received steroids received a higher total dose of vasopressors (91.2 mg vs. 39.1 mg, P = 0.04) and had a lower initial lactate level (1.8 mmol/L vs. 2.6 mmol/L, P = 0.007). The multivariate analysis included 117 patients and showed no significant differences in mortality, length of ICU admission, or length of hospital stay. Bleeding events, delirium, and renal-replacement therapy requirements were also not associated with the use of steroids. Conclusion: The use of systemic steroids was more prevalent in cirrhotic patients with higher vasopressor requirements. It was not associated with decreased mortality or increased ICU- and hospital-free days, or to adverse effects.

INTRODUCTION: Urinary neutrophil gelatinase-associated lipocalin (NGAL) has shown promise in differentiating acute tubular necrosis (ATN) from other types of acute kidney injuries (AKIs) in cirrhosis, particularly hepatorenal syndrome (HRS). However, NGAL is not currently available in clinical practice in North America. METHODS: Urinary NGAL was measured in a prospective cohort of 213 US hospitalized patients with decompensated cirrhosis (161 with AKI and 52 reference patients without AKI). NGAL was assessed for its ability to discriminate ATN from non-ATN AKI and to predict 90-day outcomes. RESULTS: Among patients with AKI, 57 (35%) had prerenal AKI, 55 (34%) had HRS, and 49 (30%) had ATN, with a median serum creatinine of 2.0 (interquartile range 1.5, 3.0) mg/dL at enrollment. At an optimal cutpoint of 244 μg/g creatinine, NGAL distinguished ATN (344 [132, 1,429] μg/g creatinine) from prerenal AKI (45 [0, 154] μg/g) or HRS (110 [50, 393] μg/g; P < 0.001), with a C statistic of 0.762 (95% confidence interval 0.682, 0.842). By 90 days, 71 of 213 patients (33%) died. Higher median NGAL was associated with death (159 [50, 865] vs 58 [0, 191] μg/g; P < 0.001). In adjusted and unadjusted analysis, NGAL significantly predicted 90-day transplant-free survival ( P < 0.05 for all Cox models) and outperformed Model for End-Stage Liver Disease score by C statistic (0.697 vs 0.686; P = 0.04), net reclassification index (37%; P = 0.008), and integrated discrimination increment (2.7%; P = 0.02). DISCUSSION: NGAL differentiates the type of AKI in cirrhosis and may improve prediction of mortality; therefore, it holds potential to affect management of AKI in cirrhosis.

Modern medical care produces large volumes of multimodal patient data, which many clinicians struggle to process and synthesize into actionable knowledge. In recent years, artificial intelligence (AI) has emerged as an effective tool in this regard. The field of hepatology is no exception, with a growing number of studies published that apply AI techniques to the diagnosis and treatment of liver diseases. These have included machine‐learning algorithms (such as regression models, Bayesian networks, and support vector machines) to predict disease progression, the presence of complications, and mortality; deep‐learning algorithms to enable rapid, automated interpretation of radiologic and pathologic images; and natural‐language processing to extract clinically meaningful concepts from vast quantities of unstructured data in electronic health records. This review article will provide a comprehensive overview of hepatology‐focused AI research, discuss some of the barriers to clinical implementation and adoption, and suggest future directions for the field.