Cirrhotic cardiomyopathy: Predictors of major adverse cardiac events and assessment of reversibility after liver transplant.

BACKGROUND: Major adverse cardiac events (MACE) are a leading cause of morbidity and mortality after orthotopic liver transplantation (OLT). Cirrhotic cardiomyopathy (CCM), initially described in 2005 and revised in 2019, is a source of MACE in patients after OLT. We sought to identify CCM-related predictors of MACE at one-year follow-up after OLT and assess for reversibility of CCM post-OLT. METHODS: This is a retrospective study of adult patients who underwent OLT between 2009 and 2019. All patients had transthoracic echocardiography pre-and post-OLT. Patients with a left ventricular ejection fraction <50 % pre-OLT were excluded. MACE was defined as death, myocardial infarction, congestive heart failure hospitalization, or cardiac arrest. RESULTS: In total, 131 patients were included in this study, of whom 103 and 23 patients met the 2005 and 2019 criteria, respectively. During the follow-up period, 42 patients had MACE and these patients were more likely to have ascites (p = 0.003), hepatorenal syndrome (p = 0.019), and CCM per 2005 criteria (p = 0.023). There were no significant differences between pre-OLT CCM per 2019 criteria (19 % vs 17 %, p = 0.758) or MELD-Na score (21.24 vs 19.40, p = 0.166) for MACE post-OLT. Per the 2005 criteria, 35 of 103 patients recovered and these patients were less likely to have MACE post-OLT (p = 0.012). Per the 2019 criteria, 13 of 23 patients recovered post-OLT but this low number precluded further statistics. CONCLUSION: The 2005 Montreal criteria for CCM were an independent predictor of MACE at one-year follow-up post-OLT while the 2019 CCC criteria for CCM were not. In addition, the 2005 Montreal criteria were more prevalent when compared to 2019 CCC criteria. Finally, the 2005 Montreal criteria were reversible post-OLT 34 % of the time compared to the 2019 CCC criteria which were reversible 57 % of the time.

Duodenal mucosal resurfacing for nonalcoholic fatty liver disease.

Content available: Author Interview and Audio Recording.

Palliative Care, Patient-Reported Measures, and Outcomes in Hospitalized Patients With Cirrhosis.

CONTEXT: Studies of palliative care (PC) in hospitalized patients with cirrhosis have been retrospective, with limited evaluation of patient-reported measures and outcomes. OBJECTIVES: To examine the relationship between PC, patient-reported measures (quality of life and functional status), and outcomes. METHODS: We performed a prospective cohort study of patients with cirrhosis hospitalized from 2014 to 2019. We recorded PC consultation details, quality of life (chronic liver disease questionnaire), and functional status (functional status questionnaire). Patients were followed for 90 days to assess readmissions, costs, and mortality. RESULTS: Seventy-four of 679 patients saw PC, often later in the hospitalization (median hospital day 8; IQR 4-16). Those who saw PC had greater Charlson comorbidity index (mean 6.8 vs. 5.9), MELD (mean 25 vs. 20), and prior 30-day admission (47% vs. 35%). Compared to those who did not see PC, PC patients had greater impairments in intermediate activities of daily living (83% vs. 72%), social activity (72% vs. 59%), quality of interactions (49% vs. 36%), abdominal symptoms (mean score 3.1 vs. 3.6), activity (mean 3.3 vs. 3.6), and overall quality of life (mean 3.6 vs. 3.8). PC was associated with fewer transfusions and upper endoscopies and with greater completion of advanced directives. After multivariable adjustment, PC was not associated with intensive care, 30-day readmissions, 90-day costs, or mortality. CONCLUSION: PC occurs infrequently and late in those with more severe liver disease and functional impairment. PC may be associated with reduction in utilization and greater completion of advanced directives. Randomized trials are needed to evaluate PC for this population.

Insight into an acute hepatitis A outbreak in Indiana.

Hepatitis A virus (HAV) infection causes an acute enteric hepatitis associated with substantial morbidity and mortality, particularly in older individuals. Incidence of HAV infection is low in the United States, mostly related to consumption of contaminated food. Starting in 2017, Indiana reported a large HAV outbreak. We sought to characterize the risk-exposures, clinical features and outcomes of HAV and examine the differences based on underlying cirrhosis and age. Adults ≥18 years diagnosed with HAV between January 2017 and April 2019 at two large healthcare systems in Indiana were identified. Demographic data, risk-exposures, clinical features, laboratory data and clinical outcomes were collected for analysis. The HAV cohort constituted 264 individuals with mean age of 41-years, 62% male and 94% Caucasian. Risk-exposures identified were illicit drug use (74%), food-borne (15%), person-to-person (11%) and incarceration (11%). Mortality rate was 2%, acute liver failure (ALF) was seen in 4% and acute on chronic liver failure (ACLF) was seen in 30% (6 of 20 with underlying cirrhosis). Admission MELD score was the only factor associated with ALF [OR = 1.17 (1.08-1.2), p < 0.0001], on multivariable logistic regression analysis. Higher proportion of individuals with underlying cirrhosis developed acute kidney injury (AKI) (26% vs. 9%, p = 0.03), ascites (45% vs. 11%, p < 0.0001) and hepatic encephalopathy (35% vs. 4%, p < 0.0001). In conclusion, illicit drug use was the predominant risk-exposure in the current HAV outbreak, which was associated with 2% mortality rate, and those with cirrhosis had worse outcomes (AKI, ascites and HE), of whom 30% developed ACLF.

Changes in Serum Myostatin Levels in Alcoholic Hepatitis Correlate with Improvement in MELD.

BACKGROUND: Alcoholic hepatitis (AH) is a serious clinical syndrome often associated with muscle wasting. Myostatin, a member of the transforming growth factor-ß superfamily, has been studied in diseases with muscle wasting; however, the role of myostatin in AH is unknown. AIMS: To investigate the association between myostatin, clinical variables, and outcomes in AH. METHODS: We analyzed data for cases of AH and controls of heavy drinkers (HD) in TREAT001 (NCT02172898) with serum myostatin levels (AH: n = 131, HD: n = 124). We compared characteristics between the two groups at baseline, 30, and 90 days and explored correlations between myostatin and clinical variables. We then modeled the relationship of myostatin to other variables, including mortality. RESULTS: Baseline median myostatin was lower in AH compared to HD (males: 1.58 vs 3.06 ng/ml, p < 0.001; females: 0.84 vs 2.01 ng/ml, p < 0.001). In multivariable linear regression, bilirubin, WBC, and platelet count remained negatively correlated with myostatin in AH. AH females who died at 90 days had significantly lower myostatin, but in a multivariable logistic model with MELD and myostatin, only MELD remained significantly associated with 90-day mortality. During 1-year follow-up, AH cases (n = 30) demonstrated an increase in myostatin (mean, 1.73 ng/ml) which correlated with decreasing MELD scores (ρ = - 0.42, p = 0.01). CONCLUSIONS: Myostatin levels are significantly lower in AH compared to HD and are negatively correlated with total bilirubin, WBC, and platelet count. Myostatin increased as patients experienced decreases in MELD. Overall, myostatin demonstrated a dynamic relationship with AH outcomes and future studies are needed to understand the prognostic role of myostatin in AH.

Karnofsky performance status predicts outcomes in candidates for simultaneous liver-kidney transplant.

Karnofsky performance status (KPS), a measure of physical frailty, predicts pre-transplant and post-transplant outcomes in liver transplantation, but has not been assessed in simultaneous liver-kidney transplantation (SLKT). We examined the association between KPS and outcomes in SLKT waitlist registrants and recipients (2005-2018) in the UNOS database. KPS was categorized into A (able to work), B (able to provide self-care), and C (unable to provide self-care). Cox regression and competing risk analysis were used to assess the association between KPS groups and outcomes. A total of 10,785 patients were waitlisted (KPS: 19% A, 46% B, 35% C), and 5,516 underwent SLKT (12% A, 36% B, 52% C). One-year waitlist mortality was 17%, 22%, and 32% for KPS A, B, and C, respectively. In adjusted competing risk regression, KPS C was associated with increased waitlist mortality (SHR 1.15, 95%CI 1.04-1.28). One-year post-transplant survival was 92%, 91%, and 87% for KPS A, B, and C, respectively. In adjusted Cox regression, KPS C was associated with increased post-transplant mortality (HR 1.32, 95%CI 1.08-1.61). It was also associated with increased liver and kidney graft losses and with hospital length of stay. Frailty, as assessed by KPS, is associated with poor outcomes in SLKT pre- and post-transplant.

Bleeding After Elective Interventional Endoscopic Procedures in a Large Cohort of Patients With Cirrhosis.

INTRODUCTION: Elective therapeutic endoscopy is an important component of care of cirrhotic patients, but there are concerns regarding the risk of bleeding. This study examined the incidence, risk factors, and outcomes of bleeding after endoscopic variceal ligation (EVL), colonoscopic polypectomy, and endoscopic retrograde cholangiopancreatography with sphincterotomy in cirrhotic patients. METHODS: A cohort study of patients with cirrhosis who underwent the above procedures at a single center between 2012 and 2014 was performed. Patients with active bleeding at the time of procedure were excluded. Patients were followed for 30 days to assess for postprocedural bleeding and for 90 days for mortality. RESULTS: A total of 1,324 procedures were performed in 857 patients (886 upper endoscopies, 358 colonoscopies, and 80 endoscopic retrograde cholangiopancreatograpies). After EVL, bleeding occurred in 2.8%; after polypectomy, bleeding occurred in 2.0%; and after sphincterotomy, bleeding occurred in 3.8%. Independent predictors of bleeding after EVL and polypectomy included younger age and lower hemoglobin. For EVL, bleeding was also associated with infection and model for end-stage liver disease-Na. International normalized ratio was associated with bleeding in univariate analysis only, and platelet count was not associated with bleeding in any procedure. Bleeding after EVL was associated with 29% 90-day mortality, and bleeding after polypectomy was associated with 14% mortality. Of the 3 patients with postsphincterotomy bleeding, none were outliers regarding their baseline characteristics. DISCUSSION: In patients with cirrhosis, bleeding occurs infrequently after elective therapeutic endoscopy and is associated with younger age, lower hemoglobin, and high mortality. Consideration of these risk factors may guide appropriate timing and preprocedural management to optimize outcomes.

Improving Outcomes of Bariatric Surgery in Patients With Cirrhosis in the United States: A Nationwide Assessment.

INTRODUCTION: With increasing burden of obesity and liver disease in the United States, a better understanding of bariatric surgery in context of cirrhosis is needed. We described trends of hospital-based outcomes of bariatric surgery among cirrhotics and determined effect of volume status and type of surgery on these outcomes. METHODS: In this population-based study, admissions for bariatric surgery were extracted from the National Inpatient Sample using International Classification of Diseases, 9th and 10th Revision, Clinical Modification codes from 2004 to 2016 and grouped by cirrhosis status, type of bariatric surgery, and center volume. In-hospital mortality, complications, and their trends were compared between these groups using weighted counts, odds ratios [ORs], and logistic regression. RESULTS: Among 1,679,828 admissions for bariatric surgery, 9,802 (0.58%) had cirrhosis. Cirrhosis admissions were more likely to be in white men, had higher Elixhauser Index, and higher in-hospital complications rates including death (1.81% vs 0.17%), acute kidney injury (4.5% vs 1.2%), bleeding (2.9% vs 1.1%), and operative complications (2% vs 0.6%) (P < 0.001 for all) compared to those without cirrhosis. Overtime, restrictive surgeries have grown in number (12%-71%) and complications rates have trended down in both groups. Cirrhotics undergoing bariatric surgery at low-volume centers (<50 procedures per year) and nonrestrictive surgery had a higher inpatient mortality rate (adjusted OR 4.50, 95% confidence interval 3.14-6.45, adjusted OR 4.00, 95% confidence interval 2.68-5.97, respectively). DISCUSSION: Contemporary data indicate that among admissions for bariatric surgery, there is a shift to restrictive-type surgeries with an improvement in-hospital complications and mortality. However, patients with cirrhosis especially those at low-volume centers have significantly higher risk of worse outcomes (see Visual abstract, Supplementary Digital Content, http://links.lww.com/AJG/B648).

Features of Blood Clotting on Thromboelastography in Hospitalized Patients With Cirrhosis.

INTRODUCTION: Thromboelastography (TEG) provides a global assessment of hemostasis and may have value for patients with cirrhosis who have multiple hemostatic defects. We sought to examine the characteristics of TEG in hospitalized patients with cirrhosis and its relationship with outcomes. METHODS: We performed a cohort study of all adults with cirrhosis hospitalized at Indiana University Hospital between November 2015 and October 2018 with a TEG. We examined the relationships among TEG, traditional measures of hemostasis, liver disease severity, and outcomes, including mortality, discharge to hospice, length of stay, and 30-day readmission. RESULTS: A total of 344 patients met inclusion and exclusion criteria. R-value was elevated (≥10 min) in 4.5%, alpha angle was low (<45°) in 9.3%, and maximum amplitude (maximum amplitude) was low (<55 mm) in 72.1%. K-value, alpha angle, and maximum amplitude were all correlated with both platelet count and fibrinogen (absolute rho range 0.52-0.67); R-value and international normalized ratio (INR) were not strongly correlated with traditional measures or TEG, respectively. Patients with bleeding had hypercoagulable profiles, and patients with infection had increased R-value and decreased alpha angle. A total of 35.8% died or were discharged to hospice, and these patients had a greater R-value and smaller alpha angle. However, after adjustment for model for end-stage liver disease (MELD), neither R-value nor alpha angle were associated with discharge outcomes. CONCLUSIONS: TEG provides insight into the hemostatic state of patients with cirrhosis beyond that of standard measures of hemostasis. It is associated with liver disease severity and outcomes and may play a role complementary to standard measures of hemostasis in this population.

Hospital-Acquired Versus Community-Acquired Acute Kidney Injury in Patients With Cirrhosis: A Prospective Study.

INTRODUCTION: In patients with cirrhosis, differences between acute kidney injury (AKI) at the time of hospital admission (community-acquired) and AKI occurring during hospitalization (hospital-acquired) have not been explored. We aimed to compare patients with hospital-acquired AKI (H-AKI) and community-acquired AKI (C-AKI) in a large, prospective study. METHODS: Hospitalized patients with cirrhosis were enrolled (N = 519) and were followed for 90 days after discharge for mortality. The primary outcome was mortality within 90 days; secondary outcomes were the development of de novo chronic kidney disease (CKD)/progression of CKD after 90 days. Cox proportional hazards and logistic regressions were used to determine the independent association of either AKI for primary and secondary outcomes, respectively. RESULTS: H-AKI occurred in 10%, and C-AKI occurred in 25%. In multivariable Cox models adjusting for significant confounders, only patients with C-AKI had a higher risk for mortality adjusting for model for end-stage liver disease-Na: (hazard ratio 1.64, 95% confidence interval [CI] 1.04-2.57, P = 0.033) and adjusting for acute on chronic liver failure: (hazard ratio 2.44, 95% CI 1.63-3.65, P < 0.001). In univariable analysis, community-acquired-AKI, but not hospital-acquired-AKI, was associated with de novo CKD/progression of CKD (odds ratio 2.13, 95% CI 1.09-4.14, P = 0.027), but in multivariable analysis, C-AKI was not independently associated with de novo CKD/progression of CKD. However, when AKI was dichotomized by stage, C-AKI stage 3 was independently associated with de novo CKD/progression of CKD (odds ratio 4.79, 95% CI 1.11-20.57, P = 0.035). DISCUSSION: Compared with H-AKI, C-AKI is associated with increased mortality and de novo CKD/progression of CKD in patients with cirrhosis. Patients with C-AKI may benefit from frequent monitoring after discharge to improve outcomes.

Palliative Care and Hospice Referrals in Patients with Decompensated Cirrhosis: What Factors Are Important?

Background: Palliative care (PC) and hospice care are underutilized for patients with end-stage liver disease, but factors associated with these patterns of utilization are not well understood. Objective: We examined patient-level factors associated with both PC and hospice referrals in patients with decompensated cirrhosis (DC). Design: Retrospective cohort study. Setting/Subjects: Patients with DC hospitalized at a single tertiary center and followed for one year. Measurements: We assessed PC and hospice referrals during follow-up and examined patient-level factors associated with the receipt of PC and/or hospice, as well as associated clinical outcomes. We also examined late referrals (within one week of death). Results: Of 397 patients, 61 (15.4%) were referred to PC, 71 (17.9%) were referred to hospice, and 99 (24.9%) were referred to PC and/or hospice. Two hundred patients (50.4%) died during the one-year follow-up. In multivariable logistic regression, referral to PC was associated with increased comorbidity burden, ascites, increased MELD (Model for End-Stage Liver Disease)-Na score, lack of listing for liver transplant, and unmarried status. Hospice referral was associated with increased comorbidities, portal vein thrombosis, and hepatocellular carcinoma. PC referrals were late in 68.5% of cases, and hospice referrals were late in 62.7%. Late PC referrals were associated with younger age and married status. Late hospice referrals were associated with younger age and recent alcohol use. Conclusions: PC and hospice is underutilized in patients with DC, and most referrals are late. Patient-level factors associated with these referrals differ between PC and hospice.

Spontaneous Fluctuations in Liver Biochemistries in Patients with Compensated NASH Cirrhosis: Implications for Drug Hepatotoxicity Monitoring.

INTRODUCTION: Patients with cirrhosis may have spontaneous fluctuations in liver enzymes, which may confound detection of drug-induced liver injury (DILI), but these fluctuations have not been described. OBJECTIVE: We sought to quantify spontaneous liver enzyme abnormalities in patients with cirrhosis due to nonalcoholic steatohepatitis (NASH) enrolled in clinical trials. METHODS: We examined the laboratory values of patients with compensated cirrhosis randomized to placebo in two clinical trials for NASH. Patients in one study were followed every 13 weeks up to week 57; patients in the other study were followed every 4 weeks up to week 120. RESULTS: In total, 53 and 85 patients were randomized to placebo in the trials. Baseline alanine aminotransferase (ALT) was greater than the laboratory upper limit of normal (ULN) in 53% and 49% of participants, aspartate aminotransferase (AST) was > ULN in 49% and 59%, alkaline phosphatase was > ULN in 36% and 27%, and bilirubin was >ULN in 13% and 19%. During follow-up, ALT increased to 2× baseline in 8% and 15%, AST increased to 2× baseline in 6% and 21%, and bilirubin increased to 2× baseline in 9% and 18%. Alkaline phosphatase did not increase to 2× baseline for any patient. The maximum ALT was 3× ULN in 9% and 12%. ALT increased to 3× baseline in three patients and to 5× ULN in two patients. No patients had elevations consistent with Hy's law. The maximum ALT for patients with abnormal baseline values was higher [median 48 U/L (range 34-299) and 56 U/L (47-85)] than for those with normal baseline values [median 26.5 U/L (range 18-33) and 29 U/L (25.5-30.5)] in both studies, respectively, with p < 0.001. CONCLUSION: Spontaneous liver enzyme abnormalities are common in patients with NASH cirrhosis in clinical trials, and these abnormalities rarely met criteria for DILI suspicion. Further work to better define these abnormalities and continued vigilance to detect DILI in this population is needed.

Development and Validation of a Model to Predict Acute Kidney Injury in Hospitalized Patients With Cirrhosis.

OBJECTIVES: Acute kidney injury (AKI) is a common complication in hospitalized patients with cirrhosis which contributes to morbidity and mortality. Improved prediction of AKI in this population is needed for prevention and early intervention. We developed a model to identify hospitalized patients at risk for AKI. METHODS: Admission data from a prospective cohort of hospitalized patients with cirrhosis without AKI on admission (n = 397) was used for derivation. AKI development in the first week of admission was captured. Independent predictors of AKI on multivariate logistic regression were used to develop the prediction model. External validation was performed on a separate multicenter cohort (n = 308). RESULTS: In the derivation cohort, the mean age was 57 years, the Model for End-Stage Liver Disease score was 17, and 59 patients (15%) developed AKI after a median of 4 days. Admission creatinine (OR: 2.38 per 1 mg/dL increase [95% CI: 1.47-3.85]), international normalized ratio (OR: 1.92 per 1 unit increase [95% CI: 1.92-3.10]), and white blood cell count (OR: 1.09 per 1 × 10/L increase [95% CI: 1.04-1.15]) were independently associated with AKI. These variables were used to develop a prediction model (area underneath the receiver operator curve: 0.77 [95% CI: 0.70-0.83]). In the validation cohort (mean age of 53 years, Model for End-Stage Liver Disease score of 16, and AKI development of 13%), the area underneath the receiver operator curve for the model was 0.70 (95% CI: 0.61-0.78). DISCUSSION: A model consisting of admission creatinine, international normalized ratio, and white blood cell count can identify patients with cirrhosis at risk for in-hospital AKI development. On further validation, our model can be used to apply novel interventions to reduce the incidence of AKI among patients with cirrhosis who are hospitalized.