Rattan, Puru

INTRODUCTION: Building on prior results, we hypothesized that an electrocardiogram (ECG)-enabled machine learning (ML) model could be used to detect advanced chronic liver disease (CLD). METHODS: A cohort with CLD and 12-lead ECGs was matched with controls from electronic health records. A ML model was trained as a binary classifier. RESULTS: There are 12,930 patients with CLD and 64,577 controls in the cohort. The model's discriminative ability to classify CLD showed an area under the receiver-operating characteristic curve 0.858 (95% confidence interval: 0.850–0.866), and at the chosen threshold, CLD ECGs had 12 times higher odds of being classified as CLD (diagnostic odds ratio 12.33, 95% confidence interval: 11.16–13.63). DISCUSSION: An ECG-enabled ML model affords great promise in identifying advanced CLD in low resource areas.

Abstract Background & Aims: Sarcopenia is common in patients with liver disease and both sarcopenia and short telomeres are associated with mortality, however their relationship in patients with liver disease remains unknown. Methods: A cohort of 16,072 adults from the National Health and Nutrition Examination Survey from 1999-2006 was analyzed. Liver disease was defined by aminotransferases and classified into etiology-based categories. Sarcopenia was defined by dual-energy x-ray absorptiometry. All analyses were conducted separately on each multiple imputation data set and combined via Rubin’s rules. P-values for group comparisons were calculated by testing logistic regression parameter estimates. Cox proportional hazards regression was used for mortality analysis with mortality data available until 2015. Results:Sarcopenia was present in 9.5% of patients with liver disease. Age, race, income, education, physical inactivity, and certain medical comorbidities were associated with sarcopenia. Patients with liver disease and sarcopenia had significantly shorter telomeres than patients with liver disease without sarcopenia when unadjusted for age. The interaction between telomere length and sarcopenia was significantly associated with all-cause mortality. Conclusions: The implications of telomere length on all-cause mortality in patients with liver disease varied by age and sarcopenia status. Shorter telomeres appear to be more highly associated with increased mortality in older patients without sarcopenia.

Background: Remote patient monitoring (RPM) is an emerging focus in health care, and specialized programs may reduce medical costs, supplement in-office visits, and improve patient satisfaction. In this study, we describe the development, feasibility, and early outcomes of an RPM program for patients with decompensated cirrhosis. Methods: Forty-six patients were offered enrollment at the time of hospital discharge in the cirrhosis RPM program (CiRPM), of which 41 completed at least 30 days of monitoring. Participants were mailed remote monitoring equipment and a tablet to be used for patient-reported outcomes. Alerts were continuously monitored by virtual nursing staff who could perform targeted interventions. A cohort of historical controls (n = 74) was created for comparison using inverse probability of treatment weighting. Results: Patients were enrolled in the program for a mean of 83.9 days, with 28 (68%) completing the full 90-day program. Participants uploaded vital signs and responded to symptom-based questionnaires on 93% of the monitored days. On end-of-program surveys, over 75% of patients expressed satisfaction with the program. Gender, age, and MELD-Na were similar between CiRPM and weighted control groups. The 90-day readmission rate was 34% in CiRPM and 47% in weighted controls. In the CiRPM group, 12% of subjects had 2 or more admissions, compared to 37% in the weighted control group. Conclusion: This study demonstrates the feasibility of a cirrhosis-specific RPM program. Overall, patient satisfaction and utilization of the CiRPM was high. Future studies are needed to confirm the impact of RPM on the reduction of hospital readmissions in decompensated cirrhosis.

Background: The Sepsis-3 guidelines have incorporated serum lactate levels of >2 mmol/L in septic shock definition to account for higher observed mortality. Further evidence is needed to support this threshold in cirrhosis, as well as target mean arterial pressure (MAP) during resuscitation. Methods: This observational cohort study investigated the association between initial serum lactate and resuscitation MAP levels on in-hospital mortality in patients with and without cirrhosis. Patients admitted to the intensive care unit for the treatment of septic shock between 2006 and 2021 in a quaternary academic center were included. Patients with cirrhosis documented on imaging and International Classification of Disease codes (n=595) were compared to patients without cirrhosis (n=575). The association of intensive care unit admission lactate levels and median 2-hour MAP with in-hospital mortality and the need for continuous renal replacement therapy was assessed. The association between median 24-hour MAP and in-hospital mortality was analyzed post hoc. Results: Within the cirrhosis group, admission lactate levels of 2–4 and >4 mmol/L were associated with increased in-hospital mortality compared to lactate <2 mmol/L [adjusted odds ratio (aOR): 1.69, CI: 1.03–2.81, aOR: 4.02, CI: 2.53–6.52]. Median 24-hour MAP 60–65 and <60 mm Hg were also associated with increased in-hospital mortality compared with MAP >65 mm Hg (aOR: 2.84, CI: 1.64–4.92 and aOR: 7.34, CI: 3.17–18.76). In the noncirrhosis group, associations with in-hospital mortality were weaker for lactate 2–4 and >4 mmol/L (aOR: 1.32, CI: 0.77–2.27 and aOR: 2.25, CI: 1.40–3.67) and median 24-hour MAP 60–65 and <60 mm Hg (aOR: 1.70, CI: 0.65–4.14 and aOR: 4.41, CI: 0.79–29.38). Conclusions: These findings support utilizing lactate >2 mmol/L in the definition of septic shock, as well as a target MAP of >65 mm Hg during resuscitation in patients with cirrhosis.

INTRODUCTION: The triglyceride (TG) threshold for diagnosis of chylous ascites in patients with portal hypertension remains uncertain. METHODS: Retrospective analysis of lipoprotein electrophoresis was conducted in 286 consecutive ascites samples. RESULTS: Ascitic TG ≥ 81 mg/dL is 95.4% sensitive and 94.6% specific for chylous ascites diagnosed by the presence of significant chylomicron population. DISCUSSION: The cutoff for chylous ascites diagnosis should be TG ≥ 81 mg/dL.

SummaryBackgroundAlcohol‐associated hepatitis is an acute manifestation of alcohol‐associated liver disease (ALD) and is associated with 30%–40% mortality at 28 days. Abstinence and corticosteroids are the mainstays of treatment, but the latter only improves short‐term mortality, so new and improved therapies remain an unmet need.AimsThe aim was to review the pathophysiology of alcohol‐associated hepatitis and how various targets can be used by current and emerging therapies as treatment.MethodsA thorough literature review was conducted on acute alcohol‐associated hepatitis, current therapies and therapies under investigation.ResultsWith the increasing prevalence of alcohol use disorder and ALD, the burden of alcohol‐associated hepatitis is also expected to rise. The current understanding of alcohol‐associated hepatitis pathophysiology has led to clinical trials of several therapies involving IL‐1 antagonism, modification of the gut microbiome and liver regeneration.ConclusionsCorticosteroid therapy for alcohol‐associated hepatitis is restricted in its applicability and has limited efficacy. Developing multidisciplinary, patient‐centred care models based on digital health technologies, in combination with continued discovery of novel therapies using multiomics data and computational biology techniques will be necessary to tackle the increasing burden of alcohol‐associated hepatitis.

INTRODUCTION: Cirrhosis is associated with cardiac dysfunction and distinct electrocardiogram (ECG) abnormalities. This study aimed to develop a proof-of-concept deep learning-based artificial intelligence (AI) model that could detect cirrhosis-related signals on ECG and generate an AI-Cirrhosis-ECG (ACE) score that would correlate with disease severity. METHODS: A review of Mayo Clinic's electronic health records identified 5,212 patients with advanced cirrhosis ≥18 years who underwent liver transplantation at the 3 Mayo Clinic transplant centers between 1988 and 2019. The patients were matched by age and sex in a 1:4 ratio to controls without liver disease and then divided into training, validation, and test sets using a 70%-10%-20% split. The primary outcome was the performance of the model in distinguishing patients with cirrhosis from controls using their ECGs. In addition, the association between the ACE score and the severity of patients' liver disease was assessed. RESULTS: The model's area under the curve in the test set was 0.908 with 84.9% sensitivity and 83.2% specificity, and this performance remained consistent after additional matching for medical comorbidities. Significant elevations in the ACE scores were seen with increasing model for end-stage liver disease-sodium score. Longitudinal trends in the ACE scores before and after liver transplantation mirrored the progression and resolution of liver disease. DISCUSSION: The ACE score, a deep learning model, can accurately discriminate ECGs from patients with and without cirrhosis. This novel relationship between AI-enabled ECG analysis and cirrhosis holds promise as the basis for future low-cost tools and applications in the care of patients with liver disease.

AbstractIntroductionThe optimal colonoscopy withdrawal time is still a controversial topic. While several studies demonstrate that longer withdrawal time improves adenoma detection rate, others have contradicted these findings.MethodsThree independent reviewers performed a comprehensive review of all original articles published from inception to January 2021 and included studies reporting comparison of the two cohorts—(i) ≥ 6 but less than 9 min of colonoscopy withdrawal time (CWT) and (ii) ≥ 9 min of CWT. The outcome measures were the following: (i) adenoma detection rate (ADR), (ii) advanced ADR, and (iii) sessile serrated adenoma detection rate (SDR). The meta‐analysis was performed, and the statistics were two‐tailed.ResultsA total of seven studies met the inclusion criteria after a thorough search of the literature was completed. The analysis revealed that ≥ 9 min of CWT had significantly higher odds of adenoma detection as compared with 6–9 min of CWT (odds ratio [OR] 1.54, 95% confidence interval [CI] 1.30–1.82; I2 = 93.7). Additionally, a significantly higher odds of sessile serrated adenoma detection (OR 1.68, 95% CI 1.28–2.22; I2 = 0) and a trend towards higher odds of advanced adenoma detection (OR 1.38, 95% CI 0.98–1.95, I2 = 90) were seen with CWT of at least 9 min when compared with 6–9 min of CWT.ConclusionThis systematic review and meta‐analysis analysis provides further evidence that at least 9 min of CWT cohort had significantly higher ADR and SDR as compared with the at least 6 min but less than 9 min of cohort.

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.